tag:blogger.com,1999:blog-16611215594751275242024-02-07T10:02:54.950-08:00Equal and Opposite ReactionHighlighting work related to the use of (bio)chemical reactions to achieve sophisticated behaviour such as sensing, signalling, inference, self-assembly and locomotion.TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.comBlogger52125tag:blogger.com,1999:blog-1661121559475127524.post-59989735195600721852022-10-19T05:36:00.001-07:002022-10-19T05:36:06.613-07:00Novel techniques in synthetic biology: ultrasound, CRISPR and more<p> <b style="text-align: justify;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Ultrasensitive ultrasound imaging of gene
expression with signal unmixing</span></b></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; text-align: justify;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Acoustic reporter genes (ARGs) that encode
air-filled gas vesicles enable ultrasound-based imaging of gene expression in
genetically modified bacteria and mammalian cells, facilitating the study of
cellular function in deep tissues. Despite the promise of this technology for
biological research and potential clinical applications, the sensitivity with
which ARG-expressing cells can be visualized is currently limited. They present
BURST, a method that improves the cellular detection limit by more than 1,000-fold
compared to conventional methods. BURST takes advantage of the unique temporal
signal pattern produced by gas vesicles as they collapse under acoustic
pressure above a threshold defined by the ARG. BURST can detect ultrasound
signals from individual bacteria and mammalian cells, enabling quantitative
single-cell imaging. <o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; text-align: justify;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.nature.com/articles/s41592-021-01229-w">https://www.nature.com/articles/s41592-021-01229-w</a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 9.0pt; mso-margin-top-alt: auto;"><b style="mso-bidi-font-weight: normal;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Dynamic modulation of enzyme
activity by synthetic CRISPR-Cas6 endonucleases<o:p></o:p></span></b></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 9.0pt; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">RNA-scaffolds
can increase flux through a given metabolic pathway by keeping the pathway’s
enzymes in close proximity to increase the local concentration of pathway
intermediates. Here, RNA scaffolds are built using the crRNA-Cas6 system:
enzymes of interest are fused to Cas6, which in turn binds a specific loop of
RNA. By engineering complementarity into the RNA sequence upstream of the
Cas6-bound loop, the RNA scaffold assembles by RNA:RNA hybridisation. The
authors can then use other input RNA strands to trigger the assembly and
disassembly of the scaffold through TSMD reactions. With this method, the
authors demonstrate controllable scaffold assembly, break-down and cycles of
assembly/disassembly <i>in vivo</i>.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 9.0pt; mso-margin-top-alt: auto;"><u><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.nature.com/articles/s41589-022-01005-7" target="_blank" title="https://www.nature.com/articles/s41589-022-01005-7"><span style="color: #6888c9;">Dynamic modulation of enzyme activity by synthetic
CRISPR–Cas6 endonucleases | Nature Chemical Biology</span></a></span></u><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">A
domain-level DNA strand displacement reaction enumerator allowing arbitrary
non-pseudoknotted secondary structures</span></b><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Domain-level
DNA strand displacement crn simulators. I've read up on visualDSD and
peppercorn enumerator. The aim of these computational models is to 1) enumerate
WC bonded domain level complexes which could from when designing DNA strand
displacement circuits, 2) to use approximate the kinetics of the systems and 3)
simulate them so that mechanisms can be inspected and designs can be updated to
yield desired results, perhaps by inspection or by algorithmic approaches.
Classic visual DSD (<a href="https://ph1ll1ps.github.io/visualdsd/index.html" target="_blank" title="https://ph1ll1ps.github.io/visualdsd/index.html">https://ph1ll1ps.github.io/visualdsd/index.html</a>)
could describe only a very limited set of toehold mediated strand displacement
and other binding mechanisms. More recently visualDSD has been converted to use
"logic dsd" semantics (<a href="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.8b00229" target="_blank" title="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.8b00229">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.8b00229</a>)
which can describe a very wide range of customizable reactions, including DNA
strand displacements and enzymatic reactions such as ligation and cleaving. It
is unclear where to find and how to use the logicDSD version, as the link
provided in the paper no longer works. Classic visualDSD is incapable of
simulating the remote toehold used in handhold mediated strand displacement.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Peppercorn
enumeration does biomolecular binding interactions and a multitude of
intramolecular reactions for non pseudoknotted secondary structured DNA
complexes (where kinetics and thermodynamics are well characterised).<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Approximate
rates for each type of reaction based upon domain lengths can be generated
within the software. Once the complexes have been enumerated and the rates of
each reaction have been estimated, a CRN can be constructed. The combinatorics
of enumerating all possible domain-level complexes can be challenging as the
number of complexes may explode with increasing number of domains. Therefore
the software has built-in coarse-graining methods based upon timescale
separation. Simulation can be separated into fast and slow reactions.
Unimolecular reactions may be fast, slow or negligible and bimolecular
reactions are slow (which is valid for low concentrations < 10nM, uni-rates
go as conc^1 and bi-rates go as conc^2). A "condensed" CRN which
features fewer species can be constructed on the basis of timescale separation
that has the same slow dynamics as the original CRN but can be simulated more
easily. Care must be taken in cases in which sequential bimolecular reactions
are required, as if all unimolecular reactions are assumed to be fast compared
to biomolecular reactions, the subsequent bimolecular reaction may never occur
in the condensed CRN. No net production or degradation reactions allowed in
peppercorn, and therefore all strands are conserved. Toeholds less than 7 nt by
default are reversible. Branch migrations are irreversible. Zero-toehold branch
migrations aren't included. peppercorn would be capable of simulating hmsd, but
this would require the implementation of custom reactions and custom rates.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://doi.org/10.1098/RSIF.2019.0866" target="_blank" title="https://doi.org/10.1098/rsif.2019.0866">https://doi.org/10.1098/RSIF.2019.0866</a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b style="mso-bidi-font-weight: normal;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Molecular filters for noise
reduction<o:p></o:p></span></b></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">In classical
signal processing a filter takes an input signal and produces an output signal
with reduced noise. This paper investigates three classes of bimolecular
chemical reaction networks (CRNs) that act as filters by producing a new output
chemical that tracks the input chemical but with reduced noise. One critical
difference between classical filters and CRN filters is that CRNs have
intrinsic noise associated with the stochastic firing of reactions as well as
noise in the input signal, where as classical filters only have noise in the
input signal.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">The first
class of CRNs that are analysed are the linear filters, the paper shows through
classical frequency domain analysis that linear filters have the same transfer
function as the low-pass filter. Low-pass filters attenuate high-frequency
oscillations while preserving the low-frequency ones. They show that the output
signal of linear filters are limited by the Poisson’s level, a lower bound on
the variance of your output signal that is at minimum the mean of the output
signal.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">They then
go onto to investigate the annihilation module which includes complex formation
reactions. They show that this can reduce the noise of the output to below the
Poisson’s level. They then introduce the annihilation filter which is similar
to the annihilation module except that the mean of the output signal is
proportional to the mean of the input signal.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Finally
they suggest that the translation and transcription of mRNA to produce proteins
can be seen as two cascading linear filters and that certain microRNA pathways
might be annihilation filters.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.sciencedirect.com/science/article/pii/S000634951830585X?via=ihub" target="_blank" title="https://www.sciencedirect.com/science/article/pii/s000634951830585x?via=ihub">Molecular
filters for noise reduction</a><o:p></o:p></span></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-50095065105753660392022-10-19T05:29:00.000-07:002022-10-19T05:29:02.859-07:00The meeting of worlds: theoretical and physical understanding of biological processes<p></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Locked nucleic acid-based DNA circuits with ultra-low leakage</span></b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This work aims to reduce leak in DNA-based strand displacement circuits
by incorporating LNAs into strands. LNAs are modified nucleotides that retain
base-pairing properties but bind DNA (or RNA/other LNAs) with increased
stability. Here, LNAs are placed at extremities of gate complexes in strand
displacement circuits, and the authors report significant leak reduction in all
circuits tested, with a signal loss of ~10% compared to control DNA-only
circuits. <o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 9.0pt; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://link.springer.com/article/10.1007/s12274-022-4761-0" target="_blank" title="https://link.springer.com/article/10.1007/s12274-022-4761-0"><span style="color: blue;">Locked nucleic acids based DNA circuits with ultra-low
leakage | SpringerLink</span></a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Detailed Balance = Complex Balance + Cycle Balance: A Graph-Theoretic
Proof for Reaction Networks and Markov Chains</span></b></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This work introduces the idea of cycle balance as an easier condition to
check than formal balance. A system is detailed balanced if the net flux along
any edge of a process is zero. A process is complex balanced if the total flux
out of any node is equal to the total flux into that node. A process if complex
balanced if the net flux around any cycle is zero. Previous work showed that if
a process was both formally balanced and complex balanced, then it was detailed
balanced. This work now defines a process to be cycle balanced if for any
cycle, there is both an edges faster in the anti-clockwise direction and an
edges faster in the clockwise direction. They then show that a system which is
complex balanced and cycle balanced is detailed balanced.</span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://link.springer.com/article/10.1007/s11538-020-00792-1" target="_blank" title="https://link.springer.com/article/10.1007/s11538-020-00792-1"><span style="color: blue;">https://link.springer.com/article/10.1007/s11538-020-00792-1</span></a></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Physical constraints in intracellular signaling: the cost of sending a
bit</span></b></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Bryant and Machta analyse a number of distinct communication channels
used by biological systems. They consider the scaling of the energy cost with
the separation of transmitter and receiver and the size of both transmitter and
receiver, for a given frequency. In general, communication beyond a certain
characteristic lengthscale is prohibitively hard. This effect is particularly
true for chemical signals that rely on diffusion, since it is impossible to
send coherent waves via this mechanism. However, the low cost of chemical
signalling makes it ideal over short distances. Neuron-like ion channels work
well over longer distances, but also suffer from the inability to transmit
coherent waves. Acoustic communication, which exploits coherent wave
propagation, is best over large distances. Before the characteristic cut-off in
distance, each mechanism has its own particular scaling of cost depending on
the system parameters.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://arxiv.org/abs/2205.15356" target="_blank" title="https://arxiv.org/abs/2205.15356"><span style="color: blue;">[2205.15356]
Physical constraints in intracellular signaling: the cost of sending a bit
(arxiv.org)</span></a></span></p>
<p class="MsoNormal" style="line-height: normal;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Branching processes with resetting as a
model for cell division</span></b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">The paper describes modelling cell division as a process involving
branching and resetting. Their model is based on 1-dimensional Brownian motion
in a potential V, with the additional possibility for particles to branch and
give birth to more particles, whose positions are reset relative to the
position of the original particles. The model is applied to three different
cell division schemes:<o:p></o:p></span></p>
<ol start="1" type="1">
<li class="MsoNormal" style="color: black; line-height: normal; mso-list: l0 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Sizer: Cells size determines
branching probability (cell size is used as the Brownian space dimension).<o:p></o:p></span></li>
<li class="MsoNormal" style="color: black; line-height: normal; mso-list: l0 level1 lfo1; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Timer: Cell age determines
branching probability (cell age is used as the Brownian space dimension).<o:p></o:p></span></li>
<li class="MsoNormal" style="color: black; line-height: normal; margin-bottom: 8.25pt; mso-list: l0 level1 lfo1; mso-margin-top-alt: auto; tab-stops: list 36.0pt;"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Adder: Branching probability
is dependent on the added volume since birth.<o:p></o:p></span></li>
</ol>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">For all three processes, branching reduces entropy (as it tends to make
more probable states even more probable), and resetting increases entropy. They
then claim that an efficiency can be measured by considering the ratio of
branching entropy to resetting entropy, and explicitly calculate this value to
be 0.41 for the timer cell division scheme in the infinite limit of a branching
rate parameter.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><u><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://iopscience.iop.org/article/10.1088/1751-8121/ac491a/meta" target="_blank" title="https://iopscience.iop.org/article/10.1088/1751-8121/ac491a/meta"><span style="color: #6888c9;">https://iopscience.iop.org/article/10.1088/1751-8121/ac491a/meta</span></a></span></u><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto; mso-outline-level: 1;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB; mso-font-kerning: 18.0pt;">An autonomously
oscillating supramolecular self-replicator<o:p></o:p></span></b></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This work describes the design of a network of sulphides and disulphides
which autonomously forms and destroys a supramolecular assembly under the
constant flow of peroxide as fuel. Disulphides with aromatic head and long
aliphatic tail forms micellar structures with can encapsulate free thiols
inside it. After a certain point, the micelle ruptures releasing the thiols
back into the reaction medium. The combination of such molecular and
supramolecular events produces sustained oscillations in the concentration of
the components.</span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.nature.com/articles/s41557-022-00949-6" target="_blank" title="https://www.nature.com/articles/s41557-022-00949-6"><span style="color: blue;">An autonomously oscillating supramolecular self-replicator |
Nature Chemistry</span></a><o:p></o:p></span></p><br /><p></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-29909968625971682932022-05-05T03:00:00.002-07:002022-05-05T03:00:28.690-07:00Exploiting and understanding cellular molecules: nucleic acids and proteins<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Strategies for Constructing and Operating DNA Origami Linear Actuators</span></b><span style="font-family: "Times New Roman", serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The authors discuss the protocol optimisation for the fabrication of a
DNA origami rotaxane. The objective is to find the protocol that produces the
highest yield of working rail/sliders systems to use as linear actuators on the
nanometric scale. The use of these sliders, when combined, will allow the
fabrication of materials with subnanometer precision using the slider as a
“printing head”.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://onlinelibrary.wiley.com/doi/10.1002/smll.202007704">https://onlinelibrary.wiley.com/doi/10.1002/smll.202007704</a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">A tractable genotype–phenotype map modelling the self-assembly of
protein quaternary structure</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The polyomino model is introduced as a high-level model of assembly of
protein sub-domains into larger complexes. The paper introduces the fundamental
features of the polyomino model, starting with the genotype to the formation of
individual assembly kits and finally the formation of complete structures from
assembly kits. The paper investigates polyominos within the wider context of
genotype-phenotype maps, with regards to genotype redundancy, phenotype bias,
component disconnectivity, shape space covering, as well as phenotypic
robustness and its relationship to evolvability, and finds that these are quite
similar to the RNA folding GP map. From a GP map perspective, this raises the
question of whether these traits are inherent to self-assembling systems.
Eventually, the polyomino model could yield insights on artificial systems like
DNA tiles.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2014.0249" target="_blank" title="https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2014.0249">https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2014.0249</a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Paper-based microfluidics for DNA diagnostics of malaria in low resource
underserved rural communities</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The researchers create a paper based lateral flow devices based on
Loop-mediated isothermal amplification (LAMP) of DNA. Although, PCR-based
amplification assays remain the gold-standard NAAT, the requirement for trained
staff and external power has limited their application in areas with reduced
resources. LAMP has recently emerged as easy-to-use alternatives to PCR, owing
to greatly simplified hardware requirements.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The paper discusses use of paper origami techniques to prepare blood
sample preparation (including magnetic beads on DNA molecules of interest),
followed by the LAMP process in a small microfluidic chamber. A hand pressed
button initiates lateral flow of the amplified DNA that travels along a small
membrane where anti-FITC antibodies and immobilized streptavidin are present as
test and control lines. Upon successful attachment of species-specific ligands
to anti-FITC antibodies, a positive signal is generated thereby enabling
detection of diseases.<o:p></o:p></span></p><p>
</p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.pnas.org/content/116/11/4834" target="_blank" title="https://www.pnas.org/content/116/11/4834">https://www.pnas.org/content/116/11/4834</a><o:p></o:p></span></p><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><div style="box-sizing: border-box;"><div style="box-sizing: border-box;"></div></div></div>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-63673202312257705882022-05-05T02:49:00.002-07:002022-05-05T02:49:33.630-07:00The beauty of nucleic acids and the scope of their application<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Continuous Cell-Free Replication and Evolution of Artificial Genomic DNA
in a Compartmentalized Gene Expression System</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">In this study, they coupled DNA replication with gene expression in
cell-free system. They performed the experiments in water-in-oil droplets in
serial dilution cycles. Circular DNA is replicated through rolling-circle
replication followed by homologous recombination catalysed by the proteins,
phi29 DNA polymerase, and Cre recombinase expressed from the DNA. Isolated
circular DNAs accumulated several common mutations that exhibited higher
replication abilities than the original DNA due to its improved ability as a
replication template, increased polymerase activity, and a reduced inhibitory
effect of polymerization by the recombinase.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://pubs.acs.org/doi/10.1021/acssynbio.1c00430">https://pubs.acs.org/doi/10.1021/acssynbio.1c00430</a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Fuel-Driven Dynamic Combinatorial Libraries</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"> </span><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The authors analyse the fuel-driven oligomerisation of isophthalic acid.
They determine that while oligomer formation is mainly driven by fuel
activation, its relaxation back to equilibrium (isophthalic acid monomers) is
not symmetrical. Instead of hydrolysing, the relaxation is produced by the
"reshuffling" of the longest oligomers with shorter ones to produce
average length oligomers. They also demonstrate that oligomers longer than 3
units can produce some sort of feedback interaction, creating insoluble
complexes that resist better the relaxation to equilibrium. Of course, they
also have some leak reactions that produce an undesired subproduct with a
constant rate. The paper presents an interesting view on a well established
far-from-equilibrium assembly reaction as the oligomerisation of isophthalic
acid. However, the control over the oligomerisation process is not impressive;
the concentration of oligomers decreases exponentially with length.</span><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><a href="https://pubs.acs.org/doi/10.1021/jacs.1c01616" title="https://pubs.acs.org/doi/10.1021/jacs.1c01616"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">https://pubs.acs.org/doi/10.1021/jacs.1c01616</span></a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">A Comparison of Genotype-Phenotype Maps for RNA and Proteins</span></b></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">This paper attempts to identify differences and similarities in the RNA
and HP-lattice Protein GP maps. To ensure appropriate comparison, the RNA GP
Map has only 2 alphabets. Similarities include the tendency for some simple
phenotypes to be highly overrepresented in genotype space. One interesting
difference is that whereas most sequences in the RNA GP-Map tend to fold to a
unique structure, only a small subset of sequences in the HP GP-Map do so. The
average size of genotype sets are much smaller in the HP GP Map, and it takes
more mutations from a given sequence to cover the whole phenotype space than in
the RNA GP Map.</span></p><p>
</p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328697/" target="_blank" title="https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3328697/">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328697/</a><o:p></o:p></span></p><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><div class="copy-paste-block"></div></div>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-55435580945539063532022-05-05T02:42:00.001-07:002022-05-05T02:42:06.891-07:00Exploiting cellular machinery for novel applications<p></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Four different mechanisms for switching cell polarity</span></b><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Cell polarity (asymmetric concentration profiles within the cell) plays
a role in migration, division, differentiation, development and signalling. The
mechanisms by which polarity is created and maintained is understood, but the
dynamics of polarity are less well studied. Here they study a model in which
the concentration profile of three interacting molecular species, a
polarization marker, an antagonist, and a recruiter, change in response to
signals of varying strength and duration. The signalling species either promote
or suppress the rate constant for one reaction within the simple reaction
network. This leads to altered phase space stability of the system in the presence
or absence of a signal. Through phase space stability analysis and simulation,
the authors exhaustively identify four distinct ways polarity can switch
in response to a signal which could be tested in future experimental studies.</span><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008587" title="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008587"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008587</span></a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="color: black; mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB; mso-hansi-font-family: Calibri;">Recovery of Information Stored in
Modified DNA with an Evolved Polymerase</span></b><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">DNA is used for digital information storage, but the potential
information loss from degradation and associated issues with error during
reading challenge its wide-scale implementation. To address this, the authors
propose using degradation-resistant analogues of natural nucleic acids (xNAs)
and they used direction evolution to create a polymerase capable of
transforming 2’-O-methyl templates into double-stranded DNA with a fully
functional proofreading domain to correct mismatches on DNA, RNA and 2’-O-methyl
templates. In addition, they implemented a downstream analysis strategy that
accommodates deletions to enable the large-scale use of nucleic acids for
information storage.</span><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB; mso-hansi-font-family: Calibri;"><a href="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.1c00575">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.1c00575</a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Stretching of a fractal polymer around a disc reveals KPZ-like
statistics</span></b><span style="color: black; font-family: "Times New Roman",serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This paper aims to study the directed polymer model around a curved
surface. This then has implications in biology for example wrapping DNA up into
chromosomes as well as other situations where polymers are wrapped up around
rods or similar. They use various scaling techniques to analyse the model
around a surface with local radius of curvature R, where the two ends of the
polymer are fixed a distance S apart. The key observations of this paper
are that the typical distance the polymer goes away from the surface, Δ, scales
as R^(1/3) for small radius of curvature and scales as S^α for large
radius, with a cross over radius which scales as R^z. This is the same
behaviour as surface roughness models mapping Δ to the roughness, R to
time and S to the interface size. Further, they note that in a certain
limit the exponents tend exactly to the 1+1D KPZ exponents.</span><span style="color: black; font-family: "Times New Roman",serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://arxiv.org/pdf/2202.00239.pdf" target="_blank" title="https://arxiv.org/pdf/2202.00239.pdf"><span style="font-family: "Segoe UI",sans-serif; font-size: 11.0pt;">https://arxiv.org/pdf/2202.00239.pdf</span></a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Cooperative Branch Migration: A Mechanism for Flexible Control of DNA
Strand Displacement</span></b><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">They basically demonstrate that if you have a strand that can sequester
a displaced domain once it detaches, the reaction will proceed even if it was
initially not favoured AG>0. They apply this to increase the rate of strand
displacement reactions producing a bulge or a mismatch.</span><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://pubs.acs.org/doi/10.1021/acsnano.1c10797" target="_blank" title="https://pubs.acs.org/doi/10.1021/acsnano.1c10797">https://pubs.acs.org/doi/10.1021/acsnano.1c10797</a><o:p></o:p></span></p><br /><p></p><p></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-85746161727914844022022-05-04T09:07:00.001-07:002022-05-04T09:07:07.342-07:00What are the odds?<p></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><a name="_GoBack"></a><b><span style="color: black; mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB; mso-hansi-font-family: Calibri;">Exact
face-landing probabilities for bouncing objects: Edge probability in the coin
toss and the three-sided die problem</span></b><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="color: black; mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB; mso-hansi-font-family: Calibri;">The paper revisits the classical
physics problem of what is the probability a thick coin lands on its side. They
study the mechanics of a cylinder of a given thickness and radius, being given
an initial random angular velocity and linear velocity. The cylinder is then
allowed to bounce inelastically until it comes to rest either on one of the
faces or on its edge. They then use the areas of phase space which correspond
to each of the resting configurations in order to compute the respective
probabilities as a function of the thickness to diameter ratio. They find that
for example a £1 coin has a probability of landing on its edge of ~1/1000.
Comparing to experimental and simulated data they find decent agreement.
Further, they calculate the thickness to diameter ratio which would provide a
1/3 probability of landing on the edge. They calculate this to be ~0.831 which
is much closer to experimental and numeric studies than previous theoretical
suggestions.</span><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><u><span style="color: black; mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB; mso-hansi-font-family: Calibri;"><a href="https://journals.aps.org/pre/pdf/10.1103/PhysRevE.105.L022201" title="https://journals.aps.org/pre/pdf/10.1103/physreve.105.l022201"><span style="color: #6888c9;">https://journals.aps.org/pre/pdf/10.1103/PhysRevE.105.L022201</span></a></span></u><span style="color: black; font-family: "Times New Roman",serif; font-size: 13.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><b><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Hamiltonian memory: An erasable classical bit</span></b></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">
The authors consider a model of an information-carrying system in which the
information is carried in the phase of a particle moving around a ring. They
show that a (magnetic) Hamiltonian can be used to compress a uniform phase
distribution to a highly-peaked one, apparently at the cost of no work input.
It is unclear to me why this doesn't violate the second law - is this density
in phase angle not exploitable as a non-equilibrium store of work? If not, why
not?</span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://journals.aps.org/prresearch/abstract/10.1103/PhysRevResearch.3.013232">https://journals.aps.org/prresearch/abstract/10.1103/PhysRevResearch.3.013232</a></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><b style="mso-bidi-font-weight: normal;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">A coarse-grained biophysical model of
sequence evolution and the population size dependence</span></b></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="color: black; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">They present a coarse grained model of sequence evolution to ask
questions about the speciation rate and how it differs due to effective
population size. They rely on a framework analogous to thermodynamics, where
the probability of a phenotype is dependent on a balance between its true
fitness and the entropy of the phenotype. Using a DNA-protein binding
co-evolving system as a framework, they show that, for smaller populations, the
most likely phenotype is closer to inviability than for larger populations due
to the greater entropic contribution in the former, and hence speciation is faster
for smaller populations. This is consistent with experimental evidence,
although theirs was a first attempt to explain this occurrence theoretically.</span></p>
<p class="MsoNormal"><a href="https://www.sciencedirect.com/science/article/pii/S0022519315002039?via%3Dihub">https://www.sciencedirect.com/science/article/pii/S0022519315002039?via%3Dihub</a></p><p></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-22373477095296247422021-11-29T08:13:00.001-08:002021-11-29T08:13:09.995-08:00DNA in self-assembly, chemical reaction networks and more<p></p><p><strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">DNA
as a universal substrate for chemical kinetics</span></strong><span style="font-size: 10.5pt;"><o:p></o:p></span></p>
<p><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">This paper
discusses development of control circuitry within a chemical system to direct
molecular events using strand displacement reactions. The authors show basic
methods to construct unimolecular and bimolecular reactions (along with a short
kinetic analysis associated with each reaction system). these 2 reaction types
can then be used to construct any complex CRN (chemical reaction network). They
show this by developing DNA reactions that recreate a Lotka-Volterra chemical
oscillator, a limit cycle oscillator, a chaotic system, and a 2-bit pulse
counter.<o:p></o:p></span></p>
<p><span style="text-decoration-line: underline;"><span style="color: #0000ee; font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">https://www.pnas.org/content/pnas/107/12/5393.full.pdf</span></span><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p>
<p><strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">Undesired
usage and the robust self-assembly of heterogeneous structures</span></strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p>
<p><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">This work
introduces a formal description of the “principle of undesired usage”. This
principle states that the yield of assembling a structure is not determined by
ensuring a perfect stoichiometry between its components but by tuning the
reagents chemical potentials, e.g. concentrations, to avoid undesired
structures. They demonstrate this principle across several types of assembly
processes, with several different modelling techniques.<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.nature.com/articles/ncomms7203" target="_blank" title="https://www.nature.com/articles/ncomms7203">https://www.nature.com/articles/ncomms7203</a></span></p>
<p class="MsoNormal"><strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;">SAT-assembly: A new approach for designing
self-assembling systems</span></strong></p>
<p class="MsoNormal"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;">This paper presents a method of identifying patchy
particle assembly components for a given structure. The foundation of the
method is based on SAT, a well-known problem in computer science. The SAT
problem consists of finding boolean values that solve a given set of boolean
equations with a fixed number of variables. The paper goes into great detail on
the variables and clauses that characterize patchy particle assembly as SAT
problems. The method is performed on a cubic diamond lattice, and the resulting
assembly kit is tested using an OxDNA simulation, which found that the correct
structure was indeed formed.</span></p>
<p class="MsoNormal"><span style="color: #0000ee; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;"><span style="text-decoration-line: underline;">https://arxiv.org/pdf/2111.04355.pdf</span></span></p><p class="MsoNormal"><span style="color: #0000ee; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;">
<!--[endif]--><span style="text-decoration-line: underline;"></span><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;"></span><o:p></o:p></span></p>
<p><strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">Local
time of random walks on graphs</span></strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p>
<p><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">This paper
looks at finding expressions for averages of functions of the local time to
be in a given state in a discrete state discrete time Markov
process. The local time for a state is the number of times that state is
visited in a given time window. The approach taken by the
authors here is inspired by path integration techniques from quantum
physics. The paper provides a method for finding the z-transform for the
average of a given function of the local time. The z-transform is similar
to a generating function for the averages of the function of local time in
a time window n. Specifically, the average of the function of local time
up to time n will be the coefficient of z^-n of the z transform expanded
in powers of 1/z. This then does have the limitation, that finding
the desired average given the z-transform can be a lot of work.
However, overall it was nice to see a more interesting way for
finding these functions of local time.<o:p></o:p></span></p>
<p><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;"><a href="https://journals.aps.org/pre/pdf/10.1103/PhysRevE.104.044302" target="_blank" title="https://journals.aps.org/pre/pdf/10.1103/physreve.104.044302">https://journals.aps.org/pre/pdf/10.1103/PhysRevE.104.044302</a><o:p></o:p></span></p>
<p><strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">Imaging
RNA polymerase III transcription using a photostable RNA-fluorophore complex.</span></strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p>
<p><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">Quantitative
measurement of transcription rates in live cells is important for revealing
mechanisms of transcriptional regulation. RNA Pol III is particulary
challenging as this RNAP transcribes RNA molecules so it is not possible to use
protein reporters. To address this issue, this group developed Corn RNA
fluorescent aptamer that resembles the fluorophore found in red fluorescent
protein. With this new tool, the authors were able to study and imaging the
corn-tagged Pol III transcript levels.<o:p></o:p></span></p>
<p><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt;"><a href="https://www.nature.com/articles/nchembio.2477.pdf" target="_blank" title="https://www.nature.com/articles/nchembio.2477.pdf">https://www.nature.com/articles/nchembio.2477.pdf</a><o:p></o:p></span></p>
<p class="MsoNormal"><strong><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;">Dissipation bounds the amplification of
transition rates far from equilibrium</span></strong></p>
<p class="MsoNormal"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;">Kuznets-Speck and Limmer seek to demonstrate an idea
that has long been gnawing at people working on the physics of computation. A
system with two metastable states is capable of acting a bit. The lifetime of
those metastable states determines how long the bit can reliably store
information. Another related timescale is the time it takes to switch the bit,
when such a switch is required. There is a general feeling that if you want
both a long reliability time, and a short switching time, this should be costly
(in terms of the energy you have to put in). However, such a tradeoff has not
been found, in general, using the tools of modern stochastic thermodynamics.
The title of this manuscript suggests that they have been able to identify a
hard tradeoff; however, this tradeoff only appears when certain conditions are
met. The authors argue that these conditions are quite general, but it is still
unclear whether there is a limit on designing a reliable bit that can be
switched quickly at low thermodynamic cost.<o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;"><o:p> </o:p></span><a href="https://www.pnas.org/content/118/8/e2020863118" style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;" target="_blank" title="https://www.pnas.org/content/118/8/e2020863118">https://www.pnas.org/content/118/8/e2020863118</a></p><br /><p></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-86444102923590156992021-07-10T09:13:00.000-07:002021-07-10T09:13:06.350-07:00The role of strand displacement: from the origin of life to current perspectives<p></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b style="mso-bidi-font-weight: normal;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Rolling-circle and
strand-displacement mechanisms for non-enzymatic RNA replication at the time of
the origin of life<o:p></o:p></span></b></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Tupper and Higgs use basic chemical reasoning illustrated with ODE-level
modelling to argue that pre-enzymatic replication of RNA templates would have
been most successful in a "rolling circle displacement" mode, wherein
a circular template is copied by a product that displaces its own tail as it
goes round the template. This tail must eventually be cleaved by some kind of
self-cleaving ribozyme, and ligated to form another circular template for the
reaction to proceed to another generation. The authors argue that a
displacement mechanism is the only way to avoid suppression of the reaction via
product inhibition, wherein copies bind strongly to their templates. Going
further than previous arguments, they claim that even in systems with time
varying external conditions that allow separation and synthesis in different
environments, products will still cause inevitable inhibition through rebinding
at a critical concentration. This critical concentration is relatively low
because pre-enzymatic extension of RNA on a template would have been slow. Moreover,
rolling circle displacement is deemed to be better than displacement on a
linear template, because linear templates suffer from the fact that the strand
that is being synthesised can be easily displaced from the template at each
(slow) synthesis step.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.sciencedirect.com/science/article/pii/S0022519321002411" title="https://www.sciencedirect.com/science/article/pii/s0022519321002411">https://www.sciencedirect.com/science/article/pii/S0022519321002411</a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">DNA computing: NOT logic gates see the light</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span lang="EN-US" style="mso-ansi-language: EN-US; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This paper describes a NOT gate for DNA
computation enabled by optical control of nucleic acid function via
light-removable nucleobase caging groups. This temporal precise control using
light allowed the authors the introduction of Boolean logic gates into single-
and multilayer DNA circuits. The design was successfully integrated within NOT,
NOR and NAND circuits demonstrating the potential of DNA circuitry.</span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><u><span lang="EN-US" style="color: blue; mso-ansi-language: EN-US; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.1c00062" target="_blank" title="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.1c00062">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.1c00062</a></span></u><span style="color: blue; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Reactor
design for minimizing product inhibition during enzymatic lignocellulose
hydrolysis<br />
II. Quantification of inhibition and suitability of membrane reactors</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This review
discusses the effect of product inhibition in the particular case of
lignocellulose hydrolysis. The authors present ways of quantifying and
experimentally characterise the inhibition and propose reactor designs that can
minimise the product inhibition effect of the enzymatic reaction.</span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm;"><span style="mso-bidi-font-family: Calibri; mso-bidi-font-weight: bold; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.sciencedirect.com/science/article/pii/S073497501000025X" target="_blank" title="https://www.sciencedirect.com/science/article/pii/s073497501000025x">https://www.sciencedirect.com/science/article/pii/S073497501000025X</a></span><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><b><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Perspective: Sloppiness and emergent theories in
physics, biology, and beyond</span></b><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This paper aims to utilise information geometry to
simplify models with a large number of parameters. They make the point that in
such models with many parameters, there are often multiple combinations of
parameters which fit the model and that certain subsets of parameters make
little difference to the predictions. This is made more formal by looking at the
Fisher Information matrix (FIM) made from the parameters and finding that its
eigenvalues have a roughly exponential structure, where the second largest is
an order of magnitude smaller than the largest etc. This means only a few
eigenvalues are relevant. Information geometry focusses on using the FIM as a
Riemannian metric on the manifold of parameters. Due to the exponential
structure of the eigenvalues the manifold has a ribbon like structure with
boundaries corresponding to simplifications of the model. Certain combinations
of parameters having little effect on the predictions translates into certain
directions in parameter space being irrelevant. Following these directions to a
boundary helps to simplify models. They give the specific example of a metabolic
pathway being reduced from 48 parameters to 12.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://aip.scitation.org/doi/10.1063/1.4923066">https://aip.scitation.org/doi/10.1063/1.4923066</a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><b style="mso-bidi-font-weight: normal;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Kinetics
of heterochiral strand displacement from PNA-DNA heteroduplexes <o:p></o:p></span></b></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">DNA comes in two distinct enantiomers (L-DNA and D-DNA).
These enantiomers can not form base pairs with each other. This paper develops
a reaction known as heterochiral strand displacement which allows displacement
of one enantiomer by the other using an achiral substrate strand made from PNA.
This study undertakes an extensive characterisation of the kinetics of
heterochiral strand displacement across a range of toehold lengths and mismatch
positions. Heterochiral strand displacement is particularly useful when
considering introduction of nanodevices into cells, as L-DNA will not interfere
with native cellular molecules or be recognised by nucleases. <o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://academic.oup.com/nar/article/49/11/6114/6298617">https://academic.oup.com/nar/article/49/11/6114/6298617</a><o:p></o:p></span></p><br /><p></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-13312083104448871322021-07-10T08:57:00.000-07:002021-07-10T08:57:23.130-07:00Room with a Re-view: A series of reviews on nucleic acid nanotechnology<p> <b>The i-Motif as a molecular target: More than a complementary DNA
secondary structure</b></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">The i-motif is a DNA structure formed by C tetrads intercalated with
small loops regions. In vitro this structure is formed at low Ph, since it
requires the protonation of the C’s. However, this structures appear inside the
cell at physiological pH. The present review discuss the functions of i-motifs
as transcription regulators inside the cell and its uses in synthetic biology
and nanotechnology. Special focus is given to the application of i-motifs
knowledge in cancer therapy, since this motif is abundant in tumor cells.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/1331208310444887132" title="https://www.mdpi.com/1424-8247/14/2/96/htm">https://www.mdpi.com/1424-8247/14/2/96/htm</a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">In Vitro selection of RNA aptamers binding to nanosized DNA for
constructing artificial riboswitches</span></b><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">The authors present a method to rationally construct artificial
riboswitches using nanosized DNA aptamers. This particular aptamer allowed them
to regulate the internal ribosome entry site-mediated translation in respond to
a ligand (nanosized DNA). They proved that the induction ratio is much higher
than the same type of riboswitch but using a different aptamer. They propose to
use nanosized nucleic acid to build bacterial riboswitches as an alternative
for other regulators such as toehold switches or small transcription activating
RNAs (STARs)<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/1331208310444887132" title="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00384">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00384</a><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><b><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Behaviour of information flow near criticality</span></b><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">In this paper the mutual information between two
spins in a two-dimensional Ising model are explored. An input spin is chosen,
and its value is set by a random telegraph process with a given timescale. An
output spin, a distance, d, away from the input is then monitored. Two measures
of the mutual information between the input and output spins are then measured:
the instantaneous mutual information of the steady state, and the rate of
increase of mutual information. For a given timescale of the input spin, both
the instantaneous information and information rate were found to express a
maximum close to, but not at, the critical temperature. Furthermore, the
information rate maximum was found to be non-monotonic as a function of the
timescale of the input. These maxima were explained to be due to the balance
between thermal noise, which increases with temperature, and the response time
of the system, which decreases with temperature.<o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><u><span style="color: blue; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/1331208310444887132" title="https://journals.aps.org/pre/pdf/10.1103/physreve.103.l010102">https://journals.aps.org/pre/pdf/10.1103/PhysRevE.103.L010102</a></span></u><span style="color: blue; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><b><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">Allosteric regulation of DNA circuits enables
minimal and rapid biosensors of small molecules</span></b><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">This paper aimed to detect small molecule
pollutants within environmental water samples, specifically two families of
antibiotics. They employed the corresponding allosteric transcription factor to
initially capture the ligand of interest e.g. TetR (tetracycline repressor).
They exploited the competition between the allosteric transcription factor and
an endonuclease to trigger a TMSD reaction and achieve signal amplification. In
the presence of tetracycline, this can bind to TetR preventing binding of TetR
to tetO (tet operator sequence) allowing the endonuclease to cleave and create
a toehold. This can be accessed by a fluorescence reporter sequence. This is
followed by cleavage cycles in order to get amplification of the signal. This
system gives a broad linear range of detection. <o:p></o:p></span></p>
<p class="MsoNormal" style="line-height: normal; mso-margin-top-alt: auto;"><span style="color: black; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><a href="https://pubs.acs.org/doi/abs/10.1021/acssynbio.0c00545">https://pubs.acs.org/doi/abs/10.1021/acssynbio.0c00545</a></span><span style="color: black; font-size: 10.5pt; mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;"><o:p></o:p></span></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-46698349518700446892021-02-02T03:19:00.004-08:002021-02-09T08:55:18.890-08:00Under pressure: DNA origami, hairpins and the effect of extreme pressure<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Robust direct digital-to-biological data storage in living cells</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">This paper describes an engineered redox-responsive CRISPR adaptation
system for direct storage of digital data in living cells. They encoded binary
data in 3-bit units into CRISPR arrays using SoxRS system and proved that it
can be maintained over many generations. This DNA-based cellular memory device
can be used not only in digital data storage but also in other biological
recording applications.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/4669834951870044689"><span style="color: blue;">https://www.nature.com/articles/s41589-020-00711-4</span></a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">How we make DNA origami</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">A practical guide on making a DNA origami object. From designing a 3D
objects, ordering to folding, purification and quantification.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/4669834951870044689"><span style="color: blue;">https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cbic.201700377</span></a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">DNA hairpin hybridization under extreme pressures: A single-molecule
FRET study</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The authors test the stability of small hairpins of DNA as a function of
temperature, pressure (1-3000 bar) and stem length. The overall results show
that, due to the increase in free volume of the hairpin, an increase in the
media pressure destabilises the hairpins. In addition, it is shown that the thermodynamic
parameters of the hairpin can be easily modelled by dividing the contribution
of the stem and loop.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/4669834951870044689" title="https://pubs.acs.org/doi/abs/10.1021/acs.jpcb.9b10131"><span style="color: blue;">https://pubs.acs.org/doi/abs/10.1021/acs.jpcb.9b10131</span></a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">First-passage probabilities and mean number of sites visited by a
persistent random walker in one- and two-dimensional lattices</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">This paper looks to solve for a few relevant statistics for persistent
random walker models in 1 and 2 dimensions. A persistent random walk is a
discrete time stochastic process and a simple example of a random walker with
memory. The walker moves in a certain direction, one step per time and at any
time has a certain probability to change direction. This paper utilises various
methods, primarily generating functions and transforms of them, to calculate
the first passage probability for a site, that is the probability that the
walker reaches a certain site for the first time at a certain time; and the
mean number of sites visited by the walker as a function of time. However, most
of the equations required to solve to find analytic solutions were not soluble,
so, instead the limiting behaviours were found. Further, the continuum limit of
these were also found to be in agreement with previous calculations. This
somewhat technical paper showcases various methods and theorems useful for
studying random walk models.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><u><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/4669834951870044689" title="https://journals.aps.org/pre/abstract/10.1103/physreve.102.062129"><span style="color: #6888c9;">https://journals.aps.org/pre/abstract/10.1103/PhysRevE.102.062129</span></a></span></u><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="color: #505050; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; mso-fareast-font-family: "Times New Roman"; mso-fareast-language: EN-GB;">An enzyme-free surface plasmon resonance biosensor for real-time
detecting microRNA based on allosteric effect of mismatched catalytic hairpin
assembly</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">This paper presents an alternative approach for miRNA detection with a
potential diagnostic outlook. This particular study aimed to achieve
enzyme-free and label-free detection. They made use of catalytic hairpin
assembly to facilitate enzyme-free amplification, and surface plasmon resonance
for label-free detection. This system realised a picomolar limit of detection,
even in the presence of total cellular RNA. This platform also shows good reusability.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/4669834951870044689"><span style="color: blue;">https://www.sciencedirect.com/science/article/pii/S0956566315304656</span></a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">DNA-based stategies for site-specific doping </span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">In the present paper the authors propose two different strategies with
which DNA origami could be used as a tool for doping in Silicon lithography. In
the first one the adsorption of DNA constructs over the surface at high
temperature results on the deposition of phosphate groups over the surface
resulting in n-type doping, whereas in the second one, the DNA origami acts as
a passive masking element that gets modified with functional groups and acts as
mask element prior to the etching process. The authors demonstrate the
viability of the process to build FET devices with the technique, but, although
the technique presents advantages such as low cost, the minimum width of the
device built is equivalent to fabrication standards from 12 years ago.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202005940" target="_blank" title="https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202005940"><span style="color: blue;">https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202005940</span></a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0cm; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"> <b>Second-generation DNA-templated macrocycle libraries for the
discovery of bioactive small molecules</b><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Here the authors improve upon an earlier method in which DNA templated
chemical synthesis is used to generate diverse DNA-tagged libraries of
bioactive molecules from a few DNA-tagged building blocks. First, a library of
20x20x20x32=256000 DNA templates with orthogonal codons is generated. Then
reagents, which have DNA tags complementary to the codons on the template,
combine to generate the macrocycle molecule encoded by the DNA template.
Effective molecules can be identified by selection (increased binding affinity
to a target molecule and filtering) and then reading the DNA templates by dna
sequencing.<o:p></o:p></span></p><p>
</p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://doi.org/10.1038/s41557-018-0033-8" target="_blank" title="https://doi.org/10.1038/s41557-018-0033-8"><span style="color: blue;">https://doi.org/10.1038/s41557-018-0033-8</span></a><o:p></o:p></span></p><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><div style="box-sizing: border-box;"></div></div>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-47744474796723709432020-12-26T03:53:00.001-08:002020-12-26T03:53:22.437-08:00From monomers to polymers<p> <b style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Kinetic roughening of the urban skyline</span></b></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 8.25pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">A neat little paper showcasing an application of a statistical mechanical model to city skylines. Kinetic roughening is a nice example of a simple model that showcases some of the main themes of modern statistical mechanics including scaling and continuum limits. These models, in the discrete regime, consist of a lattice of height vectors which evolve in time due to some rules relating them to their neighbours. The roughness is defined as the root mean square of the heights. This roughness displays scaling behaviour, in particular for this paper, the roughness scales as the system size to some power after sufficient time passes. This paper looks at a huge database of 10^7 buildings in the Netherlands and calculates this saturation exponent for many cities. Where there is significant enough data, they find that the cities can be grouped into two sets with different exponents. These exponents correspond to the two main universality classes for roughening models. Finally, they remark that it would be interesting to consider the buildings regulations for each city to explain why they would fall into a given universality class.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 8.25pt;"><u><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://journals.aps.org/pre/abstract/10.1103/PhysRevE.101.050301" target="_blank" title="https://journals.aps.org/pre/abstract/10.1103/physreve.101.050301"><span style="color: #6888c9;">https://journals.aps.org/pre/abstract/10.1103/PhysRevE.101.050301</span></a><o:p></o:p></span></u></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Characterization and mitigation of gene expression burden in mammalian cells</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><br /><br />In this work, the authors investigate the burden imposed by synthetic circuits in mammalian cells and study transcriptional and translational burden caused by cellular resource sharing. They were able to mitigate the effects of resource limitations using a microRNA-based incoherent feedforward loop (iFFL) motif. They concluded that using burden-aware designs, synthetic circuits that rely on perturbations will be able to show more accuracy and predictability.<br /><br /><a href="https://www.nature.com/articles/s41467-020-18392-x" target="_blank" title="https://www.nature.com/articles/s41467-020-18392-x">https://www.nature.com/articles/s41467-020-18392-x</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">A basic introduction to large deviations: Theory, applications, simulations</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">This approachable set of lecture notes was written following a 2009 paper reviewing the theory of large deviations (or LDT). The techniques of LDT provide a framework for a rigorous formulation of statistical mechanics. Most physicists and engineers have used the techniques of LDT at some point or another, but might not have been aware that this was the case! In essence, LDT is used to quantify the rate at which the probability that the sample mean S (of a set of samples of n independent identically distributed random variables each with mean u) is exponentially suppressed with increasing sample size n, where S is not equal to the mean u. This is a generalisation of the central limit theorem.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://arxiv.org/pdf/1106.4146.pdf" target="_blank" title="https://arxiv.org/pdf/1106.4146.pdf">https://arxiv.org/pdf/1106.4146.pdf</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Programmed spatial organization of biomacromolecules into discrete, coacervate-based protocells</span></b></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The coacervate created in this work was able to recruit his-tagged enzymes with via interaction with Nickel ion in the protocell. The increased concentration of enzymes led to acceleration in the enzymatic process. The proteins could be released by cleaving specific site as well.</span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.nature.com/articles/s41467-020-20124-0%20" target="_blank" title="https://www.nature.com/articles/s41467-020-20124-0%20">https://www.nature.com/articles/s41467-020-20124-0</a></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">DNA programmed chemical synthesis of polymers and inorganic materials </span></b></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The present review offers a general perspective on how DNA programmable interactions have been exploited in the field of chemical synthesis, first referring to the possibility of using directed interactions to perform directed polymer synthesis analogously to how copying polymers work in living cells, as well as how DNA can direct the conjugation and directed arrangement of different polymeric materials with aims as diverse as functionalisation for in vivo applications or directed assembly of conducting polymers as well as the assembly of metallic nanoparticles in prescribed arrangements that can have applications for plasmon resonance-based sensor applications. While showing that DNA nanotechnology is a powerful tool for material science-based nanotechnology applications, this review fails to specify which challenges face the field in order to be applied to other other fields (such as MOF, COF or polyoxometalate synthesis) in which the chance to implement programmable interactions could become a paradigm shift.</span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://link.springer.com/article/10.1007/s41061-020-0292-x" target="_blank" title="https://link.springer.com/article/10.1007/s41061-020-0292-x">https://link.springer.com/article/10.1007/s41061-020-0292-x</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 8.25pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Emergence of low-symmetry foldamers from single monomers</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 8.25pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Molecular self-assembly of simpler components often give rise to complex features in dynamic combinatorial libraries. In this article, the authors describe the emergence of large molecules with low symmetry unlike most previously described systems. When the monomers, capable of forming disulfide bonds among themselves, are equilibrated for several days, different libraries show the formation of predominantly one product, or a very small family of products. In some cases, large molecules were generated with very low symmetry (17 or 23 monomers). Further analysis by ion mobility mass spectrometry, NMR and CD spectroscopy showed that these large molecules are not simple 2D circular molecules, rather they all have unique complex folded structures. This was confirmed by the X-ray crystal structures of the synthesised molecules. The authors conclude that the semi-rigid backbone structures of the molecules, and the presence of several diverse sites for non-covalent interaction, which can overcome the inherent instability of large macrocycles, are crucial for spontaneous formation of newer complex foldamers.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 8.25pt;"><u><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.nature.com/articles/s41557-020-00565-2?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=JRCN_1_DD01_CN_NatureRJ_article_paid_XMOL#Sec8" target="_blank" title="https://www.nature.com/articles/s41557-020-00565-2?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=jrcn_1_dd01_cn_naturerj_article_paid_xmol#sec8"><span style="color: #6888c9;">https://www.nature.com/articles/s41557-020-00565-2?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=JRCN_1_DD01_CN_NatureRJ_article_paid_XMOL#Sec8</span></a><o:p></o:p></span></u></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal; margin-bottom: 0.0001pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Fuel-driven transient DNA strand displacement circuitry with self-resetting function</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><br /><br />The authors present an enzyme-driven mechanism to allow continuous cycling of nucleic acid strand displacement circuits. The basic idea is to have strands that are uncompetitive on their own at displacing an output from a complex, but which can be ligated to a helper duplex which in turn can be ligated to the complex, allowing displacement to proceed. The ligation is performed by specific ligase enzymes, and consumes ATP. Subsequently, restriction enzymes can cut the strands, allowing the system to revert back to its initial condition. In principle, such a system could maintain a dynamic steady state of constantly cycled outputs, but the evidence for that in this manuscript is limited. Rather, transient spikes are observed in response to a signal, since there is apparently not enough ATP to sustain the output for a long period. An interesting question to ask is whether the scheme presented can be generalised to a large strand displacement network.<br /><br /><a href="https://pubs.acs.org/doi/abs/10.1021/jacs.0c09681" target="_blank" title="https://pubs.acs.org/doi/abs/10.1021/jacs.0c09681">https://pubs.acs.org/doi/abs/10.1021/jacs.0c09681</a></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Feedback regulation of crystal growth by buffering monomer concentration</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Many reactions, like crystallisation, need to operate at a very specific reagent concentration regime. However, even if the concentration requisites are met, as the reaction proceeds, the reagents get consumed and the reaction regime will change. The authors propose a method for maintaining constant reagent concentration by using buffering species. The mechanism consists of a pool of inactive DNA bricks that are in equilibrium with its active form thanks to a toehold exchange reaction. This mechanism is then used to grow a population of DNA nanotubes of regular sizes. When the active bricks are consumed, the equilibrium is displaced to the formation of new active bricks. However, the buffering power of this method is still limited, and the desired concentration can only be maintained for a few hours. Further increments of the buffering species concentration would block the reaction sites of the active monomers, hindering nanotube formation.<o:p></o:p></span></p><p style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; margin-bottom: 11px;"></p><p class="MsoNormal" style="font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px; line-height: normal;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://www.nature.com/articles/s41467-020-19882-8">https://www.nature.com/articles/s41467-020-19882-8</a></span></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-21793590870640059812020-12-03T05:53:00.001-08:002020-12-04T03:02:05.111-08:00A communication problem: cellular signalling networks<p></p><p><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Do we understand the mechanisms used by biological systems to
correct their errors?</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">This
paper is a review of kinetic proofreading in biological systems, presented in a
mostly historical fashion. The original concept of kinetic proofreading as
introduced by Hopfield and Ninio is recounted. Following this, the concept of
trade-offs between speed, energy dissipation and accuracy is introduced. The
key results that biological systems tend to get accuracy to within acceptable
levels, then prioritise maximising speed, followed by minimising energy
dissipation is presented. In the process of explaining this, a number of
methods utilised are briefly mentioned including: first passage time analysis,
asymptotic analysis, and thermodynamic uncertainty relations. Finally, the
concept of energetic vs kinetic discrimination is briefly introduced.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt;"><u><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://pubs.acs.org/doi/10.1021/acs.jpcb.0c06180" tabindex="-1" target="_blank" title="https://pubs.acs.org/doi/10.1021/acs.jpcb.0c06180"><span style="color: #6888c9;">https://pubs.acs.org/doi/10.1021/acs.jpcb.0c06180</span></a></span></u><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">A
biomimetic DNA‐based membrane gate for protein‐controlled transport of
cytotoxic drugs</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt; text-align: justify;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The
ability to design membrane nanopores with controllable channel opening has the
potential to have many applications in biomedicine, biosensing and artificial
cells. In this paper, the researchers have shown the design and synthesis of a
membrane nanopore constructed of only seven oligonucleotides where the lid of
the nanopore is a thrombin/binding aptamer (TBA). Therefore, passage of small
molecules through the nanopore is only allowed in presence of thrombin. It is
shown that the nanopores can be incorporated in lipid vesicles.
Nanopore-incorporated vesicles containing fluorescent dye are observed to
release the dye only in presence of thrombin which proves that the channel
opening is tightly controlled. This approach is applied to release biologically
relevant molecules for controlled killing of cells. Cytotoxic drug topotecan is
filled in vesicles containing the nanopores on the membrane; and these vesicles
are added to HeLa cervical cancer cells. Upon addition of thrombin, the drug is
released to the cells, and cell viability drops to 20% after three days
compared to 95% when no thrombin is added. This paper thus shows a simple
approach for biocompatible membrane nanopore design which can be opened by the
presence of a biologically relevant substance.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt;"><u><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202011583" tabindex="-1" target="_blank" title="https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202011583"><span style="color: #6888c9;">https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202011583</span></a></span></u><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt; text-align: justify;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">DNA
origami guided self-assembly of plasmonic polymers with robust long-range
plasmonic resonance</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt; text-align: justify;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">The production
of 1D chains by assembling DNA origami tiles have been widely used in
nanofabrication. The defined geometry of the DNA tiles is harnessed to control
the distance between DNA-bound metallic nanoparticles, producing nanowires used
for plasmon propagation. However, regular origami tile assemblies are flawed by
its flexibility, which leads to defects in plasmon signal propagation due to
the variable distance between nanoparticles. The authors of this paper optimise
the rigidity of the DNA origami chains by exchanging the classical tile for a
hashtag-shaped structure. The proposed hashtag-structure can be functionalised
with nanoparticles in several ways, while increasing the persistence length of
the produced nanowires by one order of magnitude.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="background: #EFEFF0; color: #1c1d1e; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://pubs.acs.org/doi/abs/10.1021/acs.nanolett.0c04055">https://pubs.acs.org/doi/abs/10.1021/acs.nanolett.0c04055</a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px;"><strong><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Combinatorial
signal perception in the BMP pathway</span></strong><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Cells
can sense ligands in their environment which bind to receptors on their
surface, and trigger a response through intra-cellular signalling pathways.
There are many types of type 1 and type 2 receptors in the bone morphogen
pathway (BMP) that a cell could express, even more types of dimeric ligands
that could be sensed. Through a combination of an <em>in vivo </em>search and
the construction of a minimal mathematical model, Antebi et al. create a
framework through which we can understand the multifarious signal processing
operations that occur at the boundaries of cells. Crucially, the concentration
of ligands (which is assumed to greatly exceed the number of available
receptors) and the affinities between receptors and ligands determine the
equilibrium distribution of ligand-receptor configurations, but the activity
(the strength with which a ligand receptor combo can catalyse a signal) of the
configuration does not need correlate with its probability of occurrence.
Therefore, in a system with two types of surface receptors and two types of
ligands (each with an affinity and activity with each receptor), the signal
transduced can quantitatively differ when the ligands are presented alone or in
combination.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;"><a href="https://doi.org/10.1016/j.cell.2017.08.015" tabindex="-1" target="_blank" title="https://doi.org/10.1016/j.cell.2017.08.015">https://doi.org/10.1016/j.cell.2017.08.015</a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">3D engine in DNA code</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Turing-completeness of Chemical Reaction Networks as well as the
capability to be mapped into DNA Strand Displacement systems is always brought
up as a proof of their versatility. However, most of the academic literature
focuses on the implementation of CRNs in the context of building controllers,
cellular automata or other sorts of computer science model problems rather than
software applications that are found in our daily life. The present work
presents how to encode a rudimentary 3D shader engine into a CRN and how to
emulate and execute it, the most interesting part being how does it display a
mapping between a high level standard abstraction language (Like JavaScript and
CRNs). While still being impractical when compared to silicon-based devices,
it's easy to see how a bridge between regular coding skills and molecular
programming can be built. But it also must be said that in terms of software
conservation, being able to engineer a sort of CRN/DNA-based assembler code
that an be retroengineered into a high level language can be a promising
technology to preserve software in a format with a longer life than optical or
magnetic devices.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/2179359087064005981" title="https://observablehq.com/@pallada-92/3d-engine-in-dna-code?fbclid=iwar3uxq4kb-o6tttm8vhxl4oxtnnqsztelpdl_vacgtgzqhpp2-cc2dnxmkw">https://observablehq.com/@pallada-92/3d-engine-in-dna-code</a> </span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Computing signal transduction in signaling networks modeled as
Boolean Networks, Petri Nets and hypergraphs </span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Transduction networks are known for being the regular architecture
used bicellular systems to perform signal processing and decision making. Back
from the foundational work by Dennis Bray they have been described as
distributed network computing elements and mappings with computational models
(mainly neural networks) have been drawn. But alternative mappings with other
computing models can be drawn. In this paper, the authors explore other
networks computing models that can be used to model transduction such as
graphs, hypergraphs, Boolean Networks or Petri Nets, establishing the
conditions in which a model is isomorphic to another and highlighting the
strengths and weaknesses of each one. However, some of the strengths attributed
to the Boolean Network model are rarely found in a biological context and none
of the models take into account explicitly the catalytic nature of the network
elements and the implications of the system, thus leaving room to potential new
formalisms.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.biorxiv.org/content/10.1101/272344v2.full" tabindex="-1" target="_blank" title="https://www.biorxiv.org/content/10.1101/272344v2.full">https://www.biorxiv.org/content/10.1101/272344v2.full</a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><h1 style="-webkit-text-stroke-width: 0px; font-size: 1.5rem;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Self-limiting
polymerization of DNA origami subunits with strain accumulation</span><span style="font-family: "Segoe UI", sans-serif;"></span><o:p></o:p></h1><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">The polymerization of DNA origami was controlled by accumulated
strain during the growth process. The DNA origami consist of three domains with
the middle domain being shorter than others. As the three domains are connected
by linkers, they can deform while they grow, accumulating the strain coming
from short middle domain. By controlling the length of the middle domain, the
authors precisely controlled the growth of the DNA origami objects without any
external control.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/2179359087064005981" title="https://pubs.acs.org/doi/10.1021/acsnano.0c07696">https://pubs.acs.org/doi/10.1021/acsnano.0c07696</a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Single
cell characterization of a synthetic bacterial clock with a hybrid feedback
loop containing dCas9-sgRNA</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p style="-webkit-text-stroke-width: 0px; margin-bottom: 8.25pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt;">Oscillatory
dynamics facilitates the temporal orchestration of metabolic and growth
processes inside cells and organisms. In this work, they present a synthetic
oscillator gene circuit (repressilator) in which one of the repressors was
replaced by CRISPRi system and they monitored the oscillations in microfluidic
reacts using single cell experiments. They found that the period of the
oscillator is much slower since it depends on the irreversible binding of the
CRISPR system that prolongs its dilution phase. They propose to use RNA
aptamers and use CRISPRa (activation) to improve the dynamics of the oscillator
and explore the potential applications.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.blogger.com/blog/post/edit/1661121559475127524/2179359087064005981" name="_GoBack">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00438</a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><h1 id="screen-reader-main-title" style="-webkit-text-stroke-width: 0px; box-sizing: border-box; font-size: 1.5rem; margin-bottom: .0001pt; margin-left: 0px; margin-right: 0px; margin-top: 16px !important; margin: 12pt 0cm 0.0001pt; word-break: break-word;"><span style="color: #505050; font-family: "Segoe UI",sans-serif; font-size: 10.5pt;">A ratiometric electrochemical biosensor for the exosomal
microRNAs detection based on bipedal DNA walkers propelled by locked nucleic
acid modified toehold mediate strand displacement reaction</span><span style="font-family: "Segoe UI", sans-serif;"></span><o:p></o:p></h1><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">In this paper, the researchers attempted to develop a novel
biosensor for exosomal miRNAs, which achieved high sensitivity, high
specificity and high reproducibility, such that the biosensor could be used
multiple times. Their system involved locked nucleic acid capture probe
associated with a bipedal DNA walker. The presence of the target miRNA led to
release of the bipedal DNA walker by toehold-mediated strand displacement. The
DNA walker walking over the electrode surface facilitated amplification of the
electrochemical signal, allowing a low signal-to-background ratio.</span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal" style="-webkit-text-stroke-width: 0px; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="background: #EFEFF0; color: #1c1d1e; font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.sciencedirect.com/science/article/pii/S0956566317307170">https://www.sciencedirect.com/science/article/pii/S0956566317307170</a></span><span style="font-family: "Segoe UI", sans-serif; font-size: 13.5pt; line-height: 107%;"></span><o:p></o:p></p><p class="MsoNormal"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Reciprocal coupling in
chemically fueled assembly: A reaction cycle regulates self-assembly and vice
versa<br />
</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"></span><br />
The authors seek to develop a synthetic system that replicates the
behaviour of natural biopolymers such as actin, in which the constituent
monomers can adopt two states, one of which is favourable for polymerisation
("active") and the other of which is less so. Moreover, the
environment of the polymer catalyses the deactivation of the monomers, leading
to non-equilibrium "living" polymerisation. The resultant dynamics
are essential to cytoskeletal mechanics and motion. In this paper, the
assembling monomers are short peptides with a switachble chemical moiety which
can be charged (inactive) or neutral (active). Differential assembly in the two
regimes is demonstrated, as is a catalytic effect on activation/deactivation
rates of the polymer environment. However, the paper doesn't demonstrate
preferential deactivation in the polymer state, as is seen in the natural
counterpart.<br />
<br />
<span style="font-family: "Segoe UI",sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://pubs.acs.org/doi/10.1021/jacs.0c10486" target="_blank" title="https://pubs.acs.org/doi/10.1021/jacs.0c10486">https://pubs.acs.org/doi/10.1021/jacs.0c10486</a></span></p><p></p>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-11483264213306812012020-11-21T02:07:00.001-08:002020-11-21T02:07:15.323-08:00From membrane to cytoplasm: cellular applications of nucleic acid nanotechnology<p style="line-height: 107%; margin-bottom: 8.0pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Unzipping of a
double stranded block copolymer DNA by a periodic force</span></b><span style="font-size: 13.5pt; line-height: 107%;"><u1:p></u1:p><o:p></o:p></span></p><p style="line-height: 107%; margin-bottom: 8pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">In this paper, a simple model for mechanical unzipping of double
stranded DNA (dsDNA) is explored using Monte Carlo simulations. Block copolymer
DNA is considered, consisting of repeated units of different length each having
two hydrogen bond monomers and three hydrogen bond monomers. Results for a
static force applied to the tip of the dsDNA are reproduced displaying a first
order transition from zipped to unzipped states and is independent of sequence.
Simulations for a periodic force are also made and these are found to depend
greatly on the sequence. Hysteresis curves are obtained for different sequences
and the scaling of their area with frequency and amplitude of the periodic force
is studied.<u1:p></u1:p></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p style="line-height: 107%; margin-bottom: 8pt;"><u><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://arxiv.org/abs/2010.13367" target="_blank" title="https://arxiv.org/abs/2010.13367"><span style="color: #6888c9;">https://arxiv.org/abs/2010.13367</span></a></span></u><span style="font-size: 13.5pt; line-height: 107%;"><u1:p></u1:p><o:p></o:p></span></p><p class="MsoNormal"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Genetic circuit characterization by inferring RNA polymerase
movement and ribosome usage</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><br />
<br />
This paper focuses on the analysis of complete genetic circuits using -omics
tools (RNA sequencing and ribosome profiling) with pre-characterized genetic
parts. They characterized the performance of each part of the circuit as well
as the impact of the genomic context. These characterization results were used
to understand the circuit dynamics and to analyse the circuit impact on the
host cell (genetic burden).</span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.nature.com/articles/s41467-020-18630-2" target="_blank" title="https://www.nature.com/articles/s41467-020-18630-2">https://www.nature.com/articles/s41467-020-18630-2</a></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><strong><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Noise-induced symmetry breaking far from equilibrium and the
emergence of biological homochirality</span></strong><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">All biological molecules, like amino acids and sugars, are mostly
found with a single chirality i.e. the spatial arrangement of its atoms. A
specular arrangement of the molecule (enantiomer) would be equally stable;
however, they are significantly scarcer. A mechanism to explain this asymmetry
is still unknown, but some reactions networks have been proposed to explain the
homochirality of biological molecules. Previous models assumed that
homochirality is an equilibrium state. These models rely on an opposite
enantiomers annihilation reaction, which doesn't correspond with the real
dynamics of living systems.</span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">The authors of this paper propose a new model that can explain
homochirality with non-equilibrium dynamics. In the model, a single enantiomer
can be randomly formed due to the system noise. If the autocatalytic formation
of that enantiomer is faster than its degradation, it can keep replicating
itself if the system is continuously fed with the enantiomer precursor. Next
steps will validate these results in an experimental system, like Joyce's
self-replicative ribozyme.</span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://journals.aps.org/pre/abstract/10.1103/PhysRevE.95.032407" target="_blank" title="https://journals.aps.org/pre/abstract/10.1103/physreve.95.032407">https://journals.aps.org/pre/abstract/10.1103/PhysRevE.95.032407</a></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Signalling-based neural networks for cellular computation</span></b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><br />
<br />
Samaniego et al. point out that the kinase/phosphatase signal transduction
networks have properties that lend themselves towards imitating neural networks
built of molecular perceptrons. In particular, the antagonistic nature of the
phosphatase/kinase push-pull motif naturally allows the output level of a
substrate to incorporate a weighted sum over inputs with positive and negative
contributions. Moreover, mechanisms such as zero-order ultrasensitivity allow
the activity level of the substrate to show almost switch-like behaviour
relative to a threshold in this weighted sum. The authors prove certain
properties of cellular neural nets constructed in this way, demonstrating the
possibility of encoding non-linear functions in multi-layer networks. The
question of how practical this would be - particularly due to the peculiar
properties of zero-order ultrasensitivity - remains an open question.</span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.biorxiv.org/content/10.1101/2020.11.10.377077v1" target="_blank" title="https://www.biorxiv.org/content/10.1101/2020.11.10.377077v1">https://www.biorxiv.org/content/10.1101/2020.11.10.377077v1</a></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Functional and morphological adaptation in DNA protocells via
signal processing prompted by artificial metalloenzymes</span></b><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">A protocell made of pure DNA. This protocell is constructed by
annealing two types of ssDNAs produced by rolling circle polymerization from
circular DNA templates. The protocell encapsulates artificial metallozymes that
produces DNA-intercalating chemical. As the intercalating molecule gets
produced, the protocell undergoes morphological changes such as expansion.</span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.nature.com/articles/s41565-020-0761-y" target="_blank" title="https://www.nature.com/articles/s41565-020-0761-y">https://www.nature.com/articles/s41565-020-0761-y</a></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p style="line-height: 107%; margin-bottom: 8pt;"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">A DNA-nanoassembly-based approach to map membrane protein
nanoenvironments</span></b><span style="font-size: 13.5pt; line-height: 107%;"><u1:p></u1:p><o:p></o:p></span></p><p style="line-height: 107%; margin-bottom: 8pt;"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Mapping the nano-environment and the expression levels of
extracellular proteins can reveal a lot of details about the cellular
conditions associated with particular diseases. Different cancer states have
shown different levels of EGFR family proteins and their dimerization states,
especially the formation of heterodimers with Her2 protein. In this article the
researchers have devised an approach to hybridize affibody (small, engineered
proteins for high target specificity)-oligomer conjugates with a nanocomb (a
long DNA strand partially hybridized with shorter DNA oligomers with
overhangs). This nanocomb contains a Her2 binding affibody anti-Her2 attached
to one end as a reference. The other overhangs encode information of their
relative position to the reference, and a common binding domain for the oligos
conjugated with the protein-binding affibodies. The affibody-oligo conjugates
library is added to the concerned protein, and the nanocomb then binds to the
conjugates which are close to the bound reference. These partially hybridised
overhang-oligo complexes are then polymerised and nicked by enzymes, and the
resulting double stranded DNAs are analysed by NGS. This analysis provides
information about which affibodies are bound relatively close to the reference,
and the distance between them. The group has shown that this approach can
distinguish between different cells with different expression levels and
dimerization state of Her2 as a proof of principle.<u1:p></u1:p></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://www.nature.com/articles/s41565-020-00785-0">https://www.nature.com/articles/s41565-020-00785-0</a></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><b><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">Nucleic
acid strand displacement with synthetic mRNA inputs in living mammalian cells</span></b><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;">In this paper,
the authors investigated the efficiency of a basic strand displacement reaction
within living mammalian cells. Probes were designed and modified in order to
minimise the egration of nucleases and to ensure that the probes localise to
the cytoplasm. The cells are engineered to express a target mRNA with the probe
target sequence. In the 3’ UTR. Detection of the target mRNA results in
detectable fluorescence and estimation of the number of mRNA molecules per
cell. Moreover, this system can be used to follow target mRNA localisation in
real-time.</span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><p>
</p><p class="MsoNormal"><span style="font-family: "Segoe UI", sans-serif; font-size: 10.5pt; line-height: 107%;"><a href="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.8b00288">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.8b0028</a></span><span style="font-size: 13.5pt; line-height: 107%;"><o:p></o:p></span></p><div style="box-sizing: border-box;"><div style="box-sizing: border-box;"><div style="box-sizing: border-box;"><div><div style="box-sizing: border-box;"><div><div style="box-sizing: border-box;"><div><div style="box-sizing: border-box;"><p></p></div></div></div></div></div></div></div></div></div>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-50087230655657977292020-11-04T11:02:00.002-08:002020-12-04T03:00:24.634-08:00Storage Wars: A battle of nucleic proportions<p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Reading and writing digital information in TNA</span></b><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">DNA molecules have become a popular information storage system but are
susceptible to degradation in a cell-like environment. In this paper, the
authors suggest the use of the unnatural genetic framework based on TNA. The
backbone structure of this unnatural genetic polymer is recalcitrant to
nuclease digestion. 23 kilobytes of digital information were stored in TNA and
recovered with perfect accuracy after exposure to biological nucleases that
destroyed equivalent DNA messages.</span><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><a href="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00361" title="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00361"><span face=""Segoe UI",sans-serif" style="font-size: 10.5pt;">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00361</span></a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Metastable hybridization-based DNA information storage to allow rapid
and permanent erasure</span></b><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">The authors argue that data stored in DNA in the traditional manner is
hard to wipe clean - it requires enzymes, UV or extreme heat. They propose a
stable but easily-erasable memory, in which single strands carry a memory
location domain and the actual contents of the memory. Multiple distinct
strands with the same memory location domain are included, but only one is
prepared with a "truth" flag (a strand that is complementary to
the memory location domain) whilst the rest are prepared with "false"
flags (chemically modified strands). Data can be read out by performing PCR on
the system, since the modified strands that constitute the false flags cannot
be extended. Data can be easily wiped through a short heating protocol, which
will randomise the flags very quickly. While the method achieves this
functionality pretty well, it is limited - there is no scope to erase and then
re-write data, for example. </span><span style="font-family: "Times New Roman", serif; font-size: 13.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><a href="https://www.nature.com/articles/s41467-020-18842-6" title="https://www.nature.com/articles/s41467-020-18842-6">https://www.nature.com/articles/s41467-020-18842-6</a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Exponential volume dependence of entropy-current fluctuations at
first-order phase transitions in chemical reaction networks</span></b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">In this paper, the divergence of the fluctuations of a chemical switch
as a function of system size is quantified and a critical exponent is
calculated. The chemical reaction scheme of Schlögl model is studied. Here, the
steady state number of a certain chemical species X displays a first order
phase transition as the reaction rates are varied. This paper uses various
methods to analyse the chemical master equation (CME) at the transition and
calculate the variance to find an exponential dependence on system size with a
given exponent. This provides a very readable example of a few methods to
analyse CMEs.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><a href="https://journals.aps.org/pre/abstract/10.1103/PhysRevE.102.022101" target="_blank" title="https://journals.aps.org/pre/abstract/10.1103/physreve.102.022101">https://journals.aps.org/pre/abstract/10.1103/PhysRevE.102.022101</a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Single-particle cryo-EM at atomic resolution</span></b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Cryogenic electron microscopy is used to determine the atomic-scale
structure of biomolecules without needing to form a crystal of the sample, as
is required for x-ray crystallography. In single-particle cryo-EM, a sample
containing a high concentration of the molecule of interest is flash frozen and
imaged repeatedly with a beam of single electrons. The scattered electrons,
that are captured by a camera, form an image of the sample which is used to
reconstruct the shape of the molecule of interest. Here the authors report
three improvements that brought the resolution of cryo-EM below 2 Angstroms; an
electron source with a narrow energy spread that reduced chromatic aberrations,
a more effective energy filter that can separate out useful elastically and useless
inelastically scattered electrons, and an advanced camera and reconstruction
algorithm capable of capturing scattered electrons with high spatio-temporal
resolution. In a reconstruction of a 5-fold symmetric human membrane channel
protein, small molecule coordination, alternative amino acid conformations and
side chain variations were resolved. Further, using an advanced reconstruction
method of a 24-fold symmetric mouse protein, the scattering potential of
hydrogen atoms could be resolved in the most ordered parts of the structure,
enabling analysis of the hydrogen-bonding network in the protein. Atomic
resolution cryo-EM will provide insights into the mechanical function of
biomolecules and improve structure-based drug discovery.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; mso-margin-bottom-alt: auto; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><a href="https://www.nature.com/articles/s41586-020-2829-0" target="_blank" title="https://www.nature.com/articles/s41586-020-2829-0">https://www.nature.com/articles/s41586-020-2829-0</a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 0cm;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">The evolution of DNA-templated synthesis as a tool for materials
discovery</span></b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><br />
<br />
Control of reactivity and product structure is one of the main challenges
during the design of chemical reactions. A method to introduce said control is
DNA-templated synthesis (DTS), where DNA-bound chemicals are assembled over a
complementary DNA strand that acts as a template. The focus of this review is
the potential application of DTS for the directed evolution of chemicals, by
several cycles of template mutation and selection. The authors enumerate all
the possible DTS mechanisms that allow the implementation of selection cycles,
the chemical reactions templated with said mechanisms, and the challenges they
face.</span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 0cm;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><a href="https://pubs.acs.org/doi/10.1021/acs.accounts.7b00280" target="_blank" title="https://pubs.acs.org/doi/10.1021/acs.accounts.7b00280">https://pubs.acs.org/doi/10.1021/acs.accounts.7b00280</a><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Nanopore-based DNA hard drives for rewritable and secure data storage</span></b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto; text-align: justify;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Solid-state nanopores have been
demonstrated to be powerful molecular sensors for detecting nanoscale objects.
In this article, a long DNA scaffold is use as a “hard drive” to write, erase,
and rewrite data on, and read it out by passing the strand through a
solid-state nanopore. The data sites are functionalised with small
DNA-overhangs which can be hybridised with unique complementary biotinylated
strands. The unhybridised and hybridised strands generate weaker and stronger
current signals respectively when passed through the nanopore which can be read
as 0 or 1. Thus, a combination of data sites can encode meaningful data in binary
format. To erase the data, another fuel strand is added which utilises a short
toehold at the end of the biotynilated strands to detach it from the overhangs
which can be reused again to encode different data. To refine this approach,
the group has also demonstrated the utilization of two separate encoding sites
(address sites and data sites) simultaneously to encode both the data and its
sequence. Moreover, they showed the use of a physical “key” to encrypt the data
on the DNA hard drive without which the readout does not match the actual
encoded data.<o:p></o:p></span></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 8.25pt; mso-margin-top-alt: auto;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><a href="https://pubs.acs.org/doi/full/10.1021/acs.nanolett.0c00755" target="_blank" title="https://pubs.acs.org/doi/full/10.1021/acs.nanolett.0c00755">https://pubs.acs.org/doi/full/10.1021/acs.nanolett.0c00755</a><o:p></o:p></span></p><p class="MsoNormal" style="background: white; line-height: normal; margin-bottom: 3.75pt; mso-outline-level: 1;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Toehold-mediated strand displacement reaction for
dual-signal electrochemical assay of Apolipoprotein E genotyping</span></b></p><p class="MsoNormal" style="line-height: normal; margin-bottom: 0cm;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Apolipoprotein E (ApoE) is a polymorphic gene which has been identified
as an important genetic determinant for Alzheimer's disease. In the human
population six genotypes of ApoE exist, with distinct risks associated with
each. In this paper, the authors developed a toehold-mediated strand
displacement-based approach to genotype ApoE. Using an electrochemical
detection system, the authors could detect the presence of absense of mutations
at 2 codons within the gene. This system allowed for systematic
characterisation of ApoE genotype. </span></p><p>
</p><p class="MsoNormal" style="line-height: normal; margin-bottom: 0cm;"><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><a href="https://pubs.acs.org/doi/pdf/10.1021/acssensors.0c01511">https://pubs.acs.org/doi/pdf/10.1021/acssensors.0c01511</a><o:p></o:p></span></p><div style="box-sizing: border-box;"><div style="box-sizing: border-box;"><div style="box-sizing: border-box;"><div><div style="box-sizing: border-box;"><div><br /></div></div></div></div></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;">
<strong><span style="background-color: white;"><span style="color: #222222;">Proton-driven transformable nanovaccine for cancer immunotherapy</span></span></strong><br />
<br />
They developed a polymer-peptide conjugate that forms nanoscale sphere at normal pH. The polymer gets uptaken by cancer cells. When the polymer is at the endosome, it changes conformation to micrometre sized sheet and destroys the endosome. Then the peptide gets presented outside of the cell to trigger an inflammation response.</div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><br /></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><a href="https://doi.org/10.1038/s41565-020-00782-3" rel="noreferrer noopener" tabindex="-1" target="_blank" title="https://doi.org/10.1038/s41565-020-00782-3">https://doi.org/10.1038/s41565-020-00782-3</a></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;"><br /></span></b></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><b><span face=""Segoe UI", sans-serif" style="font-size: 10.5pt;">Light-activated signaling in DNA-encoded sender–receiver
architectures</span></b></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><br /></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;">In this last work from De Greef's lab, the authors present the last developments on their compartmentalized DNA strand displacement platform BIO-PC. More precisely, they show how with the introduction of a photo-cleaving group in a DNA duplex, combined with different tunable variables, this system allows them to implement localized spatial activation of strand displacement circuits with controlled diffusion. Based on this, they demonstrate how catalytic activation can transmit a given signal further than conventional activation and that this system allows them to build a spatially-coded AND gate.</div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><br /></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"><a href="https://pubs.acs.org/doi/10.1021/acsnano.0c07537" title="https://pubs.acs.org/doi/10.1021/acsnano.0c07537">https://pubs.acs.org/doi/10.1021/acsnano.0c07537</a></div><div style="box-sizing: border-box; font-family: "Segoe UI", system-ui, "Apple Color Emoji", "Segoe UI Emoji", sans-serif; font-size: 14px;"></div></div>Francesca Smithhttp://www.blogger.com/profile/11533120403105821354noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-15119841588043555142020-07-17T03:03:00.000-07:002020-07-17T03:08:54.485-07:00All about that base (or at least, more than one article about pH-triggered nucleic acid systems)<b>pH-Controlled Detachable DNA Circuitry and Its Application in Resettable Self-Assembly of Spherical Nucleic Acids</b><br />
<a href="https://pubs.acs.org/doi/abs/10.1021/acsnano.0c02329">https://pubs.acs.org/doi/abs/10.1021/acsnano.0c02329</a><br />
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Through Hogsteen interactions, DNA can form triple helices that are sensitive to PH variations. Triplexes form when pH is low, and break when pH is high. In this paper, the authors harness the formation of triplexes to build toeholds for strand displacement reactions. The kinetics of the displacement reactions are dependent of the formation of the triple helix, and they can even be stopped or resumed by changing the pH in the solution. Finally, they build a system with 2 triple helices that activate at different pH and can aggregate or disaggregate gold nanoparticles, just by changing the pH, without producing waste duplexes.<br />
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<b>Preparation of a Millimeter-Sized Supergiant Liposome That Allows for Efficient, Eukaryotic Cell-Free Translation in the Interior by Spontaneous Emulsion Transfer</b><br />
<a href="https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00173">https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00173</a><br />
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This paper describes an improved protocol to increase the efficiency of eukariotic cell-free translation. The conventional protocols are limited by high concentrations of sucrose that affect protein translation inside vesicles. They optimized the preparation conditions to permit supergiant unilamellar vesicle (SGUV) formation at a much lower concentration of sucrose that has almost no effect on translation. Under the optimized conditions, they observed a high rate of succesful SGUV formation (>90%) and a decent stability of the formed SGUVs (>60 min). These SGUVs are expected to serve as research tools in cell-free synthetic biology and as foundations for artificial cell-based biosensors.<br />
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<b>Rational design of aptamer switches with programmable pH response</b><br />
<a href="https://www.nature.com/articles/s41467-020-16808-2">https://www.nature.com/articles/s41467-020-16808-2</a><br />
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Non-conventional base-pairs (Hoogsteen, Wobble) can introduce additional degree of tuneability to standard Watson- Crick base-pairs. A change in the environmental pH, which changes the propensity of such base-pairs, can be utilised to fine tune DNA-based systems. In this paper, the authors describe a designed strand where a linker domain forms a DNA triple helix at lower pH, and therefore destabilises a duplex of an ATP aptamer and a displacement domain, and thereby allows the aptamer to bind ATP with a 1000 fold higher binding efficiency compared to an elevated pH. In a separate approach, they demonstrated another design where the aptamer binds ATP better at higher pH. By combining these two feature in orthogonal fashion, the authors demonstrate that it is indeed possible to design an aptamer which binds its target in a very narrow pH range. Furthermore, since the actual structure of the aptamer sequence is not altered during the pH change, and the added domains show the pH responsiveness, the authors argue that this strategy can turn any aptamer into a pH switch with the need minimal alterations of the sequences.<br />
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<b>DNA Logic Circuits Based on Accurate Step Function Gate</b><br />
<a href="https://ieeexplore.ieee.org/abstract/document/9121273">https://ieeexplore.ieee.org/abstract/document/9121273</a><br />
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A step function gate is achieved by combining step activation and a threshold module. This module was used to construct AND, OR, and XOR gates. The result was simulated using DSD.<br />
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<b>Aminoacyl-tRNA Synthetases </b><br />
<a href="https://rnajournal.cshlp.org/content/early/2020/04/17/rna.071720.119.abstract">https://rnajournal.cshlp.org/content/early/2020/04/17/rna.071720.119.abstract</a><br />
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This is a comprehensive review of Aminoacyl-tRNA synthetases (aaRS), the family of enzymes responsible for charging transfer-RNAs (tRNA) with their cognate amino acid (AA). There is a unique aminoacyl-tRNA synthetase for each of the 20 amino acids. The accuracy of protein synthesis relies on both the matching of mRNA:tRNA duplexes in the ribosome, and the accuracy of amino acid:tRNA charging in aaRSs. AaRSs function as templates for the specific dimerisation of the two types of genetic molecule, amino acids and nucleic acids. Therefore these are the only enzymes that really do the job of converting the genetic code from nucleic acids to amino acids.<br />
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Charged tRNAs are synthesised in two phases (AA binding and attack, followed by tRNA binding, hybridisation, and release) coupled to the turnover of one molecule of ATP to AMP. Some aaRSs exhibit post-charging editing, indicating that kinetic proofreading may be used to increase specificity beyond the equilibrium limit.<br />
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<b>Kinetic asymmetry allows macromolecular catalysts to drive an information ratchet</b><br />
<a href="https://www.nature.com/articles/s41467-019-11402-7">https://www.nature.com/articles/s41467-019-11402-7</a><br />
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The present paper details how, in molecular systems, due to the local lack of detailed balance between the fluxes in macromolecular machines, it is possible to describe the working of out-of-equilibrium systems via two different mechanisms: (a) energy ratchets (in which the driving force of the system is a change in the external conditions -such as redox potential light or pH- that drives the system to a new equilibrium) and (b) information ratchets (in which a catalyst biases the system by controlling and favouring the energy barriers we want). The paper, besides making the distinction, and showing the criteria to clasify molecular machines, shows different examples of each coming from different parts of chemistry explaining what properties of the system arise from underlying kinetic asymmetries.<br />
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<b>Programming and simulating chemical reaction networks on a surface</b><br />
<a href="https://doi.org/10.1098/rsif.2019.0790">https://doi.org/10.1098/rsif.2019.0790</a><br />
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Clamons, Qian and Winfree present an exploration of a previously-introduced surface CRN model of molecular computing. They present an authoritative review of the topic, and then demonstrate how to deal with some of the challenges of implementing complex surface-based CRNs, in particular issues with asynchronicity. The authors then show how these strategies can be used to build an extremely broad range of interesting molecular circuits. I have no concerns about the accuracy of the results.<br />
The examples and supporting code are extremely effective pedagogically and the paper is fun to read - it should inspire theorists and experimentalists alike.<br />
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<br />TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-71270917991499545162020-06-24T10:36:00.000-07:002020-06-24T10:36:19.273-07:00Reading List: Rats on the latest celebrity diet<div style="box-sizing: border-box;">
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<span style="font-family: inherit;"><b>Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging</b></span></div>
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<a href="https://www.sciencedirect.com/science/article/pii/S0092867420301525" rel="noreferrer noopener" tabindex="-1" target="_blank" title="https://www.sciencedirect.com/science/article/pii/s0092867420301525"><u><span style="font-size: 11pt;"><span style="font-family: inherit;">https://www.sciencedirect.com/science/article/pii/S0092867420301525</span></span></u></a></div>
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<span style="font-size: 10.5pt;"><span style="font-family: inherit;">Calorie Restriction (CR) leads to slow down of ageing in mammals. The statement has been passed around and been a cause for scientific debates. What is missing to substantiate the former claim is a CR cell atlas across body tissues. The research observes (in mice) the systemic effects of aging and CR on different tissues evaluated in terms of cell type composition, tissue-specific molecular programs, regulatory transcription factors (TFs), and cell-cell communication networks. It was observed that fewer lipid droplets accumulated in livers of the experimental group (excess lipids cause atherosclerosis: high cholesterol levels). An accumulation of senescent cells was found in the control group (senescence is caused by gradual telomere attrition at the ends of DNA reducing reproducibility) as compared to the experimental group. The number of immune cells in nearly every tissue studied dramatically increased as control rats aged but was not affected by age in rats with restricted calories. Levels of the transcription factor Ybx1 were altered by the diet in 23 different cell types (out of 40 chosen). The scientists believe Ybx1 may be an age-related transcription factor and are planning more research into its effects.</span></span></div>
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<b><span style="font-size: 10.5pt;"><span style="font-family: inherit;">I</span></span><span style="font-size: 14px;">nterfacing gene circuits with microelectronics through engineered population dynamics</span></b></div>
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<span style="font-size: 14px;"><a href="https://advances.sciencemag.org/content/advances/6/21/eaaz8344.full.pdf">https://advances.sciencemag.org/content/advances/6/21/eaaz8344.full.pdf</a></span></div>
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<span style="font-size: 14px;">In this paper, the authors propose an alternative to fluorescent reporters to analyse bacterial population behaviours. They interfaced synthetic biology with microelectronics through engineered population dynamics that regulate the accumulation of charged metabolites. During bacterial growth, charged ions are naturally released because of metabolic processes and the environment becomes more conductive, which decreases the impedance to electrical current. To control bacterial populations, they engineered a genetic circuit to express a bacterial killing gene that is activated upon the addition of an external stimulus. Therefore the bacterial population resembles a resistor, which is controlled by a genetic circuit. The plan is to implement this regulatory system in a microelectronic platform where several chambers may contain unique genetic circuits, connected via electrodes to an impedance output system.</span></div>
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<span style="font-size: 14px;"><b>Isothermal digital detection of microRNAs using background-free molecular circuit</b></span></div>
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<span style="font-size: 14px;"><a href="https://advances.sciencemag.org/content/6/4/eaay5952/tab-article-info">https://advances.sciencemag.org/content/6/4/eaay5952/tab-article-info</a></span></div>
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<span style="font-size: 14px;">Micro-RNAs have emerged as a class of potential biomarkers due to an increasing amount of research identify their disregulation in several diseases. But detection of very low concentration of mi-RNA with high accuracy poses a challenge for the existing techniques. One of them is background noise and nonspecific amplification of products which renders low-concentration detection of microRNA practically impossible. This article describes the utilization of already existing PEN-DNA toolbox coupled with a leak absorption mechanism to eliminate background noise. This method generates a fluorescence signal specific for the amplification of the signal strand which is produced upstream by the microRNA. The overall system can detect microRNA concentration as low as 1fM.</span></div>
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<b>Information-theoretical bound of the irreversibility in thermal relaxation processes</b></div>
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<a href="https://doi.org/10.1103/PhysRevLett.123.110603">https://doi.org/10.1103/PhysRevLett.123.110603</a></div>
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Relaxation processes must produce entropy as they cannot be quasistatic or reversible. Here Shiraishi dervied a stronger than 2nd law bound on the entropy production in for a relaxation process. The bound on the entropy production is given by the Kullback divergence between the initial and current time distribution of the system. Hence if the initial and final distributions are very different then there MUST be a large entropy production.</div>
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Brings up an interesting way of describing permissable trajectories using information geometry (interpret KL div as an euclidean distance).</div>
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<span style="font-size: 14px;"><b>Cancer Diagnosis with DNA molecular computation</b></span></div>
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<span style="font-size: 14px;"><a href="https://www.nature.com/articles/s41565-020-0699-0">https://www.nature.com/articles/s41565-020-0699-0</a></span></div>
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<span style="font-size: 14px;">A simplified winner takes all DNA computing scheme using 4 miRNA input was used to diagnose lung cancer cells. The network was trained in silico and realised with DNA.</span></div>
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<span style="font-size: 14px;"><b>The Synthesis Success Calculator: Predicting the Rapid Synthesis of DNA Fragments with Machine Learning</b></span></div>
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<span style="font-size: 14px;"><a href="https://www.biorxiv.org/content/10.1101/2020.06.05.136820v1?rss=1">https://www.biorxiv.org/content/10.1101/2020.06.05.136820v1?rss=1</a></span></div>
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<span style="font-size: 14px;">The efficiency of DNA synthesis is sequence-dependent; however, the effects of each sequence property is not well understood. To address this problem, the authors design a random forest classifier to quantify the effects of 38 sequence properties in the synthesis of more than one thousand DNA sequences. The conclusion is that only 9 properties are relevant, the most important being the length of the longest repetitive sequence within the DNA fragment (26 nt is the limit), followed by the strand GC content (between 29-63%). A predictive tool is available online to estimate the success of your DNA synthesis orders and suggest changes for synonym codons: https://salislab.net/software/</span></div>
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<b>A Dynamical Biomolecular Neural Network </b></div>
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<a href="https://ieeexplore.ieee.org/document/9030122">https://ieeexplore.ieee.org/document/9030122</a></div>
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Artificial neural networks (ANN) are amongst the most used computation models in machine learning and they have been proved to be extremely powerful for classification tasks in silico. Some DNA strand displacement implementations of these systems have been developed in the past, but this circuits were limited by its size, implementability and inability to be rebooted. In the present work, Ron Weiss and collaborators described a theoretical implementation of a perceptron (the functional unit of an ANN) in a biochemically feasable CRN. In the CRN two mutually sequestering chemical species with their production and degradation rates, encode the positive and negative weights of the perceptron. Based in this design, the authors demonstrate that perceptrons can be extended into deeper networks and implement complex behaviours.</div>
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<span style="font-size: 14px;"><b>Small RNA driven feed-forward loop: Fine-tuning of protein synthesis through sRNA mediated cross-talk</b></span></div>
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<span style="font-size: 14px;"><a href="https://arxiv.org/abs/1912.06786">https://arxiv.org/abs/1912.06786</a></span></div>
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<span style="font-size: 14px;">Tej and Mukherji present an analysis of an sRNA-mediated feed-forward loop, in which a particular sRNA not only promotes translation of a protein, but also translation of a second protein (a sigma factor) that in turn promotes transcription of the mRNA of the first protein. They show that competition between the mRNA for the sRNA leads to a non-monotonic effect of sigma factor transcription rate on output protein levels, and that relative fluctuations are smallest at the point of maximal output protein levels.</span></div>
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TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-56383516304904742772020-05-22T09:26:00.000-07:002020-05-22T09:26:03.807-07:00New paper in Nature Communications introducing a new strategy to build synthetic DNA-based networks that function more like similar systems in living cells.<div class="MsoNormal" style="line-height: 115%; margin-bottom: 10.0pt; mso-layout-grid-align: none; text-autospace: none;">
<b><span lang="EN"><a href="https://doi.org/10.1038/s41467-020-16353-y" target="_blank">Design of hidden thermodynamic driving for non-equilibrium systems via mismatch elimination during DNA strand displacement</a></span></b><span lang="EN"><o:p></o:p></span></div>
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<b>Natalie E. C. Haley, Thomas E. Ouldridge, Ismael Mullor Ruiz, Alessandro Geraldini, Ard A. Louis, Jonathan Bath & Andrew J. Turberfield </b></div>
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<span lang="EN">In recent years, scientists have sought to construct molecular systems that
reproduce the complexity of life in a synthetic (human-designed-and-built)
setting. On the one hand, building a synthetic version of a natural system
would help us to understand the natural systems more deeply, in the same way
that actually building a walking robot demonstrates just how impressive
locomotion is in the animal kingdom. On the other hand, synthetic molecular
systems have great potential as an engineering platform of the future, adding
control and designability to the power and versatility of nature.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 115%; margin-bottom: 10.0pt; mso-layout-grid-align: none; text-autospace: none;">
<span lang="EN">The use of synthetic DNA as an engineering material has been particularly
successful, leading to the growth of the field of DNA nanotechnology. Bespoke
single strands of DNA can be ordered from chemical suppliers, as easily as
personalised greetings cards. Sequences of the bases - the familiar A, C, G and
T of the genetic code - can be specified at will. These bases interact in a
highly specific and predictable way, with A-T and C-G base pairs allowing the
formation of the famous DNA double helix. If a set of strands is well designed,
they can spontaneously self-assemble into a complex structure, or implement a
computational calculation, when mixed [1,2].<o:p></o:p></span></div>
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<span lang="EN">Although these results are impressive, we are a long way from the power and
flexibility of the natural systems that inspire us. One important aspect is the
following: a defining feature of life at the molecular scale is constant
activity; a cell isn't a static structure that assembles once with all its
components in place. Instead, the molecular circuits inside are constantly on
the go, allowing for growth, replication and maintenance of the cell in a
healthy state, ready to respond to changes in the outside world. Key components
(such as enzymes) participate in reactions but are then recovered, rather than
being consumed, allowing them to continue to operate.<o:p></o:p></span></div>
<div class="MsoNormal" style="line-height: 115%; margin-bottom: 10.0pt; mso-layout-grid-align: none; text-autospace: none;">
<span lang="EN">Physicists would say that these living systems operate out of equilibrium,
and must continuously consume chemical fuel such as ATP to do so [3]. These
fuel molecules must be stable on their own, but provide a large energy boost
when they are broken down - just like the fuel in a car. In this work we present
a new strategy for designing similar behaviour in DNA-based systems: we place
mismatched base pairs (not A-T or C-G) in the interior of double-stranded DNA
reactants. These mismatches are eventually eliminated when the reactants are
converted into products. However, the reactants are essentially stable, despite
the overwhelming favourability of mismatch-free products, because the
destabilizing mismatches are well hidden. The effect of the mismatches is only
felt when additional DNA strands - the key (enzyme-like) species mentioned
above - trigger the system. These key species are recovered, as in natural
systems, and the elimination of hidden mismatches fuels the process in a
controlled way, analogous to the role of ATP in natural systems. <o:p></o:p></span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhwRE3kkdzIQ75XIIM6n0Hgh3SYA08Tq5J3h6I6B97PuV8EADk1YT-vKMciI39HE9SpFHjTuaN_3zez4qFLuCmRoHbiuYIwEOqysmEueGTRkNsbwxcpb9uXo_xuvG2zTVeg-Dxx52GrI5-o/s1600/Basic+fig+2.png" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhwRE3kkdzIQ75XIIM6n0Hgh3SYA08Tq5J3h6I6B97PuV8EADk1YT-vKMciI39HE9SpFHjTuaN_3zez4qFLuCmRoHbiuYIwEOqysmEueGTRkNsbwxcpb9uXo_xuvG2zTVeg-Dxx52GrI5-o/s1600/Basic+fig+2.png" /></a></div>
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<br /><div class="MsoNormal">
<span lang="EN"><i>Fig. 1. Analogy between hidden thermodynamic driving in our DNA-based
system and ATP in a natural context. The breakdown of ATP releases energy, but
is slow unless an enzyme is present to lower activation barriers. Similarly,
the conversion of reactants to products in our DNA system eliminates a mismatch
“X” and therefore releases energy; however, the hiding of the mismatch makes
the reaction slow unless a triggering strand is present. </i><o:p></o:p></span></div>
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<br /></div>
<div class="MsoNormal">
<span style="font-family: inherit;">[1] Rothemund, P. W. K. Folding DNA to create nanoscale
shapes and patterns. Nature 440, 297 –302 (2006).<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="font-family: inherit;">[2] Cherry, K. M. & Qian, L. Scaling up molecular
pattern recognition with DNAbased winner-take-all neural networks. Nature 559,
370–376 (2018).<o:p></o:p></span></div>
<span style="line-height: 107%;"><span style="font-family: inherit;">[3] Ouldridge, T. E. The importance of
thermodynamics for molecular systems, and the importance of molecular systems
for thermodynamics. Nat. Comput. 17, 3-29 (2018). </span></span>TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-67116362841011355652020-05-14T02:23:00.003-07:002020-05-14T02:23:45.901-07:002 weeks of the reading group - plenty of DNA nanotechnology, from assembly through detection to signalling<b>A fluorescence assay for microRNA let-7a by a double-stranded DNA modified gold nanoparticle nanoprobe combined with graphene oxide</b><br />
<a href="https://pubs.rsc.org/en/content/articlelanding/2020/an/c9an02274k/unauth#!divAbstract%C2%A0%C2%A0" target="_blank">https://pubs.rsc.org/en/content/articlelanding/2020/an/c9an02274k/unauth#!divAbstract </a><br />
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The authors used a cascaded toehold-mediated strand displacement reaction as a biosensor for miRNA. This required both a fuel strand and a target strand and the target strand was recycled as part of the reaction, to amplify the signal for detection.<br />
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<b>Orthogonal regulation of DNA nanostructure self-assembly and disassembly using antibodies</b><br />
<a href="https://www.nature.com/articles/s41467-019-13104-6">https://www.nature.com/articles/s41467-019-13104-6</a><br />
<br />
Despite tremendous developments in DNA nanotechnology and antibody research, there have been very few examples of designing a DNA-based network specifically responsive to a particular biomarker. Here the researchers demonstrate the design of an antigen-conjugated split-input invader strand which increases the rate of a TMSD reaction when it binds a specific antibody. Different antibody-controlled reactions can be triggered orthogonally in a solution with several reaction components without any crosstalk. The output strands of these reactions can be specifically tuned to trigger a dynamic self-assembly of DNA tiles into a nanostructure or the disassembly of it into individual building blocks.<br />
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<b>Availability-Driven Design of Hairpin Fuels and Small Interfering Strands for Leakage Reduction in Autocatalytic Networks</b><br />
<a href="https://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.0c01229">https://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.0c01229</a><br />
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Enzymes are hard to use in detection and amplification circuits for eg. diagnostics. Nucleic acids provide an alternative, but are subject to unintended leaks in the absence of input. In this article, the authors seek to avoid leak reactions by sequestering nucleotides that are predicted - based on simple thermodynamic models - to trigger these leaks. However, success is limited because sequestering these nucleotides, if effective, also interferes with the intended reactions in the presence of a trigger.<br />
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<b>Nicking-Assisted Reactant Recycle To Implement Entropy-Driven DNA Circuit</b><br />
<a href="https://pubs.acs.org/doi/10.1021/jacs.9b07521">https://pubs.acs.org/doi/10.1021/jacs.9b07521</a><br />
<br />
Molecular circuits implemented using nucleic acid nanotechnology typically produce double-stranded waste complexes when they run. In this work, the authors propose that these waste complexes can be reconverted into active reaction-ready multi-stranded "gates" through the action of a nicking enzyme that cleaves the backbone of one of the fuel strands. This approach means that, in the simplest of settings, only a supply of single-stranded molecules (rather than harder-to-produce gate complexes) is required to sustain circuit function.<br />
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Although impressive, these circuits show a fairly high level of unwanted leak reactions. Moreover, the recycling of waste does not occur indefinitely, and complex cascaded circuits cannot be produced due to sequence constraints. The article really emphasizes the need for in situ production of nucleic acid complexes.<br />
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<b>ATP-Triggered, Allosteric Self-Assembly of DNA Nanostructures</b><br />
<a href="https://pubs.acs.org/doi/10.1021/jacs.9b10272">https://pubs.acs.org/doi/10.1021/jacs.9b10272</a><br />
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Trigger-responsive DNA self-assembly is commonly observed in several biological processes and have potential application in sensing and smart biomaterials. In this article, the authors show the design of a double stranded DNA which, upon binding with ATP, can form T-junctions among themselves to make larger self-assembled structures. In the absence of ATP, such structures are not formed. It also demonstrated that the ATP-binding and subsequent change in the overall conformation of the DNA is the crucial part of stimulus-responsiveness.<br />
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<b>Fluorogenic probe for fast 3D whole-cell DNA-PAINT</b><br />
<a href="https://www.biorxiv.org/content/10.1101/2020.04.29.066886v1">https://www.biorxiv.org/content/10.1101/2020.04.29.066886v1</a><br />
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DNA-PAINT is a super-resolution microscopy method that uses fluorophore-modified DNA labels to image some target DNA strands. However, DNA-PAINT requires a high concentration of labels, resulting in high levels of background fluorescence during the imaging. In addition, the binding speed of the labels can hinder DNA-PAINT by reducing its imaging speed. This research introduces a new type of label for DNA-PAINT. The new labels reduce its fluorescence emission in solution by attaching a dedicated quencher. Since no hairpin in the label is needed for quenching the fluorescence, the binding rate to the target is increased. The unbinding rate is increased as well by adding mismatches between target and label. The new label design results in a higher imaging speed while still producing a low background fluorescence.<br />
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<b>Information Coding in Reconfigurable DNA Origami Domino Array</b><br />
<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202003823">https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202003823</a><br />
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DNA origami domino arrays, whose building blocks adopts two different conformations, were used to encrypt information in their 2D pattern. Additionally, strand-displacement was used to reveal overhangs with specific sequence that encodes information.<br />
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<b>Non-enzymatic primer extension with strand displacement</b><br />
<a href="https://doi.org/10.7554/eLife.51888">https://doi.org/10.7554/eLife.51888</a><br />
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Non-enzymatic template copying reactions are the precursor to biological self-replication. Separating the duplex that forms between parent and daughter strands after templated copying is key to ensuring independent function of the daughter and cyclical copying of the template. Cycling environmental conditions (hydration/pH/temperature) have been posed as solutions to the duplex separation problem. However, here an RNA template is copied by primer extension and simultaneously the previous daughter (blocker) is displaced from the template by a strand invasion reaction, enabling further extension.<br />
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Here a template RNA is occupied by a partially complete primer strand and a blocker strand (equivalent to an earlier daughter) with a large free toehold. The blocker strand prevents extension of the primer by binding to the next extension site thereby occluding the template. An invader strand is introduced that binds the blocker toehold and then invades the blocker-template bond at the extension site. The strand invasion interaction opens the template which triggers the extension of the primer. Increase in primer length is confirmed by PAGE.<br />
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<b>Artificial molecular motors</b><br />
<a href="https://pubs.rsc.org/en/content/articlelanding/2017/cs/c7cs00245a#!divAbstract">https://pubs.rsc.org/en/content/articlelanding/2017/cs/c7cs00245a#!divAbstract</a><br />
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Living cells use a plethora of molecular motors to carry out key biological processes. Muscle contraction, production of ATP from ADP, DNA transcription are all examples of molecular motors at different scales. Development of synthetic motors is a contemporary field of research in nanoscience with one application being drug delivery to cancer cells. Molecular switches and motors are 2 different types of molecular machines. In both these machines, a change in relative position of components with respect to each other occurs; the cycle of a motor, however, can perform work. Present research explains the physics of these molecular machines utilizing the chemistry (steric interactions, effect of pH, acidity) of chemical compounds.<br />
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This review focuses on molecular devices constructed using organic chemistry, rather than biomolecules. Research groups have been developing nanocars and are actively working on making them unidirectional. Unidirectionality in the presence of light has been shown at microscale (rotation of an alkene doped glass rod) and macroscale (droplet along a photo-responsive surface). Molecular motors have evolved from elegant proof-of-principles to advanced designs, the main question remains is how to convert this motion into useful functionality?<br />
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<b>Encoding multiple digital DNA signals in a single analog channel </b><a href="https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkaa303/5825621">https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkaa303/5825621</a><br />
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DNA strand displacement systems' output readouts are normally limited by the different amount of fluorophores that can be implemented and read in the fluorescent reporter systems. This limitation usually results in systems with a very limited number of outputs: one possible output per fluorescent channel. In the present work the authors propose method to overcome this limitation based on representing multiple discrete bits of information in a single analog fluorescent signal. With this method, optimizing the toehold and sequence design they are able to encode reliably a 4-bit signal in a single fluorescent signal - they could detect the presence of 4 different genes with a single fluorophore - as well as applying the methodology to two channels simultaneously, thus increasing remarkably the number of possible readable outputs of a circuit.<br />
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<b>A Coculture Based Tyrosine-Tyrosinase Electrochemical Gene Circuit for Connecting Cellular Communication with Electronic Networks</b><br />
<a href="https://pubs.acs.org/doi/abs/10.1021/acssynbio.9b00469">https://pubs.acs.org/doi/abs/10.1021/acssynbio.9b00469</a><br />
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In this paper, authors reported a cell-based synthetic biology−electrochemical device. The system builds on the tyrosinase-mediated conversion of tyrosine to L-DOPA and L-DOPA quinone which are both redox active and can be detected by a gold electrode. The use of cell consortia allows for divisions of labor to lower any particular metabolic burden in the production of tyrosine and tyrosinase. To induce the expression of these molecules, they use quorum sensing signalling molecules and pyocyanin that are secreted by Pseudomonas aeruginosa.TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-69225885013871008622020-04-12T11:59:00.000-07:002020-04-12T11:59:23.804-07:00Reading group - lots of novel DNA systems, including cryptography!<b>Self-Assembly of DNA Origami Heterodimers in High Yields and Analysis of the Involved Mechanisms</b><br />
<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201902979">https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201902979</a><br />
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DNA nanostructures can be formed of several different DNA origami units that bind between themselves with complementary extended strands. However, the binding reaction between two origamis doesn't have a perfect yield (80~90%), which decreases exponentially with the number of origami units added.<br />
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The paper demonstrates that the source of imperfect yield when binding origamis is not due to the stability of the binding, but all the possible competing reactions. Proper purification of each origami piece, especially with an agarose gel in low salt conditions, removes the excess of DNA strands used to build these origamis. The removal of excess strands helps to reduce the homodimers and other large structures, increasing binding yield up to 99%.<br />
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<b>Coupling of DNA Circuit and Templated Reactions for Quadratic Amplification and Release of Functional Molecules</b><br />
<a href="https://pubs.acs.org/doi/abs/10.1021/jacs.9b05688">https://pubs.acs.org/doi/abs/10.1021/jacs.9b05688</a><br />
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By putting a four base-pair overhang with a photocatalysis modification onto the final product of catalysed hairpin assembly, the response to the presence of an initiating strand was further amplified, resulting in quadratic amplification.<br />
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<b>Nucleobase-Templated Polymerization: Copying the Chain Length and Polydispersity of Living Polymers into Conjugated Polymers. </b><br />
<a href="https://doi.org/10.1021/ja809613n">https://doi.org/10.1021/ja809613n</a><br />
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In the absence of a template, step polymerisation processes often offer little control over the average average length and width of the distribution of polymers produced. The average molecular weight and the spread of the molecular weight distribution of an ensemble of polymers have significant effects on the macroscopic properties, such as viscosity, of the polymer bulk.<br />
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Living systems use templates to direct the synthesis of polymers. The template functions as a guide for information transfer, but also fixes the polymer length and narrows the length distribution.<br />
In this work, a thymine block template polymer was used to direct the synthesis of another polymer. To achieve a narrow polymer length distribution, the templates must also have a narrow length distribution. The template was created by 'living polymerisation'. Living polymerisation is a catch-all for polymerisation processes in which termination is prohibited and the initiation rate is much faster than the elongation rate, leading to a smaller variance in polymer length.<br />
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Once the templates were assembled, they could be used to grow templated polymers. After the templated polymers were elongated, they were non-autonomously separated from the template, which did not cause the polymers to fragment. The distribution of templated polymer lengths had an average close that of the templates and a narrow spread. By contrast, polymerisation with incompatible templates and in the absence of templates resulted in short polymers with broad length distributions.<br />
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This is experimental confirmation that templates, regardless of informational content, are unsurprisingly effective in narrowing and controlling polymer length distributions.<br />
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<b>De novo design of protein logic gates</b><br />
<a href="https://science.sciencemag.org/content/368/6486/78">https://science.sciencemag.org/content/368/6486/78</a><br />
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In the present work, the lab of David Baker demonstrate that they can design and create different alpha helical bundle motifs with tunable binding affinities. These motifs bind orthogonally only to programmed domains. With these domains, incorporated into transcription factors via fusion proteins, the authors are able to implement the six basic Boolean Logic Gate functions in genetic circuits that work independently of the type of host cell.<br />
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<b><span style="font-family: inherit;">DNA origami cryptography for secure communication</span></b></div>
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Biomolecular cryptography exploits theromdynamically controlled biomolecular interactions instead of typical computational schemes for the same level of encryption. This paper suggests a DNA origami-based encryption method with a key size of 700 bits (for comparison, typical RSA key length is 1024 bits to ensure day-to-day web browsing security).</div>
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Alice wants to pass a secret message to Bob. Alice converts the message to a spot pattern (based on binary conversion of alphabets in the message and their positions). A custom DNA scaffold sequence is routed through a defined geometry covering this spot pattern. M-strands (biotinylated message strands), corresponding to the spot patterns, are hybridized onto the scaffold strand.</div>
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The scaffold is now passed onto Bob. Bob holds the staples to fold the DNA origami structures to reveal the biotin patterns. He then uses streptavidin to make the biotin patterns recognizable and obtain the hidden secret message. The security is maintained by unpredictability of the sequence, length and folding of the scaffold strand.</div>
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<b>A blueprint for a synthetic genetic feedback controller to reprogram cell fate</b></div>
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The paper considers the problem of controlling cell phenotypes by manipulating the concentration of transcription factors in the underlying gene-regulatory networks. To this end, a fast-slow/high-gain feedback controller is developed, consisting of fast production and degradation of the transcription factors, which, for suitable multi-stable (multi-phenotypic) gene-regulatory networks, destroys all but one stable equilibrium and achieves desired uni-stability (uni-phenotype). The controller is mathematically justified at the deterministic level using suitable perturbation methods. Furthermore, an experimental implementation of the controller is also proposed, based on an intracellular integration of suitable synthetic genes which can be controlled by inducible promoters. </div>
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<b>Nicking-Assisted Reactant Recycle To Implement Entropy-Driven DNA Circuit</b></div>
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<a href="https://pubs.acs.org/doi/10.1021/jacs.9b07521">https://pubs.acs.org/doi/10.1021/jacs.9b07521</a></div>
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Molecular circuits implemented using nucleic acid nanotechnology typically produce double-stranded waste complexes when they run. In this work, the authors propose that these waste complexes can be reconverted into active reaction-ready multi-stranded "gates" through the action of a nicking enzyme that cleaves the backbone of one of the fuel strands. This approach means that, in the simplest of settings, only a supply of single-stranded molecules (rather than harder-to-produce gate complexes) is required to sustain circuit function.</div>
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Although impressive, these circuits show a fairly high level of unwanted leak reactions. Moreover, the recycling of waste does not occur indefinitely, and complex cascaded circuits cannot be produced due to sequence constraints. The article really emphasizes the need for in situ production of nucleic acid complexes.</div>
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<b>The Protection Role of Magnesium Ions on Coupled Transcription and Translation in Lyophilized Cell-Free System </b></div>
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<a href="https://pubs.acs.org/doi/10.1021/acssynbio.9b00508">https://pubs.acs.org/doi/10.1021/acssynbio.9b00508</a></div>
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The storage of a cell-free protein synthesis platform usually involves lyophilization that decreases or even inactivates transcription/translation machinery due to conformational damage of the involved enzymes. The authors proposed that two-metal-ion regulation by magnesium provides protection and regulation of the enzymes and they are essential to preserving the activity of the cell-free protein synthesis systems. This work has important implications for maximizing protein yields in cell-free systems.</div>
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<br />TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-41716208905823125962020-03-13T09:01:00.002-07:002020-03-13T09:01:38.996-07:00Kinetic Proofreading and the limits of thermodynamic uncertainty: a review. Jenny Poulton<br />
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This paper attempts to link together two important concepts
in theoretical biophysics: kinetic proofreading and the thermodynamic
uncertainty relation. It analyses both in the context of copying sequence
information in a polymer, but feels like it confuses more than it clarifies. The
paper does make some clear statements about the predictability of travelling
through a copying network. However, it fails to link this quantity to either
speed or accuracy. It further fails to
make the case for the intrinsic use of this predictability, in systems such of
this.</div>
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<o:p></o:p></div>
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It is worth taking a moment to briefly discuss the ideas of
kinetic proofreading and the thermodynamic uncertainty relation separately,
before we attempt to link the together. Kinetic proofreading was first posited
separately by Hopfield (1974) and Ninio (1975). It is a method by which biochemical
copying systems, such as RNA translation, can improve accuracy by spending
extra energy. It is also an excellent example of the motivation <span class="MsoCommentReference"><span style="font-size: 8.0pt; line-height: 107%;"><!--[if !supportAnnotations]--><a class="msocomanchor" href="file://icnas3.cc.ic.ac.uk/jp1016/downloads/Kinetic%20Proofreading%20and%20the%20limits%20of%20thermodynamic%20uncertainty%20(Autosaved).docx#_msocom_1" id="_anchor_1" language="JavaScript" name="_msoanchor_1">[TO1]</a><!--[endif]--><span style="mso-special-character: comment;"> </span></span></span>behind
using simple theoretical models to describe systems; while kinetic proofreading
was initially posited as a completely theoretical idea, it was widely adopted
by the biological community as it gave good agreement with real biological
results.<o:p></o:p></div>
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In general, simple copying systems approximate to a system
as shown in figure 1. A copy polymer is growing on a template polymer, connected
only by its final monomer. A new monomer, of either a matching or non-matching type
will bind to the template polymer. It will then polymerise into the chain, and
the previous final link between copy and template will break. <o:p></o:p></div>
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Now in a copying system, the most obvious question to ask is
about accuracy, how well does the copy match the template, and how does the
system discriminate? Discrimination comes in the very first step. Because <span style="background-color: white;"><span style="background-attachment: initial; background-clip: initial; background-image: initial; background-origin: initial; background-position: initial; background-repeat: initial; background-size: initial;">non-matching</span> </span>monomers are
more weakly bound to the template polymer, they fall off more quickly than
matching monomers. Thus, if the rates are carefully tuned, the system can
polymerise the monomer into the copy polymer chain fast enough that matching
monomers are unlikely to fall off before incorporation, but<span style="background-color: white;"> <span style="background-attachment: initial; background-clip: initial; background-image: initial; background-origin: initial; background-position: initial; background-repeat: initial; background-size: initial;">non-matching</span> </span>ones will
fall off. Thus the system can generate accuracy.<o:p></o:p></div>
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Kinetic proofreading adds an extra energy driven step.
Instead of the system polymerising the monomer into the chain directly, the
system first has to spend energy activating the monomer, and only then can the
monomer be incorporated into the chain. As long as the activation step is
driven energetically towards activation, either through a chemical gradient or
more directly, then this effectively gives the incorrect monomer two
opportunities to fall off rather than be incorporated; in some limits squaring
the discrimination term. Thus you can pay extra energy to increase accuracy.<o:p></o:p></div>
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Now before I move onto the thermodynamic uncertainty
relation, I’m going to take a moment to stress that in a kinetic proofreading
system, one is usually considering the error, ie. how alike the copy polymer
and the template polymer are. This is <i style="mso-bidi-font-style: normal;">not</i>
the same as the uncertainty in the thermodynamic uncertainty relation.<o:p></o:p></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEinLmvHRFOHeCCjvmRP1-p0rGpY1C820DMnLu2qU1xnGTLfuD_9rU9wdY76QT06rzE0lDHTLhthaImkeGtQGAWvVg8CEzmC5uoaGQZVGmek7AefwOz7CnvHiBYXQqhJPeg2YTvD-p17ujo/s1600/KPR.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="1334" data-original-width="1600" height="266" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEinLmvHRFOHeCCjvmRP1-p0rGpY1C820DMnLu2qU1xnGTLfuD_9rU9wdY76QT06rzE0lDHTLhthaImkeGtQGAWvVg8CEzmC5uoaGQZVGmek7AefwOz7CnvHiBYXQqhJPeg2YTvD-p17ujo/s320/KPR.png" width="320" /></a></div>
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<span style="mso-fareast-language: EN-GB; mso-no-proof: yes;"><v:shapetype coordsize="21600,21600" filled="f" id="_x0000_t75" o:preferrelative="t" o:spt="75" path="m@4@5l@4@11@9@11@9@5xe" stroked="f">
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<div class="MsoCaption">
Figure <!--[if supportFields]><span style='mso-no-proof:
yes'><span style='mso-element:field-begin'></span><span
style='mso-spacerun:yes'> </span>SEQ Figure \* ARABIC <span style='mso-element:
field-separator'></span></span><![endif]--><span style="mso-no-proof: yes;">1</span><!--[if supportFields]><span
style='mso-no-proof:yes'><span style='mso-element:field-end'></span></span><![endif]-->;
Left: a simple three step copying reaction in which a monomer binds to the
template, is polymerised into the chain and the previous final monomer
detaches. Right: the system with an additional proofreading step. The system
must be energetically driven to activate the monomer, at which point it has a
second opportunity to fall off before incorporation.<o:p></o:p></div>
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So what is the thermodynamic uncertainty relation? The
thermodynamic uncertainty relation considers a stochastic process, often
visualised by a network of states which outline progression through a process.
In the case of biological copying, the process is that of adding a monomer to
the end of a growing polymer as shown in figure 2. However, it could equally be
the process of a molecular walker taking a step along a track. The
thermodynamic uncertainty relation tracks the uncertainty in the net number of
times a particular thing <!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>X</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 7.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image002.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-spacerun: yes;"> </span>happens <!--[if gte msEquation 12]><m:oMath><m:sSup><m:sSupPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSupPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>ε</m:r></span></i></m:e><m:sup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>2</m:r></span></i></m:sup></m:sSup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>=</m:r></span></i><m:f><m:fPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:fPr><m:num>Var<i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>X</m:r></span></i></m:num><m:den><m:sSup><m:sSupPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSupPr><m:e><m:d><m:dPr><m:begChr
m:val="⟨"/><m:endChr m:val="⟩"/><span style='font-family:"Cambria Math",serif;
mso-ascii-font-family:"Cambria Math";mso-hansi-font-family:"Cambria Math";
font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:dPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>X</m:r></span></i></m:e></m:d></m:e><m:sup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>2</m:r></span></i></m:sup></m:sSup></m:den></m:f></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -8.5pt; position: relative; top: 8.5pt;"><v:shape id="_x0000_i1025" style="height: 21pt; width: 42pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image003.png">
</v:imagedata></v:shape></span><!--[endif]-->. For example, the number of times a system
undergoes a specific transition. In a case of a molecular walker <!--[if gte msEquation 12]><m:oMath><m:sSup><m:sSupPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSupPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>ε</m:r></span></i></m:e><m:sup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>2</m:r></span></i></m:sup></m:sSup></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 10.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image004.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-spacerun: yes;"> </span>could be the
uncertainty in how far the walker had walked with the net number of forward
steps being <!--[if gte msEquation 12]><m:oMath><i style='mso-bidi-font-style:
normal'><span style='font-family:"Cambria Math",serif'><m:r>X</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 7.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image002.png">
</v:imagedata></v:shape></span><!--[endif]-->. In the case of a copy process<span style="mso-spacerun: yes;"> </span><!--[if gte msEquation 12]><m:oMath><m:sSup><m:sSupPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSupPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>ε</m:r></span></i></m:e><m:sup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>2</m:r></span></i></m:sup></m:sSup></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 10.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image004.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-spacerun: yes;"> </span>could be the
uncertainty in the net number of correct things the system has added (ie how
many times the system has gone round the upper right loop in figure 2) or it
could be the uncertainty the net number of incorrect things that have been
added (upper left loop). Crucially <!--[if gte msEquation 12]><m:oMath><m:sSup><m:sSupPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSupPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>ε</m:r></span></i></m:e><m:sup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>2</m:r></span></i></m:sup></m:sSup></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 10.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image004.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-spacerun: yes;"> </span>would not
automatically give you a relationship between the number of right and wrong
things added. The form of the uncertainty relationship <!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>Q</m:r><m:r>=</m:r></span></i><m:acc><m:accPr><m:chr
m:val="̇"/><span style='font-family:"Cambria Math",serif;mso-ascii-font-family:
"Cambria Math";mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:accPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>Q</m:r></span></i></m:e></m:acc><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>t</m:r></span></i><m:sSup><m:sSupPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSupPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>ε</m:r></span></i></m:e><m:sup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>2</m:r></span></i></m:sup></m:sSup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>≥2</m:r></span></i><m:sSub><m:sSubPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSubPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>k</m:r></span></i></m:e><m:sub><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>B</m:r></span></i></m:sub></m:sSub><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>T</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 15pt; width: 84.75pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image005.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span></span>tells us that we can again spend energy
to reduce the uncertainty; here <!--[if gte msEquation 12]><m:oMath><m:acc><m:accPr><m:chr
m:val="̇"/><span style='font-family:"Cambria Math",serif;mso-ascii-font-family:
"Cambria Math";mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:accPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>Q</m:r></span></i></m:e></m:acc><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>t</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 15pt; width: 12pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image006.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>is the energy cost of the process per unit
time multiplied by the time.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><br /></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">So while both
relationships have a form of uncertainty, and this uncertainty can be reduced
in both cases by paying energy, the two uncertainties; the error </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>η</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 6pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image007.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>and the uncertainty </span><!--[if gte msEquation 12]><m:oMath><m:sSup><m:sSupPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSupPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>ε</m:r></span></i></m:e><m:sup><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>2</m:r></span></i></m:sup></m:sSup></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 10.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image004.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">, are not
immediately related to each other and should not be conflated.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><br /></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">Now the aspect
of kinetic proofreading which is most straightforward to link to the
thermodynamic uncertainty is not the error but the speed. Banerjee et al discusses
how for many simple copying processes such as those found in T7 DNAP enzymes
acting on DNA and TRNA selection in E. coli ribosomes, in general systems are
willing to tolerate a certain amount of error in order to maximise speed. While
the thermodynamic uncertainty relationship doesn’t directly measure speed, it
does characterise the uncertainty in progress, ie how reliable said speed is.
Someone with a stronger molecular biology background than I might be able to convince
me that predictability in copying speed is important, sadly the paper fails to
do so.<o:p></o:p></span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZKrSSkRAzfp09KjBEnIfseWbj32cD_GrIs9jk9_aQevOcfrThbEv-Evnfv3xlcDterqLNpV2Cpp2bmLTOBb5Bzkd40R99hIYIrjtA6eS-do7T7tyTJ9-rGmm2-aub-iTHohm6JFGx2CI/s1600/TUR.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="810" data-original-width="1600" height="161" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZKrSSkRAzfp09KjBEnIfseWbj32cD_GrIs9jk9_aQevOcfrThbEv-Evnfv3xlcDterqLNpV2Cpp2bmLTOBb5Bzkd40R99hIYIrjtA6eS-do7T7tyTJ9-rGmm2-aub-iTHohm6JFGx2CI/s320/TUR.png" width="320" /></a></div>
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<span style="mso-fareast-language: EN-GB; mso-no-proof: yes;"><v:shape id="Picture_x0020_5" o:spid="_x0000_i1026" style="height: 228pt; mso-wrap-style: square; visibility: visible; width: 451.5pt;" type="#_x0000_t75">
<v:imagedata o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image008.png">
</v:imagedata></v:shape></span><o:p></o:p></div>
<div class="MsoCaption">
Figure <!--[if supportFields]><span style='mso-no-proof:
yes'><span style='mso-element:field-begin'></span><span
style='mso-spacerun:yes'> </span>SEQ Figure \* ARABIC <span style='mso-element:
field-separator'></span></span><![endif]--><span style="mso-no-proof: yes;">2</span><!--[if supportFields]><span
style='mso-no-proof:yes'><span style='mso-element:field-end'></span></span><![endif]-->
The left hand side represents the network for adding a monomer in DNA related
actions, the right hand side represents that for RNA related actions. In both
the green “reduced system” at the bottom shows the path for adding a new
monomer and extending the chain whereas the blue cycle adds and removes a
monomer through kinetic proofreading. Reactions a and b are gradually turned
off later in the paper.<o:p></o:p></div>
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<br /></div>
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The paper focusses on <span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">the number of times the system above goes round the green cycles in
figure 2, with this being <span style="mso-spacerun: yes;"> </span></span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>X</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 7.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image002.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">.<span style="mso-spacerun: yes;"> </span>The thermodynamic uncertainty variable </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 7.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image009.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>is defined relative to this. They define a
lower bound on </span><!--[if gte msEquation 12]><m:oMath><i style='mso-bidi-font-style:
normal'><span style='font-family:"Cambria Math",serif;mso-fareast-font-family:
"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 7.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image009.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>by considering the reduced cycle corresponding
to that system which contains only the green cycle. For this cycle which is
unicyclic the uncertainty is well defined and here labelled; </span><!--[if gte msEquation 12]><m:oMath><m:sSub><m:sSubPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast;
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSubPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>Q</m:r></span></i></m:e><m:sub><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>RC</m:r></span></i></m:sub></m:sSub></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 18pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image010.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">. They thus
define a quantity </span><!--[if gte msEquation 12]><m:oMath><m:f><m:fPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast;
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:fPr><m:num><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:num><m:den><m:sSub><m:sSubPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast;
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSubPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:e><m:sub><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>RC</m:r></span></i></m:sub></m:sSub></m:den></m:f></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -8.5pt; position: relative; top: 8.5pt;"><v:shape id="_x0000_i1025" style="height: 21.75pt; width: 15pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image011.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>which defines the thermodynamic uncertainty
relative to the minimum uncertainty and compare this quantity for a number of
different systems. However it should be clear that it is not true that </span><!--[if gte msEquation 12]><m:oMath><m:f><m:fPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast;
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:fPr><m:num><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:num><m:den><m:sSub><m:sSubPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast;
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSubPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:e><m:sub><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>RC</m:r></span></i></m:sub></m:sSub></m:den></m:f><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>→1</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -8.5pt; position: relative; top: 8.5pt;"><v:shape id="_x0000_i1025" style="height: 21.75pt; width: 36.75pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image012.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>means lower error, it merely states that it the
net number of times the system goes round that particular cycle becomes more
predictable. They compare this variable for a series of biological systems,
with two subtly different networks shown in figure 2. These are Err ribosome
(right) WT ribosome (right), Acc ribosome (right) and T7 polymerase (left).
Recall that </span><!--[if gte msEquation 12]><m:oMath><i style='mso-bidi-font-style:
normal'><span style='font-family:"Cambria Math",serif'><m:r>Q</m:r><m:r>≥2</m:r></span></i><m:sSub><m:sSubPr><span
style='font-family:"Cambria Math",serif;mso-ascii-font-family:"Cambria Math";
mso-hansi-font-family:"Cambria Math";font-style:italic'><m:ctrlPr></m:ctrlPr></span></m:sSubPr><m:e><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>k</m:r></span></i></m:e><m:sub><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>B</m:r></span></i></m:sub></m:sSub><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif'><m:r>T</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 47.25pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image013.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>. They present these results and suggest that
a lower </span><!--[if gte msEquation 12]><m:oMath><i style='mso-bidi-font-style:
normal'><span style='font-family:"Cambria Math",serif;mso-fareast-font-family:
"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 7.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image009.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>means that the system is capable of better
trading off error and speed, although this isn’t necessarily persuasively
explained.<o:p></o:p></span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjtJIn3EjjbKHlnX7VjOCLB30WdJGMi-MSh0ad_hxMx-idO9uqVeereggS4wWdiloX5KNZXvOWqZ0CKuVUJfzk2oA3y6-2odnjrwX276NZVjlpPSZqKBtn5HjVVFaPFIBQMr7d8wtH0eYc/s1600/Tab.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="138" data-original-width="432" height="102" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjtJIn3EjjbKHlnX7VjOCLB30WdJGMi-MSh0ad_hxMx-idO9uqVeereggS4wWdiloX5KNZXvOWqZ0CKuVUJfzk2oA3y6-2odnjrwX276NZVjlpPSZqKBtn5HjVVFaPFIBQMr7d8wtH0eYc/s320/Tab.png" width="320" /></a></div>
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<span style="mso-fareast-language: EN-GB; mso-no-proof: yes;"><v:shape id="Picture_x0020_3" o:spid="_x0000_i1025" style="height: 103.5pt; mso-wrap-style: square; visibility: visible; width: 324pt;" type="#_x0000_t75">
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</v:imagedata></v:shape></span><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><o:p></o:p></span></div>
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<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">In the next
section the authors ask how turning off two of the reactions, which reduce
accessibility to parts of the network, changes </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>Q</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 7.5pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image009.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">. They<span style="mso-bidi-font-style: italic;"> relate this to error </span></span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>η</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 6pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image007.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>and </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>τ</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 5.25pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image015.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">, a time
constant which quantifies the time taken to go round the cycle.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><br /></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">Removing
reaction a) as labelled in figure 2 prevents the system from attempting to add
incorrect monomers, and removes access to the whole left hand side of the
cycle. Removing reaction b) prevents the system from removing correct monomers
via kinetic proofreading, but does not change the overall topology of the
network in the way removing a) does.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><br /></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">The authors
state that i</span><span style="mso-bidi-font-style: italic;">n both cases </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>η</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 6pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image007.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic;"><span style="mso-spacerun: yes;"> </span>is reduced when the reactions are removed.
This would seem self-evident. They also state that energy cost for faster
speeds is minimized when reactions are removed, because you don’t spend extra
energy being pushed around futile cycles. </span><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><o:p></o:p></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic;"><br /></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">The authors
point out that in case a) Q decouples from </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>τ</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 5.25pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image015.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>as the reaction is removed, but the network
retains it’s dependence on </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>τ</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 5.25pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image015.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>in case b). They then explore how </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>η</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 6pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image007.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>depends on Q. In both cases they find that as
the reactions are removed, </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>η</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 6pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image007.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>decouples from Q. This tells us that in the
accurate limit where only the reduced cycle happens, Q is not related to </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>η</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 6pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image007.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">. So the
measurement of Q seems like a curious choice when it is decoupled from both </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>η</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -4.0pt; position: relative; top: 4.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 6pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image007.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>and </span><!--[if gte msEquation 12]><m:oMath><i
style='mso-bidi-font-style:normal'><span style='font-family:"Cambria Math",serif;
mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast'><m:r>τ</m:r></span></i></m:oMath><![endif]--><!--[if !msEquation]--><span style="font-family: "Calibri",sans-serif; font-size: 11.0pt; line-height: 107%; mso-ansi-language: EN-GB; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin; mso-text-raise: -3.0pt; position: relative; top: 3.0pt;"><v:shape id="_x0000_i1025" style="height: 14.25pt; width: 5.25pt;" type="#_x0000_t75">
<v:imagedata chromakey="white" o:title="" src="file:///C:/Users/jp1016/AppData/Local/Temp/msohtmlclip1/01/clip_image015.png">
</v:imagedata></v:shape></span><!--[endif]--><span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><span style="mso-spacerun: yes;"> </span>in the accurate limit.<o:p></o:p></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;"><br /></span></div>
<div class="MsoNormal">
<span style="mso-bidi-font-style: italic; mso-fareast-font-family: "Times New Roman"; mso-fareast-theme-font: minor-fareast;">The
thermodynamic uncertainty relation seems like a tool unsuited to answer the
important questions about accurate copying. While there may be good reasons to
perform this analysis, the authors have failed to provide them.</span></div>
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<br />Jenny Poultonhttp://www.blogger.com/profile/16892801513928606834noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-75770734119704366722020-03-10T10:27:00.001-07:002020-03-10T10:27:14.056-07:00A full house of papers combining DNA with other biomolecules to stabilise, direct and monitor assembly<b>Coating and Stabilization of Liposomes by Clathrin-Inspired DNA Self-Assembly </b><br />
<a href="doi:10.1021/acsnano.9b09453" target="_blank">doi:10.1021/acsnano.9b09453</a><br />
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Assembling a DNA triskelion array layer on liposomes stabilized the membrane while keeping the fluidic nature of the lipid molecules. The vesicle did not rupture on the mica surface an nor was it dissolved by adding triton-X 100 detergent.<br />
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<b>Peptide Assembly Directed and Quantified Using Megadalton DNA Nanostructures </b><br />
<a href="https://doi.org/10.1021/acsnano.9b04251" target="_blank">https://doi.org/10.1021/acsnano.9b04251</a><br />
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Sequence-structure relationships are sufficiently well understood for alpha-helical polypeptides to enable bottom-up design of simple alpha helix complexes. Two halves of a heterodimeric peptide were each tethered to large DNA nanostructures. The DNA nanostructures could be clearly differentiated with TEM. The peptide sequences were intentionally designed with a hydrophobic seam along which two alpha-helices could form a bond, bringing together two DNA nanostructures. To prevent DNA sticking to the peptide complexes, the sequences of peptides were chosen to be charge neutral at pH 7. Multiple peptide halves can be attached to each DNA nanostructure, altering the valency of the alpha helix bonding interaction. The authors measure the Kd disassociation constant for the peptide interactions using CD melting and by counting samples using TEM. This semi-quantitative technique is a first step toward the creation of complex rationally-designed peptide-oligonucleotide nanostructures but is not the most promising route toward measuring peptide interactions.<br />
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<b>Directed Energy Transfer through DNA-Templated J-Aggregates</b><br />
<a href="https://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00043">https://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00043</a><br />
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DNA photonic wires are DNA duplexes labelled with fluorophores that are able to transfer optical excitation through long distances by FRET interactions. In Nature, optical excitation transference is usually achieved by dye clusters templated over polymeric chains, such as proteins. Cyanine dyes are able to produce such clusters by stacking their aromatic groups together.<br />
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In the present paper, the authors template the formation of dye clusters, out of the fluorophore pseudoisocyanine, over a DNA duplex of poly(A)-poly(T).The DNA scaffold is able to produce a continuous cyanine aggregate across 48 base pairs. The optical transfer of the continuous cyanine cluster is compared with a DNA scaffold that produces a gap in the cluster. A single base pair gap in the cluster results in a sensible decrease of the optical transference efficiency, remarking the importance of the continuous templating.<br />
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TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-25074866577591788862020-02-21T08:04:00.002-08:002020-02-21T08:04:36.234-08:00A DNA-based artificial metabolism, the thermodynamics of Turing machines and more...<b>Inferring dissipation from current fluctuations Todd R Gingrich, Grant M Rotskoff, and Jordan M Horowitz</b><br />
<a href="https://doi.org/10.1088/1751-8121/aa672f">https://doi.org/10.1088/1751-8121/aa672f</a><br />
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When systems are coupled to thermodynamic baths, the irreversibility of transitions in the system are constrained by dissipation in the baths. Lower bounds on the magnitude of fluctuations in certain integrated currents can be used to infer the dissipation within the system. By considering a driven diffusion process on a lattice near the continuum limit, the authors apply results usually reserved for discrete state systems to a continuum process. It is demonstrated that the dissipation can still be constrained by fluctuations in macroscopic, rather than mesoscopic currents.<br />
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<b>Homogeneous and universal detection of various targets based on dual‐step transduced toehold switch sensor</b><br />
<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/cbic.201900749">https://onlinelibrary.wiley.com/doi/abs/10.1002/cbic.201900749</a><br />
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The toehold switch system can be used to translate the nucleic acid based signals to protein level response. However, engineering and optimizing input sequence of the riboswitch system is a non-trivial task. This paper adds an additional layer of strand-displacement reactions involving an arbitrary input strand to generate a complex with a pre-existing strand to open the riboswitch. They have used in-vitro translation system to confirm the activity of their system using various targets including aptamers.<br />
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<b>Dynamic DNA material with emergent locomotion behaviour powered by artificial metabolism</b><br />
<a href="https://robotics.sciencemag.org/content/4/29/eaaw3512">https://robotics.sciencemag.org/content/4/29/eaaw3512</a><br />
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The present work by Hamada and collaborators displays the construction of an artificial DNA-based system capable of growing a pattern following a template pattern on a microfluidic chip. The material is powered by an artificial metabolism consisting of the synthesis of DNA precursors by a phage DNA polymerase and the subsequent diffusion of the molecules, dissipative assembly and degradation. With this set up and in laminar flow, the material can autonomously grow similarly to how slime molds do (according to the authors). However, there are some limitations to this system since the emergent spatial patterns come from interactions with elements of the microfluidic chip rather than being encoded in the possible interactions within the DNA species.<br />
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<b>The business of DNA nanotechnology: Commercialization of origami and other technologies</b></div>
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<a href="https://www.mdpi.com/1420-3049/25/2/377">https://www.mdpi.com/1420-3049/25/2/377</a></div>
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In this paper, Dunn analyzes the trends on both DNA nanotechnology publications and patent filings up until 2018. She describes growth trends in both sides of the field. The main conclusionis that until as recently as 2017 there was a gap between the scientific literature available - which seems to grow steady year by year - and derived applications that were commercially available - which did not seem to get the same momentum until the last year. However, in 2018 there was a noticeable surge in the number of patents filled. The paper also gives some details on the profile of some start ups on the field and they commercialized products: mainly research solutions and diagnosis applications.</div>
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<b>Mathematical Models of Protease-Based Enzymatic Biosensors</b></div>
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<a href="https://pubs.acs.org/doi/10.1021/acssynbio.9b00279">https://pubs.acs.org/doi/10.1021/acssynbio.9b00279</a></div>
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In this paper, the authors presented a rapid detection system to chosen chemical and optical inputs using protease-based logic circuits. In the presence of a specific input, the protease activity will be restored and will cleave a specific substrate to produce a read-out signal. Enzymatic-based circuits operate at much faster time scales than the transcription-based circuits. In this work, the authors modeled and optimized experimentally the reactions to build a biosensor based on Boolean OR and XOR Boolean logic gates. In conclusion, enzymatic reactions can be used to develop biosensors capable of rapidly detecting multiple inputs.</div>
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<b>An RNA polymerase ribozyme that synthesizes its own ancestor</b></div>
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<a href="https://www.pnas.org/content/117/6/2906">https://www.pnas.org/content/117/6/2906</a></div>
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By directed mutagenesis, a ligase I RNAzyme is transformed into a polymerase that can produce long RNA copies from an RNA template. The mutated RNAzyme is composed of three different RNA strands that can hybridize to form the final RNAzyme. With the correct template, the mutated RNAzyme is capable of polymerising the RNA sequences that produce the original ligase I.</div>
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However, the precision of the mutated RNAzyme is far from perfect. The average fidelity for the addition of NTPs is below 90%, thus adding several mutations to the copies, which end up losing their function in the majority of the cases. These results emphasize that one of the main challenges of polymerisation is the fidelity of the produced copies.</div>
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<b>Thermodynamic costs of Turing Machines</b></div>
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<a href="https://arxiv.org/abs/1912.04685">https://arxiv.org/abs/1912.04685</a></div>
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Kolchinsky and Wolpert present an analysis that seeks to combine statistical thermodynamics with the algorithmic information theory of Turing Machines. Their central results come in three parts.</div>
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(a) They identify conditions under which a function G(x) can be interpreted as the heat function of a physically realizable construction of a Turing machine. Here, the heat function Q_T(x) is the heat generated by running Turing machine T on input x.</div>
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(b) Using these rules, the authors argue that a UTM that is thermodynamically reversible for the coin flip distribution of inputs is physically realizable. They go on to show that the heat cost of running this coin flip realization on an input x is bounded by the sum of the length of x, -1* the Kolmogorov</div>
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complexity of x calculated via that UTM, and a constant. As a result, the authors argue that such computations generate more heat if the input program is chosen inefficiently (it is too long), and that if we happened to have the shortest program needed to calculate y, there is a finite upper bound on the</div>
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heat cost involved. However, finding the shortest algorithm is not a computable problem, and if random inputs are used, the expected heat generated is infinite.</div>
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(c) Returning to the rules, the authors show that the conditional Kolmogorov complexity of an input given its output for a TM T, K(x|T(x)), can be a heat function (ie., there is a physical realization that generates heat Q(x)=K(x|T(x)) for input x). They call this the dominating realization, and argue that for any other realization of T, Q(x) can only be lower than Q_dom if the Kolmogorov complexity K(Q) is large. Thus K(x|T(x)) is some kind of cost that is either paid for during the operation of the device, or in its design (a complex K(Q) being taken as costly to build).<br />
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<b>Scalable Computational Framework for Establishing Long-Term Behavior of Stochastic Reaction Networks.</b><br />
<a href="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003669">https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003669</a><br />
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The paper develops mathematical and computational methods for studying stability and long-time dynamics of stochastic biochemical reaction networks, mirroring analogous methods from the deterministic setting. The framework is applied to a number of examples, including a feedback loop, stochastic switch and a circadian clock. </div>
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TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-43752503892110674142020-02-10T03:42:00.000-08:002020-02-10T04:09:40.028-08:00Two papers on DNA nanostructures for scaffolding of proteins, plus some other stuff... <b>Designed Protein Cages as Scaffolds for Building Multienzyme Materials</b><br />
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In this paper, the authors developed a modular platform to produce designer nanocages that display multiple enzymes in high copy number on their exterior. This is particularly interesting because the functions of enzymes can be strongly affected by their higher-order spatial arrangements.<br />
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This approach harnesses the sequence specificity and robust ligation activity of the S. aureus sortase A (SrtA) enzyme, a widely used cysteine transpeptidase. They show that the surface of a designer nanocage can be elaborated with multiple cellulase enzymes using a sortase enzyme as the linking catalyst.<br />
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<b>Engineering a DNAzyme-Based Operon System for the Production of DNA nanoscaffolds in Living Bacteria</b><br />
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The present work describes a methodology to create DNA nanostructures in vivo that allow the directed spatial co-localization of proteins in vivo. This feat is achieved through the implementation in a single RNA transcript of all the DNA sequences that will form the structure separated in the sequence by self-cleaving DNAzymes. In order to produce the DNA nanostructure, the RNA transcript gets retrotranscribed into DNA and the DNAzymes cleave the nanoscaffold strands when Zn is present. This allows the scaffold's self-assembly, exposing in the process certain dsDNA sequences that will be recognized and bound by the Zn fingers-like domains of the proteins co-expressed in the operon.<br />
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<b>Design of thiazole orange oligonucleotide probes for detection of DNA and RNA by fluorescence and duplex melting</b><br />
<a href="https://pubs.rsc.org/en/content/articlelanding/2019/ob/c9ob00885c#!divAbstract">https://pubs.rsc.org/en/content/articlelanding/2019/ob/c9ob00885c#!divAbstract</a><br />
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The authors characterise the effect of modifying one nucleotide in a nucleic acid strand with the dye Thiazole Orange. This dye produce a higher fluorescence when the strand is hybridized with another. Changing the position of the dye in the nucleotide and in the strand, they are able to use the dye to discriminate if the strand binds DNA or RNA. They also employ the probe to detect the bound or unbound state of single mismatches in the strand.TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-49213446292874273612020-01-30T08:49:00.001-08:002020-01-30T08:52:21.015-08:00Do many-body systems learn? Can deep learning be applied to synbio and protein structure prediction? New strategies for static and dynamic DNA nanotech, and is guano the graphene dopant of the future?<span style="font-family: inherit;"><br /></span>
<b><span style="font-family: inherit;">Improved protein structure prediction using potentials from deep learning</span></b><br />
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<span style="font-family: inherit;">Deep leaning is used to predict the interaction energy (distance) between two arbitrary residues. The mean force potential generated from the interaction energy was used to describe and optimize the structure.</span><br />
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<b><span style="font-family: inherit;">Learning about learning by many-body systems</span></b></div>
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<a href="https://arxiv.org/abs/2001.03623"><span style="font-family: inherit;">https://arxiv.org/abs/2001.03623</span></a></div>
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<span style="font-family: inherit;">The authors explore the efficacy with which the states of a spin glass can be used to train a machine learning algorithm to classify time-dependent driving fields. It transpires that the algorithm is more effective if it has access to the detailed configurations rather than just global properties such as the absorbed power (which is effectively useless in this setting). The authors describe this phenomenon as the spins "learning" the applied drive, but really the states of the spins are just a communication channel from the applied drive to the machine learning algorithm; the detailed states have a higher capacity than the absorbed power, which is not much of a surprise. </span></div>
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<span style="font-family: inherit;">Fundamentally, to really <i><b>learn</b></i>, it feels to me like the state of the learning system should be updated permanently (or at least long-term) in a way so that it is better at recognising patterns in the future. In the case discussed here, the spins respond to a drive but this information is not retained long-term by the spins and used to improve the response to future drives. </span></div>
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<span style="font-family: inherit;"><b>Sequence information transfer using covalent template-directed synthesis </b><a href="https://doi.org/10.1039/c9sc01460h">https://doi.org/10.1039/c9sc01460h</a></span><br />
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<span style="font-family: inherit;">Template-directed polymer synthesis is the basis for the replication of information stored in D/RNA in living systems. Here the authors look to a synthetic oligomeric system and present a method by which information stored on the oligomer can be copied by synthesis of a new oligomer. The authors describe a general process and implement copying for a 3 unit long template. A trimer template oligomer is prepared with a binary sequence. One type of symbol (0's) is protected (covered up) along the template. The template is presented with the complement for the other symbol type and covalent ester binding occurs. The 0's are then un-protected and their complementary symbol also forms ester bonds with the template. Each site on the template is now occupied by its complementary monomer. The monomers are polymerised together, and then, as the ester bonds are broken, the copy is released from the template. Protection of sites on the template during synthesis is required to generate accuracy in this system, as there is no kinetic difference between the binding of the two different monomer types. A limitation of this procedure, for the purpose of building a synthetic molecular copier, is that it requires external manipulation of the environment of the template at each stage - it is not autonomous.</span><br />
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<b><span style="font-family: inherit;">Landauer's principle at zero temperature</span></b></div>
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<span style="color: #0000ee; text-decoration-line: underline;"><span style="font-family: inherit;">https://arxiv.org/pdf/1911.00910.pdf</span></span></div>
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<span style="font-family: inherit;">The fundamental cost of setting a bit of information to a definite value is \Delta Q= -T \Delta S . This relationship scales with temperature, and so when T=0, the limit is trivial. In this paper the authors derive a tighter bound by considering the relationship between the system and the background, allowing the background to have thermal properties. </span></div>
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<span style="font-family: inherit;"><b>Solving the chemical master equation for monomolecular </b><b>reaction systems analytically: a Doi-Peliti path integral view.</b></span></div>
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<span style="font-family: inherit;"><a data-auth="NotApplicable" href="https://arxiv.org/abs/1911.00978" id="LPlnk148801" rel="noopener noreferrer" style="border: 0px; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; padding: 0px; vertical-align: baseline;" target="_blank">https://arxiv.org/abs/1911.00978</a> .</span></div>
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<span style="font-family: inherit;"><span style="color: inherit; font-style: inherit; font-weight: inherit;"><br />The manuscript considers the problem of obtaining </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">time-dependent solutions of the chemical master equation </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">(CME) by using so-called Doi-Peliti path-integral method. </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">The method formulates the CME as an operator equation </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">for an associated generating function, which is solved </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">via a sequence of integration steps, providing time-dependent </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">probability mass-functions and the underlying moments. T</span><span style="color: inherit; font-style: inherit; font-weight: inherit;">he Doi-Peliti path-integral approach has been utilized in the manuscript </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">to recover previously obtained results for</span><span style="border: 0px; color: inherit; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; padding: 0px; vertical-align: baseline;"> so-called monomolecular </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">networks (which consist of reactions whose complexes are single species), </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">and to provide novel result for a more general (non-monomolecular) </span><span style="color: inherit; font-style: inherit; font-weight: inherit;">one-species first-order network, which includes an auto-catalytic reaction.</span></span></div>
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<span style="font-family: inherit;"><b><span style="font-family: inherit;">Deep Learning for RNA Synthetic Biology</span></b></span></div>
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<span style="font-family: inherit;">Toehold switches are a class of versatile prokaryotic riboregulators inducible by the presence of a fully programmable trans-RNA trigger sequence. These RNA synthetic biology modules hold great promise for a variety of in vitro and in vivo applications. Then, considering the wide applicability and general challenges of toehold switch design, the objective of this work is to develop a deep learning platform to predict toehold switch function as a canonical RNA switch model in synthetic biology. The authors demonstrated the benefits of using deep learning methods (a tenfold improvement) that directly analyse sequence rather than relying on calculations from mechanistic thermodynamic and kinetic models. </span></div>
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<b><span style="font-family: inherit;">Implementing digital computing with DNA-based switching circuits</span></b></div>
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<span style="font-family: inherit;">This work features a strand displacement implementation of a switching circuits formalism first described by Shannon in 1938. In this approach, the different strand displacement reactions implement switches that can be in two different states and can implement functions of different complexity ranging from the construction of Boolean logic gates to the now-classic example of the square root function of a number in a generalized manner without the need for dual-rail logic. As a result, the approach reduces the number of strands required to implement the circuit considerably from the previous implementations.</span></div>
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<b><span style="font-family: inherit;">Will any crap we we put into graphene increase its electrocatalytic effect? </span></b></div>
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<span style="font-family: inherit;"><a href="https://pubs.acs.org/doi/10.1021/acsnano.9b00184">https://pubs.acs.org/doi/10.1021/acsnano.9b00184</a></span><br />
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<span style="font-family: inherit;">In the present work, Pumera and collaborators took an unorthodox spin on current trends on graphene functionalization research. They demonstrated that, in concordance to previous research in which any kind of addition of dopant heteroatoms would enhance the performance of the material in electrocatalysis applications and the use of different heteroatoms produces a synergistic effect, the use of bird guano as such dopant does indeed improve the electrocatalytical performance of graphene for oxygen reduction reactions as well as hydrogen evolution reactions. Moreover, it is an affordable methodology for the development of metal-free catalysts for fuel cells and electrolysers</span></div>
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<b><span style="font-family: inherit;">Ordered three-dimensional nanomaterials using DNA-prescribed and valence-controlled material voxels</span></b></div>
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<a href="https://www.nature.com/articles/s41563-019-0550-x?"><span style="font-family: inherit;">https://www.nature.com/articles/s41563-019-0550-x?</span></a></div>
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<span style="font-family: inherit;">The formation of self-assembled 3D nano-structures is a challenging problem that heavily depends on the molecules used and their interactions. The authors present a generalizable approach to assemble molecules using DNA cubes, pyramids and rhomboids that mimic crystalline unit cells. Each of the DNA unit cells can contain one of the molecules of interest bound by base pairing. Once the DNA unit cells polymerise to form a 3D structure, the contained molecules of interest become arranged in 3D.</span></div>
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<b><span style="font-family: inherit;">Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase </span></b></div>
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<span style="font-family: inherit;"><a data-auth="NotApplicable" href="https://www.nature.com/articles/s41565-019-0544-5" id="LPlnk715607" rel="noopener noreferrer" style="border: 0px; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; padding: 0px; vertical-align: baseline;" target="_blank">https://www.nature.com/articles/s41565-019-0544-5</a></span></div>
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<span style="font-family: inherit;">The authors generated OR and AND logic gates for computing square-root function of 4-bit numbers. The gates are single stranded which can reduce the potential for leakage. Fuel strands anneal to the gates and followed by polymerisation; the input strands can then anneal to this complex and there is displacement of the output strand. </span></div>
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TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0tag:blogger.com,1999:blog-1661121559475127524.post-15342093700059941142019-12-09T08:09:00.000-08:002019-12-09T08:10:12.885-08:00Reading list from 2/12/2019:Cahos with no equilibrium, cellular supremacy, nanoclocks, and new ways to probe molecular systems<b>Dynamical behaviors of a chaotic system with no equilibria </b><br />
<a href="https://www.sciencedirect.com/journal/physics-letters-a/vol/376/issue/2">https://www.sciencedirect.com/journal/physics-letters-a/vol/376/issue/2</a><br />
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A relatively simple three-variable autonomous system of ordinary differential equations (ODEs) is presented, which, depending on the choice of the underlying parameters, displays zero, one or two stationary (equilibrium) points. Using Liapunov exponents, bifurcation diagrams and Poincare maps, the system is shown to display chaotic attractors, whose nature depends on the number of the underlying equilibria. In particular, the system displays a chaotic attractor even in the absence of equilibria.<br />
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<b>Pathways to cellular supremacy in biocomputing</b><br />
<a href="https://www.nature.com/articles/s41467-019-13232-z">https://www.nature.com/articles/s41467-019-13232-z</a><br />
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In the present article, the authors try to settle a new perspective with regards synthetic biology by defining the notion of cellular supremacy as the circumstance in which the implementation and execution of an algorithm would be tractable in a reasonable amount of time only in a cellular substrate rather than on a silicon microchip (akin to the notion of quantum supremacy). The authors acknowledge that analogies with the Boolean algebra logic underlying all digital computing have been used in biology since the time of Jacques Monod, but they argue that all cellular systems have a series of features (massive parallel exploration of all the space of solutions, use of stochasticity for synchronization and optimization of resources, analog signal treatment, concurrency of computational agents as well as the possibility of dealing with the increasing complexity of algorithms distributing them in cellular consortia) that put them far away from conventional computing paradigms and could lead the way to the aforementioned supremacy.<br />
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<b>Bilingual Peptide Nucleic Acids: Encoding the Languages of Nucleic Acids and Proteins in a Single Self-Assembling Biopolymer</b><br />
<a href="https://pubs.acs.org/doi/10.1021/jacs.9b09146">https://pubs.acs.org/doi/10.1021/jacs.9b09146</a><br />
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Peptide nucleic acids (PNA) are DNA/RNA mimic molecules comprising a sequence of nucleic acids joined by a peptide, rather than a de/oxyribose phosphate, backbone. PNA polymers acan exploit both the sequence-specific complementarity of the nucleotides as well as the complex chemistry of proteins. In this paper, PNA polymers were constructed with poly-peptide chain appendages, one half of which was hydrophobic and the other half hydrophilic. A fluorescent tag was attached to the hydrophobic end that increases in intensity in increasingly hydrophobic environments. The hydrophilic/phobic appendage drove the system of PNA molecules to self assemble into vesicles which, due to the accumulation of fluorophores in a hydrophobic region, had high fluorescence intensity at their centre. Upon addition of a disease-related RNA (the complement of the pre-designed PNA molecule's nucleotide sequence), binding between the PNA and the RNA destabilised the vesicles and disassembly was observed using TEM. This system brings together the highly directable chemistry of nucleotides and the structural versatility of proteins to create dynamical structures that can be triggered by their environment. The authors look to extend this system to generate many other tertiary structures using different polypeptide chains.<br />
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<b>A rotary plasmonic nanoclock</b><br />
<a href="https://www.nature.com/articles/s41467-019-13444-3">https://www.nature.com/articles/s41467-019-13444-3</a><br />
DNA-origami structures can be conjugated with metallic nanoparticles to localize them at defined positions to produce specific photoelectric effects. However, current structures are static or can only alternate between two states. This paper introduces a conjugated DNA structure that resembles a clock. The hands of this nanoclock are formed by a gold nanorod that can rotate 360 degrees with respect to an static gold nanorod. The different degrees of the rod rotation are determined by arbitrary binding points in the DNA structure and by the addition of specific strands in the solution.<br />
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<b>A multiplexed, electrochemical interface for gene-circuit-based sensors</b><br />
<a href="https://www.nature.com/articles/s41557-019-0366-y">https://www.nature.com/articles/s41557-019-0366-y</a><br />
This paper describes the first electrochemical interface that allows expanded multiplexed reporting for cell-free gene-circuit-based sensors. The authors were able to activate gene circuits using DNA nanostructured microelectrodes as electrochemical detectors. This approach uses toehold switch-based RNA sensors, which, in the presence of corresponding trigger RNA, express one of ten restriction-enzyme-based reporters to catalyse the release of specific reporter DNA. This single-stranded DNA can interact with its complementary ssDNA that is conjugated to the electronic surface. A redox reporter molecule attached to the reporter DNA is close enough to an electrode surface to produce generate an electrochemical signal. Thus, each toehold switch is engineered to produce a unique restriction-enzyme-based reporter that is coupled to a distinct reporter DNA and capture DNA pair for multiplexed signalling. The authors demonstrated with this work the power of the electrochemical interface by detecting the activation of specific toehold switch-based RNA sensors allowing to distinct and multiplexed signals to operate without crosstalk.<br />
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<b>Thermodynamics guided strand-displacement-based DNA probe for determination of the average methylation levels of multiple CpG sites</b><br />
<a href="https://pubs.acs.org/doi/10.1021/acs.analchem.9b03198">https://pubs.acs.org/doi/10.1021/acs.analchem.9b03198</a><br />
The authors measured the average degree of methylation using a mismatch-driven shift in the output of strand-displacement reactions. The substrate DNA was amplified with bisulfite PCR which changes non-methylated T base into A base which creates mismatches that participate in the strand displacement process.TomOuldridgehttp://www.blogger.com/profile/02993838123735588463noreply@blogger.com0