Reading group - lots of novel DNA systems, including cryptography!

Self-Assembly of DNA Origami Heterodimers in High Yields and Analysis of the Involved Mechanisms
https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201902979

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.

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%.


Coupling of DNA Circuit and Templated Reactions for Quadratic Amplification and Release of Functional Molecules
https://pubs.acs.org/doi/abs/10.1021/jacs.9b05688

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.


Nucleobase-Templated Polymerization: Copying the Chain Length and Polydispersity of Living Polymers into Conjugated Polymers. 
https://doi.org/10.1021/ja809613n

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.

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.
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.

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.

This is experimental confirmation that templates, regardless of informational content, are unsurprisingly effective in narrowing and controlling polymer length distributions.


De novo design of protein logic gates
https://science.sciencemag.org/content/368/6486/78

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.

DNA origami cryptography for secure communication

https://www.nature.com/articles/s41467-019-13517-3

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).

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.

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.

A blueprint for a synthetic genetic feedback controller to reprogram cell fate

https://www.ncbi.nlm.nih.gov/pubmed/28065574

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. 

Nicking-Assisted Reactant Recycle To Implement Entropy-Driven DNA Circuit

https://pubs.acs.org/doi/10.1021/jacs.9b07521

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.

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.

The Protection Role of Magnesium Ions on Coupled Transcription and Translation in Lyophilized Cell-Free System 

https://pubs.acs.org/doi/10.1021/acssynbio.9b00508

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.

Kinetic Proofreading and the limits of thermodynamic uncertainty: a review. Jenny Poulton

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.

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 [TO1] 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.

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.

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 non-matching 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 non-matching ones will fall off. Thus the system can generate accuracy.

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.

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 not the same as the uncertainty in the thermodynamic uncertainty relation.

Figure 1; 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.

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  happens . For example, the number of times a system undergoes a specific transition. In a case of a molecular walker  could be the uncertainty in how far the walker had walked with the net number of forward steps being . In the case of a copy process   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  would not automatically give you a relationship between the number of right and wrong things added. The form of the uncertainty relationship  tells us that we can again spend energy to reduce the uncertainty; here  is the energy cost of the process per unit time multiplied by the time.

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  and the uncertainty , are not immediately related to each other and should not be conflated.

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.

Figure 2 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.

The paper focusses on the number of times the system above goes round the green cycles in figure 2, with this being   .  The thermodynamic uncertainty variable  is defined relative to this. They define a lower bound on  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; . They thus define a quantity  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  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  . They present these results and suggest that a lower  means that the system is capable of better trading off error and speed, although this isn’t necessarily persuasively explained.

In the next section the authors ask how turning off two of the reactions, which reduce accessibility to parts of the network, changes . They relate this to error  and , a time constant which quantifies the time taken to go round the cycle.

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.

The authors state that in both cases  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.

The authors point out that in case a) Q decouples from  as the reaction is removed, but the network retains it’s dependence on  in case b). They then explore how  depends on Q. In both cases they find that as the reactions are removed,  decouples from Q. This tells us that in the accurate limit where only the reduced cycle happens, Q is not related to . So the measurement of Q seems like a curious choice when it is decoupled from both  and  in the accurate limit.

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.

A full house of papers combining DNA with other biomolecules to stabilise, direct and monitor assembly

Coating and Stabilization of Liposomes by Clathrin-Inspired DNA Self-Assembly 
doi:10.1021/acsnano.9b09453

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.


Peptide Assembly Directed and Quantified Using Megadalton DNA Nanostructures 
https://doi.org/10.1021/acsnano.9b04251

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.


Directed Energy Transfer through DNA-Templated J-Aggregates
https://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00043

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.

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.

A DNA-based artificial metabolism, the thermodynamics of Turing machines and more...

Inferring dissipation from current fluctuations Todd R Gingrich, Grant M Rotskoff, and Jordan M Horowitz
https://doi.org/10.1088/1751-8121/aa672f

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.


Homogeneous and universal detection of various targets based on dual‐step transduced toehold switch sensor
https://onlinelibrary.wiley.com/doi/abs/10.1002/cbic.201900749

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.


Dynamic DNA material with emergent locomotion behaviour powered by artificial metabolism
https://robotics.sciencemag.org/content/4/29/eaaw3512

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.

The business of DNA nanotechnology: Commercialization of origami and other technologies

https://www.mdpi.com/1420-3049/25/2/377

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.

Mathematical Models of Protease-Based Enzymatic Biosensors

https://pubs.acs.org/doi/10.1021/acssynbio.9b00279

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.

​An RNA polymerase ribozyme that synthesizes its own ancestor

https://www.pnas.org/content/117/6/2906

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.

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.

Thermodynamic costs of Turing Machines

https://arxiv.org/abs/1912.04685

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.

(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.

(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

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

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.

(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).


Scalable Computational Framework for Establishing Long-Term Behavior of Stochastic Reaction Networks.
https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003669

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. 

Two papers on DNA nanostructures for scaffolding of proteins, plus some other stuff...

Designed Protein Cages as Scaffolds for Building Multienzyme Materials
https://dx.doi.org/10.1021/acssynbio.9b00407

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.

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.


Engineering a DNAzyme-Based Operon System for the Production of DNA nanoscaffolds in Living Bacteria
https://pubs.acs.org/doi/abs/10.1021/acssynbio.9b00415

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.


Design of thiazole orange oligonucleotide probes for detection of DNA and RNA by fluorescence and duplex melting
https://pubs.rsc.org/en/content/articlelanding/2019/ob/c9ob00885c#!divAbstract

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.

Do 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?

Improved protein structure prediction using potentials from deep learning
https://www.nature.com/articles/s41586-019-1923-7

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.

Learning about learning by many-body systems

https://arxiv.org/abs/2001.03623

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. 

Fundamentally, to really learn, 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. 

Sequence information transfer using covalent template-directed synthesis https://doi.org/10.1039/c9sc01460h

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.

Landauer's principle at zero temperature

https://arxiv.org/pdf/1911.00910.pdf

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. 

Solving the chemical master equation for monomolecular reaction systems analytically: a Doi-Peliti path integral view.

https://arxiv.org/abs/1911.00978 .

The manuscript considers the problem of obtaining time-dependent solutions of the chemical master equation (CME) by using so-called Doi-Peliti path-integral method. The method formulates the CME as an operator equation for an associated generating function, which is solved via a sequence of integration steps, providing time-dependent probability mass-functions and the underlying moments. The Doi-Peliti path-integral approach has been utilized in the manuscript  to recover previously obtained results for so-called monomolecular networks (which consist of reactions whose complexes are single species), and to provide novel result for a more general (non-monomolecular) one-species first-order network, which includes an auto-catalytic reaction.

Deep Learning for RNA Synthetic Biology

https://www.biorxiv.org/content/10.1101/872077v1.full.pdf

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. 

Implementing  digital computing with DNA-based switching circuits

https://www.nature.com/articles/s41467-019-13980-y

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.

Will any crap we we put into graphene increase its electrocatalytic effect? 

https://pubs.acs.org/doi/10.1021/acsnano.9b00184

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

Ordered three-dimensional nanomaterials using DNA-prescribed and valence-controlled material voxels

https://www.nature.com/articles/s41563-019-0550-x?

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.

Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase 

https://www.nature.com/articles/s41565-019-0544-5

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.