Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media

Multicomponent analysis of T1 relaxation in bovine articular cartilage at low magnetic fields

European Union’s Horizon 2020 Research and Innovation Programme; Grant/Award number 668119 (project “IDentIFY”).Peer reviewedPublisher PD

Atypical AT Skew in Firmicute Genomes Results from Selection and Not from Mutation

The second parity rule states that, if there is no bias in mutation or selection, then within each strand of DNA complementary bases are present at approximately equal frequencies. In bacteria, however, there is commonly an excess of G (over C) and, to a lesser extent, T (over A) in the replicatory leading strand. The low G+C Firmicutes, such as Staphylococcus aureus, are unusual in displaying an excess of A over T on the leading strand. As mutation has been established as a major force in the generation of such skews across various bacterial taxa, this anomaly has been assumed to reflect unusual mutation biases in Firmicute genomes. Here we show that this is not the case and that mutation bias does not explain the atypical AT skew seen in S. aureus. First, recently arisen intergenic SNPs predict the classical replication-derived equilibrium enrichment of T relative to A, contrary to what is observed. Second, sites predicted to be under weak purifying selection display only weak AT skew. Third, AT skew is primarily associated with largely non-synonymous first and second codon sites and is seen with respect to their sense direction, not which replicating strand they lie on. The atypical AT skew we show to be a consequence of the strong bias for genes to be co-oriented with the replicating fork, coupled with the selective avoidance of both stop codons and costly amino acids, which tend to have T-rich codons. That intergenic sequence has more A than T, while at mutational equilibrium a preponderance of T is expected, points to a possible further unresolved selective source of skew

Beyond Gross-Pitaevskii Mean Field Theory

A large number of effects related to the phenomenon of Bose-Einstein Condensation (BEC) can be understood in terms of lowest order mean field theory, whereby the entire system is assumed to be condensed, with thermal and quantum fluctuations completely ignored. Such a treatment leads to the Gross-Pitaevskii Equation (GPE) used extensively throughout this book. Although this theory works remarkably well for a broad range of experimental parameters, a more complete treatment is required for understanding various experiments, including experiments with solitons and vortices. Such treatments should include the dynamical coupling of the condensate to the thermal cloud, the effect of dimensionality, the role of quantum fluctuations, and should also describe the critical regime, including the process of condensate formation. The aim of this Chapter is to give a brief but insightful overview of various recent theories, which extend beyond the GPE. To keep the discussion brief, only the main notions and conclusions will be presented. This Chapter generalizes the presentation of Chapter 1, by explicitly maintaining fluctuations around the condensate order parameter. While the theoretical arguments outlined here are generic, the emphasis is on approaches suitable for describing single weakly-interacting atomic Bose gases in harmonic traps. Interesting effects arising when condensates are trapped in double-well potentials and optical lattices, as well as the cases of spinor condensates, and atomic-molecular coupling, along with the modified or alternative theories needed to describe them, will not be covered here.Comment: Review Article (19 Pages) - To appear in 'Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment', Edited by P.G. Kevrekidis, D.J. Frantzeskakis and R. Carretero-Gonzalez (Springer Verlag

General Rules for Optimal Codon Choice

Different synonymous codons are favored by natural selection for translation efficiency and accuracy in different organisms. The rules governing the identities of favored codons in different organisms remain obscure. In fact, it is not known whether such rules exist or whether favored codons are chosen randomly in evolution in a process akin to a series of frozen accidents. Here, we study this question by identifying for the first time the favored codons in 675 bacteria, 52 archea, and 10 fungi. We use a number of tests to show that the identified codons are indeed likely to be favored and find that across all studied organisms the identity of favored codons tracks the GC content of the genomes. Once the effect of the genomic GC content on selectively favored codon choice is taken into account, additional universal amino acid specific rules governing the identity of favored codons become apparent. Our results provide for the first time a clear set of rules governing the evolution of selectively favored codon usage. Based on these results, we describe a putative scenario for how evolutionary shifts in the identity of selectively favored codons can occur without even temporary weakening of natural selection for codon bias

Mode-locking via dissipative Faraday instability

Emergence of coherent structures and patterns at the nonlinear stage of modulation instability of a uniform state is an inherent feature of many biological, physical and engineering systems. There are several well-studied classical modulation instabilities, such as Benjamin-Feir, Turing and Faraday instability, which play a critical role in the self-organization of energy and matter in non-equilibrium physical, chemical and biological systems. Here we experimentally demonstrate the dissipative Faraday instability induced by spatially periodic zig-zag modulation of a dissipative parameter of the system - spectrally dependent losses - achieving generation of temporal patterns and high-harmonic mode-locking in a fibre laser. We demonstrate features of this instability that distinguish it from both the Benjamin-Feir and the purely dispersive Faraday instability. Our results open the possibilities for new designs of mode-locked lasers and can be extended to other fields of physics and engineering

RNAcentral 2021: secondary structure integration, improved sequence search and new member databases

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world’s largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community. RNAcentral is freely available at https://rnacentral.org

Evidence That Mutation Is Universally Biased towards AT in Bacteria

Mutation is the engine that drives evolution and adaptation forward in that it generates the variation on which natural selection acts. Mutation is a random process that nevertheless occurs according to certain biases. Elucidating mutational biases and the way they vary across species and within genomes is crucial to understanding evolution and adaptation. Here we demonstrate that clonal pathogens that evolve under severely relaxed selection are uniquely suitable for studying mutational biases in bacteria. We estimate mutational patterns using sequence datasets from five such clonal pathogens belonging to four diverse bacterial clades that span most of the range of genomic nucleotide content. We demonstrate that across different types of sites and in all four clades mutation is consistently biased towards AT. This is true even in clades that have high genomic GC content. In all studied cases the mutational bias towards AT is primarily due to the high rate of C/G to T/A transitions. These results suggest that bacterial mutational biases are far less variable than previously thought. They further demonstrate that variation in nucleotide content cannot stem entirely from variation in mutational biases and that natural selection and/or a natural selection-like process such as biased gene conversion strongly affect nucleotide content

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur