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At least 289 records · Page 16Linked to original sources

arXiv2014

Positional information, positional error, and read-out precision in morphogenesis: a mathematical framework

The concept of positional information is central to our understanding of how cells in a multicellular structure determine their developmental fates. Nevertheless, positional information has neither been defined mathematically nor quantified in a principled way. Here we provide an information-theoretic definition in the context of developmental gene expression patterns and examine which features of expression patterns increase or decrease positional information. We connect positional information with the concept of positional error and develop tools to directly measure information and error from experimental data. We illustrate our framework for the case of gap gene expression patterns in the early Drosophila embryo and show how information that is distributed among only four genes is sufficient to determine developmental fates with single cell resolution. Our approach can be generalized to a variety of different model systems; procedures and examples are discussed in detail.

physics.bio-ph↗

arXiv2014

On the emergence of natural singularities and state transitions in living patterns

As far as human perceptions and rational thinking are concerned, contradictions constitute a non negligible part of our reality. We often refer to these phenomena, in a more informal way, as the chicken or the egg causality dilemma. However, it is not clear whether the chicken or the egg dilemma exists only within the scope of our perceptions, or contradictions have a deeper meaning towards our understanding of reality. Here we argue that if there is an element of reality such that can be adequately described in terms of the chicken or the egg dilemma, then it might lead to a spontaneous symmetry breaking by creating an alternate entity, capable of ultimately separating the chicken from the egg. We propose a formalism to describe such mechanism and discuss how it can be applied to phenomena to describe the natural emergence of singularities and state transitions in living systems.

physics.bio-ph↗

arXiv2014

Liquid Metal as Connecting or Functional Recovery Channel for the Transected Sciatic Nerve

In this article, the liquid metal GaInSn alloy (67% Ga, 20.5% In, and 12.5% Sn by volume) is proposed for the first time to repair the peripheral neurotmesis as connecting or functional recovery channel. Such material owns a group of unique merits in many aspects, such as favorable fluidity, super compliance, high electrical conductivity, which are rather beneficial for conducting the excited signal of nerve during the regeneration process in vivo. It was found that the measured electroneurographic signal from the transected bullfrog sciatic nerve reconnected by the liquid metal after the electrical stimulation was close to that from the intact sciatic nerve. The control experiments through replacement of GaInSn with the conventionally used Riger Solution revealed that Riger Solution could not be competitive with the liquid metal in the performance as functional recovery channel. In addition, through evaluation of the basic electrical property, the material GaInSn works more suitable for the conduction of the weak electroneurographic signal as its impedance was several orders lower than that of the well-known Riger Solution. Further, the visibility under the plain radiograph of such material revealed the high convenience in performing secondary surgery. This new generation nerve connecting material is expected to be important for the functional recovery during regeneration of the injured peripheral nerve and the optimization of neurosurgery in the near future.

physics.med-ph↗

arXiv2014

Conformations of Macromolecules and their Complexes from Heterogeneous Datasets

We describe a new generation of algorithms capable of mapping the structure and conformations of macromolecules and their complexes from large ensembles of heterogeneous snapshots, and demonstrate the feasibility of determining both discrete and continuous macromolecular conformational spectra. These algorithms naturally incorporate conformational heterogeneity without resort to sorting and classification, or prior knowledge of the type of heterogeneity present. They are applicable to single-particle diffraction and image datasets produced by X-ray lasers and cryo-electron microscopy, respectively, and particularly suitable for systems not easily amenable to purification or crystallization.

physics.bio-ph↗

arXiv2014

High-resolution structure of viruses from random diffraction snapshots

The advent of the X-ray Free Electron Laser (XFEL) has made it possible to record diffraction snapshots of biological entities injected into the X-ray beam before the onset of radiation damage. Algorithmic means must then be used to determine the snapshot orientations and thence the three-dimensional structure of the object. Existing Bayesian approaches are limited in reconstruction resolution typically to 1/10 of the object diameter, with the computational expense increasing as the eighth power of the ratio of diameter to resolution. We present an approach capable of exploiting object symmetries to recover three-dimensional structure to high resolution, and thus reconstruct the structure of the satellite tobacco necrosis virus to atomic level. Our approach offers the highest reconstruction resolution for XFEL snapshots to date, and provides a potentially powerful alternative route for analysis of data from crystalline and nanocrystalline objects.

physics.bio-ph↗

arXiv2014

Receivers for Diffusion-Based Molecular Communication: Exploiting Memory and Sampling Rate

In this paper, a diffusion-based molecular communication channel between two nano-machines is considered. The effect of the amount of memory on performance is characterized, and a simple memory-limited decoder is proposed and its performance is shown to be close to that of the best possible imaginable decoder (without any restriction on the computational complexity or its functional form), using Genie-aided upper bounds. This effect is specialized for the case of Molecular Concentration Shift Keying; it is shown that a four-bits memory achieved nearly the same performance as infinite memory. Then a general class of threshold decoders is considered and shown not to be optimal for Poisson channel with memory, unless SNR is higher than a value specified in the paper. Another contribution is to show that receiver sampling at a rate higher than the transmission rate, i.e., a multi-read system, can significantly improve the performance. The associated decision rule for this system is shown to be a weighted sum of the samples during each symbol interval. The performance of the system is analyzed using the saddle point approximation. The best performance gains are achieved for an oversampling factor of three.

physics.bio-ph↗

arXiv2014

Ionic Coulomb Blockade and Resonant Conduction in Biological Ion Channels

The conduction and selectivity of calcium/sodium ion channels are described in terms of ionic Coulomb blockade, a phenomenon based on charge discreteness and an electrostatic model of an ion channel. This novel approach provides a unified explanation of numerous observed and modelled conductance and selectivity phenomena, including the anomalous mole fraction effect and discrete conduction bands. Ionic Coulomb blockade and resonant conduction are similar to electronic Coulomb blockade and resonant tunnelling in quantum dots. The model is equally applicable to other nanopores.

physics.bio-ph↗

arXiv2014

Quantifying evolutionary dynamics of the basic genome of E. coli

The ~4-Mbp basic genome shared by 32 independent isolates of E. coli representing considerable population diversity has been approximated by whole-genome multiple-alignment and computational filtering designed to remove mobile elements and highly variable regions. Single nucleotide polymorphisms (SNPs) in the 496 basic-genome pairs are identified and clonally inherited stretches are distinguished from those acquired by horizontal transfer (HT) by sharp discontinuities in SNP density. The six least diverged genome-pairs each have only one or two HT stretches, each occupying 42-115-kbp of basic genome and containing at least one gene cluster known to confer selective advantage. At higher divergences, the typical mosaic pattern of interspersed clonal and HT stretches across the entire basic genome are observed, including likely fragmented integrations across a restriction barrier. A simple model suggests that individual HT events are of the order of 10-kbp and are the chief contributor to genome divergence, bringing in almost 12 times more SNPs than point mutations. As a result of continuing horizontal transfer of such large segments, 400 out of the 496 strain-pairs beyond genomic divergence of share virtually no genomic material with their common ancestor. We conclude that the active and continuing horizontal transfer of moderately large genomic fragments is likely to be mediated primarily by a co evolving population of phages that distribute random genome fragments throughout the population by generalized transduction, allowing efficient adaptation to environmental changes.

q-bio.PE↗

arXiv2014

Selection of Arginine-Rich Anti-Gold Antibodies Engineered for Plasmonic Colloid Self-Assembly

Antibodies are affinity proteins with a wide spectrum of applications in analytical and therapeutic biology. Proteins showing specific recognition for a chosen molecular target can be isolated and their encoding sequence identified in vitro from a large and diverse library by phage display selection. In this work, we show that this standard biochemical technique rapidly yields a collection of antibody protein binders for an inorganic target of major technological importance: crystalline metallic gold surfaces. 21 distinct anti-gold antibody proteins emerged from a large random library of antibodies and were sequenced. The systematic statistical analysis of all the protein sequences reveals a strong occurrence of arginine in anti-gold antibodies, which corroborates recent molecular dynamics predictions on the crucial role of arginine in protein/gold interactions. Once tethered to small gold nanoparticles using histidine tag chemistry, the selected antibodies could drive the self-assembly of the colloids onto the surface of single crystalline gold platelets as a first step towards programmable protein-driven construction of complex plasmonic architectures. Electrodynamic simulations based on the Green Dyadic Method suggest that the antibody-driven assembly demonstrated here could be exploited to significantly modify the plasmonic modal properties of the gold platelets. Our work shows that molecular biology tools can be used to design the interaction between fully folded proteins and inorganic surfaces with potential applications in the bottom-up construction of plasmonic hybrid nanomaterials.

physics.bio-ph↗

arXiv2014

Pathways for virus assembly around nucleic acids

Understanding the pathways by which viral capsid proteins assemble around their genomes could identify key intermediates as potential drug targets. In this work we use computer simulations to characterize assembly over a wide range of capsid protein-protein interaction strengths and solution ionic strengths. We find that assembly pathways can be categorized into two classes, in which intermediates are either predominantly ordered or disordered. Our results suggest that estimating the protein-protein and the protein-genome binding affinities may be sufficient to predict which pathway occurs. Furthermore, the calculated phase diagrams suggest that knowledge of the dominant assembly pathway and its relationship to control parameters could identify optimal strategies to thwart or redirect assembly to block infection. Finally, analysis of simulation trajectories suggests that the two classes of assembly pathways can be distinguished in single molecule fluorescence correlation spectroscopy or bulk time resolved small angle x-ray scattering experiments.

q-bio.BM↗

arXiv2014

Computational modeling of protein interactions and phosphoform kinetics in the KaiABC cyanobacterial circadian clock

The KaiABC circadian clock from cyanobacteria is the only known three-protein oscillatory system which can be reconstituted outside the cell and which displays sustained periodic dynamics in various molecular state variables. Despite many recent experimental and theoretical studies there are several open questions regarding the central mechanism(s) responsible for creating this ~24 hour clock in terms of molecular assembly/disassembly of the proteins and site-dependent phosphorylation and dephosphorylation of KaiC monomers. Simulations of protein-protein interactions and phosphorylation reactions constrained by analytical fits to partial reaction experimental data support the central mechanism of oscillation as KaiB-induced KaiA sequestration in KaiABC complexes associated with the extent of Ser431 phosphorylation in KaiC hexamers. A simple two-state deterministic model in terms of the degree of phosphorylation of Ser431 and Thr432 sites alone can reproduce the previously observed circadian oscillation in the four population monomer phosphoforms in terms of waveform, amplitude and phase. This suggests that a cyclic phosphorylation scheme (involving cooperativity between adjacent Ser431 and Thr432 sites) is not necessary for creating oscillations. Direct simulations of the clock predict the minimum number of serine-only monomer subunits associated with KaiA sequestration and release, highlight the role of monomer exchange in rapid synchronization, and predict the average number of KaiA dimers sequestered per KaiC hexamer.

physics.bio-ph↗

arXiv2014

Proteotronics: Electronic devices based on proteins

The convergent interests of different scientific disciplines, from biochemistry to electronics, toward the investigation of protein electrical properties, has promoted the development of a novel bailiwick, the so called proteotronics. The main aim of proteotronics is to propose and achieve innovative electronic devices, based on the selective action of specific proteins. This paper gives a sketch of the fields of applications of proteotronics, by using as significant example the detection of a specific odorant molecule carried out by an olfactory receptor. The experiment is briefly reviewed and its theoretical interpretation given. Further experiments are envisioned and expected results discussed in the perspective of an experimental validation.

cond-mat.soft↗

arXiv2014

The Habitable Zone of Inhabited Planets

In this paper we discuss and illustrate the hypothesis that life substantially alters the state of a planetary environment and therefore, modifies the limits of the HZ as estimated for an uninhabited planet. This hypothesis lead to the introduction of the Habitable Zone for Inhabited planets (hereafter InHZ), defined here as the region where the complex interaction between life and its abiotic environment is able to produce plausible equilibrium states with the necessary physical conditions for the existence and persistence of life itself. We support our hypothesis of an InHZ with three theoretical arguments, multiple evidences coming from observations of the Earth system, several conceptual experiments and illustrative numerical simulations. Conceptually the diference between the InHZ and the Abiotic HZ (AHZ) depends on unique and robust properties of life as an emergent physical phenomenon and not necesarily on the particular life forms bearing in the planet. Our aim here is to provide conceptual basis for the development of InHZ models incorporating consistently life-environment interactions. Although previous authors have explored the effects of life on habitability there is a gap in research developing the reasons why life should be systematically included at determining the HZ limits. We do not provide here definitive limits to the InHZ but we show through simple numerical models (as a parable of an inhabited planet) how the limits of the AHZ could be modified by including plausible interactions between biota and its environment. These examples aim also at posing the question that if limits of the HZ could be modified by the presence of life in those simple dynamical systems how will those limits change if life is included in established models of the AHZ.

astro-ph.EP↗

arXiv2014

The synergy between protein positioning and DNA elasticity: energy minimization of protein-decorated DNA minicircles

The binding of proteins onto DNA contributes to the shaping and packaging of genome as well as to the expression of specific genetic messages. With a view to understanding the interplay between the presence of proteins and the deformation of DNA involved in such processes, we developed a new method to minimize the elastic energy of DNA fragments at the mesoscale level. Our method makes it possible to obtain the optimal pathways of protein-decorated DNA molecules for which the terminal base pairs are spatially constrained. We focus in this work on the deformations induced by selected architectural proteins on circular DNA. We report the energy landscapes of DNA minicircles subjected to different levels of torsional stress and containing one or two proteins as functions of the chain length and spacing between the proteins. Our results reveal cooperation between the elasticity of the double helix and the structural distortions of DNA induced by bound proteins. We find that the imposed mechanical stress influences the placement of proteins on DNA and that, the proteins, in turn, modulate the mechanical stress and thereby broadcast their presence along DNA.

physics.bio-ph↗

arXiv2014

The Optimal Swimming Sheet

Propulsion at microscopic scales is often achieved through propagating traveling waves along hair-like organelles called flagella. Taylor's two-dimensional swimming sheet model is frequently used to provide insight into problems of flagellar propulsion. We derive numerically the large-amplitude waveform of the two-dimensional swimming sheet that yields optimum hydrodynamic efficiency; the ratio of the squared swimming speed to the rate-of-working of the sheet against the fluid. Using the boundary element method, we show the optimal waveform is a front-back symmetric regularized cusp that is 25% more efficient than the optimal sine-wave. This optimal two-dimensional shape is smooth, qualitatively different from the kinked form of Lighthill's optimal three-dimensional flagellum, not predicted by small-amplitude theory, and different from the smooth circular-arc-like shape of active elastic filaments.

physics.flu-dyn↗

arXiv2014

Biocompatibility of Pristine Graphene Monolayers, Nanosheets and Thin Films

There is an increasing interest to develop nanoscale biocompatible graphene structures due to their desirable physicochemical properties, unlimited application opportunities and scalable production. Here we report the preparation, characterization and biocompatibility assessment of novel graphene flakes and their enabled thin films suitable for a wide range of biomedical and electronic applications. Graphene flakes were synthesized by a chemical vapour deposition method or a liquid-phase exfoliation procedure and then thin films were prepared by transferring graphene onto glass coverslips. Raman spectroscopy and transmission electron microscopy confirmed a predominantly monolayer and a high crystalline quality formation of graphene. The biocompatibility assessment of graphene thin films and graphene flakes was performed using cultured human lung epithelial cell line A549 employing a multimodal approach incorporating automated imaging, high content screening, real-time impedance sensing in combination with biochemical assays. No detectable changes in the cellular morphology or attachment of A549 cells growing on graphene thin films or cells exposed to graphene flakes (0.1 to 5 ug/mL) for 4 to 72 h was observed. Graphene treatments caused a very low level of increase in cellular production of reactive oxygen species in A549 cells, but no detectable damage to the nuclei such as changes in morphology, condensation or fragmentation was observed. In contrast, carbon black proved to be significantly more toxic than the graphene. These data open up a promising view of using graphene enabled composites for a diverse scope of safer applications.

q-bio.CB↗

arXiv2014

LEDs for Energy Efficient Greenhouse Lighting

Light energy is an important factor for plant growth. In regions where the natural light source, i.e. solar radiation, is not sufficient for growth optimization, additional light sources are being used. Traditional light sources such as high pressure sodium lamps and other metal halide lamps are not very efficient and generate high radiant heat. Therefore, new sustainable solutions should be developed for energy efficient greenhouse lighting. Recent developments in the field of light source technologies have opened up new perspectives for sustainable and highly efficient light sources in the form of light-emitting diodes, i.e. LEDs, for greenhouse lighting. This review focuses on the potential of LEDs to replace traditional light sources in the greenhouse. In a comparative economic analysis of traditional vs. LED lighting, we show that the introduction of LEDs allows reduction of the production cost of vegetables in the long-run of several years, due to the high energy efficiency, low maintenance cost and longevity of LEDs. In order to evaluate LEDs as a true alternative to current lighting sources, species specific plant response to different wavelengths is discussed in a comparative study. However, more detailed scientific studies are necessary to understand the effect of different LED spectra on plants physiology. Technical innovations are required to design and realize an energy efficient light source with a spectrum tailored for optimal plant growth in specific plant species.

q-bio.OT↗

arXiv2014

Extensive regulation of metabolism and growth during the cell division cycle

Yeast cells grown in culture can spontaneously synchronize their respiration, metabolism, gene expression and cell division. Such metabolic oscillations in synchronized cultures reflect single-cell oscillations, but the relationship between the oscillations in single cells and synchronized cultures is poorly understood. To understand this relationship and the coordination between metabolism and cell division, we collected and analyzed DNA-content, gene-expression and physiological data, at hundreds of time-points, from cultures metabolically-synchronized at different growth rates, carbon sources and biomass densities. The data enabled us to extend and generalize an ensemble-average-over-phases (EAP) model that connects the population-average gene-expression of asynchronous cultures to the gene-expression dynamics in the single-cells comprising the cultures. The extended model explains the carbon-source specific growth-rate responses of hundreds of genes. Our data demonstrate that for a given growth rate, the frequency of metabolic cycling in synchronized cultures increases with the biomass density. This observation underscores the difference between metabolic cycling in synchronized cultures and in single cells and suggests entraining of the single-cell cycle by a quorum-sensing mechanism. Constant levels of residual glucose during the metabolic cycling of synchronized cultures indicate that storage carbohydrates are required to fuel not only the G1/S transition of the division cycle but also the metabolic cycle. Despite the large variation in profiled conditions and in the time-scale of their dynamics, most genes preserve invariant dynamics of coordination with each other and with the rate of oxygen consumption. Similarly, the G1/S transition always occurs at the beginning, middle or end of the high oxygen consumption phases, analogous to observations in human and drosophila cells.

q-bio.GN↗