Biology subjects

Hernandez, C.

Publications and source records attributed to Hernandez, C..

44 records · Page 3Linked to original sources

bioRxiv2019

Adaptive and maladaptive genetic diversity in small populations; insights from the Brook Charr (Salvelinus fontinalis) case study

Investigating the relative importance of neutral versus selective processes governing the accumulation of genetic variants is a key goal in evolutionary biology. This is particularly true in the context of small populations, where genetic drift can counteract the effect of selection. In this study, we investigated the accumulation of putatively beneficial and harmful variations using 7,950 high-quality filtered SNPs among 36 lacustrine, seven riverine and seven anadromous Brook Charr (Salvelinus fontinalis) populations (n = 1,193) from Quebec, Canada. Using the Provean algorithm, we observed an accumulation of deleterious mutations that tend to be more prevalent in isolated lacustrine and riverine populations than the more connected anadromous populations. In addition, the absence of correlation between the occurrence of putative beneficial nor deleterious mutations and local recombination rate supports the hypothesis that genetic drift might be the main driver of the accumulation of such variants. Despite the effect of pronounced genetic drift and limited gene flow in non-anadromous populations, several loci representing biological functions of potential adaptive significance were associated with environmental variables, and particularly with temperature. We also identified genomic regions associated with anadromy. We also observed an overrepresentation of transposable elements associated with variation in environmental variables, thus supporting the importance of transposable elements in adaptation.

evolutionary biology↗

bioRxiv2019

Bubble Trouble: Conquering Microbubble Limitations in Contrast Enhanced Ultrasound Imaging by Nature-Inspired Ultrastable Echogenic Nanobubbles

Advancement of ultrasound molecular imaging applications requires not only a reduction in size of the ultrasound contrast agents (UCAs) but also a significant improvement in the in vivo stability of the shell-stabilized gas bubble. The transition from first generation to second generation UCAs was marked by an advancement in stability as air was replaced by a hydrophobic gas, such as perfluoropropane and sulfur hexafluoride. Further improvement can be realized by focusing on how well the UCAs shell can retain the encapsulated gas under extreme mechanical deformations. Here we report the next generation of UCAs for which we engineered the shell structure to impart much better stability under repeated prolonged oscillation due to ultrasound, and large changes in shear and turbulence as it circulates within the body. By adapting an architecture with two layers of contrasting elastic properties similar to bacterial cell envelopes, our ultrastable nanobubbles (NBs) withstand continuous in vitro exposure to ultrasound with minimal signal decay and have a significant delay on the onset of in vivo signal decay in kidney, liver, and tumor. Development of ultrastable NBs can potentially expand the role of ultrasound in molecular imaging, theranostics, and drug delivery.

bioengineering↗

bioRxiv2019

Mechanical stress compromises multicomponent efflux complexes in bacteria

Physical forces have long been recognized for their effects on the growth, morphology, locomotion, and survival of eukaryotic organisms1. Recently, mechanical forces have been shown to regulate processes in bacteria, including cell division2, motility3, virulence4, biofilm initiation5,6, and cell shape7,8, although it remains unclear how mechanical forces in the cell envelope lead to changes in molecular processes. In Gram-negative bacteria, multicomponent protein complexes that form rigid links across the cell envelope directly experience physical forces and mechanical stresses applied to the cell. Here we manipulate tensile and shear mechanical stress in the bacterial cell envelope and use single-molecule tracking to show that shear (but not tensile) stress within the cell envelope promotes disassembly of the tripartite efflux complex CusCBA, a system used by E. coli to resist copper and silver toxicity, thereby making bacteria more susceptible to metal toxicity. These findings provide the first demonstration that mechanical forces, such as those generated during colony overcrowding or bacterial motility through submicron pores, can inhibit the contact and function of multicomponent complexes in bacteria. As multicomponent, trans-envelope efflux complexes in bacteria are involved in many processes including antibiotic resistance9, cell division10, and translocation of outer membrane components11, our findings suggest that the mechanical environment may regulate multiple processes required for bacterial growth and survival.

biophysics↗

bioRxiv2019

The Microbial Metagenome and Tissue Composition in Mice with Microbiome-Induced Reductions in Bone Strength

The genetic components of microbial species that inhabit the body are known collectively as the microbiome. Modifications to the microbiome have been implicated in disease processes throughout the body and have recently been shown to influence bone. Prior work has associated changes in the microbial taxonomy (phyla, class, species, etc.) in the gut with bone phenotypes but has provided limited information regarding mechanisms. With the goal of achieving a more mechanistic understanding of the effects of the microbiome on bone, we perform a metagenomic analysis of the gut microbiome that provides information on the functional capacity of the microbes (all microbial genes present) rather than only characterizing the microbial taxa. Male C57Bl/6 mice were subjected to disruption of the gut microbiota ({Delta}Microbiome) using oral antibiotics (from 4-16 weeks of age) or remained untreated (n=6-7/group). Disruption of the gut microbiome in this manner has been shown to lead to reductions in tissue mechanical properties and whole bone strength in adulthood with only minor changes in bone geometry and density. {Delta}Microbiome led to modifications in the abundance of microbial genes responsible for the synthesis of the bacterial cell wall and capsule; bacterially synthesized carbohydrates; and bacterially synthesized vitamins (B and K) (p <0.01). Follow up analysis focused on vitamin K, a factor that has previously been associated with bone health. The vitamin K content of the cecum, liver and kidneys was primarily microbe-derived forms of vitamin K (menaquinones) and was decreased by 32-66% in {Delta}Microbiome mice compared to untreated animals (p < 0.01). Bone mineral crystallinity was decreased (p=0.01) was decreased in {Delta}Microbiome mice (p < 0.001) and matrix carbonate-phosphoate ratio was increased. This study illustrates the use of metagenomic analysis to link the microbiome to bone phenotypes and implicates microbially synthesized vitamin-K as a regulator of bone matrix quality.

bioengineering↗

bioRxiv2018

Bone-Inspired Microarchitectured Materials with Enhanced Fatigue Life

Microarchitectured materials achieve superior mechanical properties through geometry rather than composition 1-4. Although lightweight, high-porosity microarchitectured materials can have high stiffness and strength, stress concentrations within the microstructure can cause flaw intolerance under cyclic loading 5,6, limiting fatigue life. However, it is not known how microarchitecture contributes to fatigue life. Naturally occurring materials can display exceptional mechanical performance and are useful models for the design of microarchitectured materials 7,8. Cancellous bone is a naturally occurring microarchitectured material that often survives decades of habitual cyclic loading without failure. Here we show that resistance to fatigue failure in cancellous bone is sensitive to the proportion of material oriented transverse to applied loads - a 30% increase in density caused by thickening transversely oriented struts increases fatigue life by 10-100 times. This finding is surprising in that transversely oriented struts have negligible effects on axial stiffness, strength and energy absorption. The effects of transversely oriented material on fatigue life are also present in synthetic lattice microstructures. In both cancellous bone and synthetic microarchitectures, the fatigue life can be predicted using the applied cyclic stress after adjustment for apparent stiffness and the proportion of the microstructure oriented transverse to applied loading. In the design of microarchitectured materials, stiffness, strength and energy absorption is often enhanced by aligning the microstructure in a preferred direction. Our findings show that introduction of such anisotropy, by reducing the amount of material oriented transverse to loading, comes at the cost of reduced fatigue life. Fatigue failure of durable devices and components generates substantial economic costs associated with repair and replacement. As advancements in additive manufacturing expand the use of microarchitectured materials to reusable devices including aerospace applications, it is increasingly necessary to balance the need for fatigue life with those of strength and density.

bioengineering↗

bioRxiv2018

Prediction of Mutations to Control Pathways Enabling Tumour Cell Invasion with the CoLoMoTo Interactive Notebook (Tutorial)

Boolean and multi-valued logical formalisms are increasingly used to model complex cellular networks. To ease the development and analysis of logical models, a series of software tools have been proposed, often with specific assets. However, combining these tools typically implies a series of cumbersome software installation and model conversion steps. In this respect, the CoLoMoTo Interactive Notebook provides a joint distribution of several logical modelling software tools, along with an interactive web Python interface easing the chaining of complementary analyses. In this protocol, we demonstrate the assets of this approach through the analysis of a computational model of biological network. Our computational workflow combines (1) the importation of a GINsim model and its display, (2) its format conversion using the Java library BioLQM, (3) the formal prediction of mutations using the OCaml software Pint, (4) the model checking using the C++ software NuSMV, (5) quantitative stochastic simulations using the C++ software MaBoSS, and (6) the visualisation of results using the Python library matplotlib. Starting with a recent Boolean model of the signalling network controlling tumour cell invasion and migration, our model analysis culminates with the prediction of sets of mutations presumably involved in a metastatic phenotype.

systems biology↗

bioRxiv2018

The CoLoMoTo Interactive Notebook: Accessible and Reproducible Computational Analyses for Qualitative Biological Networks

Analysing models of biological networks typically relies on workflows in which different software tools with sensitive parameters are chained together, many times with additional manual steps. The accessibility and reproducibility of such workflows is challenging, as publications often overlook analysis details, and because some of these tools may be difficult to install, and/or have a steep learning curve. The CoLoMoTo Interactive Notebook provides a unified environment to edit, execute, share, and reproduce analyses of qualitative models of biological networks. This framework combines the power of different technologies to ensure repeatability and to reduce users learning curve of these technologies. The framework is distributed as a Docker image with the tools ready to be run without any installation step besides Docker, and is available on Linux, macOS, and Microsoft Windows. The embedded computational workflows are edited with a Jupyter web interface, enabling the inclusion of textual annotations, along with the explicit code to execute, as well as the visualisation of the results. The resulting notebook files can then be shared and re-executed in the same environment. To date, the CoLoMoTo Interactive Notebook provides access to software tools including GINsim, BioLQM, Pint, MaBoSS, and Cell Collective for the modelling and analysis of Boolean and multi-valued networks. More tools will be included in the future. We developed a Python interface for each of these tools to offer a seamless integration in the Jupyter web interface and ease the chaining of complementary analyses.

bioinformatics↗

bioRxiv2018

Logical modelling and analysis of cellular regulatory networks with GINsim 3.0

The logical formalism is well adapted to model large cellular networks, for which detailed kinetic data are scarce. This tutorial focuses on this well-established qualitative framework. Relying on GINsim (release 3.0), a software implementing this formalism, we guide the reader step by step towards the definition, the analysis and the simulation of a four-node model of the mammalian p53-Mdm2 network.

systems biology↗