bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of phenotypic plasticity among populations of three Mediterranean pine species and implications for evolutionary responses to climate change
Authors: Vizcaíno-Palomar Natalia , Fady Bruno , Alía Ricardo , Raffin Annie , Mutke Sven , Garzón Marta Benito 
Published: August 2019

AbstractAimUnder rapid environmental change, phenotypic plasticity, if adaptive, could increase the odds for organisms to persist. Environmental variation over time is an important source of phenotypic plasticity. Likewise, phenotypic plasticity can vary with age in many organisms. However, little is known on phenotypic plasticity variation across species’ ranges. Our aims are: (i) to assess whether populations’ phenotypic plasticity is related to the inter-annual climate variation under which populations have evolved during the last century; (ii) to compare phenotypic plasticity among developmental classes; and (iii) to predict phenotypic plasticity across’ species ranges.LocationEurope and North-Africa.Time period1901-2014.Major taxa studiedPinus nigra, P. pinasterandP. pinea.MethodsWe used 372 646 individual tree height measurements at three developmental classes from a wide network of 38 common gardens in Europe and North Africa with provenances covering the distribution range of the species. With this data, we: i) build linear mixed-effect models of tree height as a function of tree age, population and climate; ii) estimate populations’ reaction norms from the fitted models; iii) calculate populations’ phenotypic plasticity indexes; iv) build models of populations’ phenotypic plasticity indexes as a function of inter-annual climate variation during the last century.ResultsWe found that i) most populations that have evolved under high inter-annual climate variation, in either maximum or minimum values in temperature or precipitation, exhibited high values of plasticity in tree height; ii) phenotypic plasticity for tree height was higher in young trees than in older ones, iii) phenotypic plasticity did not follow any particular geographical pattern across species’ ranges.Main conclusionsPhenotypic plasticity across the three Mediterranean pines’ ranges is related with the climate variation experienced over time and calls into question whether this plasticity could be adaptive and hence beneficial to cope with climate change in the short-term.
Inferring efficiency of translation initiation and elongation from ribosome profiling
Authors: Szavits-Nossan Juraj , Ciandrini Luca 
Published: August 2019

ABSTRACTOne of the main goals of ribosome profiling is to quantify the rate of protein synthesis at the level of translation. Here, we develop a method for inferring translation elongation kinetics from ribosome profiling data using recent advances in the mathematical modelling of mRNA translation. Our method distinguishes between the elongation rate intrinsic to the ribosome’s stepping cycle and the actual elongation rate that takes into account ribosome interference. This distinction allows us to quantify the extent of ribosomal collisions along the transcript and identify individual codons where ribosomal collisions are likely. When examining ribosome profiling in yeast, we observe that translation initiation and elongation are close to their optima, and traffic is minimised at the beginning of the transcript to favour ribosome recruitment. However, we find many individual sites of congestion along the mRNAs where the probability of ribosome interference can reach 50%. Our work provides new measures of translation initiation and elongation efficiencies, emphasising the importance of rating these two stages of translation separately.
Small molecule modulation of a redox-sensitive stress granule protein dissolves stress granules with beneficial outcomes for familial amyotrophic lateral sclerosis models
Authors: Uechi Hiroyuki , Sridharan Sindhuja , Nijssen Jik , Bilstein Jessica , Iglesias-Artola Juan M. , Kishigami Satoshi , Casablancas-Antras Virginia , Poser Ina , Martinez Eduardo J. , Boczek Edgar , Wagner Michael , Tomschke Nadine , de Jesus Domingues António M. , Pal Arun , Doeleman Thom , Kour Sukhleen , Anderson Eric Nathaniel , Stein Frank , Lee Hyun O. , Zhang Xiaojie , Fritsch Anatol W. , Jahnel Marcus , Fürsch Julius , Murthy Anastasia C. , Alberti Simon , Bickle Marc , Fawzi Nicolas L. , Nadler André , David Della C. , Pandey Udai B. , Hermann Andreas , Stengel Florian , Davis Benjamin G. , Baldwin Andrew J. , Savitski Mikhail M. , Hyman Anthony A. , Wheeler Richard J. 
Published: August 2019

AbstractNeurodegeneràve diseases such as amyotrophic lateral sclerosis (ALS) are oten associated with mutàons in proteins that are associated with stress granules. Stress granules are condensates formed by liquid-liquid phase separàon which, when aberrant, can lead to altered condensàon behaviours and disease phenotypes. Here, we identified lipoamide, a small molecule which specifically prevents cytoplasmic condensàon of stress granule proteins. Thermal proteome profiling showed that lipoamide preferentially stabilises intrinsically disordered domain-containing proteins. These include SRSF1 and SFPQ, stress granule proteins necessary for lipoamide activity. The redox state of SFPQ correlates with its condensate-dissolving behaviour, in concordance with the importance of the dithiolane ring for lipoamide activity. In animals, lipoamide ameliorates aging-associated aggregàon of a stress granule reporter, improves neuronal morphology, and recovers motor defects caused by expression of ALS-associated FUS and TDP-43 mutants. In conclusion, lipoamide is a well-tolerated small molecule modulator of stress granule condensàon and dissection of its molecular mechanism identified a cellular pathway for redox regulàon of stress granule formàon.
Fluid shear stress coupled with narrow constrictions induce cell type-dependent morphological and molecular changes in circulating tumor cells
Authors: Cognart Hamizah Ahmad , Viovy Jean-Louis , Villard Catherine 
Published: August 2019

AbstractCancer mortality mainly arises from metastases, due to cells that escape from a primary tumor, circulate in the blood as circulating tumor cells (CTCs), permeate across blood vessels and nest in distant organs. It is still unclear how CTCs overcome the harsh conditions of fluid shear stress and mechanical constraints within the microcirculation. Here, a model of the blood microcirculation was established through the fabrication of microfluidic channels comprising constrictions. Metastatic breast cancer cells of epithelial-like and mesenchymal-like phenotypes were flowed into the microfluidic device. These cells were visualized during circulation, analyzed for their dynamical behavior and retrieved post-circulation. γ-H2AX staining showed significant increase of DNA damage response in epithelial-like SK-BR-3 cells, while gene expression analysis of key regulators of epithelial-to-mesenchymal transition revealed significant increase of Twist2 relative expression in mesenchymal-like MDA-MB-231 cells post-circulation. This work documents first results of the changes at the cellular, subcellular and molecular scales induced by the two main mechanical stimuli arising from circulatory conditions.
Hot-spots and their contribution to the self-assembly of the viral capsid: in-silico prediction and analysis
Authors: Díaz-Valle Armando , Falcón-González José Marcos , Carrillo-Tripp Mauricio 
Published: August 2019

AbstractIn order to rationally design biopolymers that mimic biological functions, first, we need to elucidate the molecular mechanisms followed by nature. For example, the viral capsid is a macromolecular complex formed by self-assembled proteins which, in many cases, are biopolymers with an identical amino acid sequence. Specific protein-protein interactions drive the capsid self-assembly process, leading to several distinct protein interfaces. Following the hot-spot hypothesis, we propose a conservation-based methodology to identify those interface residues that are crucial elements on the self-assembly and thermodynamic stability of the capsid. We validate our predictions by computational free energy calculations using an atomic-scale molecular model of an icosahedral virus. Our results show that a single mutation in any of the hot-spots significantly perturbs the quaternary interaction, decreasing the absolute value of the binding free energy, without altering the tertiary structure. Our methodology can lead to a strategy to rationally modulate the capsid’s thermodynamic properties.
Exponential Growth of GlioblastomaIn VivoDriven by Rapidly Dividing and Outwardly Migrating Cancer Stem Cells
Authors: Buchauer Lisa , Khan Muhammad Amir , Zhuo Yue , Shao Chunxuan , Zou Peng , Feng Weijun , Qian Mengran , Bekki Gözde , Bunne Charlotte , Neuerburg Anna , Acikgöz Azer Aylin , Tomaschko Mona , Zhu Zhe , Alter Heike , Hartmann Katharina , Friesen Olga , Hexel Klaus , Höfer Thomas , Liu Hai-Kun 
Published: August 2019

AbstractHow overall tumor growth emerges from the properties of functionally heterogeneous tumor cell subpopulations is a fundamental question of cancer biology. Here we combined lineage tracing, continuous monitoring of tumor mass, proliferation assays and transcriptomics with mathematical modeling and statistical inference to dissect the growth of glioblastoma in mice. We found that tumors grow exponentially at the rate of symmetric divisions of brain tumor stem cells (BTSCs). Spatial modeling predicts, and data show, that BTSCs accumulate at the tumor rim rather than in the core. The physiological differentiation hierarchy downstream of BTSCs is preserved in mice and humans: transit amplifying progenitors give rise to terminally differentiated cells. Consistent with our quantification of the mechanisms underlying tumor growth, molecular data show elevated expression of cell cycle-and migration-related genes in BTSCs. Our systematic approach reveals fundamental properties of glioblastoma and may be transferable to the study of other animal models of cancer.
Mammalian musculoskeletal regeneration is associated with reduced inflammatory cytokines and an influx of T cells
Authors: Gawriluk Thomas R. , Simkin Jennifer , Hacker Corin K. , Kimani John M. , Kiama Stephen G. , Ezenwa Vanessa O. , Seifert Ashley W. 
Published: August 2019

ABSTRACTWhether the immune response to injury contributes to tissue regeneration is not well understood. We quantified systemic and local cytokines during ear pinna repair to provide the first comprehensive comparison of the immune response to injury between mammalian regeneration (A. cahirinusandA. percivali) and fibrotic repair (M. musculus). Importantly, by comparing laboratory-reared and wild-caught animals we identified responses specifically associated with healing outcome. Fibrotic repair showed a greater local release of IL-6, CCL2 and CXCL1. Conversely, regeneration showed decreased circulating IL-5, IL-6, IL-17, CCL3 and CXCL1 and increased local IL-12 and IL-17. The differential IL-6 response was substantiated by increased pSTAT3 during the inflammatory phase of fibrotic repair and with blastema formation and tissue morphogenesis inAcomys. COX-2 inhibition was not sufficient to induce regeneration. Interestingly, a unique influx of lymphocytes was coupled with regeneration and RNA-expression analysis suggested they were regulatory T cells. Together, the data support regeneration-specific inflammation and T cell responses inAcomys.
Investigating the biomechanical properties of streptococcal polysaccharide capsules using atomic force microscopy
Authors: Marshall H , Aguayo S , Kilian M , Petersen FC , Bozec L , Brown JS 
Published: August 2019

AbstractIn common with many bacterial pathogens,Streptococcus pneumoniaehas a polysaccharide capsule, which facilitates immune evasion and is a key virulence determinant. However, recent data has shown that the closely relatedStreptococcus mitiscan also express polysaccharide capsules including those with an identical chemical structure toS. pneumoniaecapsular serotypes. We have used atomic force microscopy (AFM) techniques to investigate the biophysical properties ofS. mitisandS. pneumoniaestrains expressing the same capsular serotypes that might relate to their differences in virulence potential. When comparingS. mitisandS. pneumoniaestrains with identical capsule serotypesS. mitisstrains were more susceptible to neutrophil killing and imaging using electron microscopy and AFM demonstrated significant morphological differences. Force-volume mapping using AFM showed distinct force-curve profiles for the centre and edge areas of encapsulatedS. pneumoniaeandS. mitisstrains. This “edge effect” was not observed in the unencapsulated streptococcal strains and in an unencapsulatedStaphylococcus aureusstrain, and therefore was a direct representation of the mechanical properties of the bacterial capsule. When two strains ofS. mitisandS. pneumoniaeexpressed an identical capsular serotype, they presented also similar biomechanical characteristics. This would infer a potential relationship between capsule biochemistry and nanomechanics, independent of the bacterial strains. Overall, AFM was an effective tool to explore the biophysical properties of bacterial capsules of living bacteria by reproducibly quantifying the elastic and adhesive properties of bacterial cell surfaces. Using AFM to investigate capsule differences over a wider range of strains and capsular serotypes of streptococci and correlate the data with phenotypic differences will elucidate how the biophysical properties of the capsule can influence its biological role during infection.
Discovery of a polybrominated aromatic secondary metabolite from a planctomycete points at an ambivalent interaction with its macroalgae host
Authors: Panter Fabian , Garcia Ronald , Thewes Angela , Zaburannyi Nestor , Bunk Boyke , Overmann Jörg , Gutierrez Mary Victory , Krug Daniel , Müller Rolf 
Published: August 2019

AbstractThe roles of the majority of bacterial secondary metabolites, especially those from uncommon sources are yet elusive even though many of these compounds show striking biological activities. To further investigate the secondary metabolite repertoire of underexploited bacterial families, we chose to analyze a novel representative of the yet untapped bacterial phylum Planctomycetes for the production of secondary metabolites under laboratory culture conditions. Development of a planctomycetal high density cultivation technique in combination with high resolution mass spectrometric analysis revealed Planctomycetales strain 10988 to produce the plant toxin 3,5 dibromo p-anisic acid. This molecule represents the first secondary metabolite reported from any planctomycete. Genome mining revealed the biosynthetic origin of this doubly brominated secondary metabolite and a biosynthesis model for the com-pound was devised. Comparison of the biosynthetic route to biosynthetic gene clusters responsible for formation of polybrominated small aromatic compounds reveals evidence for an evolutionary link, while the compound’s herbicidal activity points towards an ambivalent role of the metabolite in the planctomycetal ecosystem.
Death is on Our Side: Paleontological Data Drastically Modify Phylogenetic Hypotheses
Authors: Koch Nicolás Mongiardino , Parry Luke A. 
Published: August 2019

ABSTRACTFossils are the only remaining evidence of the majority of species that have ever existed, providing a direct window into events in evolutionary history that shaped the diversification of life on Earth. Phylogenies underpin our ability to make sense of evolution but are routinely inferred only from data available from living organisms. Although extinct taxa have been shown to add crucial information for inferring macroevolutionary patterns and processes including ancestral states, paleobiogeography and diversification dynamics, the role that fossils play in inferring the tree of life itself is controversial. Since the early years of phylogenetic systematics, different studies have dismissed the impact of fossils due to their incompleteness, championed their ability to overturn phylogenetic hypotheses or concluded that their behavior is indistinguishable from that of extant taxa. Here we show paleontological data has a remarkable effect in phylogenetic inference. Fossils often have higher levels of topological influence than extant taxa, while inducing unique topological rearrangements. Previous studies have proposed a suite of explanations for the topological behavior of fossils, such as their retention of unique morphologies or their ability to break long branches. We develop predictive models that demonstrate that the possession of distinctive character state combinations is the primary predictor of the degree of induced topological change, and that the relative impact of taxa (fossil and extant) can be predicted to some extent before any analysis. Our results bolster the consensus of recent empirical studies by showing the unique role of paleontological data in phylogenetic inference, and provide the first quantitative assessment of its determinants, with broad consequences for the design of taxon sampling in both morphological and total-evidence analyses.
Sequencing smart:De novosequencing and assembly approaches for non-model mammals
Authors: Etherington Graham J , Heavens Darren , Baker David , Lister Ashleigh , McNelly Rose , Garcia Gonzalo , Clavijo Bernardo , Macaulay Iain , Haerty Wilfried , Di Palma Federica 
Published: August 2019

AbstractBackgroundWhilst much sequencing effort has focused on key mammalian model organisms such as mouse and human, little is known about the correlation between genome sequencing techniques for non-model mammals and genome assembly quality. This is especially relevant to non-model mammals, where the samples to be sequenced are often degraded and low quality. A key aspect when planning a genome project is the choice of sequencing data to generate. This decision is driven by several factors, including the biological questions being asked, the quality of DNA available, and the availability of funds. Cutting-edge sequencing technologies now make it possible to achieve highly contiguous, chromosome-level genome assemblies, but relies on good quality high-molecular-weight DNA. The funds to generate and combining these data are often only available within large consortiums and sequencing initiatives, and are often not affordable for many independent research groups. For many researchers, value-for-money is a key factor when considering the generation of genomic sequencing data. Here we use a range of different genomic technologies generated from a roadkill European Polecat (Mustela putorius) to assess various assembly techniques on this low-quality sample. We evaluated different approaches forde novoassemblies and discuss their value in relation to biological analyses.ResultsGenerally, assemblies containing more data types achieved better scores in our ranking system. However, when accounting for misassemblies, this was not always the case for Bionano and low-coverage 10x Genomics (for scaffolding only). We also find that the extra cost associated with combining multiple data types is not necessarily associated with better genome assemblies.ConclusionsThe high degree of variability between eachde novoassembly method (assessed from the seven key metrics) highlights the importance of carefully devising the sequencing strategy to be able to carry out the desired analysis. Adding more data to genome assemblies not always results in better assemblies so it is important to understand the nuances of genomic data integration explained here, in order to obtain cost-effective value-for-money when sequencing genomes.
Topological data analysis to uncover the shape of immune responses during co-infection
Authors: Sasaki Karin , Bruder Dunja , Hernandez-Vargas Esteban 
Published: August 2019

AbstractCo-infections by multiple pathogens have important implications in many aspects of health, epidemiology and evolution. However, how to disentangle the contributing factors of the immune response when two infections take place at the same time is largely unexplored. Using data sets of the immune response during influenza-pneumococcal co-infection in mice, we employ here topological data analysis to simplify and visualise high dimensional data sets.We identified persistent shapes of the simplicial complexes of the data in the three infection scenarios: single viral infection, single bacterial infection, and co-infection. The immune response was found to be distinct for each of the infection scenarios and we uncovered that the immune response during the co-infection has three phases and two transition points. During the first phase, its dynamics is inherited from its response to the primary (viral) infection. The immune response has an early (few hours post co-infection) and then modulates its response to finally react against the secondary (bacterial) infection. Between 18 to 26 hours post co-infection the nature of the immune response changes again and does no longer resembles either of the single infection scenarios.Author summaryThe mapper algorithm is a topological data analysis technique used for the qualitative analysis, simplification and visualisation of high dimensional data sets. It generates a low-dimensional image that captures topological and geometric information of the data set in high dimensional space, which can highlight groups of data points of interest and can guide further analysis and quantification.To understand how the immune system evolves during the co-infection between viruses and bacteria, and the role of specific cytokines as contributing factors for these severe infections, we use Topological Data Analysis (TDA) along with an extensive semi-unsupervised parameter value grid search, and k-nearest neighbour analysis.We find persistent shapes of the data in the three infection scenarios, single viral and bacterial infections and co-infection. The immune response is shown to be distinct for each of the infections scenarios and we uncover that the immune response during the co-infection has three phases and two transition points, a previously unknown property regarding the dynamics of the immune response during co-infection.
Fine-scale seascape genomics of an exploited marine species, the common cockle Cerastoderma edule, using a multi-modelling approach
Authors: Coscia Ilaria , Wilmes Sophie B. , Ironside Joseph E. , Goward-Brown Alice , O’Dea Enda , Malham Shelagh K. , McDevitt Allan D. , Robins Peter E. 
Published: August 2019

ABSTRACTPopulation dynamics of marine species that are sessile as adults are driven by oceanographic dispersal of larvae from spawning to nursery grounds. This is mediated by life-history traits such as the timing and frequency of spawning, larval behaviour and duration, and settlement success. Here, we use 1725 single nucleotide polymorphisms (SNPs) to study the fine scale spatial genetic structure in the commercially important cockle species Cerastoderma edule and compare it to environmental variables and current-mediated larval dispersal within a modelling framework. Hydrodynamic modelling employing the NEMO Atlantic Margin Model (AMM15) was used to simulate larval transport and estimate connectivity between populations during spawning months (April - September), factoring in larval duration and seasonal variability of ocean currents. Results at neutral loci reveal the existence of three separate genetic clusters (mean FST=0.021) within a relatively fine spatial scale in the northwest Atlantic. Environmental association (EA) analysis indicates that oceanographic currents and geographical distance between the populations explain over 20% of the variance observed at neutral loci, while genetic variance (71%) at outlier loci was explained by sea surface temperatures extremes. These results fill an important knowledge gap in the management of a commercially important, overexploited species, and bring us closer to understanding the role of larval dispersal in connecting populations at a fine geographical scale.