bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using connectivity to identify climatic drivers of local adaptation
Authors: Macdonald Stewart L. , Llewelyn John , Phillips Ben L. 
Published: June 2017

AbstractThis preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100034).Despite being able to conclusively demonstrate local adaptation, we are still often unable to objectively determine the climatic drivers of local adaptation. Given the rapid rate of global change, understanding the climatic drivers of local adaptation is vital. Not only will this tell us which climate axes matter most to population fitness, but such knowledge is critical to inform management strategies such as translocation and targeted gene flow. While simple assessments of geographic trait variation are useful, geographic variation (and its associations with environment) may represent plastic, rather than evolved, differences. Additionally, the vast number of trait–environment combinations makes it difficult to determine which aspects of the environment populations adapt to. Here we argue that by incorporating a measure of landscape connectivity as a proxy for gene flow, we can differentiate between trait–environment relationships underpinned by genetic differences versus those that reflect phenotypic plasticity. By doing so, we can rapidly shorten the list of trait–environment combinations that may be of adaptive significance. We demonstrate how this reasoning can be applied using data on geographic trait variation in a lizard species from Australia's Wet Tropics rainforest. Our analysis reveals an overwhelming signal of local adaptation for the traits and environmental variables we investigated. Our analysis also allows us to rank environmental variables by the degree to which they appear to be driving local adaptation. Although encouraging, methodological issues remain: we point to these issue in the hope that the community can rapidly hone the methods we sketch here. The promise is a rapid and general approach to identifying the environmental drivers of local adaptation.
Pair Matcher (PaM): fast model-based optimisation of treatment\case-control matches using demographic and genetic data
Authors: Ryan Desmond M , Elhaik Eran 
Published: June 2017

AbstractIn clinical trials, individuals are matched for demographic criteria, paired, and then randomly assigned to treatment and control groups to determine a drug’s efficacy. The successful completion of pilot trials is a prerequisite to larger and more expensive Phase III trials. One of the chief causes for the irreproducibility of results across pilot to Phase III trials is population stratification bias caused by the uneven distribution of ancestries in the treatment and control groups. Pair Matcher (PaM) addresses stratification bias by optimising pairing assignmentsa priori- and\orposteriorito the trial using both genetic and demographic criteria. Using simulated and real datasets, we show thatPaMidentifies ideal and near-ideal pairs that are more genetically homogeneous than those identified based on racial criteria or Principal Component Analysis (PCA) alone. Homogenising the treatment (or case) and control groups can be expected to improve the accuracy and reproducibility of the study.PaM’s ability to infer the ancestry of the participants further allows identifying subgroup of responders and developing a precision medicine approach to treatment.PaMis simple to execute, fast, and can be used for clinical trials and association studies.PaMis freely available via R scripts and a web interface.
Subharmonics and chaos in simple periodically-forced biomolecular models
Authors: Nikolaev Evgeni V. , Rahi Sahand Jamal , Sontag Eduardo D. 
Published: June 2017

AbstractThis paper uncovers a remarkable behavior in two biochemical systems that commonly appear as components of signal transduction pathways in systems biology. These systems have globally attracting steady states when unforced, so they might have been considered “uninteresting” from a dynamical standpoint. However, when subject to a periodic excitation, strange attractors arise via a period-doubling cascade. Quantitative analyses of the corresponding discrete chaotic trajectories are conducted numerically by computing largest Lyapunov exponents, power spectra, and autocorrelation functions. To gain insight into the geometry of the strange attractors, the phase portraits of the corresponding iterated maps are interpreted as scatter plots for which marginal distributions are additionally evaluated. The lack of entrainment to external oscillations, in even the simplest biochemical networks, represents a level of additional complexity in molecular biology, which has previously been insufficiently recognized but is plausibly biologically important.
Effective online Bayesian phylogenetics via sequential Monte Carlo with guided proposals
Authors: Fourment Mathieu , Claywell Brian C. , Dinh Vu , McCoy Connor , Matsen Frederick A. , Darling Aaron E. 
Published: June 2017

AbstractModern infectious disease outbreak surveillance produces continuous streams of sequence data which require phylogenetic analysis as data arrives. Current software packages for Bayesian phy-logenetic inference are unable to quickly incorporate new sequences as they become available, making them less useful for dynamically unfolding evolutionary stories. This limitation can be addressed by applying a class of Bayesian statistical inference algorithms called sequential Monte Carlo (SMC) to conductonline inference, wherein new data can be continuously incorporated to update the estimate of the posterior probability distribution. In this paper we describe and evaluate several different online phylogenetic sequential Monte Carlo (OPSMC) algorithms. We show that proposing new phylogenies with a density similar to the Bayesian prior suffers from poor performance, and we develop ‘guided’ proposals that better match the proposal density to the posterior. Furthermore, we show that the simplest guided proposals can exhibit pathological behavior in some situations, leading to poor results, and that the situation can be resolved by heating the proposal density. The results demonstrate that relative to the widely-used MCMC-based algorithm implemented in MrBayes, the total time required to compute a series of phylogenetic posteriors as sequences arrive can be significantly reduced by the use of OPSMC, without incurring a significant loss in accuracy.
An intracellular pathogen response pathway promotes proteostasis inC. elegans
Authors: Reddy Kirthi C. , Dror Tal , Sowa Jessica N. , Panek Johan , Chen Kevin , Lim Efrem S. , Wang David , Troemel Emily R. 
Published: June 2017

SummaryMaintenance of proteostasis is critical for organismal health. Here we describe a novel pathway that promotes proteostasis, identified through the analysis ofC. elegansgenes upregulated by intracellular infection. We named this distinct transcriptional signature the Intracellular Pathogen Response (IPR), and it includes upregulation of several predicted ubiquitin ligase complex components such as the cullincul-6. Through a forward genetic screen we foundpals-22, a gene of previously unknown function, to be a repressor of thecul-6/Cullin gene and other IPR gene expression. Interestingly,pals-22mutants have increased thermotolerance and reduced levels of stress-induced polyglutamine aggregates, likely due to upregulated IPR expression. We found the enhanced stress resistance ofpals-22mutants to be dependent oncul-6, suggesting thatpals-22mutants have increased activity of a CUL-6/Cullin-containing ubiquitin ligase complex. pals-22mutant phenotypes are distinct from the well-studied heat shock and insulin signaling pathways, indicating that the IPR is a novel pathway that protects animals from proteotoxic stress.
KmerFinderJS: A client-server method for fast species typing of bacteria over slow Internet connections
Authors: Cineros Jose Luis Bellod , Lund Ole 
Published: June 2017

AbstractMotivationKmerFinder is a program based on K-mer statistics for identifying bacterial species in whole genome data, that as a web server that have been used more than 10.000 times. Kmer-FinderJS is a development of the KmerFinder that benefits from the downsampling of data using a prefix filtering used by KmerFinder, to minimize amount of data that needs to be transferred between the client and the server.ResultsKmerFinderJS replaces the python based hash structure for holding the databases with a true Key-value database. These improvements are shown to lead to a many-fold speed up of species identification with the internet transfer speeds that are realistic to expect today. It is also shown that the method can find the true content of an artificial metagenomic cocktail with no false positives.AvailabilityThe method is freely available athttps://cge.cbs.dtu.dk/services/KmerFinderJS/and as a source code athttps://bitbucket.org/genomicepidemiology/kmerfinderjsContactcisneros@cbs.dtu.dkSupplementary informationSupplementary data are available atbiorxivonline.
Energetic costs of cellular and therapeutic control of stochastic mtDNA populations
Authors: Hoitzing Hanne , Gammage Payam A. , Minczuk Michal , Johnston Iain G. , Jones Nick S. 
Published: June 2017

SummaryMitochondrial DNA (mtDNA) copy numbers fluctuate over time due to stochastic cellular dynamics. Understanding mtDNA dynamics and the accumulation of mutations is vital for understanding mitochondrial-related diseases. Here, we use stochastic modelling to derive general results for the impact of cellular control on mtDNA populations, the cost to the cell of different mtDNA states, and the optimisation of therapeutic control of mtDNA populations. We provide theoretical evidence that an increasing mtDNA variance can increase the energetic cost of maintaining a tissue, that intermediate levels of heteroplasmy can be more detrimental than ho-moplasmy even for a dysfunctional mutant, that het-eroplasmy distribution (not mean alone) is crucial for the success of gene therapies, and that long-term rather than short intense gene therapies are more likely to beneficially impact mtDNA populations. New experiments validate our predictions on heteroplasmy dependence of therapeutic outcomes.
Beyond brain size
Authors: Logan Corina J , Avin Shahar , Boogert Neeltje , Buskell Andrew , Cross Fiona R. , Currie Adrian , Jelbert Sarah , Lukas Dieter , Mares Rafael , Navarrete Ana F , Shigeno Shuichi , Montgomery Stephen H 
Published: June 2017

AbstractDespite prolonged interest in comparing brain size and behavioral proxies of ‘intelligence’ across taxa, the adaptive and cognitive significance of brain size variation remains elusive. Central to this problem is the continued focus on hominid cognition as a benchmark, and the assumption that behavioral complexity has a simple relationship with brain size. Although comparative studies of brain size have been criticized for not reflecting how evolution actually operates, and for producing spurious, inconsistent results, the causes of these limitations have received little discussion. We show how these issues arise from implicit assumptions about what brain size measures and how it correlates with behavioral and cognitive traits. We explore how inconsistencies can arise through heterogeneity in evolutionary trajectories and selection pressures on neuroanatomy or neurophysiology across taxa. We examine how interference from ecological and life history variables complicates interpretations of brain-behavior correlations, and point out how this problem is exacerbated by the limitations of brain and cognitive measures. These considerations, and the diversity of brain morphologies and behavioral capacities, suggest that comparative brain-behavior research can make greater progress by focusing on specific neuroanatomical and behavioral traits within relevant ecological and evolutionary contexts. We suggest that a synergistic combination of the ‘bottom up’ approach of classical neuroethology and the ‘top down’ approach of comparative biology/psychology within closely related but behaviorally diverse clades can limit the effects of heterogeneity, interference, and noise. We argue this shift away from broad-scale analyses of superficial phenotypes will provide deeper, more robust insights into brain evolution.
Mycophenolate mofetil increases inflammation resolution in zebrafish via neutrophil apoptosis
Authors: Bojarczuk Aleksandra , Johnston Simon A. 
Published: June 2017

AbstractMycophenolate mofetil (MMF) is an immunosuppressive agent used in the treatment of autoimmune and inflammatory conditions, and following organ transplant. MMF treatment results in lymphopenia via the depletion of purines required for DNA synthesis. While the primary effect of MMF treatment is thought to be via the depletion of lymphocytes, MMF has also been associated with innate immune defects, including neutropenia and neutrophil dysplasia. Here, we address the question of MMF specific effects on neutrophils in anin vivomodel of neutrophil inflammation in zebrafish. We find that, following tissue injury, MMF increases resolution of neutrophilic inflammation via increased neutrophil apoptosis. Critically, we identify that the effect of MMF is distinct from DNA synthesis inhibition by using the competitive inhibitor of purine nucleotide incorporation, azathioprine. Therefore, we propose that increased neutrophil cell death during inflammatory insult may play a role in neutrophil defects associated with MMF treatment.
Modelling personality, plasticity and predictability in shelter dogs
Authors: Goold Conor , Newberry Ruth C. 
Published: June 2017

AbstractBehavioural assessments of shelter dogs (Canis lupus familiaris) typically comprise standardised test batteries conducted at one time point but test batteries have shown inconsistent predictive validity. Longitudinal behavioural assessments offer an alternative. We modelled longitudinal observational data on shelter dog behaviour using the framework of behavioural reaction norms, partitioning variance into personality (i.e. inter-individual differences in behaviour), plasticity (i.e. individual differences in behavioural change) and predictability (i.e. individual differences in residual intra-individual variation). We analysed data on 3,263 dogs’ interactions (N = 19,281) with unfamiliar people during their first month after arrival at the shelter. Accounting for personality, plasticity (linear and quadratic trends) and predictability improved the predictive accuracy of the analyses compared to models quantifying personality and/or plasticity only. While dogs were, on average, highly sociable with unfamiliar people and sociability increased over days since arrival, group averages were unrepresentative of all dogs and predictions made at the individual level entailed considerable uncertainty. Effects of demographic variables (e.g. age) on personality, plasticity and predictability were observed. Behavioural repeatability was higher one week after arrival compared to arrival day. Our results highlight the value of longitudinal assessments on shelter dogs and identify measures that could improve the predictive validity of behavioural assessments in shelters.
Central amygdala circuits modulate food consumption through a positive valence mechanism
Authors: Douglass Amelia M. , Kucukdereli Hakan , Ponserre Marion , Markovic Milica , Gründemann Jan , Strobel Cornelia , Alcala Morales Pilar L. , Conzelmann Karl-Klaus , Lüthi Andreas , Klein Rüdiger 
Published: June 2017

SummaryThe complex behaviors underlying the pursuit and consumption of rewards are integral to an organism’s survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is not well understood. The central nucleus of the amygdala (CeA) is implicated in feeding and reward behavior, but the specific neural players and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we define the neuronal mechanisms by which the CeA promotes consumption of food. We show, usingin vivoactivity manipulations and Ca2+imaging, that CeA GABAergic neurons expressing the serotonin receptor 2a (Htr2a) modulate food consumption in multiple contexts, promote positive reinforcement and are activein vivoduring eating. We demonstrate using electrophysiology, anatomical tracing methods andin vivooptogenetics that both intra-CeA and long-range circuit mechanisms underlie these functional effects. Finally, we show that CeAHtr2aneurons are poised to regulate food consumption through inputs from feeding-relevant brain regions. Our study highlights a mechanism by which defined CeA neural circuits positively regulate food consumption.
Alkyl gallates display elicitor activities in tobacco plants
Authors: Goupil Pascale , Benouaret Razik , Richard Claire 
Published: June 2017

AbstractAlkyl gallates showed elicitor activities on tobacco in both whole plants and cell suspensions. Methyl gallate (MG), ethyl gallate (EG) andn-propyl gallate (PG) infiltration into tobacco leaves induced hypersensitive reaction-like lesions and topical production of autofluorescent compounds revealed under UV light. When sprayed on tobacco plants at 5 mM, EG promoted upregulation of defence-related genes such as the antimicrobialPR1, β-1,3-glucanasePR2, chitinasePR3and osmotinPR5target genes. Tobacco BY-2 cells challenged with EG underwent cell death in 48 h, significantly reduced in the presence of the protease inhibitor aprotinin. The three alkyl gallates all caused alkalinisation of the BY-2 extracellular medium, whereas gallic acid did not trigger any pH variation. Using EGTA or LaCl3, we showed that Ca2+mobilisation occurred in BY-2 cells elicited with EG. Overall, our findings are the first evidence of alkyl gallate elicitor properties with early perception events on plasma membrane, potential hypersensitive reactions and PR-related downstream defence responses in tobacco.Highlights–Alkyl gallates elicited defence reactions in tobacco–Alkyl gallates induced local biochemical changes in tobacco leaves–Alkyl gallates caused modification of plasma membrane properties–Ethyl gallate led to defence transcript accumulation and dose-dependent cell death associated with hypersensitive response–Alkyl gallates are novel elicitor agents well-suited to crop protection schemes.
Heme-iron plays a key role in the regulation of the Ess/Type VII secretion system ofStaphylococcus aureusRN6390
Authors: Casabona M. Guillermina , Kneuper Holger , de Lima Daniela Alferes , Harkins Catriona P. , Zoltner Martin , Hjerde Erik , Holden Matthew T.G. , Palmer Tracy 
Published: June 2017

ABSTRACTTheStaphylococcus aureusType VII protein secretion system (T7SS) plays important roles in virulence and intra-species competition. Here we show that the T7SS in strain RN6390 is activated by supplementing the growth medium with hemoglobin, and its cofactor hemin (heme B). Transcript analysis and secretion assays suggest that activation by hemin occurs at a transcriptional and a post-translational level. Loss of T7 secretion activity by deletion ofessCresults in upregulation of genes required for iron acquisition. Taken together these findings suggest that the T7SS plays a role in iron homeostasis in at least someS. aureusstrains.
High current optogenetic channels for stimulation and inhibition of primary rat cortical neurons
Authors: Jin Lei , Joest Eike Frank , Li Wenfang , Gao Shiqiang , Offenhäusser Andreas , Maybeck Vanessa 
Published: June 2017

AbstractChR2-XXL and GtACR1 are currently the cation and anion ends of the optogenetic single channel current range. These were used in primary rat cortical neuronsin vitroto manipulate neuronal firing patterns. ChR2-XXL provides high cation currents via elevated light sensitivity and a prolonged open state. Stimulating ChR2-XXL expressing putative presynaptic neurons induced neurotransmission. Moreover, stable depolarisation block could be generated in single neurons using ChR2-XXL, proving that ChR2-XXL is a promising candidate forin vivoapplications of optogenetics, for example to treat peripheral neuropathic pain. We also addressed an anion channelrhodopsin (GtACR1) for the next generation of optogenetic neuronal inhibition in primary rat cortical neurons. GtACR1‘s light-gated chloride conduction was verified in primary neurons and the efficient photoinhibition of action potentials, including spontaneous activity, was shown. Our data also implies that the chloride concentration in neurons decreases during neural development. In both cases, we find surprising applications of these high current channels. For ChR2-XXL inhibition and stimulation are possible, while for GtACR1 the role of Cl−during neural development becomes a new optogenetic target.
Haplotype and Repeat Separation in Long Reads
Authors: Tischler German 
Published: June 2017

AbstractResolving the correct structure and succession of highly similar sequence stretches is one of the main open problems in genome assembly. For non haploid genomes this includes determining the sequences of the different haplotypes. For all but the smallest genomes it also involves separating different repeat instances. In this paper we discuss methods for resolving such problems in third generation long reads by classifying alignments between long reads according to whether they represent true or false read overlaps. The main problem in this context is the high error rate found in such reads, which greatly exceeds the amount of difference between the similar regions we want to separate. Our methods can separate read classes stemming from regions with as little as 1% difference.
A Cross-Sectional Study ofStaphylococcus AureusColonization and the Nasal and Oropharyngeal Microbiomes
Authors: Kates Ashley E. , Dalman Mark , Torner James C. , Smith Tara C. 
Published: June 2017

AbstractBackgroundStaphylococcus aureusis a frequent cause of both infections globally. Colonization with the organism is known to increase the risk of developing infections and occurs in roughly one third of the general population. While many factors influence colonization, it has been demonstrated other members of the microbiome influence colonization withS. aureus. Here, we assessed the nasal and oropharyngeal microbiomes of healthy participants in relation toS. aureuscolonization in a cross-sectional study using 16s rRNA sequencing of the v1-v3 region. As livestock workers have also been shown to be at an increased risk of carriage, we have also assessed microbiota differences in colonization status in a population of livestock workers.ResultsIn both the nares and oropharynx, there were no microbiota differentially abundant between colonized and non-colonized persons. However, there was a significant difference in the beta diversity (Bray-Curtis distances) between carriers and non-carriers (P=0.002). When considering carriage stratified by livestock exposure, there were a number of differences. Most notably, colonized livestock workers had significantly morePorphyomonas(2-fold change = -8.54,P= 0.03) than the non-colonized livestock workers.ConclusionsS. aureusis a frequent colonizer of the human upper respiratory tract, including the nares and oropharynx and causes a wide range of infections. Livestock workers are at increased risk for carriage. Interventions such as improving oral hygiene may lead to decreasedS. aureuscarriage by reducing other bacterial species such asPorphyomonas. Larger, longitudinal studies are needed to better explore what microorganisms may be associated withS. aureuscolonization.