bluuebunny/crossref_metadata_2025_split huggingface dataset:
Links between mouse and vole social networks and their gut microbiomes support predictions from metacommunity theory
Authors: Jameson Joël W. , Kembel Steven W. , Réale Denis 
Published: August 2020

ABSTRACTMetacommunity theory predicts that strongly connected individuals will harbour similar gut microbiomes (GMs) and affiliating with more individuals should increase GM diversity. Additionally, cross-species bacterial transmission may play a role in how interspecific interactions affect host community dynamics. We tracked sympatric mice (Peromyscus maniculatus) and voles (Myodes gapperi) and constructed social networks for each species and both species together. We tested whether: 1) similarity in GM composition between individuals correlates with their social proximity within and across species; 2) GM diversity correlates with a host’s number of conspecific or heterospecific neighbours. We could not differentiate associations between GM composition and mouse social proximity or habitat. In voles, social proximity explained part of the GM composition. GM composition associated with interspecific social proximity, and mouse GM diversity correlated with number of vole neighbours. Contributions of host-host bacterial transmission to the GM partly follow metacommunity theory but depend on host species.
ICA-based Denoising Strategies in Breath-Hold Induced Cerebrovascular Reactivity Mapping with Multi Echo BOLD fMRI
Authors: Moia Stefano , Termenon Maite , Uruñuela Eneko , Chen Gang , Stickland Rachael C. , Bright Molly G. , Caballero-Gaudes César 
Published: August 2020

AbstractPerforming a BOLD functional MRI (fMRI) acquisition during breath-hold (BH) tasks is a non-invasive, robust method to estimate cerebrovascular reactivity (CVR). However, movement and breathing-related artefacts caused by the BH can substantially hinder CVR estimates due to their high temporal collinearity with the effect of interest, and attention has to be paid when choosing which analysis model should be applied to the data. In this study, we evaluate the performance of multiple analysis strategies based on lagged general linear models applied on multi-echo BOLD fMRI data, acquired in ten subjects performing a BH task during ten sessions, to obtain subjectspecific CVR and haemodynamic lag estimates. The evaluated approaches range from conventional regression models including drifts and motion timecourses as nuisance regressors applied on singleecho or optimally-combined data, to more complex models including regressors obtained from multi-echo independent component analysis with different grades of orthogonalization in order to preserve the effect of interest, i.e. the CVR. We compare these models in terms of their ability to make signal intensity changes independent from motion, as well as the reliability as measured by voxelwise intraclass correlation coefficients of both CVR and lag maps over time. Our results reveal that a conservative independent component analysis model applied on the optimally-combined multi-echo fMRI signal offers the largest reduction of motion-related effects in the signal, while yielding reliable CVR amplitude and lag estimates, although a conventional regression model applied on the optimally-combined data results in similar estimates. This work demonstrate the usefulness of multi-echo based fMRI acquisitions and independent component analysis denoising for precision mapping of CVR in single subjects based on BH paradigms, fostering its potential as a clinically-viable neuroimaging tool for individual patients. It also proves that the way in which data-driven regressors should be incorporated in the analysis model is not straight-forward due to their complex interaction with the BH-induced BOLD response.
A distinct growth physiology enhances bacterial growth under rapid nutrient fluctuations
Authors: Nguyen Jen , Fernandez Vicente , Pontrelli Sammy , Sauer Uwe , Ackermann Martin , Stocker Roman 
Published: August 2020

AbstractIt has been long known that bacteria coordinate their physiology with environmental nutrient, yet our current understanding offers little intuition for how bacteria respond to the second-to-minute scale fluctuations in nutrient concentration characteristic of many microbial habitats. To investigate the effects of rapid nutrient fluctuations on bacterial growth, we coupled custom microfluidics with single-cell microscopy to quantify the growth rate ofE. coliexperiencing 30 s to 60 min nutrient fluctuations. Compared to steady environments of equal average concentration, fluctuating environments reduced growth rate by up to 50%. However, measured reductions in growth rate were only 38% of the growth loss predicted from single nutrient shifts — an enhancement produced by the distinct growth response of cells grown in environments that fluctuate rather than shift once. We report an unexpected physiology adapted for growth in nutrient fluctuations and implicate nutrient timescale as a critical environmental parameter beyond nutrient concentration and source.
An inexpensive semi-automated sample processing pipeline for cell-free RNA
Authors: Moufarrej Mira N. , Quake Stephen R. 
Published: August 2020

AbstractDespite advances in automated liquid handling and microfluidics, preparing samples for RNA sequencing at scale generally requires expensive equipment, which is beyond the reach of many academic labs. Manual sample preparation remains a slow, expensive, and error-prone process. Here, we describe a low-cost, semi-automated pipeline to extract cell-free RNA (cfRNA) that like many RNA isolation protocols, can be decomposed into three subparts – RNA extraction, DNA digestion, and RNA cleaning and concentration. RT-qPCR data using a synthetic spike-in confirms comparable RNA quality as compared to manual sample processing, the gold-standard used in our prior work. The semi-automated pipeline also shows striking improvement in sample throughput (+12x), time spent (−11x), cost (−3x), and biohazardous waste produced (−4x) as compared to its manual counterpart. In total, this protocol enables cfRNA extraction from 96 samples simultaneously in 4.5 hours; in practice, this dramatically improves time to results as demonstrated in our recent work [1] where it was used to process 404 samples in 27 hours. Importantly, any lab already has most of the parts required (manual pipette, corresponding tips and kits) to build a semi-automated sample processing pipeline of their own and would only need to purchase or 3D-print a few extra parts ($5.5K total). This pipeline is also generalizable for many nucleic acid extraction applications, thereby increasing the scale of studies, which can be performed in small research labs.
Boosting photosynthetic machinery and defense priming with chitosan application on tomato plants infected withFusarium oxysporumf. sp.lycopersici
Authors: Carmona Sandra L. , del Pilar Villarreal-Navarrete Andrea , Burbano-David Diana , Gómez-Marroquín Magda , Torres-Rojas Esperanza , Soto-Suárez Mauricio 
Published: August 2020

AbstractPhysiological processes of plants infected by vascular pathogens are mainly affected by vascular bundle obstruction, decreasing the absorption of water and nutrients and gas exchange by stomatal closure, and inducing oxidative cascades and PSII alterations. Chitosan, a derivative of chitin present in the cell wall of some organisms including fungi, induces plant defense responses, activating systemic resistance. In this study, the effect of chitosan on the physiological and molecular responses of tomato plants infected withFusarium oxysporumf. sp.lycopersici(Fol) was studied, evaluating the maximum potential quantum efficiency of PSII photochemistry (Fv/Fm), photochemical efficiency of PSII (Y(II)), photochemical quenching (qP), stomatal conductance (gs), relative water content (RWC), proline content, photosynthetic pigments, dry mass, and differential gene expression (PAL, LOXA, ERF1,andPR1) of defense markers. A reduction of 70% in the incidence and 91% in the severity of the disease was achieved in plants treated with chitosan, mitigating the damage caused byFolon Fv/Fm, Y(II), and chlorophyll contents by 23%, 36%, and 47%, respectively. Less impact was observed on qP, gs, RWC, and dry mass (16%, 11%, and 26%, respectively). Chitosan-treated andFol-infected plants over-expressedPR1agene suggesting a priming-associated response. These results demonstrate the high potential of chitosan to protect tomato plants againstFolby regulating physiological and molecular responses in tomato plants.
Color compensation in anomalous trichromats assessed with fMRI
Authors: Tregillus Katherine E.M. , Isherwood Zoey J. , Vanston John E. , Engel Stephen A. , MacLeod Donald I.A. , Kuriki Ichiro , Webster Michael A. 
Published: August 2020

AbstractAnomalous trichromacy is a common form of congenital color-deficiency resulting from a genetic alteration in the photopigments of the eye’s light receptors. The changes reduce sensitivity to reddish and greenish hues, yet previous work suggests that these observers may experience the world to be more colorful than their altered receptor sensitivities would predict, potentially indicating an amplification of post-receptoral signals. However, past evidence suggesting such a gain adjustment rests on subjective measures of color appearance or salience. We directly tested for neural amplification by using fMRI to measure cortical responses in color-anomalous and normal control observers. Color contrast response functions were measured in two experiments with different tasks to control for attentional factors. Both experiments showed a predictable reduction in chromatic responses for anomalous trichromats in primary visual cortex. However, in later areas V2v and V3v, chromatic responses in the two groups were indistinguishable. Our results provide direct evidence for neural plasticity that compensates for the deficiency in the initial receptor color signals and suggest that the site of this compensation is in early visual cortex.
Epigenetic memory as a time integral over prior history of Polycomb phase separation
Authors: Eeftens Jorine M. , Kapoor Manya , Brangwynne Clifford P. 
Published: August 2020

ABSTRACTStructural organization of the genome into transcriptionally active euchromatin and silenced heterochromatin is essential for eukaryotic cell function. Heterochromatin is a more compact form of chromatin, and is associated with characteristic post-translational histone modifications and chromatin binding proteins. Phase-separation has recently been suggested as a mechanism for heterochromatin formation, through condensation of heterochromatin associated proteins. However, it is unclear how phase-separated condensates can contribute to stable and robust repression, particularly for heritable epigenetic changes. The Polycomb complex PRC1 is known to be key for heterochromatin formation, but the multitude of Polycomb proteins has hindered our understanding of their collective contribution to chromatin repression. Here, we take a quantitative live cell imaging approach to show that PRC1 proteins form multicomponent condensates through hetero-oligomerization. They preferentially seed at H3K27me3 marks, and subsequently write H2AK119Ub marks. Using optogenetics to nucleate local Polycomb condensates, we show that Polycomb phase separation can induce chromatin compaction, but phase separation is dispensable for maintenance of the compacted state. Our data are consistent with a model in which the time integral of historical Polycomb phase separation is progressively recorded in repressive histone marks, which subsequently drive chromatin compaction. These findings link the equilibrium thermodynamics of phase separation with the fundamentally non-equilibrium concept of epigenetic memory.
Probabilistic Framework for Integration of Mass Spectrum and Retention Time Information in Small Molecule Identification
Authors: Bach Eric , Rogers Simon , Williamson John , Rousu Juho 
Published: August 2020

MotivationIdentification of small molecules in a biological sample remains a major bottleneck in molecular biology, despite a decade of rapid development of computational approaches for predicting molecular structures using mass spectrometry (MS) data. Recently, there has been increasing interest in utilizing other information sources, such as liquid chromatography (LC) retention time (RT), to improve the MS based identifications.ResultsWe put forward a probabilistic modelling framework to integrate MS and RT data of multiple features in an LC-MS experiment. We model the MS measurements and all pairwise retention order information as a Markov random field and use efficient approximate inference for scoring and ranking potential molecular structures. Our experiments show improved identification accuracy by combining tandem mass spectrometry data (MS2) and retention orders using our approach, thereby outperforming state-of-the-art methods. Furthermore, we demonstrate the benefit of our model when only a subset of LC-MS features have MS2measurements available besides MS1.Availability and implementationSoftware and data is freely available athttps://github.com/aalto-ics-kepaco/msms_rt_score_integration.Contacteric.bach@aalto.fi
Ketamine selectively enhances AMPA neurotransmission onto a subgroup of identified serotoninergic neurons of the rat dorsal raphe
Authors: Hmaied Cyrine , Koulchitsky Stanislav , Gladwyn-Ng Ivan , Seutin Vincent 
Published: August 2020

ABSTRACTAlthough the fast antidepressant effect of ketamine is now well established clinically, neither its mechanism(s) nor its main site(s) of action is clearly defined. Because enhanced serotoninergic (5-HT) transmission is an important part of the antidepressant effect of various drug classes, we asked whether ketamine and one of its metabolites (hydroxynorketamine [HNK]), both used in their racemic form, may modulate the excitatory drive onto these neurons.Using whole-cell recordings from pharmacologically identified 5-HT and non-5-HT neurons in juvenile rat dorsal raphe slices, we found that both ketamine and HNK (10 µM) increase excitatory AMPA neurotransmission onto a subset (50%) of 5-HT neurons, whereas other 5-HT cells were unaffected. Both compounds increased the amplitude as well as the frequency of spontaneous excitatory post-synaptic currents (sEPSCs) mediated by AMPA receptors. The effect of ketamine was more robust than the one of HNK, since it significantly enhanced the charge transfer through AMPA channels, whereas HNK did not. The increase in the excitatory drive induced by ketamine was dependent on NMDA receptor blockade. In the presence of tetrodotoxin, the effect of ketamine was markedly reduced. Non-5-HT neurons, on the other hand, were unaffected by the drugs.We conclude that ketamine and HNK increase the excitatory drive onto a subset of 5-HT neurons by promoting glutamate release and possibly also through a postsynaptic action. The effect of ketamine is dependent on NMDA receptor modulation and appears to involve a network effect. These findings improve our understanding of the fast-acting antidepressant effect of ketamine.SIGNIFICANCE STATEMENTThe mechanisms of ketamine’s antidepressant effect are currently controversial. We asked whether the drug would produce changes is the strength of synaptic inputs onto serotoninergic neurons of the dorsal raphe. We found that this is indeed the case in about half of these neurons. The action of ketamine was mimicked to some extent by its well-known metabolite hydroxynorketamine, was dependent on NMDA receptor activation and probably involved a local network effect. It remains to be determined if the differential susceptibility of serotoninergic neurons to the drug correlates with any differential inputs and/or outputs.
Single-cell transcriptomics reveals immune response of intestinal cell types to viral infection
Authors: Triana Sergio , Stanifer Megan L. , Shahraz Mohammed , Mukenhirn Markus , Kee Carmon , Ordoñez-Rueda Diana , Paulsen Malte , Benes Vladimir , Boulant Steeve , Alexandrov Theodore 
Published: August 2020

AbstractHuman intestinal epithelial cells form a primary barrier protecting us from pathogens, yet only limited knowledge is available about individual contribution of each cell type to mounting an immune response against infection. Here, we developed a pipeline combining single-cell RNA-Seq and highly-multiplex RNA imaging and applied it to human intestinal organoids infected with human astrovirus, a model human enteric virus. We found that interferon controls the infection and that astrovirus infects all major cell types and lineages with a preferential infection of proliferating cells. Intriguingly, each intestinal epithelial cell lineage has a unique basal expression of interferon-stimulated genes and, upon astrovirus infection, undergoes an antiviral transcriptional reprogramming by upregulating distinct sets of interferon-stimulated genes. These findings suggest that in the human intestinal epithelium, each cell lineage plays a unique role in resolving virus infection. Our pipeline can be applicable to other organoids and viruses, opening new avenues to unravel roles of individual cell types in viral pathogenesis.
The double-stranded DNA-binding proteins TEBP-1 and TEBP-2 form a telomeric complex with POT-1
Authors: Dietz Sabrina , Almeida Miguel Vasconcelos , Nischwitz Emily , Schreier Jan , Viceconte Nikenza , Fradera-Sola Albert , Renz Christian , Ceron-Noriega Alejandro , Ulrich Helle D. , Kappei Dennis , Ketting René F. , Butter Falk 
Published: August 2020

AbstractTelomeres are bound by dedicated protein complexes, like shelterin in mammals, which protect telomeres from DNA damage. In the nematodeCaenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to screen for proteins binding toC. elegans telomeres, and identified TEBP-1 and TEBP-2, two paralogs that associate to telomeres in vitro and in vivo. TEBP-1 and TEBP-2 are expressed in the germline and during embryogenesis.tebp-1andtebp-2mutants display strikingly distinct phenotypes:tebp-1mutants have longer telomeres than wild-type animals, whiletebp-2mutants display shorter telomeres and a mortal germline, a phenotype characterized by transgenerational germline deterioration. Notably,tebp-1;tebp-2double mutant animals have synthetic sterility, with germlines showing signs of severe mitotic and meiotic arrest. TEBP-1 and TEBP-2 form a telomeric complex with the known single-stranded telomere-binding proteins POT-1, POT-2, and MRT-1. Furthermore, we find that POT-1 bridges the double- stranded binders TEBP-1 and TEBP-2, with the single-stranded binders POT-2 and MRT-1. These results describe the first telomere-binding complex inC. elegans, with TEBP-1 and TEBP-2, two double-stranded telomere binders required for fertility and that mediate opposite telomere dynamics.
Evolution of virulence in emerging epidemics: inference from an evolution experiment
Authors: Blanquart François , Berngruber Thomas , Choisy Marc , Gandon Sylvain 
Published: August 2020

AbstractInference using mathematical models of infectious disease dynamics is a powerful tool to analyse epidemiological data and elucidate pathogen life cycles. Key epidemiological parameters can be estimated from demographic time series by computing the likelihood of alternative models of pathogen transmission. Here we use this inference approach to analyze data from an evolution experiment in which we monitored both the epidemiology and the evolution of the temperate bacteriophageλduring an epidemic. We estimate parameter values for all the life-history traits of two distinct strains of the virus. In particular, we estimate the ability of the two virus strains to modulate plastically the rate of lysogenization with the multiplicity of infection. Our work illustrates how inference from experimental evolution data can feedback on the development of models aiming to predict the epidemiology and evolution of infectious diseases.
Optimal synaptic dynamics for memory maintenance in the presence of noise
Authors: Raman Dhruva V , O’Leary Timothy 
Published: August 2020

ABSTRACTSynaptic connections in many brain areas have been found to fluctuate significantly, with substantial turnover and remodelling occurring over hours to days. Remarkably, this flux in connectivity persists in the absence of overt learning or behavioural change. What proportion of these ongoing fluctuations can be attributed to systematic plasticity processes that maintain memories and neural circuit function? We show under general conditions that the optimal magnitude of systematic plasticity is typically less than the magnitude of perturbations due to internal biological noise. Thus, for any given amount of unavoidable noise, 50% or more of total synaptic turnover should be effectively random for optimal memory maintenance. Our analysis does not depend on specific neural circuit architectures or plasticity mechanisms and predicts previously unexplained experimental measurements of the activity-dependent component of ongoing plasticity.
Reprogramming enriches for somatic cell clones with small scale mutations in cancer-associated genes
Authors: Kosanke Maike , Osetek Katarzyna , Haase Alexandra , Wiehlmann Lutz , Davenport Colin , Schwarzer Adrian , Adams Felix , Schambach Axel , Merkert Sylvia , Wunderlich Stephanie , Menke Sandra , Dorda Marie , Martin Ulrich 
Published: August 2020

SummaryRecent studies demonstrated that the mutational load in human induced pluripotent stem cells (hiPSCs) is largely derived from their parental cells, but it is still unknown whether reprogramming may enrich for individual mutations. 30 hiPSC lines were analyzed by whole exome sequencing. High accuracy amplicon sequencing showed that all analyzed small scale variants pre-existed in their parental cells and that individual mutations present in small subpopulations of parental cells become enriched among hiPSC clones during reprogramming. Among those, putatively actionable driver mutations affect genes related to cell cycle control, cell death and pluripotency, and may confer a selective advantage during reprogramming. Finally, a shRNA-based experimental approach was applied to provide additional evidence for the individual impact of such genes on the reprogramming efficiency. In conclusion, we show that enriched mutations in curated onco- and tumor suppressor genes may account for an increased tumor risk and impact the clinical value of patient-derived hiPSCs.
Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly
Authors: Kalyana Sundaram R Venkat , Jin Huaizhou , Li Feng , Shu Tong , Coleman Jeff , Yang Jie , Pincet Frederic , Zhang Yongli , Krishnakumar Shyam S. , Rothman James E. 
Published: August 2020

ABSTRACTSynaptic vesicle fusion is mediated by membrane-bridging complexes formed by SNARE proteins - VAMP2 on the vesicle and Syntaxin-1/SNAP25 on the pre-synaptic membrane. Accumulating evidence suggest that chaperones Munc18-1 and Munc13-1 co-operatively catalyze SNARE assembly via an intermediate ‘template’ complex containing Syntaxin-1 and VAMP2. How SNAP25 is chaperoned into this nascent complex remains a mystery. Here we report that Munc13-1 recruits SNAP25 to initiate the ternary SNARE complex assembly by direct binding, as judged by bulk FRET spectroscopy and single-molecule optical tweezer studies. Detailed structure-function analyses show that the binding is mediated by the Munc13-1 MUN domain and is specific for the SNAP25 ‘linker’ region that connects the two SNARE motifs. Consequently, freely diffusing SNAP25 molecules on phospholipid bilayers are concentrated and presumably bound in ~1:1 stoichiometry by the self-assembled Munc13-1 nanoclusters. Our data suggests that Munc13-1’s capacity to bind all three synaptic SNARE proteins likely underlie its chaperone function.