bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous Absorption of Antimicrobial Peptide LL37 inEscherichia coliCells Enhances Population Survivability
Authors: Snoussi Mehdi , Talledo John Paul , Del Rosario Nathan-Alexander , Ha Bae-Yeun , Košmrlj Andrej , Taheri-Araghi Sattar 
Published: May 2018

AbstractAntimicrobial peptides (AMPs) are broad spectrum antibiotics that selectively target bacteria. Here we investigate the activity of human AMP LL37 againstEscherichia coliby integrating quantitative, population and single-cell level experiments with theoretical modeling. Our data indicate an unexpected, rapid absorption and retention of a large number of LL37 byE. colicells upon the inhibition of their growth, which increases the chance of survival for the rest of population. Cultures with high-enough cell density exhibit two distinct subpopulations: a non-growing population that absorb peptides and a growing population that survive owing to the sequestration of the AMPs by others. A mathematical model based on this binary picture reproduces the rather surprising behaviors ofE. colicultures in the presence of LL37, including the increase of the minimum inhibitory concentration with cell density (even in dilute cultures) and the extensive lag in growth introduced by sub-lethal dosages of LL37.
Efficacy of fecal sampling as a gut proxy in the study of chicken gut microbiota
Authors: Yan Wei , Zheng Jiangxia , Wen Chaoliang , Ji Congliang , Zhang Dexiang , Chen Yonghua , Sun Congjiao , Yang Ning 
Published: May 2018

AbstractBackgroundDespite the convenience and noninvasiveness of fecal sampling, the fecal microbiota does not fully represent that of the gastrointestinal (GI) tract, and the efficacy of fecal sampling to accurately represent the gut microbiota in birds is poorly understood. In this study, we aim to identify the efficacy of feces as a gut proxy in birds using chickens as a model. We collected 1,026 samples from 206 chickens, including duodenum, jejunum, ileum, cecum and feces samples, for 16S rRNA amplicon sequencing analyses.ResultsIn this study, the efficacy of feces as a gut proxy was partitioned to microbial community membership and community structure. Most taxa in the small intestine (84.11 – 87.28%) and ceca (99.39%) could be identified in feces. Microbial community membership was reflected with a gut anatomic feature, but community structure was not. Excluding shared microbes, the small intestine and ceca contributed 34.12 and 5.83% of the total fecal members, respectively. The composition of Firmicutes members in the small intestine and that of Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria members in the ceca could be well mirrored by the observations in fecal samples (ρ = 0.54 – 0.71 and 0.71 – 0.78, respectively, P < 0.001). However, there were few significant correlations for each genus between feces and each of the 4 gut segments, and these correlations were not high (ρ = −0.2 – 0.4, P < 0.05) for most genera.ConclusionsOur results provide evidence that the good potential of feces to identify most taxa in chicken guts, but it should be interpreted with caution by using feces as a proxy for gut in microbial structure analyses. This work provides insights and future directions regarding the usage of fecal samples in studies of the gut microbiome.
Sound colless-like balance indices for multifurcating trees
Authors: Mir Arnau , Rotger Lucía , Rosselló Francesc 
Published: May 2018

AbstractThe colless index is one of the most popular and natural balance indices for bifurcating phylogenetic trees, but it makes no sense for multifurcating trees. in this paper we propose a family of colless-like balance indices ℭD,f, which depend on a dissimilarity D and a function f: ℕ→ ℝ ⩾0, that generalize the colless index to multifurcating phylogenetic trees. We provide two functions f such that the most balanced phylogenetic trees according to the corresponding indices ℭD,f are exactly the fully symmetric ones. Next, for each one of these two functions f and for three popular dissimilarities D (the variance, the standard deviation, and the mean deviation from the median), we determine the range of values of ℭD,f on the sets of phylogenetic trees with a given number n of leaves. We end the paper by assessing the performance of one of these indices on TreeBASE and using it to show that the trees in this database do not seem to follow either the uniform model for multifurcating trees or the α-γ-model, for any values of α and γ.
Rapid, inexpensive measurement of synthetic bacterial community composition by Sanger sequencing
Authors: Cermak Nathan , Datta Manoshi Sen , Conwill Arolyn 
Published: May 2018

AbstractSimple synthetic bacterial communities are powerful tools for studying microbial ecology and evolution, as they enable rapid iteration between controlled laboratory experiments and theoretical modeling. However, their utility is hampered by the lack of fast, inexpensive, and accurate methods for quantifying bacterial community composition. For instance, while next-generation amplicon sequencing can be very accurate, high costs (>$30 per sample) and turnaround times (>1 month) limit the nature and pace of experiments. Here, we introduce a new approach for quantifying composition in synthetic bacterial communities based on Sanger sequencing. First, for a given community, we PCR-amplify a universal marker gene (here, the 16S rRNA gene), which yields a mixture of amplicons. Second, we sequence this amplicon mixture in a single Sanger sequencing reaction, which produces a “mixed” electropherogram with contributions from each community member. We also sequence each community member’s marker gene individually to generate “individual” electropherograms. Third, we fit the mixed electropherogram as a linear combination of time-warped individual electropherograms, thereby allowing us to estimate the fractional amplicon abundance of each strain within the community. Importantly, our approach accounts for retention-time variability in electrophoretic signals, which is crucial for accurate compositional estimates. Using synthetic communities of marine bacterial isolates, we show that this approach yields accurate and reproducible abundance estimates for two-, four-, and seven-strain bacterial communities. Furthermore, this approach can provide results within one day and costs ~$5 USD per sample. We envision this approach will enable new insights in microbial ecology by increasing the number of samples that can be analyzed and enabling faster iteration between experiments and theory. We have implemented our method in a free and open-source R package called CASEU (“Compositional Analysis by Sanger Electropherogram Unmixing”), available at https://bitbucket.org/DattaManoshi/caseu.
Retrospective harmonization of multi-site diffusion MRI data acquired with different acquisition parameters
Authors: Cetin Karayumak Suheyla , Bouix Sylvain , Ning Lipeng , Shenton Martha , Kubicki Marek , Rathi Yogesh 
Published: May 2018

AbstractA joint and integrated analysis of multi-site diffusion MRI (dMRI) datasets can dramatically increase the statistical power of neuroimaging studies and enable comparative studies pertaining to several brain disorders. However, dMRI data sets acquired on multiple scanners cannot be naively pooled for joint analysis due to scanner specific nonlinear effects as well as differences in acquisition parameters. Consequently, for joint analysis, the dMRI data has to be harmonized, which involves removing scanner-specific differences from the raw dMRI signal. In this work, we present a dMRI harmonization method that, when applied to multi-site data, is capable of removing scanner-specific effects, while accounting for minor differences in acquisition parameters such as b-value, spatial resolution and number of gradient directions in the dMRI data (typical for multi-site clinical research scans). We validate our algorithm on dMRI data acquired from two sites: Philadelphia Neurodevelopmental Cohort (PNC) with 800 healthy adolescents (ages 8 to 22 years) and Brigham and Women’s Hospital (BWH) with 70 healthy subjects (ages 14 to 54 years). In particular, we show that gender differences and maturation in different age groups are preserved after harmonization, as measured using effect sizes (small, medium and large), irrespective of the test sample size. Further, because we use matched control subjects from different scanners to estimate scanner-specific effects, we tested how many subjects are needed from each site to achieve best harmonization results. Our results indicate that at-least 16 to 18 well-matched healthy controls from each site are needed to reliably capture scanner related differences. The proposed method can thus be used for retrospective harmonization of raw dMRI data across sites despite differences in acquisition parameters, while preserving inter-subject anatomical variability.
Genetically encoded multimode reporter of adaptor protein 3 (AP-3) traffic in budding yeast
Authors: Plemel Rachael L. , Odorizzi Greg , Merz Alexey J. 
Published: May 2018

SYNOPSISThe AP-3 (adaptor complex 3) mediates traffic from the late Golgi or early endosomes to late endosomal compartments. Here, a synthetic reporter is presented that allows convenient monitoring of AP-3 traffic, and direct screening or selection for mutants with defects in the pathway. The reporter can be assayed by fluorescence microscopy or in liquid or agar plate formats and is adaptable to high-throughput screening.SUMMARYAP-3 (adaptor complex 3) mediates traffic from the late Golgi or early endosomes to late endosomal compartments. In mammals, mutations in AP-3 cause Hermansky-Pudlak Syndrome type 2, cyclic neutropenias, and a form of epileptic encephalopathy. In budding yeast, AP-3 carries cargo directly from the trans-Golgi to the lysosomal vacuole. Despite the pathway’s importance and its discovery two decades ago, rapid screens and selections for AP-3 mutants have not been available. We now report GNSI, a synthetic, genetically encoded reporter that allows rapid plate-based assessment of AP-3 functional deficiency, using either chromogenic or growth phenotype readouts. This system identifies defects in both the formation and consumption of AP-3 carrier vesicles and is adaptable to high-throughput screening or selection in both plate array and liquid batch culture formats. Episomal and integrating plasmids encoding GNSI have been submitted to the Addgene repository.
Structural basis for the RNA-guided ribonuclease activity of CRISPR-Cas13d
Authors: Zhang Cheng , Konermann Silvana , Brideau Nicholas J. , Lotfy Peter , Novick Scott J. , Strutzenberg Timothy , Griffin Patrick R. , Hsu Patrick D. , Lyumkis Dmitry 
Published: May 2018

AbstractCRISPR-Cas endonucleases directed against foreign nucleic acids mediate prokaryotic adaptive immunity and have been tailored for broad genetic engineering applications. Type VI-D CRISPR systems contain the smallest known family of single effector Cas enzymes, and their signature Cas13d ribonuclease employs guide RNAs to cleave matching target RNAs. To understand the molecular basis for Cas13d function, we resolved cryo-electron microscopy structures of Cas13d-guide RNA binary complex and Cas13d-guide-target RNA ternary complex to 3.4 and 3.3 Å resolution, respectively. Furthermore, a 6.5 Å reconstruction of apo Cas13d combined with hydrogen-deuterium exchange revealed conformational dynamics that have implications for RNA scanning. These structures, together with biochemical and cellular characterization, explain the compact molecular architecture of Cas13d and provide insights into the structural transitions required for enzyme activation. Our comprehensive analysis of Cas13d in diverse enzymatic states facilitated site-specific truncations for minimal size and delineates a blueprint for improving biomolecular applications of RNA targeting.
Detection of the altered metabolites of Raji cells in the presence of Epstein-Barr virus (EBV) using 1HNMR Spectroscopy
Authors: Dindar Zahra , Hosseini Reza Haj , Vahhabpoor Ruhollah , Zamani Zahra 
Published: May 2018

AbstractEBV is one of the most common viruses in humans and is directly implicated in carcinogenesis. The present study aimed to detect the altered metabolites of Raji cells in the presence of Epstein-Barr virus (EBV) using 1H NMR by NOESY technique. The cells and EBV were maintained in RPMI 1640 and 1 ml of cells were transfected into falcon tubes containing cells and were incubated at 37°C for 2 hours. Metabolites extracted using water or chloroform/methanol, lyophilized and sent for 1H NMR analysis by NOESY technique. The NMR spectrum comprising of Fourier Transformed information about metabolites in the control and treated were imported into MATLAB (v.7.8.0.347) software and the metabolic cycles were determined using Metabo-Analyst software. The data have demonstrated that infected cells leads to proliferation and subsequent immortalization of cell lines through cellular replication machinery recruitment and changes the metabolic profile and promotes vital metabolites such as the carbohydrates engage in pentose phosphate and glycolactic, biosynthesis of nucleotide and amino acid pathways. The results also indicate that essential amino acids are required for protecting viral structure and the function of viral genes. Therefore, EBV infection of cells leads to the sustained elevation of cell growth and cell immortalization.
The gene regulatory basis of genetic compensation during neural crest induction
Authors: Dooley Christopher M. , Wali Neha , Sealy Ian M. , White Richard J. , Stemple Derek L. , Collins John E. , Busch-Nentwich Elisabeth M. 
Published: May 2018

AbstractBackgroundThe neural crest (NC) is a vertebrate-specific cell type that contributes to a wide range of different tissues across all three germ layers. The gene regulatory network (GRN) responsible for the formation of neural crest is conserved across vertebrates. Central to the induction of the NC GRN are AP-2 and SoxE transcription factors but detailed interactions within the network remain to be resolved.ResultsWe have used gene knockout and RNA sequencing strategies to dissect NC differentiation in zebrafish. We establish that initiation of the NC GRN takes place just after genome activation. We genetically ablate the NC using double mutants of tfap2a;tfap2c or remove specific subsets of the NC with sox10 and mitfa knockouts and characterise genome-wide gene expression levels across multiple time points. We find that although a single allele of tfap2c is capable of maintaining early NC induction and differentiation in the absence of tfap2a function, expression of many target genes remains abnormal and sensitive to tfap2 dosage. This separation of morphological and molecular phenotypes identifies a core set of genes required for early NC development. Using gene knockouts, we associate previously uncharacterised genes with pigment cell development and establish a role for maternal Hippo signalling in melanocyte differentiation.ConclusionsStepwise genetic ablation of the NC identifies the core gene module required for neural crest induction. This work extends and refines the NC GRN while also uncovering the complex transcriptional basis of genetic compensation via paralogues.
Genomic determinants of speciation and spread of theMycobacterium tuberculosiscomplex
Authors: Chiner-Oms Álvaro , Sánchez-Busó Leonor , Corander Jukka , Gagneux Sebastien , Harris Simon , Young Douglas , González-Candelas Fernando , Comas Iñaki 
Published: May 2018

ABSTRACTBACKGROUNDModels on how bacterial lineages differentiate increase our understanding on early bacterial speciation events and about the genetic loci involved. Here, we analyze the population genomics events leading to the emergence of the tuberculosis pathogen.RESULTSThe emergence is characterized by a combination of recombination events involving core pathogenesis functions and purifying selection on early diverging loci. We identify thephoRgene, the sensor kinase of a two-component system involved in virulence, as a key functional player subject to pervasive positive selection after the divergence of the MTBC from its ancestor. Previous evidence showed thatphoRmutations played a central role in the adaptation of the pathogen to different host species. Now we show thatphoRhave been under selection during the early spread of human tuberculosis, during later expansions and in on-going transmission events.CONCLUSIONSOur results show that linking pathogen evolution across evolutionary and epidemiological timescales point to past and present virulence determinants.
Genomic prediction using individual-level data and summary statistics from multiple populations
Authors: Vandenplas Jeremie , Calus Mario P.L. , Gorjanc Gregor 
Published: May 2018

ABSTRACTThis study presents a method for genomic prediction that uses individual-level data and summary statistics from multiple populations. Genome-wide markers are nowadays widely used to predict complex traits, and genomic prediction using multi-population data is an appealing approach to achieve higher prediction accuracies. However, sharing of individual-level data across populations is not always possible. We present a method that enables integration of summary statistics from separate analyses with the available individual-level data. The data can either consist of individuals with single or multiple (weighted) phenotype records per individual. We developed a method based on a hypothetical joint analysis model and absorption of population specific information. We show that population specific information is fully captured by estimated allele substitution effects and the accuracy of those estimates, i.e. the summary statistics. The method gives identical result as the joint analysis of all individual-level data when complete summary statistics are available. We provide a series of easy-to-use approximations that can be used when complete summary statistics are not available or impractical to share. Simulations show that approximations enables integration of different sources of information across a wide range of settings yielding accurate predictions. The method can be readily extended to multiple-traits. In summary, the developed method enables integration of genome-wide data in the individual-level or summary statistics form from multiple populations to obtain more accurate estimates of allele substitution effects and genomic predictions.
Estrus-Cycle Regulation of Cortical Inhibition
Authors: Clemens Ann M. , Lenschow Constanze , Beed Prateep , Li Lanxiang , Sammons Rosanna , Naumann Robert K. , Wang Hong , Schmitz Dietmar , Brecht Michael 
Published: May 2018

SummaryFemale mammals experience cyclical changes in sexual receptivity known as the estrus-cycle. Little is known about how estrus affects the cortex although alterations in sensation, cognition and the cyclic occurrence of epilepsy suggest brain-wide processing changes. We performedin vivojuxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus-cycle potently altered cortical inhibition. Fast-spiking interneurons strongly varied their activity with the estrus-cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change.In vivowhole-cell recordings revealed a varying excitation-to-inhibition-ratio with estrus.In situhybridization for estrogen receptor β (Esr2) showed co-localization with parvalbumin-positive interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings.In vivoandin vitroexperiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen receptor β mechanism. We conclude that sex hormones powerfully modulate cortical inhibition in the female brain.
IdentifyingStreptococcus pneumoniaegenes associated with invasive disease using pangenome-based whole genome sequence typing
Authors: Obolski Uri , Gori Andrea , Lourenço José , Thompson Craig , Thompson Robin , French Neil , Heyderman Robert , Gupta Sunetra 
Published: May 2018

AbstractStreptococcus pneumoniaeis a normal commensal of the upper respiratory tract but can also invade the bloodstream or CSF (cerebrospinal fluid), causing invasive pneumococcal disease (IPD). In this study, we attempt to identify genes associated with IPD by applying a random forest machine-learning algorithm to whole genome sequence (WGS) data. We find 43 genes consistently associated with IPD across three geographically distinct WGS data sets of pneumococcal carriage isolates. Of these genes, 23 genes have previously shown to be directly relevant to IPD, while the other 18 are uncharacterized.
Grapevine virus L: a Novel Vitivirus in Grapevine
Authors: Debat Humberto , Zavallo Diego , Brisbane Reid Soltero , Vončina Darko , Almeida Rodrigo P.P. , Blouin Arnaud G. , Rwahnih Maher Al , Gomez-Talquenca Sebastian , Asurmendi Sebastian 
Published: May 2018

AbstractVitivirus are ssRNA(+) viruses in the family Betaflexiviridae (subfamily Trivirinae). There are currently ten ICTV recognized virus species in the genus; nevertheless, the extended use of NGS technologies is rapidly expanding their diversity and six more have been proposed recently. Here, we present the characterization of a novel virus from grapevines, which fits the genomic architecture and evolutionary constraints to be classifiable within the Vitivirus genus. The detected virus sequence is 7,607 nt long, including a typical genome organization of ORFs encoding a replicase (RP), a 22 kDa protein, a movement protein, a coat protein (CP) and a nucleic acid binding protein. Here, we present the characterization of a novel virus from grapevines. Phylogenetic analyses based on the predicted RP and CP protein unequivocally places the new virus within the Vitivirus genus. Multiple independent RNAseq data confirmed the presence of the detected virus in berries at diverse developmental stages. Additionally, we detected, confirmed, and assembled virus sequences from grapevine samples of distinct cultivars from America, Europe, Asia and Oceania, sharing 74.9%-97.9% nt identity, suggesting that the identified virus is widely distributed and diverse. We propose the name grapevine virus L (GVL) to the detected Vitivirus.
A conformational sensor based on genetic code expansion reveals an autocatalytic component in EGFR activation
Authors: Baumdick Martin , Gelléri Márton , Uttamapinant Chayasith , Beránek Václav , Chin Jason W , Bastiaens Philippe IH 
Published: May 2018

AbstractEpidermal growth factor receptor (EGFR) activation by growth factors (GFs) relies on dimerization and allosteric activation of its intrinsic kinase activity, resulting in trans-phosphorylation of tyrosines on its C-terminal tail. While structural and biochemical studies identified this EGF-induced allosteric activation, imaging collective EGFR activation in cells and molecular dynamics simulations pointed at additional catalytic EGFR activation mechanisms. To gain more insight in EGFR activation mechanisms in living cells, we developed a Förster Resonance Energy Transfer (FRET) basedconformationalEGFRindicator (CONEGI) using genetic code expansion that reports on conformational transitions in the EGFR activation loop. Comparing conformational transitions, self-association and auto-phosphorylation of CONEGI and its Y845F mutant revealed that Y845phosphorylation induces a catalytically active conformation in EGFR monomers. This conformational transition depends on EGFR kinase activity and auto-phosphorylation on its C–terminal tail, generating a looped causality that leads to autocatalytic amplification of EGFR phosphorylation at low EGF dose.