bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decline in pneumococcal disease in unimmunized adults is associated with vaccine-associated protection against colonization in toddlers and preschool-aged children
Authors: Weinberger Daniel M. , Pitzer Virginia E. , Regev-Yochay Gili , Givon-Lavi Noga , Dagan Ron 
Published: April 2018

ABSTRACTVaccinating children with pneumococcal conjugate vaccines disrupts transmission, reducing disease rates in unvaccinated adults. When considering changes in vaccination strategies (e.g., removing doses), it is critical to understand which groups of children contribute most to transmission. We used data from Israel to evaluate how the build-up of vaccine-associated immunity in children was associated with declines in IPD due to vaccine-targeted serotypes in unimmunized adults. Data on vaccine uptake and prevalence of colonization with PCV-targeted serotypes were obtained from a unique study conducted among children visiting an emergency department in southern Israel and from surveys of colonization from central Israel. Data on invasive pneumococcal disease in adults were obtained from a nationwide surveillance study. We compared the trajectory of decline of IPD due to PCV-targeted serotypes in adults with the trajectory of decline of colonization prevalence and trajectory of increase in vaccine-derived protection against pneumococcal carriage among different age groupings of children. The declines in IPD in adults were most closely associated with the declines in colonization and increased vaccination coverage in children in the range of 36-59 months of age. This suggests that preschool-aged children, rather than infants, are responsible for maintaining the indirect benefits of PCVs.
Terrestriality and bacterial transfer: A comparative study of gut microbiomes in sympatric Malagasy mammals
Authors: Perofsky Amanda C. , Lewis Rebecca J. , Meyers Lauren Ancel 
Published: April 2018

AbstractThe gut microbiomes of mammals appear to mirror their hosts’ phylogeny, suggesting a shared history of co-speciation. Yet, much of this evidence stems from comparative studies of distinct wild or captive populations that lack data for disentangling the relative influences of shared phylogeny and environment. Here, we present phylogenetic and multivariate analyses of gut microbiomes from six sympatric (i.e., co-occurring) mammal species inhabiting a 1-km2area in western Madagascar—three lemur and three non-primate species—that consider genetic, dietary, and ecological predictors of microbiome functionality and composition. Host evolutionary history, indeed, appears to drive gut microbial patterns among distantly related species. However, we also find that diet—reliance on leaves versus fruit—is the best predictor of microbiome similarity among closely related lemur species, and that host substrate preference—ground versus tree— constrains horizontal transmission via incidental contact with feces, with arboreal species harboring far more distinct communities than those of their terrestrial and semi-terrestrial counterparts.
mCSEA: Detecting subtle differentially methylated regions
Authors: Martorell-Marugán Jordi , González-Rumayor Víctor , Carmona-Sáez Pedro 
Published: April 2018

AbstractMotivationThe identification of differentially methylated regions (DMRs) among phenotypes is one of the main goals of epigenetic analysis. Although there are several methods developed to detect DMRs, most of them are focused on detecting relatively large differences in methylation levels and fail to detect moderate, but consistent, methylation changes that might be associated to complex disorders.ResultsWe present mCSEA, an R package that implements a Gene Set Enrichment Analysis method to identify differentially methylated regions from Illumina 450K and EPIC array data. It is especially useful for detecting subtle, but consistent, methylation differences in complex phenotypes. mCSEA also implements functions to integrate gene expression data and to detect genes with significant correlations among methylation and gene expression patterns. Using simulated datasets, we show that mCSEA outperforms other tools in detecting DMRs. In addition, we applied mCSEA to a previously published dataset of sibling pairs discordant for intrauterine hyperglycemia exposure. We found several differentially methylated promoters in genes related to metabolic disorders like obesity and diabetes, demonstrating the potential of mCSEA to identify differentially methylated regions not detected by other methods.AvailabilitymCSEA is freely available from the Bioconductor repository.Contactpedro.carmona@genyo.es
Serotonergic regulation of corticoamygdalar neurons in the mouse prelimbic cortex
Authors: Avesar Daniel , Stephens Emily K. , Gulledge Allan T. 
Published: April 2018

AbstractNeuromodulatory transmitters, such as serotonin (5-HT), selectively regulate the excitability of subpopulations of cortical projection neurons to gate cortical output to specific target regions. For instance, in the mouse prelimbic cortex, 5-HT selectively excites commissurally projecting intratelencephalic (COM) neurons via activation of 5-HT2A (2A) receptors, while simultaneously inhibiting corticofugally projecting pyramidal neurons targeting the pons via 5-HT1A (1A) receptors. Here we characterize the physiology, morphology, and serotonergic regulation of corticoamygdalar (CAm) projection neurons in the mouse prelimbic cortex. Layer 5 CAm neurons shared a number of physiological and morphological characteristics with COM neurons, including higher input resistances, smaller HCN-channel mediated responses, and sparser dendritic arbors than corticopontine neurons. Across cortical lamina, CAm neurons also resembled COM neurons in their serotonergic modulation; focally applied 5-HT (100 µM; 1 s) generated 2A-receptor-mediated excitation, or 1A- and 2A- dependent biphasic responses, in ipsilaterally and contralaterally projecting CAm neurons. Serotonergic excitation depended on extrinsic excitatory drive, as 5-HT failed to depolarize CAm neurons from rest, but could enhance the number of action potentials generated by simulated barrages of synaptic input. Finally, using dual tracer injections, we identified double-labeled CAm/COM neurons that displayed primarily excitatory or biphasic responses to 5-HT. Overall, our findings reveal that prelimbic CAm neurons overlap with COM neurons, and that both neuron subtypes exhibit 2A-dependent serotonergic excitation. Our findings suggest that 5-HT, acting at 2A receptors, will promote cortical output to the amygdala.Significance StatementCortical projections to the amygdala allow for executive “top-down” control of emotional responses. Corticoamygdalar (CAm) neurons in the prelimbic cortex contribute to the learning and expression of conditioned fear responses, processes that may also be regulated by serotonin (5-HT). Our study provides a physiological and morphological characterization of prelimbic CAm neurons, and demonstrates that the excitability of CAm neurons is regulated by 5-HT acting at 5-HT2A receptors alone, or in combination with 5-HT1A receptors. Our results suggest that 5-HT may regulate corticoamygdalar circuits during the learning and expression of conditioned fear.
Effect Size and Power in fMRI Group Analysis
Authors: Geuter Stephan , Qi Guanghao , Welsh Robert C. , Wager Tor D. , Lindquist Martin A. 
Published: April 2018

AbstractMulti-subject functional magnetic resonance imaging (fMRI) analysis is often concerned with determining whether there exists a significant population-wide ‘activation’ in a comparison between two or more conditions. Typically this is assessed by testing the average value of a contrast of parameter estimates (COPE) against zero in a general linear model (GLM) analysis. In this work we investigate several aspects of this type of analysis. First, we study the effects of sample size on the sensitivity and reliability of the group analysis, allowing us to evaluate the ability of small sampled studies to effectively capture population-level effects of interest. Second, we assess the difference in sensitivity and reliability when using volumetric or surface based data. Third, we investigate potential biases in estimating effect sizes as a function of sample size. To perform this analysis we utilize the task-based fMRI data from the 500-subject release from the Human Connectome Project (HCP). We treat the complete collection of subjects (N = 491) as our population of interest, and perform a single-subject analysis on each subject in the population. We investigate the ability to recover population level effects using a subset of the population and standard analytical techniques. Our study shows that sample sizes of 40 are generally able to detect regions with high effect sizes (Cohen’s d > 0.8), while sample sizes closer to 80 are required to reliably recover regions with medium effect sizes (0.5 < d < 0.8). We find little difference in results when using volumetric or surface based data with respect to standard mass-univariate group analysis. Finally, we conclude that special care is needed when estimating effect sizes, particularly for small sample sizes.
BayesENproteomics: Bayesian elastic nets for quantification of proteoforms in complex samples
Authors: Mallikarjun Venkatesh , Richardson Stephen M. , Swift Joe 
Published: April 2018

AbstractMultivariate regression modelling provides a statistically powerful means of quantifying the effects of a given treatment while compensating for sources of variation and noise, such as variability between human donors and the behaviour of different peptides during mass spectrometry. However, methods to quantify endogenous post-translational modifications (PTMs) are typically reliant on summary statistical methods that fail to consider sources of variability such as changes in levels of the parent protein. Here, we compare three multivariate regression methods, including a novel Bayesian elastic net algorithm (BayesENproteomics) that enables assessment of relative protein abundances while also quantifying identified PTMs for each protein. We tested the ability of these methods to accurately quantify expression of proteins in a mixed-species benchmark experiment, and to quantify synthetic PTMs induced by stable isotope labelling. Finally, we extended our regression pipeline to calculate fold changes at the pathway level, providing a complement to commonly used enrichment analysis. Our results show that BayesENproteomics can quantify changes to protein levels across a broad dynamic range while also accurately quantifying PTM and pathway-level fold changes. Raw data has been deposited to the ProteomeXchange with identifiers PXD012784, PXD012782 and PXD012772. BayesENproteomics is available for Matlab: www.github.com/VenkMallikarjun/BayesENproteomics and Python3: www.github.com/VenkMallikarjun/BENPPy
Nucleosome conformational variability in solution and in interphase nuclei evidenced by cryo-electron miocroscopy of vitreous sections
Authors: Eltsov Mikhail , Grewe Diana , Lemercier Nicolas , Frangakis Achilleas , Livolant Françoise , Leforestier Amélie 
Published: April 2018

AbstractIn Eukaryotes, DNA is wound around the histone core octamer to form the basic chromatin unit, the nucleosome. Atomic resolution structures have been obtained from crystallography and single particle cryo-electron microscopy of identical engineered particles. But native nucleosomes are dynamical entities with diverse DNA sequence and histone content, and little is known about their conformational variability, especially in the cellular context. Using cryo-electron microscopy and tomography of vitreous sections we analyse the conformation of native nucleosomes, bothin vitro, using purified particles solubilised at physiologically relevant concentrations (25-50 %), andin situ, within interphase nuclei. We visualise individual nucleosomes at a level of detail that allows us to analyse the conformation of the DNA wrapped around, and measure the distance between the DNA gyres. We evidence a variety of conformations. In interphase nuclei open nucleosomes predominate, with an average inter-gyre distance larger than that of the canonical particle. In concentrated solutions, we evidence a salt–dependant transition, with high salt compact conformations resembling the canonical nucleosome, and open low salt ones, closer to nuclear nucleosomes. Although further particle characterisation and cartography are needed to understand the relationship between this conformational variability and chromatin functional states, this work opens a route to chromatin explorationin situ.
Accurate informatic modeling of tooth enamel pellicle interactions by training substitution matrices with Mat4Pep
Authors: Horst Jeremy A. , Seto Jong , Oren Ersin Emre , Horst Orapin V. , Hung Ling-Hong , Samudrala Ram 
Published: April 2018

AbstractMotivationProtein-hydroxyapatite interactions govern the development and homeostasis of teeth and bone. Characterization would enable design of peptides to regenerate mineralized tissues and control attachments such as ligaments and dental plaque. Progress has been limited because no available methods produce robust data for assessing phase interfaces.ResultsWe show that tooth enamel pellicle peptides contain subtle sequence similarities that encode hydroxyapatite binding mechanisms, by segregating pellicle peptides from control sequences using our previously developed substitution matrix-based peptide comparison protocol (Oren et al., 2007), with improvements. Sampling diverse matrices, adding biological control sequences, and optimizing matrix refinement algorithms improves discrimination from 0.81 to 0.99 AUC in leave-one-out experiments. Other contemporary methods fail on this problem. We find hydroxyapatite interaction sequence patterns by applying the resulting selected refined matrix (“pellitrix”) to cluster the peptides and build subgroup alignments. We identify putative hydroxyapatite maturation domains by application to enamel biomineralization proteins and prioritize putative novel pellicle peptides identified by In stageTip (iST) mass spectrometry. The sequence comparison protocol outperforms other contemporary options for this small and heterogeneous group, and is generalized for application to any group of peptides.AvailabilitySoftware to apply this protocol is freely available at github.com/JeremyHorst/Mat4Pep and compbio.org/protinfo/ Mat4Pep.Contactjahorst@gmail.com, ram@compbio.org.Supplementary informationAvailable at Bioinformatics online.
Rearing temperature and fatty acid supplementation jointly affect membrane fluidity and heat tolerance inDaphnia
Authors: Martin-Creuzburg D. , Coggins B.L. , Ebert D. , Yampolsky L.Y. 
Published: April 2018

AbstractThe homeoviscous adaptation hypothesis states that the relative abundance of polyunsaturated fatty acids (PUFA) decreases in the membrane phospholipids of ectothermic organisms at higher temperatures to maintain vital membrane properties. We hypothesized that the well-documented reduced heat tolerance of cold-rearedDaphniais due to the accumulation of PUFA in their body tissues and that heat-rearedDaphniacontain reduced amounts of PUFA even when receiving a high dietary supply of PUFA. InDaphniareared at 15°C, supplementation of a PUFA-deficient food with the long-chain PUFA eicosapentaenoic acid (EPA) resulted in an increase in the relative abundance of EPA in body tissues and a decrease in heat tolerance. However, the same was observed inDaphniareared at 25°C, indicating that the ability of heat-acclimatedDaphniato adjust EPA body concentrations is limited when exposed to high dietary EPA concentrations.Daphniareared at 25°C showed the lowest change in membrane fluidity, measured as fluorescence polarization. ForDaphniareared at three different temperatures, thermal tolerance (time to immobility at a lethally high temperature) and increasing dietary EPA concentrations correlated with fluorescence polarization and the degree of fatty acid unsaturation. Overall, our results support the homeoviscous adaptation hypothesis by showing that cold-rearedDaphnia,which accumulate PUFA within their tissues, are more susceptible to heat than hot-rearedDaphnia,which contain less PUFA.
Development of a GFP Fluorescent Bacterial Biosensor for the Detection and Quantification of Silver and Copper Ions
Authors: Martinez Adam R. , Heil John R. , Charles Trevor C. 
Published: April 2018

AbstractIonic silver is known to be an effective antimicrobial agent widely used in the cleaning and medical industries, however, there are several concerns regarding the release of silver pollutants into the environment. Presented here are two engineered bacterial biosensors for the detection and quantification of silver. The biosensors contain a silver resistance operon and a GFP gene that is strictly regulated through silver activated regulatory regions that control expression of thesiloperons. The two biosensors are responsive to a wide range of silver ion concentrations, and a correlation between silver and GFP signal is seen at select concentration ranges. The biosensors were shown to detect silver ions released from silver nanoparticles, and have the potential to become a method for monitoring ion release rates of different nanoparticles. Interestingly, the close homology of the silver resistance and copper resistance genes allowed for the biosensor to also be responsive to copper ions, implying that copper ions activate silver resistance. Further development of this biosensor could lead to commercial applications for environmental monitoring.ImportanceIonic silver is known to have many harmful environmental effects. Silver pollutants have been found in various environmental settings such as natural waterways and tailings from mining operations, raising concern. In addition, persistent exposure to silver in medical and environmental settings has led to the development of silver resistant bacteria, many of which are also resistant to a wide range of antibiotics. Some of these have the potential to develop into human pathogens. It then becomes important to have standardized methods for detecting and monitoring silver concentrations in various environments so that appropriate measures can be taken to prevent further silver ion release. This research shows that bacterial biosensors engineered to detect and quantify silver ions can be developed as effective alternatives to traditional analytical techniques. Further development of such biosensors could result in a commercial system for short and long term environmental monitoring, which is important as products containing silver and other heavy metals become increasingly popular.
Integrative visual omics of the white-rot fungus Polyporus brumalis exposes the biotechnological potential of its oxidative enzymes for delignifying raw plant biomass
Authors: Miyauchi Shingo , Rancon Anaïs , Drula Elodie , Chaduli Delphine , Favel Anne , Grisel Sacha , Henrissat Bernard , Herpoël-Gimbert Isabelle , Ruiz-Dueñas Francisco J. , Chevret Didier , Heinaut Matthieu , Lin Junyan , Wang Mei , Pangilinan Jasmyn , Lipzen Anna , Lesage-Meessen Laurence , Navarro David , Riley Robert , Grigoriev Igor V. , Zhou Simeng , Raouche Sana , Rosso Marie-Noëlle 
Published: April 2018

AbstractWhite-rot fungi are wood decayers able to degrade all polymers from lignocellulosic biomass including cellulose, hemicelluloses, and lignin. The white-rot fungus Polyporus brumalis efficiently breaks down lignin and is regarded as having a high potential for the initial treatment of plant biomass in its conversion to bio-energy. We performed integrative multi-omics analyses by combining data from the fungal genome, transcriptomes, and secretomes. We found the fungus possessed an unexpectedly large set of genes coding for enzymes related to lignin degradation, and that these were highly expressed and massively secreted under solid-state fermentation conditions. The examination of interrelated multi-omics patterns revealed the coordinated regulation of lignin-active peroxidases and H2O2-generating enzymes along with the activation of cellular mechanisms for detoxification, which combined to result in the efficient lignin breakdown by the fungus.ImportancePlant biomass conversion for green chemistry and bio-energy is a current challenge for a modern sustainable bioeconomy. The complex polyaromatic lignin polymers in raw biomass feedstocks (i.e. agriculture and forestry by-products) are major obstacles for biomass conversions. From a biotechnological aspect, these compounds could be a potential source of aromatic platform molecules for bio-based polymers. Here we describe the extraordinary ability of Polyporus brumalis for lignin degradation using its enzymatic arsenal to break down wheat straw, a lignocellulosic substrate that is considered as a biomass feedstock worldwide. We observed unusual expansions of gene families coding for; 1) Class II peroxidases involved in lignin degradation; and 2) GMC oxidoreductases/dehydrogenases involved in generating the hydrogen peroxide required for lignin peroxidase activity. Our findings suggested the fungus massively mobilizes this oxidative machinery during growth on wheat straw. Overall, we identified sets of co-regulated enzymes, which could potentially augment the efficiency of biotechnological plant biomass conversions.
Pathological Oxidation of PTPN12 Underlies ABL1 Phosphorylation in HLRCC
Authors: Xu Yang , Taylor Paul , Andrade Joshua , Ueberheide Beatrix , Shuch Brian , Glazer Peter M. , Bindra Ranjit S. , Moran Michael F. , Linehan Marston W. , Neel Benjamin G. 
Published: April 2018

AbstractHereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an inherited cancer syndrome associated with a highly aggressive form of type 2 papillary renal cell carcinoma (PRCC). Germ line inactivating alterations in Fumarate Hydratase (FH) cause HLRCC, and result in elevated levels of reactive oxygen species (ROS). Recent work indicates that FH -/-PRCC cells have increased ABL1 activation, which promotes tumor growth, but how ABL1 is activated remained unclear. Oxidation can regulate protein-tyrosine phosphatase (PTP) catalytic activity; conceivably, ROS-catalyzed inactivation of an ABL-directed PTP might account for ABL1 activation in this malignancy. Previously, our group developed “q-oxPTPome,” a method that can globally monitor the oxidation of classical PTPs. We have now refined the q-oxPTPome approach, increasing its sensitivity by >10X. Applying q-oxPTPome to FH-deficient cell models shows that multiple PTPs are either highly oxidized (including PTPN12) or overexpressed. In general, highly oxidized PTPs were those that have relatively high sensitivity to exogenous H2O2. Most PTP oxidation in FH-deficient cells is reversible, although nearly 40% of PTPN13 is oxidized irreversibly to the sulfonic acid state. Using “substrate-trapping mutants”, we mapped PTPs to their putative substrates, and found that only PTPN12 could target ABL1. Furthermore, knockdown experiments identify PTPN12 as the major ABL1 phosphatase in HLRCC. Overall, our results show that ROS-induced PTPN12 oxidation accounts for ABL1 phosphorylation in HLRCC-associated PRCC, reveal a novel mechanism for inactivating a tumor suppressor gene product, and establish a direct link between pathological PTP oxidation and neoplastic disease.