bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium chloride is an ionic checkpoint for human Th2 cell responses and shapes the atopic skin microenvironment
Authors: Matthias Julia , Maul Julia , Noster Rebecca , Meinl Hanna , Chao Ying-Yin , Gerstenberg Heiko , Jeschke Florian , Gasparoni Gilles , Welle Anna , Jörn Walter , Nordström Karl , Eberhardt Klaus , Renisch Dennis , Donakonda Sainitin , Knolle Percy , Soll Dominik , Grabbe Stephan , Garzorz-Stark Natalie , Eyerich Kilian , Biedermann Tilo , Baumjohann Dirk , Zielinski Christina E. 
Published: August 2018

One sentence summarySodium is an ionic checkpoint for the induction and amplification of human Th2 cell responses and shapes the atopic skin microenvironment, where it could serve as a novel therapeutic target for Th2 mediated diseases.AbstractThere has been a strong increase in the incidence of allergic diseases over the last 50 years. Environmental factors most likely account for this phenomenon. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation, which is characteristic of atopic diseases, remains unclear. It has previously been reported that dietary sodium chloride promotes the polarization of Th17 cells with implications for autoimmune diseases such as multiple sclerosis. Here, we demonstrate that sodium chloride also potently promotes Th2 cell responses on multiple regulatory levels. Sodium chloride enhanced IL-4 and IL-13 production while suppressing IFN-γproduction in effector T cells. It diverted alternative T cell fates into the Th2 cell phenotype and also inducedde novoTh2 cell polarization from naïve T cell precursors. Mechanistically, it exerted its effects via the osmosensitive transcription factor NFAT-5 and the kinase SGK-1, which regulated Th2 signature cytokines and master transcription factors in hyperosmolar salt conditions. The skin of patients suffering from atopic dermatitis contained highly elevated amounts of sodium compared to non-lesional atopic and healthy skin. This demonstrates that sodium chloride represents a so far overlooked cutaneous microenvironmental factor in atopic dermatitis that can induce Th2 cell responses, the orchestrators of allergic diseases. Together, our data propose ionic signaling through sodium chloride as a novel checkpoint and potential therapeutic target for type 2 immunity and its associated allergic diseases.
Flux balance analysis predicts NADP phosphatase and NADH kinase are critical to balancing redox during xylose fermentation inScheffersomyces stipitis
Authors: Correia Kevin , Khusnutdinova Anna , Li Peter Yan , Joo Jeong Chan , Brown Greg , Yakunin Alexander F. , Mahadevan Radhakrishnan 
Published: August 2018

ABSTRACTXylose is the second most abundant sugar in lignocellulose and can be used as a feedstock for next-generation biofuels by industry.Saccharomyces cerevisiae, one of the main workhorses in biotechnology, is unable to metabolize xylose natively but has been engineered to ferment xylose to ethanol with the xylose reductase (XR) and xylitol dehydrogenase (XDH) genes fromScheffersoymces stipitis. In the scientific literature, the yield and volumetric productivity of xylose fermentation to ethanol in engineeredS. cerevisiaestill lagsS. stipitis, despite expressing of the same XR-XDH genes. These contrasting phenotypes can be due to differences inS. cerevisiae’sredox metabolism that hinders xylose fermentation, differences inS. stipitis’redox metabolism that promotes xylose fermentation, or both. To help elucidate howS. stipitisferments xylose, we used flux balance analysis to test various redox balancing mechanisms, reviewed published omics datasets, and studied the phylogeny of key genes in xylose fermentation.In vivoandin silicoxylose fermentation cannot be reconciled without NADP phosphatase (NADPase) and NADH kinase. We identified eight candidate genes for NADPase.PHO3.2was the sole candidate showing evidence of expression during xylose fermentation. Pho3.2p and Pho3p, a recent paralog, were purified and characterized for their substrate preferences. Only Pho3.2p was found to have NADPase activity. Both NADPase and NAD(P)H-dependent XR emerged from recent duplications in a common ancestor ofScheffersoymcesandSpathasporato enable efficient xylose fermentation to ethanol. This study demonstrates the advantages of using metabolic simulations, omics data, bioinformatics, and enzymology to reverse engineer metabolism.
Cell-cell signaling elicits local Ca2+ transients in melanocyte dendrites and dendritic spine-like structures
Authors: Belote Rachel L. , Simon Sanford M. 
Published: August 2018

AbstractCompartmentalized cytoplasmic fluctuations of Ca2+ within dendrites and dendritic spines regulate a variety of neuronal functions. Like some neurons and glia, melanocytes are neural crest derived and possess dendrites (Adameyko et al., 2009; Erickson et al., 1992; Fitzpatrick and Szabo, 1959). Here, we show that primary human melanocytes, when observed in situ have extensive dendritic branches with dendritic spines similar to neurons. When co-cultured with primary human keratinocytes, they have local Ca2+ transients within these spines and within the dendrites. These are elicited by secreted factors from adjacent keratinocytes. Thus other cell types with dendrites are capable of compartmentalized Ca2+ fluctuations in response to cell-cell communication. Furthermore, our observations within intact human skin suggest a more complex communication network between adjacent melanocytes and keratinocytes, and thus a more complex physiology to skin than previous appreciated.
Engineering a model cell for rational tuning of GPCR signaling
Authors: Shaw William M. , Yamauchi Hitoshi , Mead Jack , Gowers Glen-Oliver F. , Öling David , Larsson Niklas , Wigglesworth Mark , Ladds Graham , Ellis Tom 
Published: August 2018

AbstractG protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we here constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose-response. Using four different receptors, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites and hormones relevant to human health. This work enables rational tuning of cell sensing, while providing a framework to guide reprogramming of GPCR-based signaling in more complex systems.
Divergent methyl-coenzyme M reductase genes in a deep-subseafloor Archaeoglobi
Authors: Boyd Joel A. , Jungbluth Sean P. , Leu Andy O. , Evans Paul N. , Woodcroft Ben J. , Chadwick Grayson L. , Orphan Victoria J. , Amend Jan P. , Rappé Michael S. , Tyson Gene W. 
Published: August 2018

AbstractThe methyl-coenzyme M reductase (MCR) complex is a key enzyme in archaeal methane generation and has recently been proposed to also be involved in the oxidation of short-chain hydrocarbons including methane, butane and potentially propane. The number of archaeal clades encoding the MCR complex continues to grow, suggesting that this complex was inherited from an ancient ancestor, or has undergone extensive horizontal gene transfer. Expanding the representation of MCR-encoding lineages through metagenomic approaches will help resolve the evolutionary history of this complex. Here, a near-complete Archaeoglobi metagenome-assembled genome (MAG; rG16) was recovered from the deep subseafloor along the Juan de Fuca Ridge flank that encodes two divergent McrABG operons similar to those found inCandidatusBathyarchaeota andCandidatusSyntrophoarchaeum MAGs. rG16 is basal to members of the class Archaeoglobi, and encodes the genes for β-oxidation, potentially allowing an alkanotrophic metabolism similar to that proposed forCa.Syntrophoarchaeum. rG16 also encodes a respiratory electron transport chain that can potentially utilize nitrate, iron, and sulfur compounds as electron acceptors. As the first Archaeoglobi with the MCR complex, rG16 extends our understanding of the evolution and distribution of novel MCR encoding lineages among the Archaea.
Quality of eyeglass prescriptions from a low-cost wavefront autorefractor evaluated in rural India: results of a 708-participant field study
Authors: Durr Nicholas J. , Dave Shivang R. , Lim Daryl , Joseph Sanil , Ravilla Thulasiraj D , Lage Eduardo 
Published: August 2018

ABSTACTAimTo assess the quality of eyeglass prescriptions provided by an affordable wavefront autorefractor operated by a minimally-trained technician in a low-resource setting.Methods708 participants were recruited from consecutive patients registered for routine eye examinations at Aravind Eye Hospital in Madurai, India, or an affiliated rural satellite vision centre. Visual acuity (VA) and patient preference were compared for eyeglasses prescribed from a novel wavefront autorefractor versus eyeglasses prescribed from subjective refraction by an experienced refractionist.ResultsMean ± standard deviation VA was 0.30 ± 0.37, −0.02 ± 0.14, and −0.04 ± 0.11 LogMAR units before correction, with autorefractor correction, and with subjective refraction correction, respectively (all differences P < 0.01). Overall, 25% of participants had no preference, 33% preferred eyeglasses from autorefractor prescriptions, and 42% preferred eyeglasses from subjective refraction prescriptions (P < 0.01). Of the 438 patients 40 years old and younger, 96 had no preference and the remainder had no statistically-significant difference in preference for subjective refraction prescriptions (51%) versus autorefractor prescriptions (49%) (P = 0.52).ConclusionsAverage VAs from autorefractor-prescribed eyeglasses were one letter worse than those from subjective refraction. More than half of all participants either had no preference or preferred eyeglasses prescribed by the autorefractor. This marginal difference in quality may warrant autorefractor-based prescriptions, given the portable form-factor, short measurement time, low-cost, and minimal training required to use the autorefractor evaluated here.SYNOPSISEyeglass prescriptions can be accurately measured by a minimally-trained technician using a low-cost wavefront autorefractor in rural India. Objective refraction may be a feasible approach to increasing eyeglass accessibility in low-resource settings.
pWGBSSimla: a profile-based whole-genome bisulphite sequencing data simulator incorporating methylation QTLs, allele-specific methylations and differentially methylated regions
Authors: Chung Ren-Hua , Kang Chen-Yu 
Published: August 2018

AbstractMotivationDNA methylation plays an important role in regulating gene expression. There has been growing interest in investigating the roles that genetic variants play in changing the methylation levels (i.e., methylation quantitative trait loci or meQTLs), how methylation regulates the imprinting of gene expression (i.e., allele-specific methylation or ASM), and the differentially methylated regions (DMRs) among different cell types. However, none of the current simulation tools can generate whole-genome bisulphite sequencing (WGBS) data while modeling meQTLs, ASM, and DMRs.ResultsWe developed pWGBSSimla, a profile-based WGBS data simulator, which simulates WGBS data for 29 cell types based on real data. meQTLs and ASM are modeled based on the block structures of methylation status at CpGs, and DMRs are simulated based on observations of methylation rates in real data.AvailabilitypWGBSSimla is available at http://omicssimla.sourceforge.io.
A model of repetitive mild brain injury without symptoms – risk for Parkinson’s disease with aging?
Authors: Kulkarni Praveen , Morrison Thomas R , Cai Xuezhu , Iriah Sade , Lang Mary S. , Kennedy Laporsha , Sabrick Julia , Neuroth Lucas , Hoffman Gloria E , Ferris Craig F 
Published: August 2018

AbstractObjectivesTo test the hypothesis that repetitive mild traumatic brain injury in early life may be a potential risk factor for Parkinson’s disease.MethodsA closed-head momentum exchange model was used to produce one or three mild concussions in young adult male rats as compare to non-injured, age and weight-matched controls. Six-seven weeks post-injury, rats were studied for deficits in cognitive and motor function Changes in brain anatomy and function were evaluated through analysis of resting state functional connectivity, diffusion weighted imaging with quantitative anisotropy and immunohistochemistry for neuroinflammation.ResultsHead injuries occurred without skull fracture or signs of intracranial bleeding or contusion. There were no significant differences in cognitive or motors behaviors between experimental groups. Rats concussed three times showed altered diffusivity in white matter tracts, basal ganglia, central amygdala, brainstem, and cerebellum. With a single concussion, the affected areas were limited to the caudate/putamen and central amygdala. Disruption of functional connectivity was most pronounced with three concussions as the midbrain dopamine system, hippocampus and brainstem/cerebellum showed hypoconnectivity. The suprachiasmatic nucleus was isolated from all functional connections. Interestingly, rats exposed to one concussion showedenhancedfunctional connectivity (or hyperconnectivity) across brain sites, particularly between the olfactory system and the cerebellum. Immunostaining for microglia activation showed inflammation in striatum and substantia nigra with three concussions but not with one.InterpretationNeuroradiological and immunohistochemical evidence of altered brain structure and function, particularly in striatal and midbrain dopaminergic areas, persists long after mild repetitive head injury. These changes may be long lasting and serve as early biomarkers of neurodegeneration and risk for Parkinson’s disease with aging.
droplet-Tn-Seq combines microfluidics with Tn-Seq identifying complex single-cell phenotypes
Authors: Thibault Derek , Wood Stephen , Jensen Paul , Opijnen Tim van 
Published: August 2018

AbstractWhile Tn-Seq is a powerful tool to determine genome-wide bacterial fitness in high-throughput, culturing transposon-mutant libraries in pools can mask community or other complex single-cell phenotypes. droplet-Tn-seq solves that problem by microfluidics facilitated encapsulation of individual transposon mutants into liquid-in-oil droplets, thereby enabling isolated growth, free from the influence of the population. Importantly, all advantages of Tn-Seq are conserved, while reducing costs and greatly extending its applicability.
Conserved phosphorylation hotspots in eukaryotic protein domain families
Authors: Strumillo Marta J. , Oplová Michaela , Viéitez Cristina , Ochoa David , Shahraz Mohammed , Busby Bede P. , Sopko Richelle , Studer Romain A. , Perrimon Norbert , Panse Vikram G. , Beltrao Pedro 
Published: August 2018

AbstractProtein phosphorylation is the best characterized post-translational modification that regulates almost all cellular processes through diverse mechanisms such as changing protein conformations, interactions, and localization. While the inventory for phosphorylation sites across different species has rapidly expanded, their functional role remains poorly investigated. Here, we have combined 537,321 phosphosites from 40 eukaryotic species to identify highly conserved phosphorylation “hotspot” regions within domain families. Mapping these regions onto structural data revealed that they are often found at interfaces, near catalytic residues and tend to harbor functionally important phosphosites. Notably, functional studies of a phospho-deficient mutant in the C-terminal hotspot region within the Ribosomal S11 domain in the yeast ribosomal protein uS11 showed cold-sensitive phenotype and impaired 20S pre-rRNA processing. Altogether, our study identified phosphorylation hotspots for 162 protein domains suggestive of an ancient role for the control of diverse eukaryotic domain families.
Reconciling fMRI and EEG indices of attentional modulations in human visual cortex
Authors: Itthipuripat Sirawaj , Sprague Thomas C , Serences John T 
Published: August 2018

AbstractFunctional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are the two most popular non-invasive methods used to study the neural mechanisms underlying human cognition. These approaches are considered complementary: fMRI has higher spatial resolution but sluggish temporal resolution, whereas EEG has millisecond temporal resolution, but only at a broad spatial scale. Beyond the obvious fact that fMRI measures properties of blood and EEG measures changes in electric fields, many foundational studies assume that, aside from differences in spatial and temporal precision, these two methods index the same underlying neural modulations. We tested this assumption by using EEG and fMRI to measure attentional modulations of neural responses to stimuli of different visual contrasts. We found that equivalent experiments performed using fMRI and EEG on the same participants revealed remarkably different patterns of attentional modulations: event-related fMRI responses provided evidence for an additive increase in responses across all contrasts equally, whereas early stimulus-evoked event-related potentials (ERPs) showed larger modulations with increasing stimulus contrast and only a later negative-going ERP and low-frequency oscillatory EEG signals showed effects similar to fMRI. These results demonstrate that there is not a one-to-one correspondence between the physiological mechanisms that give rise to modulations of fMRI responses and the most commonly used ERP markers, and that the typical approach of employing fMRI and EEG to gain complementary information about localization and temporal dynamics is over-simplified. Instead, fMRI and EEG index different physiological modulations and their joint application affords synergistic insights into the neural mechanisms supporting human cognition.
The genome of the soybean cyst nematode (Heterodera glycines) reveals complex patterns of duplications involved in the evolution of parasitism genes
Authors: Masonbrink Rick , Maier Tom R. , Muppiral Usha , Seetharam Arun S. , Lord Etienne , Juvale Parijat S. , Schmutz Jeremy , Johnson Nathan T. , Korkin Dmitry , Mitchum Melissa G. , Mimee Benjamin , Akker Sebastian Eves-van den , Hudson Matthew , Severin Andrew J. , Baum Thomas J. 
Published: August 2018

AbstractHeterodera glycines, commonly referred to as the soybean cyst nematode (SCN), is an obligatory and sedentary plant parasite that causes over a billion-dollar yield loss to soybean production annually. Although there are genetic determinants that render soybean plants resistant to certain nematode genotypes, resistant soybean cultivars are increasingly ineffective because their multi-year usage has selected for virulentH. glycinespopulations. The parasitic success ofH. glycinesrelies on the comprehensive re-engineering of an infection site into a syncytium, as well as the long-term suppression of host defense to ensure syncytial viability. At the forefront of these complex molecular interactions are effectors, the proteins secreted byH. glycinesinto host root tissues. The mechanisms of effector acquisition, diversification, and selection need to be understood before effective control strategies can be developed, but the lack of an annotated genome has been a major roadblock. Here, we use PacBio long-read technology to assemble aH. glycinesgenome of 738 contigs into 123Mb with annotations for 29,769 genes. The genome contains significant numbers of repeats (34%), tandem duplicates (18.7Mb), and horizontal gene transfer events (151 genes). Using previously published effector sequences, the newly generatedH. glycinesgenome, and comparisons to other nematode genomes, we investigate the evolutionary mechanisms responsible for the emergence and diversification of effector genes.
Micro Computed Tomography as an Accessible Imaging Platform for Exploring Organism Development and Human Disease Modeling
Authors: Schoborg Todd A. , Smith Samantha L. , Smith Lauren N. , Morris H. Douglas , Rusan Nasser M. 
Published: August 2018

ABSTRACTUnderstanding how events at the molecular and cellular scales contribute to tissue form and function is key to uncovering mechanisms driving animal development, physiology and disease. Elucidating these mechanisms has been enhanced through the study of model organisms and the use of sophisticated genetic, biochemical and imaging tools. Here we present an optimized method for non-invasive imaging of Drosophila melanogaster at high resolution using micro computed tomography (μ-CT). Our method allows for rapid processing of intact animals at any developmental stage, provides precise quantitative assessment of tissue size and morphology, and permits analysis of inter-organ relationships. We then use the power of μ-CT imaging to model human diseases through the characterization of microcephaly in the fly. Our work demonstrates that μ-CT is a versatile and accessible tool that complements standard imaging techniques, capable of uncovering novel biological mechanisms that have remained undocumented due to limitations of current methods.
Multi-Scale Neural Sources of EEG: Genuine, Equivalent, and Representative. A Tutorial Review
Authors: Nunez Paul L. , Nunez Michael D. , Srinivasan Ramesh 
Published: August 2018

AbstractA biophysical framework needed to interpret electrophysiological data recorded at multiple spatial scales of brain tissue is developed. Micro current sources at membrane surfaces produce local field potentials (LFP), electrocorticography (ECoG), and electroencephalography (EEG). We categorize multi-scale sources asgenuine,equivalent, orrepresentative.Genuine sourcesoccur at the micro scale of cell surfaces.Equivalent sourcesprovide identical experimental outcomes over a range of scales and applications. In contrast, eachrepresentative source distributionis just one of many possible source distributions that yield similar experimental outcomes. Macro sources (“dipoles”) may be defined at the macrocolumn (mm) scale and depend on several features of the micro sources—magnitudes, micro synchrony within columns, and distribution through the cortical depths. These micro source properties are determined by brain dynamics and the columnar structure of cortical tissue. The number ofrepresentative sourcesunderlying EEG data depends on the spatial scale of neural tissue under study. EEG inverse solutions (e.g. dipole localization) and high resolution estimates (e.g. Laplacian, dura imaging) have both strengths and limitations that depend on experimental conditions. The proposed theoretical framework informs studies of EEGsource localization,source characterization, andlow passes filtering. It also facilitates interpretations of brain dynamics and cognition, including measures ofsynchrony,functional connections between cortical locations, and other aspects ofbrain complexity.