bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental Exposures Influence Nasal Microbiome Composition in a Longitudinal Study of Division I Collegiate Athletes
Authors: Kask Oliver , Kyman Shari , Conn Kathryn A. , Gormley Jenny , Gardner Julia , Johns Robert A. , Caporaso J. Gregory , Bycura Dierdra , Sutliffe Jay T. , Cope Emily K. 
Published: February 2020

AbstractBackgroundThe anterior nares host a complex microbial community that contributes to upper airway health. Although the bacterial composition of the nasal passages have been well characterized in healthy and diseased cohorts, the role of prolonged environmental exposures and exercise in shaping the nasal microbiome in healthy adults is poorly understood. In this study, we longitudinally sampled female collegiate Division I athletes from two teams experiencing a similar athletic season and exercise regimen but vastly different environmental exposures (Swim/Dive and Basketball). Using 16S rRNA gene sequencing, we evaluated the longitudinal dynamics of the nasal microbiome pre-, during-, and at the end of the athletic season.ResultsThe nasal microbiota of the Swim/Dive and Basketball teams were distinct from each other at each time point sampled, driven by either low abundance (Jaccard, PERMANOVA p<0.05) or high-abundance changes in composition (Bray-Curtis, PERMANOVA p<0.05). The rate of change of microbial communities were greater in the Swim/Dive team compared to the Basketball team characterized by an increase inStaphylococcusin Swim/Dive and a decrease inCorynebacteriumin both teams over time.ConclusionsThis is the first study that has evaluated the nasal microbiome in athletes. We obtained longitudinal nasal swabs from two gender-matched teams with similar age distributions (18-22 years old) over a 6 month period. Differences in the microbiota between teams and over time indicate that chlorine exposure, and potentially athletic training, induced changes in the nasal microbiome.
Targeted attenuation of elevated histone marks atSNCAalleviates α-synuclein in Parkinson’s disease
Authors: Guhathakurta Subhrangshu , Kim Jinil , Basu Sambuddha , Adler Evan , Je Goun , Fiadeiro Mariana Bernardo , Kim Yoon-Seong 
Published: February 2020

AbstractEpigenetic de-regulation of α-synuclein plays a key role in Parkinson’s disease (PD). Analysis of theSNCApromoter using the ENCODE database revealed the presence of important histone posttranslational modifications (PTMs) including transcription-promoting marks, H3K4me3 and H3K27ac, and repressive mark, H3K27me3. We investigated these histone marks in postmortem brains of controls and PD patients and observed that only H3K4me3 was significantly elevated at theSNCApromoter of the substantia nigra (SN) of PD patients both in punch biopsy as well as in NeuN positive neuronal nuclei samples. To understand the importance of H3K4me3 in regulation of α-synuclein, we developed CRISPR/dCas9-based locus-specific H3K4me3 demethylating system where the catalytic domain of JARID1A was recruited to theSNCApromoter. This CRISPR/dCas9 SunTag-JARID1A significantly reduced H3K4me3 atSNCApromoter and concomitantly decreased α-synuclein both in the neuronal cell line SH-SY5Y and idiopathic PD-iPSC derived dopaminergic neurons. In sum, this study indicates that α-synuclein expression in PD is controlled bySNCA’shistone PTMs and modulation of the histone landscape ofSNCAcan reduce α-synuclein expression.
Structure-based identification and functional characterization of an essential lipocalin in the malaria parasitePlasmodium falciparum
Authors: Burda Paul-Christian , Crosskey Thomas , Lauk Katharina , Zurborg Aimo , Söhnchen Christoph , Liffner Benjamin , Wilcke Louisa , Strauss Jan , Jeffries Cy , Svergun Dmitri I. , Wilson Danny W. , Wilmanns Matthias , Gilberger Tim-Wolf 
Published: February 2020

SUMMARYProteins of the lipocalin family are known to bind small hydrophobic ligands and are involved in various physiological processes ranging from lipid transport to oxidative stress responses. The genome of the malaria parasitePlasmodium falciparumcontains a single protein PF3D7_0925900 with a lipocalin signature. Using crystallography and small-angle X-ray scattering, we show that the protein has a tetrameric structure of typical lipocalin monomers, hence we name itP. falciparumlipocalin (PfLCN), the first lipocalin structurally and functionally characterized in a single-celled eukaryote. We show thatPfLCN is expressed in the intraerythrocytic stages of the parasite and localizes to the parasitophorous and food vacuoles. Conditional knockdown ofPfLCN impairs parasite development, which can be rescued by treatment with the radical scavenger Trolox or by temporal inhibition of hemoglobin digestion. This suggests a key function ofPfLCN in counteracting oxidative stress induced cell damage during multiplication of parasites within red blood cells.
Revisiting the links-species scaling relationship in food webs
Authors: MacDonald Andrew , Banville Francis , Poisot Timothée 
Published: February 2020

AbstractPredicting the number of interactions that species in a food web will establish is an important task. These trophic interactions underlie many ecological and evolutionary processes, ranging from biomass fluxes, ecosystem stability, resilience to extinction, and resistance against novel species. We investigate and compare several ways to predict the number of interactions in food webs. We conclude that a simple beta-binomial model outperforms other models, with the added desirable property of respecting biological constraints. We show how this simple relationship gives rise to a predicted distribution of several quantities related to link number in food webs, including the scaling of network structure with space, and the probability that a network will be stable.
Neonatal levels of acute phase proteins and risk of autism spectrum disorders
Authors: Gardner Renee M. , Lee Brian K. , Brynge Martin , Sjöqvist Hugo , Dalman Christina , Karlsson Håkan 
Published: February 2020

AbstractBackgroundImmune signaling pathways influence neurodevelopment and are hypothesized to contribute to the etiology of autism spectrum disorders (ASD). We aimed to assess risk of ASD in relation to levels of neonatal acute phase proteins, key components of innate immune function, measured in neonatal dried blood spots.MethodWe included 924 ASD cases, 1092 unaffected population-based controls, and 203 unaffected siblings to ASD cases in this case-control study nested within the register-based Stockholm Youth Cohort. Concentrations of nine different acute phase proteins were measured in eluates from neonatal dried blood spots from cases, controls, and siblings using a bead-based multiplex assay.ResultsC reactive protein was consistently associated with odds of ASD in case-control comparisons, with higher odds associated with the highest quintile compared to the middle quintile (OR 1.50, 95% CI 1.10 – 2.04) in adjusted analyses. In contrast, the lowest quintiles of alpha-2-macroglobulin (3.71, 1.21 – 11.33), ferritin (4.20, 1.40 – 12.65), and Serum Amyloid P (3.05, 1.16 – 8.01) were associated with odds of ASD in the matched sibling comparison. Neonatal acute phase proteins varied with perinatal environmental factors and maternal/fetal phenotypes. Significant interactions in terms of risk for ASD were observed between neonatal acute phase proteins and maternal infection in late pregnancy, maternal anemia, and maternal psychiatric history.ConclusionsIndicators of the neonatal innate immune response are associated with risk for ASD, though the nature of these associations varies considerably with factors in the perinatal environment and the genetic background of the comparison group.
A Critical Role for Perivascular Cells in Amplifying Viral Haemorrhage Induced by Dengue Virus Non-Structural Protein 1
Authors: Cheung Yin P. , Mastrullo Valeria , Maselli Davide , Butsabong Teemapron , Madeddu Paolo , Maringer Kevin , Campagnolo Paola 
Published: February 2020

ABSTRACTDengue is the most prevalent arthropod-borne viral disease affecting humans, with severe dengue typified by potentially fatal microvascular leakage and hypovolaemic shock. Blood vessels of the microvasculature are composed of a tubular structure of endothelial cells ensheathed by perivascular cells (pericytes). Pericytes support endothelial cell barrier formation and maintenance through paracrine and contact-mediated signalling, and are critical to microvascular integrity. Pericyte dysfunction has been linked to vascular leakage in noncommunicable pathologies such as diabetic retinopathy, but has never been linked to infection-related vascular leakage. Dengue vascular leakage has been shown to result in part from the direct action of the secreted dengue virus (DENV) non-structural protein NS1 on endothelial cells. Using primary human vascular cells, we show here that NS1 also causes pericyte dysfunction, and that NS1-induced endothelial hyperpermeability is more pronounced in the presence of pericytes. Notably, NS1 specifically disrupted the ability of pericytes to support endothelial cell function in a 3D microvascular assay, with no effect on pericyte viability or physiology. These effects are mediated at least in part through contact-independent paracrine signals involved in endothelial barrier maintenance by pericytes. We therefore identify a role for pericytes in amplifying NS1-induced microvascular hyperpermeability in severe dengue, and thus show that pericytes can play a critical role in the aetiology of an infectious vascular leakage syndrome. These findings open new avenues of research for the development of drugs and diagnostic assays for combating infection-induced vascular leakage, such as severe dengue.SIGNIFICANCE STATEMENTThe World Health Organisation considers dengue one of the top ten global public health problems. There is no specific antiviral therapy to treat dengue virus and no way of predicting which patients will develop potentially fatal severe dengue, typified by vascular leakage and circulatory shock. We show here that perivascular cells (pericytes) amplify the vascular leakage-inducing effects of the dengue viral protein NS1 through contact-independent signalling to endothelial cells. While pericytes are known to contribute to noncommunicable vascular leakage, this is the first time these cells have been implicated in the vascular effects of an infectious disease. Our findings could pave the way for new therapies and diagnostics to combat dengue, and potentially other infectious vascular leakage syndromes.
β-L-1-[5-(E-2-Bromovinyl)-2-(Hydroxymethyl)-1,3-Dioxolan-4-yl)] Uracil (L-BHDU) Inhibits Varicella Zoster Virus Replication by Depleting the Cellular dTTP Pool
Authors: De Chandrav , Liu Dongmei , Singh Uma S. , Chu Chung K. , Moffat Jennifer F. 
Published: February 2020

Abstractß-L-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (L-BHDU) inhibits varicella zoster virus (VZV) replication in cultured cells, human skin, and in SCID-Hu mice with skin xenografts. VZV thymidine kinase converts L-BHDU to monophosphate (MP) and diphosphate (DP) forms, but the triphosphate form was not detected in infected cells and the antiviral mechanism was unknown. Given its similar structure to uridine, we asked if L-BHDU interfered with viral DNA replication via inhibition of the purine and/or pyrimidine biosynthesis pathways. Addition of purines to the medium was unable to restore VZV replication in the presence of L-BHDU. In contrast, excess thymidine and uridine in proportion to L-BHDU restored VZV replication, suggesting that the active form of L-BHDU interfered with pyrimidine biosynthesis. However, addition of thymidine and uridine failed to restore VZV replication in non-dividing cells treated with L-BHDU. Like other herpesviruses, VZV infection increased thymidine triphosphate (dTTP) in confluent cells while L-BHDU treatment decreased the dTTP pool by nearly 4-fold. The active form(s) of L-BHDU did not interfere with cellular metabolism, suggesting viral target(s).
Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency
Authors: Perdue Lacey A , Do Priscilla , David Camille , Chyong Andrew , Kellner Anna , Ruggieri Amanda , Kim Hye Ryong , Salaita Khalid , Lesinski Gregory B , Porter Christopher C , Dreaden Erik C 
Published: February 2020

ABSTRACTCytokine signaling is challenging to study and therapeutically exploit as the effects of these protein are often pleiotropic. A subset of cytokines can, however, exert signal specificity via association with latency-inducing proteins which cage the cytokine until disrupted by discreet biological stimuli. Inspired by this precision, here we describe a strategy for synthetic induction of cytokine latency via modification with photo-labile polymers that mimic latency while attached, then restore protein activity in response to light, thus controlling the magnitude, duration, and location of cytokine signals. We characterize the high dynamic range of latent cytokine activity modulation and find that polymer-induced latency, alone, can prolongin vivocirculation and bias receptor subunit binding. We further show that protein de-repression can be achieved with near single-cell resolution and demonstrate the feasibility of transcutaneous photoactivation. Future extensions of this approach could enable multicolor, optical reprogramming of cytokine signaling networks and more precise immunotherapies.
Co-expression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders
Authors: Pang Kaifang , Wang Li , Wang Wei , Zhou Jian , Cheng Chao , Han Kihoon , Zoghbi Huda Y. , Liu Zhandong 
Published: February 2020

AbstractRecent large-scale sequencing studies have identified a great number of genes whose disruptions cause neurodevelopmental disorders (NDDs). However, cell-type-specific functions of NDD genes and their contributions to NDD pathology are unclear. Here, we integrated NDD genetics with single-cell RNA sequencing data to identify cell-type and temporal convergence of genes involved in different NDDs. By assessing the co-expression enrichment pattern of various NDD gene sets, we identified mid-fetal cortical neural progenitor cell development—more specifically, ventricular radial glia-to-intermediate progenitor cell transition at gestational week 10—as a key convergent point in autism spectrum disorder (ASD) and epilepsy. Integrated gene ontology-based analyses further revealed that ASD genes function as upstream regulators to activate neural differentiation and inhibit cell cycle during the transition, whereas epilepsy genes function as downstream effectors in the same processes, offering a potential explanation for the high comorbidity rate of the two disorders. Together, our study provides a framework for investigating the cell-type-specific pathophysiology of NDDs.
A GT-seq panel for walleye (Sander vitreus) provides a generalized workflow for efficient development and implementation of amplicon panels in non-model organisms
Authors: Bootsma Matthew L. , Gruenthal Kristen M. , McKinney Garrett J. , Simmons Levi , Miller Loren , Sass Greg G. , Larson Wesley A. 
Published: February 2020

AbstractTargeted amplicon sequencing methods, such as genotyping-in-thousands by sequencing (GT-seq), facilitate rapid, accurate, and cost-effective analysis of hundreds of genetic loci in thousands of individuals, but studies describing detailed workflows of GTseq panel development are rare. Here, we develop a dual-purpose GT-seq panel for walleye (Sander vitreus) and discuss trade-offs associated with different development and genotyping approaches. Our GT-seq panel was developed using restriction site-associated DNA data from 954 individuals sampled from 23 populations in Minnesota and Wisconsin, USA. We then conducted simulations to test the utility of loci for parentage analysis and genetic stock identification and designed 600 primer pairs to maximize joint accuracy for these analyses. We conducted three rounds of primer optimization to remove loci that overamplified and our final panel consisted of 436 loci. Optimization focused on reducing variation in amplification rate among loci and minimizing the proportion of off-target sequence, both of which are important considerations for developing large GT-seq panels. We also explored different approaches for DNA extraction, multiplexed polymerase chain reaction (PCR) amplification, and cleanup steps during the GT-seq process and discovered the following: (1) inexpensive Chelex extractions performed well for genotyping, (2) the exonuclease I and shrimp alkaline phosphatase (ExoSAP) procedure included in some current protocols did not improve results substantially and was likely unnecessary, and (3) it was possible to PCR amplify panels separately and combine them prior to adapter ligation. Well-optimized GT-seq panels are valuable resources for conservation genetics and our findings should aid in their construction in myriad taxa.
Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration
Authors: Yang Leilei , Liang Jingjing , Lam Sin Man , Yavuz Ahmet , Wang Meng C. , Shui Guanghou , Ding Mei , Huang Xun 
Published: February 2020

AbstractLipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genesatgl-1andlid-1lead to LD appearance in neurons ofCaenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation-triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects, synergistically with decreased lipolysis. Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in regulating neural functions and neurodegeneration cell-autonomously.HighlightsNeuronal lipolysis prevents LD accumulation in neurons.Defective neuronal lipolysis leads to touch sensation defect.Blocking neuronal lipolysis alleviates neurodegeneration.Neuronal lipolysis andde novoPUFA biosynthesis have a synergistic effect in neurodegeneration.The incorporation of PUFAs into phospholipids promotes neurodegeneration.
Slow oscillation-spindle coupling predicts sequence-based language learning
Authors: Cross Zachariah R. , Helfrich Randolph F. , Corcoran Andrew W. , Dede Adam J. O. , Kohler Mark J. , Coussens Scott W. , Zou-Williams Lena , Schlesewsky Matthias , Gaskell M. Gareth , Knight Robert T. , Bornkessel-Schlesewsky Ina 
Published: February 2020

AbstractSentence comprehension involves the rapid decoding of both semantic and grammatical information, a process fundamental to communication. As with other complex cognitive processes, language comprehension relies, in part, on long-term memory. However, the electrophysiological mechanisms underpinning the initial encoding and generalisation of higher-order linguistic knowledge remain elusive, particularly from a sleep-based consolidation perspective. One candidate mechanism that may support the consolidation of higher-order language is the temporal coordination of slow oscillations (SO) and sleep spindles during non-rapid eye movement sleep (NREM). To examine this hypothesis, we analysed electroencephalographic (EEG) data recorded from 35 participants (Mage= 25.4, SD = 7.10; 16 males) during an artificial language learning task, contrasting performance between individuals who were given an 8hr nocturnal sleep period or an equivalent period of wake. We found that sleep relative to wake was associated with superior performance for rules that followed a sequence-based word order. Post-sleep sequence-based word order processing was further associated with less task-related theta desynchronisation, an electrophysiological signature of successful memory consolidation, as well as cognitive control and working memory. Frontal NREM SO-spindle coupling was also positively associated with behavioural sensitivity to sequence-based word order rules, as well as with task-related theta power. As such, theta activity during retrieval of previously learned information correlates with SO-spindle coupling, thus linking neural activity in the sleeping and waking brain. Taken together, this study presents converging behavioral and neurophysiological evidence for a role of NREM SO-spindle coupling and task-related theta activity as signatures of successful memory consolidation and retrieval in the context of higher-order language learning.SIGNIFICANCE STATEMENTThe endogenous temporal coordination of neural oscillations supports information processing during both wake and sleep states. Here we demonstrate that slow oscillation-spindle coupling during non-rapid eye movement sleep predicts the consolidation of complex grammatical rules and modulates task-related oscillatory dynamics previously implicated in sentence processing. We show that increases in theta power predict enhanced sensitivity to grammatical violations after a period of sleep and strong slow oscillation-spindle coupling modulates subsequent task-related theta activity to influence behaviour. Our findings reveal a complex interaction between both wake- and sleep-related oscillatory dynamics during the early stages of language learning beyond the single word level.
CGGBP1-regulated cytosine methylation at CTCF-binding motifs resists stochasticity
Authors: Patel Manthan , Patel Divyesh , Datta Subhamoy , Singh Umashankar 
Published: February 2020

ABSTRACTThe human CGGBP1 is implicated in a variety of cellular functions. It regulates genomic integrity, cell cycle, gene expression and cellular response to growth signals. Evidence suggests that these functions of CGGBP1 manifest through binding to GC-rich regions in the genome and regulation of interspersed repeats. Recent works show that CGGBP1 is needed for cytosine methylation homeostasis and genome-wide occupancy patterns of the epigenome regulator protein CTCF. It has remained unknown if cytosine methylation regulation and CTCF occupancy regulation by CGGBP1 are independent or interdependent processes. By sequencing immunoprecipitated methylated DNA, we have found that some transcription factor-binding sites resist stochastic changes in cytosine methylation. Of these, we have analyzed the CTCF-binding sites thoroughly and show that cytosine methylation regulation at CTCF-binding DNA sequence motifs by CGGBP1 is deterministic. These CTCF-binding sites are positioned at locations where the spread of cytosine methylationin cisdepends on the levels of CGGBP1. Our findings suggest that CTCF occupancy and functions are determined by CGGBP1-regulated cytosine methylation patterns.