bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG signal diversity during propofol sedation: an increase in sedated but responsive, a decrease in sedated and unresponsive subjects
Authors: Bola Michał , Orłowski Paweł , Płomecka Martyna , Marchewka Artur 
Published: October 2018

AbstractTransitions between wakefulness and anesthesia are accompanied by profound changes in brain functioning. A key challenge is thus to disentangle neuronal mechanisms specific to loss and recovery of consciousness, from more general effects that are not directly related to the capacity for conscious experience. Measures of neuronal diversity have been recently proposed to constitute a robust correlate of the global states of consciousness. In the present study we investigated whether EEG signal diversity is indeed related to behavioral responsiveness during propofol sedation, or rather to the general drug-related effects. To this end, we reanalyzed data collected from 20 subjects sedated with propofol. Based on the responsiveness to auditory stimuli all subjects were subdivided into two subgroups - responsive (n = 13), who remains awake throughout the experiment, and drowsy (n = 7), who becomes unresponsive during moderate sedation. Resting state EEG recorded during wakefulness and sedation was characterized by the Mean Information Gain (MIG) and Fluctuation complexity (FC) - information-theory measures estimating signal diversity or complexity, respectively. The main finding is that the drowsy group exhibited a decrease in diversity during sedation but, unexpectedly, the responsive group exhibited a robust increase in diversity (ANOVA group x state interaction: F(3) = 7.81, p < 0.001; BF10 > 197). However, signal complexity neither differentiated the subgroups, nor decreased reliably during sedation (t-test wake vs. moderate sedation: t(19) = 2.57, p = 0.092; BF10 = 3.08). Further, we show that a change in signal diversity is negatively correlated with a delta power change (r = −0.62, p = 0.002), and positively correlated with a beta power change (r = 0.84, p < 0.001). Finally, we show that MIG behaves in a qualitatively similar manner to Lempel-Ziv – another diversity measures used in several recent studies. Overall, we revealed that propofol sedation is initially related to an increase in EEG signal diversity, and that only upon loss of responsiveness EEG diversity decreases. The qualitatively different pattern of changes in the responsive and drowsy groups makes EEG diversity a robust indirect index of responsiveness and, presumably, consciousness.
Genetic networks underlying natural variation in basal and induced activity levels inDrosophila melanogaster
Authors: Watanabe Louis P. , Gordon Cameron , Momeni Mina Y. , Riddle Nicole C. 
Published: October 2018

ABSTRACTExercise is recommended by health professionals across the globe as part of a healthy lifestyle to prevent and/or treat the consequences of obesity. While overall, the health benefits of exercise and an active lifestyle are well understood, very little is known about how genetics impacts an individual’s inclination for and response to exercise. To address this knowledge gap, we investigated the genetic architecture underlying natural variation in activity levels in the model systemDrosophila melanogaster. Activity levels were assayed in the Drosophila Genetics Reference Panel 2 fly strains at baseline and in response to a gentle exercise treatment using the Rotational Exercise Quantification System. We found significant, sex-dependent variation in both activity measures and identified over 100 genes that contribute to basal and induced exercise activity levels. This gene set was enriched for genes with functions in the central nervous system and in neuromuscular junctions and included several candidate genes with known activity phenotypes such as flightlessness or uncoordinated movement. Interestingly, there were also several chromatin proteins among the candidate genes, two of which were validated and shown to impact activity levels. Thus, the study described here reveals the complex genetic architecture controlling basal and exercise-induced activity levels inD. melanogasterand provides a resource for exercise biologists.
Association study of long-term kidney transplant rejection using whole-exome sequencing
Authors: Gioia Louis , Kurian Sunil , Mondala Tony S. , Bassaganyas Laia , Kwok Pui-Yan , Salomon Daniel R. , Su Andrew I. 
Published: October 2018

AbstractLong-term renal allograft rejection is the most common outcome in kidney transplantation. Continuing the crusade to extend allograft function after the first year post-transplantation, we attempted to associate genetic factors that might contribute to long-term allograft outcomes by sequencing the exomes of patients diagnosed with chronic allograft nephropathy/interstitial fibrosis and tubular atrophy. A variety of association analyses were employed, but these analyses failed to identify statistically significant associations. The study was underpowered to detect the association of rare genomic variants with small effect sizes. However, it confirmed previous reports of the absence of large effects from common variants. We have made both the study data and analysis workflow available for public use, and we hope that these resources will help to power future meta-analyses that may detect smaller effects.
Rhizosphere microbes influence host circadian clock function
Authors: Hubbard Charley J. , McMinn Robby , Weinig Cynthia 
Published: October 2018

AbstractThe circadian clock is an important determinant of individual fitness that is entrained by local conditions. In addition to known abiotic inputs that entrain the circadian clock, individual pathogenic soil bacteria affect the circadian period of plant hosts. Yet, in nature, plants interact with diverse microbial communities including hundreds to thousands of microbial taxa, and the effect of these communities on clock function remains unclear. In Arabidopsis thaliana, we used diverse rhizosphere inoculates and both wild-type and clock mutant genotypes to test the effect of complex rhizosphere microbial communities on the host circadian clock. Host plants with an intact rhizosphere microbiome expressed a circadian period that was closer to 24 hrs in duration and significantly shorter (by 60 minutes on average) relative to plants grown with a disrupted microbiome. Wild-type host genotypes differed significantly in clock sensitivity to microbiome treatments, where the effect was most pronounced in the Landsberg erecta genotype and least in the Columbia genotype. Rhizosphere microbes collected from a host genotype with a short-period phenotype (toc1-21) and used as inoculate significantly shortened the long-period phenotype of the ztl-1 clock mutant genotype. The results indicate that complex rhizosphere microbial communities significantly affect host clock function.
Crystal structure of m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon receptor binding
Authors: Bitra Aruna , Doukov Tzanko , Destito Giuseppe , Croft Michael , Zajonc Dirk M. 
Published: October 2018

ABSTRACTThe interaction between the 4-1BB and its ligand 4-1BBL provides co-stimulatory signals for T cell activation and proliferation, but differences in the mouse and human molecules might result in differential engagement of this pathway. Here, we report the crystal structure of mouse 4-1BBL and of the mouse 4-1BB/4-1BBL complex, together provide insights into the molecular recognition of the cognate receptor by m4-1BBL. In contrast to all human or mouse TNF ligands that form non-covalent mostly trimeric assemblies, the m4-1BBL structure formed a novel disulfide linked dimeric assembly. The structure showed that certain differences in the amino acid composition along the intramolecular interface, together with two specific residues (Cys 246 and Ser 256) that are exclusively present in m4-1BBL, are responsible for unique dimerization. Unexpectedly, upon binding to m4-1BB, m4-1BBL undergoes structural changes within each protomer, in addition the individual m4-1BBL protomers rotate with respect to each other, leading to a different dimerization interface with more inter-subunit interactions. In the m4-1BB/4-1BBL complex, each receptor monomer binds exclusively to a single ligand subunit with contributions of cysteine-rich domain (CRD) 1, CRD2 and CRD3. Furthermore, structure-guided mutagenesis of the binding interface revealed that novel binding interactions with the GH loop, rather than the DE loop, are energetically critical and define the species based receptor selectivity for m4-1BBL. A comparison with the human 4-1BB/4-1BBL complex highlighted several differences between the ligand and receptor binding interfaces and provide an explanation for the absence of inter species cross-reactivity between human and mouse 4-1BB and 4-1BBL molecules.
Value-based Decision Making Takes Place in the Action Domain in the Prefrontal Cortex
Authors: Lin Zhongqiao , Nie Chechang , Zhang Yuanfeng , Chen Yang , Yang Tianming 
Published: October 2018

AbstractValue-based decision making is a process in which humans or animals maximize their gain by selecting appropriate options and performing the corresponding actions to acquire them. Whether the evaluation process of the options in the brain can be independent from their action contingency has been hotly debated. To address the question, we trained rhesus monkeys to make decisions by integrating evidence and studied whether the integration occurred in the stimulus or the action domain in the brain. After the monkeys learned the task, we recorded both from the orbitofrontal (OFC) and dorsolateral prefrontal (DLPFC) cortices. We found that the OFC neurons encoded the value associated with the single piece of evidence in the stimulus domain. Importantly, the representations of the value in the OFC was transient and the information was not integrated across time for decisions. The integration of evidence was observed only in the DLPFC and only in the action domain. We further used a neural network model to show how the stimulus-to-action transition of value information may be computed in the DLPFC. Our results indicated that the decision making in the brain is computed in the action domain without an intermediate stimulus-based decision stage.
Nanopore formation in the cuticle of an insect olfactory sensillum
Authors: Ando Toshiya , Sekine Sayaka , Inagaki Sachi , Misaki Kazuyo , Badel Laurent , Moriya Hiroyuki , Sami Mustafa M. , Itakura Yuki , Chihara Takahiro , Kazama Hokto , Yonemura Shigenobu , Hayashi Shigeo 
Published: October 2018

SummaryNanometer-level patterned surface structures form the basis of biological functions including superhydrophobicity, structural coloration, and light absorption [1-3]. In insects, the cuticle overlying the olfactory sensilla has multiple small (50–200-nm diameter) pores [4-8], which are supposed to function as a filter that admits odorant molecules, while preventing the entry of larger airborne particles and limiting water loss. However, the cellular processes underlying the patterning of extracellular matrices into functional nano-structures remain unknown. Here we show that cuticular nanopores inDrosophilaolfactory sensilla originate from a curved ultrathin film that is formed in the outermost envelope layer of the cuticle, and secreted from specialized protrusions in the plasma membrane of the hair forming (trichogen) cell. The envelope curvature coincides with plasma membrane undulations associated with endocytic structures. Thegore-tex/Osiris23gene encodes an endosomal protein that is essential for envelope curvature, nanopore formation, and odor receptivity, and is expressed specifically in developing olfactory trichogen cells. The 24-memberOsirisgene family is expressed in cuticle-secreting cells, and is found only in insect genomes. These results reveal an essential requirement for nanopores for odor reception and identifyOsirisgenes as a platform for investigating the evolution of surface nano-fabrication in insects.
Epigenetic drift during long-term culture of cells in vitro
Authors: Franzen Julia , Georgomanolis Theodoros , Selich Anton , Kuo Chao-Chung , Stöger Reinhard , Brant Lilija , Mulabdić Melita Sara , Fernandez-Rebollo Eduardo , Grezella Clara , Ostrowska Alina , Begemann Matthias , Nikolić Miloš , Rath Björn , Ho Anthony D. , Rothe Michael , Schambach Axel , Papantonis Argyris , Wagner Wolfgang 
Published: October 2018

AbstractCulture expansion of primary cells evokes highly reproducible DNA methylation (DNAm) changes at specific sites in the genome. These changes might be due to an directly regulated epigenetic process, or to gradual deregulation of the epigenetic state, which is often referred to as “epigenetic drift”. We have identified CG dinucleotides (CpGs) that become continuously hyper- or hypomethylated in the course of culture expansion of mesenchymal stem cells (MSCs) and other cell types. During reprogramming into induced pluripotent stem cells (iPSCs) particularly the culture-associated hypomethylation is reversed simultaneously with age-associated and pluripotency-associated DNAm changes. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated that upon passaging the DNAm patterns of neighboring CpGs become more complex without evidence of continuous pattern development and without association to oligoclonal subpolulations of MSCs at later passages. Circularized chromatin conformation capture (4C) revealed reproducible changes in nuclear organization between early and late passages, while there was no preferential interaction with other genomic regions that also harbor culture-associated DNAm changes. Chromatin immunoprecipitation of CTCF did not show significant differences during long-term culture of MSCs, however culture-associated hypermethylation was enriched at CTCF binding sites and hypomethylated CpGs were devoid of CTCF. Taken together, our results indicate that DNAm changes during culture-expansion resembles epigenetic drift, which seems to occur in relation to chromatin conformation.
A global survey of arsenic related genes in soil microbiomes
Authors: Dunivin Taylor K , Yeh Susanna Y , Shade Ashley 
Published: October 2018

AbstractEnvironmental resistomes include transferable microbial genes. One important resistome component is resistance to arsenic, a ubiquitous and toxic metalloid that can have negative and chronic consequences for human and animal health. The distribution of arsenic resistance and metabolism genes in the environment is not well understood. However, microbial communities and their resistomes mediate key transformations of arsenic that are expected to impact both biogeochemistry and local toxicity. We examined the phylogenetic diversity, genomic location (chromosome or plasmid), and biogeography of arsenic resistance and metabolism genes in 922 soil genomes and 38 metagenomes. To do so, we developed a bioinformatic toolkit that includes BLAST databases, hidden Markov models and resources for gene-targeted assembly of nine arsenic resistance and metabolism genes: acr3, aioA, arsB, arsC (grx), arsC (trx), arsD, arsM, arrA, and arxA. Though arsenic related genes were common, they were not universally detected, contradicting the common conjecture that all organisms have them. From major clades of arsenic related genes, we inferred their potential for horizontal and vertical transfer. Different types and proportions of genes were detected across soils, suggesting microbial community composition will, in part, determine local arsenic toxicity and biogeochemistry. While arsenic related genes were globally distributed, particular sequence variants were highly endemic (e.g., acr3), suggesting dispersal limitation. The gene encoding arsenic methylase arsM was unexpectedly abundant in soil metagenomes (median 48%), suggesting that it plays a prominent role in global arsenic biogeochemistry. Our analysis advances understanding of arsenic resistance, metabolism, and biogeochemistry, and our approach provides a roadmap for the ecological investigation of environmental resistomes.
Joint single cell DNA-Seq and RNA-Seq of cancer reveals subclonal signatures of genomic instability and gene expression
Authors: Andor Noemi , Lau Billy T. , Catalanotti Claudia , Kumar Vijay , Sathe Anuja , Belhocine Kamila , Wheeler Tobias D. , Price Andrew D. , Song Maengseok , Džakula Željko , Sorenson Jon , Stafford David , Bent Zachary , DeMare Laura , Hepler Lance , Jett Susana , Lin Bill Kengli , Maheshwari Shamoni , Makarewicz Anthony J. , Rahimi Mohammad , Sawhney Sanjam S. , Sauzade Martin , Shuga Joe , Sullivan-Bibee Katrina , Weinstein Adam , Yang Wei , Yin Yifeng , Kubit Matthew , Chen Jiamin , Grimes Susan M. , Suarez Carlos Jose , Poultsides George A. , Schnall-Levin Michael , Bharadwaj Rajiv , Ji Hanlee P. 
Published: October 2018

ABSTRACTSequencing the genomes of individual cancer cells provides the highest resolution of intratumoral heterogeneity. To enable high throughput single cell DNA-Seq across thousands of individual cells per sample, we developed a droplet-based, automated partitioning technology for whole genome sequencing. We applied this approach on a set of gastric cancer cell lines and a primary gastric tumor. In parallel, we conducted a separate single cell RNA-Seq analysis on these same cancers and used copy number to compare results. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection – where the percentage of replicating cells per clone is higher than expected – indicating ongoing tumor evolution. Our study demonstrates that joining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.SIGNIFICANCEWe conducted a massively parallel DNA sequencing analysis on a set of gastric cancer cell lines and a primary gastric tumor in combination with a joint single cell RNA-Seq analysis. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection where the percentage of replicating cells per clone is higher than expected indicating ongoing tumor evolution. Our study demonstrates that combining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.
IsoProt: A complete and reproducible workflow to analyse iTRAQ/TMT experiments
Authors: Griss Johannes , Vinterhalter Goran , Schwämmle Veit 
Published: October 2018

AbstractReproducibility has become a major concern in biomedical research. In proteomics, bioinformatic workflows can quickly consist of multiple software tools each with its own set of parameters. Their usage involves the definition of often hundreds of parameters as well as data operations to ensure tool interoperability. Hence a manuscript’s methods section is often insufficient to completely describe and reproduce a data analysis workflow. Here we present IsoProt: A complete and reproducible bioinformatic workflow deployed on a portable container environment to analyse data from isobarically-labeled, quantitative proteomics experiments. The workflow uses only open source tools and provides a user-friendly and interactive browser interface to configure and execute the different operations. Once the workflow is executed, the results including the R code to perform statistical analyses can be downloaded as an HTML or PDF document providing a complete record of the performed analyses. IsoProt therefore represents a reproducible bioinformatics workflow that will yield identical results on any computer platform.
Glass confers rhabdomeric photoreceptor identity inDrosophila, but not across all metazoans
Authors: Bernardo-Garcia F. Javier , Syed Maryam , Jékely Gáspár , Sprecher Simon G. 
Published: October 2018

ABSTRACTAcross metazoans, visual systems employ different types of photoreceptor neurons to detect light. These include rhabdomeric PRs, which exist in distantly related phyla and possess an evolutionarily conserved phototransduction cascade. While the development of rhabdomeric PRs has been thoroughly studied in the fruit flyDrosophila melanogaster, we still know very little about how they form in other species. To investigate this question, we tested whether the transcription factor Glass, which is crucial for instructing rhabdomeric PR formation inDrosophila, may play a similar role in other metazoans. Glass homologues exist throughout the animal kingdom, indicating that this protein evolved prior to the metazoan radiation. Interestingly, our work indicates thatglassis not expressed in rhabdomeric photoreceptors in the planarianSchmidtea mediterraneanor in the annelidPlatynereis dumerilii. Combined with a comparative analysis of the Glass DNA-binding domain, our data suggest that the fate of rhabdomeric PRs is controlled by Glass-dependent and Glass-independent mechanisms in different animal clades.
Teaching methods shape neural tuning to visual words in beginning readers
Authors: van de Walle de Ghelcke Alice , Rossion Bruno , Schiltz Christine , Lochy Aliette 
Published: October 2018

AbstractThe impact of global vs. phonics teaching methods for reading on the emergence of left hemisphere neural specialization for word recognition is unknown in children. We tested 42 first graders behaviorally and with electroencephalography with Fast Periodic Visual Stimulation to measure selective neural responses to letter strings. Letter strings were inserted periodically (1/5) in pseudofonts in 40sec sequences displayed at 6Hz and were either words globally taught at school, eliciting visual whole-word form recognition (global method), or control words/pseudowords eliciting grapheme-phoneme mappings (phonic method). Selective responses (F/5, 1.2Hz) were left lateralized for control stimuli but bilateral for globally taught words, especially in poor readers. These results show that global method instruction induces activation in the right hemisphere, involved in holistic processing and visual object recognition, rather than in the specialized left hemisphere for reading. Poor readers, given their difficulties in automatizing grapheme-phoneme mappings, mostly rely on this alternative inadequate strategy.
PACS-1 and Adaptor Protein-1 Mediate ACTH Trafficking to the Regulated Secretory Pathway
Authors: Dirk Brennan S. , End Christopher , Pawlak Emily N. , Van Nynatten Logan R. , Jacob Rajesh Abraham , Heit Bryan , Dikeakos Jimmy D. 
Published: October 2018

ABSTRACTThe regulated secretory pathway is a specialized form of protein secretion found in endocrine and neuroendocrine cell types. Pro-opiomelanocortin (POMC) is a pro-hormone that utilizes this pathway to be trafficked to dense core secretory granules (DCSGs). Within this organelle, POMC is processed to multiple bioactive hormones that play key roles in cellular physiology. However, the complete set of cellular membrane trafficking proteins that mediate the correct sorting of POMC to DCSGs remain unknown. Here, we report the roles of the phosphofurin acidic cluster sorting protein – 1 (PACS-1) and the clathrin adaptor protein 1 (AP-1) in the targeting of POMC to DCSGs. Upon knockdown of PACS-1 and AP-1, POMC is readily secreted into the extracellular milieu and fails to be targeted to DCSGs.