bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a “Treadmill Test” for Cognition: Reliable Prediction of Intelligence From Whole-Brain Task Activation Patterns
Authors: Sripada Chandra , Angstadt Mike , Rutherford Saige 
Published: September 2018

AbstractIdentifying brain-based markers of general cognitive ability, i.e., “intelligence”, has been a longstanding goal of cognitive and clinical neuroscience. Previous studies focused on relatively static, enduring features such as gray matter volume and white matter structure. In this report, we investigate prediction of intelligence based on task activation patterns during theN-back working memory task as well as six other tasks in the Human Connectome Project dataset, encompassing 19 task contrasts. We find that whole brain task activation patterns are a highly effective basis for prediction of intelligence, achieving a 0.68 correlation with intelligence scores in an independent sample, which exceeds results reported from other modalities. Additionally, we show that tasks that tap executive processing and that are more cognitively demanding are particularly effective for intelligence prediction. These results suggest a picture analogous to treadmill testing for cardiac function: Placing the brain in an activated task state improves brain-based prediction of intelligence.
Natural selection of glycoprotein B (gB) mutations that rescue the small plaque phenotype of a fusion-impaired herpes simplex virus (HSV) mutant
Authors: Fan Qing , Kopp Sarah J. , Byskosh Nina C. , Connolly Sarah A. , Longnecker Richard 
Published: September 2018

ABSTRACTGlycoprotein B (gB) is a conserved viral fusion protein that is required for herpesvirus entry. To mediate fusion with the cellular membrane, gB refolds from a prefusion to a postfusion conformation. We hypothesize that an interaction between the C-terminal arm and the central coiled-coil of the herpes simplex virus 1 (HSV-1) gB ectodomain is critical for fusion. We previously reported that three mutations in the C-terminal arm (I671A/H681A/F683A, called gB3A) greatly reduced cell-cell fusion and that virus carrying these mutations had a small plaque phenotype and delayed entry into cells. By serially passaging gB3A virus, we selected three revertant viruses with larger plaques. These revertant viruses acquired mutations in gB that restore the fusion function of gB3A, including gB-A683V, gB-S383F/G645R/V705I/A855V, and gB-T509M/N709H. V705I and N709H are novel mutations that map to the portion of domain V that enters domain I in the postfusion structure. S383F, G645R, and T509M are novel mutations that map to an intersection of three domains in a prefusion model of gB. We introduced these second-site mutations individually and in combination into wild-type gB and gB3A to examine the impact of the mutations on fusion and expression. V705I and A855V (a known hyperfusogenic mutation) restored the fusion function of gB3A, whereas S383F and G645R dampened fusion and T509M and N709H worked in concert to restore gB3A fusion. The results identify two regions in the gB ectodomain that modulate the fusion activity of gB, potentially by impacting intramolecular interactions and stability of the prefusion and/or postfusion gB trimer.IMPORTANCEGlycoprotein B (gB) is an essential viral protein that is conserved in all herpesviruses and is required for virus entry. gB is thought to undergo a conformational change that provides the energy to fuse the viral and cellular membranes, however the details of this conformational change and the structure of the prefusion and intermediate conformations of gB are not known. Previously, we demonstrated that mutations in the gB “arm” region inhibit fusion and impart a small plaque phenotype. Using serial passage of a virus carrying these mutations, we identified revertants with restored plaque size. The revertant viruses acquired novel mutations in gB that restored fusion function and mapped to two sites in the gB ectodomain. This work supports our hypothesis that an interaction between the gB arm and the core of gB is critical for gB refolding and provides details about the function of gB in herpesvirus mediated fusion and subsequent virus entry.
The Helicobacter pylori biofilm involves a multi-gene stress-biased response including a structural role for flagella
Authors: Hathroubi Skander , Zerebinski Julia , Ottemann Karen M. 
Published: September 2018

AbstractHelicobacter pylori has an impressive ability to persist chronically in the human stomach. Similar characteristics are associated with biofilm formation in other bacteria. The H. pylori biofilm process, however, is poorly understood. To gain insight into this mode of growth, we carried out comparative transcriptomic analysis between H. pylori biofilm and planktonic cells, using the mouse colonizing strain SS1. Optimal biofilm formation was obtained with low serum and three-day growth, conditions which caused both biofilm and planktonic cells to be ∼80% coccoid. RNA-seq analysis found that 8.18% of genes were differentially expressed between biofilm and planktonic cell transcriptomes. Biofilm-downregulated genes included those involved in metabolism and translation, suggesting these cells have low metabolic activity. Biofilm-upregulated genes included those whose products were predicted to be at the cell envelope, involved in regulating a stress response, and surprisingly, genes related to formation of the flagellar apparatus. Scanning electron microscopy visualized flagella that appeared to be a component of the biofilm matrix, supported by the observation that an aflagellated mutant displayed a less robust biofilm with no apparent filaments. We observed flagella in the biofilm matrix of additional H. pylori strains, supporting that flagellar use is widespread. Our data thus supports a model in which H. pylori biofilm involves a multi-gene stress-biased response, and that flagella play an important role in H. pylori biofilm formation.IMPORTANCEBiofilms, communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances, pose a substantial health risk and are key contributors to many chronic and recurrent infections. Chronicity and recalcitrant infections are also common features associated with the ulcer-causing human pathogen H. pylori. However, relatively little is known about the role of biofilms in H. pylori pathogenesis as well as the biofilm structure itself and the genes associated with this mode of growth. In the present study, we found that H. pylori biofilm cells highly expressed genes related to cell envelope, stress response and those encoding the flagellar apparatus. Flagellar filaments were seen in high abundance in the biofilm. Flagella are known to play a role in initial biofilm formation, but typically are downregulated after that state. H. pylori instead appears to have co-opted these structures for non-motility roles, including a role building a robust biofilm.
Multivariate Computational Analysis of Gamma Delta T cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging
Authors: Belkina Anna C. , Starchenko Alina , Drake Katherine A. , Proctor Elizabeth A. , Pihl Riley M.F. , Olson Alex , Lauffenburger Douglas A. , Lin Nina , Snyder-Cappione Jennifer E. 
Published: September 2018

AbstractEven with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic HIV infection are not yet elucidated. Also, whether ART-suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear. In this study we measured combinational expression of five inhibitory receptors (IRs) on seven immune cell subsets and 16 plasma markers from peripheral blood mononuclear cells (PBMC) and plasma samples, respectively, from a HIV and Aging cohort comprised of ART-suppressed HIV-infected and uninfected controls stratified by age (≤35 or ≥50 years old). For data analysis, multiple multivariate computational algorithms (cluster identification, characterization, and regression (CITRUS), partial least squares regression (PLSR), and partial least squares-discriminant analysis (PLS-DA)) were used to determine if immune parameter disparities can distinguish the subject groups and to investigate if there is a cross-impact of aviremic HIV and age on immune signatures. IR expression on gamma delta (γδ) T cells exclusively separated HIV+ subjects from controls in CITRUS analyses and secretion of inflammatory cytokines and cytotoxic mediators from γδ T cells tracked with TIGIT expression among HIV+ subjects. Also, plasma markers predicted the percentages of TIGIT+ γδ T cells in subjects with and without HIV in PSLR models, and a PLS-DA model of γδ T cell IR signatures and plasma markers significantly stratified all four of the subject groups (uninfected younger, uninfected older, HIV+ younger, and HIV+ older). These data implicate γδ T cells as an inflammatory driver in ART-suppressed HIV infection and provide evidence of distinct ‘inflamm-aging’ processes with and without ART-suppressed HIV infection.
The emergence of dynamical instantaneous memory in the spontaneous activity of spatially confined neuronal assemblies in vitro
Authors: Piasetzky Y. , Bisio M. , Kanner S. , Goldin M , Olivenbaum M. , Ben-Jacob E. , Hanein Y , Chiappalone M. , Barzilai A. , Bonifazi P. 
Published: September 2018

AbstractUnderstanding the dynamics between communicating cell assemblies is essential for deciphering the neural code and identifying the mechanism underlying memory formation. In this work, in order to unveil possible emergent intrinsic memory phenomena in the communication between cell assemblies, we study the spontaneous dynamics of in vitro spatially confined inter-connected neuronal circuits grown on multi-electrode arrays. The spontaneous dynamics of the global network was characterized by the coupling of the activity independently generated by each circuit. The asymptotic functional connectivity of the network reflected its modular organization. Instantaneous functional connectivity maps on ten seconds epochs, revealed more complex dynamical states with the simultaneous activation of distinct circuits. When looking at the similarity of the generated network events, we observed that spontaneous network events occurring at temporal distances below two dozens of seconds had an average higher similarity compared to randomly played network events. Such a memory phenomenon was not observed in networks where spontaneous events were less frequent and in networks topologically organized as open lines. These results support the hypothesis that dynamical instantaneous memory, characterized by drifting network dynamics with decaying degree of similarity, is an intrinsic property of neuronal networks.
Pan-genome-scale network reconstruction: a framework to increase the quantity and quality of metabolic network reconstructions throughout the tree of life
Authors: Correia Kevin , Mahadevan Radhakrishnan 
Published: September 2018

ABSTRACTA genome-scale network reconstruction (GENRE) represents the knowledgebase of an organism and can be used in a variety of applications. The drop in genome sequencing costs has led to an increase in sequenced genomes, but the number of curated GENRE’ s has not kept pace. This gap hinders our ability to study physiology across the tree of life. Furthermore, our analysis of yeast GENRE’ s has found they contain significant commission and omission errors, especially in central metabolism. To address these quantity and quality issues for GENRE’ s, we propose open and transparent curation of the pan-genome, pan-reactome, pan-metabolome, and pan-phenome for taxons by research communities, rather than for a single species. We outline our approach with a Fungi pan-GENRE by integrating AYbRAH, our ortholog database, and AYbRAHAM, our new fungal reaction database. This pan-GENRE was used to compile 33 yeast/fungi GENRE’ s in the Dikarya subkingdom, spanning 600 million years. The fungal pan-GENRE contains 1547 orthologs, 2726 reactions, 2226 metabolites, and 10 compartments. The strain GENRE’ s have a wider genomic and metabolic than previous yeast and fungi GENRE’ s. Metabolic simulations show the amino acid yields from glucose differs between yeast lineages, indicating metabolic networks have evolved in yeasts. Curating ortholog and reaction databases for a taxon can be used to increase the quantity and quality of strain GENRE’ s. This pan-GENRE framework provides the ability to scale high-quality GENRE’ s to more branches in the tree of life.
Drift-diffusion explains response variability and capacity for tracking objects
Authors: Daneshi Asieh , Azarnoush Hamed , Towhidkhah Farzad , Ghazizadeh Ali 
Published: September 2018

1.AbstractBeing able to track objects that surround us is key for planning actions in dynamic environments. However, rigorous cognitive models for tracking of one or more objects are currently lacking. In this study, we asked human subjects to judge the time to contact (TTC) a finish line for one or two objects that became invisible shortly after moving. We showed that the pattern of subject responses had an error variance best explained by an inverse Gaussian distribution and consistent with the output of a biased drift-diffusion model. Furthermore, we demonstrated that the pattern of errors made when tracking two objects showed a level of dependence that was consistent with subjects using a single decision variable for reporting the TTC for two objects. This finding reveals a serious limitation in the capacity for tracking multiple objects resulting in error propagation between objects. Apart from explaining our own data, our approach helps interpret previous findings such as asymmetric interference when tracking multiple objects.
Emergence of social inequality in a spatial-ecological public goods game
Authors: Joshi Jaideep , Brännström Åke , Dieckmann Ulf 
Published: September 2018

AbstractSpatial ecological public goods, such as forests, grasslands, and fish stocks risk being overexploited by selfish consumers, a phenomenon called “the tragedy of commons”. The spatial and ecological dimensions introduce new features absent in non spatio-ecological contexts, such as consumer mobility, incomplete information availability, and rapid evolution by social learning. It is unclear how these different processes interact to influence the harvesting and dispersal strategies of consumers. To answer these questions, we develop and analyze an individual-based, spatially-structured evolutionary model with explicit resource dynamics. We find that, 1) When harvesting efficiency is low, consumers evolve a sedentary harvesting strategy, with which resources are harvested sustainably, but harvesting rates remain far below their maximum sustainable value. 2) As harvesting efficiency increases, consumers adopt a mobile ‘consume-and-disperse’ strategy, which is sustainable, equitable, and allows for maximum sustainable yield. 3) Further increase in harvesting efficiency leads to large-scale overexploitation. 4) If costs of dispersal are significant, increased harvesting efficiency also leads to social inequality between frugal sedentary consumers and overexploitative mobile consumers. Whereas overexploitation can occur without social inequality, social inequality always leads to overexploitation. Thus, we identify four conditions, which are characteristic (and as such positive) features of modern societies resulting from technological progress, but also risk promoting social inequality and unsustainable resource use: high harvesting efficiency, moderately low costs of dispersal, high consumer density, and consumers’ tendency to rapidly adopt new strategies. We also show that access to global information, which is also a feature of modern societies, may help mitigate these risks.
Projection layers improve deep learning models of regulatory DNA function
Authors: Hawkins-Hooker Alex , Kenlay Henry , Reid John 
Published: September 2018

AbstractWith the increasing application of deep learning methods to the modelling of regulatory DNA sequences has come an interest in exploring what types of architecture are best suited to the domain. Networks designed to predict many functional characteristics of noncoding DNA in a multitask framework have to recognise a large number of motifs and as a result benefit from large numbers of convolutional filters in the first layer. The use of large first layers in turn motivates an exploration of strategies for addressing the sparsity of output and possibility for overfitting that result. To this end we propose the use of a dimensionality-reducing linear projection layer after the initial motif-recognising convolutions. In experiments with a reduced version of the DeepSEA dataset we find that inserting this layer in combination with dropout into convolutional and convolutional-recurrent architectures can improve predictive performance across a range of first layer sizes. We further validate our approach by incorporating the projection layer into a new convolutional-recurrent architecture which achieves state of the art performance on the full DeepSEA dataset. Analysis of the learned projection weights shows that the inclusion of this layer simplifies the network’s internal representation of the occurrence of motifs, notably by projecting features representing forward and reverse-complement motifs to similar positions in the lower dimensional feature space output by the layer.
Agrobacterium tumefaciensdivisome proteins regulate the transition from polar growth to cell division
Authors: Howell Matthew , Aliashkevich Alena , Sundararajan Kousik , Daniel Jeremy J. , Lariviere Patrick J. , Goley Erin D. , Cava Felipe , Brown Pamela J.B. 
Published: September 2018

AbstractThe mechanisms that restrict peptidoglycan biosynthesis to the pole during elongation and re-direct peptidoglycan biosynthesis to mid-cell during cell division in polar-growing Alphaproteobacteria are largely unknown. Here, we demonstrate that although two of the three FtsZ homologs localize to mid-cell, exhibit GTPase activity and form co-polymers, only one, FtsZAT, is required for cell division. We find that FtsZATis required not only for constriction and cell separation, but also for the termination of polar growth and regulation of peptidoglycan synthesis at mid-cell. Depletion of FtsZ inA. tumefacienscauses a striking phenotype: cells are extensively branched and accumulate growth active poles through tip splitting events. When cell division is blocked at a later stage, polar growth is terminated and ectopic growth poles emerge from mid-cell. Overall, this work suggests thatA. tumefaciensFtsZ makes distinct contributions to the regulation of polar growth and cell division.
Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies
Authors: Gileta Alexander F. , Fitzpatrick Christopher J. , Chitre Apurva S. , St. Pierre Celine L. , Joyce Elizabeth V. , Maguire Rachael J. , McLeod Africa M. , Gonzales Natalia M. , Williams April E. , Morrow Jonathan D. , Robinson Terry E. , Flagel Shelly B. , Palmer Abraham A. 
Published: September 2018

AbstractSprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 291,438 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (FST > 0.4). Furthermore, even for rats obtained from the same vendor, there was strong population structure across breeding facilities and even between rooms at the same facility. We performed multiple separate GWAS by fitting a linear mixed model that accounted population structure and using meta-analysis to jointly analyze all cohorts. Our study examined Pavlovian conditioned approach (PavCA) behavior, which assesses the propensity for rats to attribute incentive salience to reward-associated cues. We identified 46 significant associations for the various metrics used to define PavCA. The surprising degree of population structure among SD rats from different sources has important implications for their use in both genetic and non-genetic studies.Author SummaryOutbred Sprague Dawley rats are among the most commonly used rats for neuroscience, physiology and pharmacological research; in the year 2020, 4,188 publications contained the keyword “Sprague Dawley”. Rats identified as “Sprague Dawley” are sold by several commercial vendors, including Charles River Laboratories and Harlan Sprague Dawley Inc. (now Envigo). Despite their widespread use, little is known about the genetic diversity of SD. We genotyped more than 4,000 SD rats, which we used for a genome-wide association study (GWAS) and to characterize genetic differences between SD rats from Charles River Laboratories and Harlan. Our analysis revealed extensive population structure both between and within vendors. The GWAS for Pavlovian conditioned approach (PavCA) identified a number of genome-wide significant loci for that complex behavioral trait. Our results demonstrate that, despite sharing an identical name, SD rats that are obtained from different vendors are very different. Future studies should carefully define the exact source of SD rats being used and may exploit their genetic diversity for genetic studies of complex traits.
Predominance ofcis-regulatory changes in parallel expression divergence of sticklebacks
Authors: Verta Jukka-Pekka , Jones Felicity C. 
Published: September 2018

AbstractRegulation of gene expression is thought to play a major role in adaptation but the relative importance ofcis- andtrans-regulatory mechanisms in the early stages of adaptive divergence is unclear. Using RNAseq of threespine stickleback fish gill tissue from four independent marine-freshwater ecotype pairs and their F1 hybrids, we show thatcis-acting (allele-specific) regulation consistently predominates gene expression divergence. Genes showing parallel marine-freshwater expression divergence are found near to adaptive genomic regions, show signatures of natural selection around their transcription start sites and are enriched forcis-regulatory control. For genes with parallel increased expression among freshwater fish, the quantitative degree ofcis-andtrans-regulation is also highly correlated across populations, suggesting a shared genetic basis. Compared to other forms of regulation,cis-regulation tends to show greater additivity and stability across different genetic and environmental contexts, making it a fertile substrate for the early stages of adaptive evolution.