bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Content Evolution in the Arthropods
Authors: Thomas Gregg W.C. , Dohmen Elias , Hughes Daniel S.T. , Murali Shwetha C. , Poelchau Monica , Glastad Karl , Anstead Clare A. , Ayoub Nadia A. , Batterham Phillip , Bellair Michelle , Binford Gretta J. , Chao Hsu , Chen Yolanda H. , Childers Christopher , Dinh Huyen , Doddapaneni HarshaVardhan , Duan Jian J. , Dugan Shannon , Esposito Lauren A. , Friedrich Markus , Garb Jessica , Gasser Robin B. , Goodisman Michael A.D. , Gundersen-Rindal Dawn E. , Han Yi , Handler Alfred M. , Hatakeyama Masatsugu , Hering Lars , Hunter Wayne B. , Ioannidis Panagiotis , Jayaseelan Joy C. , Kalra Divya , Khila Abderrahman , Korhonen Pasi K. , Lee Carol Eunmi , Lee Sandra L. , Li Yiyuan , Lindsey Amelia R.I. , Mayer Georg , McGregor Alistair P. , McKenna Duane D. , Misof Bernhard , Munidasa Mala , Munoz-Torres Monica , Muzny Donna M. , Niehuis Oliver , Osuji-Lacy Nkechinyere , Palli Subba R. , Panfilio Kristen A. , Pechmann Matthias , Perry Trent , Peters Ralph S. , Poynton Helen C. , Prpic Nikola-Michael , Qu Jiaxin , Rotenberg Dorith , Schal Coby , Schoville Sean D. , Scully Erin D. , Skinner Evette , Sloan Daniel B. , Stouthamer Richard , Strand Michael R. , Szucsich Nikolaus U. , Wijeratne Asela , Young Neil D. , Zattara Eduardo E. , Benoit Joshua B. , Zdobnov Evgeny M. , Pfrender Michael E. , Hackett Kevin J. , Werren John H. , Worley Kim C. , Gibbs Richard A. , Chipman Ariel D. , Waterhouse Robert M. , Bornberg-Bauer Erich , Hahn Matthew W. , Richards Stephen 
Published: August 2018

AbstractBackgroundArthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods.ResultsUsing 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality and chemoperception.ConclusionsThese analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity.
Inference of genomic spatial organization from a whole genome bisulfite sequencing sample
Authors: Raineri Emanuele , Serra François , Beekman Renée , García Torre Beatriz , Vilarrasa-Blasi Roser , Martin-Subero Iñaki , Martí-Renom Marc A. , Gut Ivo , Heath Simon 
Published: August 2018

AbstractCommon approaches to characterize the structure of the DNA in the nucleus, such as the different Chromosome Conformation Capture methods, have not currently been widely applied to different tissue types due to several practical difficulties including the requirement for intact cells to start the sample preparation. In contrast, techniques based on sodium bisulfite conversion of DNA to assay DNA methylation, have been widely applied to many different tissue types in a variety of organisms. Recent work has shown the possibility of inferring some aspects of the three dimensional DNA structure from DNA methylation data, raising the possibility of three dimensional DNA structure prediction using the large collection of already generated DNA methylation datasets. We propose a simple method to predict the values of the first eigenvector of the Hi-C matrix of a sample (and hence the positions of the A and B compartments) using only the GC content of the sequence and a single whole genome bisulfite sequencing (WGBS) experiment which yields information on the methylation levels and their variability along the genome. We train and test our model on 10 samples for which we have data from both bisulfite sequencing and chromosome conformation experiments and our most relevant finding is that the variability of DNA methylation along the sequence is often a better predictor than methylation itself. We then run a prediction on 206 DNA methylation profiles produced by the Blueprint project and use ChIP-Seq and RNA-Seq data to confirm that the forecasted eigenvector delineates correctly the physical chromatin compartments observed with the Hi-C experiment.
Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis
Authors: Ramesh Akshaya , Nakielny Sara , Hsu Jennifer , Kyohere Mary , Byaruhanga Oswald , Bourcy Charles de , Egger Rebecca , Dimitrov Boris , Juan Yun-Fang , Sheu Jonathan , Wang James , Kalantar Katrina , Langelier Charles , Ruel Theodore , Mpimbaza Arthur , Wilson Michael R. , Rosenthal Philip J. , DeRisi Joseph L. 
Published: August 2018

AbstractBackgroundFebrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. We built and employed IDseq, a cloud-based, open access, bioinformatics platform and service to identify microbes from metagenomic next-generation sequencing of tissue samples. In this pilot study, we evaluated blood, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda.ResultsThe most common pathogens identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from blood; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. Among other potential pathogens, we identified one novel orthobunyavirus, tentatively named Nyangole virus, from the blood of a child diagnosed with malaria and pneumonia, and Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis. We also identified two novel human rhinovirus C species.ConclusionsThis exploratory pilot study demonstrates the utility of mNGS and the IDseq platform for defining the molecular landscape of febrile infectious diseases in resource limited areas. These methods, supported by a robust data analysis and sharing platform, offer a new tool for the surveillance, diagnosis, and ultimately treatment and prevention of infectious diseases.
Transcriptome analyses of tumor-adjacent somatic tissues reveal genes co-expressed with transposable elements
Authors: Chung Nicky , Jonaid G.M. , Quinton Sophia , Ross Austin , Sexton Corinne E. , Alberto Adrian , Clymer Cody , Churchill Daphnie , Leija Omar Navarro , Han Mira V. 
Published: August 2018

AbstractBackgroundDespite the long-held assumption that transposons are normally only expressed in the germ-line, recent evidence shows that transcripts of transposable element (TE) sequences are frequently found in the somatic cells. However, the extent of variation in TE transcript levels across different tissues and different individuals are unknown, and the co-expression between TEs and host gene mRNAs have not been examined.ResultsHere we report the variation in TE derived transcript levels across tissues and between individuals observed in the non-tumorous tissues collected for The Cancer Genome Atlas. We found core TE co-expression modules consisting mainly of transposons, showing correlated expression across broad classes of TEs. Despite this co-expression within tissues, there are individual TE loci that exhibit tissue-specific expression patterns, when compared across tissues. The core TE modules were negatively correlated with other gene modules that consisted of immune response genes in interferon signaling. KRAB Zinc Finger Proteins (KZFPs) were over-represented gene members of the TE modules, showing positive correlation across multiple tissues. But we did not find overlap between TE-KZFP pairs that are co-expressed and TE-KZFP pairs that are bound in published ChIP-seq studies.
ConclusionsWe find unexpected variation in TE derived transcripts, within and across non-tumorous tissues. We describe a broad view of the RNA state for non-tumorous tissues exhibiting higher level of TE transcripts. Tissues with higher level of TE transcripts have a broad range of TEs co-expressed, with high expression of a large number of KZFPs, and lower RNA levels of immune genes.
Signals of variation in human mutation rate at multiple levels of sequence context
Authors: Aikens Rachael C. , Johnson Kelsey E. , Voight Benjamin F. 
Published: August 2018

ABSTRACTOur understanding of mutation rate helps us build evolutionary models and make sense of genetic variation. Recent work indicates that the frequencies of specific mutation types have been elevated in Europe, and that many more, subtler signatures of global polymorphism variation may yet remain unidentified. Here, we present an analysis of the 1,000 Genomes Project (phase 3), suggesting additional putative signatures of mutation rate variation across populations and the extent to which they are shaped by local sequence context. First, we compiled a list of the most significantly variable polymorphism types in a cross-continental statistical test. Clustering polymorphisms together, we observed four sets of substitution types that showed similar trends of relative mutation rate across populations, and describe the patterns of these mutational clusters among continental groups. For the majority of these signatures, we found that a single flanking base pair of sequence context was sufficient to determine the majority of enrichment or depletion of a mutation type. However, local genetic context up to 2-3 base pairs away contributes additional variability, and helps to interpret a previously noted enrichment of certain polymorphism types in some East Asian groups. Building our understanding of mutation rate in this way can help us to construct more accurate evolutionary models and better understand the mechanisms that underlie genetic change.
Overlaps in Brain Dynamic Functional Connectivity between Schizophrenia and Autism Spectrum Disorder
Authors: Andriamananjara Andry , Muntari Rayan , Crimi Alessandro 
Published: August 2018

AbstractSchizophrenia and autism share some genotipic and phenotypic aspects as connectome miswiring and common cognitive deficits. Currently, there are no medical tests available for either disorders, and diagnostics for both of them include direct reports of relatives and clinical evaluation by a psychiatrist. Despite several medical imaging biomarkers have been proposed in the past, novel effective biomarkers or improvements of the existing ones is still need. This work proposes a dynamic functional connectome analysis combined with machine learning techniques to complement the present diagnostic procedure. We used the moving window technique to locate a set of dynamic functional connectivity states, and then use them as features to classify subjects as autism/schizophrenia or control. Moreover, by using dynamic functional connectivity measures we investigate the question whether those two disorders overlap, namely whether schizophrenia is part of the autism spectrum and which brain region could be involved in both disorders. The results reveal that both static and dynamic functional connectivity can be used to classify subjects with schizophrenia or autism. Lastly, some brain regions show similar functional flexibility in both autism and schizophrenia cohorts giving further possible proofs of their overlaps.
Molecular Heterogeneity and Early Metastatic Clone Selection in Testicular Germ Cell Cancer Development
Authors: Dorssers Lambert C.J. , Gillis Ad J.M. , Stoop Hans , Marion Ronald van , Nieboer Marleen M. , Riet Job van , van de Werken Harmen J.G. , Oosterhuis J. Wolter , Ridder Jeroen de , Looijenga Leendert H.J. 
Published: August 2018

AbstractBackgroundTesticular germ cell cancer (TGCC), being the most frequent malignancy in young Caucasian males, is initiated from an embryonic germ cell. This study determines intratumor heterogeneity to unravel tumor progression from initiation till metastasis.MethodsIn total 42 purified samples of four treatment-resistant nonseminomatous TGCC (NS) were investigated, including the precursor germ cell neoplasia in situ (GCNIS) and metastatic specimens, using whole genome- and targeted sequencing. Their evolution was reconstructed.ResultsIntratumor molecular heterogeneity did not correspond to the supposed primary tumor histological evolution. Metastases after systemic treatment could be derived from cancer stem cells not identified in the primary cancer. GCNIS mostly lacked the molecular marks of the primary NS and comprised dominant clones that failed to progress. A BRCA-like mutational signature was observed without evidence for direct involvement ofBRCA1andBRCA2genes.ConclusionsOur data strongly support the hypothesis that NS is initiated by whole genome duplication, followed by chromosome copy number alterations in the cancer stem cell population, and accumulation of low numbers of somatic mutations. These observations of heterogeneity at all stages of tumorigenesis should be considered when treating patients with GCNIS-only disease, or with clinically overt NS.
Neural processing of communication signals: The extent of sender-receiver matching varies across species ofApteronotus
Authors: Allen K.M. , Marsat G. 
Published: August 2018

ABSTRACTAs communication signal properties change, through genetic drift or selective pressure, the sensory systems that receive these signals must also adapt to maintain sensitivity and adaptability in an array of contexts. Shedding light on this process helps us understand how sensory codes are tailored to specific tasks. In a species of weakly electric fish,Apteronotus albifrons, we examined the unique neurophysiological properties that support the encoding of electrosensory communication signals that the animal encounters in social exchanges. We compare our findings to known coding properties of the closely related species,Apteronotus leptorhynchus, to establish how these animals differ in their ability to encode their distinctive communication signals. While there are many similarities between these two species, we found notable differences leading to relatively poor coding of the details of chirp structure occurring on high-frequency background beats. As a result, small differences in chirp properties are poorly resolved by the nervous system. We performed behavioral tests to relateA. albifronschirp coding strategies to its use of chirps during social encounters. Our results suggest thatA. albifronsdo not exchange frequent chirps in non-breeding condition, particularly when the beat frequency is high. These findings parallel the mediocre chirp coding accuracy in that they both point to a reduced reliance on frequent and rich exchange of information through chirps during these social interactions. Therefore, our study suggests that neural coding strategies in the central nervous system vary across species in a way that parallels the behavioral use of the sensory signals.SIGNIFICANCESender-receiver matching is a phenomenon commonly observed in the peripheral nervous system. It enables communication production and reception to evolve together so that conspecifics remain sensitive to important signals. In this manuscript we examine this phenomenon in the central nervous system of the weakly electric fishA. albifronsand compare its processing of communication signals to a closely related species (A. leptorhynchus).Although some differences across the two species can help tailor the system for processing species-specific signals, our data indicate that encoding of communication signals inA. albifronsis not as sensitive as inA. leptorhynchusfor certain categories of signals. Our data support the idea that the extent of sender-receiver matching can vary as a function of behavioral needs.
A pivotal role of serine 225 phosphorylation in the function of hepatitis C virus NS5A revealed with the application of a phosphopeptide antiserum and super-resolution microscopy
Authors: Goonawardane Niluka , Yin Chunhong , Harris Mark 
Published: August 2018

AbstractNS5A is a multi-functional phosphoprotein that plays a key role in both viral replication and assembly. The identity of the kinases that phosphorylate NS5A, and the consequences for HCV biology, remain largely undefined. We previously identified serine 225 (S225) within low complexity sequence (LCS) I as a major phosphorylation site and used a phosphoablatant mutant (S225A) to define a role for S225 phosphorylation in the regulation of genome replication, interactions of NS5A with several host proteins and the sub-cellular localisation of NS5A. To investigate this further, we raised an antiserum to S225 phosphorylated NS5A (pS225). Western blot analysis revealed that pS225 was exclusively found in the hyper-phosphorylated NS5A species. Furthermore, using kinase inhibitors we demonstrated that S225 was phosphorylated by casein kinase 1α (CK1α) and polo-like kinase 1 (PLK1). Using a panel of phosphoablatant mutants of other phosphorylation sites in LCSI we obtained the first direct evidence of bidirectional hierarchical phosphorylation initiated by phosphorylation at S225.Using super-resolution microscopy (Airyscan and Expansion), we revealed a unique architecture of NS5A-positive clusters in HCV-infected cells - pS225 was concentrated on the surface of these clusters, close to lipid droplets. Pharmacological inhibition of S225 phosphorylation resulted in the condensation of NS5A-positive clusters into larger structures, recapitulating the S225A phenotype. Although S225 phosphorylation was not specifically affected by daclatasvir treatment, the latter also resulted in a similar condensation. These data are consistent with a key role for S225 phosphorylation in the regulation of NS5A function.ImportanceNS5A has obligatory roles in the hepatitis C virus lifecycle, and is proposed to be regulated by phosphorylation. As NS5A is a target for highly effective direct-acting antivirals (DAAs) such as daclatasvir (DCV) it is vital to understand how phosphorylation occurs and regulates NS5A function. We previously identified serine 225 (S225) as a major phosphorylation site. Here we used an antiserum specific for NS5A phosphorylated at S225 (pS225-NS5A) to identify which kinases phosphorylate this residue. Using super-resolution microscopy we showed that pS225 was present in foci on the surface of larger NS5A-positive clusters likely representing genome replication complexes. This location would enable pS225-NS5A to interact with cellular proteins and regulate the function and distribution of these complexes. Both loss of pS225 and DCV treatment resulted in similar changes to the structure of these complexes, suggesting that DAA treatment might target a function of NS5A that is also regulated by phosphorylation.
Tracking a Serial Killer: Integrating Phylogenetic Relationships, Epidemiology, and Geography for Two Invasive Meningococcal Disease Outbreaks
Authors: Ezeoke Ifeoma , Galac Madeline R. , Lin Ying , Liem Alvin T. , Roth Pierce A. , Kilianski Andrew , Gibbons Henry S. , Bloch Danielle , Kornblum John , Rosso Paula Del , Janies Daniel A. , Weiss Don 
Published: August 2018

AbstractBackgroundWhile overall rates of meningococcal disease have been declining in the United States for the past several decades, New York City (NYC) has experienced two serogroup C meningococcal disease outbreaks in 2005-2006 and in 2010-2013. The outbreaks were centered within drug use and sexual networks, were difficult to control, and required vaccine campaigns.MethodsWhole Genome Sequencing (WGS) was used to analyze preserved meningococcal isolates collected before and during the two outbreaks. We integrated and analyzed epidemiologic, geographic, and genomic data to better understand transmission networks among patients. Betweenness centrality was used as a metric to understand the most important geographic nodes in the transmission networks. Comparative genomics was used to identify genes associated with the outbreaks.ResultsNeisseria meningitidis serogroup C (ST11/ET-37) was responsible for both outbreaks with each outbreak having distinct phylogenetic clusters. WGS did identify some misclassifications of isolates that were more distant from the rest of the outbreak, as well as those that should have been included based on high genomic similarity. Genomes for the second outbreak were more similar than the first and no mutation was found to either be unique or specific to either outbreak lineage. Betweenness centrality as applied to transmission networks based on phylogenetic analysis demonstrated that the outbreaks were transmitted within focal communities in NYC with few transmission events to other locations.ConclusionsNeisseria meningitidis is an ever changing pathogen and comparative genomic analyses can help elucidate how it spreads geographically to facilitate targeted interventions to interrupt transmission.
Mediating role of students’ engagement to their classes
Authors: Siddiqi Ahmed 
Published: August 2018

PurposeThe purpose of this paper is to establish the mediating role of students’ engagement to their classes, for the conventional relationship between teachers’ efforts and students’ development, for a better understanding of the instruction-based classroom learning.Design/methodology/approachThe investigation is made using a mult-istage-stratified-systematic sample of 500 students from business and engineering schools with an almost equal representation of both the genders and the type of schools’ ownership. A structural equation modeling is used for this mediation analysis.FindingsThe mediating role of students’ engagement is identically established both for business and engineering schools and for both genders. However, in public sector universities, this mediation is insignificant.Research limitations/implicationsThe investigation is limited only to business and engineering schools, and this limitation may conceal some factor(s) more important for other schools. Further, the investigation is reading data from Lahore, a metropolitan, which may hide some factor(s) some appropriate for smaller cities.Originality/valueThe data are gathered, analyzed and discussed through the lens of the socio-cultural theory, allowing for a comprehensive understanding to emerge for students’ engagement to their classes.