bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locating highly correlated sources from MEG with (recursive) (R)DS-MUSIC
Authors: Mäkelä Niko , Stenroos Matti , Sarvas Jukka , Ilmoniemi Risto J. 
Published: December 2017

AbstractWe introduce a source localization method of the MUltiple Signal Classification (MUSIC) family that can locate brain-signal sources robustly and reliably, irrespective of their temporal correlations. The method, double-scanning (DS) MUSIC, is based on projecting out the topographies of source candidates during topographical scanning in a way that breaks the mutual dependence of highly correlated sources, but keeps the uncorrelated sources intact. We also provide a recursive version of DS-MUSIC (RDS-MUSIC), which overcomes the peak detection problem present in the non-recursive methods. We compare DS-MUSIC and RDS-MUSIC with other localization techniques in numerous simulations with varying source configurations, correlations, and signal-to-noise ratios. DS- and RDS-MUSIC were the most robust localization methods; they had a high success rate and localization accuracy for both uncorrelated and highly correlated sources. In addition, we validated RDS-MUSIC by showing that it successfully locates bilateral synchronous activity from measured auditory-evoked MEG.
FtsW activity and lipid II synthesis are required for recruitment of MurJ to midcell during cell division inEscherichia coli
Authors: Liu Xiaolong , Meiresonne Nils Y. , Bouhss Ahmed , den Blaauwen Tanneke 
Published: December 2017

AbstractPeptidoglycan (PG) is the unique cell shape-determining component of the bacterial envelope, and is a key target for antibiotics. PG synthesis requires the transmembrane movement of the precursor lipid II, and MurJ has been shown to provide this activity inE. coli.However, how MurJ functionsin vivohas not been reported. Here we show that MurJ localizes both in the lateral membrane and at midcell, and is recruited to midcell simultaneously with late-localizing divisome proteins and proteins MraY and MurG. MurJ septal localization is dependent on the presence of a complete and active divisome, lipid II synthesis and PBP3/FtsW activities. Inactivation of MurJ, either directly by mutation or through binding with MTSES, did not affect the midcell localization of MurJ. Our study visualizes MurJ localizationin vivoand reveals a possible mechanism of how MurJ functions during cell division, which gives possibilities for future investigations and further antibiotics developments.
Integrated analysis of anatomical and electrophysiological human intracranial data
Authors: Stolk Arjen , Griffin Sandon M. , van der Meij Roemer , Dewar Callum , Saez Ignacio , Lin Jack J. , Piantoni Giovanni , Schoffelen Jan-Mathijs , Knight Robert T. , Oostenveld Robert 
Published: December 2017

AbstractThe exquisite spatiotemporal precision of human intracranial EEG recordings (iEEG) permits characterizing neural processing with a level of detail that is inaccessible to scalp-EEG, MEG, or fMRI. However, the same qualities that make iEEG an exceptionally powerful tool also present unique challenges. Until now, the fusion of anatomical data (MRI and CT images) with the electrophysiological data and its subsequent analysis has relied on technologically and conceptually challenging combinations of software. Here, we describe a comprehensive protocol that addresses the complexities associated with human iEEG, providing complete transparency and flexibility in the evolution of raw data into illustrative representations. The protocol is directly integrated with an open source toolbox for electrophysiological data analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible analysis methods that, over the past decade, have been developed and employed by a large research community. We demonstrate the protocol for an example complex iEEG data set to provide an intuitive and rapid approach to dealing with both neuroanatomical information and large electrophysiological data sets. We explain how the protocol can be largely automated, taking under an hour to complete, and readily adjusted to iEEG data sets with other characteristics.
Genome wide association analysis in a mouse advanced intercross line
Authors: Gonzales Natalia M. , Seo Jungkyun , Hernandez-Cordero Ana Isabel , Pierre Celine L. St. , Gregory Jennifer S. , Distler Margaret G. , Abney Mark , Canzar Stefan , Lionikas Arimantas , Palmer Abraham A. 
Published: December 2017

AbstractThe LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50 traits relevant to human health and disease. We also identify thousands ofcis-andtrans-eQTLs in the hippocampus, striatum, and prefrontal cortex of ∼200 mice. We replicate an association between locomotor activity andCsmd1, which we identified in an earlier generation of this AIL, and show thatCsmd1mutant mice recapitulate the locomotor phenotype. Our results demonstrate the utility of the LG x SM AIL as a mapping population, identify numerous novel associations, and shed light on the genetic architecture of mammalian behavior.
Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
Authors: Vivek-Ananth R.P. , Mohanraj Karthikeyan , Vandanashree Muralidharan , Jhingran Anupam , Craig James P. , Samal Areejit 
Published: December 2017

AbstractAspergillus fumigatus and multiple other Aspergillus species cause a wide range of lung infections, collectively termed aspergillosis. Aspergilli are ubiquitous in environment with healthy immune systems routinely eliminating inhaled conidia, however, Aspergilli can become an opportunistic pathogen in immune-compromised patients. The aspergillosis mortality rate and emergence of drug-resistance reveals an urgent need to identify novel targets. Secreted and cell membrane proteins play a critical role in fungal-host interactions and pathogenesis. Using a computational pipeline integrating data from high-throughput experiments and bioinformatic predictions, we have identified secreted and cell membrane proteins in ten Aspergillus species known to cause aspergillosis. Small secreted and effector-like proteins similar to agents of fungal-plant pathogenesis were also identified within each secretome. A comparison with humans revealed that at least 70% of Aspergillus secretomes has no sequence similarity with the human proteome. An analysis of antigenic qualities of Aspergillus proteins revealed that the secretome is significantly more antigenic than cell membrane proteins or the complete proteome. Finally, overlaying an expression dataset, four A. fumigatus proteins upregulated during infection and with available structures, were found to be structurally similar to known drug target proteins in other organisms, and were able to dock in silico with the respective drug.
Rapid diversification ofPseudomonas aeruginosain cystic fibrosis lung-like conditions
Authors: Schick Alana , Kassen Rees 
Published: December 2017

AbstractChronic infection of the cystic fibrosis (CF) airway by the opportunistic pathogenPseudomonas aeruginosais the leading cause of morbidity and mortality for adult CF patients. Prolonged infections are accompanied by adaptation ofP. aeruginosato the unique conditions of the CF lung environment as well as marked diversification of the pathogen into phenotypically and genetically distinct strains that can coexist for years within a patient. Little is known, however, about the causes of this diversification and its impact on patient health. Here, we show experimentally that, consistent with ecological theory of diversification, the nutritional conditions of the CF airway can cause rapid and extensive diversification ofP. aeruginosa.The increased viscosity associated with the thick mucous layer in the CF airway had little impact on within-population diversification but did promote divergence among populations. Notably,in vitroevolution recapitulated patho-adaptive traits thought to be hallmarks of chronic infection, including reduced motility and increased biofilm formation, and the range of phenotypes observed in a collection of clinical isolates. Our results suggest that nutritional complexity and reduced dispersal can drive evolutionary diversification ofP. aeruginosaindependent of other features of the CF lung such as an active immune system or the presence of competing microbial species. They also underscore the need to obtain diverse samples ofP. aeruginosawhen developing treatment plans. We suggest that diversification, by generating extensive phenotypic and genetic variation on which selection can act, may be a key first step in the transition from transient to chronic infection.Significance StatementChronic infection with the opportunistic pathogenPseudomonas aeruginosais the leading cause of lung transplant or death in cystic fibrosis patients.P. aeruginosadiversifies in the CF lung, although why this happens remains a mystery. We allowedP. aeruginosato evolve in the laboratory under a range of conditions approximating the CF lung. The diversity of evolved populations was highest, and most closely resembled the range of phenotypes among clinical isolates, in environments resembling the spectrum of nutritional resources available in the CF lung. Our results point to the nutritional complexity of the CF lung as a major driver of diversification and they suggest that diversity could be important in the development of chronic infections.
Increased glutaminolytic flux and activation of mitochondrial metabolism by BCL2 hyperactivity in lymphoma
Authors: Kaur Kirandeep , Singh Simar , Zecena Helma , Dejean Laurent , Filipp Fabian V. 
Published: December 2017

AbstractB-cell lymphoma 2 (BCL2) is an important apoptosis regulator during developmental and pathological states, and its overexpression is a key feature of several malignancies. Genomic data from The Cancer Genome Atlas (TCGA) reveals significant somatic copy number amplification, overexpression, and/or elevated protein activity of BCL2 in 50 % of diffuse large B-cell lymphoma (DLBC) patients. While its canonical role in mitochondria-directed apoptosis is well established, the effect of BCL2 on transcriptional and metabolic networks remains elusive. Using an established lymphocytic pro-B-cell line overexpressing BCL2, we identified dysregulated transcriptional and metabolic networks by transcriptomic profiling arrays. Elevated BCL2 levels affect transcription factor complexes and mitogenic programs of NF-κB/REL, HIF1A/ARNT, AP1, E2F, and STAT factors. Using stable isotope-assisted metabolic flux measurements we quantify that elevated BCL2 expression increases carbon utilization boosting cellular proliferation. Tumorigenic overexpression of BCL2 significantly increases glycolytic flux, glutaminolysis, and anaplerotic flux into the TCA cycle. At the same time, the mitochondrial acetyl-CoA pool is separated from the glycolytic one by inactivating the pyruvate dehydrogenase complex via transcriptional regulation of pyruvate dehydrogenase kinase (PDK3). As compensatory fuel, mitochondrial TCA cycle metabolism is supported by asparagine synthase (ASNS) and oxidative glutaminolysis creating targets for small molecule inhibition of glutaminase. Lymphoma cells overexpressing BCL2 contained more mitochondrial mass and were more sensitive to L-glutamine deprivation and glutaminase inhibition. Cells overexpressing a mutant BCL2 G145E, which is incapable of binding BH domain members, failed to increase proliferation, glycolysis, or glutaminolysis. Taken together, the oncogene BCL2 has the ability to ramp up a metabolic phenotype supporting proliferation independent of its anti-apoptotic role. The cellular model of BCL2 activation supports NF-KB-positive subtypes of DLBC and identifies metabolic bottlenecks with dependency on anaplerotic flux as an actionable BCL2 effector network in cancer.
Examination of the Shared Genetic Basis of Anorexia Nervosa and Obsessive-Compulsive Disorder
Authors: Yilmaz Zeynep , Halvorsen Matthew , Bryois Julien , Yu Dongmei , Thornton Laura M. , Zerwas Stephanie , Micali Nadia , Moessner Rainald , Burton Christie L. , Zai Gwyneth , Erdman Lauren , Kas Martien J. , Arnold Paul D. , Davis Lea K. , Knowles James A. , Breen Gerome , Scharf Jeremiah M. , Nestadt Gerald , Mathews Carol A. , Bulik Cynthia M. , Mattheisen Manuel , Crowley James J. 
Published: December 2017

ABSTRACTAnorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a crossdisorder GWAS meta-analysis of 3,495 AN cases, 2,688 OCD cases and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg= 0.49 ± 0.13,p= 9.07×10−7) and a sizable SNP heritability (SNPh2= 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., bipolar disorder, schizophrenia, neuroticism) and negative correlations with metabolic phenotypes (e.g., BMI, triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN/OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.
Programmable transport of micro- and nanoparticles byParamecium caudatum
Authors: Mayne Richard , Morgan Jack , Phillips Neil , Whiting James , Adamatzky Andrew 
Published: December 2017

AbstractWe exploit chemo- and galvanotactic behaviour ofParamecium caudatumto design a hybrid device that allows for controlled uptake, transport and deposition of environmental micro- and nanoparticulates in an aqueous medium. Manipulation of these objects is specific, programmable and parallel. We demonstrate how device operation and output interpretation may be automated via a DIY low-cost fluorescence spectrometer, driven by a microprocessor board. The applications of the device presented range from collection and detoxification of environmental contaminants (e.g. nanoparticles), to micromixing, to natural expressions of computer logic.
Comparative Annotation Toolkit (CAT) - simultaneous clade and personal genome annotation
Authors: Fiddes Ian T. , Armstrong Joel , Diekhans Mark , Nachtweide Stefanie , Kronenberg Zev N. , Underwood Jason G. , Gordon David , Earl Dent , Keane Thomas , Eichler Evan E. , Haussler David , Stanke Mario , Paten Benedict 
Published: December 2017

ABSTRACTThe recent introductions of low-cost, long-read, and read-cloud sequencing technologies coupled with intense efforts to develop efficient algorithms have made affordable, high-qualityde novosequence assembly a realistic proposition. The result is an explosion of new, ultra-contiguous genome assemblies. To compare these genomes we need robust methods for genome annotation. We describe the fully open source Comparative Annotation Toolkit (CAT), which provides a flexible way to simultaneously annotate entire clades and identify orthology relationships. We show that CAT can be used to improve annotations on the rat genome, annotate the great apes, annotate a diverse set of mammals, and annotate personal, diploid human genomes. We demonstrate the resulting discovery of novel genes, isoforms and structural variants, even in genomes as well studied as rat and the great apes, and how these annotations improve cross-species RNA expression experiments.
Defining a landscape of molecular phenotypes using a simple single sample scoring method
Authors: Foroutan Momeneh , Bhuva Dharmesh D. , Horan Kristy , Lyu Ruqian , Cursons Joseph , Davis Melissa J. 
Published: December 2017

AbstractBackgroundGene set scoring provides a useful approach for quantifying concordance between sample transcriptomes and selected molecular signatures. Most methods use information from all samples to score an individual sample, leading to unstable scores in small data sets and introducing biases from sample composition across a data set (e.g. varying numbers of samples for different cancer subtypes). To address these issues we have developed a truly single sample scoring method, and associated R/Bioconductor package singscore.ResultsWe have developed a rank-based single sample scoring method, implemented as a Bioconductor package. We use multiple cancer data sets to compare it against widely-used scoring methods, including GSVA, z-scores, PLAGE, and ssGSEA. Our approach does not depend upon background samples and thus the scores are stable regardless of the composition and number of samples in the gene expression data set. In contrast, scores obtained by GSVA, z-score, PLAGE and ssGSEA can be unstable when less data are available (nsamples < 25). We show that the computational time for singscore is faster than current implementations of GSVA and ssGSEA, and is comparable with that of z-score and PLAGE. The singscore package also produces visualisations and interactive plots that enable exploration of molecular phenotypes.ConclusionsThe single sample scoring method described here is independent of sample composition in gene expression data and thus it provides stable scores that are less likely to be influenced by unwanted variation across samples. These scores can be used for dimensional reduction of transcriptomic data and the phenotypic landscapes obtained by scoring samples against multiple molecular signatures may provide insights for sample stratification.
HumCFS: A database of fragile sites in human chromosomes
Authors: Kumar Rajesh , Nagpal Gandharva , Kumar Vinod , Usmani Salman Sadullah , Agrawal Piyush , Raghava Gajendra P.S. 
Published: December 2017

AbstractGenomic instability is the hallmark of cancer and several other pathologies, such as mental retardation; preferentially occur at specific loci in genome known as chromosomal fragile sites. HumCFS (http://webs.iiitd.edu.in/raghava/humcfs/) is a manually curated database provides comprehensive information on 118 experimentally characterized fragile sites present in human chromosomes. HumCFS comprises of 19068 entries with wide range of information such as nucleotide sequence of fragile sites, their length, coordinates on the chromosome, cytoband, their inducers and possibility of fragile site occurrence i.e. either rare or common etc. Each fragile region gene is further annotated to disease database DisGenNET, to understand its disease association. Protein coding genes are identified by annotating each fragile site to UCSC genome browser (GRCh38/hg38). To know the extent of miRNA lying in fragile site region, miRNA from miRBase has been mapped. Comprehensively, HumCFS encompasses mapping of 5010 genes with 19068 transcripts, 1104 miRNA and 3737 disease-associated genes on fragile sites. In order to facilitate users, we integrate standard web-based tools for easy data retrieval and analysis.
Characterization of siderophore producing arsenic-resistantStaphylococcus sp. strain TA6 isolated from contaminated groundwater of Jorhat, Assam and its possible role in arsenic geocycle
Authors: Das Saurav , Barooah Madhumita 
Published: December 2017

AbstractThe presence of arsenic in sediments, carbonaceous rocks are geogenic, while its entry into the aquifers is mediated by several factors including microorganisms. It is well known that the microorganisms play a crucial role in the biogeochemical cycle of different elements. However, the precise role of bacteria in regulating the concentration of arsenic in Brahmaputra valley has not been investigated in detail. In this paper, we report the isolation of arsenic resistant bacterium TA6 with active arsenate reduction efficiency. The isolate was able to grow in arsenate concentration (250 mM) and arsenite (30 mM). Along with resistance to inorganic arsenic, it showed cross-tolerance to other heavy metals like Hg+2, Cd+2, Co+2, Ni+2, Cr+2. The bacterium also had a high siderophore activity (78.7 ± 0.004 μmol), which is positively correlated with the resistance aptitude. The biochemical test showed the TA6, a gram-positive bacterium which can hydrolyze starch and casein, produce catalase enzyme and utilizes citrate as a metabolic trait. Molecular and chemotaxonomic identification of TA6 based on 16S rRNA and FMAE analysis showed similarity with members ofStaphylococcusgenus with significant difference in sequence similarity and fatty acid composition. Based on 16S rRNA and FAME analysis it was identified asStaphylococcus sp.TA6. Rate of biotransformation showed bacterium could reduce ~88.2% of initial 2mM As(V) into As(III). The characterization of arsenate reductase enzyme with NADPH coupled assay showed the highest activity at pH 5.5 and temperature 50°C.
The fruitENCODE project sheds light on the genetic and epigenetic basis of convergent evolution of climacteric fruit ripening
Authors: Lü Peitao , Yu Sheng , Zhu Ning , Chen Yun-Ru , Zhou Biyan , Pan Yu , Tzeng David , Fabi Joao Paulo , Argyris Jason , Garcia-Mas Jordi , Ye Nengui , Zhang Jianhua , Grierson Donald , Xiang Jenny , Fei Zhangjun , Giovannoni Jim , Zhong Silin 
Published: December 2017

AbstractFleshy fruit evolved independently multiple times during angiosperm history. Many climacteric fruits utilize the hormone ethylene to regulate ripening. The fruitENCODE project shows there are multiple evolutionary origins of the regulatory circuits that govern climacteric fruit ripening. Eudicot climacteric fruits with recent whole-genome duplications (WGDs) evolved their ripening regulatory systems using the duplicated floral identity genes, while others without WGD utilised carpel senescence genes. The monocot banana uses both leaf senescence and duplicated floral-identity genes, forming two interconnected regulatory circuits. H3K27me3 plays a conserved role in restricting the expression of key ripening regulators and their direct orthologs in both the ancestral dry fruit and non-climacteric fleshy fruit species. Our findings suggest that evolution of climacteric ripening was constrained by limited availability of signalling molecules and genetic and epigenetic materials, and WGD provided new resources for plants to circumvent this limit. Understanding these different ripening mechanisms makes it possible to design tailor-made ripening traits to improve quality, yield and minimize postharvest losses.One Sentence SummaryThe fruitENCODE project discovered three evolutionary origins of the regulatory circuits that govern climacteric fruit ripening.