bluuebunny/crossref_metadata_2025_split huggingface dataset:
Index and biological spectrum of accessible DNA elements in the human genome
Authors: Meuleman Wouter , Muratov Alexander , Rynes Eric , Halow Jessica , Lee Kristen , Bates Daniel , Diegel Morgan , Dunn Douglass , Neri Fidencio , Teodosiadis Athanasios , Reynolds Alex , Haugen Eric , Nelson Jemma , Johnson Audra , Frerker Mark , Buckley Michael , Sandstrom Richard , Vierstra Jeff , Kaul Rajinder , Stamatoyannopoulos John 
Published: October 2019

AbstractDNase I hypersensitive sites (DHSs) are generic markers of regulatory DNA and harbor disease- and phenotypic trait-associated genetic variation. We established high-precision maps of DNase I hypersensitive sites from 733 human biosamples encompassing 439 cell and tissue types and states, and integrated these to precisely delineate and numerically index ~3.6 million DHSs encoded within the human genome, providing a common coordinate system for regulatory DNA. Here we show that the expansive scale of cell and tissue states sampled exposes an unprecedented degree of stereotyped actuation of large sets of elements, signaling the operation of distinct genome-scale regulatory programs. We show further that the complex actuation patterns of individual elements can be captured comprehensively by a simple regulatory vocabulary reflecting their dominant cellular manifestation. This vocabulary, in turn, enables comprehensive and quantitative regulatory annotation of both protein-coding genes and the vast array of well-defined but poorly-characterized non-coding RNA genes. Finally, we show that the combination of high-precision DHSs and regulatory vocabularies markedly concentrate disease- and trait-associated non-coding genetic signals both along the genome and across cellular compartments. Taken together, our results provide a common and extensible coordinate system and vocabulary for human regulatory DNA, and a new global perspective on the architecture of human gene regulation.
Establishment of an eHAP1 Human Haploid Cell Line Hybrid Reference Genome Assembled from Short and Long Reads
Authors: Law William D. , Warren René L. , McCallion Andrew S. 
Published: October 2019

AbstractBackgroundHaploid cell lines are a valuable research tool with broad applicability for genetic assays. As such the fully haploid human cell line, eHAP1, has been used in a wide array of studies. However, the absence of a corresponding reference genome sequence for this cell line has limited the potential for more widespread applications to experiments dependent on available sequence, like capture-clone methodologies.ResultsWe generated ~15x coverage Nanopore long reads from ten GridION flowcells. We utilized this data to assemble a de novo draft genome using minimap and miniasm and subsequently polished using Racon. This assembly was further polished using previously generated, low-coverage, Illumina short reads with Pilon and ntEdit. This resulted in a hybrid eHAP1 assembly with >90% complete BUSCO scores. We further assessed the eHAP1 long read data for structural variants using Sniffles and identify a variety of rearrangements, including a previously established Philadelphia translocation. Finally, we demonstrate how some of these variants overlap open chromatin regions, potentially impacting regulatory regions.ConclusionsBy integrating both long and short reads, we generated a high-quality reference assembly for eHAP1 cells. We identify structural variants using long reads, including some that may impact putative regulatory elements. The union of long and short reads demonstrates the utility in combining sequencing platforms to generate a high-quality reference genome de novo solely from low coverage data. We expect the resulting eHAP1 genome assembly to provide a useful resource to enable novel experimental applications in this important model cell line.
Cerebellar lesions disrupt spatial and temporal visual attention
Authors: Craig B.T. , Morrill A. , Anderson B. , Danckert J. , Striemer C.L. 
Published: October 2019

AbstractThe current study represents the first comprehensive examination of spatial, temporal and sustained attention following cerebellar damage. Results indicated that, compared to controls, cerebellar damage resulted in a larger cueing effect at the longest SOA – possibly reflecting a slowed the onset of inhibition of return (IOR) during a reflexive covert attention task, and reduced the ability to detect successive targets during an attentional blink task. However, there was little evidence to support the notion that cerebellar damage disrupted voluntary covert attention or the sustained attention to response task (SART). Lesion overlay data and supplementary voxel-based lesion symptom mapping (VLSM) analyses indicated that impaired performance on the reflexive covert attention and attentional blink tasks were related to damage to Crus II of the left posterior cerebellum. In addition, subsequent analyses indicated our results are not due to either general motor impairments or to damage to the deep cerebellar nuclei. Collectively these data demonstrate, for the first time, that the same cerebellar regions may be involved in both spatial and temporal visual attention.
Assembling a corpus of phosphoproteomic annotations using ProtMapper to normalize site information from databases and text mining
Authors: Bachman John A. , Sorger Peter K. , Gyori Benjamin M. 
Published: October 2019

AbstractProtein phosphorylation regulates numerous cellular processes and is highly studied in biology.However, the analysis of phosphoproteomic datasets remains challenging due to limited information on upstream regulators of phosphosites, which is fragmented across multiple curated databases and unstructured literature. When aggregating information on phosphosites from six databases and three text mining systems, we found that a substantial proportion of phosphosites were mentioned at residue positions not matching the reference sequence. These errors were often attributable to the use of residue numbers from non-canonical protein isoforms, mouse or rat proteins, or post-translationally processed proteins. Non-canonical site numbering is also prevalent in mass spectrometry datasets from large-scale efforts such as the Clinical Proteomic Tumor Analysis Consortium (CPTAC). To address these issues, we developed ProtMapper, an open-source Python tool that automatically normalizes site positions to human protein reference sequences. We used ProtMapper coupled with the INDRA knowledge assembly system to create a corpus of 37,028 regulatory annotations for 16,332 sites – to our knowledge, the most comprehensive corpus of literature-derived information about phosphosite regulation currently available. This work highlights how automated phosphosite normalization coupled to text mining and knowledge assembly allows researchers to leverage phosphosite information that exists within the scientific literature.
A comparative analysis among ADAR mutant mice reveals site-specific regulation of RNA editing
Authors: Cruz Pedro Henrique Costa , Kato Yuki , Nakahama Taisuke , Shibuya Toshiharu , Kawahara Yukio 
Published: October 2019

ABSTRACTAdenosine-to-inosine RNA editing is an essential posttranscriptional modification catalyzed by adenosine deaminase acting on RNA (ADAR)1 and ADAR2 in mammals. For numerous sites in coding sequences (CDS) and microRNAs (miRNAs), editing is highly conserved and has significant biological consequences, for example, by altering amino acid residues and target recognition. However, technical limitations have prevented a comprehensive and quantitative study to determine how specific ADARs contribute to each site. Here, we developed a simple method in which each RNA region with an editing site was amplified separately and combined for deep sequencing. Using this method, we compared the editing ratios of all sites that were either definitely or possibly conserved in CDS and miRNAs in the cerebral cortex and spleen of wild-type mice, Adar1E861A/E861AIfih−/− mice expressing inactive ADAR1 (Adar1 KI) and Adar2−/−Gria2R/R (Adar2 KO) mice. We found that the editing ratio was frequently upregulated in either Adar mutant mouse strain. In contrast, we found that the presence of both ADAR1 and ADAR2 was required for the efficient editing of specific sites. In addition, some sites, such as miR-3099-3p, showed no preference for either ADAR. We further created double mutant Adar1 KI Adar2 KO mice and observed viable and fertile animals with complete absence of editing, suggesting that ADAR1 and ADAR2 are the sole enzymes responsible for all editing sites in vivo. Collectively, these findings indicate that editing is regulated in a site-specific manner by the different interplay between ADAR1 and ADAR2.
Refined mechanism ofMycoplasma mobilegliding based on structure, ATPase activity, and sialic acid binding of machinery
Authors: Nishikawa Miyuki S , Nakane Daisuke , Toyonaga Takuma , Kawamoto Akihiro , Kato Takayuki , Namba Keiichi , Miyata Makoto 
Published: October 2019

ABSTRACTMycoplasma mobile, a fish pathogen, glides on solid surfaces by repeated catch, pull, and release of sialylated oligosaccharides by a unique mechanism based on ATP energy. The gliding machinery is composed of huge surface proteins and an internal jellyfish -like structure. Here, we elucidated the detailed three-dimensional structures of the machinery by electron cryotomography. The internal tentacle -like structure hydrolyzed ATP, which was consistent with the fact that the paralogs of the α- and β-subunits of F1-ATPase are at the tentacle structure. The electron microscopy suggested conformational changes of the tentacle structure depending on the presence of ATP analogs. The gliding machinery was isolated and shown that the binding activity to sialylated oligosaccharide was higher in the presence of ADP than in the presence of ATP. Based on these results, we proposed a model to explain the mechanism ofM. mobilegliding.IMPORTANCEThe genusMycoplasmais made up of the smallest parasitic and sometimes commensal bacteria;Mycoplasma pneumoniae, which causes human walking pneumonia, is representative. More than tenMycoplasmaspecies glide on host tissues by novel mechanisms always in the direction of the distal side of the machinery.Mycoplasma mobile, the fastest species in the genus, catches, pulls, and releases sialylated oligosaccharides (SOs), the carbohydrate molecules also targeted by influenza viruses, by means of a specific receptor and using ATP hydrolysis for energy. Here, the architecture of the gliding machinery was visualized three-dimensionally by electron cryotomography (ECT), and changes in the structure and binding activity coupled to ATP hydrolysis were discovered. Based on the results, a refined mechanism was proposed for this unique motility.
Species richness increases fitness differences, but does not affect niche differences
Authors: Spaak Jurg W. , Carpentier Camille , De Laender Frederik 
Published: October 2019

AbstractA key question in ecology is what limits species richness. Modern coexistence theory presents the persistence of species as a balance between niche differences and fitness differences that favor and hamper coexistence, respectively. With most applications focusing on species pairs, however, we know little about if and how this balance changes with species richness. Here, we present the first mathematical proof that the average fitness difference among species increases with richness, while the average niche difference stays constant. Extensive simulations with more complex models and analyses of empirical data confirmed these mathematical results. Taken together, our work suggests that, as species accumulate in ecosystems, ever-increasing fitness differences will at some point exceed constant niche differences, limiting species richness. Our results contribute to the expansion of modern coexistence theory towards multi-species communities.
Genetic analysis ofAedes aegypticaptured in two international airports serving to the Greater Tokyo Area during 2012—2015
Authors: Itokawa Kentaro , Hu Jinping , Sukehiro Nayu , Tsuda Yoshio , Komagata Osamu , Kasai Shinji , Tomita Takashi , Minakawa Noboru , Sawabe Kyoko 
Published: October 2019

AbstractIntroduction of exotic diseases vectors into a new habitat can drastically change the local epidemiological situation. During 2012—2015, larvae and an adult of the yellow-fever mosquito,Aedes aegypti, were captured alive in two international airports serving to the Greater Tokyo Area, Japan. Because this species does not naturally distribute in this country, those mosquitoes were considered to be introduced from overseaviaair-transportation. To infer the places of origin of those mosquitoes, we genotyped 12 microsatellite loci for which the most comprehensive population genetic reference is available. Although clustering by Bayesian and multivariate methods both suggested all those airport mosquitoes belong to Asia/Pacific population, they were not clustered into a single population. Also, there was variation in mitochondrialCox1haplotypes among mosquitoes collected in different incidents of discovery which indicated the existence of multiple maternal origins. Whereas we conclude there is little evidence to support overwintering ofAe. aegyptiin the airports in this study, special attention is still desired to prevent the invasion of this prominent arbovirus vector.
Phenotypic diversity of Methylobacterium associated with rice landraces in Northeast India
Authors: Sanjenbam Pratibha , Buddidathi Radhika , Venkatesan Radhika , Shivaprasad P V , Agashe Deepa 
Published: October 2019

ABSTRACTThe ecology and distribution of many bacteria is strongly associated with specific eukaryotic hosts. However, the impact of such host association on bacterial ecology and evolution is not well understood. Bacteria from the genus Methylobacterium consume plant-derived methanol, and are some of the most abundant and widespread plant-associated bacteria. In addition, many of these species impact plant fitness. To determine the ecology and distribution of Methylobacterium in nature, we sampled bacteria from 36 distinct rice landraces, traditionally grown in geographically isolated locations in North-East (NE) India. These landraces have been selected for diverse phenotypic traits by local communities, and we expected that the divergent selection on hosts may have also generated divergence in associated Methylobacterium strains. We determined the ability of 91 distinct rice-associated Methylobacterium isolates to use a panel of carbon sources, finding substantial variability in carbon use profiles. Consistent with our expectation, across spatial scales this phenotypic variation was largely explained by host landrace identity rather than geographical factors or bacterial taxonomy. However, variation in carbon utilisation was not correlated with sugar exudates on leaf surfaces, suggesting that bacterial carbon use profiles do not directly determine bacterial colonization across landraces. Finally, experiments showed that at least some rice landraces gain an early growth advantage from their specific phyllosphere-colonizing Methylobacterium strains. Together, our results suggest that landrace-specific host-microbial relationships may contribute to spatial structure in rice-associated Methylobacterium in a natural ecosystem. In turn, association with specific bacteria may provide new ways to preserve and understand diversity in one of the most important food crops of the world.
Relationship between True Digestibility of dietary Phosphorus and Gastrointestinal Bacteria of Goats
Authors: Wang Lizhi , Shah Ali Mujtaba , Liu Yuehui , Jin Lei , Wang Zhisheng , Xue Bai , Peng Quanhui 
Published: October 2019

AbstractThe present research was conducted to evaluate the connection between the true digestibility of Phosphorus (TDP) in diet and bacterial community structure in the gastrointestinal tract (GIT) of goats. Twenty-eight Nubian goats were chosen and metabolic experiment was conducted to analyze TDP of research animals. Eight goats were grouped into the high digestibility of phosphorus (HP) phenotype, and another 8 were grouped into the low digestibility of phosphorus (LP) phenotype. And from the rumen, abomasum, jejunim, cecum and colon content of the goats, bacterial 16S rRNA gene amplicons were sequenced. In the rumen 239 genera belonging to 23 phyla, in abomasum 319 genera belonging to 30 phyla, in jejunum 248 genera belonging to 36,in colon 248 genera belonging to 25 phyla and in cecum 246 genera belonging to 23 phyla were noticed. In addition, there was a significant correlation between the TDP and the abundance of Ruminococcaceae_UCG-010, Ruminococcus_2, Ruminococcaceae_UCG-014, Selenomonas_1 and Prevotella in the rumen, Lachnospiraceae_ND3007_group, Saccharofermentans, Ruminococcus_1, Ruminococcaceae_UCG-014, Lachnospiraceae_XPB1014_group and Desulfovibrio in the abomasum, Prevotella, Clostridium_sensu_stricto_1, Fibrobacter, Desulfovibrio and Ruminococcus_2 in the jejunum, Ruminococcaceae_UCG-014 in the colon, and Desulfovibrio in the cecum. Present research trial recommended that the community of gastrointestinal microbiota is a factor affecting TDP in goats.
Dynamic-ultrastructural cell volume (3D) correlative microscopy facilitated by intracellular fluorescent nanodiamonds as multi-modal probes
Authors: Prabhakar Neeraj , Belevich Ilya , Peurla Markus , Heiligenstein Xavier , Chang Huan-Cheng , Sahlgren Cecilia , Jokitalo Eija , Rosenholm Jessica M. 
Published: October 2019

ABSTRACTThree-dimensional correlative light and electron microscopy (3D CLEM) are attaining popularity as a potential technique to explore the functional aspects of a cell together with high-resolution ultrastructural details across the cell volume. In order to perform such a 3D CLEM experiment, there is an imperative requirement for multi-modal probes that are both fluorescent and electron-dense. These multi-modal probes will serve as landmarks in matching up the large full cell volume datasets acquired by different imaging modalities. Fluorescent nanodiamonds (FNDs) are a unique nanosized, fluorescent, and electron-dense material from the nanocarbon family. We hereby propose a novel and straightforward method for executing 3D CLEM using FNDs as multi-modal landmarks. We demonstrate that FNDs is biocompatible and easily identified both in living cell fluorescence imaging and in serial block-face scanning electron microscopy (SB-EM). We illustrate the 3D CLEM method by registering multi-modal datasets.
PopInf: An approach for reproducibly visualizing and assigning population affiliation in genomic samples of uncertain origin
Authors: Taravella Oill Angela M. , Deshpande Anagha J. , Natri Heini M. , Wilson Melissa A. 
Published: October 2019

ABSTRACTGermline genetic variation contributes to cancer etiology, but self-reported race is not always consistent with genetic ancestry, and samples may not have identifying ancestry information. Here we describe a flexible computational pipeline, PopInf, to visualize principal components analysis output and assign ancestry to samples with unknown genetic ancestry, given a reference population panel of known origins. PopInf is implemented as a reproducible workflow in Snakemake with a tutorial on GitHub. We provide a pre-processed reference population panel that can be quickly and efficiently implemented in cancer genetics studies. We ran PopInf on TCGA liver cancer data and identify discrepancies between reported race and inferred genetic ancestry.SignificanceThe PopInf pipeline facilitates visualization and identification of genetic ancestry across samples, so that this ancestry can be accounted for in studies of disease risk. All code and a tutorial are available on Github: https://github.com/SexChrLab/PopInf.
Molecular principles of Piezo1 activation by increased membrane tension
Authors: De Vecchis Dario , Beech David J , Kalli Antreas C 
Published: October 2019

SUMMARY PARAGRAPHPiezo1 is a mechanosensitive channel involved in many cellular functions and responsible for sensing shear-stress and pressure forces in cells1–3. Piezo1 plays a critical role in the circulatory system and tissue development. Mutations on Piezo1 are linked to human diseases such as lymphedema2,4 or hematological disorders such as hemolytic anaemia5 and resistance to malaria6. Hypotheses for Piezo1 gating include the “force-from-lipids” principle7,8 that suggests that Piezo1 senses mechanical forces through the bilayer1,9 and a direct involvement of the cytoskeleton as well as the extracellular matrix in Piezo1 activation10,11. However, the molecular and structural changes underpinning the Piezo1 gating mechanism and how the channel senses forces in the membrane remain unknown. Here we reveal the activation mechanism of Piezo1 and the structural rearrangements that occur when Piezo1 moves from a closed to an open state when mechanical tension is applied to the cell membrane. Our results show that Piezo1’s curved shape is stable in a native-like model membrane without tension creating a membrane indentation with a trilobed topology. Upon stretching Piezo1 adapts to the stretched bilayer by flattening and expansion of its blade region. In our simulations Piezo1 expands up to a planar circular area of ∼680 nm2 comparable with previous structural data and hypotheses12–14. Piezo1 flattening and expansion results in changes in the beam helix tilt angle. These movements result in the tilting and lateral movement of the pore lining TM37 and TM38 helices. This leads to the opening of the channel and to the movement of lipids that occupy Piezo1 pore region outside of this region, revealing for the first time the structural changes that happen during Piezo1 mechanical activation. The changes in the blade region are transmitted to helices TM37 and 38 via hydrophobic interactions and by interactions of neighbouring subunits via the elbow region. The flat structure of Piezo1 identified in this study exposes the C-terminal extracellular domain (CED) that in the closed state is hidden in the membrane and presumably from shear stress. Our results provide new structural data for different states of Piezo1 and suggest the molecular principles by which mechanical force opens the Piezo1 channel, thus coupling force to physiological effect via ion permeation.
Presynaptic development is controlled by the core active zone proteins CAST/ELKS
Authors: Radulovic Tamara , Dong Wei , Goral R. Oliver , Thomas Connon I. , Veeraraghavan Priyadharishini , Montesinos Monica Suarez , Guerrero-Given Debbie , Goff Kevin , Lübbert Matthias , Kamasawa Naomi , Ohtsuka Toshihisa , Young Samuel M. 
Published: October 2019

AbstractMany presynaptic active zone proteins have multiple regulatory roles that vary during distinct stages of neuronal circuit development. However, our understanding how presynaptic active zone proteins regulate synapse development during neuronal circuit maturation is in its early stages. Although CAST/ELKS are presynaptic active zone core proteins, their roles in synapse development in the mammalian central nervous system remain enigmatic. To unravel CAST/ELKS roles in glutamatergic synapse development, we analyzed how their loss during the early stages of circuit maturation impacted the calyx of Held presynaptic terminal development and function. We found a reduction in presynaptic surface area and volume, but an increase in active zone size. Additionally, we found a reduction in all presynaptic Cav2 channel subtype currents. Surprisingly, these changes did not impair synaptic transmission. We propose that CAST/ELKS are involved in pathways regulating presynaptic morphological properties and Cav2 channel subtype levels during early stages of neuronal circuit maturation.