bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-read only assembly of Drechmeria coniospora genomes reveals widespread chromosome plasticity and illustrates the limitations of current nanopore methods
Authors: Courtine Damien , Provaznik Jan , Reboul Jerome , Blanc Guillaume , Benes Vladimir , Ewbank Jonathan J. 
Published: December 2019

AbstractLong read sequencing is increasingly being used to determine eukaryotic genomes. We used nanopore technology to generate chromosome-level assemblies for 3 different strains of Drechmeria coniospora, a nematophagous fungus used extensively in the study of innate immunity in Caenorhabditis elegans. One natural geographical isolate demonstrated high stability over decades, whereas a second isolate, not only had a profoundly altered genome structure, but exhibited extensive instability. We conducted an in-depth analysis of sequence errors within the 3 genomes and established that even with state-of-the-art tools, nanopore methods alone are insufficient to generate eukaryotic genome sequences of sufficient accuracy to merit inclusion in public databases.
LandScape: a web application for interactive genomic summary visualization
Authors: Jia Wenlong , Li Hechen , Li Shiying , Li Shuaicheng 
Published: December 2019

ABSTRACTSummaryVisualizing integrated-level data from genomic research remains a challenge, as it requires sufficient coding skills and experience. Here, we present LandScapeoviz, a web-based application for interactive and real-time visualization of summarized genetic information. LandScape utilizes a well-designed file format that is capable of handling various data types, and offers a series of built-in functions to customize the appearance, explore results, and export high-quality diagrams that are available for publication.Availability and implementationLandScape is deployed at bio.oviz.org/demo-project/analyses/landscape for online use. Documentation and demo data are freely available on this website and GitHub (github.com/Nobel-Justin/Oviz-Bio-demo).Contactshuaicli@cityu.edu.hk
Global atlas tree of natural proteins based on sorted composition vectors
Authors: Tian Pu 
Published: December 2019

AbstractSequence comparison is the cornerstone of bioinformatics and is traditionally realized by alignment. Unfortunately, exponential computational complexity renders rigorous multiple sequence alignment (MSA) intractable. Approximate algorithms and heuristics provide acceptable performance for relatively small number of sequences but engender prohibitive computational cost and unbounded accumulation of error for massive sequence sets. Alignment free algorithms achieved linear computational cost for sequence pair comparison but the challenge for multiple sequence comparison (MSC) remains. Meanwhile, various number of parameters and procedures need to be empirically adjusted for different MSC tasks with their complex interactions and impact not well understood. Therefore, development of efficient and nonparametric global sequence comparison method is essential for explosive sequencing data. It is shown here that sorted composition vector (SCV), which is based on a physical perspective on sequence composition constraint, is a feasible non-parametric encoding scheme for global protein sequence comparison and classification with linear computational complexity, and provides a global atlas tree for natural protein sequences. This finding renders massive sequence comparison and classification, which is infeasible on supercomputers, routine on a workstation. SCV sets an example of one-way encoding that might revolutionize recognition and classification tasks in general.
Molecular Docking Studies of Phytochemicals of Allophylus serratus Against Cyclooxygenase-2 Enzyme
Authors: Jemal Kero 
Published: December 2019

AbstractAllophylus serratus is a medicinal plant used traditionally as anti-inflammatory agent. The main objectives of this study are to identify phytochemical compounds that have anti-inflammatory properties from the leaf extracts of Allophylus serratus and to search for cyclooxygenase-2 (COX-2) enzyme inhibitors through molecular docking. From the GC-MS analysis of leaf extracts of this plant, various phytochemicals were identified. About 10of these phytochemical compounds were analyzed for their drug likeliness based on Lipinski’s rule of five and inhibitor property against the cyclooxygenase (COX-2) enzyme, a protein responsible for inflammation The phytochemical compounds which satisfy the Lipinski’s rule such as 1H-Benzocycloheptene, 2,4a,5,6,7,8-hexahydro-3,5,5,9-tetramethyl-,(R) and Sulfurous acid, dipentyl ester were subjected to docking experiments using AutoDock Vina. The results from molecular docking study revealed that 1H-Benzocycloheptene, 2,4a,5,6,7,8-hexahydro-3,5,5,9-tetramethyl-, (R)-, Sulfurous acid, dipentyl ester and 1,2-Benzenedicarboxylic acid, bis(2-methylpropyl) ester bind effectively to the active site region of COX-2 with a binding energy of −8.9, −8.4, and −7.9, respectively. The binding energy of the phyto-compounds were compared with the known antiinflammatory drug Diclofenac that inhibit COX-2 enzyme. It was found that the phytochemical compounds from leaf extracts of Allophylus serratus have strong inhibitory effect on COX-2 enzyme and as a result they have potential anti-inflammatory medicinal values. Thus the study puts forth experimental validation for traditional antidote and these phyto-compounds could be further promoted as potential lead molecule.
A revised mechanism of action of hyperaldosteronism-linked mutations in cytosolic domains of GIRK4 (KCNJ5)
Authors: Shalomov Boris , Handklo-Jamal Reem , Reddy Haritha P. , Theodor Neta , Bera Amal K. , Dascal Nathan 
Published: December 2019

AbstractG-protein gated, inwardly rectifying potassium channels (GIRK) mediate inhibitory transmission in brain, heart, and adrenal cortex. GIRK4 (KCNJ5) subunits are abundant in the heart and adrenal cortex. Multiple mutations ofKCNJ5cause primary aldosteronism (PA). According to a leading concept, mutations in the pore region of GIRK4 cause loss of K+selectivity; the ensuing Na+influx depolarizes zona glomerulosa cells and activates voltage gated Ca2+channels, inducing hypersecretion of aldosterone. The concept of selectivity loss has been extended to mutations in cytosolic domains of GIRK4 channels, remote from the pore region. We expressed GIRK4R52H, GIRK4E246K, and GIRK4G247Rmutants inXenopusoocytes and human adrenocortical carcinoma cell line (HAC15). Whole-cell currents of heterotetrameric GIRK1/4R52Hand GIRK1/4E246K(but not GIRK1/4G247R) channels were greatly reduced compared to GIRK1/4WT. Nevertheless, all heterotetrameric mutants retained full K+selectivity and inward rectification. When expressed as homotetramers, only GIRK4WT, but none of the mutants, produced whole-cell currents. Confocal imaging, single channel and Förster Resonance Energy Transfer (FRET) analyses showed: 1) reduction of membrane abundance of all mutated channels, especially as homotetramers, 2) impaired interaction with Gβγ subunits, and 3) reduced open probability of GIRK1/4R52H. VU0529331, a GIRK4 opener, activated homotetrameric GIRK4G247Rchannels, but not GIRK4R52Hand GIRK4E246K. Our results suggest impaired gating (GIRK4R52H) and expression in plasma membrane (all mutants). We suggest that, contrary to the previously proposed mechanism, R52H and E246K mutants are loss-of-function rather than gain-of-function/selectivity-loss mutants. Hence, GIRK4 openers may be a potential course of treatment for patients with cytosolic N- and C-terminal mutations.Significance StatementMutations in KCNJ5 gene, which encodes for the GIRK4 subunit of G-protein inwardly rectifying K+ channels, are the main cause of primary aldosteronism, a major contributor to secondary hypertension. We report that three mutations in the cytosolic domain of GIRK4 cause loss-of-function, contrary to the prevailing concept that these mutations cause loss of selectivity and subsequent depolarization, i.e. essentially gain-of-function. Our findings correct the existing misconception regarding the biophysical mechanism that impairs the channel function, and may provide indications for future personalized treatment of the disease.
Phage T5 two-step injection
Authors: Davison John 
Published: December 2019

AbstractEscherichia colibacteriophage T5 differs from most phages in that it injects its genome in two steps: First Step Transfer, FST, corresponding to leftmost 7.9% of the genome and Second Step Transfer, SST, corresponding to the remainder of the genome. Expression of genesA1andA2is required for SST. DNA injection stops at a site known as the injection stop signal (iss) which is a cis acting site located in the large untranslated region of the Left Terminal Repeat (LTR). Theissregion is extremely complicated with many repeats, inverted repeats and palindromes. This report compares theissregions of 25 T5-like phages and shows that all have a common conserved structure including a series of 8 DnaA boxes arranged in a highly specific manner; reminiscent of the origin of replication(oriC)ofE. coli.DnaA protein, which binds to DnaA boxes, is a mostly membrane bound. A new, radically different, mechanism of T5 2-step injection is proposed whereby injecting T5 DNA stops at the plasma membrane due to the binding of theissDnaA boxes to membrane-bound DnaA protein. Injection of the SST continues later via the combined action of the A1 and A2 proteins which cleave the FST DNA at a site upstream (right) of theissregion, thereby liberating it. They also cleave the incoming SST DNA at the same site on the RTR thus facilitating circularisation of one complete genome via the cohesive ends. Circle formation protects the T5 DNA from the degradative action of the RecBCD nuclease and eventually leads to rolling circle DNA replication.
Prokaryotic Single-Cell RNA Sequencing by In Situ Combinatorial Indexing
Authors: Blattman Sydney B. , Jiang Wenyan , Oikonomou Panos , Tavazoie Saeed 
Published: December 2019

AbstractDespite longstanding appreciation of gene expression heterogeneity in isogenic bacterial populations, affordable and scalable technologies for studying single bacterial cells have been limited. While single-cell RNA sequencing (scRNA-seq) has revolutionized studies of transcriptional heterogeneity in diverse eukaryotic systems, application of scRNA-seq to prokaryotes has been hindered by their extremely low mRNA abundance, lack of mRNA polyadenylation, and thick cell walls. Here, we present Prokaryotic Expression-profiling by Tagging RNA In Situ and sequencing (PETRI-seq), a low-cost, high-throughput, prokaryotic scRNA-seq pipeline that overcomes these technical obstacles. PETRI-seq uses in situ combinatorial indexing to barcode transcripts from tens of thousands of cells in a single experiment. PETRI-seq captures single cell transcriptomes of Gram-negative and Gram-positive bacteria with high purity and low bias, with median capture rates >200 mRNAs/cell for exponentially growing E. coli. These characteristics enable robust discrimination of cell-states corresponding to different phases of growth. When applied to wild-type S. aureus, PETRI-seq revealed a rare sub-population of cells undergoing prophage induction. We anticipate broad utility of PETRI-seq in defining single-cell states and their dynamics in complex microbial communities.
GHSR-1a is not Required for Ghrelin’s Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia
Authors: Liu Haiming , Luo Jiaohua , Guillory Bobby , Chen Ji-an , Zang Pu , Yoeli Jordan K. , Hernandez Yamileth , Lee Ian (In-gi) , Anderson Barbara , Storie Mackenzie , Tewnion Alison , Garcia Jose M. 
Published: December 2019

ABSTRACTAdipose tissue (AT) atrophy is a hallmark of cancer cachexia contributing to increased morbidity/mortality. Ghrelin has been proposed as a treatment for cancer cachexia partly by preventing AT atrophy. However, the mechanisms mediating ghrelin’s effects are incompletely understood, including the extent to which its only known receptor, GHSR-1a, is required for these effects. This study characterizes the pathways involved in AT atrophy in the Lewis Lung Carcinoma (LLC)-induced cachexia model and those mediating the effects of ghrelin in Ghsr+/+ and Ghsr−/− mice. We show that LLC causes AT atrophy by inducing anorexia, and increasing AT inflammation, thermogenesis and energy expenditure. These changes were greater in Ghsr−/−. Ghrelin administration prevented LLC-induced anorexia only in Ghsr+/+, but prevented WAT inflammation and atrophy in both genotypes, although its effects were greater in Ghsr+/+. LLC-induced increases in BAT inflammation, WAT and BAT thermogenesis, and energy expenditure were not affected by ghrelin. In conclusion, ghrelin ameliorates WAT inflammation, fat atrophy and anorexia in LLC-induced cachexia. GHSR-1a is required for ghrelin’s orexigenic effect but not for its anti-inflammatory or fat-sparing effects.
Material aging causes centrosome weakening and disassembly during mitotic exit
Authors: Mittasch Matthäus , Tran Vanna M. , Rios Manolo U. , Fritsch Anatol W. , Enos Stephen J. , Gomes Beatriz Ferreira , Bond Alec , Kreysing Moritz , Woodruff Jeffrey B. 
Published: December 2019

ABSTRACTCentrosomes must resist microtubule-mediated forces for mitotic chromosome segregation. During mitotic exit, however, centrosomes are deformed and fractured by those same forces, which is a key step in centrosome disassembly. How the functional material properties of centrosomes change throughout the cell cycle, and how they are molecularly tuned remain unknown. Here, we used optically-induced flow perturbations to determine the molecular basis of centrosome strength and ductility in C. elegans embryos. We found that both properties declined sharply at anaphase onset, long before natural disassembly. This mechanical transition required PP2A phosphatase and correlated with inactivation of PLK-1 (Polo Kinase) and SPD-2 (Cep192). In vitro, PLK-1 and SPD-2 directly protected centrosome scaffolds from force-induced disassembly. Our results suggest that, prior to anaphase, PLK-1 and SPD-2 confer strength and ductility to the centrosome scaffold so that it can resist microtubule-pulling forces. In anaphase, centrosomes lose PLK-1 and SPD-2 and transition to a weak, brittle state that enables force-mediated centrosome disassembly.
Hidden dynamic signatures drive substrate selectivity in the disordered phosphoproteome
Authors: Cho Min-Hyung , Wrabl James O. , Taylor James , Hilser Vincent J. 
Published: December 2019

AbstractPhosphorylation sites are hyper-abundant in the disordered proteins of eukaryotes, suggesting that conformational dynamics (or heterogeneity) may play a major role in determining to what extent a kinase interacts with a particular substrate. In biophysical terms, substrate selectivity may be determined not just by the structural and chemical complementarity between the kinase and its protein substrates, but also by the free energy difference between the conformational ensembles that are recognized by the kinase and those that are not. To test this hypothesis, we developed an informatics framework based on statistical thermodynamics, which allows us to probe for dynamic contributions to phosphorylation, as evaluated by the ability to predict Ser/Thr/ Tyr phosphorylation sites in the disordered proteome. Essential to this framework is a decomposition of substrate sequence information into two types: vertical information encoding conserved kinase specificity motifs and horizontal (distributed) information encoding substrate conformational dynamics that are embedded, but often not apparent, within position specific conservation patterns. We find not only that conformational dynamics play a major role, but that they are the dominant contribution to substrate selectivity. In fact, the main substrate classifier distinguishing selectivity is the magnitude of change in compaction of the disordered chain upon phosphorylation. Thus, in addition to providing fundamental insights into the underlying mechanistic consequences of phosphorylation across the entire proteome, our approach provides a novel statistical thermodynamic strategy for partitioning any sequence-based search into contributions from direct chemical and structural complementarity and those from changes in conformational dynamics. Using this framework, we developed a high-performance open-source phosphorylation site predictor, PHOSforUS, which is freely available athttps://github.com/bxlab/PHOSforUS.
Reversible Loss of Hippocampal Function in a Mouse Model of Demyelination/Remyelination
Authors: Das Aniruddha , Bastian Chinthasagar , Trestan Lexie , Suh Jason , Dey Tanujit , Trapp Bruce , Baltan Selva , Dana Hod 
Published: December 2019

AbstractDemyelination of axons in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and other demyelinating diseases. Cycles of demyelination, followed by remyelination, appear in the majority of MS patients, and are associated with the onset and quiescence of disease-related symptoms, respectively. Previous studies have shown in human patients and animal models that vast demyelination is accompanied by wide-scale changes to brain activity, but details of this process are poorly understood. We use electrophysiological recordings and nonlinear imaging of fluorescence from genetically-encoded calcium indicators to monitor the activity of hippocampal neurons during demyelination and remyelination processes over a period of 100 days. We find in vitro that synaptic transmission in CA1 neurons is diminished, and in vivo both CA1 and dentate gyrus (DG) neuronal firing rates are substantially reduced during demyelination and partially recover after a short remyelination period. This new approach allows monitoring how synaptic transmission changes, induced by cuprizone diet, are affecting neuronal activity, and can potentially be used to study the effects of therapeutic interventions in protecting the functionality of CNS neurons.
Comprehensive single-PCR 16S and 18S rRNA community analysis validated with mock communities and denoising algorithms
Authors: Yeh Yi-Chun , McNichol Jesse C. , Needham David M. , Fichot Erin B. , Fuhrman Jed A. 
Published: December 2019

AbstractUniversal SSU rRNA primers allow comprehensive quantitative profiling of natural communities by simultaneously amplifying templates from Bacteria, Archaea, and Eukaryota in a single PCR reaction. Despite the potential to show all rRNA gene relative gene abundances, they are rarely used due to concerns about length bias against 18S amplicons and bioinformatic challenges converting mixed 16S/18S sequences into amplicon sequence variants. We thus developed 16S and 18S rRNA mock communities and a bioinformatic pipeline to validate this three-domain approach. To test for length biases, we mixed eukaryotic and prokaryotic mocks before PCR, and found consistent two-fold underestimation of longer 18S sequences due to sequencing but not PCR bias. Using these mocks, we show universal V4-V5 primers (515Y/926R) outperformed eukaryote-specific V4 primers in observed vs. expected abundance correlations and sequences with single mismatches to the primer were strongly underestimated (3-8 fold). A year of monthly time-series data from a protist-enriched 1.2-80 μm size fraction yielded an average of 9% 18S, 17% chloroplast 16S, and 74% prokaryote 16S rRNA gene amplicons. These data demonstrate the potential for universal primers to generate quantitative and comprehensive microbiome profiles, although gene copy and genome size variability should be considered - as for any quantitative genetic analysis.
Neural speech restoration at the cocktail party: Auditory cortex recovers masked speech of both attended and ignored speakers
Authors: Brodbeck Christian , Jiao Alex , Hong L. Elliot , Simon Jonathan Z. 
Published: December 2019

AbstractHumans are remarkably skilled at listening to one speaker out of an acoustic mixture of several speech sources. Two speakers are easily segregated, even without binaural cues, but the neural mechanisms underlying this ability are not well understood. One possibility is that early cortical processing performs a spectro-temporal decomposition of the acoustic mixture, allowing the attended speech to be reconstructed via optimally weighted recombinations that discount spectro-temporal regions where sources heavily overlap. Using human magnetoencephalography (MEG) responses to a two-talker mixture, we show evidence for an alternative possibility, in which early, active segregation occurs even for strongly spectro-temporally overlapping regions. Early (∼70 ms) responses to non-overlapping spectro-temporal features are seen for both talkers. When competing talkers’ spectro-temporal features mask each other, the individual representations persist, but they occur with a ∼20 ms delay. This suggests that the auditory cortex recovers acoustic features that are masked in the mixture, even if they occurred in the ignored speech. The existence of such noise-robust cortical representations, of features present in attended as well as ignored speech, suggests an active cortical stream segregation process, which could explain a range of behavioral effects of ignored background speech.
Environment affects specialisation of plants and pollinators
Authors: Cagua E. Fernando , Lustig Audrey , Tylianakis Jason M. , Stouffer Daniel B. 
Published: December 2019

AbstractWhat determines whether or not a species is a generalist or a specialist? Evidence that the environment can influence species interactions is rapidly accumulating. However, a systematic link between environment and the number of partners a species interacts with has been elusive so far. Presumably, because environmental gradients appear to have contrasting effects on species depending on the environmental variable. Here, we test for a relationship between the stresses imposed by the environment, instead of environmental gradients directly, and species specialisation using a global dataset of plant-pollinator interactions. We found that the environment can play a significant effect on specialisation, even when accounting for community composition, likely by interacting with species’ traits and evolutionary history. Species that have a large number of interactions are more likely to focus on a smaller number of, presumably higher-quality, interactions under stressful environmental conditions. Contrastingly, the specialists present in multiple locations are more likely to broaden their niche, presumably engaging in opportunistic interactions to cope with increased environmental stress. Indeed, many apparent specialists effectively behave as facultative generalists. Overall, many of the species we analysed are not inherently generalist or specialist. Instead, species’ level of specialisation should be considered on a relative scale depending on where they are found and the environmental conditions at that location.