bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling Structural Constraints on Protein Evolution via Side-Chain Conformational States
Authors: Perron Umberto , Kozlov Alexey M , Stamatakis Alexandros , Goldman Nick , Moal Iain H 
Published: May 2019

AbstractFew models of sequence evolution incorporate parameters describing protein structure, despite its high conservation, essential functional role and increasing availability. We present a structurally aware empirical substitution model for amino acid sequence evolution in which proteins are expressed using an expanded alphabet that relays both amino acid identity and structural information. Each character specifies an amino acid as well as information about the rotamer configuration of its side-chain: the discrete geometric pattern of permitted side-chain atomic positions, as defined by the dihedral angles between covalently linked atoms. By assigning rotamer states in 251,194 protein structures and identifying 4,508,390 substitutions between closely related sequences, we generate a 55-state “Dayhoff-like” model that shows that the evolutionary properties of amino acids depend strongly upon side-chain geometry. The model performs as well as or better than traditional 20-state models for divergence time estimation, tree inference, and ancestral state reconstruction. We conclude that not only is rotamer configuration a valuable source of information for phylogenetic studies, but that modeling the concomitant evolution of sequence and structure may have important implications for understanding protein folding and function.
BioUML: an integrated environment for systems biology and collaborative analysis of biomedical data
Authors: Kolpakov Fedor , Akberdin Ilya , Kashapov Timur , Kiselev llya , Kolmykov Semyon , Kondrakhin Yury , Kutumova Elena , Mandrik Nikita , Pintus Sergey , Ryabova Anna , Sharipov Ruslan , Yevshin Ivan , Kel Alexander 
Published: May 2019

AbstractBioUML (homepage: http://www.biouml.org, main public server: https://ict.biouml.org) is a web-based integrated environment (platform) for systems biology and the analysis of biomedical data generated by omics technologies. The BioUML vision is to provide a computational platform to build virtual cell, virtual physiological human and virtual patient. BioUML spans a comprehensive range of capabilities, including access to biological databases, powerful tools for systems biology (visual modelling, simulation, parameters fitting and analyses), a genome browser, scripting (R, JavaScript) and a workflow engine. Due to integration with the Galaxy platform and R/Bioconductor, BioUML provides powerful possibilities for the analyses of omics data. The plug-in-based architecture allows the user to add new functionalities using plug-ins. To facilitate a user focus on a particular task or database, we have developed several predefined perspectives that display only those web interface elements that are needed for a specific task. To support collaborative work on scientific projects, there is a central authentication and authorization system (https://bio-store.org). The diagram editor enables several remote users to simultaneously edit diagrams.
Halo concentration, galaxy red fraction, and gas properties of optically defined merging clusters
Authors: Okabe Nobuhiro , Oguri Masamune , Akamatsu Hiroki , Hamabata Akinari , Nishizawa Atsushi J , Medezinski Elinor , Koyama Yusei , Hayashi Masao , Okabe Taizo , Ueda Shutaro , Mitsuishi Ikuyuki , Ota Naomi 
Published: May 2019

Abstract
We present multi-wavelength studies of optically defined merging clusters, based on the Hyper Suprime-Cam Subaru Strategic Program. Luminous red galaxies, tracing cluster mass distributions, enable us to identify cluster subhalos at various merging stages, and thus make a homogeneous sample of cluster mergers that is unbiased with respect to the merger boost of the intracluster medium (ICM). We define, using a peak-finding method, merging clusters with multiple peaks and single clusters with single peaks from the CAMIRA cluster catalog. Stacked weak-lensing analysis indicates that our sample of merging clusters is categorized into major mergers. The average halo concentration for the merging clusters is ∼70% smaller than that of the single-peak clusters, which agrees well with predictions of numerical simulations. The spatial distribution of subhalos is less centrally concentrated than the mass distribution of the main halo. The fractions of red galaxies in the merging clusters are not higher than those of the single-peak clusters. We find a signature of the merger boost of the ICM from the stacked Planck Sunyaev–Zel’dovich effect and ROSAT X-ray luminosity, but not in optical richness. The stacked X-ray surface brightness distribution, aligned with the main subhalo pairs of low-redshift and massive clusters, shows that the central gas core is elongated along the merger axis, and overall gas distribution is misaligned by ∼60°. The homogeneous, unbiased sample of cluster mergers and multi-wavelength follow-up studies provide a unique opportunity to make a complete picture of merger physics over the whole process.
AtCERK1 Phosphorylation Site S493 Contributes to the Transphosphorylation of Downstream Components for Chitin-Induced Immune Signaling
Authors: Suzuki Maruya , Yoshida Issei , Suto Kenkichi , Desaki Yoshitake , Shibuya Naoto , Kaku Hanae 
Published: May 2019

Abstract
While ligand-induced autophosphorylation of receptor-like kinases (RLKs) is known to be critical for triggering the downstream responses, biochemical mechanism by which each phosphorylation site contributes to the initiation of corresponding signaling cascades is only poorly understood, except the involvement of some phosphorylation sites in the regulation of catalytic activity of these RLKs. In this article, we first confirmed that the phosphorylation of S493 of AtCERK1 is involved in the regulation of chitin-induced defense responses by the complementation of an atcerk1 mutant with AtCERK1(S493A) cDNA. In vitro kinase assay with the heterologously expressed kinase domain of AtCERK1, GST-AtCERK1cyt, showed that the S493A mutation did not affect the autophosphorylation of AtCERK1 itself but diminished the transphosphorylation of downstream signaling components, PBL27 and PUB4. On the other hand, a phosphomimetic mutant, GST-AtCERK1(S493D)cyt, transphosphorylated these substrates as similar to the wild type AtCERK1. These results suggested that the phosphorylation of S493 does not contribute to the regulation of catalytic activity but plays an important role for the transphosphorylation of the downstream signaling components, thus contributing to the initiation of chitin signaling. To our knowledge, it is a novel finding that a specific phosphorylation site contributes to the regulation of transphosphorylation activity of RLKs. Further studies on the structural basis by which S493 phosphorylation contributes to the regulation of transphosphorylation would contribute to the understanding how the ligand-induced autophosphorylation of RLKs properly regulates the downstream signaling.
Automatic plankton quantification using deep features
Authors: González Pablo , Castaño Alberto , Peacock Emily E , Díez Jorge , Del Coz Juan José , Sosik Heidi M 
Published: May 2019

Abstract
The study of marine plankton data is vital to monitor the health of the world’s oceans. In recent decades, automatic plankton recognition systems have proved useful to address the vast amount of data collected by specially engineered in situ digital imaging systems. At the beginning, these systems were developed and put into operation using traditional automatic classification techniques, which were fed with hand-designed local image descriptors (such as Fourier features), obtaining quite successful results. In the past few years, there have been many advances in the computer vision community with the rebirth of neural networks. In this paper, we leverage how descriptors computed using convolutional neural networks trained with out-of-domain data are useful to replace hand-designed descriptors in the task of estimating the prevalence of each plankton class in a water sample. To achieve this goal, we have designed a broad set of experiments that show how effective these deep features are when working in combination with state-of-the-art quantification algorithms.
Impact of flare on radiographic progression after etanercept continuation, tapering or withdrawal in patients with rheumatoid arthritis
Authors: Smolen Josef S , Pedersen Ronald , Jones Heather , Mahgoub Ehab , Marshall Lisa 
Published: May 2019

Abstract

Objectives
The structural consequences of flare after dose reduction/discontinuation of biologic DMARDs in patients with RA who achieve remission are unclear. We compared the incidence of radiographic progression in patients with RA who did and did not experience flare after etanercept (ETN) reduction/withdrawal.

Methods
Eligible adults with moderately active RA despite MTX received ETN 50 mg plus MTX weekly in a 36-week, open-label induction period; patients achieving sustained low disease activity by week 36 were randomized to ETN 50 mg plus MTX, ETN 25 mg plus MTX, or placebo plus MTX in a 52-week, double-blind maintenance period. In post hoc analyses, radiographic progression (Δ modified total Sharp score ⩾0.5 units/year) was compared in patients with and without flare [based on DAS28 relapse (main analysis), and clinical disease activity index and simplified disease activity index relapse (sensitivity analyses)]. Findings from patients receiving full- and reduced-dose combination therapy were pooled for comparison with those from patients receiving MTX only.

Results
Significantly more patients receiving MTX monotherapy experienced flare, defined as DAS28 relapse (62% vs 21%; P &lt; 0.0001) and radiographic progression (17% vs 9%; P &lt; 0.001), than patients receiving full-/reduced-dose combination therapy in the double-blind period. Patients with flare defined as clinical disease activity index and simplified disease activity index relapse had higher rates of radiographic progression than those without flare in the full-/reduced-dose combination therapy group (P &lt; 0.01).

Conclusion
Radiographic progression may be a consequence of flare after biologic DMARD dose reduction/withdrawal in patients with RA. If these approaches are taken, careful monitoring for signs/symptoms of relapse is needed.

Trial registration
ClinicalTrials.gov, https://clinicaltrials.gov, NCT00565409.
Dissecting the functions of NIPBL using genome editing: The importance of the N-terminus of NIPBL in transcriptional regulation
Authors: Izumi Kosuke , Akiyama Kazuhiro , Fujiki Katsunori , Masuda Koji , Nakato Ryuichiro , Otsubo Aiko , Bando Masashige , Shirahige Katsuhiko 
Published: May 2019

ABSTRACTCornelia de Lange syndrome (CdLS) is characterized by craniofacial dysmorphisms, intellectual disabilities, growth retardation, and several other systemic abnormalities. CdLS is caused by heterozygous germline mutations in structural and regulatory components of cohesin. Mutations in NIPBL, which encodes regulatory subunit of cohesin, are frequently found in individuals with CdLS. CdLS is associated with a currently unknown mechanism of global transcriptional dysregulation. In this study, NIPBL mutants were generated using the CRISPR/Cas9 system to study this mechanism. Clones with a biallelic frameshift mutation in exon 3 of NIPBL, resulting in a truncated N-terminus, displayed transcriptional dysregulation without sister chromatid separation defects. Detailed transcriptome analysis revealed the overexpression of genes in NIPBL mutants that are typically expressed at low levels in wild type and the reduced expression of genes that are typically expressed at high levels in wild type. This result suggested that NIPBL plays a role in fine-tuning gene expression levels. MAU2 protein, that closely interacts with NIPBL, was nearly absent in these clones. The reduction of MAU2 observed in NIPBL mutants points to the importance of the NIPBL N-terminus/MAU2 interaction in transcriptional regulatory role of NIPBL.
Estimation of biodiversity metrics by environmental DNA metabarcoding compared with visual and capture surveys of river fish communities
Authors: Doi Hideyuki , Inui Ryutei , Matsuoka Shunsuke , Akamatsu Yoshihisa , Goto Masuji , Kono Takanori 
Published: May 2019

AbstractInformation on alpha (local), beta (between habitats), and gamma (regional) diversity is fundamental to understanding biodiversity as well as the function and stability of community dynamics. Methods like environmental DNA (eDNA) metabarcoding are currently considered useful to investigate biodiversity.We compared the performance of eDNA metabarcoding with visual and capture surveys for estimating alpha and gamma diversity of river fish communities, and nestedness and turnover in particular.In five rivers across west Japan, by comparison to visual/capture surveys, eDNA metabarcoding detected more species in the study sites (i.e., alpha diversity). Consequently the overall number of species in the region (i.e., gamma diversity) was higher. In particular, the species found by visual/capture surveys were encompassed by those detected by eDNA metabarcoding.Estimates of community diversity within rivers differed between survey methods. Although we found that the methods show similar levels of community nestedness and turnover within the rivers, visual/capture surveys showed more distinct community differences from upstream to downstream. Our results suggest that eDNA metabarcoding may be a suitable method for community assemblage analysis, especially for understanding regional community patterns, for fish monitoring in rivers.
Demonstration of different entity of appendicitis and related causes of disease through study of cluster/outbreak: Systematic Review and Meta Analysis
Authors: Guo Yi-Tian , Liu Guo-Zhen , Tan Shi-Yun , Guo Yi 
Published: May 2019

AbstractObjectiveTo demonstrate different entities of appendicitis and causal association between microbiota and different types of appendicitis through studying cluster/outbreak, and providing guidance to find new cluster/outbreak of appendicitis and the epidemiological evidences of infectious etiology of appendicitis.Data SourcesPubMed, Embase, CNKI, WanFang, VIP, CBM from their establishment to Jan, 2019, and the references lists from retrieved reports.Study EligibilityReports on cluster/outbreak of appendicitis and reports of case series occurring in cluster/outbreak worldwide according to CDC’s definition of cluster/outbreak.Data Extraction and SynthesisTwo researchers independently assessed report quality and extracted data according to Moose. We used random effect model for meta-analysis by Meta-Analyst ß3.13 software. Study-level assessment was conducted according to investigation methods introduced by Reingold and outcome-level assessment by GRADE system. We selected outcome measures before data collection began.ResultsWe included 10 clusters/outbreaks of appendicitis from China and USA with total 626 patients. We demonstrated two entities, type 1 appendicitis (455 patients) and type 2 appendicitis (151patients). 20 patients left were unclassified type. For type 1 appendicitis, Natural history showed progression from a non-perforated appendicitis to perforated appendicitis as described traditionally. More than 88% of patients had elevated body temperature, WBC and neutrophil percentage. For type 2 appendicitis, natural history showed that only a few patients developed into phlegmonous appendicitis (6.9%,) or acute gangrenous appendicitis (1.4%) and no perforation or periappendicular abscess. More than 78% of patients had normal body temperature, WBC and NP. The patients’ time of type 1 appendicitis is shorter than that of type 2 appendicitis. Type 2 appendicitis had different histological features from type 1 appendicitis and was associated with fusobacteria. 9 of 10 cluster/outbreak occurred in group living unity such as school and camps, and many of them showed features of infectious diseases. The bodies of evidence were high quality in Meta analysis.ConclusionCluster/outbreak of appendicitis is more often than expected worldwide and occurred in group living unity. Sporadic perforated appendicitis and non-perforated appendicitis may be not two different entities, but different stages of a same entity, which is inconsistent with modern classification of appendicitis. Type 2 appendicitis is a new entities. Studying cluster/outbreak is a new method in finding of new entity and causal association between microbiota and different types of appendicitis. Epidemiological evidence supported infectious etiology of appendicitis.
Emergence and Genetic Analysis of Avian Gyrovirus 2 Variants-RelatedGyrovirusin Farmed King-ratsnakes (Elaphe carinata): the First Report in China
Authors: Wu Qianqian , Chen Qinxi , Hu Wen , Wang Xueyu , Ji Jun 
Published: May 2019

ABSTRACTAvian gyrovirus 2 (AGV2), which is similar to chicken infectious anemia virus, is a new member of theCircovirusgenus. AGV2 has been detected not only in chicken but also in human tissues and feces. In this study, a total of 91 samples (8 liver tissues and 83 faecal samples) collected from king-ratsnakes (Elaphe carinata) at 7 separate farms in Hubei and Henan, China, were analyzed to detect AGV2 DNA via specific PCR. The results indicated a low positive rate of AGV2 (6.59%, 6/91) in the studied animals, and all of the positive samples were from the same farm. The AGV2 strain HB2018S1 was sequenced, and the genome with a total length of 2376 nt contained three partially overlapping open reading frames: VP1, VP2, and VP3. Phylogenetic tree analysis revealed that the HB2018S1, NX1506-1 strain from chickens in China belong to the same clade, with nucleotide homology as high as 99.5%. In total, 10 amino acid mutation sites, including 44R/K, 74T/A, 256 C/R, 279L/Q, and 373V/A in AGV2 VP1; 60I/T, 125T/I, 213D/N, and 215L/S in AGV2 VP2; and 83H/Y in AGV2 VP3, were found in the genome of HB2018S1 that were different from those observed in most reference strains, suggesting that the differences are related to an transboundary movement among hosts which needs to be further elucidated.IMPORTANCERecently, AGV2 has been detected in live poultry markets and human blood in mainland China. Previous findings indicated future studies should investigate the large geographic distribution of AGV2 and monitor the variants, the host range, and the associated diseases. To the best of our knowledge, this study is the first report on AGV2 infected poikilotherm, suggested that cross-host transmission of viruses with circular single-stranded DNA genomes would be a public health concern.
How well do routine molecular diagnostics detect rifampicin heteroresistance inMycobacterium tuberculosis?
Authors: Ng Kamela C. S. , Supply Philip , Cobelens Frank G. J. , Gaudin Cyril , Gonzalez-Martin Julian , de Jong Bouke C. , Rigouts Leen 
Published: May 2019

ABSTRACTRifampicin heteroresistance – where rifampicin-resistant and -susceptible tuberculosis (TB) bacilli co-exist – may result in failed standard TB treatment and potential spread of rifampicin-resistant strains. Detection of rifampicin heteroresistance in routine rapid diagnostic tests (RDTs) allows for patients to receive prompt and effective multidrug-resistant-TB treatment, and may improve rifampicin-resistant TB control.The limit of detection (LOD) of rifampicin heteroresistance for phenotypic drug susceptibility testing by the proportion method is 1%, yet is insufficiently documented for RDTs. We therefore aimed to determine, for the four RDTs (XpertMTB/RIF, XpertMTB/RIF Ultra, GenoTypeMTBDRplusv2.0, and GenoscholarNTM+MDRTBII), the LOD per probe and mutation, validated by colony-forming-unit-counting and targeted deep sequencing (Deeplex-MycTB).We selected one rifampicin-susceptible and four rifampicin-resistant strains, with mutation D435V, H445D, H445Y, and S450L respectively, mixed them in various proportions in triplicate, tested them with each RDT, and determined the LODs per mutation type. Deeplex-MycTB revealed concordant proportions of the minority resistant variants in the mixtures. The Deeplex-MycTB-validated-LODs ranged from 20-80% for XpertMTB/RIF, 20-70% for Xpert Ultra, 5-10% for GenoTypeMTBDRplusv2.0, and 1-10% for GenoscholarNTM+MTBII for the different mutations.Deeplex-MycTB, GenoTypeMTBDRplusv2.0, and GenoscholarNTM+MDRTBII, provide explicit information on rifampicin heteroresistance for the most frequently detected mutations. Classic Xpert and Ultra report rifampicin heteroresistance as rifampicin resistance, while Ultra may denote rifampicin heteroresistance through ‘mixed patterns’ of wild-type and mutant melt probe melt peak temperatures.Overall, our findings inform end-users that the threshold for reporting resistance in case of rifampicin heteroresistance is the highest for Classic Xpert and Ultra, to resolve phenotypic and genotypic discordant rifampicin-resistant TB results.
Novel cytokinetic ring components drive negative feedback in cortical contractility
Authors: Bell Kathryn Rehain , Werner Michael E. , Doshi Anusha , Cortes Daniel B. , Sattler Adam , Vuong-Brender Thanh , Labouesse Michel , Maddox Amy Shaub 
Published: May 2019

AbstractActomyosin cortical contractility drives many cell shape changes including cytokinetic furrowing. While positive regulation of contractility is well characterized, counterbalancing negative regulation and mechanical brakes are less well understood. The small GTPase RhoA is a central regulator, activating cortical actomyosin contractility during cytokinesis and other events. Here we report how two novel cytokinetic ring components, GCK-1 and CCM-3, participate in a negative feedback loop among RhoA and its cytoskeletal effectors to inhibit contractility. GCK-1 and CCM-3 are recruited by active RhoA and anillin to the cytokinetic ring, where they in turn limit RhoA activity and contractility. This is evidenced by increased RhoA activity, anillin and non-muscle myosin II in the cytokinetic ring, and faster cytokinetic furrowing, following depletion of GCK-1 or CCM-3. GCK-1 or CCM-3 depletion also reduced RGA-3 levels in pulses, and increased baseline RhoA activity and pulsed contractility during zygote polarization. Together, our findings suggest that GCK-1 and CCM-3 regulate cortical actomyosin contractility via negative feedback.SummaryNovel cytokinetic ring proteins, the Ste20 family kinase GCK-1 and its heterodimeric cofactor Cerebral Cavernous Malformations-3, close a negative feedback loop involving the RhoA GAP RGA-3/4, RhoA, and its cytoskeletal effector anillin to limit actomyosin contractility in cytokinesis and during polarization of the C. elegans zygote.