bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of SARS-CoV-2 in the first COVID-19 cluster in France reveals an amino-acid deletion in nsp2 (Asp268Del)
Authors: Bal Antonin , Destras Grégory , Gaymard Alexandre , Bouscambert-Duchamp Maude , Valette Martine , Escuret Vanessa , Frobert Emilie , Billaud Geneviève , Trouillet-Assant Sophie , Cheynet Valérie , Brengel-Pesce Karen , Morfin Florence , Lina Bruno , Josset Laurence 
Published: March 2020

AbstractWe present the first genetic characterization of a COVID-19 cluster in Europe using metagenomic next-generation sequencing (mNGS). Despite low viral loads, the mNGS workflow used herein allowed to characterize the whole genome sequences of SARS-CoV2 isolated from an asymptomatic patient, in 2 clinical samples collected 1 day apart. Comparison of these sequences suggests viral evolution with development of quasispecies. In addition, the present workflow identified a new deletion in nsp2 (Asp268Del) which was found in all 3 samples originating from this cluster as well as in 37 other viruses collected in England and in Netherlands, suggesting the spread of this deletion in Europe. The impact of Asp268Del on SARS-CoV-2 transmission and pathogenicity, as well as on PCR performances and anti-viral strategy should be rapidly evaluated in further studies.
Genomic Surveillance ofPseudomonas aeruginosain the Philippines from 2013-2014
Authors: Chilam Jeremiah , Argimón Silvia , Limas Marilyn T. , Masim Melissa L. , Gayeta June M. , Lagrada Marietta L. , Olorosa Agnettah M. , Cohen Victoria , Hernandez Lara T. , Jeffrey Benjamin , Abudahab Khalil , Hufano Charmian M. , Sia Sonia B. , Holden Matthew T.G. , Stelling John , Aanensen David M. , Carlos Celia C. ,   on behalf of the Philippines Antimicrobial Resistance Surveillance Program
Published: March 2020

AbstractPseudomonas aeruginosais an opportunistic pathogen often causing nosocomial infections that are resilient to treatment due to an extensive repertoire of intrinsic and acquired resistance mechanisms. In recent years, increasing resistance rates to antibiotics such as carbapenems and extended-spectrum cephalosporins have been reported, as well as multi-drug resistant and possible extremely drug-resistant rates of approximately 21% and 15%, respectively. However, the molecular epidemiology and AMR mechanisms of this pathogen remains largely uncharacterized.We sequenced the whole genomes of 176P. aeruginosaisolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.Carbapenem resistance was associated namely with loss-of function of the OprD porin, and acquisition of the metallo-β-lactamase VIM. The concordance between phenotypic and genotypic resistance was 93.27% overall for 6 antibiotics in 3 classes, but varied widely between aminoglycosides. The population ofP. aeruginosain the Philippines was diverse, with clonal expansions of XDR genomes belonging to multi-locus sequence types ST235, ST244, ST309, and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, as well as transfer between hospitals. Most of the ST235 genomes formed a distinct Philippine lineage when contextualized with international genomes, thus raising the possibility that this is a lineage unique to the Philippines. This was further supported by long-read sequencing of one representative XDR isolate, which revealed the presence of an integron carrying multiple resistance genes, includingblaVIM-2, with differences in gene composition and synteny to otherP. aeruginosaclass 1 integrons described before.We produced the first comprehensive genomic survey ofP. aeruginosain the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance. Our results also highlight the importance of infection control interventions aimed to curtail the spread of international epidemic clone ST235 within the country.
Evaluating institutional open access performance: Methodology, challenges and assessment
Authors: Huang Chun-Kai , Neylon Cameron , Hosking Richard , Montgomery Lucy , Wilson Katie , Ozaygen Alkim , Brookes-Kenworthy Chloe 
Published: March 2020

AbstractOpen Access to research outputs is becoming rapidly more important to the global research community and society. Changes are driven by funder mandates, institutional policy, grass-roots advocacy and culture change. It has been challenging to provide a robust, transparent and updateable analysis of progress towards open access that can inform these interventions, particularly at the institutional level. Here we propose a minimum reporting standard and present a large-scale analysis of open access progress across 1,207 institutions world-wide that shows substantial progress being made. The analysis detects responses that coincide with policy and funding interventions. Among the striking results are the high performance of Latin American and African universities, particularly for gold open access, whereas overall open access levels in Europe and North America are driven by repository-mediated access. We present a top-100 of global universities with the world’s leading institutions achieving around 80% open access for 2017 publications.
Genomic Surveillance of Methicillin-ResistantStaphylococcus aureusin the Philippines from 2013-2014
Authors: Masim Melissa L. , Argimón Silvia , Espiritu Holly O. , Magbanua Mariane A. , Lagrada Marietta L. , Olorosa Agnettah M. , Cohen Victoria , Gayeta June M. , Jeffrey Benjamin , Abudahab Khalil , Hufano Charmian M. , Sia Sonia B. , Holden Matthew T.G. , Stelling John , Aanensen David M. , Carlos Celia C. ,   on behalf of the Philippines Antimicrobial Resistance Surveillance Program
Published: March 2020

AbstractMethicillin ResistantStaphylococcus aureus(MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about theS. aureuscirculating clones in the Philippines.We sequenced the whole genomes of 116S. aureusisolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type,spatype, SCC-mectype, presence of antimicrobial resistance (AMR) determinants and virulence genes, and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.The MRSA population in the Philippines was composed of a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV, and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South West Pacific clone, but formed a distinct and diverse lineage, with evidence of global dissemination. We showed the independent acquisition of resistance to sulfamethoxazole/trimethoprim across different locations and genetic clones, but mostly in pediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for 8 antibiotics in 7 classes.We produced the first comprehensive genomic survey ofS. aureusin the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance.
Genomic surveillance ofNeisseria gonorrhoeaein the Philippines, 2013–2014
Authors: Jamoralin Manuel C. , Argimón Silvia , Lagrada Marietta L. , Villamin Alfred S. , Masim Melissa L. , Gayeta June M. , Boehme Karis D. , Olorosa Agnettah M. , Sia Sonia B. , Hufano Charmian M. , Cohen Victoria , Hernandez Lara T. , Jeffrey Benjamin , Abudahab Khalil , Stelling John , Holden Matthew T.G. , Aanensen David M. , Carlos Celia C. 
Published: March 2020

AbstractAntimicrobial-resistantNeisseria gonorrhoeaeis a major threat to public health and is of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but genomic epidemiology studies on this pathogen are lacking in the Philippines.We sequenced the whole genomes of 21N. gonorrhoeaeisolates collected in 2013–2014 by the ARSP. The multilocus sequence type, multiantigen sequence type, presence of determinants of antimicrobial resistance and relatedness among the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.Ten of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, due mainly to the presence ofblaTEMgene, the S91F mutation in thegyrAgene and thetetMgene, respectively. None of the isolates was resistant to ceftriaxone or cefixime. The concordance between phenotypic and genotypic resistance was 92.38% overall for five antibiotics in four classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, theN. gonorrhoeaemultiantigen sequence typing types and the tree. Comparison with global genomes placed the Philippine genomes within global lineage A and led to identification of an international transmission route.This first genomic survey ofN. gonorrhoeaeisolates collected by ARSP will be used to contextualize prospective surveillance. It highlights the importance of genomic surveillance in the Western Pacific and other endemic regions for understanding the spread of drug-resistant gonorrhoea worldwide.
Evaluating institutional open access performance: Sensitivity analysis
Authors: Huang Chun-Kai , Neylon Cameron , Hosking Richard , Montgomery Lucy , Wilson Katie , Ozaygen Alkim , Brookes-Kenworthy Chloe 
Published: March 2020

AbstractIn the article “Evaluating institutional open access performance: Methodology, challenges and assessment” we develop the first comprehensive and reproducible workflow that integrates multiple bibliographic data sources for evaluating institutional open access (OA) performance. The major data sources include Web of Science, Scopus, Microsoft Academic, and Unpaywall. However, each of these databases continues to update, both actively and retrospectively. This implies the results produced by the proposed process are potentially sensitive to both the choice of data source and the versions of them used. In addition, there remain the issue relating to selection bias in sample size and margin of error. The current work shows that the levels of sensitivity relating to the above issues can be significant at the institutional level. Hence, the transparency and clear documentation of the choices made on data sources (and their versions) and cut-off boundaries are vital for reproducibility and verifiability.
Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment
Authors: Baryawno Ninib , Kfoury Youmna , Severe Nicolas , Mei Shenglin , Gustafsson Karin , Hirz Taghreed , Brouse Thomas , Scadden Elizabeth W. , Igolkina Anna A. , Choi Bryan D. , Barkas Nikolas , Shin John H. , Saylor Philip J. , Scadden David T. , Sykes David B. , Kharchenko Peter V. ,   as part of the Boston Bone Metastasis Consortium
Published: March 2020

AbstractBone metastases are devastating complications of cancer. They are particularly common in prostate cancer, represent incurable disease and are refractory to immunotherapy. We sought to define distinct features of the bone marrow microenvironment by analyzing single cells from prostate cancer patients’ involved bone, uninvolved bone and distant bone sites as well as bone from cancer-free, orthopedic patients and healthy individuals. Metastatic prostate cancer was associated with multifaceted immune distortion, specifically exhaustion of distinct T cell subsets, appearance of macrophages with states specific to prostate cancer bone metastases. The chemokine CCL20 was notably overexpressed by myeloid cells, as was its cognate CCR6 receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic prostate bone metastases restored T cell reactivity and significantly prolonged animal survival. Comparative high resolution analysis of prostate cancer bone metastasis shows a targeted approach for relieving local immunosuppression for therapeutic effect.
All-in-One Dual CRISPR-Cas12a (AIOD-CRISPR) Assay: A Case for Rapid, Ultrasensitive and Visual Detection of Novel Coronavirus SARS-CoV-2 and HIV virus
Authors: Ding Xiong , Yin Kun , Li Ziyue , Liu Changchun 
Published: March 2020

AbstractA recent outbreak of novel coronavirus (SARS-CoV-2), the causative agent of COVID-19, has spread rapidly all over the world. Human immunodeficiency virus (HIV) is another deadly virus and causes acquired immunodeficiency syndrome (AIDS). Rapid and early detection of these viruses will facilitate early intervention and reduce disease transmission risk. Here, we present anAll-In-OneDualCRISPR-Cas12a (termed “AIOD-CRISPR”) assay method for simple, rapid, ultrasensitive, one-pot, and visual detection of coronavirus SARS-CoV-2 and HIV virus. In our AIOD CRISPR assay, a pair of crRNAs was introduced to initiate dual CRISPR-Cas12a detection and improve detection sensitivity. The AIOD-CRISPR assay system was successfully utilized to detect nucleic acids (DNA and RNA) of SARS-CoV-2 and HIV with a sensitivity of few copies. Also, it was evaluated by detecting HIV-1 RNA extracted from human plasma samples, achieving a comparable sensitivity with real-time RT-PCR method. Thus, our method has a great potential for developing next-generation point-of-care molecular diagnostics.
Mutational synergy coordinately remodels chromatin accessibility, enhancer landscape and 3-Dimensional DNA topology to alter gene expression during leukemia induction
Authors: Yun Haiyang , Vohra Shabana , Mupo Annalisa , Giotopoulos George , Sasca Daniel , Horton Sarah J. , Agrawal-Singh Shuchi , Meduri Eshwar , Basheer Faisal , Marando Ludovica , Gozdecka Malgorzata , Dovey Oliver M. , Castillo-Venzor Aracely , Wang Xiaonan , Gallipoli Paolo , Müller-Tidow Carsten , Osborne Cameron S. , Vassiliou George S. , Huntly Brian J. P. 
Published: March 2020

AbstractAltered transcription is a cardinal feature of acute myeloid leukemia (AML), however, exactly how mutations synergize to remodel the epigenetic landscape and rewire 3-Dimensional (3-D) DNA topology is unknown. Here we apply an integrated genomic approach to a murine allelic series that models the two most common mutations in AML,Flt3-ITD andNpm1c. We then deconvolute the contribution of each mutation to alterations of the epigenetic landscape and genome organization, and infer how mutations synergize in the induction of AML. These analyses allow the identification of long-rangecis-regulatory circuits, including a novel super-enhancer of theHoxalocus, as well as larger and more detailed gene-regulatory networks, whose importance we demonstrate through perturbation of network members.
Biochemical paedomorphosis and genetic assimilation in the hypoxia adaptation of Tibetan antelope
Authors: Signore Anthony V. , Storz Jay F. 
Published: March 2020

AbstractDevelopmental shifts in stage-specific gene expression can provide a ready mechanism of phenotypic change by altering the rate or timing of ontogenetic events. We discovered that the high-altitude Tibetan antelope (Panthelops hodgsonii) has evolved an adaptive increase in blood–O2affinity by truncating the ancestral ontogeny of globin gene expression such that a high-affinity juvenile hemoglobin isoform (isoHb) completely supplants the lower-affinity isoHb that is expressed in the adult red blood cells of other bovids. This juvenilization of blood properties represents a canalization of an acclimatization response to hypoxia that has been well-documented in adult goats and sheep. We also discovered the genomic mechanism underlying this regulatory isoHb switch, revealing how a reversible acclimatization response became genetically assimilated as an irreversible adaptation to chronic hypoxia.
The Irish potato famine pathogen subverts host vesicle trafficking to channel starvation-induced autophagy to the pathogen interface
Authors: Pandey Pooja , Leary Alexandre Y , Tümtas Yasin , Savage Zachary , Dagvadorj Bayantes , Tan Emily , Khandare Virendrasinh , Duggan Cian , Yusunov Temur , Madalinski Mathias , Mirkin Federico Gabriel , Schornack Sebastian , Dagdas Yasin , Kamoun Sophien , Bozkurt Tolga O. 
Published: March 2020

SummaryEukaryotic cells deploy autophagy to eliminate invading microbes. In turn, pathogens have evolved effector proteins to counteract antimicrobial autophagy. How and why adapted pathogens co-opt autophagy for their own benefit is poorly understood. The Irish famine pathogen Phythophthora infestans secretes the effector protein PexRD54 that selectively activates an unknown plant autophagy pathway, while antagonizing antimicrobial autophagy. Here we show that PexRD54 induces autophagosome formation by bridging small GTPase Rab8a-decorated vesicles with autophagic compartments labelled by the core autophagy protein ATG8CL. Rab8a is required for pathogen-triggered and starvation-induced but not antimicrobial autophagy, revealing that specific trafficking pathways underpin selective autophagy. We discovered that Rab8a contributes to basal immunity against P. infestans, but PexRD54 diverts a sub-population of Rab8a vesicles to lipid droplets that associate with autophagosomes. These are then diverted towards pathogen feeding structures that are accommodated within the host cells. We propose that PexRD54 mimics starvation-induced autophagy by channeling host endomembrane trafficking towards the pathogen interface possibly to acquire nutrients. This work reveals that effectors can interconnect independent host compartments to stimulate complex cellular processes that benefit the pathogen.Graphical abstract
Presynaptically silent synapses are modulated by the density of surrounding astrocytes
Authors: Oyabu Kohei , Takeda Kotomi , Kawano Hiroyuki , Kubota Kaori , Watanabe Takuya , Harata N. Charles , Katsurabayashi Shutaro , Iwasaki Katsunori 
Published: March 2020

ABSTRACTThe astrocyte, a major glial cell type, is involved in formation and maturation of synapses, and thus contributes to sustainable synaptic transmission between neurons. Given that the animals in the higher phylogenetic tree have brains with higher density of glial cells with respect to neurons, there is a possibility that the relative astrocytic density directly influences synaptic transmission. However, the notion has not been tested thoroughly. Here we addressed it, by using a primary culture preparation where single hippocampal neurons are surrounded by a variable but countable number of cortical astrocytes in dot-patterned microislands, and recording synaptic transmission by patch-clamp electrophysiology. Neurons with a higher astrocytic density showed a higher amplitude of evoked excitatory postsynaptic current (EPSC) than that of neurons with a lower astrocytic density. The size of readily releasable pool of synaptic vesicles per neuron was significantly higher. The frequency of spontaneous synaptic transmission (miniature EPSC) was higher, but the amplitude was unchanged. The number of morphologically identified glutamatergic synapses was unchanged, but the number of functional ones was increased, indicating a lower ratio of presynaptically silent synapses. Taken together, the higher astrocytic density enhanced excitatory synaptic transmission by increasing the number of functional synapses through presynaptic un-silencing.
The mid-lateral cerebellum is necessary for reinforcement learning
Authors: Sendhilnathan Naveen , Goldberg Michael E. 
Published: March 2020

SummaryThe cerebellum has long been considered crucial for supervised motor learning and its optimization1-3. However, new evidence has also implicated the cerebellum in reward based learning4-8, executive function9-12, and frontal-like clinical deficits13. We recently showed that the simple spikes of Purkinje cells (P-cells) in the mid-lateral cerebellar hemisphere (Crus I and II) encode a reinforcement error signal when monkeys learn to associate arbitrary symbols with hand movements4. However, it is unclear if the cerebellum is necessary for any process beyond motor learning. To investigate if the mid-lateral cerebellum is actually necessary for learning visuomotor associations, we reversibly inactivated the mid-lateral cerebellum of two primates with muscimol while they learned to associate arbitrary symbols with hand movements. Here we show that cerebellar inactivation impaired the monkey’s ability to learn new associations, although it had no effect on the monkeys’ performance on a task with overtrained symbols. A computational model corroborates our results. Cerebellar inactivation increased the reaction time, but there were no deficits in any motor kinematics such as the hand movement, licking or eye movement. There was no loss of function when we inactivated a more anterior region of the cerebellum that is implicated in motor control. We suggest that the mid-lateral cerebellum, which provides a reinforcement learning error signal4, is necessary for visuomotor association learning. Our results have implications for the involvement of cerebellum in cognitive control, and add critical constraints to brain models of non-motor learning14,15.
Isolation and genome sequencing of 14Spongiasp. bacterial associates expands the taxonomic and functional breadth of the cultivatable marine sponge microbiome
Authors: Karimi Elham , Costa Rodrigo 
Published: March 2020

AbstractMarine sponges live with complex microbial consortia, which have been considered as potential sources of novel natural products. However, the usual recalcitrance of host-associated microorganisms to cultivation makes studying sponge symbionts challenging. To tackle this complexity, exploration of cultivated sponge-associated bacteria and their coding potential is unavoidable. In this study, we isolate and report the draft genome sequences of 14 bacterial strains from the marine spongeSpongiasp. using R2A and VXA media. The strains belong to the classesActinobacteria, Gammaproteobacteria, Alphaproteobacteria,andCytophagiaspanning 11 formally described genera plus two potentially novel genera in theRhodobacteraceaefamily and one potentially novel family in theCytophagalesorder. Functional genomics revealed presumed symbiosis factors typical of specific taxonomic groups (i.e. taurine metabolism genes among theAlphaproteobacteria,chitinase encoding genes and eukaryotic-like proteins in theCytophagiagenome) while multidrug efflux pumps, also important in host-microbe interactions, were common across all genomes. Moreover, we detected 76 secondary-metabolite biosynthetic gene clusters putatively involved in the production of drug-like compounds or signalling molecules across all genomes, warranting future biotechnologically driven research into their coding potential.