bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Genomic Analysis of Fifty-TwoStaphylococcus aureusIsolates Identified from Uncharacterized Staphylococcus Genomes in the NCBI database
Authors: Abouelkhair Mohamed A. 
Published: June 2020

AbstractBackgroundStaphylococcus aureusis a major bacterial pathogen that causes a variety of diseases, ranging from wound infections to severe bacteremia or food poisoning. The course and severity of the disease are mainly dependent on the bacterium genotype as well as host factors. Whole-genome sequencing (WGS) is currently the most extensive genotyping method available, followed by bioinformatic sequence analysis.MethodsA total of 253 uncharacterized staphylococcus genome sequences were downloaded from the National Center for Biotechnology Information (NCBI) (August 2012 to March 2020) from different studies. Samples were clustered based on core and accessory pairwise distances between isolates and then analyzed by multilocus sequence typing tool (MLST). Staphylococcal Cassette Chromosomemec(SCCmec), spa typing, variant calling, core genome alignment, and recombination sites prediction were performed on detectedS. aureusisolates.S. aureusisolates were also analyzed for the presence of genes coding for virulence factors and antibiotic resistance.Results and conclusionUncategorized genome sequences were clustered into 24 groups. About 182 uncharacterized Staphylococcus genomes were identified at the species level based on MLST, including 32S. lugdunensisgenome sequence, thus doubling the number of the publicly accessibleS. lugdunensisgenome sequence in Genbank. MLST identified another four species (S. epidermidis(33/253),S. lugdunensis(32/253),S. haemolyticus(41/253),S. hominis(24/253)and S. aureus(52/253)). Among the 52S. aureusisolates, 21 (40.38%) isolates carriedmecA gene, with 57.14% classified as SCCmecIV. The results of this study provide knowledge that facilitates evolutionary studies of staphylococcal species and other bacteria at the genome level.
The influence of axial length upon the retinal ganglion cell layer of the human eye
Authors: Chen Min , Nofziger Jill , Datta Ritobrato , Gee James C. , Morgan Jessica , Aguirre Geoffrey K 
Published: June 2020

AbstractPurposeWe examined the relationship between axial length and the thickness and volume of the ganglion cell layer (GCL) of the retina, and related these measures to the size of the optic chiasm.MethodsWe used optical coherence tomography to measure the thickness of the GCL over a 50° extent of the horizontal meridian in 50 normally-sighted participants with a wide range of axial lengths. Using a model eye informed by individual biometry, we converted GCL thickness to tissue volume per square degree. The volume of the optic chiasm was measured for 40 participants using magnetic resonance imaging.ResultsWhile GCL thickness decreases with increasing axial length, there is a positive relationship between GCL tissue volume and axial length, leading us to conclude that increasing axial length is associated with decreased retinal ganglion cell packing, increased cell size, or both. We characterize how retinal ganglion cell tissue varies systematically in volume and spatial distribution as a function of axial length. This model allows us to remove the effect of axial length from individual difference measures of GCL volume. We find that variation in GCL volume correlates well with the size of the optic chiasm as measured using magnetic resonance imaging.ConclusionsOur results provide the volume of ganglion cell tissue in the retina, adjusted for the effects of axial length upon ganglion cell size and/or packing. The resulting volume measure accounts for individual differences in the size of the optic chiasm, supporting its use to characterize the post-retinal visual pathway.
A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death and modulation of growth and synaptic assembly
Authors: Iqbal Fahad , Pehar Marcus , Thompson Andrew J. , Azeem Urva , Jahanbakhsh Kiana , Jimenez-Tellez Nerea , Sabouny Rasha , Batool Shadab , Syeda Atika , Chow Jennifer , Machiraju Pranav , Shutt Timothy , Yusuf Kamran , Shearer Jane , Rice Tiffany , Syed Naweed I. 
Published: June 2020

AbstractAnesthetics, although necessary for many modern procedures, exert neurotoxic effects in various experimental models; the underlying mechanisms, however, remain unknown. In the absence of this information, anyin vivomitigation strategy would be challenging. To help address these gaps, we sought to determine whether preserving mitochondrial network integrity with a non-toxic, short-life synthetic peptide, P110, could protect cortical neurons against both inhalational and intravenous anesthetic-induced neurotoxicity. This study provides the first direct comparative account of three key general anesthetics (desflurane, propofol, and ketamine) under identical conditions and demonstrates their impact on cellular viability, neurite outgrowth, and synaptic network assembly on neonatal rat cortical neurons. Further, we discovered that the inhibition of Fis1 receptor-mediated fission reverses anesthetic-induced aberrations in an agent-specific manner. Our data thus underscore the importance of a reductionist approach, offering unique opportunities to explore non-toxic, mitochondria-based therapeutic tools for mitigating anesthetic-induced harm to the developing brain.
Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart
Authors: Brennan Jaclyn A. , Chen Qing , Gams Anna , Dyavanapalli Jhansi , Mendelowitz David , Peng Weiqun , Efimov Igor R. 
Published: June 2020

AbstractThe initiation of rhythmic heartbeat is the earliest manifestation of new life after conception. A normal heartbeat originates as an action potential in a group of pacemaker cells of the sinoatrial node (SAN)1. Pacemaker cells are evident since early embryogenesis when the entire sinus venosus exhibits electric automaticity and possesses specific gene expression profile distinct from that of working myocardium2,3. During the subsequent looping and ballooning stages of cardiac development, pacemaker cells eventually localize into SAN near the superior vena cava (SVC) when the two horns of the sinus venosus coil in formation of the atria2. The heart rate and anatomical site of origin of pacemaker activity dynamically change in response to various physiological input such as autonomic stimuli and pharmacological interventions4. However, the mechanisms of dominant pacemaker shift are not well understood. Here, we present functional and molecular evidence of two competing right atrial pacemakers localized near the SVC and the inferior vena cava (IVC), which we call the superior and inferior SANs: sSAN and iSAN. Usingex vivooptical mapping techniques and RNA sequencing of rat and human hearts, we demonstrate that sSAN and iSAN preferentially control the fast and slow heart rates during sympathetic or parasympathetic stimulation, respectively. RNAseq confirmed unique transcriptional profiles of sSAN and iSAN, which differs from both atria and ventricles. We speculate that the anatomical locations of sSAN and iSAN are a result of the way the two horns of the sinus venosus twist into a mature chambered heart. We anticipate these findings would clarify previously observed migration of dominant pacemaker and corresponding changes in P-wave morphology in many species. Furthermore, we expect these findings will shed light onto pathogenesis of aberrant pacemakers responsible for life-threatening arrhythmias near orifices of other major vessels: SVC and IVC, coronary sinus, pulmonary veins, aorta and the right ventricular outflow tract.
Using rat operant delayed match-to-sample task to identify neural substrates recruited with increased working memory load
Authors: Gobin Christina , Wu Lizhen , Schwendt Marek 
Published: June 2020

AbstractThe delayed match-to-sample task (DMS) is used to probe working memory (WM) across species. While the involvement of the PFC in this task has been established, limited information exists regarding the recruitment of broader circuitry, especially under the low- versus high-WM load. We sought to address this question by using a variable-delay operant DMS task. Male Sprague-Dawley rats were trained and tested to determine their baseline WM performance across all (0-24s) delays. Next, rats were tested in a single DMS test with either 0s or 24s fixed delay, to assess low-/high-load WM performance.c-FosmRNA expression was quantified within cortical and subcortical regions and correlated with WM performance. High WM load upregulated overallc-FosmRNA expression within the PrL, as well as within a subset of mGlu5+ cells, with load-dependent, local activation of protein kinase C as the proposed underlying molecular mechanism. The PrL activity negatively correlated with choice accuracy during high load WM performance. A broader circuitry, including several subcortical regions, was found to be activated under low and/or high load conditions. These findings highlight the role of mGlu5 and/or PKC dependent signaling within the PrL, and corresponding recruitment of subcortical regions during high-load WM performance.
Drosophilamodel of Anti-retroviral therapy Induced Peripheral Neuropathy and Nociceptive Hypersensitivity
Authors: Bush Keegan M. , Barber Kara R. , Martinez Jade A. , Tang Shao-Jun , Wairkar Yogesh P. 
Published: June 2020

AbstractThe success of antiretroviral therapy (ART) has improved the survival of HIV-infected patients significantly. However, significant numbers of patients on ART whose HIV disease is well controlled show peripheral sensory neuropathy (PSN), suggesting that ART may cause PSN. Although the nucleoside reverse transcriptase inhibitors (NRTIs), one of the vital components of ART, are thought to contribute to PSN, the mechanisms underlying the PSN induced by NRTIs are unclear. In this study, we developed aDrosophilamodel of NRTI-induced PSN that recapitulates the salient features observed in patients undergoing ART: PSN and nociceptive hypersensitivity. Furthermore, our data demonstrate that pathways known to suppress PSN induced by chemotherapeutic drugs are ineffective in suppressing the PSN or nociception induced by NRTIs. Instead, we found that increased dynamics of a peripheral sensory neuron may underlie NRTI-induced PSN and nociception. Our model provides a solid platform in which to investigate further mechanisms of ART-induced PSN and nociceptive hypersensitivity.
Phenome-scale causal network discovery with bidirectional mediated Mendelian randomization
Authors: Brown Brielin C. , Knowles David A. 
Published: June 2020

AbstractInference of directed biological networks from observational genomics datasets is a crucial but notoriously difficult challenge. Modern population-scale biobanks, containing simultaneous measurements of traits, biomarkers, and genetic variation, offer an unprecedented opportunity to study biological networks. Mendelian randomization (MR) has received attention as a class of methods for inferring causal effects in observational data that uses genetic variants as instrumental variables, but MR methods rely on assumptions that limit their application to complex traits at the biobank-scale. Moreover, MR estimates the total effect of one trait on another, which may be mediated by other factors. Biobanks include measurements of many potential mediators, in principle enabling the conversion of MR estimates into direct effects representing a causal network. Here, we show that this can be accomplished by a flexible two stage procedure we callbidirectional mediated Mendelian randomization(bimmer). First, bimmer estimates the effect of every trait on every other. Next, bimmer finds a parsimonious network that explains these effects using direct and mediated causal paths. We introduce novel methods for both steps and show via extensive simulations that bimmer is able to learn causal network structures even in the presence of non-causal genetic correlation. We apply bimmer to 405 phenotypes from the UK biobank and demonstrate that learning the network structure is invaluable for interpreting the results of phenome-wide MR, while lending causal support to several recent observational studies.
Environmental conditions define the energetics of bacterial dormancy and its antibiotic susceptibility
Authors: Mancini L , Pilizota T 
Published: June 2020

ABSTRACTBacterial cells that stop growing but maintain viability and the capacity to regrow are termed dormant and have been shown to transiently tolerate high concentrations of antimicrobials. The proposed mechanism behind the enhanced survival capabilities of these cells is the reduced energy supply. However, not all reported results are in agreement, and the exact role of energetics remains unsolved. Because dormancy merely indicates growth arrest, which can be induced by various stimuli, we hypothesise that dormant cells may exist in a range of energetic states that depend on the environment. We first establish conditions that are capable of inducing dormancy, and subsequently measure the energy profiles they elicit in single dormant cells. Our simultaneous measurements of proton motive force (PMF), cytoplasmic pH and ATP concentrations confirm that dormant cells exhibit characteristic energetic profiles that can vary in level and dynamics, depending on the stimulus leading to growth arrest. We test whether the energetic makeup is associated with survival to antibiotics of different classes and find that, while growth arrest remains the dominant mechanism enabling survival, some correlations with cellular energetics exist. Our results pave the way to a classification of dormant states based on energy profiles, support a novel relationship between environment and drug susceptibility of dormant cells and suggest that knowledge of the conditions present at the infection site is necessary to design appropriate treatments.
Functional Characterization of the Lin28/let-7 Circuit during Forelimb Regeneration inAmbystoma mexicanumand its Influence on Metabolic Reprogramming
Authors: Varela-Rodríguez Hugo , Abella-Quintana Diana G. , Varela-Rodríguez Luis , Gomez-Zepeda David , Espinal-Centeno Annie , Caballero-Pérez Juan , Ordaz-Ortiz José Juan , Cruz-Ramírez Alfredo 
Published: June 2020

ABSTRACTThe axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored. However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events.
Crinet: A computational tool to infer genome-wide competing endogenous RNA (ceRNA) interactions
Authors: Kesimoglu Ziynet Nesibe , Bozdag Serdar 
Published: June 2020

AbstractTo understand driving biological factors for complex diseases like cancer, regulatory circuity of genes needs to be discovered. Recently, a new gene regulation mechanism called competing endogenous RNA (ceRNA) interactions has been discovered. Certain genes targeted by common microRNAs (miRNAs) “compete” for these miRNAs, thereby regulate each other by making others free from miRNA regulation. Several computational tools have been published to infer ceRNA networks. In most existing tools, however, expression abundance sufficiency, collective regulation, and groupwise effect of ceRNAs are not considered. In this study, we developed a computational tool named Crinet to infer genome-wide ceRNA networks addressing critical drawbacks. Crinet considers all mRNAs, lncRNAs, and pseudogenes as potential ceRNAs and incorporates a network deconvolution method to exclude the spurious ceRNA pairs. We tested Crinet on breast cancer data in TCGA. Crinet inferred reproducible ceRNA interactions and groups, which were significantly enriched in the cancer-related genes and processes. We validated the selected miRNA-target interactions with the protein expression-based benchmarks and also evaluated the inferred ceRNA interactions predicting gene expression change in knockdown assays. The hub genes in the inferred ceRNA network included known suppressor/oncogene lncRNAs in breast cancer showing the importance of non-coding RNA’s inclusion for ceRNA inference. The source code of Crinet could be accessed on Github athttps://github.com/bozdaglab/crinet.
Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate
Authors: Fox Jonathan J. , Hashimoto Takao , Navarro Héctor I. , Garcia Alejandro J. , Shou Benjamin L. , Goldstein Andrew S. 
Published: June 2020

SUMMARYAging is a significant risk factor for cancer in several tissues, including the prostate. Defining the kinetics of age-related changes in these tissues is critical for identifying regulators of aging and evaluating interventions to slow the aging process and reduce disease risk. An altered microenvironment is characteristic of prostatic aging in mice. Whether features of aging in the prostate emerge predominantly in old age or earlier in adulthood has not previously been established. Using comprehensive immune profiling and time-course analysis, we show that populations of T and B lymphocytes increase in the mouse prostate between 6 and 12 months of age. When comparing the prostate to other urogenital tissues, we found similar features of age-related inflammation in the mouse bladder. In summary, our study offers new insight into the kinetics of prostatic inflammaging and the window when interventions to slow down age-related changes may be most effective.
Microbial dark matter filling the niche in hypersaline microbial mats
Authors: Wong Hon Lun , MacLeod Fraser I. , White Richard Allen , Visscher Pieter T. , Burns Brendan P. 
Published: June 2020

AbstractShark Bay, Australia, harbours one of the most extensive and diverse systems of living microbial mats, that are proposed to be analogs of some of the earliest ecosystems on Earth. These ecosystems have been shown to possess a substantial abundance of uncultivable microorganisms. These enigmatic groups - ‘microbial dark matter’ (MDM) - are hypothesised to play key roles in microbial mats. We reconstructed 115 metagenome-assembled genomes (MAGs) affiliated to MDM, spanning 42 phyla within the bacterial and archaeal domains. We classified bacterial MDM from the PVC group, FCB group, Microgenomates, Parcubacteria, and Peregrinibacteria, as well as a high proportion of archaeal MDM under the TACK, DPANN, Altiarchaeales, and Asgard archaea. The latter includes the first putative Heimdallarchaeota MAG obtained from any microbial mat system. This study reports novel microorganisms (Zixibacterial order GN15) putatively taking part in dissimilatory sulfate reduction in surface hypersaline settings, as well as novel eukaryote signature proteins in the Asgard archaea. Despite possessing reduced-size genomes, the MDM MAGs are capable of fermenting and degrading organic carbon, suggesting a role in recycling organic carbon. Several forms of RuBisCo were identified, allowing putative CO2incorporation into nucleotide salvaging pathways, which may act as an alternative carbon and phosphorus source. High capacity of hydrogen production was found among Shark Bay MDM. Putative schizorhodopsins were also identified in Parcubacteria, Asgard archaea, DPANN archaea, and Bathyarchaeota, allowing these members to potentially capture light energy. Diversity-generating retroelements were prominent in DPANN archaea that likely facilitate the adaptation to a dynamic, host-dependent lifestyle. In light of our findings, we propose H2, ribose and CO/CO2as the main energy currencies of the MDM community in these mat systems.
A single dose of recombinant VSV-ΔG-spike vaccine provides protection against SARS-CoV-2 challenge
Authors: Yahalom-Ronen Yfat , Tamir Hadas , Melamed Sharon , Politi Boaz , Shifman Ohad , Achdout Hagit , Vitner Einat B. , Israeli Ofir , Milrot Elad , Stein Dana , Cohen-Gihon Inbar , Lazar Shlomi , Gutman Hila , Glinert Itai , Cherry Lilach , Vagima Yaron , Lazar Shirley , Weiss Shay , Ben-Shmuel Amir , Avraham Roy , Puni Reut , Lupu Edith , Bar David Elad , Sittner Assa , Erez Noam , Zichel Ran , Mamroud Emanuelle , Mazor Ohad , Levy Haim , Laskar Orly , Yitzhaki Shmuel , Shapira Shmuel C. , Zvi Anat , Beth-Din Adi , Paran Nir , Israely Tomer 
Published: June 2020

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 that emerged in December 2019 in China resulted in over 7.8 million infections and over 430,000 deaths worldwide, imposing an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we generated a replication competent recombinant VSV-ΔG-spike vaccine, in which the glycoprotein of VSV was replaced by the spike protein of the SARS-CoV-2. In vitro characterization of the recombinant VSV-ΔG-spike indicated expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in vivo model for COVID-19 was implemented. We show that vaccination of hamsters with recombinant VSV-ΔG-spike results in rapid and potent induction of neutralizing antibodies against SARS-CoV-2. Importantly, single-dose vaccination was able to protect hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss of the immunized hamsters compared to unvaccinated hamsters. Furthermore, whereas lungs of infected hamsters displayed extensive tissue damage and high viral titers, immunized hamsters’ lungs showed only minor lung pathology, and no viral load. Taken together, we suggest recombinant VSV-ΔG-spike as a safe, efficacious and protective vaccine against SARS-CoV-2 infection.