bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV coinfection is associated with low fitnessrpoBvariants in rifampicin-resistantMycobacterium tuberculosis
Authors: Loiseau Chloé , Brites Daniela , Reinhard Miriam , Zürcher Kathrin , Borrell Sonia , Ballif Marie , Fenner Lukas , Cox Helen , Rutaihwa Liliana K. , Wilkinson Robert J. , Yotebieng Marcel , Carter E Jane , Abimiku Alash’le , Marcy Olivier , Gotuzzo Eduardo , Avihingsanon Anchalee , Zetola Nicola , Doulla Basra , Böttger Erik C. , Egger Matthias , Gagneux Sebastien 
Published: July 2020

AbstractWe analysed 312 drug-resistant genomes ofMycobacterium tuberculosis (Mtb)collected from HIV coinfected and HIV negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistantMtbstrains isolated from HIV coinfected patients carried disproportionally more resistance-conferring mutations inrpoBthat are associated with a low fitness in the absence of the drug, suggesting these low fitnessrpoBvariants can thrive in the context of reduced host immunity.
Berberine Alleviates Adiposity and Cardiac Dysfunction in Offspring Exposed to Gestational Diabetes Mellitus
Authors: Cole Laura K. , Chen Li , Sparagna Genevieve C. , Vandel Marilyne , Xiang Bo , Dolinsky Vernon W. , Hatch Grant M. 
Published: July 2020

AbstractThe most robust risk factor for type 2 diabetes in childhood is prior exposure to diabetes during gestation. Currently, there are few evidence-based strategies to attenuate the of risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. It has been used safely for centuries in humans. Our objective was to determine whether BBR treatment improves health outcomes in the mouse offspring of GDM dams. Dams were fed either a lean low-fat diet (Lean, LF,10% kcal fat) or a GDM-inducing high-fat/high sucrose diet (GDM, HF, 45% kcal fat) prior to breeding and throughout pregnancy. The resulting Lean and GDM-exposed offspring were randomly assigned a LF, HF or HF diet containing BBR (160 mg/kg/d) for 12 weeks. We determined that BBR treatment significantly reduced body weight (∼20%), % body fat (∼40%) and gonadal fat pad mass (∼60%) compared to HF-fed GDM offspring. Furthermore, BBR treatment of HF-fed GDM offspring normalized insulin levels in the plasma and isolated pancreatic islets. Differences in food consumption did not contribute to altered body composition in BBR treated mice, as levels remained similar between experimental groups. Alternatively, BBR-treatment was associated with increased whole-body oxygen consumption (VO2), activity and heat production. Additionally, we determined that HF-fed GDM offspring developed a cardiomyopathy, characterized by increased isovolumetric contraction (∼150%, IVCT), relaxation time (∼70%, IVRT), elevated cardiac triglyceride (∼120%) and reduced mitochondrial function (30%, spare capacity) compared to LF fed Lean controls. BBR treatment normalized heart function, reduced triglyceride levels and maintained mitochondrial function. Our data supports BBR as a potential pharmacotherapeutic approach to improve health outcomes in individuals exposed to GDM.Key Points SummaryGestational diabetes mellitus is a common metabolic complication of pregnancy which is increasing worldwide due to the prevalence of obesity.It is known that individuals exposed to gestational diabetes have elevated risk of developing metabolic syndrome however there are few evidence-based strategies which provide protection.Berberine is a natural compound found in Chinese herbs which has been safely used for centuries to treat type 2 diabetes mellitus.We determined that berberine treatment of offspring exposed to gestational diabetes attenuated weight gain, reduced insulin levels and normalized both heart and pancreatic function.Our data supports berberine as a potential pharmacotherapeutic approach to improve health outcomes in individuals exposed to gestational diabetes.
MicrobeAnnotator: a user-friendly, comprehensive microbial genome annotation pipeline
Authors: Ruiz-Perez Carlos A. , Conrad Roth E. , Konstantinidis Konstantinos T. 
Published: July 2020

AbstractSummaryHigh-throughput sequencing has increased the number of microbial genomes from isolates, single cells, and metagenomes available. To analyze and compare these genomes, fast and comprehensive annotation pipelines are needed. Although several approaches exist for genome annotation, these are typically not designed for easy incorporation into analysis pipelines, do not combine results from several annotation databases or offer easy-to-use summaries of metabolic reconstructions in a high-throughput mode. Here, we introduce MicrobeAnnotator, a fully automated pipeline for the comprehensive annotation of microbial genomes that combines results from several reference protein databases to reliably summarize the metabolic potential of the genomes based on KEGG modules.AvailabilityMicrobeAnnotator is implemented in Python and is freely available under an open source Artistic Licence 2.0 fromhttps://github.com/cruizperez/MicrobeAnnotatorContactcruizperez3@gatech.edu;kostas@ce.gatech.edu
Accel-Align: A Fast Sequence Mapper and Aligner Based on the Seed–Embed–Extend Method
Authors: Yan Yiqing , Chaturvedi Nimisha , Appuswamy Raja 
Published: July 2020

AbstractBackgroundImprovements in sequencing technology continue to drive sequencing cost towards $100 per genome. However, mapping sequenced data to a reference genome remains a computationally-intensive task due to the dependence on edit distance for dealing with indels and mismatches introduced by sequencing. All modern aligners use seed–filter–extend (SFE) methodology and rely on filtration heuristics to reduce the overhead of edit distance computation. However, filtering has inherent performance–accuracy trade-offs that limits its effectiveness.ResultsMotivated by algorithmic advances in randomized low-distortion embedding, we introduceseed– embed–extend(SEE), a new methodology for developing sequence mappers and aligners. While SFE focuses on eliminating sub-optimal candidates, SEE focuses instead on identifying optimal candidates. To do so, SEE transforms the read and reference strings from edit distance regime to the Hamming regime by embedding them using a randomized algorithm, and uses Hamming distance over the embedded set to identify optimal candidates. To show that SEE performs well in practice, we present Accel-Align, an SEE-based short-read sequence mapper and aligner that is 3-12×faster than state-of-the-art aligners on commodity CPUs, without any special-purpose hardware, while providing comparable accuracy.ConclusionsAs sequencing technologies continue to increase read length while improving throughput and accuracy, we believe that randomized embeddings open up new avenues for optimization that cannot be achieved by using edit distance. Thus, the techniques presented in this paper have a much broader scope as they can be used for other applications like graph alignment, multiple sequence alignment, and sequence assembly.Availabilityhttps://github.com/raja-appuswamy/accel-align-release
Spatio-temporal patterns of population responses in the visual cortex under Isoflurane: from wakefulness to loss of consciousness
Authors: Margalit Shany Nivinsky , Golomb Neta Gery , Tsur Omer , Raz Aeyal , Slovin Hamutal 
Published: July 2020

AbstractAnesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Despite the vast use of anesthesia, how LOC affects cortical sensory processing and the underlying neural circuitry, is not well understood. We measured neuronal population activity in the visual cortices of awake and isoflurane anesthetized mice and compared the visually evoked responses under different levels of consciousness. We used voltage-sensitive dye imaging (VSDI) to characterize the temporal and spatial properties of cortical responses to visual stimuli over a range of states from wakefulness to deep anesthesia. VSDI enabled measuring the neuronal population responses at high spatial (meso-scale) and temporal resolution from several visual regions (V1, extrastiate-lateral (ESL) and extrastiate-medial (ESM)) simultaneously. We found that isoflurane has multiple effects on the population evoked response that augmented with anesthetic depth, where the largest changes occurred at LOC. Isoflurane reduced the response amplitude and prolonged the latency of response in all areas. In addition, the intra-areal spatial spread of the visually evoked activity decreased. During visual stimulation, intra-areal and inter-areal correlation between neuronal populations decreased with increasing doses of isoflurane. Finally, while in V1 the majority of changes occurred at higher doses of isoflurane, higher visual areas showed marked changes at lower doses of isoflurane. In conclusion, our results demonstrate a reverse hierarchy shutdown of the visual cortices regions: low-dose isoflurane diminishes the visually evoked activity in higher visual areas before lower order areas and cause a reduction in inter-areal connectivity leading to a disconnected network.
Direct Photon-by-photon Analysis of Time-Resolved Pulsed Excitation Data using Bayesian Nonparametrics
Authors: Tavakoli Meysam , Jazani Sina , Sgouralis Ioannis , Heo Wooseok , Ishii Kunihiko , Tahara Tahei , Pressé Steve 
Published: July 2020

AbstractLifetimes of chemical species are typically estimated, across each illuminated spot of a sample, by either fitting time correlated single photon counting (TCSPC) decay histograms or, more recently, through phasor analysis from time-resolved photon arrivals. While both methods yield lifetimes in a computationally efficient manner, the performance of both methods is limited by the choices made when fitting a TCSPC histogram. In addition, phasor analysis also requires setting the number of chemical species by hand before lifetimes can be determined. Yet the number of species itself is encoded in the photon arrival times collected for each illuminated spot and need not be set by handa priori. Here we propose a direct photo-by-photon analysis of data drawn from pulsed excitation experiments to infer, simultaneously and self-consistently, the number of species and their associated lifetimes from as little as a few thousand photons for two species. We do so by leveraging new mathematical tools within the Bayesian nonparametric (BNP) paradigm that we have previously exploited in the analysis of single photon arrivals from single spot confocal microscopy. We benchmark our method on simulated as well as experimental data for one, two, three, and four species with data sets from both immobilized and freely diffusing molecules at the level of one illuminated spot.SUMMARYPhoton arrivals obtained from fluorescence experiments encode not only the lifetimes of chemical species but also the number of chemical species involved in the experiment. Traditional methods of analysis, such as phasor methods and methods relying on maximum likelihood or (parametric) Bayesian analysis of photon arrivals or photon arrival histograms of TCSPC data, must first ascertain the number of chemical species separately and, once specified, determine their associated lifetimes. Here we develop a method to learn the number of fluorescence species and their associated lifetimes simultaneously. We achieve this by exploiting Bayesian nonparametrics. We benchmark our approach on both simulated and experimental data for one species and mixtures of two to four species.
Basolateral amygdala to nucleus accumbens projections differentially mediate flexibility of sign- and goal-tracking rats
Authors: Kochli Daniel E. , Keefer Sara E. , Gyawali Utsav , Calu Donna J 
Published: July 2020

AbstractRats rely on communication between basolateral amygdala (BLA) and nucleus accumbens (NAc) to express lever directed approach in a Pavlovian lever autoshaping (PLA) task that distinguishes sign- and goal-tracking rats. While sign-tracking rats inflexibly respond to cues even after the associated outcome is devalued, goal-tracking rats flexibly suppress conditioned responding during outcome devaluation. Here, we sought to determine whether BLA-NAc communication in sign-trackers drives rigid appetitive approach that is insensitive to manipulations of outcome value. Using a contralateral chemogenetic inactivation design, we injected contralateral BLA and NAc core with inhibitory DREADD (hm4D-mcherry) or control (mcherry) constructs. To determine sign- and goal-tracking groups, we trained rats in five PLA sessions in which brief lever insertion predicts food pellet delivery. We sated rats on training pellets (devalued condition) or chow (valued condition) prior to systemic clozapine injections (0.1 mg/kg) to inactivate BLA and contralateral NAc during two outcome devaluation probe tests, in which we measured lever and foodcup approach. Contralateral BLA-NAc chemogenetic inactivation promoted flexible lever approach in sign-tracking rats, but disrupted flexible food-cup approach in goal-tracking rats. Consistent with a prior BLA-NAc disconnection lesion study, we find contralateral chemogenetic inactivation of BLA and NAc core reduces lever, but not foodcup approach in PLA. Together these findings suggest rigid appetitive associative encoding in BLA-NAc of sign-tracking rats hinders the expression of flexible behavior when outcome value changes.
Single cell RNA sequencing of blood antigen-presenting cells in severe Covid-19 reveals multi-process defects in antiviral immunity
Authors: Saichi Melissa , Ladjemi Maha Zohra , Korniotis Sarantis , Rousseau Christophe , Ait-Hamou Zakaria , Massenet Lucile , Amblard Elise , Noel Floriane , Marie Yannick , Bouteiller Delphine , Medvedovic Jasna , Pène Frédéric , Soumelis Vassili 
Published: July 2020

AbstractCOVID-19 can lead to life-threatening acute respiratory failure, characterized by simultaneous increase in inflammatory mediators and viral load. The underlying cellular and molecular mechanisms remain unclear. We performed single-cell RNA-sequencing to establish an exhaustive high-resolution map of blood antigen-presenting cells (APC) in 7 COVID-19 patients with moderate or severe pneumonia, at day-1 and day-4 post-admission, and two healthy donors. We generated a unique dataset of 31,513 high quality APC, including monocytes and rare dendritic cell (DC) subsets. We uncovered multiprocess and previously unrecognized defects in anti-viral immune defense in specific APC compartments from severe patients: i) increase of pro-apoptotic genes exclusively in pDC, which are key effectors of antiviral immunity, ii) sharp decrease of innate sensing receptors, TLR7 and DHX9, in pDC and cDC1, respectively, iii) down-regulation of antiviral effector molecules, including Interferon stimulated genes (ISG) in all monocyte subsets, and iv) decrease of MHC class II-related genes, and MHC class II transactivator (CIITA) activity in cDC2, suggesting a viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore defective immune defense.
Impact of COVID-19 on Public Research Recruitment
Authors: Hsieh Yichuan Grace , Parker Holly , Estey Greg , Lorenz Stephen , Wylie Mark , Zhang Xiaofeng , Lopiccolo Joseph , Clarke Lloyd , Chung Jeanhee 
Published: July 2020

AbstractThe coronavirus disease 2019 (COVID-19) pandemic created a major challenge for clinical trials recruitment as early attention was focused on matters of public health and clinical care, and research--outside of COVID-19-- essentially shut down. Rally with Partners (rally.partners.org), an Internet-based portal for clinical research volunteer recruitment, continued to support studies that continued their recruitment during this period and additionally, implemented several measures to support COVID-19 research. In this paper, we summarize our experiences and preliminary results.
Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: results from the prospective AspCOVID-19 study
Authors: Lahmer Tobias , Kriescher Silja , Herner Alexander , Rothe Kathrin , Spinner Christoph D. , Schneider Jochen , Mayer Ulrich , Neuenhahn Michael , Hoffmann Dieter , Geisler Fabian , Heim Markus , Schneider Gerhard , Schmid Roland M , Huber Wolfgang , Rasch Sebastian 
Published: July 2020

SummaryBackgroundSuperinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.MethodsWe prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from bronchial aspirates. We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.FindingsCAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort.In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p=0.340) and days of mechanical ventilation (20 versus 15 days; p=0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.InterpretationCAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.FundingNone
Characterization ofPlasmodium falciparumNEDD8 and identification of cullins as its substrates
Authors: Bhattacharjee Manish , Adhikari Navin , Sudhakar Renu , Rizvi Zeba , Das Divya , Palanimurugan R , Sijwali Puran Singh 
Published: July 2020

ABSTRACTA variety of post-translational modifications ofPlasmodium falciparumproteins, including phosphorylation and ubiquitination, are shown to have key regulatory roles. The neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is a ubiquitin-like modifier of cullin-RING E3 ubiquitin ligases, which regulate diverse cellular processes, including the cell-cycle. Although neddylation pathway is conserved in eukaryotes, it is yet to be characterized in Plasmodium and related apicomplexan parasites. Towards studying the neddylation pathway in malaria parasites, we characterizedP. falciparumNEDD8 (PfNEDD8) and identified cullins as its physiological substrates. PfNEDD8 is a 76 amino acid residue protein without the C-terminal tail, indicating that it can be readily conjugated. The wild type and mutant (Gly75Gly76 mutated to Ala75Ala76) PfNEDD8 were expressed inP. falciparum. Western blot of wild type PfNEDD8-expressing parasites indicated multiple high molecular weight conjugates, which were absent in the parasites expressing the mutant, indicating conjugation of NEDD8 to proteins through Gly76. Immunoprecipitation followed by mass spectrometry of wild type PfNEDD8-expressing parasites identified several proteins, including two putative cullins. Furthermore, we expressed PfNEDD8 in mutantS. cerevisiaestrains that lacked endogenous NEDD8 (Δrub1) or NEDD8 conjugating E2 enzyme (ΔUbc12). The western blot of complemented strains and mass spectrometry of PfNEDD8 immunoprecipitate showed conjugation of PfNEDD8 toS. cerevisiaecullin cdc53, demonstrating functional conservation and cullins as the physiological substrates of PfNEDD8. The characterization of PfNEDD8 and identification of cullins as its substrates make ground for investigation of specific roles and drug target potential of neddylation pathway in malaria parasites.
Plasma microRNAs as predictive biomarkers of liver fibrosis and cirrhosis in patients with HBV-associated disease
Authors: Wang Tie-Zheng , Lin Dong-Dong , Zhang Yong-Hong , Zhang Yue-Wei , Li Ning 
Published: July 2020

AbstractBoth pathogenesis and detection of liver fibrosis and early cirrhosis are elusive. Our study focused on role of microRNAs (miRNAs) as predictive biomarkers of liver fibrosis and early cirrhosis. Methods: We recruited patients with chronic hepatitis B background and divided them into three subgroups according to the pathological staging results: no liver fibrosis group (CHB 11, 12.0%), liver fibrosis group but without liver cirrhosis (LF 41, 44.6%), and early liver cirrhosis group (LC 40, 43.4%). Results: Levels of miR-122 in the CHB and LF group were significantly elevated compared with the LC group. Meanwhile, upregulation levels of miR-146a-5p, miR-29c-3p, miR-223 were seen in the CHB group versus LC. MiR-122-5p was best able to differentiate between patients with LC and without LC (area under the curve (AUC) 0.734). It can also distinguish patients with LF from those without LF (AUC 0.681). Panel including miR-122-5p miR-29c-3p and miR-381-3p resulted in an AUC of 0.700 in detection of LF. Meanwhile panel including miR-122-5p, miR-29c-3p, MiR-223 turned out to be good predictors, resulted in an AUC of 0.752 to discriminate LC in HBV-associated disease. HBV load, ALT and AST showed significant positive correlation with miR-122-5p and miR-381-3p. Conclusions: Our study explored changes of plasm miRNA levels in HBV-associated disease patients, constructed diagnostic miRNAs panel to predict liver fibrosis and early cirrhosis. Meanwhile In the process of liver fibrosis and cirrhosis, there are involving not only common pathway molecules, but also its specific pathway molecules.