bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vulnerabilities in coronavirus glycan shields despite extensive glycosylation
Authors: Watanabe Yasunori , Berndsen Zachary T. , Raghwani Jayna , Seabright Gemma E. , Allen Joel D. , McLellan Jason S. , Wilson Ian A. , Bowden Thomas A. , Ward Andrew B. , Crispin Max 
Published: February 2020

AbstractSevere acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development has focussed on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein, which mediates receptor recognition and membrane fusion. Coronavirus S proteins are extensively glycosylated viral fusion proteins, encoding around 69-87 N-linked glycosylation sites per trimeric spike. Using a multifaceted structural approach, we reveal a specific area of high glycan density on MERS S that results in the formation of under-processed oligomannose-type glycan clusters, which was absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes. Consistent with the ability of the antibody-mediated immune response to effectively target and neutralize coronaviruses, we demonstrate that the glycans of coronavirus spikes are not able to form an efficacious high-density global shield to thwart the humoral immune response. Overall, our data reveal how differential organisation of viral glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the viral protein surface.
Influenza-induced oxidative stress sensitizes lung cells to bacterial toxin-mediated necroptosis
Authors: Gonzalez-Juarbe Norberto , Riegler Ashleigh N. , Jureka Alexander S. , Gilley Ryan P. , Brand Jeffrey , Trombley John E. , Scott Ninecia R. , Dube Peter H. , Petit Chad M. , Harrod Kevin S. , Orihuela Carlos J. 
Published: February 2020

ABSTRACTRationalePneumonia caused by Influenza A virus (IAV) co- and secondary bacterial infections are characterized by their severity. Previously we have shown that pore-forming toxin (PFT)-mediated necroptosis is a key driver of acute lung injury during bacterial pneumonia. Here, we evaluate the impact of IAV on PFT-induced acute lung injury during co- and secondaryStreptococcus pneumoniae(Spn) infection.ObjectivesDetermine the impact of IAV infection on bacterial PFT-mediated lung epithelial cell (LEC) necroptosis. Determine the molecular basis for increased sensitivity and if inhibition of necroptosis or oxidative stress blocks IAV sensitization of LEC to PFT.MethodsMice and cells were challenged with IAV followed bySpn. Necroptosis was monitored by measuring cell death at fixed time points post-infection and immunofluorescent detection of necroptosis. Wildtype mice and LEC were treated with necroptosis inhibitors. Necroptosis effector molecule MLKL deficiency was tested for infection synergy. Oxidative damage to DNA and lipids as result of infection was measuredin vitroandin vivo. Necroptosis and anti-oxidant therapy efficacy to reduce disease severity was testedin vivo.Measurements and Main ResultsIAV synergistically sensitized LEC for PFT-mediated necroptosisin vitroand in murine models ofSpnco-infection and secondary infection. Pharmacological induction of oxidative stresssansvirus sensitized cells for PFT-mediated necroptosis. Necroptosis inhibition reduced disease severity during secondary bacterial infection.ConclusionsIAV-induced oxidative stress sensitizes LEC for PFT-mediated necroptosis. This is a new molecular explanation for severe influenza-associated bacterial infections. Necroptosis inhibitors are potential therapeutic strategies to reduce IAV-primed bacterial pneumonia severity.SummaryHere we demonstrate that Influenza A virus (IAV) infection synergistically sensitizes lung cells to bacterial pore-forming toxin (PFT)-mediated necroptosis. Moreover, this contributes to the severity of lung injury that is observed during co- and secondary infection withStreptococcus pneumoniae. IAV-induced oxidative stress was identified as a key factor contributing to cell sensitization and induction of oxidative stresssansvirus was sufficient to synergistically enhance susceptibility to PFT-mediated killing. Our results advance our understanding on the molecular basis of co- and secondary bacterial infection to influenza and identifies necroptosis inhibition and antioxidant therapy as potential intervention strategies.
Population dynamics ofDiatraeaspp. Under different climate offer conditions in Colombia
Authors: Arbeláez Julián Andrés Valencia , Giraldo Alberto Soto , Villa Gabriel Jaime Castaño , Espinosa Luis Fernando Vallejo , Gutiérrez Melba Ruth Salazar , Orozco Germán Andrés Vargas 
Published: February 2020

AbstractSeasonal temperature and precipitation patterns on a global scale are the main factors to identify the sharing of organisms. Accordingly, insects and plants come to adapt to combinations of various factors through natural selection, although periodic outbreaks in insect populations occur especially in areas where they have not been previously reported, is a phenomenon that is considered as a consequence of global warming. In the study, we sought estimate the distribution of the sugarcane stem borers,Diatraeaspp., under different climate scenarios. Weekly collections were carried out in four sugarcane field plots in four different towns from the Colombian department of Caldas during a consecutive year, and also from sugarcane plots from the Cauca river valley between 2010 and 2017. The influence of climatic variables on the climate in different agro-ecological zones of sugarcane crops (Saccharumsp.) was defined by using climatic data (maximum, minimum and daily temperatures; accumulated precipitation) on a daily scale between 2010 and 2017. MODESTR® was used to generate the distribution maps to estimate probability distributions subject to restrictions given by the environmental information.Diatraeaspp. is strongly influenced by the effects of climate change, considerably reducing its population niches as well as the number of individuals. The estimate of an optimal niche forDiatraeaspp. includes temperatures between 20°C and 23°C, accumulated annual rainfall between 1200 and 1500 mm, months with dry conditions, whose precipitation is below 50 mm, slopes below 0.05, crop heterogeneity with an index of 0.2 and primary production values of 1.0.Summary statementDiatraeaspp. is susceptible to temperature variations due to climate change, it is presumed that its adaptability could benefitDiatraeaspp. in establishing itself in new areas.
Are Antisense Proteins in Prokaryotes Functional?
Authors: Ardern Zachary , Neuhaus Klaus , Scherer Siegfried 
Published: February 2020

AbstractMany prokaryotic RNAs are transcribed from loci outside of annotated protein coding genes. Across bacterial species hundreds of short open reading frames antisense to annotated genes show evidence of both transcription and translation, for instance in ribosome profiling data. Determining the functional fraction of these protein products awaits further research, including insights from studies of molecular interactions and detailed evolutionary analysis. There are multiple lines of evidence however that many of these newly discovered proteins are of use to the organism. Condition-specific phenotypes have been characterised for a few. These proteins should be added to genome annotations, and the methods for predicting them standardised. Evolutionary analysis of these typically young sequences also may provide important insights into gene evolution. This research should be prioritised for its exciting potential to uncover large numbers of novel proteins with extremely diverse potential practical uses, including applications in synthetic biology and responding to pathogens.
Deep Neural Networks Carve the Brain at its Joints
Authors: Bertolero Maxwell A. , Bassett Danielle S. 
Published: February 2020

AbstractHow an individual’s unique brain connectivity determines that individual’s cognition, behavior, and risk for pathology is a fundamental question in basic and clinical neuroscience. In seeking answers, many have turned to machine learning, with some noting the particular promise of deep neural networks in modelling complex non-linear functions. However, it is not clear that complex functions actually exist between brain connectivity and behavior, and thus if deep neural networks necessarily outperform simpler linear models, or if their results would be interpretable. Here we show that, across 52 subject measures of cognition and behavior, deep neural networks fit to each brain region’s connectivity outperform linear regression, particularly for the brain’s connector hubs—regions with diverse brain connectivity—whereas the two approaches perform similarly when fit to brain systems. Critically, averaging deep neural network predictions across brain regions results in the most accurate predictions, demonstrating the ability of deep neural networks to easily model the various functions that exists between regional brain connectivity and behavior, carving the brain at its joints. Finally, we shine light into the black box of deep neural networks using multislice network models. We determined that the relationship between connector hubs and behavior is best captured by modular deep neural networks. Our results demonstrate that both simple and complex relationships exist between brain connectivity and behavior, and that deep neural networks can fit both. Moreover, deep neural networks are particularly powerful when they are first fit to the various functions of a system independently and then combined. Finally, deep neural networks are interpretable when their architectures are structurally characterized using multislice network models.
Achieving symptom relief in patients with Myalgic encephalomyelitis by targeting the neuro-immune interface and inducing disease tolerance
Authors: Rodriguez Lucie S.T. , Pou Christian , Lakshmikanth Tadepally , Zhang Jingdian , Mugabo Constantin Habimana , Wang Jun , Mikes Jaromir , Olin Axel , Chen Yang , Rorbach Joanna , Juto Jan-Erik , Li Tie Qiang , Julin Per , Brodin Petter 
Published: February 2020

AbstractMyalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and induce a sustainable, ∼30% reduction in overall symptom scores after eight weeks of treatment. By performing longitudinal, systems-level monitoring of the blood immune system in these patients, we uncover chronic immune activation in ME, as well as immunological correlates of improvement that center around the IL-17 axis, gut-homing immune cells and reduced inflammation. The mechanisms of symptom relief remains to be determined, but transcriptional analyses suggest an upregulation of disease tolerance mechanisms. We wish for these results to bring some hope to patients suffering from ME and inspire researchers to help test our new hypothesis that ME is a condition caused by a failure of inducing disease tolerance upon infection and persistent immune activation.
Mapping human laryngeal motor cortex during vocalization
Authors: Eichert Nicole , Papp Daniel , Mars Rogier B. , Watkins Kate E. 
Published: February 2020

AbstractThe representations of the articulators involved in human speech production are organized somatotopically in primary motor cortex. The neural representation of the larynx, however, remains debated. Both a dorsal and a ventral larynx representation have been previously described. It is unknown, however, whether both representations are located in primary motor cortex. Here, we mapped the motor representations of the human larynx using fMRI and characterized the cortical microstructure underlying the activated regions. We isolated brain activity related to laryngeal activity during vocalization while controlling for breathing. We also mapped the articulators (the lips and tongue) and the hand area. We found two separate activations during vocalization – a dorsal and a ventral larynx representation. Structural and quantitative neuroimaging revealed that myelin content and cortical thickness underlying the dorsal, but not the ventral larynx representation, are similar to those of other primary motor representations. This finding confirms that the dorsal larynx representation is located in primary motor cortex and that the ventral one is not. We further speculate that the location of the ventral larynx representation is in premotor cortex, as seen in other primates. It remains unclear, however, whether and how these two representations differentially contribute to laryngeal motor control.
Metabolic defects cause hyperactive mitochondria and Parkinson’s disease-like traits
Authors: Mor Danielle E. , Sohrabi Salman , Kaletsky Rachel , Keyes Will , Kalia Vrinda , Miller Gary W. , Murphy Coleen T. 
Published: February 2020

AbstractMetabolic dysfunction is a facet of many age-related neurodegenerative diseases, yet its role in disease etiology remains poorly understood1. We recently discovered a potential causal link between the branched-chain amino acid transferase,BCAT-1, and the neurodegenerative movement disorder, Parkinson’s disease (PD)2. Knockdown ofC. elegans bcat-1recapitulates PD-like features, including progressive motor deficits and neurodegeneration with age2. Using transcriptomic, metabolomic, and imaging approaches, we show thatbcat-1knockdown increases mitochondrial activity and induces oxidative damage in neurons through mTOR-independent mechanisms. We recently developed a high-throughput screening platform to identify drugs that may be repurposed for PD, and found that metformin, the leading type 2 diabetes medication, significantly improves motor function inbcat-1(RNAi)worms3. Late-in-life metformin treatment restores normal mitochondrial activity levels and protects againstbcat-1-associated neurodegeneration. Our results suggest that PD may originate as a metabolic disorder, and highlight metformin as a promising new drug candidate for PD treatment.
Network fingerprint of stimulation-induced speech impairment in essential tremor
Authors: Petry-Schmelzer Jan Niklas , Jergas Hannah , Thies Tabea , Steffen Julia K. , Reker Paul , Dafsari Haidar S. , Mücke Doris , Fink Gereon R. , Visser-Vandewalle Veerle , Dembek Till A. , Barbe Michael T. 
Published: February 2020

AbstractObjectiveTo gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS).MethodsMonopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was than validated in a leave-one-out design.ResultsFibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brainstem. In the thalamic area, they ran laterally to the thalamus and postero-medially to the subthalamic nucleus, in close proximity, mainly antero-laterally, to fibers beneficial for tremor control as published by Al-Fatly et al. (2019). The overlap of the respective clinical stimulation setting’s VTAs with these fibers explained 62.4% (p<0.001) of the variance of stimulation-induced change in intelligibility in a leave-one out analysis.InterpretationThis study demonstrates that SID in essential tremor patients is associated with both, motor cortex and cerebellar connectivity. Furthermore, the identified fiber-based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in ET patients with thalamic DBS.
Bound2Learn: A Machine Learning Approach for Classification of DNA-Bound Proteins from Single-Molecule Tracking Experiments
Authors: Kapadia Nitin , El-Hajj Ziad W. , Reyes-Lamothe Rodrigo 
Published: February 2020

AbstractDNA-bound proteins are essential elements for the maintenance, regulation, and use of the genome. The time they spend bound to DNA provides useful information on their stability within protein complexes and insight into the understanding of biological processes. Single-particle tracking allows for direct visualization of protein-DNA kinetics, however, identifying whether a molecule is bound to DNA can be non-trivial. Further complications arise when tracking molecules for extended durations in processes with slow kinetics. We developed a machine learning approach, termed Bound2Learn, using output from a widely used tracking software, to robustly classify tracks in order to accurately estimate residence times. We validated our approachin silico, and in live-cell data fromEscherichia coliandSaccharomyces cerevisiae. Our method has the potential for broad utility and is applicable to other organisms.
Systematic determination of the mitochondrial proportion in human and mice tissues for single-cell RNA sequencing data quality control
Authors: Osorio Daniel , Cai James J. 
Published: February 2020

AbstractMotivationQuality control (QC) is a critical step in single-cell RNA-seq (scRNA-seq) data analysis. Low-quality cells are removed from the analysis during the QC process to avoid misinterpretation of the data. One of the important QC metrics is the mitochondrial proportion (mtDNA%), which is used as a threshold to filter out low-quality cells. Early publications in the field established a threshold of 5% and since then, it has been used as a default in several software packages for scRNA-seq data analysis and adopted as a standard in many scRNA-seq studies. However, the validity of using a uniform threshold across different species, single-cell technologies, tissues, and cell types has not been adequately assessed.ResultsWe systematically analyzed 5,530,106 cells reported in 1,349 annotated datasets available in the PanglaoDB database and found that the average mtDNA% in scRNA-seq data across human tissues is significantly higher than in mouse tissues. This difference is not confounded by the platform used to generate the data. Based on this finding, we propose new reference values of the mtDNA% for 121 tissues of mice and 44 tissues of humans. In general, for mouse tissues, the 5% threshold performs well to distinguish between healthy and low-quality cells. However, for human tissues, the 5% threshold should be reconsidered as it fails to accurately discriminate between healthy and low-quality cells in 29.5% (13 of 44) tissues analyzed. We conclude that omitting the mtDNA% QC filter or adopting a suboptimal mtDNA% threshold may lead to erroneous biological interpretations of scRNA-seq data.AvailabilityThe code used to download datasets, perform the analyzes, and produce the figures is available athttps://github.com/dosorio/mtProportionContactdcosorioh@tamu.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Molecular Characterization of invasiveEnterobacteriaceaefrom Pediatric Patients in Central and Northwestern Nigeria
Authors: Duru Carissa , Olanipekun Grace M , Odili Vivian , Kocmich Nicholas J , Rezac Amy , Ajose Theresa O , Medugu Nubwa , Ebruke Bernard , Esimone Charles , Obaro Stephen 
Published: February 2020

AbstractBackgroundBacteremia is a leading cause of death in developing countries but etiologic evaluation is infrequent and empiric antibiotics are not evidence-based. Very little is known about the types of extended-spectrum β-lactamases (ESBL) in pediatric bacteremia patients in Nigeria. We evaluated the patterns of ESBL resistance in children enrolled into surveillance for community acquired bacteremic syndromes across health facilities in Central and Northwestern Nigeria.MethodBlood culture from suspected cases of sepsis from children age less than 5 years were processed using automated Bactec®incubator System from Sept 2008-Dec 2016.Enterobacteriaceawere identified to the species level using Analytical Profile Index (API20E®) identification strip and antibiotic susceptibility profile was determined by the disc diffusion method. The multidrug resistant strains were then screened and confirmed for extended spectrum beta lactamase (ESBL) production by the combination disc method as recommended by Clinical and Laboratory Standard Institute (CLSI). Real time PCR was used to elucidate the genes responsible for ESBL production characterize the resistance genesResultOf 21,000 children screened from Sept 2008-Dec 2016, 2,625(12.5%) were culture-positive. A total of 413Enterobacteriaceaeavailable for analysis were screened for ESBL. ESBL production was detected in 160/413(38.7%), comprisingKlebsiella pneumoniae105/160(65.6%),Enterobacter cloacae21/160(13.1%),Escherichia coli22/160(13.8%),Serratiaspecies 4/160(2.5%),Pantoeaspecies 7/160(4.4%) andCitrobacterspecies 1/160(0.6%). Of the 160 ESBL-producing isolates, high resistance rates were observed among ESBL-positive isolates for Ceftriaxone (92.3%), Aztreonam (96.8%), Cefpodoxime (96.25%), Cefotaxime (98.75%) and sulphamethoxazole-trimethoprim (90%), while 87.5 %, 90.63%, and 91.87% of the isolates were susceptible to Imipenem, Amikacin and Meropenem respectively. Frequently detected resistance genes wereblaTEM 83.75%) (134/160), and,blaCTX-M 83.12% (133/160) followed byblaSHV genes 66.25% (106/160). Co-existence ofblaCTX-M,blaTEM andblaSHV was seen in 94/160 (58.8%),blaCTX-M andblaTEM in 118/160 (73.8%),blaTEM andblaSHV in 97/160 (60.6%) andblaCTX-M andblaSHV in 100/160 (62.5%) of isolates tested.ConclusionOur results indicate a high prevalence of ESBL resistance to commonly used antibiotics inEnterobacteriaceaeisolates from bloodstream infections in children in this study. Careful choice of antibiotic treatment options and further studies to evaluate transmission dynamics of resistance genes could help in the reduction of ESBL resistance in these settings.