bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ab-initio determination of the shape of membrane proteins in a nanodisc
Authors: Orioli Simone , Hansen Carl G. Henning , Arleth Lise 
Published: September 2020

AbstractWe introduce a new software, calledMarbles, that employs SAXS intensities to predict the shape of membrane proteins embedded into membrane nanodiscs. To gain computational speed and efficient convergence, the strategy is based on a hybrid approach that allows one to account for the nanodisc contribution to the SAXS intensity through a semi-analytical model, while the embedded membrane protein is treated as set of beads, similarly to well known ab-initio methods. The code, implemented in C++ with a Python user interface, provides a good performance and includes the possibility to systematically treat unstructured domains. We prove the reliability and flexibility of our approach by benchmarking the code on a toy model and two proteins of very different geometry and size.
Vulnerability of Elevation-Restricted Endemic Birds of the Cordillera de Talamanca (Costa Rica and Panama) to Climate Change
Authors: Liu Zhen , Sandoval Luis , Sherman Lauren , Wilson Andrew 
Published: September 2020

ABSTRACTAnimals endemic to tropical mountains are known to be especially vulnerable to climate change. The Cordillera de Talamanca (Costa Rica and Panama) is a geographically isolated mountain chain and global biodiversity hotspot, home to more than 50 endemic bird species. We used eBird community science observations to predict the distributions of a suite of 48 of these endemic birds in 2006-2015, and in 2070, under four climate change scenarios. Species distributions were predicted using program Maxent, incorporating elevation, satellite derived habitat data, and WorldClim climate variables. Model fit, as assessed by Area under the Receiver Operator Curve (AUC) was very high for most species, ranging from 0.877 to 0.992 (mean of 0.94). We found that most species are predicted to undergo range contractions by 2070, with a mean of 15% under modest climate change (RCP 2.6) up to a mean of 40% under more severe climate change (RCP 8.5). Most of the current ranges of these species are within existing protected areas (average of 59% in 2006-2015), and with prospective range contractions, the importance of these protected areas is forecast to increase. We suggest that these predicted range declines should elevate conservation concerns for this suite of species, and vigilance, in the form of better population monitoring, is urgently needed.
The KCNQ4-mediated M-current regulates the circadian rhythm in mesopontine cholinergic neurons
Authors: Bayasgalan T. , Stupniki S. , Kovács A. , Csemer A. , Szentesi P. , Pocsai K. , Dionisio L. , Spitzmaul G. , B. Pál 
Published: September 2020

AbstractThe M-current is a voltage gated potassium current inhibited by muscarinic activation and affected by several other G-protein coupled receptors. Its channels are formed by KCNQ subunits, from which KCNQ4 is restricted to certain brainstem structures. We sought evidence for the function of the M-current in the pedunculopontine nucleus (PPN) and the contribution of KCNQ4 subunits to the M-current and aimed to find its functional significance in the PPN. We found that cholinergic inputs of the PPN can effectively inhibit M-current. This current is capable of synchronizing neighboring neurons and inhibition of the M-current decreases neuronal synchronization. We showed that only a subpopulation of cholinergic neurons has KCNQ4-dependent M-current. The KCNQ4 subunit expression potentially regulates the presence of other KCNQ subunits. Deletion of KCNQ4 leads to alterations in adaptation of activity to light-darkness cycles, thus representing the potential role of KCNQ4 in regulation of sleep-wakefulness cycles. The presence of this protein restricted to certain brainstem nuclei raises the possibility that it might be a potential target for selective therapeutic interventions affecting the reticular activating system.
Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement
Authors: Song Eric , Bartley Christopher M. , Chow Ryan D. , Ngo Thomas T. , Jiang Ruoyi , Zamecnik Colin R. , Dandekar Ravi , Loudermilk Rita P. , Dai Yile , Liu Feimei , Hawes Isobel A. , Alvarenga Bonny D. , Huynh Trung , McAlpine Lindsay , Rahman Nur-Taz , Geng Bertie , Chiarella Jennifer , Goldman-Israelow Benjamin , Vogels Chantal B.F. , Grubaugh Nathan D. , Casanovas-Massana Arnau , Phinney Brett S. , Salemi Michelle , Alexander Jessa , Gallego Juan A. , Lencz Todd , Walsh Hannah , Lucas Carolina , Klein Jon , Mao Tianyang , Oh Jieun , Ring Aaron , Spudich Serena , Ko Albert I. , Kleinstein Steven H. , DeRisi Joseph L. , Iwasaki Akiko , Pleasure Samuel J. , Wilson Michael R. , Farhadian Shelli F. 
Published: September 2020

AbstractOne third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients’ CSF and show that these target both anti-viral and anti-neural antigens—including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients.One Sentence SummaryA subset of COVID-19 patients with neurologic impairment show cerebrospinal fluid-specific immune alterations that point to both neuroinvasion and anti-neural autoimmunity as potential causes of impairment.
Secondhand homes: Woodpecker cavity location and structure influences secondary nester’s success
Authors: Hardin Faith O. , Leivers Samantha , Grace Jacquelyn K. , Cairns David M. , Campbell Tyler , Pierce Brian , Morrison Michael L. 
Published: September 2020

AbstractUnderstanding how ecosystem engineers influence other organisms has long been a goal of ecologists. Woodpeckers select nesting sites with high food availability and will excavate and then abandon multiple cavities through their lifetime. These cavities are crucial to secondary cavity nesting birds (SCB) that are otherwise limited by the availability of naturally occurring cavities.Our study examined the role food resources have on the nest site location and home range size of woodpeckers, and the respective influence woodpeckers and the construction of cavities have on the nesting success of SCB.Using five years of avian point count data to locate golden-fronted woodpeckers (GFWO:Melanerpes aurifrons), we correlated insect availability with GFWO home range size and determined differences in insect availability between GFWO occupied and unoccupied sites, while recording nesting success (success: ≥ 1 fledgling) for the GFWO and common SCB in south Texas: Black-crested Titmouse (Baeolophus atricristatus), Ash-throated Flycatcher (Myiarchus cinerascens), Brown-crested Flycatcher (Myiarchus tyrannulus), and Bewick’s Wren (Thryomanes bewickii). We used model averaging to fit species-specific logistic regression models to predict nest success based on cavity metrics across all species.Sites occupied by GFWO had a higher biomass of insects in orders Coleoptera, Hymenoptera, and Orthoptera than unoccupied sites, and there was a negative correlation between the availability of these insect orders and home-range size. GFWO had increased nest success in trees with increased vegetation cover and lower levels of decay, whileSCB had higher levels of nesting success in abandoned GFWO cavities opposed to naturally occurring ones, and in trees with low decay.Our results suggest that SCB may be drawn to nest in abandoned woodpecker cavities where they have higher rates of nest success compared to natural cavities. Additionally, the prevalence for GFWO to excavate cavities in trees with lower levels of decay contradicts previous literature and may indicate a novel temperature trade-off, with live trees requiring more energy to excavate, but providing more protection from high breeding season temperatures in arid and semi-arid areas.
Robust Tobacco Smoking Self-Report in two Cohorts of Vulnerable Pregnant Women and Adults
Authors: Saberi Sara , Smith Marie-Soleil R. , Ajaykumar Abhinav , Zhu Mayanne M. T. , Gadawski Izabelle , Sattha Beheroze , Maan Evelyn J. , Van Schalkwyk Julie , Elwood Chelsea , Boucoiran Isabelle , Money Deborah M. , Côté Hélène C.F. ,   CIHR Team in Cellular Aging and HIV Comorbidities in Women and Children (CARMA)
Published: September 2020

AbstractBackgroundStigma associated with tobacco smoking, especially during pregnancy, may lead to underreporting and possible bias in studies relying on self-reported smoking data. Cotinine, a nicotine metabolite with a ∼20h half-life in blood, is often used as a biomarker of smoking. The objective of this study was to examine the concordance between self-reported smoking and plasma cotinine concentration among participants enrolled in two related cohorts of vulnerable individuals: human immunodeficiency virus (HIV)-positive and HIV-negative pregnant women enrolled in the CARMA-PREG cohort and HIV-positive and HIV-negative non-pregnant women and men enrolled in the CARMA-CORE cohort.MethodsFor HIV-positive (n=76) and negative (n=24) pregnant women, plasma cotinine was measured by ELISA in specimens collected during the third trimester, between 28 and 38 weeks of gestation. Plasma cotinine was also measured in HIV-positive (n=43) and negative (n=57) women and men enrolled in the CARMA-CORE cohort.ResultsSelf-reported smokers were more likely to have low income (p<0.001) in both cohorts, and to deliver preterm (p=0.007) in CARMA-PREG. In the CARMA-PREG cohort, concordance between plasma cotinine was 95% for self-reported smoking, and 89% for self-reported non-smoking. In the CARMA-CORE cohort we observed similarly high concordances of 96% and 92% for self-reported smoking and non-smoking, respectively. In this sample, the odds of discordance between self-reported smoking status and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others. Taken together, the overall concordance between plasma cotinine and self-reported data was 94% with a Cohen’s kappa coefficient of 0.860 among all participants.ConclusionsGiven the high proportion of vulnerable people in the CARMA-PREG and CARMA-CORE cohorts, our results may not be fully generalizable to the general population. However, they demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report data.ImplicationsReliable self-reported smoking data is necessary to account for smoking status in subsequent studies. Our results suggest that future studies should ensure that study participants feel sale to speak candidly to non-judgemental research staff to obtain reliable self-report data.
Recoveries of Ringed Red-Footed Falcons (Falco vespertinus) in Germany - An update documentation
Authors: Kunze Dietmar , Nennstiel Lisa 
Published: September 2020

AbstractBird ringing is used for a long time for scientific investigation of migration routes and to better understand breeding events as well as population ecological aspects. It is applied as an inexpensive method although the well-known and major disadvantage of bird ringing is the usually low response rate. In the case of rarer species such as the Red-Footed Falcon (RFF), however, this quota could be higher due to the exclusivity and greater attention of observers. Motivated by own field observations of color-ringed RFF south of Brunswick, Germany in 2019 and no clear and comprehensive publication of verified additional recoveries and ringings, we did further research regarding this issue by following methods: 1) Contacting European Bird Ringing Centers and associated projects, 2) Query and comparison of files with the three national German Bird Ringing Stations, 3) Expanded literature research, 4) Evaluating reports in the citizen science platform ornitho.de, 5) Checking websites of ringing projects (in particular satellite tracking programs) and 6) Own observations.Surprisingly, this study revealed 18 recovered RFF ringed in foreign countries (14 Hungary, 3 Italy, 1 Romania (GPS tracked bird)) during migration or post-nuptial pre-migration time. Additionally, 1 RFF that was caught and ringed in Germany was recovered abroad.This result updates and increases the number of recoveries of RFF in Germany compared to the actual published state on the order of 18 (so far none) and on the order of 6 concerning ID-encoded RFF (GPS-bird excluded) compared to documentation state of the three Bird Ringing Centers in Germany (so far 3 at Beringungszentrale [BZ] Hiddensee, 1 at Institut für Vogelforschung [IfV] Heligoland). Our research and evaluation of raw data succeeded to a 100% identification rate of the bird’s origin countries (n=18) while the rate of ID-encoded RFF by color ring codes revealed 58.8% (n=10, GPS-bird excluded). The reported-by-observer response rate was 41.2%. Interesting data of about the phenology, age and origin of the RFF recovered in Germany are presented. Questions and considerations about the recent reporting system of ringed birds and the increased numbers of RFF during the last years in Germany are discussed.
Convergent evolution of increased urine concentrating ability in desert mammals
Authors: Rocha Joana L. , Brito José C. , Nielsen Rasmus , Godinho Raquel 
Published: September 2020

AbstractOne of the most celebrated textbook examples of physiological adaptations to desert environments is the unique ability that desert mammals have to produce hyperosmotic urine. Commonly perceived as an adaptation mainly observed in small rodents, the extent to which urine concentrating ability has independently evolved in distinct lineages, including medium-sized and large desert mammals, has not previously been assessed using modern phylogenetic approaches. Here, we explicitly test the general hypothesis that desert-dwelling mammals have evolved increased ability to concentrate urine compared to non-desert species, controlling for body mass and other covariates. Phylogenetic generalized least-squares models show that the mean aridity index of a species distribution range largely predicts its urine concentrating ability, even when accounting for body mass differences and phylogenetic correlations. In contrast, we find much weaker correlations between mass-adjusted basal metabolic rate and environmental variables.
Galectin-1-deficient mice are protected againstTrypanosoma cruziinfection through altered neutrophil migration and production of reactive oxygen species and nitric oxide
Authors: Riul Thalita Bachelli , de Campos Helioswilton Sales , de Souza Lima-Junior Djalma , Azzolini Ana Elisa Caleiro Seixas , de Barros Cardoso Cristina Ribeiro , Stowell Sean R. , Cummings Richard D. , Valim Yara Maria Lucisano , Dias-Baruffi Marcelo 
Published: September 2020

SUMMARYTrypanosoma cruziis an intracellular parasite that causes Chagas disease that affects millions of people worldwide. Many cellular and molecular aspects of this neglected disease are not fully understood. Prior studies have shown that galectin-1 (Gal-1), a β-galactoside-binding protein that regulates leukocyte recruitment to the inflammatory site, and promotesT. cruziinfection, but the mechanism is unclear. Here, we report that C57BL/6 mice lacking Gal-1 (Lgals1−/−) exhibited lower parasitemia and higher survival rates than their wildtype (WT) counterparts when infected withT. cruziY strain. Two weeks after infection,Lgals1−/−mice displayed greater neutrophil accumulation in infection site and heart tissue than WT mice. InT. cruzi-infectedLgals1−/−mice, infiltrated neutrophils produced increased levels of reactive oxygen species (ROS), while macrophages and neutrophils produced increased levels of nitric oxide (NO), which reduced replication and viability of parasitesin vitroand downregulated IL-1β production. Pharmacological inhibition of NADPH oxidase and NO synthase during earlyin vivoinfection reversed the protective effect of Gal-1 deficiency inLgals1−/−mice. Together, our findings demonstrate that lacking Gal-1 favors neutrophil migration to the infection site and increases production of ROS and NO, thereby controlling the early steps ofT. cruziinfection by reducing parasitemia and prolonging survival of infected mice.
Type I Interferon Limits Viral Dissemination-Driven Clinical Heterogeneity in a Native Murine Betacoronavirus Model of COVID-19
Authors: Qing Hua , Sharma Lokesh , Hilliard Brandon K. , Peng Xiaohua , Swaminathan Anush , Tian Justin , Israni-Winger Kavita , Zhang Cuiling , Leão Delva , Ryu Seungjin , Habet Victoria , Wang Lin , Tian Xuefei , Ma Yina , Ishibe Shuta , Young Lawrence H. , Kotenko Sergei , Compton Susan , Booth Carmen J. , Ring Aaron M. , Dixit Vishwa Deep , Wilen Craig B. , Pereira João P. , Dela Cruz Charles S. , Wang Andrew 
Published: September 2020

SummaryEmerging clinical data demonstrates that COVID-19, the disease caused by SARS-CoV2, is a syndrome that variably affects nearly every organ system. Indeed, the clinical heterogeneity of COVID-19 ranges from relatively asymptomatic to severe disease with death resultant from multiple constellations of organ failures. In addition to genetics and host characteristics, it is likely that viral dissemination is a key determinant of disease manifestation. Given the complexity of disease expression, one major limitation in current animal models is the ability to capture this clinical heterogeneity due to technical limitations related to murinizing SARS-CoV2 or humanizing mice to render susceptible to infection. Here we describe a murine model of COVID-19 using respiratory infection with the native mouse betacoronavirus MHV-A59. We find that whereas high viral inoculums uniformly led to hypoxemic respiratory failure and death, lethal dose 50% (LD50) inoculums led to a recapitulation of most hallmark clinical features of COVID-19, including lymphocytopenias, heart and liver damage, and autonomic dysfunction. We find that extrapulmonary manifestations are due to viral metastasis and identify a critical role for type-I but not type-III interferons in preventing systemic viral dissemination. Early, but not late treatment with intrapulmonary type-I interferon, as well as convalescent serum, provided significant protection from lethality by limiting viral dissemination. We thus establish a Biosafety Level II model that may be a useful addition to the current pre-clinical animal models of COVID-19 for understanding disease pathogenesis and facilitating therapeutic development for human translation.
A bacterial artificial chromosome (BAC)-vectored noninfectious replicon of SARS-CoV-2
Authors: Zhang Yang , Song Wuhui , Chen Shuiye , Yuan Zhenghong , Yi Zhigang 
Published: September 2020

AbstractVaccines and antiviral agents are in urgent need to stop the COVID-19 pandemic. To facilitate antiviral screening against SARS-CoV-2 without requirement for high biosafety level facility, we developed a bacterial artificial chromosome (BAC)-vectored replicon of SARS-CoV-2, nCoV-SH01 strain, in which secretedGaussialuciferase (sGluc) was encoded in viral subgenomic mRNA as a reporter gene. The replicon was devoid of structural genes spike (S), membrane (M), and envelope (E). Upon transfection, the replicon RNA replicated in various cell lines, and was sensitive to interferon alpha (IFN-α), remdesivir, but was resistant to hepatitis C virus inhibitors daclatasvir and sofosbuvir. Replication of the replicon was also sensitive overexpression of zinc-finger antiviral protein (ZAP). We also constructed a four-plasmidin-vitroligation system that is compatible with the BAC system, which makes it easy to introduce desired mutations into the assembly plasmids forin-vitroligation. This replicon system would be helpful for performing antiviral screening and dissecting virus-host interactions.
Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model
Authors: Ryu Seungjin , Shchukina Irina , Youm Yun-Hee , Qing Hua , Hilliard Brandon K. , Dlugos Tamara , Zhang Xinbo , Yasumoto Yuki , Booth Carmen J. , Fernández-Hernando Carlos , Suárez Yajaira , Khanna Kamal M. , Horvath Tamas L. , Dietrich Marcelo O. , Artyomov Maxim N. , Wang Andrew , Dixit Vishwa Deep 
Published: September 2020

SUMMARYIncreasing age is the strongest predictor of risk of COVID-19 severity. Unregulated cytokine storm together with impaired immunometabolic response leads to highest mortality in elderly infected with SARS-CoV-2. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain MHV-A59 (mCoV-A59) that recapitulated majority of clinical hallmarks of COVID-19. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Ketogenic diet increases beta-hydroxybutyrate, expands tissue protective γδ T cells, deactivates the inflammasome and decreases pathogenic monocytes in lungs of infected aged mice. These data underscore the value of mCoV-A59 model to test mechanism and establishes harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against COVID-19 in the elderly.Highlights-Natural MHV-A59 mouse coronavirus infection mimics COVID-19 in elderly.-Aged infected mice have systemic inflammation and inflammasome activation-Murine beta coronavirus (mCoV) infection results in loss of pulmonary γδ T cells.-Ketones protect aged mice from infection by reducing inflammation.eTOC BlurbElderly have the greatest risk of death from COVID-19. Here, Ryu et al report an aging mouse model of coronavirus infection that recapitulates clinical hallmarks of COVID-19 seen in elderly. The increased severity of infection in aged animals involved increased inflammasome activation and loss of γδ T cells that was corrected by ketogenic diet.