bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-cell atlas of the peripheral immune response to severe COVID-19
Authors: Wilk Aaron J. , Rustagi Arjun , Zhao Nancy Q. , Roque Jonasel , Martinez-Colon Giovanny J. , McKechnie Julia L. , Ivison Geoffrey T. , Ranganath Thanmayi , Vergara Rosemary , Hollis Taylor , Simpson Laura J. , Grant Philip , Subramanian Aruna , Rogers Angela J. , Blish Catherine A. 
Published: April 2020

ABSTRACTThere is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.
Trends of SARS-Cov-2 infection in 67 countries: Role of climate zone, temperature, humidity and curve behavior of cumulative frequency on duplication time
Authors: Berumen Jaime , Schmulson Max , Guerrero Guadalupe , Barrera Elizabeth , Larriva-Sahd Jorge , Olaiz Gustavo , Garcia-Leyva Rebeca , Wong Chew Rosa María , Betancourt-Cravioto Miguel , Gallardo Héctor , Fajardo-Dolci Germán , Tapia-Conyer Roberto 
Published: April 2020

SummaryObjectiveTo analyze the role of temperature, humidity, date of first case diagnosed (DFC) and the behavior of the growth-curve of cumulative frequency (CF) [number of days to rise (DCS) and reach the first 100 cases (D100), and the difference between them (ΔDD)] with the doubling time (Td) of Covid-19 cases in 67 countries grouped by climate zone.DesignRetrospective incident case study.SettingWHO based register of cumulative incidence of Covid-19 cases.Participants1,706,914 subjects diagnosed between 12-29-2019 and 4-15-2020.ExposuresSARS-Cov-2 virus, ambient humidity, temperature and climate areas (temperate, tropical/subtropical).Main outcome measuresComparison of DCS, D100, ΔDD, DFC, humidity, temperature, Td for the first (Td10) and second (Td20) ten days of the CF growth-curve between countries according to climate zone, and identification of factors involved in Td, as well as predictors of CF using lineal regression models.ResultsTd10 and Td20 were ≥3 days longer in tropical/subtropical vs. temperate areas (2.8±1.2 vs. 5.7±3.4; p=1.41E-05 and 4.6±1.8 vs. 8.6±4.2; p=9.7E-05, respectively). The factors involved in Td10 (DFC and ΔDD) were different than those in Td20 (Td10 and climate areas). After D100, the fastest growth-curves during the first 10 days, were associated with Td10<2 and Td10<3 in temperate and tropical/subtropical countries, respectively. The fold change Td20/Td10 >2 was associated with earlier flattening of the growth-curve. In multivariate models, Td10, DFC and ambient temperature were negatively related with CF and explained 44.7% (r2 = 0.447) of CF variability at day 20 of the growth-curve, while Td20 and DFC were negatively related with CF and explained 63.8% (r2 = 0.638) of CF variability towards day 30 of the growth-curve.ConclusionsThe larger Td in tropical/subtropical countries is positively related to DFC and temperature. Td and environmental factors explain 64% of CF variability in the best of cases. Therefore, other factors, such as pandemic containment measures, would explain the remaining variability.
Identification of super-transmitters of SARS-CoV-2
Authors: Yang Xuemei , Dong Ning , Chan Edward Wai-Chi , Chen Sheng 
Published: April 2020

AbstractA newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2.
Impact of control strategies on COVID-19 pandemic and the SIR model based forecasting in Bangladesh
Authors: Rahman Mohammad Mahmudur , Ahmed Asif , Hossain Khondoker Moazzem , Haque Tasnima , Hussain Anowar 
Published: April 2020

ABSTRACTBackgroundCOVID-19 is transmitting worldwide drastically and infected nearly two and half million of people so far. Till date 2144 cases of COVID-19 is confirmed in Bangladesh till 18th April though the stage-3/4 transmission is not validated yet.MethodsTo project the final infection numbers in Bangladesh we used the SIR mathematical model. Confirmed cases of infection data were obtained from Institute of Epidemiology, Disease Control and Research (IEDCR) of BangladeshResultsThe confirmed cases in Bangladesh follow our SIR model prediction cases. By the end of April the predicted cases of infection will be 17450 to 21616 depending on the control strategies. Due to large population and socio-economic characteristics, we assumed 60% social distancing and lockdown can be possible. Assuming that, the predicated final size of infections will be 3782558 on the 92th day from the first infections and steadily decrease to zero infection after 193 daysConclusionTo estimate the impact of social distancing we assumed eight different scenarios, the predicted results confirmed the positive impact of this type of control strategies suggesting that by strict social distancing and lockdown, COVID-19 infection can be under control and then the infection cases will steadily decrease down to zero.
Dynamics of Transmission and Control of COVID-19: A Real-time Estimation Using the Kalman Filter
Authors: Marioli Francisco Arroyo , Bullano Francisco , Rondón-Moreno Carlos 
Published: April 2020

AbstractThe COVID-19 pandemic has become the center of attention for both researchers and authorities. In this paper, we propose and test a methodology to estimate the daily effective reproduction number (ℛt) through the lens of the Kalman Filter and Bayesian estimation. Moreover, we apply our method to data from the current COVID-19 pandemic in China, Italy, Japan, and South Korea. We correlate our findings with the implementation of control measures in each of these countries. Our results show that China, Italy, and South Korea have been able to reduce ℛt over time. We find significant heterogeneity in the way ℛt decreases across countries. For instance, China reduced ℛt from its peak to below one in 19 days, while South Korea achieved the same reduction in 12 days. In contrast, it has taken Italy almost a month to reach similar levels. We hypothesize this is related to how strict, enforceable, and comprehensive are the implemented policies.
Community and Socioeconomic Factors Associated with COVID-19 in the United States: Zip code level cross sectional analysis
Authors: Guha Avirup , Bonsu Janice M. , Dey Amit Kumar , Addison Daniel 
Published: April 2020

AbstractBackgroundMultiple reports have pointed towards involvement of community and socioeconomic characteristics of people in the United States may be associated with COVID-19 cases and deaths.MethodsIn this study, zip-code level data from 5 major metropolitan areas, was utilized to study the effect of multiple demographic & socioeconomic factors – including race, age, income, chronic disease comorbidity, population density, number of people per household on number of positive cases and ensuing death. Adjusted linear regression analysis using 13 to 16 such variables was performed.ResultsOverall, 442 zip codes reporting 93,170 positive COVID-19 cases and 138 zip codes reporting mortality ranging from 0 to 25 were included in this study. A multivariable linear regression model noted that 1% increase in the proportion of residents above the age of 65 years, proportion of African American residents, proportion of females, persons per household and population density of the zip code increased the proportion of positive cases by 0.77%, 0.23%, 1.64%, 1.83% and 0.46% respectively (P<0.01) with only population density remaining significant in zip codes with greater than median number of cases. In zips with greater than median number of deaths, no community/socio-economic factor contributed significantly to death.ConclusionThis study gives early signals of gender, and racial inequalities while providing overwhelming evidence of how population density may contribute to an increase in the number of positive cases of COVID-19.
Fruit bromelain derived peptides destabilize growth of amyloidal fibrils
Authors: Das Sromona , Dutta Sangita , Paidi Ramesh K , Biswas Subhas C , Halder Umesh C , Bhattacharyya Debasish 
Published: April 2020

ABSTRACTβ-Amyloid deposition as fibrillar plaques in brain is the primary cause of Alzheimer’s disease. We report potency of cysteine protease ‘fruit bromelain’ from pineapple in destabilising Aβ fibrils. Bromelain peptide pool (Mw<500 Da) obtained mimicking human alimentary tract digestion inhibited fibrillation from monomeric and oligomeric states of A and irreversibly dissociated preformed fibrils into small oligomers of varied sizes. Time kinetics was followed by Thioflavin-T assay and microscopic imaging. Synthetic bromelain peptides corresponding to Aβ sticky region found using ClustalW analysis revealed specificity of peptides in destabilisation of amyloidal structures. Spectra of different molecular states of Aβ obtained from application of 8-anilino-1-naphthalenesulfonic acid, circular dichroism and Fourier-Transformed Infrared spectroscopy collectively indicated interaction dependent structural change. Probable mechanism for fibril dissociation was thus predicted. Peptides relieved Aβ cytotoxicity on pheochromcytoma cells and dissociated plaques in AD-type rats prepared by bilateral intracerebroventricular administration of Aβ in rat brain cortex. Pineapple being a phytoceutical, its efficiency to disaggregate amyloid bodies warrant further investigation.GRAPHICAL ABSTRACT
Tissue accumulation and the effects of long-term dietary copper contamination on osmoregulation in the mudflat fiddler crabMinuca rapax(Crustacea, Ocypodidae)
Authors: Capparelli MV , McNamara JC , Grosell MG 
Published: April 2020

AbstractWe examined copper accumulation in the hemolymph, gills and hepatopancreas, and hemolymph osmolality, Na+and Cl-concentrations, together with gill Na+/K+-ATPase and carbonic anhydrase activities, after dietary copper delivery (0, 100 or 500 µg Cu/g) for 12 days in a fiddler crab,Minuca rapax. In contaminated crabs, copper concentration decreased in the hemolymph and hepatopancreas, but increased in the gills. Hemolymph osmolality and gill Na+/K+-ATPase activity increased while hemolymph [Na+] and [Cl-] and gill carbonic anhydrase activity decreased. Excretion likely accounts for the decreased hemolymph and hepatopancreas copper titers. Dietary copper clearly affects osmoregulatory ability and hemolymph Na+and Cl-regulation inM. rapax. Gill copper accumulation decreased carbonic anhydrase activity, suggesting that dietary copper affects acid-base balance. Elevated gill Na+/K+-ATPase activity appears to compensate for the ion-regulatory disturbance. These effects of dietary copper illustrate likely impacts on semi-terrestrial species that feed on metal contaminated sediments.
Neural markers of vulnerability to anxiety outcomes following traumatic brain injury
Authors: Popovitz Juliana , Mysore Shreesh P. , Adwanikar Hita 
Published: April 2020

SUMMARYAnxiety outcomes following traumatic brain injury (TBI) are complex, and the underlying neural mechanisms are poorly understood. Here, we developed a multidimensional behavioral profiling approach to investigate anxiety-like outcomes in mice that takes into account individual variability. Departing from the tradition of comparing outcomes in TBI versus sham groups, we identified animals within the TBI group that are vulnerable to anxiety dysfunction by applying dimensionality reduction, clustering and post-hoc validation to behavioral data obtained from multiple assays for anxiety at several post-injury timepoints. These vulnerable animals expressed distinct molecular profiles in the corticolimbic network, with downregulation in GABA and glutamate, and upregulation in NPY markers. Indeed, among vulnerable animals, not resilient or sham controls, severity of anxiety outcomes correlated strongly with expression of molecular markers. Our results establish a foundational approach, with predictive power, for reliably identifying maladaptive anxiety outcomes following TBI and uncovering neural signatures of vulnerability to anxiety.
A Thermodynamic Interpretation of the Stimulated Raman Spectroscopic Signature of an Action Potential in a Single Neuron
Authors: Shrivastava Shamit , Lee Hyeon Jeong , Cheng Ji-Xin 
Published: April 2020

AbstractIt has previously been suggested that the plasma membrane condenses and melts reversibly during an action potential in a neuron, analogous to an acoustic wave travelling in the compressive membrane region. If true it has fundamental consequences for our understanding of the regulation of biological functions during an action potential. It has long been known that the electrical dipoles in the neuronal membrane reorient during an action potential, observed through a variety of optical methods. However, this information has been insufficient to confirm if and how the collective thermodynamic state of the neuronal membrane changes during an action potential. Here, we show that hyperspectral stimulated Raman spectroscopy (SRS) can resolve the thermodynamic state of the neuronal membranes in a single neuron during an action potential. These measurements indicate that the system becomes ordered and compressed during the de-polarisation phase and disordered and expanded during hyper polarisation Therefore, the observation is consistent with the acoustic hypothesis and SRS provides a powerful tool to not only further validate the hypothesis in future, but also explore the role of membrane thermodynamics during an action potential.
Reference-free andde novoIdentification of Circular RNAs
Authors: Qin Yangmei , Xu Tingting , Lin Wenbo , Jia Qingjie , He Qiushun , Liu Ke , Du Juan , Chen Linshan , Yang Xiaozhen , Du Fei , Li Mengjun , Chen Min , Tao Tao , Ji Zhi-Liang 
Published: April 2020

AbstractBackgroundEarly studies have unveiled multiple regulatory functions of circular RNAs (circRNAs); however, accurate detection and quantification of circRNAs, especially in understudied organisms, is unsolved yet.ResultsIn this study, we developed a new reference-free method, namely Cirit, tode novodetect circRNAs with sequence support from the next generation sequencing (NGS) transcriptome. The Cirit showed remarkable performance in accurate detection and quantification of circRNAs via comparing with current methods from different aspects. Using Cirit, we detected 28,813 nonredundant human circRNAs from 91 transcriptome datasets, as well as 2,385 circRNAs from four understudied organisms. Subsequent analyses found that the majority of human circRNAs expressed spatiotemporally; only a very small portion of circRNAs were back-splice junction (BSJ)-consistent (maximally 5.17%) or sequence-consistent (under 2%). Furthermore, circRNA genesis were relatively flexible that only about 60% of human circRNAs used the canonical GT-AG pattern for back-splice. The inconsistent expression of circRNAs challenges their roles as precise transcriptional regulators.ConclusionsIn summary, the reference-free method provides a straightforward and universal way for reliable circRNA research. It will largely boost the successful rate in designing highly specific probes to monitor circRNA behavior in cell. In particular, it brings circRNA research to the organisms that have no genome or draft genome.
Allosteric HSP70 inhibitors perturb mitochondrial proteostasis and overcome proteasome inhibitor resistance in multiple myeloma
Authors: Ferguson Ian D. , Lin Yu-Hsiu T. , Lam Christine , Shao Hao , Hale Martina , Tharp Kevin M. , Mariano Margarette C. , Steri Veronica , Wang Donghui , Phojanokong Paul , Tuomivaara Sami T. , Hann Byron , Driessen Christoph , Van Ness Brian , Gestwicki Jason E. , Wiita Arun P. 
Published: April 2020

AbstractProteasome inhibitor (PI) resistance remains a central challenge in multiple myeloma. To identify pathways mediating resistance, we first map proteasome-associated genetic co-dependencies. We identify cytosolic heat shock protein 70 (HSP70) chaperones as potential targets, consistent with proposed mechanisms of myeloma tumor cells overcoming PI-induced stress. These results lead us to explore allosteric HSP70 inhibitors (JG compounds) as myeloma therapeutics. We show these compounds exhibit increased efficacy against acquired and intrinsic PI-resistant myeloma models, unlike HSP90 inhibition. Surprisingly, shotgun and pulsed-SILAC proteomics reveal that JGs overcome PI resistance not via the expected mechanism of inhibiting cytosolic HSP70s, but instead through mitochondrial-localized HSP70, HSPA9, destabilizing the 55S mitoribosome. Analysis of myeloma patient data further supports strong effects of global proteostasis capacity, and particularlyHSPA9expression, on PI response. Our results characterize dynamics of myeloma proteostasis networks under therapeutic pressure while motivating further investigation of HSPA9 as a specific vulnerability in PI-resistant disease.
Negative feedback may suppress variation to improve collective foraging performance
Authors: Reina Andreagiovanni , Marshall James A. R. 
Published: April 2020

AbstractSocial insect colonies use negative as well as positive feedback signals to regulate foraging behaviour. In ants and bees individual foragers have been observed to use negative pheromones or mechano-auditory signals to indicate that forage sources are not ideal, for example being unrewarded, crowded, or dangerous. Here we propose an additional function for negative feedback signals during foraging, variance reduction. We show that while on average populations will converge to desired distributions over forage patches both with and without negative feedback signals, in small populations negative feedback reduces variation around the target distribution compared to the use of positive feedback alone. Our results are independent of the nature of the target distribution, providing it can be achieved by foragers collecting only local information. Since robustness is a key aim for biological systems, and deviation from target foraging distributions may be costly, we argue that this could be a further important and hitherto overlooked reason that negative feedback signals are used by foraging social insects.
Membrane estrogen receptor (GPER) and follicle-stimulating hormone receptor heteromeric complexes promote human ovarian follicle survival
Authors: Casarini Livio , Lazzaretti Clara , Paradiso Elia , Limoncella Silvia , Riccetti Laura , Sperduti Samantha , Melli Beatrice , Marcozzi Serena , Anzivino Claudia , Sayers Niamh S. , Czapinski Jakub , Brigante Giulia , Potì Francesco , Marca Antonio La , De Pascali Francesco , Reiter Eric , Falbo Angela , Daolio Jessica , Villani Maria Teresa , Lispi Monica , Orlando Giovanna , Klinger Francesca G. , Fanelli Francesca , Rivero-Müller Adolfo , Hanyaloglu Aylin C. , Simoni Manuela 
Published: April 2020

AbstractClassically, follicle stimulating hormone receptor (FSHR) driven cAMP-mediated signaling boosts human ovarian follicle growth and would be essential for oocyte maturation. However, contradictingin vitrosuggest a different view on physiological and clinical significance of FSHR-mediated cAMP signaling. We found that the G protein coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are effectively delivered upon equal expression levels of both receptors, while they are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with FSH responsiveness of patients undergoing controlled ovarian stimulation. Consistent with high FSHR expression levels during follicular selection, cell viability is dramatically reduced in FSHR overexpressing cells due to preferential coupling to the Gαs protein/cAMP pathway. In contrast, FSHR/GPER heteromer formation resulted in FSH-triggered anti-apoptotic/proliferative signaling delivered via the Gβγ dimer while heteromer impairment or GPER-associated Gαs inhibitory protein complexes resulted in cell death. GPER-depleted granulosa cells have an amplified FSH-dependent decrease in cell viability and steroidogenesis, consistent with the requirement of estrogen signaling for successful oocyte growth. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation.One Sentence SummaryFSHR/GPER heteromers block cAMP-dependent selection of ovarian follicles and target tumor growth and poor FSH-response in women.