bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis of severe COVID-19 patients reveals a monocyte-driven inflammatory storm attenuated by Tocilizumab
Authors: Guo Chuang , Li Bin , Ma Huan , Wang Xiaofang , Cai Pengfei , Yu Qiaoni , Zhu Lin , Jin Liying , Jiang Chen , Fang Jingwen , Liu Qian , Zong Dandan , Zhang Wen , Lu Yichen , Li Kun , Gao Xuyuan , Fu Binqing , Liu Lianxin , Ma Xiaoling , Weng Jianping , Wei Haiming , Jin Tengchuan , Lin Jun , Qu Kun 
Published: April 2020

ABSTRACTDespite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8+T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab’s powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms.
Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux
Authors: Nilsson Oktawia , Lindvall Mikaela , Obici Laura , Ekström Simon , Lagerstedt Jens O. , Del Giudice Rita 
Published: April 2020

AbstractSpecific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis. Carriers do not exhibit increased cardiovascular disease risk despite reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of L75P and L174S patients presents a higher relative abundance of the 8.4 nm vs 9.6 nm particles, and that serum from patients, as well as reconstituted 8.4 and 9.6 nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4 nm rHDL have altered secondary structure composition and display a more flexible binding to lipids compared to their native counterpart. The reduced HDL-cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles and better cholesterol efflux due to altered, region-specific protein structure dynamics.
Measuring the quality of scientific references in Wikipedia: an analysis of more than 115M citations to over 800,000 scientific articles
Authors: Nicholson Joshua M. , Uppala Ashish , Sieber Matthias , Grabitz Peter , Mordaunt Milo , Rife Sean 
Published: April 2020

AbstractWikipedia is a widely used online reference work which cites hundreds of thousands of scientific articles across its entries. The quality of these citations has not been previously measured, and such measurements have a bearing on the reliability and quality of the scientific portions of this reference work. Using a novel technique, a massive database of qualitatively described citations, and machine learning algorithms, we analyzed 1,923,575 Wikipedia articles which cited a total of 824,298 scientific articles, and found that most scientific articles (57%) are uncited or untested by subsequent studies, while the remainder show a wide variability in contradicting or supporting evidence (2-41%). Additionally, we analyzed 51,804,643 scientific articles from journals indexed in the Web of Science and found that most (85%) were uncited or untested by subsequent studies, while the remainder show a wide variability in contradicting or supporting evidence (1-14%).
Computational search of hybrid human/ SARS-CoV-2 dsRNA reveals unique viral sequences that diverge from those of other coronavirus strains
Authors: Pasquier Claude , Robichon Alain 
Published: April 2020

AbstractThe role of the RNAi/Dicer/Ago system to degrade RNA viruses has been elusive in mammals, which prompted authors to think that interferon (IFN) synthesis is essential in this clade relegating the RNAi defense strategy against viral infection as accessory function. We explore the theoretical possibilities that RNAi triggered by SARS-CoV-2 might degrade some host transcripts in the opposite direction although this hypothesis seems counter intuitive. SARS-CoV-2 genome was therefore computational searched for exact intra pairing within the viral RNA and also hybrid exact pairing with human transcriptome over a minimum 20 bases length. Minimal segments of 20 bases length of SARS-CoV-2 RNA were found based on the theoretical matching with existing complementary strands in the human host transcriptome. Few human genes potentially annealing with SARS-CoV-2 RNA, among them mitochondrial deubiquitinase USP30, a subunit of ubiquitin protein ligase complex FBXO21 along with two long coding RNAs were retrieved. The hypothesis that viral originated RNAi might mediate degradation of messengers of the host transcriptome was corroborated by clinical observation and phylogenetic comparative analysis indicating a strong specificity of these hybrid pairing sequences for both SARS-CoV-2 and human genomes.
A new model for vertebrate mineralization via stabilized amorphous calcium carbonate for avian eggshell formation
Authors: Stapane Lilian , Le Roy Nathalie , Ezagal Jacky , Rodriguez-Navarro Alejandro B. , Labas Valérie , Combes-Soia Lucie , Hincke Maxwell T. , Gautron Joël 
Published: April 2020

ABSTRACTAmorphous calcium carbonate (ACC) is an unstable mineral phase, which is progressively transformed into aragonite or calcite in biomineralization of marine invertebrate shells or avian eggshells, respectively. We have previously proposed a model of vesicular transport to provide stabilized ACC in chicken uterine fluid where mineralization takes place. Herein, we report further experimental evidence for this model. We confirmed the presence of extracellular vesicles (EVs) that contain ACC in uterine fluid using transmission electron microscopy and elemental analysis. We also demonstrate high levels of expression of vesicular markers in the oviduct segments where eggshell is formed. Moreover, proteomics and immunofluorescence confirmed the presence of major vesicular, mineralization-specific and eggshell matrix proteins in the uterus and in purified EVs. We propose a comprehensive role for EVs in eggshell mineralization, in which annexins transfer calcium into vesicles and carbonic anhydrase 4 catalyzes the formation of HCO3−, for accumulation of ACC in vesicles. We hypothesize that ACC is stabilized by ovalbumin and/or lysozyme or additional vesicle proteins identified in this study. Finally, EDIL3 and MFGE8 are proposed to serve as guidance molecules to target EVs to the mineralization site. We therefore report for the first time experimental evidence for the components of vesicular transport to supply ACC in vertebrate biomineralization. These results could give insight to understand the mineralization of otoconia, which are calcium carbonate biomineralized structures present in all vertebrates and necessary for balance and sensing linear acceleration.
M2 Cortex-Dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington’s Disease
Authors: Fernández-García Sara , Conde-Berriozabal Sara , García-García Esther , Gort-Paniello Clara , Bernal-Casas David , Barriga Gerardo García-Díaz , López-Gil Javier , Muñoz-Moreno Emma , Sòria Guadalupe , Campa Leticia , Artigas Francesc , Rodriguez Manuel J , Alberch Jordi , Masana Mercè 
Published: April 2020

AbstractHuntington’s disease (HD) is a neurological disorder characterized by motor disturbances. HD pathology is most prominent in the striatum, the central hub of basal ganglia. The cortex is the main striatal afference and progressive cortico-striatal disconnection characterizes HD. We mapped cortico-striatal dysfunction in HD mice to ultimately modulate the activity of selected cortico-striatal circuits to ameliorate motor symptoms and recover synaptic plasticity. Multimodal MRIin vivosuggested prominent functional network deficits in fronto-striatal compared to motor-striatal pathways, which were accompanied by reduced glutamate levels in the striatum of HD mice. Moreover, optogenetically-stimulated glutamate release from fronto-striatal terminals was reduced in HD mice and electrophysiological responses in striatal neurons were blunted. Remarkably, repeated M2 Cortex-dorsolateral striatum optogenetic stimulation normalized motor behavior in HD mice and evoked a sustained increase of synaptic plasticity. Overall, these results reveal that the selective stimulation of fronto-striatal pathways can become an effective therapeutic strategy in HD.
Lipidomic and Ultrastructural Characterization of Cell Envelope ofStaphylococcus aureusGrown in the Presence of Human Serum
Authors: Hines Kelly M. , Alvarado Gloria , Chen Xi , Gatto Craig , Pokorny Antje , Alonzo Francis , Wilkinson Brian J. , Xu Libin 
Published: April 2020

ABSTRACTStaphylococcus aureuscan incorporate exogenous straight-chain unsaturated and saturated fatty acids (SCUFAs and SCFAs, respectively) to replace some of the normally biosynthesized branched-chain fatty acids and SCFAs. In this study, the impact of human serum on theS. aureuslipidome and cell envelope structure was comprehensively characterized. When grown in the presence of 20% human serum, typical human serum lipids, such as cholesterol, sphingomyelin, phosphatidylethanolamines, and phosphatidylcholines, were present in the total lipid extracts. Mass spectrometry showed that SCUFAs were incorporated into all majorS. aureuslipid classes,i.e., phosphatidylglycerols, lysyl-phosphatidylglycerols, cardiolipins, and diglucosyldiacylglycerols. Heat-killedS. aureusretained much fewer serum lipids and failed to incorporate SCUFAs, suggesting that association and incorporation of serum lipids withS. aureusrequires a living or non-denatured cell. Cytoplasmic membranes isolated from lysostaphin-produced protoplasts of serum-grown cells retained serum lipids, but washing cells with Triton X-100 removed most of them. Furthermore, electron microscopy studies showed that serum-grown cells had thicker cell envelopes and associated material on the surface, which was partially removed by Triton X-100 washing. To investigate which serum lipids were preferentially hydrolyzed byS. aureuslipases for incorporation, we incubated individual serum lipid classes withS. aureusand found that cholesteryl esters (CEs) and triglycerides (TGs) are the major donors of the incorporated fatty acids. Further experiments using purified Geh lipase confirmed CEs and TGs being the substrates of this enzyme. Thus, growth in the presence of serum altered the nature of the cell surface with implications for interactions with the host.IMPORTANCEComprehensive lipidomics ofS. aureusgrown in the presence of human serum suggests human serum lipids can associate with the cell envelope without being truly integrated into the lipid membrane. However, fatty acids-derived from human serum lipids, including unsaturated fatty acids, can be incorporated into lipid classes that can be biosynthesized byS. aureusitself. Cholesteryl esters and triglycerides are found to be the major source of incorporated fatty acids upon hydrolysis by lipases. These findings have significant implications for the nature of theS. aureuscell surface when grownin vivo. Changes in phospholipid and glycolipid abundances and fatty acid composition could affect membrane biophysics and function and the activity of membrane-targeting antimicrobials. Finally, the association of serum lipids with the cell envelope has implications for the physicochemical nature of the cell surface and its interaction with host defense systems.
Spatial modeling cannot currently differentiate SARS-CoV-2 coronavirus and human distributions on the basis of climate in the United States
Authors: Harbert Robert , Cunningham Seth W. , Tessler Michael 
Published: April 2020

AbstractThe SARS-CoV-2 coronavirus is wreaking havoc globally, yet knowledge of its biology is limited. Climate and seasonality influence the distributions of many diseases, and studies suggest a link between SARS-CoV-2 and cool weather. One such study, building species distribution models (SDMs), predicted SARS-CoV-2 risk may remain concentrated in the Northern Hemisphere, shifting northward in summer months. Others have highlighted issues with SARS-CoV-2 SDMs, notably: the primary niche of the virus is the host it infects, climate may be a weak distributional predictor, global prevalence data have issues, and the virus is not in a population equilibrium. While these issues should be considered, climate still may be important for predicting the future distribution of SARS-CoV-2. To further examine if there is a link, we model with raw cases and population scaled cases for SARS-CoV-2 county-level data from the United States. We show that SDMs built from population scaled cases data cannot be distinguished from control models built from raw human population data, while SDMs built on raw data fail to predict the current known distribution of cases in the US. The population scaled analyses indicate that climate may not play a central role in current US viral distribution and that human population density is likely a primary driver. Still, we do find slightly more population scaled viral cases in cooler areas. This coupled with our geographically constrained focus make it so we cannot rule out climate as a partial driver of the US SARS-CoV-2 distribution. Climate’s role on SARS-CoV-2 should continue to be cautiously examined, but at this time we should assume that SARS-CoV-2 can spread anywhere in the US.
Protocol for a multicentre study of nosocomial SARS-CoV2 transmission The NOSO-COR Project
Authors: Saadatian-Elahi Mitra , Picot-Sanchez Valentina , Henaff Laetitia , Pradel Florence , Escuret Vanessa , Dananché Cédric , Elias Christelle , Endtz Hubert , Vanhems Philippe 
Published: April 2020

AbstractIntroductionThe newly identified SARS-CoV2 can cause serious acute respiratory infections such as pneumonia with a mortality rate of approximately 2% to 4%. In the current context of high incidence rates of SARS-CoV2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to study and document suspected or confirmed cases of nosocomial SARS-CoV2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals.Methods and analysisThis will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients, care givers and healthcare professionals in France and hospitals affiliated with the GABRIEL network.Demographic and clinical data will be collected using case-report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV2 by RT-PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV2 infections relative to all patients with syndromes suggestive of 2019-nCoV infection will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset.Ethics and disseminationThis study was approved by the clinical research and committee of Ile de France V on March 8, 2020.Registration detailsThe trial was registered in ClinicalTrials (NCT04290780).Strengths and limitations of the study➢This prospective study will generate and evaluate original data on nosocomial SARS-CoV2 infection in France and in the low-income countries of the GABRIEL network using the same protocol and standardised CRF.➢The results will provide the opportunity to compare the management of nosocomial Covid-19 infection in different settings for mutual exchanges and optimisation.➢The results will make it possible to refine the definition of nosocomial SARS-CoV2 infection, strengthen preventive campaigns for in-hospital transmission of SARS-CoV2 and pave the way for new recommendations in terms of preventive measures.➢Selection bias owing to access to care in different populations and bias owing to the extent of access to personal protective equipment, in particular, in low-income countries may occur.➢The non-exhaustivity of the confounders to be collected should be considered for interpretation of the results.
Robust Estimation of Infection Fatality Rates during the Early Phase of a Pandemic
Authors: Simon Perikles 
Published: April 2020

AbstractDuring a pandemic, robust estimation of case fatality rates (CFRs) is essential to plan and control suppression and mitigation strategies. At present, estimates for the CFR of COVID-19 caused by SARS-CoV-2 infection vary considerably. Expert consensus of 0.1–1% covers in practical terms a range from normal seasonable Influenza to Spanish Influenza. In the following, I deduce a formula for an adjusted Infection Fatality Rate (IFR) to assess mortality in a period following a positive test adjusted for selection bias.Official datasets on cases and deaths were combined with data sets on number of tests. After data curation and quality control, a total of IFR (n=819) was calculated for 21 countries for periods of up to 26 days between registration of a case and death.Estimates for IRFs increased with length of period, but levelled off at >9days with a median for all 21 countries of 0.11 (95%-CI: 0.073–0.15). An epidemiologically derived IFR of 0.040 % (95%-CI: 0.029%– 0.055%) was determined for Iceland and was very close to the calculated IFR of 0.057% (95%-CI: 0.042– 0.078), but 2.7–6-fold lower than CFRs. IFRs, but not CFRs, were positively associated with increased proportions of elderly in age-cohorts (n=21, spearman’s ρ=.73, p =.02).Real-time data on molecular and serological testing may further displace classical diagnosis of disease and its related death. I will critically discuss, why, how and under which conditions the IFR, provides a more solid early estimate of the global burden of a pandemic than the CFR.
Innovation, conservation and repurposing of gene function in plant root cell type development
Authors: Kajala Kaisa , Shaar-Moshe Lidor , Mason G. Alex , Gouran Mona , Rodriguez-Medina Joel , Kawa Dorota , Pauluzzi Germain , Reynoso Mauricio , Canto-Pastor Alex , Lau Vincent , Artur Mariana A. S. , West Donnelly A. , Manzano Concepcion , Gray Sharon B. , Yao Andrew I. , Bajic Marko , Formentin Elide , Nirmal Niba , Rodriguez Alan , Pasha Asher , Borowsky Alexander T. , Deal Roger B. , Kliebenstein Daniel , Hvidsten Torgeir R. , Provart Nicholas J. , Sinha Neelima , Runcie Daniel E. , Bailey-Serres Julia , Brady Siobhan M. 
Published: April 2020

AbstractPlant species have evolved myriads of solutions to adapt to dynamic environments, including complex cell type development and regulation. To understand this diversity, we profiled tomato root cell type translatomes and chromatin accessibility. Using xylem differentiation in tomato, relative to Arabidopsis, examples of functional innovation, repurposing and conservation of transcription factors are described. Repurposing and innovation of genes are further observed within an exodermis regulatory network and illustrate its function. Translatome analyses of rice, tomato and Arabidopsis tissues suggest that root meristems are more conserved, and that the functions of constitutively expressed genes are more conserved than those of cell type/tissue-enriched genes. These observations suggest that higher-order properties of cell type and pan-cell type regulation are conserved between plants and animals.One Sentence SummaryPan-species cell type translatome and chromatin accessibility data reveal novelty, conservation and repurposing of gene function.
NUDT21 links mitochondrial IPS-1 to RLR-containing stress granules and activates host antiviral defense
Authors: Aoyama-Ishiwatari Saeko , Okazaki Tomohiko , Iemura Shun-ichiro , Natsume Tohru , Okada Yasushi , Gotoh Yukiko 
Published: April 2020

SummaryViral RNA in the cytoplasm of mammalian host cells is recognized by retinoic acid– inducible protein–I (RIG-I)–like receptors (RLRs), which localize to cytoplasmic stress granules (SGs). Activated RLRs associate with the mitochondrial adaptor protein IPS-1, which activates antiviral host defense mechanisms including type I interferon (IFN) induction. It has remained unclear, however, how RLRs in SGs and IPS-1 in the mitochondrial outer membrane associate physically and engage in information transfer. Here we show that NUDT21, an RNA binding protein that regulates alternative transcript polyadenylation, physically associates with IPS-1 and mediates its localization to SGs in response to transfection with poly(I:C), a mimic of viral double-stranded RNA. We found that, despite its well-established function in the nucleus, a fraction of NUDT21 localizes to mitochondria in resting cells and becomes localized to SGs in response to poly(I:C) transfection. NUDT21 was also found to be required for efficient type I IFN induction in response to viral infection. Our results together indicate that NUDT21 links RLRs in SGs to mitochondrial IPS-1 and thereby activates host defense responses to viral infection.
In silicoAPC/C substrate discovery reveals cell cycle degradation of chromatin regulators including UHRF1
Authors: Kernan Jennifer L. , Martinez-Chacin Raquel C. , Wang Xianxi , Tiedemann Rochelle L. , Bonacci Thomas , Choudhury Rajarshi , Bolhuis Derek L. , Damrauer Jeffrey S. , Yan Feng , Harrison Joseph S. , Major Michael Ben , Hoadley Katherine , Suzuki Aussie , Rothbart Scott B. , Brown Nicholas G. , Emanuele Michael J. 
Published: April 2020

AbstractThe Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substratesin silico. This analysis identified many known substrates and suggested numerous candidates. Unexpectedly, chromatin regulatory proteins are enriched among putative substrates and we show that several chromatin proteins bind APC/C, oscillate during the cell cycle and are degraded following APC/C activation, consistent with being direct APC/C substrates. Additional analysis revealed detailed mechanisms of ubiquitylation for UHRF1, a key chromatin regulator involved in histone ubiquitylation and DNA methylation maintenance. Disrupting UHRF1 degradation at mitotic exit accelerates G1-phase cell cycle progression and perturbs global DNA methylation patterning in the genome. We conclude that APC/C coordinates crosstalk between cell cycle and chromatin regulatory proteins. This has potential consequences in normal cell physiology, where the chromatin environment changes depending on proliferative state, as well as in disease.