bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of SARS-CoV-2 spike protein binding to human, pet, farm animals, and putative intermediate hosts ACE2 and ACE2 receptors
Authors: Zhai Xiaofeng , Sun Jiumeng , Yan Ziqing , Zhang Jie , Zhao Jin , Zhao Zongzheng , Gao Qi , He Wan-Ting , Veit Michael , Su Shuo 
Published: May 2020

ABSTRACTThe emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used recently released X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, pigs and dogs which are not or not effectively infected, respectively, have only a few changes in the binding site have relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from bat and pangolin revealed that the latter contains only one substitution, whereas the bat virus exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-COV-2.IMPORTANCESARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. However, the lower expression of ACE2 in the upper respiratory tract of some pets and livestock means more research and monitoring should be done to explore the animal source of infection and the risk of potential cross-species transmission. Finally, the analysis also showed that SARS-CoV-2 may not specifically adapted to any of its putative intermediate hosts.
AI334 and AQ806 antibodies recognize the spike S protein from SARS-CoV-2 by ELISA
Authors: Hammel Philippe , Marchetti Anna , Lima Wanessa C. , Lau Kelvin , Pojer Florence , Hacker David , Cosson Pierre 
Published: May 2020

AbstractWe tested 10 recombinant antibodies directed against the spike S protein from SARS-CoV-1. Among them, antibodies AI334 and AQ806 detect by ELISA the spike S protein from SARS-CoV-2.
The consensus Nglyco-X-S/T motif and a previously unknown Nglyco-N -linked glycosylation are necessary for growth and pathogenicity ofPhytophthora
Authors: Zhang Can , Chen Shanshan , Zhang Fan , Cui Tongshan , Xue Zhaolin , Wang Weizhen , Zhang Borui , Liu Xili 
Published: May 2020

AbstractAsparagine (Asn, N) -linked glycosylation within the glycosylation motif (Nglyco-X-S/T; X≠P) is a ubiquitously distributed post-translational modification that participates in diverse eukaryotic cellular processes. However, little is known about the characteristic features and roles of N-glycosylation in oomycetes. In this work, it found that 2.5 μg/ml tunicamycin (N-glycosylation inhibitor) completely inhibitedPhytophthora sojaegrowth, suggesting that N-glycosylation is necessary for oomycete development. We conducted a glycoproteomic analysis ofP. sojaeto identify and map all N-glycosylated proteins and to quantify differentially expressed glycoproteins associated with mycelia, asexual cysts, and sexual oospores. A total of 355 N-glycosylated proteins were found, containing 496 glycosites that likely participate in glycan degradation, carbon metabolism, glycolysis, or other central metabolic pathways. To verify the glycoproteomic results and further examine the function of N-glycosylation inP. sojae, two proteins were selected for PNGase F deglycosylation assays and CRISPR/Cas9-mediated site-directed mutagenesis, including a GPI transamidase protein (GPI16) up-regulated in cysts, with the consensus Nglyco-X-S/T motif at Asn 94, and a heat shock protein 70 (HSP70) up-regulated in cysts and oospores with a previously unknown Nglyco-N motif at Asn 270. We demonstrated that the GPI16 and HSP70 are both N-glycosylated proteins, confirming that the Nglyco-N motif is a target site for asparagine - oligosaccharide N-glycosidic linkage. Glycosite mutations of Asn 94 in the GPI16 led to impaired cyst germination and pathogenicity, while HSP70 mutants exhibited decreased cyst germination and oospore production. This work describes an integrated map of oomycete N-glycoproteomes and advances our understanding of N-glycosylation in oomycetes. Moreover, we confirm that the consensus Nglyco-X-S/T and the Nglyco-N -linked glycosites are both essential for the growth ofPhytophthora sojae, indicating that there are multiple N-glycosylation motifs in oomycetes.
A Genetic Model Therapy Proposes a Critical Role for Liver Dysfunction in Mitochondrial Biology and Disease
Authors: Sabharwal Ankit , Wishman Mark D. , Cervera Roberto Lopez , Serres MaKayla R. , Anderson Jennifer L. , Treichel Anthony J. , Ichino Noriko , Liu Weibin , Yang Jingchun , Ding Yonghe , Deng Yun , Farber Steven A. , Clark Karl J. , Xu Xiaolei , Ekker Stephen C. 
Published: May 2020

AbstractThe clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Here we present a new animal model that recapitulates key components of Leigh Syndrome, French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the Leucine Rich Pentatricopeptide repeat-containing motif (LRPPRC) gene.LRPPRChas native functions related to mitochondrial mRNA polyadenylation and translation as well as a role in gluconeogenesis. We used the Gene-Breaking Transposon (GBT) cassette to create a revertible, insertional mutant zebrafish line in theLRPPRCgene.lrpprczebrafish homozygous mutants displayed impaired muscle development, liver function and lowered levels of mtDNA transcripts and are lethal by 12dpf, all outcomes similar to clinical phenotypes observed in patients. Investigations using anin vivolipidomics approach demonstrated accumulation of non-polar lipids in these animals. Transcript profiling of the mutants revealed dysregulation of clinically important nuclearly encoded and mitochondrial transcripts. Using engineered liver-specific rescue as a genetic model therapy, we demonstrate survival past the initial larval lethality, as well as restored normal gut development, mitochondrial morphology and triglyceride levels functionally demonstrating a critical role for the liver in the pathophysiology of this model of mitochondrial disease. Understanding the molecular mechanism of the liver-mediated genetic rescue underscores the potential to improve the clinical diagnostic and therapeutic developments for patients suffering from these devastating disorders.
Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19
Authors: Dong Cheng , Nakagawa Reiko , Oyama Kyohei , Yamamoto Yusuke , Zhang Weilian , Li Yanjun , Yoshimura Yuriko , Kamiya Hiroyuki , Nakayama Jun-ichi , Ueda Jun , Min Jinrong 
Published: May 2020

AbstractThe PRC2 (Polycomb repressive complex 2) complex is a multi-component histone H3K27 methyltransferase, best known for silencingHoxgenes during embryonic development. The Polycomb-like proteins PHF1, MTF2 and PHF19 are critical components of PRC2 by stimulating its catalytic activity in embryonic stem (ES) cells. The Tudor domains of PHF1/19 have been previously shown to be readers of H3K36me3in vitro. However, some other studies suggest that PHF1 and PHF19 co-localize with the H3K27me3 mark, but not H3K36me3 in cells. Here, we provide further evidence that PHF1 co-localizes with H3tK27 in testis, and its Tudor domain preferentially binds to H3tK27me3 over canonical H3K27me3in vitro. Our complex structures of the Tudor domains of PHF1 and PHF19 with H3tK27me3 shed light on the molecular basis for preferential recognition of H3tK27me3 by PHF1 and PHF19 over canonical H3K27me3, implicating that H3tK27me3 might be a physiological ligand of PHF1/19.
Strong Effects of Population Density and Social Characteristics on Distribution of COVID-19 Infections in the United States
Authors: Rajan Kumar B. , Dhana Klodian , Barnes Lisa L. , Aggarwal Neelum T. , Evans Laura E. , McAninch Elizabeth A. , Weuve Jennifer , Wilson Robert S. , DeCarli Charles , Evans Denis A. 
Published: May 2020

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19) has devastated global populations and has had a large impact in the United States. The objective of this manuscript is to study the relation of population demographics, social characteristics, and social distancing on the number of infections and deaths in the US.MethodsData came from publicly available sources. Social distancing was measured by the change in the rate of human encounters per km2 relative to the pre-COVID-19 national average. A smooth generalized additive model for counts of total infections and deaths at US county-level included population demographics, social characteristics, and social distancing.ResultsThe model strongly predicted the geo-spatial variations in COVID-19 infections and deaths, 97.2% of variation in infections and 99.3% of variation in deaths from March 15, 2020. US counties with higher population density, poverty index, civilian population, and minorities, especially African Americans, had a higher rate of infections and deaths, and social distancing was associated with a slower rate of infections and deaths. The number of people infected was increasing; however, the rate of increase of new infections was showing signs of plateauing from the second week of April. Our model estimates that 1,865,580 US residents will test positive for infections and 117,246 fatalities by June 1, 2020. Importantly, our model suggests significant social differences in the infections and deaths across US communities. Areas with a larger African American population and a higher poverty index are expected to show higher rates of infections and deaths.ConclusionPreventive steps, including social distancing and community closures, have been a cornerstone in slowing the transmission and potentially reducing the spread of the disease. Crucial knowledge of the role of social characteristics in disease transmission is essential to understand and predict current and future disease distribution and plan additional preventive steps.
CORRELATION BETWEEN CHEST COMPUTED TOMOGRAPHY AND LUNG ULTRASONOGRAPHY IN PATIENTS WITH CORONAVIRUS DISEASE 2019 (COVID-19)
Authors: Tung-Chen Yale , de Gracia Milagros Martí , Díez-Tascón Aurea , Agudo-Fernández Sergio , Alonso-González Rodrigo , Rodríguez-Fuertes Pablo , Parra-Gordo Luz , Ossaba-Vélez Silvia , Llamas-Fuentes Rafael 
Published: May 2020

ABSTRACTINTRODUCTIONThere is growing evidence regarding the imaging findings of Coronavirus Disease 2019 (COVID-19), in chest X-ray and Computed Tomography scan (CT). At this moment, the role of Lung Ultrasonography (LUS) has yet to be explored.OBJECTIVESThe main purpose of this study is to evaluate the correlation between LUS findings and chest CT in confirmed (positive RT-PCR) or clinically highly suspicious (dyspnea, fever, myasthenia, gastrointestinal symptoms, dry cough, ageusia or anosmia) of COVID-19 patients.METHODSProspective study carried out in the emergency department (ED) of confirmed or clinically highly suspicious COVID-19 patients who were subjected to a chest CT and concurrent LUS exam. An experienced ED physician performed the LUS exam blind to the clinical history and results of the CT scan, which were reviewed by two radiologists in consensus for signs compatible with COVID-19 (bilateral ground-glass opacities in peripheral distribution). Compatible LUS exam was considered a bilateral pattern of B-lines, irregular pleural line and subpleural consolidations.RESULTSBetween March and April 2020, fifty-one patients were consecutively enrolled. The indication for CT was a negative or indeterminate RT-PCR test (49.0%) followed by suspicion of pulmonary embolism (41.2%). Radiological signs compatible with COVID-19 were present in thirty-seven patients (72.5%) on CT scan and forty patients (78.4%) on LUS exam. The presence of LUS findings was correlated with a positive CT scan suggestive of COVID-19 (OR: 13.3, 95%CI: 4.539.6, p<0.001) with a sensitivity of 100.0% and a specificity of 78.6%, positive predictive value of 92.5% and negative of 100.0%. There was no missed diagnosis of COVID-19 with LUS compared to CT in our cohort. The LUS Score had a good correlation with CT total severity score (ICC 0.803, 95% CI 0.60-0.90, p<0.001).CONCLUSIONLUS presents similar accuracy compared to chest CT to detect lung abnormalities in COVID-19 patients.Summary StatementLUS presents similar accuracy compared to chest CT to detect lung abnormalities in COVID-19 patients.Key Results-Common LUS findings mirror those previously described for CT: bilateral, peripheral, consolidation and/or ground glass opacities.-LUS findings correlated with CT scan with a sensitivity of 100.0% and a specificity of 78.6%, positive predictive value of 92.5% and negative of 100.0%. The Lung score had a good correlation with CT total severity score (ICC 0.803, 95% CI 0.601-0.903, p < 0.001).-There were no missed diagnosis of COVID-19 with LUS compared to CT in our cohort.
Global analysis of daily new COVID-19 cases reveals many static-phase countries including US and UK potentially with unstoppable epidemics
Authors: Fu Xinmiao 
Published: May 2020

AbstractThe COVID-19 epidemics are differentially progressing in different countries. Here, comparative analyses of daily new cases reveal that 61 most affected countries can be classified into four types: downward (22), upward (20), static-phase (12) and uncertain ones (7). In particular, the 12 static-phase countries including US and UK are characterized by largely constant numbers of daily new cases in the past over 14 days. Furthermore, these static-phase countries are overall significantly lower in testing density but higher in the level of positive COVID-19 tests than downward countries. These findings suggest that the testing capacity in static-phase countries is lagging behind the spread of the outbreak, i.e., daily new cases (confirmed) are likely less than daily new infections and the remaining undocumented infections are thus still expanding, resulting in unstoppable epidemics. As such, increasing the testing capacity and/or reducing the COVID-19 transmission are urgently needed to stop the severing crisis in static-phase countries.Highlights61 most affected countries can be classified into four types: downward, upward, static-phase and uncertain ones.The 12 static-phase countries including US and UK are characterized by largely constant numbers of daily new cases in the past over 14 days.Static-phase countries show lower testing density but higher level of positive COVID-19 tests than downward countries.In static-phase countries, daily new cases (confirmed) are likely less than daily new infections and the remaining undocumented infections are thus still expanding.
Nilotinib in Patients with Advanced Parkinson’s Disease: A Randomized Phase 2A Study (NILO-PD)
Authors: Simuni Tanya , Fiske Brian , Merchant Kalpana , Coffey Christopher S. , Klingner Elizabeth , Caspell-Garcia Chelsea , Lafontant David-Erick , Matthews Helen , Wyse Richard K. , Brundin Patrik , Simon David K. , Schwarzschild Michael , Weiner David , Adams Jaime , Venuto Charles , Dawson Ted M. , Baker Liana , Kostrzebski Melissa , Ward Tina , Rafaloff Gary 
Published: May 2020

AbstractBackgroundNilotinib, a tyrosine kinase Abelson inhibitor, exhibits neuroprotective effects in preclinical Parkinson disease (PD) models.MethodsThis Phase 2A double-blind placebo-controlled study in moderate/advanced PD randomized participants 1:1:1 to placebo:150:300 mg nilotinib in matching capsules once daily for 6 months. The primary outcomes were safety and tolerability, the latter defined as ability to complete the study on assigned dose. Secondary outcomes included change in PD disability (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Part 3 OFF/ON). Additional exploratory outcomes included serum and cerebrospinal fluid (CSF) pharmacokinetic (PK) profile, and CSF dopamine metabolites.FindingsThe study screened 125 and enrolled 76 participants (39% screen failure) between November 2017 and December 2018 at 25 US sites. The last participant completed the study in September 2019. At baseline, mean (standard deviation) age was 64.6 years (7.5), disease duration 9.9 years (4.7), MDS-UPDRS Part 1-3 OFF score 66.4(19.3) and ON score 48.4(16.2), Montreal Cognitive Assessment (MoCA) score 27.1(2.2). Tolerability was 21(84%):19 (76%):20 (77%) in placebo:150:300 mg arm, respectively. Both active doses were safe. The most common reasons for drug suspension were elevations of amylase and/or lipase, which were dose-dependent. The 300 mg group had transitory worsening of MDS-UPDRS-3 ON at 1 month compared to placebo (p<0.01), which resolved by 6 months. There was no difference in the change of MDS-UPDRS-3 OFF from baseline to 6 months between the groups (p=0.17). CSF/serum PK ratio was 0.2-0.3%. There was no evidence of treatment-related elevation of any dopamine metabolites.InterpretationBoth doses of nilotinib were safe and tolerable in these participants, who were selected with strict inclusion/exclusion criteria. There was no evidence of any symptomatic benefit of nilotinib. The drug had low CSF exposure and failed to change dopamine metabolites. These findings do not warrant further testing of nilotinib in PD.FundingThe study was funded by Funded by Michael J Fox Foundation for Parkinson’s Research / The Cure Parkinson Trust / Van Andel Institute. Clinicaltrials.gov NCT03205488
Impact of governance structures on environmental disclosures in the Middle East and Africa
Authors: Kilincarslan Erhan , Elmagrhi Mohamed H. , Li Zezeng 
Published: May 2020

PurposeThis study aims to investigate the impact of corporate governance structures on environmental disclosure practices in the Middle East and Africa (MEA).Design/methodology/approachThe research model uses a panel data set of 121 publicly listed (non-financial and non-utility) firms from 11 MEA countries over the period 2010-2017, uses alternative dependent variables and regression techniques and is applied to various sub-groups to improve robustness.FindingsThe empirical results strongly indicate that MEA firms with high governance disclosures tend to have better environmental disclosure practices. The board characteristics of gender diversity, size, CEO/chairperson duality and audit committee size impact positively on MEA firms’ voluntary environmental disclosures, whereas board independence has a negative influence.Research limitations/implicationsThis study advances research on the relationship between corporate governance structures and environmental disclosure practices in MEA countries, but is limited to firms for which data are available from Bloomberg.Practical implicationsThe results have important practical implications for MEA policymakers and regulators. The positive impact of board gender diversity on firms’ environmental disclosures, policy reforms should aim to increase female directors. MEA corporations aiming to be more environmentally friendly should recruit women to top managerial positions.Originality/valueThis is thought to be the first study to provide insights from the efficiency and legitimation perspectives of neo-institutional theory to explain the relationship between MEA firms’ internal governance structures and environmental disclosures.
Simulation analysis of incentives on employees' acceptance of foreign joint venture management practices: a case study
Authors: Zhang Jingxiao , Ouyang You , Li Hui , Ballesteros-Pérez Pablo , Skitmore Martin 
Published: May 2020

PurposeCultural differences between employees of different nationalities are hindering the development of some transnational joint ventures. Describing and modelling the positive (or negative) factors that cause joint venture employees to accept (or reject) joint management business practices is of great value to all corporations operating abroad with locally sourced employees.Design/methodology/approachThis study uses a Sino-Japan construction joint venture project as a representative case study. First, structural equation modelling is used to identify the factors influencing Chinese employees' acceptance of joint venture management practices. Then, a system dynamics model is adopted to simulate the time-dependent effects of the incentives.FindingsThe study results (1) indicate which incentives strongly affect employee acceptance of joint venture management practices; (2) identify inefficient management practices in cross-cultural joint ventures; and (3) provide evidence that the employees' perceptions of clear purpose, good working relationships and helpful mechanisms positively and directly also support their acceptance of joint management practices.Originality/value–A dynamic simulation method is used to analyse the influence of various incentive factors on employee acceptance of joint management. This provides unprecedented information regarding how these factors interact with each other, hence how their effectiveness varies (both positively and negatively) over time. Further findings also provide new ideas for joint venture managers to adopt more effective management methods.