bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral-mediated ubiquitination impacts interactions of host proteins with viral RNA and promotes viral RNA processing
Authors: Herrmann Christin , Dybas Joseph M. , Liddle Jennifer C. , Price Alexander M , Hayer Katharina E. , Lauman Richard , Purman Caitlin E. , Charman Matthew , Kim Eui Tae , Garcia Benjamin A , Weitzman Matthew D 
Published: June 2020

ABSTRACTViruses promote infection by hijacking host ubiquitin machinery to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defenses and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6-mediated ubiquitination that facilitate RNA processing. While all currently known cellular substrates of E1B55K/E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins (RBPs) as high-confidence substrates which are not decreased in overall abundance. We focused on two RBPs, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C increased levels of viral RNA splicing, protein abundance, and progeny production during infection with E1B55K-deleted virus. Furthermore, infection with virus deleted for E1B55K resulted in increased interaction of hnRNP-C with viral RNA, and attenuation of viral RNA processing. These data suggest viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing, revealing an unexpected role for non-degradative ubiquitination in manipulation of cellular processes during virus infection.
Cytoplasmic CPSF6 regulates HIV-1 capsid trafficking and infection in a cyclophilin A-dependent manner
Authors: Zhong Zhou , Ning Jiying , Boggs Emerson A. , Jang Sooin , Wallace Callen , Telmer Cheryl , Bruchez Marcel P. , Ahn Jinwoo , Engelman Alan N. , Zhang Peijun , Watkins Simon C. , Ambrose Zandrea 
Published: June 2020

SummaryHuman immunodeficiency virus type 1 (HIV-1) capsid binds host proteins during infection, including cleavage and polyadenylation specificity factor 6 (CPSF6) and cyclophilin A (CypA). We observe that HIV-1 infection induces higher-order CPSF6 formation and capsid-CPSF6 complexes co-traffic on microtubules. CPSF6-capsid complex trafficking is impacted by capsid alterations that reduce CPSF6 binding or by excess cytoplasmic CPSF6 expression, both of which are associated with decreased HIV-1 infection. Higher-order CPSF6 complexes bind and disrupt HIV-1 capsid assembliesin vitro. Disruption of HIV-1 capsid binding to CypA leads to increased CPSF6 binding and altered capsid trafficking, resulting in reduced infectivity. Our data reveal an interplay between CPSF6 and CypA that is important for cytoplasmic capsid trafficking and HIV-1 infection. We propose that CypA prevents HIV-1 capsid from prematurely engaging cytoplasmic CPSF6 and that differences in CypA cellular localization and innate immunity may explain cell-specific variations in HIV-1 capsid trafficking and uncoating.Graphical Abstract
Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo
Authors: Jia Xiao-wei , Fang Dong-liang , Shi Xin-yi , Lu Tao , Yang Chun , Gao Yan 
Published: June 2020

ABSTRACTBeige adipocytes are emerging as an interesting issue in obesity and metabolism research. There is a neglected possibility that brown adipocytes are equally activated when external stimuli induce beige adipocytes. Thus, a question is whether beige adipocytes have the same functions as brown adipocytes when brown adipose tissue (BAT) is lacking. This question has not been well studied. Therefore we determine the beneficial effects of beige adipocytes upon cold challenge or CL316243 treatments in animal models of BAT ablation by surgical denervation. The data show that beige adipocytes partly contribute to impaired glucose metabolism resulting from denervated BAT. Whereas, we found that denervated BAT were activated by cold exposure and CL316243. Thus, we further used BAT-removal animal models to abolish BAT functions completely. We found that beige adipocytes upon cold challenge or CL316243 treatments independently improved impaired glucose metabolism in BAT-removal mice. The insulin signaling was activated in BAT-removal mice upon cold exposure. Whereas, both the activation of insulin signaling and up-regulation of glucose transporter expression were observed in BAT-removal mice with CL316243 treatments. The data show that beige adipocytes induced by cold exposure or CL316243 may have different mechanisms to improve impaired glucose metabolism. Beige adipocytes can also enhance energy expenditure and lipolytic activity of white adipose tissue when BAT is lacking. We provide direct evidences for the beneficial effect of beige adipocytes in glucose metabolism and energy expenditure in the absence of BAT in vivo.
Predictive modeling of single-cell DNA methylome data enhances integration with transcriptome data
Authors: Uzun Yasin , Wu Hao , Tan Kai 
Published: June 2020

AbstractDespite rapid advances in single-cell DNA methylation profiling methods, computational tools for data analysis are lagging far behind. A number of tasks, including cell type calling and integration with transcriptome data, requires the construction of a robust gene activity matrix as the prerequisite but challenging task. The advent of multi-omics data enables measurement of both DNA methylation and gene expression for the same single cells. Although such data is rather sparse, they are sufficient to train supervised models that capture the complex relationship between DNA methylation and gene expression and predict gene activities at single-cell level. Here, we present MAPLE (Methylome Association by Predictive Linkage to Expression), a computational framework that learns the association between DNA methylation and expression using both gene- and cell-dependent statistical features. Using multiple datasets generated with different experimental protocols, we show that using predicted gene activity values significantly improves several analysis tasks, including clustering, cell type identification and integration with transcriptome data. With the rapid accumulation of single-cell epigenomics data, MAPLE provides a general framework for integrating such data with transcriptome data.
Ancient viral genomes reveal introduction of HBV and B19V into Mexico during the transatlantic slave trade
Authors: Guzmán-Solís Axel A. , Blanco-Melo Daniel , Villa-Islas Viridiana , Bravo-López Miriam J. , Sandoval-Velasco Marcela , Wesp Julie K. , Gómez-Valdés Jorge A. , de la Luz Moreno-Cabrera María , Meraz-Moreno Alejandro , Solís-Pichardo Gabriela , Schaaf Peter , tenOever Benjamin R. , Ávila-Arcos María C. 
Published: June 2020

ABSTRACTAfter the European colonization of the Americas there was a dramatic population collapse of the Indigenous inhabitants caused in part by the introduction of new pathogens. Although there is much speculation on the etiology of the Colonial epidemics, direct evidence for the presence of specific viruses during the Colonial era is lacking. To uncover the diversity of viral pathogens during this period, we designed an enrichment assay targeting ancient DNA (aDNA) from viruses of clinical importance and applied it on DNA extracts from individuals found in a Colonial hospital and a Colonial chapel (16thc. – 18thc.) where records suggest victims of epidemics were buried during important outbreaks in Mexico City. This allowed us to reconstruct three ancient human parvovirus B19 genomes, and one ancient human hepatitis B virus genome from distinct individuals. The viral genomes are similar to African strains, consistent with the inferred morphological and genetic African ancestry of the hosts as well as with the isotopic analysis of the human remains, suggesting an origin on the African continent. This study provides direct molecular evidence of ancient viruses being transported to the Americas during the transatlantic slave trade and their subsequent introduction to New Spain. Altogether, our observations enrich the discussion about the etiology of infectious diseases during the Colonial period in Mexico.
HIF2α is a Direct Regulator of Neutrophil Motility
Authors: Sormendi Sundary , Deygas Mathieu , Sinha Anupam , Krüger Anja , Kourtzelis Ioannis , Le Lay Gregoire , Bernard Mathilde , Sáez Pablo J. , Gerlach Michael , Franke Kristin , Meneses Ana , Kräter Martin , Palladini Alessandra , Guck Jochen , Coskun Ünal , Chavakis Triantafyllos , Vargas Pablo , Wielockx Ben 
Published: June 2020

AbstractOrchestrated recruitment of neutrophils to inflamed tissue is essential during initiation of inflammation. Inflamed areas are usually hypoxic, and adaptation to reduced oxygen pressure is typically mediated by hypoxia pathway proteins. However, it is still unclear how these factors influence the migration of neutrophils to and at the site of inflammation either during their transmigration through the blood-endothelial cell barrier, or their motility in the interstitial space. Here, we reveal that activation of the Hypoxia Inducible Factor-2 (HIF2α) due to deficiency of HIF-prolyl hydroxylase domain protein-2 (PHD2) boosts neutrophil migration specifically through highly confined microenvironments.In vivo,the increased migratory capacity of PHD2-deficient neutrophils resulted in massive tissue accumulation in models of acute local inflammation. Using systematic RNAseq analyses and mechanistic approaches, we identified RhoA, a cytoskeleton organizer, as the central downstream factor that mediates HIF2α-dependent neutrophil motility. Thus, we propose that the here identified novel PHD2-HIF2α-RhoA axis is vital to the initial stages of inflammation as it promotes neutrophil movement through highly confined tissue landscapes.
Tocilizumab is associated with reduced risk of ICU admission and mortality in patients with SARS-CoV-2 infection
Authors: Moreno-García Estela , Rico Verónica , Albiach Laia , Agüero Daiana , Ambrosioni Juan , Bodro Marta , Cardozo Celia , Chumbita Mariana , De la Mora Lorena , García-Pouton Nicole , Garcia-Vidal Carolina , González-Cordón Ana , Hernández-Meneses Marta , Inciarte Alexy , Laguno Montse , Leal Lorna , Linares Laura , Macaya Irene , Meira Fernanda , Mensa Josep , Moreno Antonio , Morata Laura , Puerta-Alcalde Pedro , Rojas Jhon , Solá Montse , Torres Berta , Torres Manuel , Tomé Adrià , Castro Pedro , Fernández Sara , Nicolás Josep Maria , Almuedo-Riera Alex , Muñoz Jose , Fernandez-Pittol Mariana Jose , Marcos Maria Angeles , Soy Dolors , Martínez José Antonio , García Felipe , Soriano Alex 
Published: June 2020

AbstractBackgroundIn some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management worldwide; therefore, clinical strategies to avoid ICU admission are needed.ObjectiveWe aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients.MethodsA retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first.Results77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P= 0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0·1, P=0.0001) of ICU admission or death.ConclusionTocilizumab in the early stages of the inflammatory flare, could reduce ICU admissions and mechanical ventilation use. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports.Clinical implicationOur results suggest that tocilizumab administered to non-critically ill patients could reduce ICU admissions and mortality.Capsule summaryTocilizumab administered to non-critically ill patients with SARS-CoV-2 infection in the early stages of the inflammatory flare, could reduce an important number of ICU admissions and mechanical ventilation use.
Impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists
Authors: Gomes Cristiano M. , Favorito Luciano , Henriques João Victor T. , Canalini Alfredo F. , Anzolch Karin M. J. , de C. Fernandes Roni , Bellucci Carlos H S , Silva Caroline S , Wroclawski Marcelo L. , Pompeo Antonio Carlos L. , de Bessa Jose 
Published: June 2020

ABSTRACTObjectivesTo evaluate the impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists during the month of April 2020.Materials and MethodsA 39-question, web-based survey was sent to all urologist members of the Brazilian Society of Urology. We assessed socio-demographic, professional, health and behavior parameters. The primary goal was to evaluate changes in urologists’ clinical practice and income after two months of COVID-19. We also looked at geographical differences based on the incidence rates of COVID-19 in different states.ResultsAmong 766 urologists who completed the survey, a reduction ≥ 50% of patient visits, elective and emergency surgeries was reported by 83.2%, 89.6% and 54.8%, respectively. An income reduction of ≥ 50% was reported by 54.3%. Measures to reduce costs were implemented by most. Video consultations were performed by 38.7%. Modifications in health and lifestyle included weight gain (32.9%), reduced physical activity (60.0%), increased alcoholic intake (39.9%) and reduced sexual activity (34.9%). Finally, 13.5% of Brazilian urologists were infected with SARS-CoV-2 and about one third required hospitalization. Urologists from the highest COVID-19 incidence states were at a higher risk to have a reduction of patient visits and non-essential surgeries (OR = 2.95, 95% CI 1.86 – 4.75; p < 0.0001) and of being infected with SARS-CoV-2 (OR = 4.36 95%CI 1.74–10.54, p = 0.012).ConclusionsCOVID-19 produced massive disturbances in Brazilian urologists’ practice, with major reductions in patient visits and surgical procedures. Distressing consequences were also observed on physicians’ income, health and personal lives. These findings are probably applicable to other medical specialties.
Managing Knowledge in Computational Models for Global Food, Nutrition and Health Technologies
Authors: Dube Kudakwashe , McLachlan Scott , Zanamwe Ngonidzashe , Kyrimi Evangelia , Thomson Jasmine S , Fenton Norman 
Published: June 2020

AbstractComputational models that need to incorporate domain knowledge for realistic solutions to problems often lead to technologies that get transferred to developing countries. The support for managing the knowledge incorporated into these technologies is important for customisation to suit local conditions. This work investigates this problem through the challenge of incorporating food and nutrition therapy guidelines (FNTG) into ICT-based solution models for the meal planning problem (MPP) for HIV/AIDS patients in developing countries. An experiment is undertaken to demonstrate the limitations of existing approaches and framework is investigated for manageable incorporation of knowledge into solution models. The paper contributes a clear understanding of, and directions for addressing, the problem of support for managing the knowledge incorporated into solutions models to support customisability of technologies. The significance of this contribution is that solutions will allow resulting technologies to be customised for use in different global contexts.
In SilicoAnalysis Predicting Effects of Deleterious SNPs of HumanRASSF5Gene on its Structure and Functions
Authors: Hossain Md. Shahadat , Roy Arpita Singha , Islam Md. Sajedul 
Published: June 2020

AbstractRas association domain-containing protein 5 (RASSF5), one of the prospective biomarkers for tumors, generally plays a crucial role as a tumor suppressor. As deleterious effects can result from functional differences through SNPs, we sought to analyze the most deleterious SNPs ofRASSF5as well as predict the structural changes associated with the mutants that hamper the normal protein-protein interactions. We adopted both sequence and structure based approaches to analyze the SNPs of RASSF5 protein. We also analyzed the putative post translational modification sites as well as the altered protein-protein interactions that encompass various cascades of signals. Out of all the SNPs obtained from the NCBI database, only 25 were considered as highly deleterious by sixin silicoSNP prediction tools. Among them, upon analyzing the effect of these nsSNPs on the stability of the protein, we found 17 SNPs that decrease the stability. Significant deviation in the energy minimization score was observed in P350R, F321L, and R277W. Besides this, docking analysis confirmed that P350R, A319V, F321L, and R277W reduce the binding affinity of the protein with H-Ras, where P350R shows the most remarkable deviation. Protein-protein interaction analysis revealed that RASSF5 acts as a hub connecting two clusters consisting of 18 proteins and alteration in the RASSF5 may lead to disassociation of several signal cascades. Thus, based on these analyses, our study suggests that the reported functional SNPs may serve as potential targets for different proteomic studies, diagnosis and therapeutic interventions.
A systematic literature review of closed-loop supply chains
Authors: Raza Syed Asif 
Published: June 2020

PurposeThis study research contributes in fulfilling the gap by carrying out a systematic literature review (SLR) of contemporary research studies in closed-loop supply chain (CLSC). To the best of the author’s knowledge, an SLR rooted in bibliometric analysis has not been carried focusing on advent developments in CLSC. SLR employs scientific methodologies to select papers from standard databases. The SLR using advanced bibliometric and network analysis enables unveiling the key features of the contemporary literature.Design/methodology/approachThe author has analyzed over 333 documents published from 2008 and onward. Using the contemporary tools from bibliometric analysis tools, the author presented an exploratory analysis. A network analysis is utilized to visualize literature and create clusters for the cocited research studies, keywords and publication sources. A detailed multivariate analysis of most influential works published based top 100 articles via a cocitation matrix is done. The multivariate analysis used k-means clustering in which optimal number of clusters are estimated. The analysis is further extended by using a factor analysis, which enables determining the most influential clusters in the k-means clustering analysis.FindingsThe SLR using a bibliometric and network analysis enables unveiling the key features of the contemporary literature in CLSC. The author examined published research for influential authors, sources, region, among other key aspects. Network analysis enabled visualizing the clusters of cocited research studies, cowords and publication sources. Cluster analysis of cocited research studies is further explored using k-means clustering. Factor analysis extends findings by identifying most contributing grouping of research areas within CLSC research. Each clustering technique disclosed a unique grouping structure.Originality/valueCLSC has received considerable attention, and its core areas start with focusing on reverse logistics concepts relating reuse, recycling, remanufacturing, among others. Contemporarily, the studies have enhanced reverse logistics core functionalities interfaced with the other interesting avenues related to CO2emission reduction, greening and environmental protection, sustainability, product design and governmental policies. Earlier studies have presented a literature review of CLSC; however, these reviews are commonly conducted in the traditional manner where the authors select papers based on their area of expertise, interest and experience. As such these reviews fall short in utilizing the advanced tools from bibliometric analysis.
A fuzzy DEMATEL – Fuzzy Binary Logistic Regression approach to evaluate and prioritize risks and simulated annealing optimization algorithm (an empirical study in energy projects)
Authors: Hashemi Reyhane , Kamranrad Reza , Bagheri Farnoosh , Emami Iman 
Published: June 2020

PurposeThe aim of this paper is to predict and minimize the risks of oil, gas and petrochemical projects. Besides, reducing the likelihood of occurrence and minimizing risks impact on the projects to reduce the probable costs and improve the economic situation is another purpose of this paper.Design/methodology/approachThis paper provides a fuzzy Decision-Making Trial and Evaluation Laboratory (DEMATEL) – a technique that assist to solve decision-making problems – and IP (Impact & Probability) table methods to identify and analyze critical risks in energy projects, and then fuzzy Binary Logistic Regression (BLR) in order to predict the probability of each level of risk for more efficient risk management in projects. Furthermore, in this paper, the fuzzy BLR (FBLR) is optimized such that the probability of a high level of risk for the implementation of the project has been minimized using meta-heuristic algorithm.FindingsThe results from the point of view of experts show that combination of fuzzy DEMATEL with FBLR approach as well as using SA algorithm, in order to optimize the high level of risks, can provide a smart approach to managing risks with more success.Practical implicationsThe application of the proposed method is illustrated via a real data set from energy projects.Originality/valueWe propose combined fuzzy DEMATEL and FBLR methods to predict and optimize the risks of the energy projects, which is the innovation of this paper.