bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple infiltration and cross-species transmission of foamy viruses across Paleozoic to Cenozoic era
Authors: Chen Yicong , Zhang Yu-Yi , Wei Xiaoman , Cui Jie 
Published: December 2020

AbstractFoamy viruses (FVs) are complex retroviruses that can infect humans and other animals. In this study, by integrating transcriptomic and genomic data, we discovered 412 FVs from 6 lineages in amphibians, which significantly increased the known set of FVs in amphibians. Among these lineages, salamander FVs maintained a co-evolutionary pattern with their hosts that could be dated back to the Paleozoic era, while, on the contrary, frog FVs were much more likely acquired from cross-species (class level) transmission in the Cenozoic era. In addition, we found three distinct FV lineages had integrated into the genome of a salamander. Unexpectedly, we identified a potential exogenous form of FV circulated in caecilian, demonstrating the existence of exogenous form of FV besides mammals. Our discovery of rare phenomena in amphibian FVs has overturned our collective understanding of the macroevolution of the complex retrovirus.ImportanceFoamy viruses (FVs) represent, more so than other viruses, the best model of co-evolution between a virus and a host. This study represents so far, the largest investigation of amphibian FVs and revealed 412 FVs of 6 distinct lineages from three major orders of amphibians. Besides co-evolutionary pattern, cross-species and repeated infection were also observed during evolution of amphibian FVs. Remarkably, expressed FVs including a potential exogenous form were discovered, suggesting live FVs could be underestimated in nature. These findings revealed the multiple origin and complex evolution of amphibian FVs started from the Paleozoic era.
Reconciling Membrane Protein Simulations with Experimental DEER Spectroscopy Data
Authors: Mittal Shriyaa , Shukla Diwakar 
Published: December 2020

AbstractSpectroscopy experiments are crucial to study membrane proteins for which traditional structure determination methods still prove challenging. Double electron-electron resonance (DEER) spectroscopy experiments provide protein residue-pair distance distributions that are indicative of their conformational heterogeneity. Atomistic molecular dynamics (MD) simulations are another tool that have proved vital to study the structural dynamics of membrane proteins such as to identify inward-open, occluded, and outward-open conformations of transporter membrane proteins, among other partially open or closed states of the protein. Yet, studies have reported that there is no direct consensus between distributional data from DEER experiments and MD simulations, which has challenged validation of structures obtained from long-timescale simulations and using simulations to design experiments. Current coping strategies for comparisons rely on heuristics, such as mapping nearest matching peaks between two ensembles or biased simulations. Here we examine the differences in residue-pair distance distributions arising due to choice of membrane around the protein and covalent modification of a pair of residues to nitroxide spin labels in DEER experiments. Through comparing MD simulations of two proteins, PepTSoand LeuT - both of which have been characterized using DEER experiments previously - we show that the proteins’ dynamics are similar despite the choice of the detergent micelle as a membrane mimetic in DEER experiments. On the other hand, covalently modified residues show slight local differences in their dynamics and a huge divergence when the spin labels’ anointed oxygen atom pair distances are measured rather than protein backbone distances. Given the computational expense associated with pairwise MTSSL labeled MD simulations, we examine the use of biased simulations to explore the conformational dynamics of the spin labels only to reveal that such simulations alter the underlying protein dynamics. Our study identifies the main cause for the mismatch between DEER experiments and MD simulations and will accelerate developing potential mitigation strategies to improve simulation observables match with DEER spectroscopy experiments.
Protocol for an interdisciplinary cross-sectional study investigating the social, biological and community-level drivers of antimicrobial resistance (AMR): Holistic Approach to Unravelling Antibiotic Resistance in East Africa (HATUA)
Authors: Asiimwe Benon B. , Kiiru John , Mshana Stephen E. , Neema Stella , Keenan Katherine , Kesby Mike , Mwanga Joseph R. , Sloan Derek J. , Mmbaga Blandina T. , Smith V Anne , Gillespie Stephen , Lynch Andy G. , Sandeman Alison , Stelling John , Elliott Alison , Aanensen David M. , Kibiki Gibson S. , Sabiiti Wilber , Holden Matthew T. G. ,   HATUA CONSORTIUM, Kansiime Catherine , Mushi Martha F. , Decano Arun Gonzales , Green Dominique L. , Mwaniki John , Ntinginya Nyanda E , Bazira Joel 
Published: December 2020

AbstractIntroductionAntimicrobial resistance (AMR) is a global health threat that requires urgent research using a multidisciplinary approach. The biological drivers of AMR are well understood, but factors related to treatment-seeking and the social contexts of antibiotic (AB) use behaviours are less understood. Here we describe the Holistic Approach to Unravelling Antibacterial Resistance in East Africa (HATUA), a multi-centre consortium that investigates the diverse drivers of drug-resistance in urinary tract infections (UTIs) in East Africa.Methods and AnalysisThis study will take place in Uganda, Kenya and Tanzania. We will conduct geospatial mapping of AB sellers, and conduct mystery client studies and in-depth interviews (IDI) with drug sellers to investigate AB provision practices. In parallel, we will conduct IDIs with doctors, alongside community focus groups. Clinically diagnosed UTI patients will be recruited from healthcare centres, provide urine samples, and complete a questionnaire capturing retrospective treatment pathways, socio-demographic characteristics, attitudes and knowledge. Bacterial isolates from urine and stool samples will be subject to culture and antibiotic susceptibility testing (C&AST). Genomic DNA from bacterial isolates will be extracted with a subset being sequenced. A follow-up household interview will be conducted with 1800 UTI-positive patients, where further environmental samples will be collected. A sub-sample of patients will be interviewed using qualitative tools. Questionnaire data, microbiological analysis and qualitative data will be linked at the individual level. Quantitative data will be analysed using statistical modelling including Bayesian network analysis, and all forms of qualitative data analysed through iterative thematic content analysis.Ethics and DisseminationApprovals have been obtained from all national and local ethical review bodies in East Africa and the UK. Results will be disseminated in communities, with local and global policy stakeholders, and in academic circles. They will have great potential to inform policy, improve clinical practice and build regional pathogen surveillance capacity.
Healthcare worker intentions to receive a COVID-19 vaccine and reasons for hesitancy: A survey of 16,158 health system employees on the eve of vaccine distribution
Authors: Meyer Michelle N. , Gjorgjieva Tamara , Rosica Daniel 
Published: December 2020

AbstractHealthcare workers (HCWs) have been recommended to receive first priority for limited COVID-19 vaccines. They have also been identified as potential ambassadors of COVID-19 vaccine acceptance, helping to ensure that sufficient members of a hesitant public accept COVID-19 vaccines to achieve population immunity. Yet HCWs themselves have shown vaccine hesitancy in other contexts and the few prior surveys of U.S. HCW intentions to receive a COVID-19 vaccine report acceptance rates of only 28% to 34%. However, it is unknown whether HCW acceptance remains low following mid-November announcements of the efficacy of the first COVID-19 vaccines and the issuance of two emergency use authorizations (EUA) in December. We report the results of a December 2020 survey (N= 16,158; response rate 61%) administered by a large Pennsylvania health system to determine the intentions of its employees to receive a vaccine when it is offered to them. In a mixed sample of individuals serving in patient-facing and other roles, 55% would decide to receive a COVID-19 vaccine when offered, 16.4% would not, and 28.5% reported being undecided. The distribution of responses varied little across hospital campuses, between those in patient-facing roles and other HCWs, or by area or department of work. The higher rate of COVID-19 vaccine acceptance we observe may reflect the framing and timing of our survey. Among hesitant respondents, an overwhelming majority (90.3%) reported concerns about unknown risks and insufficient data. Other commonly reported concerns included known side effects (57.4%) and wanting to wait until they see how it goes with others (44.4%). We observed a substantial increase in self-reported intent to receive a COVID-19 vaccine after an FDA advisory committee voted to recommend an EUA. Among respondents who completed the survey after that point in time, 79% intend to receive a COVID-19 vaccine (n= 1155). Although only suggestive, this trend offers hope that rates of COVID-19 vaccine acceptance may be higher among HCWs and, perhaps, the general public than more hypothetical survey results have indicated.
Conservative treatment of partial-thickness rotator cuff tears and tendinopathy with platelet-rich plasma: a systematic review and meta-analysis
Authors: Xiang Xiao-Na , Deng Jie , Liu Yan , Yu Xi , Cheng Biao , He Hong-Chen 
Published: December 2020

AbstractPurposeTo assess the effect of platelet-rich plasma (PRP) as a conservative therapy on individuals with partial-thickness rotator cuff tears (PTRCs) or tendinopathy in terms of pain, and function.MethodsA systematic review and meta-analysis of randomized controlled trials were conducted. Short-term (6±1 months) and long-term (≥1 year) outcomes were analysed, including the visual analogue scale (VAS), Constant-Murley score (CMS), Shoulder Pain and Disability Index (SPADI), as well as American Shoulder and Elbow Surgeons (ASES) score. The weighted mean difference (MD) with 95% confidence interval (CI) was used.ResultsTen studies were eligible in this review, nine studies with 561 patients were included in this meta-analysis. The meta-analysis showed statistically significant differences in the decrease in short-term VAS (MD=-1.56; 95% CI -2.82 to -0.30), and increase in CMS (MD=16.48; 95% CI 12.57 to 20.40), and SPADI (MD=-18.78 95% CI -36.55 to -1.02). Nonetheless, no long-term effect was observed on pain and function, except CMS (MD=24.30). The results of mean important differences (MIDs) reached the minimal clinically important differences, except ASES. For subgroup analysis, short-term VAS scores were decreased in PRP-treated patients with double centrifugation (MD=-1.99), single injection (MD=-0.71) and post-injection rehabilitation (MD=-1.59).ConclusionPRP-treated patients with PTRCs and rotator cuff tendinopathy demonstrated improvements in pain and function, although the effect may not last for a long time. Overall, our results suggest that PRP may have positive clinical outcomes, but limited data, and study heterogeneity hinder firm conclusions.
Naa12compensates forNaa10in mice in the amino-terminal acetylation pathway
Authors: Kweon Hyae Yon , Lee Mi-Ni , Dörfel Max , Seo Seungwoon , Gottlieb Leah , Papazyan Thomas , McTiernan Nina , Ree Rasmus , Bolton David , Garcia Andrew , Flory Michael , Crain Jonathan , Sebold Alison , Lyons Scott , Ismail Ahmed , Marchi Elaine , Sonn Seong-keun , Jeong Se-Jin , Jeon Sejin , Ju Shinyeong , Conway Simon J. , Kim TaeSoo , Kim Hyun-Seok , Lee Cheolju , Roh Tae-Young , Arnesen Thomas , Marmorstein Ronen , Oh Goo Taeg , Lyon Gholson J. 
Published: December 2020

AbstractAmino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals. Male mice lackingNaa10show no globally apparentin vivoamino-terminal acetylation impairment and do not exhibit complete embryonic lethality. RatherNaa10nulls display increased neonatal lethality, and the majority of surviving undersized mutants exhibit a combination of hydrocephaly, cardiac defects, homeotic anterior transformation, piebaldism and urogenital anomalies.Naa12is a previously unannotatedNaa10-like paralogue with NAT activity that genetically compensates forNaa10. Mice deficient forNaa12have no apparent phenotype, whereas mice deficient forNaa10andNaa12display embryonic lethality. The discovery ofNaa12adds to the currently known machinery involved in amino-terminal acetylation in mice.
Enhancing cassava reproductive development does not negatively impact shoot to root ratio and dry matter content in storage roots
Authors: Deborah Oluwasanya , Tim Setter 
Published: December 2020

AbstractFrom previous studies we developed treatments that significantly improved cassava female flower and fruit development, using a combination of the anti-ethylene, silver thiosulfate (STS), and the cytokinin, benzyladenine (BA); collectively referred to as plant growth regulators (PGR). In this study, we investigated whether the benefit derived from this treatment altered partitioning of photosynthate to other sinks and general vegetative growth of cassava in the first six months of plants growth, when reproductive growth initiates and peaks. Our flower enhancing treatment did not significantly alter shoot and storage root fresh weight, partitioning index on a fresh weight basis and percent dry matter content of storage roots between Months 2 and 5. With the onset of the dry season in Month 6, PGR treated plants had higher shoot and storage root fresh weight than controls but these plant parts responded proportionally and so partitioning index between controls and treated plants was not significantly different. The nighttime starch export under PGR treatments was reduced at Months 2, 4 and 5 but this was not correlated with flower development at these months. The survival of PGR treated plants until harvest was however reduced owing to increased mortality arising from phytotoxicity and increased susceptibility to disease. We therefore conclude that PGRs have effects more directly on flower and fruit reproductive signaling and regulatory pathways rather than on an indirect effect on resource partitioning.
Tuning the transglycosylation reaction of a GH11 xylanase by a delicate enhancement of its thumb flexibility
Authors: Marneth Kim , van den Elst Hans , Cramer-Blok Anneloes , Codee Jeroen , Overkleeft Hermen S. , Aerts Johannes M. F. G. , Ubbink Marcellus , Bdira Fredj Ben 
Published: December 2020

AbstractGlycoside hydrolases (GH) are attractive tools for multiple biotechnological applications. In conjunction with their hydrolytic function, GH can perform transglycosylation reaction under specific conditions. In nature, oligosaccharides synthesis is performed by glycosyltransferase (GT). However, the industrial utilization of GT is limited by their instability in solution. A key difference between GT and GH is the flexibility of their binding sites architecture. In this report, we used the xylanase fromBacillus circulans(BCX) to study the interplay between active site flexibility and the transglycosylation reaction. Residues of the BCX thumb were substituted to increase the flexibility of the enzyme binding site. Replacement of the highly conserved residue P116 with glycine shifted the balance of the BCX enzymatic reaction toward transglycosylation. The effects of this point mutation on the structure and dynamics of BCX were investigated by NMR spectroscopy. The P116G mutation induces subtle changes in the configuration of the thumb and enhances the millisecond dynamics of the active site. Based on our findings, we propose the remodeling of the GH enzymes glycon site flexibility as a strategy to improve the transglycosylation efficiency of these biotechnologically important catalysts.
Evolutionary coupling range varies widely among enzymes depending on selection pressure
Authors: Echave Julian 
Published: December 2020

ABSTRACTRecent studies proposed that enzyme active sites induce evolutionary constraints at long distances. The physical origin of such long-range evolutionary coupling is unknown. Here, I use a recent biophysical model of evolution to study the relationship between physical and evolutionary couplings on a diverse data set of monomeric enzymes. I show that evolutionary coupling is not universally long-range. Rather, range varies widely among enzymes, from 2Å to 20Å. Furthermore, the evolutionary coupling range of an enzyme does not inform on the underlying physical coupling, which is short-range for all enzymes. Rather, evolutionary coupling range is determined by functional selection pressure.SIGNIFICANCEUntil recently, only residues near enzyme active sites were thought to be evolutionarily constrained. However, recent studies proposed that active sites induce long-range evolutionary constraints. This seems to conflict with the common finding that physical couplings in proteins are short-range. This raises the question of how short-range physical couplings may cause long-range evolutionary couplings. Here, I show that the function that maps physical coupling into evolutionary coupling depends on functional selection pressure. Under weak selection, both couplings are similarly short-range; under strong selection, short-range physical coupling is non-linearly turned into long-range evolutionary coupling. Thus, due to a huge variation of selection pressure, evolutionary coupling range varies widely among enzymes, from very short (2 Å) to very long (20 Å).
Co-translational folding of the first transmembrane domain of ABC-transporter CFTR is supported by assembly with the first cytosolic domain
Authors: Kleizen Bertrand , van Willigen Marcel , Mijnders Marjolein , Peters Florence , Grudniewska Magda , Hillenaar Tamara , Thomas Ann , Kooijman Laurens , Peters Kathryn W. , Frizzell Raymond , van der Sluijs Peter , Braakman Ineke 
Published: December 2020

ABSTRACTABC-transporters transport a wealth of molecules across membranes and consist of transmembrane and cytosolic domains. Their activity cycle involves a tightly regulated and concerted domain choreography. Regulation is driven by the cytosolic domains and function by the transmembrane domains. Folding of these polytopic multidomain proteins to their functional state is a challenge for cells, which is mitigated by co-translational and sequential events. We here reveal the first stages of co-translational domain folding and assembly of CFTR, the ABC-transporter defective in the most abundant rare inherited disease cystic fibrosis. We have combined biosynthetic radiolabeling with protease-susceptibility assays and domain-specific antibodies. The most N-terminal domain, TMD1 (transmembrane domain 1), folds both its hydrophobic and soluble helices during translation: the transmembrane helices pack tightly and the cytosolic N- and C-termini assemble with the first cytosolic helical loop ICL1, leaving only ICL2 exposed. This N-C-ICL1 assembly is strengthened by two independent events: i) assembly of ICL1 with the N-terminal subdomain of the next domain, cytosolic NBD1 (nucleotide-binding domain 1); and ii) in the presence of corrector drug VX-809, which rescues cell-surface expression of a range of disease-causing CFTR mutants. Both lead to increased shielding of the CFTR N-terminus, and their additivity implies different modes of action. Early assembly of NBD1 and TMD1 is essential for CFTR folding and positions both domains for the required assembly with TMD2. Altogether, we have gained insights into this first, nucleating, VX-809-enhanced domain-assembly event during and immediately after CFTR translation, involving structures conserved in type-I ABC exporters.
COVID-19: An analysis of social media and research publication activity during the early stages of the pandemic
Authors: Taneja Sonia L. , Passi Monica , Bhattacharya Sumona , Schueler Samuel A. , Gurram Sandeep , Koh Christopher 
Published: December 2020

ABSTRACTObjectivesThe COVID-19 pandemic has highlighted the importance of rapid dissemination of scientific and medical discovery. Social media (SoMe) has become an invaluable platform in science and medicine. This study analyzed activity of SoMe (Twitter), preprints, and publications related to COVID-19 and gastroenterology (GI) during the COVID-19 pandemic.MethodsData from Twitter, preprint servers and PubMed was collected and analyzed from December 2019 through May 2020. Global and regional geographic and gastrointestinal organ specific social media trends were compared to preprint and publication activity; any associations were identified.ResultsOver the 6-month period, there were 73,079 tweets from 44,609 users, 7,164 publications, and 4,702 preprints. Twitter activity peaked during March while preprints and publications peaked in April 2020. Strong correlations were identified between Twitter and both preprints and publications activity (p<0.001 for both). While COVID-19 data across the 3 platforms concentrated on pulmonology/critical care, the majority of GI tweets pertained to pancreatology, most publications focused on hepatology, and most preprints covered hepatology and luminal GI (LGI). There were significant associations between Twitter activity and research for all GI subfields (p=0.009 for LGI, p=0.006 for hepatology and IBD, p=0.007 for endoscopy), except pancreatology (p=0.2). Twitter activity was highest in the US (7,331 tweets) whereas PubMed activity was highest in China (1,768 publications).ConclusionsThe COVID-19 pandemic has highlighted the utility of SoMe as a vehicle for disseminating scientific information during a public health crisis. Scientists and clinicians should consider the use of SoMe in augmenting public awareness of their scholarly pursuits.
Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance
Authors: Yang Shuo , Tian Meijie , Dai Yulong , Feng Shengyong , Wang Yunyun , Chhangani Deepak , Ou Tiffany , Li Wenle , Yang Ze , McAdow Jennifer , Rincon-Limas Diego E. , Yin Xin , Tai Wanbo , Cheng Gong , Johnson Aaron 
Published: December 2020

Graphic abstractSummaryInfections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show a number of non-neural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood, so we developed three models to investigate the impact of neuroinflammation on muscle performance. We found that bacterial infection, COVID-like viral infection, and expression of a neurotoxic protein associated with Alzheimer′ s disease promoted the accumulation of reactive oxygen species (ROS) in the brain. Excessive ROS induces the expression of the cytokine Unpaired 3 (Upd3) in insects, or its orthologue IL-6 in mammals, and CNS-derived Upd3/IL-6 activates the JAK/Stat pathway in skeletal muscle. In response to JAK/Stat signaling, mitochondrial function is impaired and muscle performance is reduced. Our work uncovers a brain-muscle signaling axis in which infections and chronic diseases induce cytokine-dependent changes in muscle performance, suggesting IL-6 could be a therapeutic target to treat muscle weakness caused by neuroinflammation.