bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal Structure of a Retroviral Polyprotein: Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT)
Authors: Harrison Jerry Joe E. K. , Tuske Steve , Das Kalyan , Ruiz Francesc X. , Bauman Joseph D. , Boyer Paul , DeStefano Jeffrey J. , Hughes Stephen H. , Arnold Eddy 
Published: November 2020

AbstractIn most cases, proteolytic processing of the retroviral Pol portion of the Gag-Pol polyprotein precursor produces protease (PR), reverse transcriptase (RT), and integrase (IN). However, foamy viruses (FVs), express Pol separately from Gag and, when Pol is processed, only the IN domain is released. Here, we report a 2.9 Å resolution crystal structure of the mature PR-RT from prototype FV (PFV) that carries out both proteolytic processing and reverse transcription. PFV PR-RT is monomeric and the architecture of PFV PR is similar to one of the subunits of HIV-1 PR, which is a dimer. There is a C-terminal extension of PFV PR (101-145) that consists of two helices which are adjacent to the base of the RT palm subdomain, and anchors PR to RT. The polymerase domain of PFV RT consists of fingers, palm, thumb, and connection subdomains whose spatial arrangements are similar to the p51 subunit of HIV-1 RT. The RNase H and polymerase domains of PFV RT are connected by flexible linkers. Significant spatial and conformational (sub)domain rearrangements are therefore required for nucleic acid binding. The structure of PFV PR-RT provides insights into the conformational maturation of retroviral Pol polyproteins.IMPORTANCERetroviruses such as HIV and other human and animal pathogens have evolved to maximize the protein-coding capacity of their genomes. Retroviruses synthesize large polyprotein precursors that are subsequently cleaved to produce mature functional enzymes and structural proteins from the same mRNA template. These polyproteins play an important role in the viral life cycle. We report the monomeric structure of the prototype foamy virus protease-reverse transcriptase fusion (PR-RT) which serves as both a protease and reverse transcriptase. The monomeric PR domain is folded in a similar way as a single subunit of dimeric HIV-1 PR. PR is anchored close to the fingers subdomain of the RT by a long C-terminal extension (CTE) that folds into two helices that pack against the palm subdomain of the RT. The RT is folded similarly to the p51 subunit of HIV-1 RT with the RNase H subdomain packed against the thumb and opposite the connection and palm subdomains. This structure offers insight into the structural arrangement of the domains and subdomains of immature retroviral polyproteins and provides support for the concept of developing drugs that target interfaces between immature enzymes that are present only in retroviral polyprotein precursors.
Protein kinases mediate anti-inflammatory effects of cannabidiol and estradiol against high glucose in cardiac sodium channels
Authors: Fouda Mohamed A. , Ruben Peter C. 
Published: November 2020

AbstractBackground and purposeCardiovascular anomalies are predisposing factors for diabetes-induced morbidity and mortality. Recently, we showed that high glucose induces changes in the biophysical properties of Nav1.5 that could be strongly correlated to diabetes-induced arrhythmia. However, the mechanisms underlying hyperglycemia-induced inflammation, and how inflammation provokes cardiac arrhythmia, are not well understood. We hypothesized that inflammation could mediate the high glucose-induced biophyscial changes on Nav1.5 through protein phosphorylation by protein kinases A and C. We also hypothesized that this signaling pathway is, at least partly, involved in the cardiprotective effects of CBD and E2.Experimental approachTo test these ideas, we used Chinese hamster ovarian (CHO) cells transiently co-transfected with cDNA encoding human Nav1.5 α-subunit under control, a cocktail of inflammatory mediators or 100 mM glucose conditions (for 24 hours). We used electrophysiological experiments and action potential modelling.Key ResultsInflammatory mediators, similar to 100 mM glucose, right shifted the voltage dependence of conductance and steady state fast inactivation and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. In addition, activators of PK-A or PK-C replicated the inflammation-induced gating changes of Nav1.5. Inhibitors of PK-A or PK-C, CBD or E2mitigated all the potentially deleterious effects provoked by high glucose/inflammation.Conclusions and implicationsThese findings suggest that PK-A and PK-C may mediate the anti-inflammatory effects of CBD and E2against high glucose-induced arrhythmia. CBD, via Nav1.5, may be a cardioprotective therapeutic approach in diabetic postmenopausal population.Bullet pointsWhat is already known:Arrhythmias are among the common cardiac causes of morbidity and mortality in diabetes-related hyperglycemia.One of the diabetes-induced arrhythmias is long-QT syndrome, caused by gating defects in the cardiac voltage-gated sodium channel (Nav1.5).What this study adds:Inflammation and subsequent activation of PK-A and PK-C mediate the high glucose-induced electrophysiological changes of Nav1.5 in a manner consistent with the gating defects that underlie long-QT arrhythmia.Cannabidiol and estradiol rescue the high glucose induced Nav1.5 gating defects through, at least partly, this signaling pathway.Clinical significance:Inflammation/PK-A and PK-C signaling pathway could be a potential therapeutic target to prevent arrhythmias associated with diabetes.Cannabidiol may be a therapeutic approach to prevent cardiac complications in diabetes, especially in postmenopausal populations due to the decreased levels of the cardioprotective estrogen.
Reference-Aided Full-length Transcript Assembly, cDNA Cloning, and Molecular Characterization ofCoronatine-insensitive 1b(COI1b) Gene in Coconut (Cocos nuciferaL.)
Authors: Pammit Frenzee Kroeizha L. , Manohar Anand Noel C. , Lantican Darlon V. , Gardoce Roanne R. , Galvez Hayde F. 
Published: November 2020

AbstractIn the Philippines, 26% of the total agricultural land is devoted to coconut production making coconut one of the most valuable industrial crop in the country. However, the country’s multimillion-dollar coconut industry is threatened by the outbreak of coconut-scale insect (CSI) and other re-emerging insect pests promoting national research institutes to work jointly on developing new tolerant coconut varieties. Here, we report the cloning and characterization ofcoronatine-insensitive 1(COI1) gene, one of the candidate insect defense genes, using ‘Catigan Green Dwarf’ (CATD) genome sequence assembly as reference. Two (2) splicing variants were identified and annotated – CnCOI1b-1 and CnCOI1b-2. The full-length cDNA of CnCOI1b-1 was 7,919 bp with an ORF of 1,176 bp encoding for a deduced protein of 391 amino acids while CnCOI1b-2 has 2,360 bp full-length cDNA with an ORF of 1,743 bp encoding a deduced protein of 580 amino acids. The 3D structural model for the two (2) isoforms were generated through homology modelling. Functional analysis revealed that both isoforms are involved in various physiological and developmental plant processes including defense response of plants to insects and pathogens. Phylogenetic analysis confirms high degree of COI1 protein conservation during evolution, especially among monocot species.Key MessageThis paper reports the molecular cloning and characterization ofcorononatine-insensitive I(COI1)gene in coconut using reference-guided transcript assembly approach. As a well-known insect defense-response gene in other crops, the results of this study are expected to assist in the development of new resistant coconut varieties as one of the strategies to address threats in coconut production.
Pro108Ser mutant of SARS-CoV-2 3CLpro reduces the enzymatic activity and ameliorates COVID-19 severity in Japan
Authors: Abe Kodai , Kabe Yasuaki , Uchiyama Susumu , Iwasaki Yuka W. , Ishizu Hirotsugu , Uwamino Yoshifumi , Takenouchi Toshiki , Uno Shunsuke , Ishii Makoto , Maruno Takahiro , Noda Masanori , Murata Mitsuru , Hasegawa Naoki , Saya Hideyuki , Kitagawa Yuko , Fukunaga Koichi , Amagai Masayuki , Siomi Haruhiko , Suematsu Makoto , Kosaki Kenjiro ,   Keio Donner Project
Published: November 2020

AbstractSARS-CoV-2 genome accumulates point mutations constantly. However, whether non-synonymous mutations affect COVID-19 severity through altering viral protein function remains unknown. SARS-CoV-2 genome sequencing revealed that the number of non-synonymous mutations correlated inversely with COVID-19 severity in Tokyo Metropolitan area. Phylogenic tree analyses identified two predominant groups which were differentiated by a set of six-point mutations (four non-synonymous amino acid mutations). Among them, Pro108Ser in 3 chymotrypsin-like protease (3CLpro) and Pro151Leu in nucleocapsid protein occurred at conserved locations among β-coronaviruses. Patients with these mutations (N = 48) indicated significantly lower odds ratio for developing hypoxia which required supplemental oxygen (odds ratio 0.24 [95% CI 0.07-0.88, p-value = 0.032]) after adjustments for age and sex, versus those lacking this haplotype in the canonical Clade 20B (N = 37). The Pro108Ser 3CLpro enzyme in vitro decreases in the activity by 58%, and the hydrogen/deuterium exchange mass spectrometry reveals that mechanisms for reduced activities involve structural perturbation at the substrate-binding region which is positioned behind and distant from the 108th amino acid residue of the enzyme. This mutant strain rapidly outcompeted pre-existing variants to become predominant in Japan. Our results may benefit the efforts underway to design small molecular compounds or antibodies targeting 3CLpro.
Associations between alcohol use and accelerated biological ageing
Authors: Bøstrand Sunniva M. K. , Vaher Kadi , De Nooij Laura , Harris Mathew A. , Cole James H. , Cox Simon R. , Marioni Riccardo E. , McCartney Daniel L. , Walker Rosie M. , McIntosh Andrew M. , Evans Kathryn L. , Whalley Heather C. , Wootton Robyn E. , Clarke Toni-Kim 
Published: November 2020

AbstractBackgroundHarmful alcohol use is a leading cause of premature death, and is associated with age-related disease. Ageing is highly variable between individuals, and may deviate from chronological ageing, suggesting that biomarkers of biological ageing (based on DNA methylation or brain structural measures) may be clinically relevant. Here, we investigated the relationships between alcohol phenotypes and both brain and DNA methylation age estimates.MethodsFirst, using data from UK Biobank and Generation Scotland, we tested the association between alcohol consumption (units/week) or hazardous use (AUDIT scores), and accelerated brain and epigenetic ageing in 20,258 and 8,051 individuals, respectively. Second, we used Mendelian randomization to test for a causal effect of alcohol consumption levels and alcohol use disorder (AUD) on biological ageing.ResultsAlcohol use showed a consistent positive association with higher predicted brain age (AUDIT-C: β=0.053, p=3.16×10−13; AUDIT-P: β=0.052, p=1.6×10−13; total AUDIT score: β=0.062, p=5.52×10−16; units/week: β=0.078, p=2.20×10−16), and DNA methylation GrimAge (Units/week: β=0.053, p=1.48×10− 7) and PhenoAge (Units/week: β=0.077, p=2.18×10−10). Mendelian randomization analyses revealed some evidence for a causal effect of AUD on accelerated brain ageing (β=0.272, p=0.044), and no evidence for a causal effect of alcohol consumption levels on accelerated biological ageing.ConclusionsWe provide consistent phenotypic evidence linking alcohol use with accelerated biological ageing. There is possible evidence for a causal effect of AUD on brain age, but not for any other alcohol-related trait on brain or epigenetic age acceleration. Future studies investigating the mechanisms associating alcohol use with accelerated biological ageing are warranted.
Demography, social contact patterns and the COVID-19 burden in different settings of Ethiopia: a modeling study
Authors: Trentini Filippo , Guzzetta Giorgio , Galli Margherita , Zardini Agnese , Manenti Fabio , Putoto Giovanni , Marziano Valentina , Gamshie Worku Nigussa , Tsegaye Ademe , Greblo Alessandro , Melegaro Alessia , Ajelli Marco , Merler Stefano , Poletti Piero 
Published: November 2020

AbstractBackgroundCOVID-19 spread may have a dramatic impact in countries with vulnerable economies and limited availability of, and access to, healthcare resources and infrastructures. However, in sub-Saharan Africa a low prevalence and mortality have been observed so far.MethodsWe collected data on individuals’ social contacts in Ethiopia across geographical contexts characterized by heterogeneous population density, work and travel opportunities, and access to primary care. We assessed how socio-demographic factors and observed mixing patterns can influence the COVID-19 disease burden, by simulating SARS-CoV-2 transmission in remote settlements, rural villages, and urban neighborhoods, under the current school closure mandate.ResultsFrom national surveillance data, we estimated a net reproduction number of 1.62 (95%CI 1.55-1.70). We found that, at the end of an epidemic mitigated by school closure alone, 10-15% of the overall population would have been symptomatic and 0.3-0.4% of the population would require mechanical ventilation and/or possibly result in a fatal outcome. Higher infection attack rates are expected in more urbanized areas, but the highest incidence of critical disease is expected in remote subsistence farming settlements.ConclusionsThe relatively low burden of COVID-19 in Ethiopia can be explained by the estimated mixing patterns, underlying demography and the enacted school closures. Socio-demographic factors can also determine marked heterogeneities across different geographical contexts within the same country. Our findings can contribute to understand why sub-Saharan Africa is experiencing a relatively lower attack rate of severe cases compared to high income countries.
Nurses’ burnout and associated risk factors during the COVID-19 pandemic: a systematic review and meta-analysis
Authors: Galanis Petros , Vraka Irene , Fragkou Despoina , Bilali Angeliki , Kaitelidou Daphne 
Published: November 2020

AbstractBackgroundDuring the COVID-19 pandemic, physical and mental health of the nurses is greatly challenged since they work under unprecedented pressure and they are more vulnerable to the harmful effects of the disease.AimTo examine the impact of the COVID-19 pandemic on nurses’ burnout and to identify associated risk factors.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for this systematic review and meta-analysis. PubMed, Scopus, ProQuest and pre-print services (medRχiv and PsyArXiv) were searched from January 1, 2020 to November 15, 2020 and we removed duplicates. We applied a random effect model to estimate pooled effects since the heterogeneity between results was very high.FindingsFourteen studies, including 17,390 nurses met the inclusion criteria. Five standardized and valid questionnaires were used to measure burnout among nurses; Maslach Burnout Inventory, Copenhagen Burnout Inventory, Professional Quality of Life Scale version 5, Mini-Z, and Spanish Burnout Inventory. The overall prevalence of emotional exhaustion was 34.1% (95% confidence interval [CI]: 22.5-46.6%), of depersonalization was 12.6% (95% CI: 6.9-19.7%), and of lack of personal accomplishment was 15.2% (95% CI: 1.4-39.8%). The following factors were associated with increased nurses’ burnout: younger age, higher educational level, higher degree, decreased social support, having a relative/friend diagnosed with COVID-19, low family and colleagues readiness to cope with COVID-19 outbreak, increased perceived threat of Covid-19, longer working time in quarantine areas, working in a high-risk environment (a COVID-19 designated hospital, a COVID-19 unit, etc.), working in hospitals with inadequate and insufficient material and human resources, decreased working safety while caring for COVID-19 patients, increased workload, decreased self-confidence in self-protection, and lower levels of specialized training regarding COVID-19, job experience, and self-confidence in caring for COVID-19.ConclusionNurses experience high levels of burnout during the COVID-19 pandemic, while several sociodemographic, social and occupational factors affect this burnout. Several interventions need to be implemented to mitigate mental health impact of the COVID-19 pandemic on nurses, e.g. screening for mental health illness and early supportive interventions for high-risk nurses, immediate access to mental health care services, social support to reduce feelings of isolation, sufficient personal protective equipment for all nurses to provide security etc. Governments, health care organizations and policy makers should act in this direction to prepare health care systems, individuals and nurses for a better response against the COVID-19 pandemic.
Protein coevolution and physicochemical adaptation in the APAF-1/apoptosome: structural and functional implications
Authors: Sánchez-Borbón José A , Massey Steven E , Hernández-Martich José D 
Published: November 2020

AbstractThe apoptosome is involved in the mitochondrial pathway of apoptosis, consisting of APAF-1, caspase 9 and cytochrome c, forming a heptamer that activates effector caspases, causing cell death. This protein complex has also been characterized in Drosophila melanogaster (DARK) and Caenorhabditis elegans (CED-4). Here we present an evolutionary guided in silico characterization of the APAF-1/apoptosome. The evolutionary history of the apoptosome was determined, taking the possible orthologs of the APAF-1 version, and executing a protein coevolution and a positive selection analysis, to make structural and functional inferences and identify residues under destabilizing changes, respectively. Results suggests that the APAF-1/apoptosome is not unique to vertebrates, but also some basal invertebrates could possess orthologous copies. New possible versions were also detected in other taxa. Not all insects and other arthropods have the DARK version, just as not all nematodes have the CED-4 version. In the APAF-1 version, amino acid clusters with coevolution signal located in the interior, gave more insights on new potential interactions, allowing us to infer a more detailed model that includes allosterism, of how cytochrome c associates with β propellers during APAF-1 activation, as well as interactions essential for nucleotide exchange, activation of CASP9, the molecular timer and other pathways in mitochondria to induce apoptosis. Residues on the surface under destabilizing changes have guided the protein complex in adaptations necessary for conformational changes, interactions and folding.
Shaking hands is a putative terminal selector and controls axon outgrowth of central complex neurons in the insect modelTribolium
Authors: Garcia-Perez Natalia Carolina , Bucher Gregor , Buescher Marita 
Published: November 2020

AbstractIndividual cell types are specified by transcriptional programs which act during development. Gene regulatory mechanisms which specify subtype identity of central complex (CX) neurons are the subject of intense investigation. The CX is a compartment within the brain common to all insect species. The CX functions as a “command center” by initiating motor actions in response to incoming information. The CX is made up of several thousand neurons with more than 60 morphologically distinct identities. Accordingly, transcriptional programs must effect the specification of at least as many neuronal subtypes. Here we demonstrate a role for the transcription factor Shaking hands (Skh) in the specification of embryonic CX neurons inTribolium. The developmental dynamics ofTc-skhexpression are characteristic for terminal selectors of neuronal subtype identity. In the embryonic brainTc-skhexpression is restricted to a subset of neurons, many of which survive to adulthood and contribute to the mature CX.Tc-skhexpression is maintained throughout the lifetime of the respective CX neurons.Tc-skhknock-down results in severe axon outgrowth defects thus preventing the formation of an embryonic CX primordium. The as yet unstudiedDrosophila skhshows a similar embryonic expression pattern suggesting that subtype specification of CX neurons may be conserved.
Impacts of environmental factors on seed germination and seedling emergence of white clover (Trifolium repens L.)
Authors: Chu Lei , Gao Yiping , Chen Lingling , McCullough Patrick E. , Jespersen David , Sapkota Suraj , Li Xiao , Yu Jialin 
Published: November 2020

AbstractWhite clover (Trifolium repens L.) is cultivated as a forage crop and planted in various landscapes for soil conservation. There are numerous reports of failed white clover stands each year. A good understanding of seed germination biology of white clover in relation to environmental factors is essential to achieve successful stand establishment. A series of experiments were conducted to investigate the impacts of light, temperature, planting depth, drought, and salt stress on seed germination and emergence of white clover. White clover is negatively photoblastic, and seed germination averaged 63 and 66% under light and complete dark conditions at 4 weeks after planting (WAP), respectively. Temperature affected seed germination speed and rate. At 1 WAP, seeds incubated at 15 to 25 °C demonstrated significantly higher germination rate than the low temperatures at 5 and 10 °C; however, the germination rate did not differ among the temperature treatments at 4 WAP. Results suggest that white clover germination decreases with increasing sowing depths and the seeds should be sown on the soil surface or shallowly buried at a depth ≤1 cm to achieve an optimal emergence. White clover seeds exhibited high sensitivity to drought and salinity stress. The osmotic potential and NaCl concentration required to inhibit 50% seed germination was −0.19 MPa and 62.4 mM, respectively. Overall, these findings provide quantifiable explanations for inconsistent establishment observed in field conditions. The findings obtained in this research can be used to develop effective planting strategies and support the successful establishment of white clover stands.