bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of sleep disturbance and associated risk factors in UK Biobank participants with alcohol use disorders and major depression
Authors: Kolla Bhanu Prakash , Biernacka Joanna M. , Mansukhani Meghna P. , Colby Colin , Coombes Brandon J. 
Published: March 2021

AbstractIntroductionCurrent understanding of the differences in sleep disturbance (SD) and associated risk factors in patients with alcohol use disorders (AUD), major depressive disorders (MDD), and comorbid AUD+MDD is limited.MethodsData from the UK Biobank (UKB) (n=47,825) were utilized to categorize subjects into those with MDD (n=5,991), AUD (n=12,952), both (MDD+AUD)(n=3,219), and controls (n=25,663). We used generalized linear models (GLMs) to test whether rates of SD and sleep duration differed among the groups and determine the clinical predictors of SD. Rates of SD and sleep duration were compared using regression analyses accounting for demographic (age, sex, ethnicity, and Townsend deprivation index) and clinical (body mass index, neuroticism score, and alcohol consumption) factors.ResultsAfter accounting for diagnostic category, SD was associated with age, female sex, white ethnicity, and higher BMI, neuroticism and alcohol consumption scores (all p<0.0001).The unadjusted prevalence of SD was 25.6%, 25.9%, 39.2%, and 41.1% in control, AUD, MDD, and MDD+AUD categories respectively. Rates of SD in controls and AUD group as well as MDD alone and MDD+AUD did not differ in unadjusted models (p=0.45 and 0.075, respectively). Prevalence of SD differed in the four groups (p<0.0001 for all pairwise comparisons) after adjusting for demographic confounders. After further adjustment for clinical factors, effect sizes were reduced, but pairwise comparisons remained significant, except in the AUD versus MDD group (all p<0.05). After adjusting for demographic and clinical factors, sleep duration did not differ among the groups.ConclusionDemographic and clinical characteristics associated with SD were similar in patients with MDD, AUD, and MDD+AUD. The differences in rates of SD between the diagnostic groups were attenuated but persisted after accounting for these confounders. Genetic and other factors capable of influencing SD in patients with MDD, AUD, and comorbid MDD+AUD merit future investigation.
Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors
Authors: De Giorgi Valeria , West Kamille A , Henning Amanda N , Chen Leonard , Holbrook Michael R , Gross Robin , Liang Janie , Postnikova Elena , Trenbeath Joni , Pogue Sarah , Scinto Tania , Alter Harvey J , Cantilena Cathy Corny 
Published: March 2021

ABSTRACTBackgroundCharacterizing the kinetics of the antibody response to SARS□CoV□2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection.Methods/MaterialsWe conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period. At each study visit, subjects either donated plasma or only had study samples drawn. In all cases, anti-SARS-CoV-2 donor testing was performed using semi-quantitative chemiluminescent immunoassays (ChLIA) targeting subunit 1 (S1) of the SARS-CoV-2 spike (S) protein, and an in-house fluorescence reduction neutralization assay (FRNA).ResultsFrom April to November 2020 we enrolled 202 donors, mean age 47.3 ±14.7 years, 55% female, 75% Caucasian. Most donors reported a mild clinical course (91%, n=171) without hospitalization. One hundred and five (105) (52%) donors presented for repeat visits with a median 42 (12-163) days between visits. The final visit occurred at a median 160 (53-273) days post-symptom resolution. Total anti-SARS-CoV-2 antibodies (Ab), SARS-CoV-2 specific IgG and neutralizing antibodies were detected in 97.5%, 91.1%, and 74% of donors respectively at initial presentation. Neutralizing Ab titers based on FRNA50 were positively associated with mean IgG levels (p = <0.0001). Mean IgG levels and neutralizing titers were positively associated with COVID-19 severity, increased donor age and BMI (p=0.0006 and p=0.0028, p=0.0083 and p=0.0363, (p=0.0008 and p=0.0018, respectively). Over the course of repeat visits, IgG decreased in 74.1% of donors; FRNA50 decreased in 44.4% and remained unchanged in 33.3% of repeat donors. A weak negative correlation was observed between total Ab levels and number of days post-symptom recovery (r = 0.09).ConclusionAnti-SARS-CoV-2 antibodies were identified in 97% of convalescent donors at initial presentation. In a cohort that largely did not require hospitalization. IgG and neutralizing antibodies were positively correlated with age, BMI and clinical severity, and persisted for up to 9 months post-recovery from natural infection. On repeat presentation, IgG anti-SARS-CoV-2 levels decreased in 56% of repeat donors. Overall, these data suggest that CP donors possess a wide range of IgG and neutralizing antibody levels that are proportionally distributed across demographics, with the exception of age, BMI and clinical severity.
Association of plasma and CSF cytochrome P450, soluble epoxide hydrolase and ethanolamides metabolism with Alzheimer’s disease
Authors: Borkowski Kamil , Pedersen Theresa L. , Seyfried Nicholas T. , Lah James J. , Levey Allan I. , Hales Chadwick M. , Dammer Eric B. , Blach Colette , Louie Gregory , Kaddurah-Daouk Rima , Newman John W. ,   Alzheimer’s Disease Metabolomics Consortium
Published: March 2021

AbstractAlzheimer’s disease shares inflammatory origin with cardiometabolic disorders. Lipid mediators, including oxylipins, endocannabinoids, bile acids and steroids are potent regulators of inflammation, energy metabolism and cell proliferation with well-established involvement in cardiometabolic diseases. However, their role in Alzheimer’s disease is poorly understood. In the current study we provide comprehensive analysis of plasma and CSF lipid mediators in a case-control comparison of patients with Alzheimer’s disease, utilizing a targeted quantitative mass spectrometry approach. In both plasma and CSF, we observed Alzheimer’s disease patients to have elevated components of cytochrome P450/soluble epoxide hydrolase pathway and lower levels of fatty acids ethanolamides, when compared to the healthy controls. Multivariate analysis revealed that circulating metabolites of soluble epoxide hydrolase together with ethanolamides are strong and independent predictors for Alzheimer’s disease. Both metabolic pathways are potent regulators of inflammation with soluble epoxide hydrolase being reported to be upregulated in the brains of Alzheimer’s disease patients. This study provides further evidence for the involvement of inflammation in Alzheimer’s disease and argues for further research into the role of the cytochrome P450/soluble epoxide hydrolase pathway and fatty acid ethanolamides in this disorder. Further, these findings suggest that a combined pharmacological intervention targeting both metabolic pathways may have therapeutic benefits for Alzheimer’s disease.
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Authors:   The RECOVERY Collaborative Group, Horby Peter W , Estcourt Lise , Peto Leon , Emberson Jonathan R , Staplin Natalie , Spata Enti , Pessoa-Amorim Guilherme , Campbell Mark , Roddick Alistair , Brunskill Nigel E , George Tina , Zehnder Daniel , Tiberi Simon , Aung Ni Ni , Uriel Alison , Widdrington John , Koshy George , Brown Thomas , Scott Steven , Baillie J Kenneth , Buch Maya H , Chappell Lucy C , Day Jeremy N , Faust Saul N , Jaki Thomas , Jeffery Katie , Juszczak Edmund , Lim Wei Shen , Montgomery Alan , Mumford Andrew , Rowan Kathryn , Thwaites Guy , Mafham Marion , Roberts David , Haynes Richard , Landray Martin J 
Published: March 2021

ABSTRACTBackgroundTreatment of COVID-19 patients with plasma containing anti-SARS-CoV-2 antibodies may have a beneficial effect on clinical outcomes. We aimed to evaluate the safety and efficacy of convalescent plasma in patients admitted to hospital with COVID-19.MethodsIn this randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) several possible treatments are being compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to receive either usual care plus high titre convalescent plasma or usual care alone. The primary outcome was 28-day mortality.FindingsBetween 28 May 2020 and 15 January 2021, 5795 patients were randomly allocated to receive convalescent plasma and 5763 to usual care alone. There was no significant difference in 28-day mortality between the two groups: 1398 (24%) of 5795 patients allocated convalescent plasma and 1408 (24%) of 5763 patients allocated usual care died within 28 days (rate ratio [RR] 1·00; 95% confidence interval [CI] 0·93 to 1·07; p=0·93). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (66%vs. 67%; rate ratio 0·98; 95% CI 0·94-1·03, p=0·50). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of progression to invasive mechanical ventilation or death (28%vs. 29%; rate ratio 0·99; 95% CI 0·93-1·05, p=0·79).InterpretationAmong patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant refs: MC_PC_19056; COV19-RECPLA).
Efficient and Economical Targeted Insertion in Plant Genomes via Protoplast Regeneration
Authors: Hsu Chen-Tran , Yuan Yu-Hsuan , Lin Yao-Cheng , Lin Steven , Cheng Qiao-Wei , Wu Fu-Hui , Sheen Jen , Shih Ming-Che , Lin Choun-Sea 
Published: March 2021

AbstractVersatile genome editing can be facilitated by the insertion of DNA sequences into specific locations. Current protocols involving clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins rely on low efficiency homology-directed repair or non-homologous end joining with modified double-stranded DNA oligonucleotides as donors. Our simple protocol eliminates the need for expensive equipment, chemical and enzymatic donor DNA modification or plasmid construction by using polyethylene glycol-calcium to deliver non-modified single-stranded DNA oligonucleotides and CRISPR-Cas9 ribonucleoprotein into protoplasts. Plants regenerated via edited protoplasts achieved targeted insertion frequencies of up to 50.0% inNicotiana benthamianaand 13.6% in rapid cyclingBrassica oleraceawithout antibiotic selection. Using a 60-nt donor containing 27 nt in each homologous arm, 6 of 22 regeneratedN. benthamianaplants showed targeted insertions, and one contained a precise insertion of a 6-bpHindIII site. The inserted sequences were transmitted to the next generation and invite the possibility of future exploration of versatile genome editing by targeted DNA insertion in plants.
Synchronization Temperature Determines the Location of RSV Fusion During Entry in Cultured Cells
Authors: Cadena-Cruz Christian , De-Avila-Arias Marcio , Costello Heather M. , Hurtado-Gomez Leidy , Martínez-De-La-Rosa Walter , Macchia-Ceballos Gigliola , Rosales-Rada Wendy , Valencia-Villa Gerardo , Villalba-Amarís Pedro , Kararoudi Meisam Naeimi , Peeples Mark E. , San-Juan-Vergara Homero 
Published: March 2021

AbstractRespiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in children under five years of age. No vaccines against this virus are currently available. RSV infection of a cell is initiated by fusion between the virion membrane and a cellular membrane, but it is not clear if the fusion process takes place at the plasma membrane or within an endosome. Most such experiments have been initiated at the traditional synchronization temperature of 4°C, an abnormal temperature for animal cells and one at which cellular homeostasis may be negatively affected. We have compared two synchronization temperatures (4°C and 22°C) to determine the kinetics of RSV entry into human bronchial epithelial cells. Following inoculation, virus entry was halted at different times by the addition of neutralizing antibody or temperature reduction to 4°C. We engineered a virus that encodes an extra viral gene, beta-lactamase fused to the viral phosphoprotein (P), to enable rapid detection after infection initiation. We found that the synchronization temperature used during inoculation determines the site of fusion. Transition from 4°C to 37°C resulted in RSV entry via the endosomal pathway but also induced F-actin disruption and plasma membrane blebbing, whether the cells were inoculated with RSV or not. Transition from 22°C to 37°C resulted in RSV entry by fusion at the plasma membrane and without the F-actin and plasma membrane disruptions. These results suggest that RSV normally enters cells by fusion at the plasma membrane and that the induction of endocytosis by infection synchronization at 4°C may be an artefact caused by distortion of the plasma membrane-supporting cytoskeleton.Author SummaryIn order to understand the overall mechanism driving infection, it is important to determine how the virus enters cells. The pathway that RSV uses to infect cells is unclear. It is a common practice to attach the virions at 4°C to synchronize the viral infection. In this report, we found that warming up primary cultures of undifferentiated normal human bronchial epithelial cells to 37°C from 4°C triggered dramatic changes in their cell membrane and cytoskeleton totally unrelated to the presence of the virions. The assessment of viral content delivery to the cytoplasm using RSV engineered to express BlaM allowed us to find that the virions attached at 4°C or 22°C fused their envelope with endosome or plasma membrane, respectively. Consequently, the entry via endosome after attachment at 4°C is an experimental artefact and RSV infects by fusing its envelope with the plasma membrane. The implications go beyond RSV since the entry of several virus species have been explored by synchronizing the infection after attachment at 4°C.
Dynamics of Florida milk production and total phosphate in Lake Okeechobee
Authors: Park Joseph , Saberski Erik , Stabenau Erik , Sugihara George 
Published: March 2021

AbstractA central tenant of the Comprehensive Everglades Restoration Plan (CERP) is nutrient reduction to levels supportive of ecosystem health. A particular focus is phosphorus. We examine links between agricultural production and phosphorus loadings in the Everglades headwaters: Kissimmee River basin and Lake Okeechobee, considered an important source of water for restoration efforts. Over a span of 47 years we find strong correspondence between milk production in Florida and total phosphate in the lake, and, over the last decade, evidence that phosphorus in the lake may have initiated a long-anticipated decline in water column loading.
Detection of the germline specific NAC protein paralog enriched by intrinsically disordered regions inDrosophila melanogaster
Authors: Kogan Galina L. , Mikhaleva Elena A. , Olenkina Oxana M. , Ryazansky Sergei S. , Galzitskaya Oxana V. , Abramov Yuri A. , Leinsoo Toomas A. , Akulenko Natalia V. , Gvozdev Vladimir A. 
Published: March 2021

AbstractNascent polypeptide associated complex (NAC) consisting of α- and β-subunits is an essential conserved ubiquitously expressed ribosome-associated protein in eukaryotes. NAC is considered as a chaperone and co-translational regulator of nascent protein sorting providing homeostasis of cellular proteins. Here we discovered the germinal cell specific NAC (gNAC) homologue, which differs from the ubiquitously expressed NAC by the presence of expanded intrinsically disordered regions (IDRs) at the N- and C-ends of the α- and β-subunits, respectively. We propose these evolutionary acquisition of long IDRs drive gNAC to endow both the specific conformational plasticity for binding client proteins and novel functions regulated by post-transcriptional modifications (PTM). At the same time, we demonstrated that the well-known lethal effect of the loss of ubiquitous NAC-β is suppressed by ectopic expression of its germinal paralog indicating the absence of strict functional differences between the ubiquitous and germline NAC-β subunit paralogs for protein homeostasis.
Automated video tracking and flight analysis show how bumblebees solve a pattern discrimination task using active vision
Authors: MaBouDi HaDi , Roper Mark , Guiraud Marie , Marshall James A.R. , Chittka Lars 
Published: March 2021

AbstractActive vision, the ability of the visual system to actively sample and select relevant information out of a visual scene through eye and head movements, has been explored in a variety of animal species. Small-brained animals such as insects might rely even more on sequential acquisition of pattern features since there might be less parallel processing capacity in their brains than in vertebrates. To investigate how active vision strategies enable bees to solve visual tasks, here, we employed a simple visual discrimination task in which individual bees were presented with a multiplication symbol and a 45° rotated version of the same pattern (“plus sign”). High-speed videography of unrewarded tests and analysis of the bees’ flight paths shows that only a small region of the pattern is inspected before successfully accepting a target or rejecting a distractor. The bees’ scanning behaviour of the stimuli differed for plus signs and multiplication signs, but for each of these, the flight behaviour was consistent irrespective of whether the pattern was rewarding or unrewarding. Bees typically oriented themselves at ~±30° to the patterns such that only one eye had an unobscured view of stimuli. There was a significant preference for initially scanning the left side of the stimuli. Our results suggest that the bees’ movement may be an integral part of a strategy to efficiently analyse and encode their environment.Summary statementAutomated video tracking and flight analysis is proposed as the next milestone in understanding mechanisms underpinning active vision and cognitive visual abilities of bees.
Bilateral symmetry of linear streptomycete chromosomes
Authors: Algora-Gallardo Lis , Schniete Jana K , Mark David R. , Hunter Iain S. , Herron Paul R. 
Published: March 2021

AbstractHere we characterise an uncommon set of telomeres fromStreptomyces rimosusATCC 10970, the parental strain of a lineage of one of the earliest-discovered antibiotic-producers. Following the closure of its genome sequence, we then compared unusual telomeres from this organism with the other five classes of replicon ends found amongst streptomycetes. Closed replicons of streptomycete chromosomes were organised with respect to their phylogeny and physical orientation, which demonstrated that different telomeres were not associated with particular clades and were likely shared amongst different strains by plasmid-driven horizontal gene transfer. Furthermore, we identified a ~50 kb origin island with conserved synteny that is located at the core of all streptomycete chromosomes and forms an axis around which symmetrical chromosome inversions can take place. Despite this chromosomal bilateral symmetry, a bias inparSsites to the right oforiCis maintained across the familyStreptomycetaceaeand suggests that the formation of ParB/parSnucleoprotein complexes on the right replichore is a conserved feature in streptomycetes. Consequently our studies reveal novel features of linear bacterial replicons that, through their manipulation, may lead to improvements in growth and productivity of this important industrial group of bacteria.
Function ofAtPGAP1in GPI anchor lipid remodeling and transport to the cell surface of GPI-anchored proteins
Authors: Bernat-Silvestre César , Sanchez-Simarro Judit , Ma Yingxuan , Johnson Kim , Aniento Fernando , Marcote María Jesús 
Published: March 2021

ABSTRACTGPI-anchored proteins (GPI-APs) play an important role in a variety of plant biological processes including growth, stress response, morphogenesis, signalling and cell wall biosynthesis. The GPI-anchor contains a lipid-linked glycan backbone that is synthesized in the endoplasmic reticulum (ER) where it is subsequently transferred to the C-terminus of proteins containing a GPI signal peptide by a GPI transamidase. Once the GPI anchor is attached to the protein, the glycan and lipid moieties are remodelled. In mammals and yeast, this remodelling is required for GPI-APs to be included in Coat Protein II (COPII) coated vesicles for their ER export and subsequent transport to the cell surface. The first reaction of lipid remodelling is the removal of the acyl chain from the inositol group by Bst1p (yeast) and PGAP1 (mammals). In this work, we have used a loss-of-function approach to study the role ofPGAP1/Bst1like genes in plants. We have found thatArabidopsisPGAP1 localizes to the ER and probably functions as the GPI inositol-deacylase which cleaves the acyl chain from the inositol ring of the GPI anchor. In addition, we show that PGAP1 function is required for efficient ER export and transport to the cell surface of GPI-APs.One sentence summaryGPI anchor lipid remodeling in GPI-anchored proteins is required for their transport to the cell surface inArabidopsis.
Naturally-acquired immunity in Syrian Golden Hamsters provides protection from re-exposure to emerging heterosubtypic SARS-CoV-2 variants B.1.1.7 and B.1.351
Authors: Clark Jordan J. , Sharma Parul , Bentley Eleanor G. , Harding Adam C. , Kipar Anja , Neary Megan , Box Helen , Hughes Grant L. , Patterson Edward I. , Sharp Jo , de Oliveira Tulio , Sigal Alex , Hiscox Julian A. , James William S. , Carroll Miles W. , Owen Andrew , Stewart James P. 
Published: March 2021

AbstractThe ability of acquired immune responses against SARS-CoV-2 to protect after subsequent exposure to emerging variants of concern (VOC) such as B1.1.7 and B1.351 is currently of high significance. Here, we use a hamster model of COVID-19 to show that prior infection with a strain representative of the original circulating lineage B of SARS-CoV-2 induces protection from clinical signs upon subsequent challenge with either B1.1.7 or B1.351 viruses, which recently emerged in the UK and South Africa, respectively. The results indicate that these emergent VOC may be unlikely to cause disease in individuals that are already immune due to prior infection, and this has positive implications for overall levels of infection and COVID-19 disease.