bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sero-prevalence of anti-SARS-CoV-2 antibodies in Chattogram Metropolitan Area, Bangladesh
Authors: Ara Jahan , Islam Md. Sirazul , Quader Md. Tarek Ul , Das Anan , Hasib F. M. Yasir , Islam Mohammad Saiful , Rahman Tazrina , Das Seemanta , Chowdhury M.A. Hassan , Das Goutam Buddha , Chowdhury Sharmin 
Published: February 2022

AbstractBackgroundSeroprevalence studies of coronavirus disease 2019 (COVID-19) assess the degree of undetected transmission in the community. Different groups, such as healthcare workers (HCWs), garment workers, and others, are deemed vulnerable due to their workplace hazards and immense responsibility.PurposeThe present study was conducted to estimate the seroprevalence of anti-SARS-CoV-2 antibody (IgG) and its association with different explanatory variables. Further, the antibody was quantified to assess the increasing or decreasing trend over different intervention periods and according to other factors.MethodologyThis cross-sectional study observed health workers - doctor, nurse, hospital staff, etc. in and outpatients (non-COVID-19) and garments workers of Chattogram metropolitan area (CMA, N=748) from randomly selected six government and private hospitals and two garment factories. Study subjects were included upon written consent, fulfilling specific inclusion criteria. Venous blood was collected following standard aseptic methods. Qualitative and quantitative ELISA was used to identify and quantify antibodies (IgG) in serum samples. Descriptive, univariable, and multivariable statistical analysis was performed.ResultsOverall seroprevalence was estimated as 66.99% (95% CI: 63.40%-70.40%). Seroprevalence among HCWs, in and outpatients, and garments workers were 68.99 % (95% CI: 63.8%-73.7%), 81.37 % (95% CI: 74.7%-86.7%), and 50.56 % (95% CI: 43.5%-57.5%), respectively. Seroprevalence was 44.47 % (95% CI: 38.6%-50.4%) in the non-vaccinated population while it was significantly (p <0.001) higher in the population receiving the first dose (61.66 %, 95% CI: 54.8%-68.0%) and both (first and second) doses of vaccine (100%, 95% CI: 98.4%-100%). The mean titer of the antibody was estimated as 255.46 DU/ml and 159.08 DU/ml in the population with both doses and one dose of vaccine, respectively, compared to 53.71 DU/ml of the unvaccinated population. A decreasing trend in the titer of antibodies with increasing time after vaccination was observed.ConclusionsSeroprevalence and mean antibody titer varied according to different factors in this study. The second dose of vaccine significantly increased the seroprevalence and titer, which decreased to a certain level over time. Although antibody was produced following natural infection, the mean titer was relatively low compared to antibody after vaccination. This study emphasizes the role of the vaccine in antibody production. Based on the findings, interventions like continuing extensive mass vaccination of the leftover unvaccinated population and bringing the mass population with a second dose under a third dose campaign might be planned.
Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study
Authors: Walmsley Sharon , Szadkowski Leah , Wouters Bradly , Clarke Rosemarie , Colwill Karen , Rochon Paula , Brudno Michael , Ravindran Rizani , Raboud Janet , McGeer Allison , Oza Amit , Graham Christopher , Silva Amanda , Manase Dorin , Parente Laura , Simpson Jacqueline , Dayam Roaya Monica , Pasculescu Adrian , Gingras Anne-Claude 
Published: February 2022

AbstractBackgroundTo partially immunize more persons against COVID-19 during a time of limited vaccine availability, Canadian public health officials recommended extending the vaccine dose interval and brand mixing. Impact on the antibody response among the older ambulatory population was unclear.MethodsDecentralized prospective cohort study with self-report of adverse events and collection of dried blood spots. Data is presented for 1193 (93%) of the 911 older (aged >70 years) and 375 younger (30-50 years) recruits.FindingsLocal and systemic reactivity rates were high but short-lived, particularly in the younger cohort and with mRNA-1273 vaccine. After a single COVID-19 vaccine, 84% younger but only 46% older participants had positive IgG antibodies to both spike protein and receptor binding domain (RBD) antigens, increasing to 100/98% with the second dose respectively. In multivariable linear regression model, lower normalized IgG RBD antibody ratios two weeks after the second dose were statistically associated with older age, male gender, cancer diagnosis, lower body weight, BNT162b2 relative to mRNA-1273 and longer dose intervals. Antibody ratios in both cohorts declined 12 weeks post second vaccine dose.InterpretationWe report success of a decentralized serology study. Antibody responses were higher in the younger than older cohort and were greater for those with at least one mRNA-1273 dose. The immunity threshold is unknown but correlations between binding and neutralizing antibodies are strongly positive. Trends with time and at breakthrough infection will inform vaccine booster strategies.FundingSupported by the Public Health Agency of Canada and the University Health Network Foundation.
Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission
Authors: Wenzel Dawn M. , Mackay Douglas R. , Skalicky Jack J. , Paine Elliott L. , Miller Matthew S. , Ullman Katharine S. , Sundquist Wesley I. 
Published: February 2022

AbstractThe 12 related human ESCRT-III proteins form filaments that constrict membranes and mediate fission, including during cytokinetic abscission. The C-terminal tails of polymerized ESCRT-III subunits also bind proteins that contain Microtubule-Interacting and Trafficking (MIT) domains. MIT domains can interact with ESCRT-III tails in many different ways to create a complex binding code that recruits essential cofactors to sites of ESCRT activity. Here, we have comprehensively and quantitatively mapped the interactions between all known ESCRT-III tails and 19 pure recombinant human MIT domains. We measured 228 pairwise interactions, quantified 58 positive interactions, and discovered 16 previously unreported interactions. We also report the crystal structure of the SPASTIN MIT domain in complex with the IST1 C-terminal tail. Three MIT enzymes were studied in detail and shown to: 1) localize to cytokinetic midbody membrane bridges through interactions with their specific ESCRT-III binding partners (SPASTIN-IST1, KATNA1-CHMP3, and CAPN7-IST1), 2) function in abscission (SPASTIN, KATNA1, and CAPN7), and 3) function in the “NoCut” abscission checkpoint (SPASTIN and CAPN7). Our studies define the human MIT-ESCRT-III interactome, identify new factors and activities required for cytokinetic abscission and its regulation, and provide a platform for analyzing ESCRT-III and MIT cofactor interactions in all ESCRT-mediated processes.
A catalytic mechanism for Renilla-type bioluminescence
Authors: Schenkmayerova Andrea , Toul Martin , Pluskal Daniel , Baatallah Racha , Gagnot Glwadys , Pinto Gaspar P. , Santana Vinicius T. , Stuchla Marketa , Neugebauer Petr , Chaiyen Pimchai , Damborsky Jiri , Bednar David , Janin Yves L. , Prokop Zbynek , Marek Martin 
Published: February 2022

AbstractThe widely used coelenterazine-powered Renilla luciferase was discovered over 40 years ago but the oxidative mechanism by which it generates blue photons remains unclear. Here we decipher Renilla-type bioluminescence through crystallographic, spectroscopic, and computational experiments. Structures of ancestral and extant luciferases complexed with the substrate-like analogue azacoelenterazine or a reaction product were obtained, providing unprecedented snapshots of coelenterazine-to-coelenteramide oxidation. Bound coelenterazine adopts a Y-shaped conformation, enabling the deprotonated imidazopyrazinone component to attack O2 via a radical charge-transfer mechanism. A high emission intensity is secured by an aspartate from a conserved proton-relay system, which protonates the excited coelenteramide product. Another aspartate on the rim of the catalytic pocket fine-tunes the electronic state of coelenteramide and promotes the formation of the blue light-emitting phenolate anion. The results obtained also reveal structural features distinguishing flash-type from glow-type bioluminescence, providing insights that will guide the engineering of next-generation luciferase–luciferin pairs for ultrasensitive optical bioassays.
The structure, binding, and function of a Notch transcription complex involving RBPJ and the epigenetic reader protein L3MBTL3
Authors: Hall Daniel , Giaimo Benedetto Daniele , Park Sung-Soo , Hemmer Wiebke , Friedrich Tobias , Ferrante Francesca , Bartkuhn Marek , Yuan Zhenyu , Oswald Franz , Borggrefe Tilman , Rual Jean-François , Kovall Rhett A. 
Published: February 2022

AbstractThe highly conserved Notch pathway transmits signals between neighboring cells to elicit distinct downstream transcriptional programs. In given contexts, Notch is a major regulator of cell fate specification, proliferation, and apoptosis, such that aberrant Notch signaling leads to a pleiotropy of human diseases, including developmental disorders and cancers. The canonical pathway signals through the transcription factor CSL (RBPJ in mammals), which forms a transcriptional activation complex with the intracellular domain of the Notch receptor and the coactivator Mastermind. CSL can also function as a transcriptional repressor by forming complexes with one of several different corepressor proteins, such as FHL1 or SHARP in mammals and Hairless in Drosophila. Recently, we identified the malignant brain tumor (MBT) family member L3MBTL3 as a bona fide RBPJ binding corepressor that recruits the repressive lysine demethylase LSD1/KDM1A to Notch target genes. Here we define the RBPJ-interacting domain (RBP-ID) of L3MBTL3 and report the 2.06 Å crystal structure of the complex formed between RBPJ, the RBP-ID of L3MBTL3 and DNA. The structure reveals the molecular interactions underlying L3MBTL3 complexation with RBPJ, which we comprehensively analyze with a series of L3MBTL3 and RBPJ mutations that span the binding interface. Compared to other RBPJ-binding proteins, we find that L3MBTL3 interacts with RBPJ via an unusual binding motif, which is sensitive to mutations throughout its RBPJ-interacting region. We also show that these disruptive mutations affect RBPJ and L3MBTL3 function in cells, providing further insights into Notch mediated transcriptional regulation.
A Multiscale study of phosphorylcholine driven cellular phenotypic targeting
Authors: Acosta-Gutiérrez Silvia , Matias Diana , Avila-Olias Milagros , Gouveia Virginia M. , Scarpa Edoardo , Forth Joe , Contini Claudia , Duro-Castano Aroa , Rizzello Loris , Battaglia Giuseppe 
Published: February 2022

AbstractPhenotypic targeting requires the ability of the drug delivery system to discriminate over cell populations expressing a particular receptor combination. Such selectivity control can be achieved using multiplexed-multivalent carriers often decorated with multiple ligands. Here, we demonstrate that the promiscuity of a single ligand can be leveraged to create multiplexed-multivalent carriers achieving phenotypic targeting. We show how the cellular uptake of poly(2-methacryloyloxyethyl phosphorylcholine)-poly(2- (diisopropylamino)ethyl methacrylate) (PMPC-PDPA) polymersomes varies depending on the receptor expression among different cells. We investigate the PMPC-PDPA polymersome insertion at the single chain/receptor level using all-atom molecular modelling. We propose a theoretical statistical mechanics-based model for polymersome-cell association that explicitly considers the interaction of the polymersome with the cell glycocalyx shedding light on its effect on the polymersome binding. We validate our model experimentally and show that the binding energy is a non-linear function, allowing us to tune interaction by varying the radius and degrees of polymerisation. Finally, we show that PMPC-PDPA polymersomes can be used to target monocytes in vivo due to their promiscuous interaction with SRB1, CD36 and CD81.
Controversy over the decline of arthropods: a matter of temporal baseline?
Authors: Duchenne François , Porcher Emmanuelle , Mihoub Jean-Baptiste , Loïs Grégoire , Fontaine Colin 
Published: February 2022

AbstractRecently, a number of studies have reported somewhat contradictory patterns of temporal trends in arthropod abundance, from decline to increase. Arthropods often exhibit non-monotonous variation in abundance over time, making it important to account for temporal coverage in interpretation of abundance trends, which is often overlooked in statistical analysis. Combining four recently analysed datasets that led to contrasting outcomes, we first show that temporal abundance variations of arthropods are non-monotonous. Using simulations, we show non-monotony is likely to bias estimated linear abundance trends. Finally, analysing empirical data, we show that heterogeneity in estimated abundance trends is significantly related to the variation in temporal baseline of analysed time series. Once differences in baseline years, habitats and continents are accounted for, we do not find any statistical difference in estimated linear abundance trends among the four datasets. We also show that short time series produce more stochastic abundance trends than long series, making the dearth of old and long-term time series a strong limitation in the assessment of temporal trends in arthropod abundance. The lack of time series with a baseline year before global change acceleration is likely to lead to an underestimation of global change effects on biodiversity.
The genome of tropically adapted Brahman cattle (Bos taurus indicus) reveals novel genome variation in production animals
Authors: Ross Elizabeth M , Nguyen Loan T , Lamb Harrison J , Moore Stephen S , Hayes Ben J 
Published: February 2022

AbstractRecent advances in sequencing technology have revolutionised access to large scale genomic data that can be assembled into a platinum quality genome. Here we present a high quality genome assembly with less than 300 gaps of a Brahman cow (B. taurus indicus). The assembly was generated using 195GB of PacBio and 169GB of Oxford Nanopore Technologies sequence data. The high quality genome assembly allows us to identify substantial GC content variation that is positively associated with gene rich islands, and negatively associated with genetic variation in the form of structural variants. In addition, 92371 structural variants that are segregating in the brahman population were identified. Gene ontology analysis revealed that genes with varying copy numbers were enriched for gene ontology terms related to immune function. This analysis has revealed the complex structure of the mammalian genome of an outbred species, and identifies the ability of long read data from diploid species can be used to not only assemble a high quality genome, but also discover novel genetic variation within that genome.
In-shoe plantar pressure depends on walking speed and type of weight-bearing activity in people with diabetes at high risk of ulceration
Authors: Hulshof Chantal M , van Netten Jaap J , Dekker Maartje G , Pijnappels Mirjam , Bus Sicco A 
Published: February 2022

AbstractBackgroundIn evaluating the biomechanical properties of therapeutic footwear, most often in-shoe plantar pressure is obtained during mid-gait steps at self-selected speed in a laboratory setting. However, this may not represent plantar pressures or indicate the cumulative stress experienced in daily life, where people adopt different walking speeds and weight-bearing activities.Research questionIn people with diabetes at high risk of ulceration, 1) what is the effect of walking speed on plantar pressure measures, and 2) what is the difference in plantar pressure measures between walking at self-selected speed and other weight-bearing activities?MethodsIn a cross-sectional study, we included 59 feet of 30 participants (5 females, mean age: 63.8 (SD 9.2) years). We assessed in-shoe plantar pressure with the Pedar-X system during three standardized walking speeds (0.8, 0.6 and 0.4 m/s) and eight types of activities versus walking at self-selected speed (3 components of the Timed Up and Go test (TUG), standing, accelerating, decelerating, stair ascending and descending and standing). Peak plantar pressure (PPP) and pressure-time integral (PTI) were determined for the hallux, metatarsal 1, metatarsal 2-3 and metatarsal 4-5. For statistical comparisons we used linear mixed models (α<0.05) with Holm-Bonferroni correction.ResultsWith increasing walking speed, PPP increased and PTI decreased for all regions (p≤0.001). Standing, decelerating, stair ascending and TUG showed lower PPP than walking at self-selected speed for most regions (p≤0.004), whereas accelerating and stair descending showed similar PPP. Stair ascending and descending showed higher PTI than walking at self-selected speed (p≤0.002), standing showed lower PTI (p≤0.001), while the other activities showed similar PTI for most regions.SignificanceTo best evaluate the biomechanical properties of therapeutic footwear, and to assess cumulative plantar tissue stress of people with diabetes at high risk of ulceration, plantar pressures during different walking speeds and activities of daily living should be considered.
Narrow transmission bottlenecks and limited within-host viral diversity during a SARS-CoV-2 outbreak on a fishing boat
Authors: Hannon William W. , Roychoudhury Pavitra , Xie Hong , Shrestha Lasata , Addetia Amin , Jerome Keith R. , Greninger Alexander L. , Bloom Jesse D. 
Published: February 2022

AbstractThe long-term evolution of viruses is ultimately due to viral mutants that arise within infected individuals and transmit to other individuals. Here we use deep sequencing to investigate the transmission of viral genetic variation among individuals during a SARS-CoV-2 outbreak that infected the vast majority of crew members on a fishing boat. We deep-sequenced nasal swabs to characterize the within-host viral population of infected crew members, using experimental duplicates and strict computational filters to ensure accurate variant calling. We find that within-host viral diversity is low in infected crew members. The mutations that did fix in some crew members during the outbreak are not observed at detectable frequencies in any of the sampled crew members in which they are not fixed, suggesting viral evolution involves occasional fixation of low-frequency mutations during transmission rather than persistent maintenance of within-host viral diversity. Overall, our results show that strong transmission bottlenecks dominate viral evolution even during a superspreading event with a very high attack rate.
Parallel Expansion and Divergence of an Adhesin Family in Pathogenic Yeasts IncludingCandida auris
Authors: Smoak Rachel A. , Snyder Lindsey F. , Fassler Jan S. , He Bin Z. 
Published: February 2022

AbstractOpportunistic yeast pathogens evolved multiple times in the Saccharomycetes class, including the recently emerged, multidrug-resistantCandida auris. We show that homologs of a known yeast adhesin family inCandida albicans, the Hyr/Iff-like (Hil) family, are enriched in distinct clades ofCandidaspecies as a result of multiple, independent expansions. Following gene duplication, the tandem repeat-rich region in these proteins diverged extremely rapidly and generated large variations in length and β-aggregation potential, both of which were known to directly affect adhesion. The conserved N-terminal effector domain was predicted to adopt a β-helical fold followed by an α-crystallin domain, making it structurally similar to a group of unrelated bacterial adhesins. Nonsynonymous-to-synonymous substitution rate analysis of the effector domain inC. aurisrevealed relaxed selective constraint and signatures of positive selection, suggesting functional diversification after gene duplication. Lastly, we found the Hil family genes to be enriched at chromosomal ends, which likely contributed to their expansion via ectopic recombination and break-induced replication. We hypothesize that the expansion and diversification of adhesin families are a key step toward the emergence of fungal pathogens and also generate variation in adhesion and virulence within and between species.
Delayed puberty, gonadotropin abnormalities and subfertility in malePadi2/Padi4double knockout mice
Authors: Sams Kelly L. , Mukai Chinatsu , Marks Brooke A. , Mittal Chitvan , Demeter Elena Alina , Nelissen Sophie , Grenier Jennifer K. , Tate Ann E. , Ahmed Faraz , Coonrod Scott A. 
Published: February 2022

ABSTRACTBackgroundPeptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signalingin vitroand the goal of this study was to test for links between PAD2/PAD4 and hormone signalingin vivo.MethodsPreliminary analysis ofPadi2andPadi4single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created aPadi2/Padi4double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects.ResultsControlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO and WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis.ConclusionsThePadi2/Padi4DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the firstin vivoevidence linking PADs with hormone signaling.
Crowdsourced EEG Experiments: A proof of concept for remote EEG acquisition using EmotivPRO Builder and EmotivLABS
Authors: Williams Nikolas S , King William , Mackellar Geoffrey , Randeniya Roshini , McCormick Alicia , Badcock Nicholas A 
Published: February 2022

AbstractOnline research platforms have enabled mass data collection enabling representative samples for cognitive behavioural studies. However, the benefits of online data collection have not been available for cognitive neuroscience fields such as electroencephalography (EEG). In this study, we introduce an approach for remote EEG data collection. We demonstrate how an experiment can be built via the EmotivPRO Builder and deployed to the EmotivLABS website where it can be completed by participants who own EMOTIV EEG headsets. To demonstrate the data collection technique, we collected EEG while participants engaged in a resting state task where participants sat with their eyes open and then eyes closed for two minutes each. We observed a significant difference in alpha power between the two conditions thereby demonstrating the well-known alpha suppression effect. Thus, we demonstrate that EEG data collection, particularly for frequency domain analysis, can be successfully conducted online with remote users.