bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody Responses in Elderly Residential Care Persons following COVID-19 mRNA Vaccination
Authors: Nace David A. , Kip Kevin E. , Palmer Octavia M. Peck , Shurin Michael R. , Mulvey Katie , Crandall Melissa , Kane April L. , Lukanski Amy , Kip Paula L. , Wells Alan L. 
Published: April 2021

ABSTRACTObjectiveCOVID-19 disproportionately impacts older adults residing at long-term care facilities. Data regarding antibody response to COVID-19 vaccines in this population is limited. Our objective was to quantify the presence and magnitude of antibody response in older, vaccinated residents at assisted living, personal care, and independent living facilities.DesignA cross-sectional quality improvement study was conducted March 15 – April 1, 2021 in the Pittsburgh region.Setting and PopulationParticipants were volunteers at assisted living, personal care, and independent living facilities, who received mRNA COVID-19 vaccine. Conditions that obviate immune responses were exclusionary criteria.MethodsSera were collected to measure IgG anti-SARS-CoV-2 antibody level with reflex to total anti-SARS-CoV-2 immunoglobulin levels. Descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis were performed to evaluate relationships between factors potentially associated with antibody levels.ResultsAll participants (N=70) had received two rounds of vaccination for COVID-19 and were found to have antibodies to SARS-CoV-2. There was wide variation in relative levels of antibodies as determined by extinction coefficients. Antibody levels trended lower in male sex, advanced age, steroid medications, and longer length of time from vaccination.Conclusions and ImplicationsHigher functioning long-term care residents mounted detectable antibody responses when vaccinated with COVID-19 mRNA-based vaccines. This study provides preliminary information on level of population risk of assisted living, personal care, and independent living residents which can inform reopening strategies. Data suggests some degree of immunity is present during the immediate period following vaccination. However, protective effects of such vaccination programs remain to be determined in larger studies. Clinical protection is afforded not just by pre-formed antibody levels, but by ongoing adaptive immunity, which is known to be decreased in older individuals. Thus, the implications of these levels of antibodies in preventing COVID-19 disease must be determined by clinical follow-up.
A rare congenital anemia is caused by mutations in the centralspindlin complex
Authors: Wontakal Sandeep N. , Britto Mishan , Tannenbaum Sarah , Durham Benjamin H. , Lee Margaret T. , Mishima Masanori 
Published: April 2021

AbstractCongenital dyserythropoietic anemias (CDAs) are rare disorders characterized by morphologic abnormalities of erythroid precursors leading to ineffective erythropoiesis. CDA type III (CDAIII), characterized by erythroblast multinucleation, represents the rarest form with only ∼60 patients described in the literature. Previous work, studying two independent families, identified a causative dominant missense mutation in KIF23, which encodes for the kinesin MKLP1. Here, we describe a sporadic CDAIII case associated with compound heterozygous variants in RACGAP1, a gene not previously associated with any disease. RACGAP1 encodes CYK4, a GTPase activating protein (GAP) for Rho-family GTPases, which interacts with MKLP1 to form the centralspindlin complex. Functional assays show these RACGAP1 variants cause cytokinesis defects due, at least in part, to altering the substrate specificities of the GAP activity of CYK4. These findings provide novel insights into the structural determinants of the GAP activity and demonstrates that cytokinesis failure due to centralspindlin defects leads to CDAIII. Our findings highlight the importance of viewing diseases as malfunctions of common biological pathways/complexes and suggests that next-generation sequencing analysis pipelines should integrate a systems approach in order to identify such functionally related variants.
Metabolomics strategy for diagnosing urinary tract infections
Authors: Gregson Daniel B. , Wildman Spencer D. , Chan Carly C.Y. , Bihan Dominique G. , Groves Ryan A. , Aburashed Raied , Rydzak Thomas , Pittman Keir , Van Bavel Nicolas , Lewis Ian A. 
Published: April 2021

AbstractMetabolomics has emerged as a mainstream approach for investigating complex metabolic phenotypes but has yet to be integrated into routine clinical diagnostics. Metabolomics-based diagnosis of urinary tract infections (UTIs) is a logical application of this technology since microbial waste products are concentrated in the bladder and thus could be suitable markers of infection. We conducted an untargeted metabolomics screen of clinical specimens from patients with suspected UTIs and identified two metabolites, agmatine and N6-methyladenine, that are predictive of culture positive samples. We developed a 3.2-minute LC-MS assay to quantify these metabolites and showed that agmatine and N6-methyladenine correctly identify UTIs caused by 13Enterobacteralesspecies and 3 non-Enterobacteralesspecies, accounting for over 90% of infections (agmatine AUC > 0.95; N6-methyladenine AUC > 0.89). These markers were robust predictors across two blinded cohorts totaling 1,629 patient samples. These findings demonstrate the potential utility of metabolomics in clinical diagnostics for rapidly detecting UTIs.
Novel, User-friendly Experimental and Analysis Strategies for Fast Voltammetry: 1. “The Analysis Kid” for FSCV
Authors: Mena Sergio , Dietsch Solene , Berger Shane N. , Witt Colby E. , Hashemi Parastoo 
Published: April 2021

ABSTRACTFast-scan cyclic voltammetry at carbon fiber microelectrodes measures low concentrations of analytes in biological systems. There are ongoing efforts to simplify FSCV analysis and several custom platforms are available for filtering and multi-modal analysis of FSCV signals but there is no single, easily accessible platform that has capacity for all these features. Here we presentThe Analysis Kid: a free, open-source cloud application that does not require a specialized runtime environment and is easily accessible via common browsers. We show that a user-friendly interface can analyze multi-platform file formats to provide multimodal visualization of FSCV color plots with digital background subtraction. We highlight key features that allow interactive calibration and parametric analysisviapeak finding algorithms to automatically detect the maximum amplitude, area under the curve and clearance rate of the signal. Finally,The Analysis Kidenables semi-automatic fitting of data with Michaelis Menten kinetics with single or dual reuptake models.The Analysis Kidcan be freely accessed athttps://analysis-kid.herokuapp.com/. The web application code is found, under an MIT license, athttps://github.com/sermeor/The-Analysis-Kid.
Multi-parameter photon-by-photon hidden Markov modeling
Authors: Harris Paul David , Narducci Alessandra , Gebhardt Christian , Cordes Thorben , Weiss Shimon , Lerner Eitan 
Published: April 2021

AbstractSingle-molecule Förster resonance energy transfer (smFRET) is a unique biophysical approach for studying conformational dynamics in biomacro-molecules. Photon-by-photon hidden Markov modelling (H2MM) is an analysis tool that can quantify FRET dynamics of single biomolecules, even if they occur on the sub-millisecond timescale. However, dye photophysical transitions intertwined with FRET dynamics may introduce artefacts. Here, we introduce multi-parameter H2MM (mpH2MM), which assists in identifying FRET dynamics based on simultaneous observation of multiple experimentally-derived parameters. We show the importance of using mpH2MM to decouple FRET dynamics caused by conformational changes from photophysical transitions in confocal-based smFRET measurements of a DNA hairpin, the maltose binding protein, MalE, and the type-III secretion system effector, YopO, fromYersiniaspecies all exhibiting conformational dynamics ranging from the sub-second to microsecond timescales. Overall, we show that using mpH2MM facilitates the identification and quantification of biomolecular sub-populations and their origin.
NaCT (SLC13A5) facilitates citrate import and metabolism under nutrient-limited conditions
Authors: Kumar Avi , Cordes Thekla , Thalacker-Mercer Anna E. , Pajor Ana M. , Murphy Anne N. , Metallo Christian M. 
Published: April 2021

SummaryCitrate lies at a critical node of metabolism linking tricarboxylic acid metabolism and fatty acid synthesis via acetyl-coenzyme A. Recent studies have linked the sodium citrate transporter (NaCT), encoded bySLC13A5, to dysregulated hepatic metabolism and pediatric epilepsy. To examine how NaCT-mediated citrate metabolism contributes to the pathophysiology of these diseases we applied13C isotope tracing toSLC13A5-deficient hepatocellular carcinoma (HCC) cell lines and primary rat cortical neurons. Exogenous citrate contributed to intermediary metabolism at appreciable levels only under hypoxic conditions. In the absence of glutamine, citrate supplementation increasedde novolipogenesis and growth of HCC cells. Knockout ofSLC13A5in Huh7 cells compromised citrate uptake and catabolism. Citrate supplementation rescued Huh7 cell viability in response to glutamine deprivation and Zn2+treatment, and these effects were mitigated by NaCT deficiency. Collectively, these findings demonstrate that NaCT-mediated citrate uptake is metabolically important under nutrient limited conditions and may facilitate resistance to metal toxicity.
Exploring zebrafish larvae as a COVID-19 model: probable SARS-COV-2 replication in the swim bladder
Authors: Laghi Valerio , Rezelj Veronica , Boucontet Laurent , Frétaud Maxence , Costa Bruno da , Boudinot Pierre , Salinas Irene , Lutfalla Georges , Vignuzzi Marco , Levraud Jean-Pierre 
Published: April 2021

AbstractAnimal models are essential to understand COVID-19 pathophysiology and for pre-clinical assessment of drugs and other therapeutic or prophylactic interventions. We explored the small, cheap and transparent zebrafish larva as a potential host for SARS-CoV-2. Bath exposure, as well as microinjection in the coelom, pericardium, brain ventricle, bloodstream, or yolk, did not result in detectable SARS-CoV-2 replication in wild-type larvae. However, when the virus was inoculated in the swim bladder, a modest increase in viral RNA was observed after 24 hours, suggesting a successful infection in some animals. This was confirmed by immunohistochemistry, with cells positive for SARS-CoV-2 nucleoprotein observed in the swim bladder. Several variants of concern were also tested with no evidence of increased infectivity in our model. Low infectivity of SARS-CoV-2 in zebrafish larvae was not due to the host type I interferon response, as comparable viral loads were detected in type I interferon-deficient animals. Mosaic overexpression of human ACE2 was not sufficient to increase SARS-CoV-2 infectivity in zebrafish embryos or in fish cells in vitro. In conclusion, wild-type zebrafish larvae appear mostly non-permissive to SARS-CoV-2, except in the swim bladder, an aerial organ sharing similarities with the mammalian lung.
Cell type and subcellular compartment specific APEX2 proximity labeling proteomics in the mouse brain
Authors: Dumrongprechachan V. , Soto G. , MacDonald M.L. , Kozorovitskiy Y. 
Published: April 2021

AbstractThe vertebrate brain consists of diverse neuronal types, classified by distinct anatomy and function, along with divergent transcriptomes and proteomes. Defining the cell type-specific neuroproteome is important for understanding the development and functional organization of neural circuits. This task remains challenging in complex tissue, due to suboptimal protein isolation techniques that often result in loss of cell-type specific information and incomplete capture of subcellular compartments. Here, we develop a genetically targeted proximity labeling approach to identify cell-type specific subcellular proteome in the mouse brain. Using adeno- associated viral transduction, we express subcellular-localized APEX2 to map the proteome of the nucleus, cytosol, and cell membrane of Drd1 receptor-positive striatal neurons. We show that each APEX2 construct can differentially and rapidly biotinylate proteinsin situacross various subcellular compartments, confirmed by imaging, electron microscopy, and mass spectrometry. This method enables flexible, cell-type specific quantitative profiling of subcellular proteome in the mouse brain.
Effects of learning and escitalopram administration on serum BDNF levels, a randomised placebo-controlled trial
Authors: Unterholzner J , Godbersen GM , Klöbl M , Ritter V , Pacher D , Seiger R , Varghese N , Eckert A , Lanzenberger R , Vanicek T 
Published: April 2021

AbstractBackgroundThe brain-derived neurotrophic factor (BDNF) has been implicated in processes essential for neuroplasticity. Learning and serotonin reuptake inhibitors (SSRI) foster neuronal reorganization, a mechanism potentially related to BDNF. This study aims to assess the effects of associative learning and escitalopram on serum BDNF (sBDNF) levels, to gain further knowledge on their dynamic interplay.MethodsFor three weeks, 37 participants performed one of two associative learning paradigms with either emotional or semantic content daily. During a subsequent three-week period of reversal learning, subjects either received escitalopram (10mg per day) or placebo. Before and after each learning period sBDNF values were assessed. Citalopram plasma levels were measured at the last time point. Linear mixed effects models (LME) and partial Spearman’s rank and Pearson correlations were used for statistical analyses.ResultsOne-way LME resulted in a significant effect of time during the first learning period over both groups (p<0.01). Two-way LME revealed a significant interaction effect of the emotional content learning group and time (p=0.02). Three-way LME (time x reversal learning group x substance) showed no significant effects (all p> 0.05). Furthermore, correlation between citalopram and sBDNF level after three weeks of escitalopram administration exhibit a negative trend (partial Pearson correlation: r=-0.30, p=0.05; partial Spearman’s rank: r=-0.22, p=0.15).ConclusionThe results suggest that three weeks of associative emotional content learning affect sBDNF levels, while subsequently assessed citalopram plasma and sBDNF levels tend to correlate negatively.Key PointsEmotional learning may affect serum BDNF levels in healthy human subjectsBlood levels of citalopram and serum BDNF exhibit a negative correlation
Recursive MAGUS: scalable and accurate multiple sequence alignment
Authors: Smirnov Vladimir 
Published: April 2021

AbstractMultiple sequence alignment tools struggle to keep pace with rapidly growing sequence data, as few methods can handle large datasets while maintaining alignment accuracy. We recently introduced MAGUS, a new state-of-the-art method for aligning large numbers of sequences. In this paper, we present a comprehensive set of enhancements that allow MAGUS to align vastly larger datasets with greater speed. We compare MAGUS to other leading alignment methods on datasets of up to one million sequences. Our results demonstrate the advantages of MAGUS over other alignment software in both accuracy and speed. MAGUS is freely available in open-source form athttps://github.com/vlasmirnov/MAGUS.
Vibrio choleraemay be transmitted to humans from bullfrog through food or water
Authors: Yang Yibin , Zhu Xia , Chen Yuhua , Liu Yongtao , Song Yi , Ai Xiaohui 
Published: April 2021

AbstractBullfrog is one of the most important economic aquatic animals in China. It is widely cultured in southern China, and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and even anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified asVibrio choleraeusing morphological, biochemical and 16S rRNA phylogenetic analysis. In this study,V. choleraewas isolated and identified from diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. At the same time, it was also found thatV. choleraemay be transmitted to humans from bullfrogs through bullfrog food and aquaculture water, creating a serious threat for human health. Therefore, society should pay attention to the modes of transmission ofVibrio choleraefrom bullfrog and formulate reasonable safety measures to avoid disasters.
The volatile cedrene from plant beneficialTrichoderma guizhouensemodulatesArabidopsisroot development through auxin transport and signaling
Authors: Li Yucong , Shao Jiahui , Fu Yansong , Chen Yu , Wang Hongzhe , Xu Zhihui , Feng Haichao , Xun Weibing , Liu Yunpeng , Zhang Nan , Shen Qirong , Xuan Wei , Zhang Ruifu 
Published: April 2021

ABSTRACTRhizosphere microorganisms interact with plant roots by producing chemical signals to regulate root development. However, the involved distinct bioactive compounds and the signal transduction pathways are remaining to be identified. Here, we show that sesquiterpenes (SQTs) are the main volatile compounds produced by plant beneficialTrichoderma guizhouenseNJAU 4742, inhibition of SQTs synthesis in this strain indicated their involvement in plant-fungus cross-kingdom signaling. SQTs component analysis further identified the cedrene, a high abundant SQT in strain NJAU 4742, could stimulate plant growth and root development. Genetic analysis and auxin transport inhibition showed that auxin receptor TIR1, AFB2, auxin-responsive protein IAA14, and transcription factor ARF7, ARF19 affect the response of lateral roots to cedrene. Moreover, auxin influx carrier AUX1, efflux carrier PIN2 were also indispensable for cedrene-induced lateral root formation. Confocal imaging showed that cedrene affected the expression ofpPIN2:PIN2:GFPandpPIN3:PIN3:GFP, which may be related to the effect of cedrene on root morphology. These results suggest that a novel SQT molecule from plant beneficialT. guizhouensecan regulate plant root development through auxin transport and signaling.One-sentence SummaryCedrene, a high- abundance sesquiterpenes produced by plant beneficialTrichoderma guizhouenseNJAU 4742, stimulatesArabidopsislateral root formation and primary root elongation by relying on auxin signaling pathway and auxin transporter PIN2 and AUX1.
Isolation and characterization of a novel bacteriophage, Kapi1, capable of O-antigen modification in commensalEscherichia coli
Authors: Pick Kat , Raivio Tracy 
Published: April 2021

AbstractIn this study, we describe the isolation and characterization of novel bacteriophage Kapi1 (vB_EcoP_Kapi1) isolated from a strain of commensalEscherichia coliinhabiting the gastrointestinal tract of healthy mice. We show that Kapi1 is a temperate phage integrated into tRNAargWof strain MP1 and describe its genome annotation and structure. Kapi1 shows limited homology to other characterized prophages but is most similar to the phages ofShigella flexneri, and clusters taxonomically with P22-like phages. Investigation of the lifestyle of Kapi1 shows that this phage displays unstable lysogeny and influences the growth of its host. The receptor for Kapi1 is the lipopolysaccharide O-antigen, and we further show that Kapi1 alters the structure of its hosts O-antigen in multiple ways. We hope to use MP1 and Kapi1 as a model system to explore molecular mechanisms of mammalian colonization byE. coliand ask what the role(s) of prophages in this context might be.ImportanceAlthough research exploring the microbiome has exploded in recent years, our understanding of the viral component of the microbiome is lagging far behind our understanding of the bacterial component. The vast majority of intestinal bacteria carry prophages integrated into their chromosomes, but most of these bacteriophages remain uncharacterized and unexplored. Here, we isolate and characterize a novel temperate bacteriophage infecting a commensal strain ofEscherichia coli.We aim to explore the interactions between bacteriophages and their hosts in the context of the gastrointestinal tract, asking what role(s) temperate bacteriophage may play in growth and survival of bacteria in the gastrointestinal tract. Understanding the fundamental biology of commensal bacteria in the gastrointestinal tract can inform the development of novel antimicrobial or probiotic strategies for intestinal infections.
The role of Education 5.0 in accelerating the implementation of SDGs and challenges encountered at the University of Zimbabwe
Authors: Togo Muchaiteyi , Gandidzanwa Crecentia Pamidzai 
Published: April 2021

Purpose
Higher education can play a role in the implementation of sustainable development goals (SDGs). However, there are steps and structures which are necessary for this to be possible. This paper aims to establish how the University of Zimbabwe (UZ)’s innovation hub is implementing SDGs for water, energy and food, resources which are in critical shortage in Harare; as part of its mandate to implement the newly introduced Education 5.0.

Design/methodology/approach
This paper is based on qualitative research. Interview guides were used to gather information from Harare residents, university staff and students. Observations were undertaken and review of secondary data was done. The data was collated into a narrative and content analysis was used to analyse it.

Findings
The UZ innovation hub is aimed to deliver Education 5.0. It houses research projects on energy and food. Water-related projects are still in the pipeline. The research revealed challenges that call for mobilisation of funding to support the projects, to protect researchers’ intellectual property rights and to strengthen interdisciplinary research and information flows between the university and the community. The paper argues for higher and tertiary education institutions to work directly with policymakers and societies in implementing SDGs.

Originality/value
Education 5.0 is relatively new and not much research has been done to establish how it intends to deliver its objectives. The innovation hub model has the potential to yield positive results in SDGs implementation. This research can motivate other universities to work with policymakers and communities in implementing SDGs for urban transformative adaptation.