bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteobacteria Contain Diverse flg22 Epitopes That Elicit Varying Immune Responses in Arabidopsis thaliana
Authors: Cheng Janis H. T. , Bredow Melissa , Monaghan Jacqueline , diCenzo George C. 
Published: February 2021

Bacterial flagellin protein is a potent microbe-associated molecular pattern. Immune responses are triggered by a 22-amino-acid epitope derived from flagellin, known as flg22, upon detection by the pattern recognition receptor FLAGELLIN-SENSING2 (FLS2) in multiple plant species. However, increasing evidence suggests that flg22 epitopes of several bacterial species are not universally immunogenic to plants. We investigated whether flg22 immunogenicity systematically differs between classes of the phylum Proteobacteria, using a dataset of 2,470 flg22 sequences. To predict which species encode highly immunogenic flg22 epitopes, we queried a custom motif (11[ST]xx[DN][DN]xAGxxI21) in the flg22 sequences, followed by sequence conservation analysis and protein structural modeling. These data led us to hypothesize that most flg22 epitopes of the γ- and β-Proteobacteria are highly immunogenic, whereas most flg22 epitopes of the α-, δ-, and ε-Proteobacteria are weakly to moderately immunogenic. To test this hypothesis, we generated synthetic peptides representative of the flg22 epitopes of each proteobacterial class, and we monitored their ability to elicit an immune response in Arabidopsis thaliana. The flg22 peptides of γ- and β-Proteobacteria triggered strong oxidative bursts, whereas peptides from the ε-, δ-, and α-Proteobacteria triggered moderate, weak, or no response, respectively. These data suggest flg22 immunogenicity is not highly conserved across the phylum Proteobacteria. We postulate that sequence divergence of each taxonomic class was present prior to the evolution of FLS2, and that the ligand specificity of A. thaliana FLS2 was driven by the flg22 epitopes of the γ- and β-Proteobacteria, a monophyletic group containing many common phytopathogens. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Activin A correlates with the worst outcomes in COVID-19 patients, and can be induced by cytokines via the IKK/NF-kappa B pathway
Authors: McAleavy Megan , Zhang Qian , Xu Jianing , Pan Li , Wakai Matthew , Ehmann Peter J. , Wipperman Matthew F. , Shavlakadze Tea , Hamon Sara C. , Boyapati Anita , Morton Lori G. , Kyratsous Christos A. , Glass David J. 
Published: February 2021

SummaryA fraction of COVID-19 patients develop the most severe form, characterized by Acute Respiratory Disease Syndrome (ARDS). The molecular mechanisms causing COVID-19-induced ARDS have yet to be defined, though many studies have documented an increase in cytokines known as a “cytokine storm.” Here, we demonstrate that cytokines that activate the NF-kappaB pathway can induce Activin A and its downstream marker, FLRG. In hospitalized COVID-19 patients elevated Activin A/FLRG at baseline were predictive of the most severe longitudinal outcomes of COVID-19, including the need for mechanical ventilation, lack of clinical improvement and all-cause mortality. Patients with Activin A/FLRG above the sample median were 2.6/2.9 times more likely to die, relative to patients with levels below the sample median, respectively. The study indicates high levels of Activin A and FLRG put patients at risk of ARDS, and blockade of Activin A may be beneficial in treating COVID-19 patients experiencing ARDS.
Impact on Mental Health of students due to restriction caused by COVID-19 pandemic: Cross-sectional study
Authors: Chaudhary Amar Prashad , Sonar Narayan Sah , TR Jamuna , Banerjee Moumita , Yadav Shailesh 
Published: February 2021

AbstractBackgroundThe aim of the study was to investigate fear, depression and anxiety symptoms among students of India due to COVID-19 pandemic and its restriction.MethodThe cross-sectional web-based research was conducted between mid-November and mid-December 2020 with the objective of understanding the psychological and behavioral consequences of the COVID-19 pandemic effect on students due to the constraint of forced control. The questionnaire included a) socio-demographic questions and b) psychometric scales evaluating the psychological and behavioral impact caused by COVID-19 pandemic and restrictions.ResultsTotal number of 324 students participated in this study in which 44.4% were male and 55.6% were female. Fear of COVID-19 scale showed 68.8% of students had high fear, 24.4% had moderate to severe depression and 51.5% had moderate to severe anxiety. The correlation of fear of COVID-19 scale (FCV-19s) with Generalized Anxiety scale (GAD-7) and brief patient health questionnaire scale (PHQ-9) was found to be 0.492 and 0.474 respectively.ConclusionThis research concludes that there is a very strong fear of COVID-19 among students, along with anxiety and depression symptoms. This study also concludes that the fear of the COVID-19 scale has strong positive correlation with the anxiety (GAD-7) and depression (PHQ-9) scales.
Influence of sex on disease severity in children with COVID-19 and Multisystem Inflammatory Syndrome in Latin America
Authors: Brizuela Martin , Lenzi Jacopo , Ulloa-Gutiérrez Rolando , Yassef Antúnez-Montes Omar , Aida Jorge Alberto Rios , del Aguila Olguita , Arteaga-Menchaca Erick , Campos Francisco , Uribe Fadia , Buitrago Andrea Parra , Londoño Lina Maria Betancur , Gómez-Vargas Jessica , Yock-Corrales Adriana , Buonsenso Danilo 
Published: February 2021

SummaryData from adult studies how that COVID-19 is more severe in men than women. However, no data are available for the pediatric population. For this reason, we performed this study aiming to understand if sex influenced disease severity and outcomes in a large cohort of latin-american children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). We found that a higher percentage of male children developed MIS-C (8.9% vs 5% in females) and died (1.2% and 0.4% in females), although on multivariate adjusted analyses the only statistically significant difference was found in need of hospitalization, with females less frequently admitted compared with boys (25.6% vs 35.4%). This data are preliminary and need further independent studies to better assess the role of sex.
L18F substrain of SARS-CoV-2 VOC-202012/01 is rapidly spreading in England
Authors: Grabowski Frederic , Kochańczyk Marek , Lipniacki Tomasz 
Published: February 2021

AbstractThe Variant of Concern (VOC)-202012/01 (also known as B.1.1.7) is a rapidly growing lineage of SARS-CoV-2. In January 2021, VOC-202012/01 constituted about 80% of SARS-CoV-2 genomes sequenced in England and was present in 27 out of 29 countries that reported at least 50 viral genomes. As this strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. Based on GISAID data we systematically estimated growth rates of mutations acquired by the VOC lineage to find that L18F substitution in viral spike protein has initiated a substrain characterized by replicative advantage of 1.70 [95% CI: 1.56–1.96] in relation to the remaining VOC-202012/01 substrains. The L18F mutation is of significance because when recently analyzed in the context of the South African strain 501Y.V2 it has been found to compromise binding of neutralizing antibodies. We additionally indicate three mutations that were acquired by VOC-202012/01 in the receptor binding motif of spike, specifically E484K, F490S, and S494P, that may also give rise to escape mutants. Such mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence.
Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients
Authors: Cervantes-Alvarez Eduardo , Rosa Nathaly Limon-de la , Salgado-de la Mora Moisés , Valdez-Sandoval Paola , Palacios-Jiménez Mildred , Rodriguez-Alvarez Fátima , Vera-Maldonado Brenda I. , Aguirre-Aguilar Eduardo , Escobar-Valderrama Juan Manuel , Alanis-Mendizabal Jorge , Méndez-Guerrero Osvely , Tejeda-Dominguez Farid , Torres-Ruíz Jiram , Gómez-Martín Diana , Colborn Kathryn L , Kershenobich David , Huang Christene A , Navarro-Alvarez Nalu 
Published: February 2021

ABSTRACTBACKGROUNDPrognostic biomarkers are needed to identify patients at high-risk for severe COVID-19. Galectin-3 is known to drive neutrophil infiltration and release of pro-inflammatory cytokines contributing to airway inflammation.METHODSIn this prospective cohort, we assessed galectin-3 levels in 156 hospitalized patients with confirmed COVID-19. COVID-19 patients were diagnosed as eithercritical(>50% lung damage) ormoderate(<50% of lung damage) based on computerized tomography. Patients who required invasive mechanical ventilation (IMV) and/or died during hospitalization were categorized as having asevere outcome, and anon-severe outcomeif they were discharged and none of the former occurred.RESULTSElevated serum galectin-3 was significantly higher in critical patients compared to moderate ones (35.91 ± 19.37 ng/mL vs. 25 ± 14.85 ng/mL, p<0.0001). Patients who progressed to asevere outcomeincluding IMV and/or in-hospital death, presented higher galectin-3 levels (41.17 ng/mL [IQR 29.71 – 52.25] vs. 23.76 ng/mL [IQR 15.78 – 33.97] compared to those of a non-severe outcome, p<0.0001). Galectin-3 discriminated well between those with severe and non-severe outcome, with an AUC of 0.75 (95% CI 0.67 – 0.84, p<0.0001) and was found to be an independent predictor of severe outcome regardless of the percentage of lung involvement. Additionally, the combination of galectin-3, CRP and albumin, significantly improved its individual predicting ability with an AUC 0.84 (95% CI 0.77 – 0.91, p<0.0001).CONCLUSIONCirculating galectin-3 levels can be used to predict severe outcomes in COVID-19 patients, including the requirement of mechanical ventilation and/or death, regardless of the initial severity of the disease.
Development of a Community Orientation Program (COP) as a Community-Based Medical Education method for undergraduate medical students: An experience from India
Authors: Narapureddy Bayapa Reddy , Kahn Shakeer Patan , Deepthi C Sravana , Chaudhuri Sirshendu , John KR , Chandrasekar Chittooru , Babu Surendra , Nagoor Khadervali , Jeeragyal Devika , Jawahar Basha K. , Nell Theo 
Published: February 2021

AbstractBackgroundIntraregional cultural and linguistic differences are common in the Low- and Middle-income countries. They must focus on innovative teaching for the undergraduate (UG) medical students to make them sensitive to the social and contextual determinants of health to achieve the health for all goal. The early introduction of community-based medical education could be a game changing strategy.ObjectivesTo describe the methods, evaluation, implication, and challenges of a Community Orientation Programme (COP) adopted for the Indian Medical Graduates (IMG). Methods: The COP was arranged for the first-year UG students, including the community and the local administration. The program was divided into phases like-initial preparation, theoretical sessions, field visits, group activities, data analysis, and dissemination of the findings. In this learner-centric, supervised educational program, the key aim was to focus on developing students’ communication skills, observation power and enhancing their motivation for learning new things through collaborative learning. A mixture of adult learning theories like behaviorism, cognitivism, constructivism, sociocultural theory, critical theory, and humanism included keeping the students’ needs, cultural differences, and varying motivational levels. A structured feedback mechanism from the students was developed to identify the gaps.ConclusionThe COP has provided a holistic learning framework for the students based on several complementary learning theories in the Indian context. It has touched upon most of the national- and institutional-level objectives envisioned by the regulatory body for the IMGs. All stakeholders should promote such programs and solve the challenges collectively.
Multivariate spatio-temporal analysis of the global COVID-19 pandemic
Authors: Xiang Wen , Swallow Ben 
Published: February 2021

AbstractThe COVID-19 pandemic has caused significant mortality and disruption on a global scale not seen in living memory. Understanding the spatial and temporal vectors of transmission as well as similarities in the trajectories of recorded cases and deaths across countries can aid in understanding the benefit or otherwise of varying interventions and control strategies on virus transmission. It can also highlight emerging globa trends as they occur. Data on number of cases and deaths across the globe have been made available through a variety of databases and provide a wide range of opportunities for the application of multivariate statistical methods to extract information on similarity or difference from them. Here we conduct spatial and temporal multivariate statistical analyses of global COVID-19 cases and deaths for the period spanning January to August 2020, using a variety of distance based multivariate methods to cluster countries according to similar temporal trends in cases and deaths resulting from COVID-19. We also use novel air passenger data as a proxy for movement between countries. The air passenger movement can act as an important vector of transmission and thus scaling covariance matrices before conducting dimension reduction techniques can account for known structures in the data and help highlight important residual spatial and/or temporal trends that may then be attributable to the success of interventions or other cultural differences. Global temporal structure is found to be of significantly more importance than local spatial structure in terms of global dynamics. Our results highlight a significant global change in case and mortality daynamics from early-August, consistent in timing with the emergence of new strains with highger levels of transmission. We propose the methodology offers great potential in real-time analysis of complex, noisy spatio-temporal data and the extraction of emerging changes in pandemic dynamics that can support policy and decision makers.
Two forms of sexual dimorphism in gene expression inDrosophila melanogaster: their coincidence and evolutionary genetics
Authors: Singh Amardeep , Agrawal Aneil F. 
Published: February 2021

AbstractPhenotypic sexual dimorphism can be mediated by sex differences in gene expression. We examine two forms of sexual dimorphism in gene expression inDrosophila melanogaster: (i) sex-biased gene expression (SBGE) in which the sexes differ in the amount a gene is expressed and (ii) sexual dimorphism in isoform usage, i.e., sex-specific splicing (SSS). In whole body (but not head) expression, we find a negative association between SBGE and SSS, possibly suggesting these are alternate routes to resolving sexual antagonistic selection. Next, we evaluate whether expression dimorphism contributes to the heterogeneity among genes inrmf, the intersexual genetic correlation in body expression that constrains the extent to which a gene’s expression can evolve independently between the sexes. We find lowerrmfvalues for genes with than without SSS. We find higherrmfvalues for male- than female-biased genes (except genes with extreme male-bias), even though male-biased genes are known to have greater evolutionary divergence in expression. Finally, we examine population genetic patterns in relation to SBGE and SSS because genes with expression dimorphism have likely experienced a history of sex differences in selection. SSS is associated with reduced values of Tajima’sDand elevatedDirection of Selection(DoS) values, suggestive of higher rates of adaptive evolution. ThoughDoSis highly elevated for genes with extreme male bias,DoSotherwise tends to decline from female-biased to unbiased to male-biased genes. Collectively, the results indicate that SBGE and SSS are differentially distributed across the genome and are associated with different forms of selection.
Acyl chain shortening induced by inhibition of acetyl-CoA carboxylase renders phosphatidylcholine redundant
Authors: Bao Xue , Koorengevel Martijn C. , Koerkamp Marian J.A. Groot , Homavar Amir , Weijn Amrah , Crielaard Stefan , Renne Mike F. , Geerts Willie J.C. , Surma Michal A. , Mari Muriel , Holstege Frank C.P. , Klose Christian , Kroon Anton I.P.M. de 
Published: February 2021

ABSTRACTPhosphatidylcholine (PC) is an abundant membrane lipid component in most eukaryotes including yeast. PC has been assigned a multitude of functions in addition to that of building block of the lipid bilayer. Here we show that PC is evolvable essential in yeast by isolating suppressor mutants devoid of PC that exhibit robust growth. The requirement for PC is suppressed by monosomy of chromosome XV, or by a point mutation in theACC1gene encoding acetyl-CoA carboxylase. Although these two genetic adaptations rewire lipid biosynthesis differently, both decrease Acc1 activity thereby reducing the average acyl chain length. Accordingly, soraphen A, a specific inhibitor of Acc1, rescues a yeast mutant with deficient PC synthesis. In the aneuploid suppressor, up-regulation of lipid synthesis is instrumental to accomplish feed-back inhibition of Acc1 by acyl-CoA produced by the fatty acid synthase (FAS). The results show that yeast regulates acyl chain length by fine-tuning the activities of Acc1 and FAS, and indicate that PC evolved by benefitting the maintenance of membrane fluidity.
The role of arbuscular mycorrhiza and organosulfur mobilizing bacteria in plant sulphur supply
Authors: Gahan Jacinta , O’Sullivan Orla , Cotter Paul , Schmalenberger Achim 
Published: February 2021

AbstractAM fungi are enhancing growth and health of many land plants but only some of these beneficial mechanisms are well understood. This study aimed to uncover the role of bacteria colonising AM fungi in organically-bound sulfur (S) mobilisation, the dominant S pools in soil that are not directly available to plants. The effect of an intact AM symbiosis with access to stable isotope organo-34S enriched soils encased in 35 µm mesh cores was tested in microcosms withAgrostis stoloniferaandPlantago lanceolata. At 3 month intervals, the plant shoots were analysed for34S uptake. After 9 months, hyphae and associated soil was picked from static (mycorrhizal) and rotating (severed hyphae) mesh cores and corresponding rhizosphere soil was sampled for bacterial analysis. AM symbiosis increased uptake of34S from organo-34S enriched soil at early stages of plant growth when S demand appeared to be high. The static (mycorrhizal) treatments were shown to harbour larger populations of cultivable heterotrophs and sulfonate mobilising bacteria. Microbial communities were significantly different in the hyphosphere of mycorrhizal hyphae and hyphae not associated to plant hosts. Sulfate ester (arylsulfatase enzyme assay,atsAgene) and sulfonate mobilising activity (asfAgene) was altered by an intact AM symbiotic partnership which stimulated the generaAzospirillum, BurkholderiaandPolaromonas. Illumina sequencing revealed that AM symbiosis led to community shifts, reduced diversity and dominance of the Planctomycetes and Proteobacteria. This study demonstrated that AM symbioses can promote organo-S mobilization and plant uptake through interaction with hyphospheric bacteria.Research highlightsAM hyphae enhanced uptake of organically bound34S at early stages of growth.AM hyphosphere harboured a large population of organo-S desulfurizing bacteria.Microbial communities significantly differed in rotating and static mesh cores.AM hyphae influenced bacterial sulfate ester and sulfonate mobilising activity.AM hyphae reduced bacterial diversity, increased Planctomycetes and Proteobacteria abundance.
Pkd1mutation has no apparent effects on peroxisome structure or lipid metabolism
Authors: Terabayashi Takeshi , Menezes Luis F , Zhou Fang , Cai Hongyi , Walter Peter J , Garraffo Hugo M , Germino Gregory G 
Published: February 2021

AbstractBackgroundMultiple studies of tissue and cell samples from patients and pre-clinical models of autosomal dominant polycystic kidney disease report abnormal mitochondrial function and morphology and suggest metabolic reprogramming is an intrinsic feature of this disease. Peroxisomes interact with mitochondria physically and functionally, and congenital peroxisome biogenesis disorders can cause various phenotypes, including mitochondrial defects, metabolic abnormalities and renal cysts. We hypothesized that a peroxisomal defect might contribute to the metabolic and mitochondrial impairments observed in autosomal dominant polycystic kidney disease.MethodsUsing control andPkd1-/-kidney epithelial cells, we investigated peroxisome abundance, biogenesis and morphology by immunoblotting, immunofluorescent and live cell imaging of peroxisome-related proteins and assayed peroxisomal specific β-oxidation. We further analyzed fatty acid composition by mass spectrometry in kidneys ofPkd1fl/fl;Ksp-Cremice. We also evaluated peroxisome lipid metabolism in published metabolomics datasets ofPkd1mutant cells and kidneys. Lastly, we investigated if the C-terminus or full-length polycystin-1 co-localize with peroxisome markers by imaging studies.ResultsPeroxisome abundance, morphology and peroxisome-related protein expression inPkd1-/-cells were normal, suggesting preserved peroxisome biogenesis. Peroxisomal β-oxidation was not impaired inPkd1-/-cells, and there was no obvious accumulation of very long chain fatty acids in kidneys of mutant mice. Re-analysis of published datasets provide little evidence of peroxisomal abnormalities in independent sets ofPkd1mutant cells and cystic kidneys, while providing further evidence of mitochondrial fatty acid oxidation defects. Imaging studies with either full length polycystin-1 or its C-terminus, a fragment previously shown to go to the mitochondria, showed minimal co-localization with peroxisome markers.ConclusionsOur studies showed that loss ofPkd1does not disrupt peroxisome biogenesis nor peroxisome-dependent fatty acid metabolism.Key points-While mitochondrial abnormalities and fatty acid oxidation impairment have been reported in ADPKD, no studies have investigated if peroxisome dysfunction contributes to these defects.-We investigated peroxisome morphology, biogenesis and function in cell and animal models of ADPKD and investigated whether polycystin-1 co-localized with peroxisome proteins.-Our studies show that loss ofPkd1does not disrupt peroxisome biogenesis nor peroxisome-dependent fatty acid metabolism.
Molecular evolutionary dynamics of energy limited microorganisms
Authors: Shoemaker William R. , Polezhaeva Evgeniya , Givens Kenzie B. , Lennon Jay T. 
Published: February 2021

AbstractMicroorganisms have the unique ability to survive extended periods of time in environments with extremely low levels of exploitable energy. To determine the extent that energy limitation affects microbial evolution, we examined the molecular evolutionary dynamics of a phylogenetically diverse set of taxa over the course of 1,000-days. We found that periodic exposure to energy limitation affected the rate of molecular evolution, the accumulation of genetic diversity, and the rate of extinction. We then determined the degree that energy limitation affected the spectrum of mutations as well as the direction of evolution at the gene level. Our results suggest that the initial depletion of energy altered the direction and rate of molecular evolution within each taxon, though after the initial depletion the rate and direction did not substantially change. However, this consistent pattern became diminished when comparisons were performed across phylogenetically distant taxa, suggesting that while the dynamics of molecular evolution under energy limitation are highly generalizable across the microbial tree of life, the targets of adaptation are specific to a given taxon.