bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactive analysis of functional residues in protein families
Authors: Price Morgan N. , Arkin Adam P. 
Published: July 2022

AbstractA protein’s function depends on functional residues that determine its binding specificity or its catalytic activity, but these residues are typically not considered when annotating a protein’s function. To help biologists investigate the functional residues of proteins, we developed two interactive web-based tools, SitesBLAST and Sites on a Tree. Given a protein sequence, SitesBLAST finds homologs that have known functional residues and shows whether the functional residues are conserved. Sites on a Tree shows how functional residues vary across a protein family by showing them on a phylogenetic tree. These tools are available at http://papers.genomics.lbl.gov/sites.
Transcriptional Profiles Analysis of COVID-19 and Malaria Patients Reveals Potential Biomarkers in Children
Authors: Lambert Nzungize , Kengne-Ouafo Jonas A. , Rissy Wesonga Makokha , Diane Umuhoza , Murithi Ken , Kimani Peter , Awe Olaitan I. , Dillman Allissa 
Published: July 2022

AbstractThe clinical presentation overlap between malaria and COVID-19 poses special challenges for rapid diagnosis in febrile children. In this study, we collected RNA-seq data of children with malaria and COVID-19 infection from the public databases as raw data in fastq format paired end files. A group of six, five and two biological replicates of malaria, COVID-19 and healthy donors respectively were used for the study. We conducted differential gene expression analysis to visualize differences in the expression profiles. Using edgeR, we explored particularly gene expression levels in different phenotype groups and found that 1084 genes and 2495 genes were differentially expressed in the malaria samples and COVID-19 samples respectively when compared to healthy controls. The highly expressed gene in the COVID-19 group we found CD151 gene which is facilitates in T cell proliferation, while in the malaria group, among the highly expressed gene we identified GBP5 gene which involved in inflammatory response and response to bacterium. By comparing both malaria and COVID-19 infections, the overlap of 62 differentially expressed genes patterns were identified. Among them, three genes (ENSG00000234998, H2AC19 and TXNDC5) were highly upregulated in both infections. Strikingly, we observed 13 genes such as HBQ1, HBM, SLC7A5, SERINC2, ATP6V0C, ST6GALNAC4, RAD23A, PNPLA2, GAS2L1, TMEM86B, SLC6A8, UBALD1, RNF187 were downregulated in children with malaria and uniquely upregulated in children with COVID-19, thus may be further validated as potential biomarkers to delineate COVID-19 from malaria-related febrile infection. The hemoglobin complexes and lipid metabolism biological pathways are highly expressed in both infections. Our study provided new insights for further investigation of the biological pattern in hosts with malaria and COVID-19 coinfection.
D/E-rich peptides are less suitable than D/E-deficient peptides for identification by negative-ion HCD due to scarce production of sequencing ions from multiply charged precursors
Authors: Zuo Mei-Qing , Sun Rui-Xiang , Dong Meng-Qiu 
Published: July 2022

ABSTRACTHighly acidic, D/E-rich peptides or proteins are difficult to identify by positive-ion-mode mass spectrometry (MS), and negative-ion-mode MS is an attractive but insufficiently explored alternative. Based on high-resolution and accurate-mass MS analysis of 115 synthetic peptides of 5-28 amino acids, we confirmed that higher-energy collisional dissociation (HCD) of deprotonated peptides induced abundant backbone or side-chain neutral losses (NL), and updated the ranking list of NLs by abundance. The most abundant fragment ion types arey->x-, z->c-if the NL ions are included, orc->y->z->b-if not. The most frequent side-chain NLs involve amino acids C, S, T, D, E, N, Q, and R. Although NL of CO2is common for all peptides, it is markedly enhanced in D/E-containing peptides. Long peptides and D/E-rich peptides are prone to carrying multiple negative charges. HCD spectra produced from multiply deprotonated peptides have a lower fraction of sequencing ions (i.e.,a-, b-, c-, x-, y-, z-ions) than those produced from 1-([M-H]-) and 2-([M-2H]2-) precursors. Based on the above findings, we predict that under negative-ion HCD, D/E-rich peptides should be difficult to identify and that choosing a protease to generate peptides containing fewer D/E residues will improve identification of highly acidic proteins.
BmHen1 plays an essential role in the regulation of eupyrene sperm development in Bombyx mori
Authors: Yang Xu , Chen Dongbin , Zheng Shirui , Yi Meiyan , Liu Zulian , Liu Yongjian , Yang Dehong , Liu Yujia , Tang Linmeng , Zhu Chenxu , Huang Yongping 
Published: July 2022

AbstractIn lepidopteran insects, sperm polymorphism is a remarkable feature, in which males exhibit two different types of sperms. Both sperm morphs are essential for fertilization as eupyrene (nucleate) sperm carries DNA and fertilizes the egg, while apyrene (anucleate) sperm is necessary for transporting eupyrene sperm into females. To date, the functional genetic study on dichotomous spermatogenesis has been limited. It is known that, in the model species including mice, worms, and flies, the components in piRNA biogenesis pathway play an important role in gonad development. In this study, we characterize BmHen1 as a new critical component involved in the regulation of eupyrene sperm development in B. mori. We generated the loss-of-function mutant of BmHen1 (ΔBmHen1) through CRISPR/Cas9-based gene editing, and found that it is both female- and male-sterile. ΔBmHen1 females lay significantly fewer eggs than wild-type, which display morphological defects. Fluorescence staining assays show that the ΔBmHen1 eupyrene sperms exhibit severe defects in nuclei formation, while its apyrene sperms are normal. We then constructed the loss-of-function mutants of Siwi and BmAgo3 (ΔSiwi and ΔBmAgo3) through CRISPR/Cas9-based gene editing, which encode PIWI proteins acting as the core elements in piRNA biogenesis, and explored whether they might be involved in spermatogenesis. To our surprise, ΔSiwi and ΔBmAgo3 mutants develop normal male reproduction system, indicating that they don’t participate in sperm development. As the activity of BmHen1 depends on BmPnldc1 during piRNA biogenesis, and ΔBmHen1 and ΔBmPnldc1 mutants display similar defects in sperm development, we performed RNA sequencing analysis to look for the genes that might be co-regulated by BmHen1 and BmPnldc1. Our results indicate that the defects in ΔBmHen1 and ΔBmPnldc1 eupyrene sperms could be attributed to dysregulated genes involved in energy metabolism and cell differentiation. Furthermore, we found that the piRNA biogenesis is inhibited in ΔBmHen1 and ΔBmPnldc1 sperm bundles, whereas the transposon activity was induced. Taken together, our findings suggest that BmHen1 is a new crucial component regulating eupyrene sperm development in B. mori, whereas the PIWI proteins Siwi and BmAgo3 are not involved in this process. Our results may provide a potential gene target for genetic modification of sterility in B. mori.
Lepidopteran prolegs are novel traits, not leg homologs
Authors: Matsuoka Yuji , Murugesan Suriya Narayanan , Prakash Anupama , Monteiro Antónia 
Published: July 2022

AbstractLepidopteran larvae have both thoracic legs and abdominal prolegs, yet it is unclear whether these are serial homologs. We examined the role of three Hox genes in proleg development in Bicyclus anynana butterflies using CRISPR-Cas9 and discovered that under a partial segment abdominal-A (abd-A) knockout, both types of appendages can develop in the same segment, arguing for prolegs being a novel trait, not a leg serial homolog. We also discover that specificity protein (sp) genes do not co-localize with Distal-less (Dll) in prolegs, as they do in legs, and that the proleg gene-regulatory network (GRN) mostly resembles the head-horn GRN, another novel trait in the lepidoptera. We propose that larval prolegs evolved from the co-option of a partial limb GRN into novel embryonic coordinates in the abdomen.One-Sentence SummaryThe chubby legs of caterpillars are evolutionary innovations
Hydroxychloroquine pre-exposure prophylaxis to prevent SARS-CoV-2 among health care workers at risk for SARS-CoV-2 exposure: A nonrandomized controlled trial
Authors: Raabe Vanessa N. , Fleming Andrew , Samanovic Marie I. , Lai Lilin , Belli Hayley M. , Mulligan Mark J. , Belmont H. Michael 
Published: July 2022

AbstractBackgroundAerosol-generating procedures increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs). An effective pre-exposure prophylaxis would mitigate this risk.ObjectiveTo determine the efficacy of pre-exposure prophylactic hydroxychloroquine for the prevention of SARS-CoV-2 infection and symptomatic coronavirus 19 disease (COVID-19) among HCWs at high occupational risk of SARS-CoV-2 exposure.Methods130 HCWs in the New York University Langone Health System (NYULHS) who performed aerosol-generating procedures on patients with COVID-19 or provided bedside care for inpatients with COVID-19 or persons with suspected COVID-19 in an emergency department, for at least three shifts in a 7-day period, during the first 2020 COVID-19 wave in New York City were enrolled. Participants elected to take oral hydroxychloroquine, 600 mg on day 1 followed by 200 mg daily, or not take hydroxychloroquine for up to 90 days. Participants self-collected dried blood spots and completed digital questionnaires regarding COVID-19 symptoms, adverse events, and other COVID-19 medication use.ResultsSix participants (7.5%) seroconverted during the trial: four who took hydroxychloroquine (6.8%) and two who declined hydroxychloroquine (9.5%). All participants not taking hydroxychloroquine reported COVID-19 symptoms at seroconversion compared to one of four participants (25%) who took hydroxychloroquine. Adverse events occurred in eight participants (9.6%) on hydroxychloroquine and were mostly mild.ConclusionsThis study (ClinicalTrials.govNCT04354870) did not demonstrate a statistically significant difference in SARS-CoV-2 seroconversion associated with hydroxychloroquine pre-exposure prophylaxis among HCWs at high risk of occupational SARS-CoV-2 exposure, although was underpowered and a high rate of hydroxychloroquine discontinuation was observed.
B cell response six months after SARS-CoV-2 mRNA vaccination in people living with HIV under antiretroviral therapy
Authors: Polvere Jacopo , Fabbiani Massimiliano , Pastore Gabiria , Rancan Ilaria , Rossetti Barbara , Durante Miriam , Zirpoli Sara , Morelli Enrico , Pettini Elena , Lucchesi Simone , Fiorino Fabio , Tumbarello Mario , Ciabattini Annalisa , Montagnani Francesca , Medaglini Donata 
Published: July 2022

AbstractBackgroundSARS-CoV-2 mRNA vaccines have demonstrated high immunogenicity in healthy subjects and preliminary results for people living with HIV (PLWHIV) are promising too. We have previously reported the persistence of spike-specific circulating IgG and memory B cells in healthy adults up to six months after mRNA SARS-CoV-2 vaccination. Unfortunately, limited longitudinal data are available for PLWHIV and no evidence of persistent spike-specific B cells have been reported yet.MethodsWe investigated the humoral response and the persistence of spike-specific memory B cells up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under ART and compared them to healthy controls (HCs). Humoral response was analyzed with enzyme-linked immunosorbent assay and with an angiotensin-converting enzyme 2 (ACE2) and receptor binding domain (RBD) inhibition assay. PBMCs were analyzed with a cytofluorimetric approach for B cell phenotyping.FindingsSpike-specific IgG peaked 1 month after second dose and persisted up to six months after vaccination with no significant differences compared to HCs. The stratification of patients according to CD4+ T cell count showed a significantly lower IgG response in case of CD4<350/µl, remarking the relevance of immune reconstitution. The ability of IgG of blocking the binding between ACE2 and RBD was detected in 58·4% of PLWHIV, compared to 86·2% in HCs. The amount of circulating spike-specific memory B cells detected in PLWHIV six months after vaccination was not significantly different from HCs, while there was prevalence of antigen-specific double negative (IgD-/CD27-) cells, compared to controls.InterpretationIn conclusion, the majority of PLWHIV developed spike-specific humoral and B cell responses that persist for at least six months after SARS-CoV-2 mRNA vaccination. However, hints of HIV-dependent immune impairment were revealed by altered spike-specific B cell phenotypes and by reduced spike-specific humoral response in patients with low CD4+ T cell count (<350/µl).
CovidOutcome2: a tool for SARS-CoV2 mutation identification and for disease severity prediction
Authors: Kalcsevszki Regina , Horváth András , Győrffy Balázs , Pongor Sándor , Ligeti Balázs 
Published: July 2022

Our goal was to develop a platform, CovidOutcome2, capable of predicting disease severity from viral mutation profiles using automated machine learning (autoML) and deep neural networks applied to the available large corpus of sequenced SARS-CoV2 genomes. CovidOutcome2 accepts either user-submitted genomes or user defined mutation combinations as the input. The output is a predicted severity score plus a list of identified, annotated mutations and their functional effects in VCF format. The best model performance is a ROC-AUC 0.899 for the model including patient age and ROC-AUC 0.83 for the model without patient age.AvailabilityCovidOutcome is freely available online under the URL https://www.covidoutcome.bio-ml.com as well as in a standalone version https://github.com/bio-apps/covid-outcome.
Anellovirus Structure Reveals a Mechanism for Immune Evasion
Authors: Liou Shu-hao , Cohen Noah , Zhang Yue , Acharekar Nidhi Mukund , Rodgers Hillary , Islam Saadman , Zeheb Lynn , Pitts Jared , Arze Cesar , Swaminathan Harish , Yozwiak Nathan , Ong Tuyen , Hajjar Roger J. , Chang Yong , Swanson Kurt A. , Delagrave Simon 
Published: July 2022

AbstractThe significant impact of the human virome on human physiology is beginning to emerge thanks to modern sequencing methods and bioinformatic tools1. Anelloviruses, the principal constituent of the commensal human virome, are universally acquired in infancy and found throughout the body2,3,4. Since the discovery of the original torque teno virus in 19975, three genera of the Anelloviridae family, each extremely diverse genetically, have been found in humans. These viruses elicit weak immune responses that permit multiple strains to co-exist and persist for years in a typical individual6. However, because they do not cause disease7 and due to the lack of an in vitro culture system, anelloviruses remain poorly understood8,9. Basic features of the virus, such as the identity of its structural protein, have been unclear until now. Here, we describe the first structure of an anellovirus particle, which includes a jelly roll domain that forms a 60-mer icosahedral particle core from which spike domains extend to form a salient part of the particle surface. The spike domains come together around the 5-fold symmetry axes to form crown-like features. Relatively conserved patches of amino acids are near the base of the spike domain while a hypervariable region is at the apex. We propose that this structure renders the particle less susceptible to antibody neutralization by hiding vulnerable conserved epitopes while exposing highly diverse epitopes as immunological decoys, thereby contributing to the immune evasion properties of anelloviruses. This would contrast with viruses such as beak and feather disease virus, canine parvovirus or adeno-associated virus which lack such pronounced surface features. These results shed light on the structure of anelloviruses and provide a framework to understand their interactions with the immune system.
Genome duplication and transposon mediated gene alteration shapes the pathogenicity of Rhizoctonia solani AG1-IA
Authors: Francis Aleena , Ghosh Srayan , Tyagi Kriti , Prakasam V. , Rani Mamta , Singh Nagendra Pratap , Pradhan Amrita , Sundaram R. M. , Priyanka C. , Laha G.S. , Kannan C. , Prasad M.S. , Chattopadhyay Debasis , Jha Gopaljee 
Published: July 2022

AbstractRhizoctonia solani AG1-IA is a polyphagous basidiomycete fungal pathogen that causes sheath blight disease in rice. In a high-quality genome assembly-based analysis, we report a recent whole genome duplication in R. solani AG1-IA. Duplicated syntenic gene blocks showed presence of district clusters of transposable elements (TEs), which introduced disruption in the continuity of synteny and caused alterations in gene structures. Genome duplication followed by TE-mediated gene structure alterations caused neofunctionalization of genes associated with pathogenicity, as experimentally shown by variation in expression patterns and their involvement during plant colonization. High throughput genome sequencing of forty-two rice field isolates of R. solani AG1-IA from different agro-climatic zones of India profiled the population genetic structure of the Indian isolates and classified those into three distinct groups and a subgroup of admixture, emphasizing exchange of genetic material under field conditions. Genetic diversity analysis of this population predicted the regions that are that are targets for diversifying and purifying selections. Experimental evidence showed that the genes undergoing diversifying and purifying selections were essential for pathogenicity. Together, our data and the analysis revealed profound impact of genome duplication and the transposable elements on genomic diversity and evolution that shaped the pathogenicity of R. solani AG1- IA.
APC couples neuronal mRNAs to multiple kinesins, EB1 and shrinking microtubule ends for bidirectional mRNA motility
Authors: Baumann Sebastian J. , Grawenhoff Julia , Rodrigues Elsa C. , Speroni Silvia , Gili Maria , Komissarov Artem , Maurer Sebastian P. 
Published: July 2022

AbstractUnderstanding where in the cytoplasm mRNAs are translated is increasingly recognised as being as important as knowing the timing and level of protein expression. mRNAs are localised via active motor-driven transport along microtubules (MTs) but the underlying essential factors and dynamic interactions are largely unknown. Using biochemical in vitro reconstitutions with purified mammalian proteins, multi-colour TIRF-microscopy (TIRF-M), and interaction kinetics measurements, we show that adenomatous polyposis coli (APC) enables kinesin-1- and kinesin-2-based mRNA transport, and that APC is an ideal adaptor for long-range mRNA transport as it forms highly stable complexes with 3’UTR fragments of several neuronal mRNAs (APC-RNPs). The kinesin-1 KIF5A binds and transports several neuronal mRNP components such as FMRP, PURα, and mRNA fragments weakly, whereas the transport frequency of the mRNA fragments is significantly increased by APC. APC-RNP-motor complexes can assemble on MTs, generating highly processive mRNA transport events. We further find that EB1 recruits APC-RNPs to dynamically growing MT ends and APC-RNPs track shrinking MTs, producing MT minus-end-directed RNA motility due to the high dwell times of APC on MTs. Our findings establish APC as a versatile mRNA-kinesin adaptor and a key factor for the assembly and bidirectional movement of neuronal transport mRNPs.
Fishing Cat Cell Biobanking for Conservation
Authors: Sukparangsi Woranop , Thongphakdee Ampika , Karoon Santhita , Suban Na Ayuttaya Nattakorn , Hengkhunthod Intira , Parkongkeaw Rachapon , Bootsri Rungnapa , Sikaeo Wiewaree 
Published: July 2022

AbstractEstablishment of biobank to keep wildlife cells secure long-term conservation. Fishing cat (Prionailurus viverrinus) is one of Vulnerable wild felids, currently under threaten by wetland destruction and other human activities. Here we aimed to generate cell biobanking of fishing cats by deriving various sources of primary cells from the living and postmortem animals and enhancing their expandable potency by virus-free cellular reprogramming. We show that cells can be propagated from several tissues harvested from both living and dead fishing cats with different derivation efficiency. Testes from the postmortem animals contain several tissues that can be derived primary cells as well as putative alkaline phosphatase positive and SOX2 positive adult spermatogonial stem cells. Primary cells from ear pinna and abdomen sources can only be obtained from the living fishing cats. These primary cells exhibited sign of cell senescence after a few sub-cultures, limited its usability for downstream applications. This obstacle can be overcome by reprogramming via either nucleofection or liposome-based DNA/RNA delivery. The putative iPSC colonies as well as expandable induced cells from episomal-based reprogramming appeared to be a suitable choice for expansion of cells for cryopreservation. Thus, here we provide current conservation plan using cell technology for fishing cats and also recommendation of tissue collection and culture procedures for zoo researches to facilitate the preservation of cells from postmortem animals and living animals.HighlightBiobanking of viable cells is essential to provide long-term security of wildlife existence. Current cell technology enables us to cultivate primary cells and adult germ cells from tissues of living and postmortem fishing cats for cryopreservation. The primary cells exhibited limited proliferation and cell senescence, which can be overcome by reprogramming the somatic cells toward pluripotent state. Here we explored the challenge of tissue collection from fishing cat and several virus-free approaches to induce cellular reprogramming in the fishing cat cells and provided insight into the techniques and conditions to enhance cell expansion, which support the success of generation of fishing cat cell biobank.