bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genome-Scale Metabolic Model for the Smut-FungusUstilago maydis
Authors: Liebal Ulf W. , Ullmann Lena , Lieven Christian , Kohl Philipp , Wibberg Daniel , Zambanini Thiemo , Blank Lars M. 
Published: March 2022

AbstractUstilago maydisis an important plant pathogen causing corn-smut disease and an effective biotechnological production host. The lack of a comprehensive metabolic overview hinders a full understanding of environmental adaptation and a full use of the organism’s metabolic potential. Here, we report the first genome scale metabolic model (GSMM) ofUstilago maydis(iUma22) for the simulation of metabolic activities. iUma22 was reconstructed from sequencing and annotation using PathwayTools, the biomass equation was derived from literature values and from the codon composition. The final model contains over 25% of annotated genes in the sequenced genome. Substrate utilization was corrected by Biolog-Phenotype arrays and exponential batch cultivations were used to test growth predictions. A pan-genome of four differentU. maydisstrains revealed missing metabolic pathways in iUma22. The majority of metabolic differences between iUma22 and the pangenome occurs in the inositol, purine and starch metabolic pathways. The new model allows studies of metabolic adaptations to different environmental niches as well as for biotechnological applications.
PtRNAdb: A web resource of Plant tRNA genes from a wide range of plant species
Authors: Das Durdam , Zahra Shafaque , Singh Ajeet , Kumar Shailesh 
Published: March 2022

AbstracttRNA, as well as their derived products such as short interspersed nuclear elements (SINEs), pseudogenes and transfer-RNA, derived fragments (tRFs) has now been shown to be vital for cellular life, functioning and adaptation during different stress conditions in all diverse life forms. In this study, we have developed PtRNAdb (www.nipgr.ac.in/PtRNAdb), a plant exclusive tRNA database containing 113849 tRNA gene sequences from phylogenetically diverse plant species. We have analysed a total of 106 nuclear, 89 plastidial and 38 mitochondrial genomes of plants by tRNAscan-SE software package, and after careful curation of the output data, we developed this database and integrated the data. The information about the tRNA gene sequences obtained, were further enriched with consensus sequence based study of tRNA genes based on their isoacceptors and isodecoders. We have also built covariance models based on the isoacceptors and isodecoders of all the tRNA sequences using infernal tool. The user can also perform BLAST not only against PtRNAdb entries but also against all the tRNA sequences stored in PlantRNA databases; and annotated tRNA genes across the plant kingdom available at NCBI. For the users’ ease, we have also incorporated the tRNAscan-SE tool for tRNA gene prediction, and ViennaRNA package for structural analysis on the home page of PtRNAdb. This resource is believed to be of high utility for plant researchers as well as molecular biologists to carry out further exploration of plant tRNAome on a wider spectrum, as well as for performing comparative and evolutionary studies related to tRNAs and their derivatives across all domains of life.Database URLhttp://www.nipgr.ac.in/PtRNAdb/
Life history trade-offs in glucocorticoid-mediated habitat selection
Authors: Newediuk Levi , Mastromonaco Gabriela F. , Eric Vander Wal 
Published: March 2022

AbstractThe cort-adaptation and cort-fitness hypotheses both propose glucocorticoids produced by parents mediate trade-offs between their own survival and that of their offspring. The contribution of glucocorticoids to offspring provisioning can quantify these trade-offs because provisioning poses a risk to parents. However, attributing provisioning behaviour to glucocorticoids is difficult because glucocorticoids often drive foraging behaviours to store energy for later provisioning. We compared the effects of glucocorticoids on habitat selection before and after calving to test for the trade-offs female elk make when provisioning offspring. Despite finding that female elk with elevated glucocorticoids selected more strongly for high-risk, high-forage cropland, we found no difference in glucocorticoid production nor a significant change in the effect of glucocorticoids on cropland selection at calving time when lactating elk required the more energy. However, we found a gradual increase in the effect of glucocorticoids on cropland selection by female elk as their calves grew, suggesting the growing energy requirements of calves encouraged more risky habitat selection behaviours by their parents over time. We suggest trade-offs in investment between parents and offspring across life history stages can be tested by integrating glucocorticoids into habitat selection models. Ultimately, this integration will help elucidate the adaptive function of glucocorticoids.
SUMOylation of ABCD3 restricts bile acid synthesis and regulates metabolic homeostasis
Authors: Goyon Vanessa , Besse-Patin Aurèle , Zunino Rodolfo , Nguyen Mai , Coyaud Étienne , Lee Jonathan M. , Nguyen Bich N. , Raught Brian , McBride Heidi M. 
Published: March 2022

AbstractMitochondrial anchored protein ligase (MAPL) has been shown to function as both a SUMO and ubiquitin ligase with multiple roles in mitochondrial quality control, cell death pathways and inflammation. To examine the global function of MAPL we generated a knock-out mouse model and sought functional insight through unbiased BioID, transcriptomics and metabolic analysis. MAPL KO mice are lean and highly insulin sensitive, ultimately developing fully penetrant, spontaneous hepatocellular carcinoma after 18 months. BioID revealed the peroxisomal bile acid transporter ABCD3 as a primary MAPL interacting partner, which we show is SUMOylated in a MAPL-dependent manner. MAPL KO animals showed increased bile acid secretion in vivo and in isolated primary hepatocytes, along with robust compensatory changes in the expression of enzymes synthesizing and detoxifying bile acid. In addition, MAPL KO livers showed signs of ER stress and secreted high levels of Fgf21, the starvation hormone known to drive the reduction of white fat stores and promote insulin sensitivity. Lastly, during aging all MAPL KO mice developed hepatocellular carcinomas. These data reveal a major function for MAPL in the regulation of bile acid synthesis leading to profound changes in whole body metabolism and the ultimate generation of liver cancer when MAPL is lost.
Bioluminescent zebrafish transplantation model for drug discovery
Authors: Hason Martina , Jovicic Jovana , Vonkova Ivana , Bojic Milan , Simon-Vermot Theresa , White Richard M. , Bartunek Petr 
Published: March 2022

ABSTRACTIn the last decade, zebrafish have accompanied the mouse as a robust animal model for cancer research. The possibility of screening small-molecule inhibitors in a large number of zebrafish embryos makes this model particularly valuable. However, the dynamic visualization of fluorescently labeled tumor cells needs to be complemented by a more sensitive, easy, and rapid mode for evaluating tumor growthin vivoto enable high-throughput screening of clinically relevant drugs. In this study we proposed and validated a pre-clinical screening model for drug discovery by utilizing bioluminescence as our readout for the determination of transplanted cancer cell growth and inhibition in zebrafish embryos. For this purpose, we used NanoLuc luciferase, which ensured rapid cancer cell growth quantificationin vivowith high sensitivity and low background when compared to conventional fluorescence measurements. This allowed us large-scale evaluation ofin vivodrug responses of 180 kinase inhibitors in zebrafish. Our bioluminescent screening platform could facilitate identification of new small-molecules for targeted cancer therapy as well as for drug repurposing.
Using machine learning to understand microgeographic determinants of the Zika vector, Aedes aegypti
Authors: Alexander Jagger , Bruno Wilke André Barreto , Mantero Alejandro , Vasquez Chalmers , Petrie William , Kumar Naresh , Beier John 
Published: March 2022

AbstractThere are limited data on why the 2016 Zika outbreak in Miami-Dade County, Florida was confined to certain neighborhoods. In this research, Aedes aegypti, the primary vector of Zika virus, are studied to examine neighborhood-level differences in their population dynamics and underlying processes. Weekly mosquito data were acquired from the Miami-Dade County Mosquito Control Division from 2016 to 2020 from 172 traps deployed around Miami-Dade County. Using Random Forest, a machine learning method, predictive models of spatiotemporal dynamics of Ae. aegypti in response to meteorological conditions and neighborhood-specific socio-demographic and physical characteristics, such as land-use and land-cover type and income level, were created. The study area was divided into two groups: areas affected by local transmission of Zika during the 2016 outbreak and unaffected areas. Aedes aegypti populations in areas affected by Zika were more strongly influenced by 14- and 21-day lagged weather conditions. In the unaffected areas, mosquito populations were more strongly influenced by land-use and day-of-collection weather conditions. There are neighborhood-scale differences in Ae. aegypti population dynamics. These differences in turn influence vector-borne disease diffusion in a region. These results have implications for vector control experts to lead neighborhood-specific vector control strategies and for epidemiologists to guide vector-borne disease risk preparations, especially for containing the spread of vector-borne disease in response to ongoing climate change.
Development of a Method Combining Peptidiscs and Proteomics to Identify, Stabilize and Purify a Detergent-Sensitive Membrane Protein Assembly
Authors: Young John William , Wason Irvinder Singh , Zhao Zhiyu , Kim Sunyoung , Aoki Hiroyuki , Phanse Sadhna , Rattray David G , Foster Leonard J. , Babu Mohan , van Hoa Franck Duong 
Published: March 2022

ABSTRACTThe peptidisc membrane mimetic enables global reconstitution of the bacterial membrane proteome into water-soluble detergent-free particles, termed peptidisc libraries. We present here a method that combines peptidisc libraries and chromosomal-level gene tagging technology with affinity purification and mass spectrometry (AP/MS) to stabilize and identify fragile membrane protein complexes that exist at native expression levels. This method circumvents common artifacts caused by bait protein overproduction and protein complex dissociation due to lengthy exposure to detergents during protein isolation. Using the E. coli Sec system as a case study, we identify an expanded version of the translocon, termed the HMD complex, consisting of 9 different integral membrane subunits. This complex is stable in peptidiscs but dissociates in detergent. Guided by this native-level proteomic information, we design and validate a procedure that enables purification of the HMD complex with minimal protein dissociation. These results highlight the utility of peptidiscs and AP/MS to discover and stabilize fragile membrane protein assemblies.
Gut microbe Lactiplantiballus plantarum undergoes different evolutionary trajectories between insects and mammals
Authors: Maritan Elisa , Gallo Marialaura , Srutkova Dagmar , Jelinkova Anna , Benada Oldrich , Kofronova Olga , Silva-Soares Nuno F. , Hudcovic Tomas , Gifford Isaac , Barrick Jeffrey E. , Schwarzer Martin , Martino Maria Elena 
Published: March 2022

ABSTRACTAnimals form complex symbiotic associations with their gut microbes, whose evolution is determined by an intricate network of host and environmental factors. In many insects, such as Drosophila melanogaster, the microbiome is flexible, environmentally determined and less diverse than in mammals. In contrast, mammals maintain complex multispecies consortia that are able to colonize and persist in the gastrointestinal tract. Understanding the evolutionary and ecological dynamics of gut microbes in different hosts is challenging. This requires disentangling the ecological factors of selection, determining the timescales over which evolution occurs, and elucidating the architecture of such evolutionary patterns. Here, we employ experimental evolution to track the pace of the evolution of a common gut commensal, Lactiplantibacillus plantarum, within invertebrate (Drosophila melanogaster) and vertebrate (Mus musculus) hosts and their respective diets. While the symbiosis between Drosophila and L. plantarum is mainly determined by host diet, with the host influencing the fitness of its gut microbes only over short timescales, bacterial evolution within the mammalian host follows a divergent evolutionary path. Here, the host and its intrinsic factors play a critical role in selection and influence both the phenotypic and genomic evolution of its gut microbes, as well as the outcome of their symbiosis.
Chimeric mRNA based COVID-19 vaccine induces protective immunity against Omicron and Delta
Authors: Hu Qidong , Zhao Ying , Shaabani Namir , Lyu Xiaoxuan , Sun Haotian , Cruz Vincent , Kao Yi , Xu Jia , Fossier Amber , Stegman Karen , Wang Zhihao , Wang Zhenping , Hu Yue , Zheng Yi , Kyaw Lilian , Zuluaga Cipriano , Wang Hua , Pei Hong , Powers Colin , Allen Robert , Xie Hui , Ji Henry , Chen Runqiang 
Published: March 2022

AbstractThe emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines. Here, we explored various strategies to develop novel mRNAs vaccines to achieve safer and wider coverage of VOCs. Firstly, we constructed a cohort of mRNAs that feature a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Not present in the mRNA vaccines currently in use, the mutation abolished the cleavage between the S1 and S2 subunits, potentially enhancing the safety profile of the immunogen. Secondly, we systematically evaluated the induction of neutralizing antibodies (nAb) in vaccinated mice, and discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. Thirdly, the IgG produced in mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs, which was further corroborated by challenging vaccinated mice with the live virus of VOCs. However, neither WA-Furin nor Beta-Furin mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original and the sublineages of Omicron variant. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we tested the concept of bivalent immunogen. Instead of just fusing two RBDs head-to-tail, we for the first time constructed an mRNA-based chimeric immunogen by introducing the RBD of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA was capable of inducing potent and broadly acting nAb against Omicron (both BA.1 and BA.2) and Delta, which paves the way to develop new vaccine candidate to target emerging variants in the future.
Cilia regulate meiotic recombination in zebrafish
Authors: Xie Haibo , Wang Xiaosi , Jin Minjun , Li Lanqin , Zhu Junwen , Kang Yunsi , Chen Zhe , Sun Yonghua , Zhao Chengtian 
Published: March 2022

AbstractMeiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both spermatocytes and primary oocytes. By developing a novel germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.
iPheGWAS: an intelligent computational framework to integrate and visualise genome-phenome wide association results
Authors: George Gittu , Huang Yu , Gan Sushrima , Nar Aditya S. , Ha Jason , Venkatesan Radha , Mohan Viswanathan , Wang Huan , Brown Andrew , Palmer Colin N. A. , Doney Alex S. F. 
Published: March 2022

AbstractEstimating the genetic correlations by LDSC is computationally demanding and visualising multiple GWAS results along with their genetic relationships is restricted. This study developed iPheGWAS, a novel approach which applied hierarchical clustering to GWAS summary statistics to (i) calculate their genetic relatedness, and (ii) enable three-dimensional visualisation of multiple ordered GWAS plots. Simulation and real-world data analysis demonstrated that when investigating genetic relationships among multiple phenotypes, iPheGWAS can deliver comparable results with LDSC but with 8 times faster computational speed. It can also provide novel findings in studying genetically-correlated comorbidities, such as mental illness and rheumatoid arthritis.
Molecular mechanisms underlying Warburgia salutaris effects on oxidative stress and apoptotic parameters in Human Hepatoma Cells
Authors: Maruma Lebogang N. , Somboro Anou M. , Amoako Daniel G. , Khumalo Hezekiel M. , Khan Rene B. 
Published: March 2022

AbstractThis study aims to determine the molecular effects of Warburgia salutaris extract in HepG2 cells and elucidate the possible mechanisms. The MTT assay was employed to determine cell viability and the half maximal inhibitory concentration (IC50) of Warburgia salutaris-treated in HepG2 cells (0-5mg/ml). Extracellular lactate dehydrogenase and ATP were also quantified as a measure of cell viability. The production of reactive oxygen species (ROS) was assessed by quantifying lipid peroxidation and oxidative DNA damage, and reactive nitrogen species (RNS) in treated HepG2 cells. The cells response to free radicals was assessed by measuring GSH. Stress response antioxidant and apoptotic markers were detected using western blotting and /or qPCR. Cell death parameters assayed included annexin V, caspase activity and necrosis. Single-cell gel electrophoresis (SCGE) was used to visualise DNA damage in the HepG2 cells and confirmed with DNA fragmentation assay. The Hoechst assay allowed the visualisation of the nucleus to assess cell growth and apoptosis. Decreased cell viability was associated with a decreased level of ATP. The presence of oxidative stress was suggested by increased HSP70 and Nrf2 protein expression and confirmed by increase ROS, RNS, GPx and catalase; and a corresponding decrease of SOD2 and glutathione. Caspase 8 showed no significant difference between treatment concentrations, caspase 9 was decreased and caspase 3/7 increased. A reduction in p53 correlated with chromatin changes, increase in comet lengths and DNA fragmentation. NFκB protein was significantly decreased at the IC50, along with decreased cMyc protein expression. Our findings shows that Warburgia salutaris promotes apoptosis by inducing oxidative stress in HepG2 cells and may be a potential anti-cancer agent that would serve as an alternative to conventional therapeutic agents.
A molecular dynamic investigation of Human Rhinovirus 3C Protease Drug Target: Insights towards the design of potential Inhibitors
Authors: Buthelezi Ndumiso M , Amoako Daniel G. , Somboro Anou M. , Khan Rene B. , Kumalo Hezekiel M. 
Published: March 2022

AbstractThe 3C protease is distinguished from most proteases due to the presence of cysteine nucleophile that plays an essential role in viral replication. This peculiar structure encompassed with its role in viral replication has promoted 3C protease as an interesting target for therapeutic agents in the treatment of diseases caused by human rhinovirus (HRV). Herein we present a comprehensive molecular dynamics study of the comparison of two potent inhibitors, sg85 and rupintrivir complexed with HRV-3C protease. The binding free energy studies revealed a higher binding affinity for sg85 −58.853 kcal/mol than for rupintrivir −54.0873 kcal/mol and this was found to be in correlation with the experimental data. The energy decomposition analysis showed that, residues Leu 127, Thr 142, Ser 144, Gly 145, Tyr 146, Cys 147, His 161, Val 162, Gly 163, Gly 164, Asn 165, Phe 170 largely contributed to the binding of sg85, whereas His 40, Leu 127 and Gly 163 impacted the binding of rupintrivir. It further showed that His 40, Glu 71, Leu 127, Cys 147 Gly 163 and Gyl 164 are crucial residues that play a key role in ligand-enzyme binding; amongst these residues are residues of the conserved active site (His 40, Glu 71 and Cys 147). These findings provide a comprehensive understanding of the dynamics and structural features and will serve as guidance in the design and development of potent novel inhibitors of HRV.Graphical Abstract
Factors influencing parasocial relationship in the virtual reality shopping environment: the moderating role of celebrity endorser dynamism
Authors: Yuan Chunlin , Wang Shuman , Liu Yue , Ma Jenny Weichen 
Published: March 2022

PurposeThis paper explores the driving factors of parasocial relationship (PSR) in the virtual reality (VR) shopping environment, and how this relationship affects brand equity. The study also investigates the moderating role of the celebrity endorser dynamism (CED) in the relationship between PSR and its antecedents.Design/methodology/approachThe primary data collection tool is a survey administered to Chinese consumers (n = 531) who have experienced the products of UNIQLO brand on Taobao Buy + platform, and who had a PSR with the endorser in their VR shopping process. Structural equation modeling is employed to examine the hypothesized relationships among all variables.FindingsThe findings show that VR shopping factors (i.e. physical attractiveness, social presence and technology novelty) perceived by consumers to affect PSR, and this relationship and brand equity are positively associated, while CED moderates the relationship between PSR and its antecedents.Originality/valueThis study sheds light on how PSR in the VR shopping environment can improve brand equity. It contributes to the theory of PSR and persuasion as well as marketing strategies. From a managerial perspective, guidelines are provided for firms to implement value communication activities using VR, and to increase their brand equity.