bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment in O-acetylserine-(thiol) lyase A and B, but not C, confers higher selenate sensitivity and uncovers role for A, B and C as L-Cys and L-SeCys desulfhydrases inArabidopsis
Authors: Kurmanbayeva Assylay , Bekturova Aizat , Soltabayeva Aigerim , Srivastava Sudhakar , Oshanova Dinara , Nurbekova Zhadyrassyn , Sagi Moshe 
Published: September 2020

ABSTRACTThe role of the cytosolic O-acetylserine-(thiol) lyase A (OASTLA), chloroplastic OASTLB and mitochondrion OASTLC in plant resistance/sensitivity to selenate was studied inArabidopsisplants. Impairment in OASTLA and B resulted in reduced biomass, chlorophyll and soluble protein levels compared with impaired OASTL C and Wild-Type treated with selenate. The lower organic-Se and protein-Se levels followed by decreased organic-S, S in proteins and total glutathione inoastlAandoastlBcompared to Wild-Type andoastlCare indicative that Se accumulation is not the main cause for the stress symptoms, but rather the interference of Se with the S-reduction pathway. The increase in sulfite oxidase, adenosine 5′-phosphosulfate reductase, sulfite reductase and OASTL activity levels, followed by enhanced sulfite and sulfide, indicate a futile anabolic S-starvation response to selenate-induced organic-S catabolism inoastlAandoastlBcompared to Wild-Type andoastlC.Additionally, the catabolic pathway of L-cysteine degradation was enhanced by selenate, and similar to L-cysteine producing activity,oastlAandBexhibited a significant decrease in L-cysteine desulfhydrase (DES) activity, compared with WT, indicating a major role of OASTLs in L-cysteine degradation. This notion was further evidenced by sulfide dependent DES in-gel activity, immunoblotting, immunoprecipitation with specific antibodies and identification of unique peptides in activity bands generated by OASTLA, B and C. Similar responses of the OASTLs in Seleno-Cysteine degradation was demonstrated in selenate stressed plants. Notably, no L-cysteine and L-Seleno-Cysteine DES activity bands but those related to OASTLs were evident. These results indicate the significance of OASTLs in degrading L-cysteine and L-SelenoCysteine inArabidopsis.SummaryThe cytosolic OASTLA and chloroplastic OASTLB have significantly higher desulfhydrase activity rates than the cytosolic DES1 and are able to degrade L-Cys and L-SeCys to sulfide and selenide, respectively inArabidopsis.
HGNChelper: identification and correction of invalid gene symbols for human and mouse
Authors: Oh Sehyun , Abdelnabi Jasmine , Al-Dulaimi Ragheed , Aggarwal Ayush , Ramos Marcel , Davis Sean , Riester Markus , Waldron Levi 
Published: September 2020

AbstractGene symbols are recognizable identifiers for gene names but are unstable and error-prone due to aliasing, manual entry, and unintentional conversion by spreadsheets to date format. Official gene symbol resources such as HUGO Gene Nomenclature Committee (HGNC) for human genes and the Mouse Genome Informatics project (MGI) for mouse genes provide authoritative sources of valid, aliased, and outdated symbols, but lack a programmatic interface and correction of symbols converted by spreadsheets. We present HGNChelper, an R package that identifies known aliases and outdated gene symbols based on the HGNC human and MGI mouse gene symbol databases, in addition to common mislabeling introduced by spreadsheets, and provides corrections where possible. HGNChelper identified invalid gene symbols in the most recent Molecular Signatures Database (mSigDB 7.0) and in platform annotation files of the Gene Expression Omnibus, with prevalence ranging from ∼3% in recent platforms to 30-40% in the earliest platforms from 2002-03. HGNChelper is installable from CRAN, with open development and issue tracking on GitHub and an associated pkgdown sitehttps://waldronlab.io/HGNChelper/.
Inference of recent admixture using genotype data
Authors: Pfaffelhuber Peter , Sester-Huss Elisabeth , Baumdicker Franz , Naue Jana , Lutz-Bonengel Sabine , Staubach Fabian 
Published: September 2020

AbstractThe inference of biogeographic ancestry (BGA) has become a focus of forensic genetics. Misinference of BGA can have profound unwanted consequences for investigations and society. We show that recent admixture can lead to misclassification and erroneous inference of ancestry proportions, using state of the art analysis tools with (i) simulations, (ii) 1000 genomes project data, and (iii) two individuals analyzed using the ForenSeq DNA Signature Prep Kit. Subsequently, we extend existing tools for estimation of individual ancestry (IA) by allowing for different IA in both parents, leading to estimates of parental individual ancestry (PIA), and a statistical test for recent admixture. Estimation of PIA outperforms IA in most scenarios of recent admixture. Furthermore, additional information about parental ancestry can be acquired with PIA that may guide casework.HighlightsWe improve statistical methods as used in STRUCTURE and ADMIXTURE for Biogeographical Ancestry (BGA) inference to account for recent admixture, i.e. different admixture of both parents.The resulting recent admixture model has a higher accuracy in estimating individual admixture in most cases.We give a likelihood ratio test for recent admixture, which is both highly specific and sensitive for recent admixture.We find evidence of recent admixture in the 1000 genomes dataset.The self-report on recent admixture of two self-sequenced samples was only confirmed in one case.
A Novel DNA Chromatography Method to DistinguishM. abscessusSubspecies and Macrolide Susceptibility
Authors: Yoshida Mitsunori , Sano Sotaro , Chien Jung-Yien , Fukano Hanako , Suzuki Masato , Asakura Takanori , Morimoto Kozo , Murase Yoshiro , Miyamoto Shigehiko , Kurashima Atsuyuki , Hasegawa Naoki , Hsueh Po-Ren , Mitarai Satoshi , Ato Manabu , Hoshino Yoshihiko 
Published: September 2020

AbstractRationaleThe clinical impact of infection withMycobacterium abscessuscomplex (MABC), a group of emerging non-tuberculosis mycobacteria (NTM), is increasing.Mycobacterium abscessussubsp.abscessus/bolletiifrequently shows natural resistance to macrolide antibiotics, whereasMycobacterium abscessussubsp.massilienseis generally susceptible. Therefore, rapid and accurate discrimination of macrolide-susceptible MABC subgroups is required for effective clinical decisions about macrolide treatments for MABC infection.ObjectivesTo develop a simple and rapid diagnostic that can identify MABC isolates showing macrolide susceptibility.MethodsWhole genome sequencing (WGS) was performed for 148 clinical or environmental MABC isolates from Japan to identify genetic markers that can discriminate three MABC subspecies and the macrolide-susceptibleerm(41) T28C sequevar. Using the identified genetic markers, we established PCR based- or DNA chromatography-based assays. Validation testing was performed using MABC isolates from Taiwan.Measurements and Main ResultsWe identified unique sequence regions that could be used to differentiate the three subspecies. Our WGS-based phylogenetic analysis indicated thatM. abscessuscarrying the macrolide-susceptibleerm(41) T28C sequevar were tightly clustered, and identified 11 genes that were significantly associated with the lineage for use as genetic markers. To detect these genetic markers and theerm(41) locus, we developed a DNA chromatography method that identified three subspecies, theerm(41) T28C sequevar and intacterm(41) for MABC in a single assay within one hour. The agreement rate between the DNA chromatography-based and WGS-based identification was 99.7%.ConclusionsWe developed a novel, rapid and simple DNA chromatography method for identification of MABC macrolide susceptibility with high accuracy.
GeneCup: mine PubMed for gene relationships using custom ontology and deep learning
Authors: Gunturkun Mustafa Hakan , Flashner Efraim , Wang Tengfei , Mulligan Megan K. , Williams Robert W. , Prins Pjotr , Chen Hao 
Published: September 2020

AbstractInterpreting and integrating results from omics studies typically requires a comprehensive and time consuming survey of extant literature. Here, we introduce GeneCup, an easy to use literature mining web service that searches all PubMed abstracts for user-provided gene symbols in conjunction with a set of custom keywords organized into a customized ontology, as well as results from human genome-wide association studies (GWAS). As an example, we organized over 300 keywords related to drug addiction into seven categories. The literature search is conducted by querying the NIH PubMed server using a programming interface, which is followed by retrieving abstracts from a local copy of the PubMed archive. The main results presented to the user are individual sentences containing the gene symbol, organized by the keywords they also contain. These sentences are presented through an interactive graphical interface or as tables. GWAS results are displayed using a similar method. All results are linked to the original abstract in PubMed. In addition, a convolutional neural network is employed to distinguish sentences describing systemic stress from those describing cellular stress. The automated and comprehensive search strategy provided by GeneCup facilitates the integration of new discoveries from omic studies with existing literature. GeneCup is free and open source software. The source code of GeneCup and the link to a running instance is available athttps://github.com/hakangunturkun/GeneCup
RhoGAP19D inhibits Cdc42 laterally to control epithelial cell shape and prevent invasion
Authors: Fic Weronika , Bastock Rebecca , Raimondi Francesco , Los Erinn , Inoue Yoshiko , Gallop Jennifer , Russell Robert B. , St Johnston Daniel 
Published: September 2020

SummaryCdc42-GTP is required for apical domain formation in epithelial cells where it recruits and activates the Par-6/aPKC polarity complex, but how the activity of Cdc42 itself is restricted apically unclear. We used sequence analysis and 3D structure modelling to determine whichDrosophilaGTPase Activating Proteins (GAPs) are likely to interact with Cdc42 and identified RhoGAP19D as the sole Cdc42GAP required for polarity in the follicle cell epithelium. RhoGAP19D is recruited by α-catenin to lateral E-cadherin adhesion complexes, resulting in exclusion of active Cdc42 from the lateral domain.rhogap19dmutants therefore lead to lateral Cdc42 activity, which expands the apical domain through increased Par-6/aPKC activity and stimulates lateral contractility through the myosin light chain kinase, Genghis khan (MRCK). This causes buckling of the epithelium and invasion into the adjacent tissue, a phenotype resembling that of pre-cancerous breast lesions. Thus, RhoGAP19D couples lateral Cadherin adhesion to the apical localisation of active Cdc42, thereby suppressing epithelial invasion.
Structural and Functional Comparison of SARS-CoV-2-Spike Receptor Binding Domain Produced inPichia pastorisand Mammalian Cells
Authors:   Argentinian AntiCovid Consortium, Arbeitman Claudia R. , Auge Gabriela , Blaustein Matías , Bredeston Luis , Corapi Enrique S. , Craig Patricio O. , Cossio Leandro A. , Dain Liliana , D’Alessio Cecilia , Elias Fernanda , Fernández Natalia B. , Gasulla Javier , Gorojovsky Natalia , Gudesblat Gustavo E. , Herrera María G. , Ibañez Lorena I. , Idrovo Tommy , Randon Matías Iglesias , Kamenetzky Laura , Nadra Alejandro D. , Noseda Diego G. , Paván Carlos H. , Pavan María F. , Pignataro María F. , Roman Ernesto , Ruberto Lucas A. M. , Rubinstein Natalia , Santos Javier , Duarte Francisco Velazquez , Zelada Alicia M. 
Published: September 2020

AbstractThe yeastPichia pastorisis a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from SARS-CoV-2 Spike protein expressed inP. pastorisand in the well established HEK-293T mammalian cell system. RBD obtained from both yeast and mammalian cells was properly folded, as indicated by UV-absorption, circular dichroism and tryptophan fluorescence. They also had similar stability, as indicated by temperature-induced unfolding (observedTmwere 50 °C and 52 °C for RBD produced inP. pastorisand HEK-293T cells, respectively). Moreover, the stability of both variants was similarly reduced when the ionic strength was increased, in agreement with a computational analysis predicting that a set of ionic interactions may stabilize RBD structure. Further characterization by HPLC, size-exclusion chromatography and mass spectrometry revealed a higher heterogeneity of RBD expressed inP. pastorisrelative to that produced in HEK-293T cells, which disappeared after enzymatic removal of glycans. The production of RBD inP. pastoriswas scaled-up in a bioreactor, with yields above 45 mg/L of 90% pure protein, thus potentially allowing large scale immunizations to produce neutralizing antibodies, as well as the large scale production of serological tests for SARS-CoV-2.
Three-dimensional structure of a flavivirus dumbbell RNA reveals molecular details of an RNA regulator of replication
Authors: Akiyama Benjamin M. , Graham Monica E. , O′Donoghue Zoe , Beckham J. David , Kieft Jeffrey S. 
Published: September 2020

ABSTRACTMosquito-borne flaviviruses (MBFVs) including dengue, West Nile, yellow fever, and Zika viruses have an RNA genome encoding one open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). The 3′ UTRs of MBFVs contain regions of high sequence conservation in structured RNA elements known as dumbbells (DBs) that regulate translation and replication of the viral RNA genome, functions proposed to depend on the formation of an RNA pseudoknot. To understand how DB structure provides this function, we used x-ray crystallography and structural modeling to reveal the details of its three-dimensional fold. The structure confirmed the predicted pseudoknot and molecular modeling revealed how conserved sequences form a four-way junction that appears to stabilize the pseudoknot. Single-molecule FRET suggests that the DB pseudoknot is a stable element that can regulate the switch between translation and replication during the viral lifecycle by modulating long-range RNA conformational changes.
Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway inC. elegans
Authors: Ju Shouyong , Chen Hanqiao , Wang Shaoying , Lin Jian , Aroian Raffi V , Peng Donghai , Sun Ming 
Published: September 2020

AbstractPathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, usingBacillus thuringiensis-Caenorhabditis elegansas a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reportedC. eleganscan monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.
Lactose intolerance: Magnitude and Associated factors among malnourished under-five Children in Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia
Authors: Gebremariam Birhane , Edao Abebe , Bacha Tigist , Wolde Mistire 
Published: September 2020

AbstractBackgroundLactose intolerance (LI) is a pathological condition characterized by the inability to digest sugar, lactose, due to the absence or insufficient activity of the lactase enzyme (β-galactosidase). Currently, laboratory diagnostic procedures for LI are poorly practiced in Ethiopia, and so LI treatment is based on an empirical diagnosis. Thus, theobjectiveof the study was to determine the magnitude and associated factors of lactose intolerance among malnourished under-five children in Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia from March 2018 – July 2018.MethodsA cross-sectional study was conducted among malnourished under-five children admitted in the pediatric unit, Yekatit 12 Hospital Medical College, Ethiopia. By using a convenient sampling technique structured questionnaire was administered to gather information on the socio-demographic characteristics of study participants and associated risk factors of LI. Moreover, a fresh stool sample was collected from the study participants to measure stool pH, reducing substances, and microscopy examination for intestinal parasites. Data entery and analysis was done using the Statistical Package for Social Sciences (SPSS 21) software.ResultsThe study included 169 malnourished under-five children. Among those 90 (53.3%) were male with a median age of 12 months. The magnitude of LI was 18.3%. Among the study participants, the highest numbers of LI cases were in the age group of less than 12 months; 17(10.1%) followed by 13-24 months; 13(7.7%). Factors that show significant association with LI on bi-variate logistic analysis were family history of lactose intolerance (P=0.043) and diarrhea (P=0.001). In addition; the problem after taking milk (P=0.007), type of therapeutic milk formula (P=0.001), and frequency of stool/24hr (P=0.023) were found to be independent predictors factors of lactose intolerance in the study population.ConclusionThe magnitude of LI was high in the study setting. Thus, more attention should be given on the proper laboratory diagnosis of LI, for better management of cases at the Yekatit 12 hospital. In addition, similar large scale studies at the molecular level are required to strengthen the present findings of LI in Ethiopia.
Expression of a gene for an MLX56 defense protein derived from mulberry latex confers strong resistance against a broad range of insect pests on transgenic tomato lines
Authors: Murata Mika , Konno Kotaro , Wasano Naoya , Mochizuki Atsushi , Mitsuhara Ichiro 
Published: September 2020

AbstractInsect pests cause serious damage in crop production, and various attempts have been made to produce insect-resistance crops, including the expression of genes for proteins with anti-herbivory activity, such as BT toxins. However, the number of available genes with sufficient anti-herbivory activity is limited. MLX56 is an anti-herbivory protein isolated from the latex of mulberry plants, and has been shown to have a strong growth-suppressing activity against the larvae of a variety of lepidopteran species. As a model of herbivore-resistant plants, we produced transgenic tomato lines expressing the gene for MLX56. The transgenic tomato lines showed strong anti-herbivory activities against the larvae of the common cutworm,Spodoptera litura. Surprisingly, the transgenic tomato lines also exhibited strong activity against the attack of the western flower thrips,Frankliniera occidentalis. Further, growth of the hadda beetle,Henosepilachna vigintioctopunctatafed on leaves of transgenic tomato was significantly retarded. The levels of damage caused by both western flower thrips and hadda beetles were negligible in the high-MLX56-expressing tomato line. These results indicate that introduction of the gene for MLX56 into crops can enhance crop resistance against a wide range of pest insects, and that MLX56 can be utilized in developing pest-resistance GM crops.
Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract in the hCD46 IFNα/β receptor knockout mice
Authors: Kurup Drishya , Wirblich Christoph , Schnell Matthias J. 
Published: September 2020

AbstractZika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested a combination of two MV-based vaccines, the MV-E2 and a vaccine expressing NS1 (MV-NS1[2]), and we observed durable plasma cell responses, complete clearance of ZIKV from the female reproductive tract, and complete fetal protection in the lethal African challenge model. Our findings suggest that NS1 antibodies are required to enhance the protection achieved by ZIKV-E antibodies in the female reproductive tract.
MicroRNA775 Promotes Intrinsic Leaf Size and Reduces Cell Wall Pectin Level via a Target Galactosyltransferase inArabidopsis
Authors: Zhang He , Guo Zhonglong , Zhuang Yan , Suo Yuanzhen , Du Jianmei , Gao Zhaoxu , Pan Jiawei , Li Li , Wang Tianxin , Xiao Liang , Qin Genji , Jiao Yuling , Cai Huaqing , Li Lei 
Published: September 2020

AbstractPlants possess unique primary cell walls made of complex polysaccharides that play critical roles in determining intrinsic cell and organ size. How genes responsible for synthesizing and modifying the polysaccharides are regulated by microRNAs (miRNAs) to control plant size remains largely unexplored. Here we identified 23 putative cell wall related miRNAs, termed CW-miRNAs, inArabidopsis thalianaand characterized miR775 as an example. We showed that miR775 post-transcriptionally silencesGALT9, which encodes an endomembrane-located galactosyltransferase belonging to the glycosyltransferase 31 family. Over-expression of miR775 and deletion ofGALT9significantly enlarged leaf-related organs, primarily owing to increases in cell size. Monosaccharide quantification, confocal Raman imaging, and immunolabelling combined with atomic force microscopy (AFM) revealed that theMIR775A-GALT9circuit modulates pectin level and elastic modulus of the cell wall. We further showed thatMIR775Ais directly repressed by the transcription factor ELONGATED HYPOCOTYL 5 (HY5). Genetic analysis confirmed thatHY5is a negative regulator of leaf size and acts through theHY5-MIR775A-GALT9repression cascade to control pectin level. These results demonstrate that miR775-regulated cell wall remodeling is an integral determinant for intrinsic leaf size inA. thalianaand highlight the need to study other CW-miRNAs for more insights into cell wall biology.