bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-regulation of alternative splicing by hnRNPM and ESRP1 during EMT
Authors: Harvey Samuel E. , Xu Yilin , Lin Xiaodan , Gao Xin D. , Qiu Yushan , Ahn Jaegyoon , Xiao Xinshu , Cheng Chonghui 
Published: April 2018

ABSTRACTThe epithelial-mesenchymal transition (EMT) is a fundamental developmental process that is abnormally activated in cancer metastasis. Dynamic changes in alternative splicing occur during EMT. ESRP1 and hnRNPM are splicing regulators that promote an epithelial splicing program and a mesenchymal splicing program, respectively. The functional relationships between these splicing factors in the genome-scale remain elusive. Comparing alternative splicing targets of hnRNPM and ESRP1 revealed that they co-regulate a set of cassette exon events, with the majority showing discordant splicing regulation. hnRNPM discordantly regulated splicing events show a positive correlation with splicing during EMT while concordant splicing events do not, highlighting the antagonistic role of hnRNPM and ESRP1 during EMT. Motif enrichment analysis near co-regulated exons identifies guanine-uridine rich motifs downstream of hnRNPM-repressed and ESRP1-enhanced exons, supporting a model of competitive binding to these cis-elements to antagonize alternative splicing. The set of co-regulated exons are enriched in genes associated with cell-migration and cytoskeletal reorganization, which are pathways associated with EMT. Splicing levels of co-regulated exons are associated with breast cancer patient survival and correlate with gene sets involved in EMT and breast cancer subtypes. These data identify complex modes of interaction between hnRNPM and ESRP1 in regulation of splicing in disease-relevant contexts.
The E3 ubiquitin ligase MIB-1 is necessary to form the nuclear halo inC. eleganssperm
Authors: Herrera Leslie A. , Starr Daniel A. 
Published: April 2018

AbstractUnlike the classical nuclear envelope with two membranes found in other eukaryotic cells, most nematode sperm nuclei are not encapsulated by membranes. Instead, they are surrounded by a nuclear halo of unknown composition. How the halo is formed and regulated is unknown. We used forward genetics to identify molecular lesions behind three classicalfer(fertilization defective) mutations that disrupt the ultrastructure of theC. eleganssperm nuclear halo. We foundfer-2andfer-4alleles to be nonsense mutations inmib-1.fer-3was caused by a nonsense mutation ineri-3. GFP::MIB-1 was expressed in the germline during early spermatogenesis, but not in mature sperm.mib-1encodes a conserved E3 ubiquitin ligase homologous to vertebrate Mib1 and Mib2, which function in Notch signaling. However,C. elegans mib-1has no Notch-related phenotypes. Thus,mib-1has been co-opted to regulate the formation of the nuclear halo during nematode spermatogenesis.
Loss of charge at solvent exposed Lys residues does not induce the aggregation of superoxide dismutase 1
Authors: Crosby Keith , Crown Anthony M. , Roberts Brittany L. , Brown Hilda , Ayers Jacob I. , Borchelt David R. 
Published: April 2018

ABSTRACTMutations in superoxide dismutase 1 (SOD1) associated with familial amyotrophic lateral sclerosis (fALS) induce the protein to misfold and aggregate. To date, missense mutations at more than 80 different amino acid positions have been associated with disease. How these mutations perturb native structure to heighten the propensity to misfold and aggregate is unclear. One potential mechanism that has been suggested is that when mutations occur at positions occupied by charged amino acids, then repulsive forces that would inhibit aberrant protein:protein interactions would be reduced. Mutations at twenty-one charged residues in SOD1 have been associated with fALS. Here, we examined whether loss of positively charged surface Lys residues would induce the misfolding and aggregation of SOD1. We randomly mutated four different Lys residues (K30, K36, K75, K91) in SOD1 and expressed these variants as fusion proteins with yellow fluorescent protein (YFP). We also assessed whether these mutations induced binding to a conformation-restricted SOD1 antibody, designated C4F6, which recognizes non-natively folded protein. Our findings indicate that SOD1 generally tolerates mutations at surface exposed lysine residues, and that loss of positive charge is insufficient to induce aggregation. Our findings may explain why mutations at these Lys residues have not been identified in ALS patients.
MGDb: An analyzed database and a genomic resource of mango (Mangifera Indica L.) cultivars for mango research
Authors: Qamar-ul-Islam Tayyaba , Khan M. Ahmed , Faizan Rabia , Mahmood Uzma 
Published: April 2018

AbstractMango is one of the famous and fifth most important subtropical/tropical fruit crops worldwide with the production centered in India and South-East Asia. Recently, there has been a worldwide interest in mango genomics to produce tools for Marker Assisted Selection and trait association. There are no web-based analyzed genomic resources available for mango particularly. Hence a complete mango genomic resource was required for improvement in research and management of mango germplasm. In this project, we have done comparative transcriptome analysis of four mango cultivars i.e. cv. Langra, cv. Zill, cv. Shelly and cv. Kent from Pakistan, China, Israel, and Mexico respectively. The raw data is obtained through De-novo sequence assembly which generated 30,953-85,036 unigenes from RNA-Seq datasets of mango cultivars. The project is aimed to provide the scientific community and general public a mango genomic resource and allow the user to examine their data against our analyzed mango genome databases of four cultivars (cv. Langra, cv. Zill, cv. Shelly and cv. Kent). A mango web genomic resource MGdb, is based on 3-tier architecture, developed using Python, flat file database, and JavaScript. It contains the information of predicted genes of the whole genome, the unigenes annotated by homologous genes in other species, and GO (Gene Ontology) terms which provide a glimpse of the traits in which they are involved. This web genomic resource can be of immense use in the assessment of the research, development of the medicines, understanding genetics and provides useful bioinformatics solution for analysis of nucleotide sequence data. We report here world’s first web-based genomic resource particularly of mango for genetic improvement and management of mango genome.
Directed evolution of Escherichia coli with lower-than-natural plasmid mutation rates
Authors: Deatherage Daniel E. , Leon Dacia , Rodriguez Álvaro E. , Omar Salma K. , Barrick Jeffrey E. 
Published: April 2018

ABSTRACTUnwanted evolution of designed DNA sequences limits metabolic and genome engineering efforts. Engineered functions that are burdensome to host cells and slow their replication are rapidly inactivated by mutations, and unplanned mutations with unpredictable effects often accumulate alongside designed changes in large-scale genome editing projects. We developed a directed evolution strategy, Periodic Reselection for Evolutionarily Reliable Variants (PResERV), to discover mutations that prolong the function of a burdensome DNA sequence in an engineered organism. Here, we used PResERV to isolate E. coli cells that replicate ColE1 plasmids with higher fidelity. We found mutations in DNA polymerases I and IV and in RNase E that reduce plasmid mutation rates by 6-to 30-fold. The PResERV method implicitly selects to maintain the growth rate of host cells, and high plasmid copy numbers and gene expression levels are maintained in some of the evolved E. coli strains, indicating that it is possible to improve the genetic stability of cellular chassis without encountering trade-offs in other desirable performance characteristics. Utilizing these new antimutator E. coli and applying PResERV to other organisms in the future promises to prevent evolutionary failures and unpredictability to provide a more stable genetic foundation for synthetic biology.
Integrated proteogenomic analysis of metastatic thoracic tumors identifies APOBEC mutagenesis and copy number alterations as drivers of proteogenomic tumor evolution and heterogeneity
Authors: Roper Nitin , Gao Shaojian , Maity Tapan K. , Banday A. Rouf , Zhang Xu , Venugopalan Abhilash , Cultraro Constance M. , Patidar Rajesh , Sindiri Sivasish , Goncearenco Alexandr , Panchenko Anna R. , Biswas Romi , Thomas Anish , Rajan Arun , Carter Corey A. , Kleiner David , Hewitt Stephen , Khan Javed , Prokunina-Olsson Ludmila , Guha Udayan 
Published: April 2018

ABSTRACTElucidation of the proteogenomic evolution of metastatic tumors may offer insight into the poor prognosis of patients harboring metastatic disease. We performed whole-exome and transcriptome sequencing, copy number alterations (CNA) and mass spectrometry-based quantitative proteomics of 37 lung adenocarcinoma (LUAD) and thymic carcinoma (TC) metastases obtained by rapid autopsy and found evidence of patient-specific, multi-dimensional heterogeneity. Extreme mutational heterogeneity was evident in a subset of patients whose tumors showed increased APOBEC-signature mutations and expression of APOBEC3 region transcripts compared to patients with lesser mutational heterogeneity. TP53 mutation status was associated with APOBEC hypermutators in our cohort and in three independent LUAD datasets. In a thymic carcinoma patient, extreme heterogeneity and increased APOBEC3AB expression was associated with a high-risk germline APOBEC3AB variant allele. Patients with CNA occurring late in tumor evolution had corresponding changes in gene expression and protein abundance indicating genomic instability as a mechanism of downstream transcriptomic and proteomic heterogeneity between metastases. Across all tumors, proteomic heterogeneity was greater than copy number and transcriptomic heterogeneity. Enrichment of interferon pathways was evident both in the transcriptome and proteome of the tumors enriched for APOBEC mutagenesis despite a heterogeneous immune microenvironment across metastases suggesting a role for the immune microenvironment in the expression of APOBEC transcripts and generation of mutational heterogeneity. The evolving, heterogeneous nature of LUAD and TC, through APOBEC-mutagenesis and CNA illustrate the challenges facing treatment outcomes.
Microevolution of aquaticStreptococcus agalactiaeST-261 from Australia indicates dissemination via imported tilapia and ongoing adaptation to marine hosts or environment
Authors: Kawasaki Minami , Delamare-Deboutteville Jerome , Bowater Rachel O , Walker Mark J , Beatson Scott , Zakour Nouri L Ben , Barnes Andrew C 
Published: April 2018

AbstractStreptococcus agalactiae(GBS) causes disease in a wide range of animals. The serotype 1b lineage is highly adapted to aquatic hosts, exhibiting substantial genome reduction compared with terrestrial con-specifics. Here we sequence genomes from 40 GBS isolates including 25 from wild fish and captive stingrays in Australia, six local veterinary or human clinical isolates, and nine isolates from farmed tilapia in Honduras and compare with 42 genomes from public databases. Phylogenetic analysis based on non-recombinant core genome SNPs indicated that aquatic serotype Ib isolates from Queensland were distantly related to local veterinary and human clinical isolates. In contrast, Australian aquatic isolates are most closely related to a tilapia isolate from Israel, differing by only 63 core-genome SNPs. A consensus minimum spanning tree based on core genome SNPs indicates dissemination of ST-261 from an ancestral tilapia strain, which is congruent with several introductions of tilapia into Australia from Israel during the 1970s and 1980s. Pan-genome analysis identified 1,440 genes as core with the majority being dispensable or strain-specific with non-protein-coding intergenic regions (IGRs) divided amongst core and strain-specific genes. Aquatic serotype Ib strains have lost many virulence factors during adaptation, but six adhesins were well conserved across the aquatic isolates and might be critical for virulence in fish and targets for vaccine development. The close relationship amongst recent ST-261 isolates from Ghana, USA and China with the Israeli tilapia isolate from 1988 implicates the global trade in tilapia seed for aquaculture in the widespread dissemination of serotype Ib fish-adapted GBS.ImportanceStreptococcus agalactiae(GBS) is a significant pathogen of humans and animals. Some lineages have become adapted to particular hosts and serotype Ib is highly specialized to fish. Here we show that this lineage is likely to have been distributed widely by the global trade in tilapia for aquaculture, with probable introduction into Australia in the 1970s and subsequent dissemination in wild fish populations. We report variability in the polysaccharide capsule amongst this lineage, but identify a cohort common surface proteins that may be a focus of future vaccine development to reduce the biosecurity risk in international fish trade.
Whole genome sequence analysis of 91SalmonellaEnteritidis isolates from mice caught on poultry farms in the mid 1990s
Authors: Guard Jean , Cao Guojie , Luo Yan , Baugher Joseph D. , Davison Sherrill , Yao Kuan , Hoffmann Maria , Zhang Guodong , Bell Rebecca , Zheng Jie , Brown Eric , Allard Marc 
Published: April 2018

AbstractSalmonella entericaserovar Enteritidis (SE), the most commonly reported serovar of human salmonellosis, has been frequently associated with poultry farms, eggs and egg products. Mice are known vectors of SE contamination in these facilities. The objective of this study was to use whole-genome sequencing (WGS) to analyze SE from mice obtained at poultry farms in Pennsylvania. Documenting pathogen diversity can identify reliable biomarkers for rapid detection and speed up outbreak investigations. We sequenced 91 SE isolates from 83 mice (62 spleen isolates, 29 intestinal isolates) caught at 15 poultry farms between 1995-1998 using an Illumina NextSeq 500. We identified 742 single nucleotide polymorphisms (SNPs) capable of distinguishing each isolate from one another. Isolates were divided into two major clades: there were more SNPs differences within Clade B than counterparts in Clade A. All isolates containing antimicrobial resistance genes belong to Subgroup B2. Clade-defining SNPs provided biomarkers distinguishing isolates from 12 individual subgroups, which were separated by farm location or year of collection. Nonsynonymous changes from the clade-defining SNPs proffered a better understanding of possible genetic variations among these isolates. For a broader view of SE diversity, we included data from NCBI Pathogen Detection Isolates Browser, in which subgroups in Clade B formed new SNP Clusters.ImportanceWGS and SNPs analyses are excellent and powerful tools for investigating SE phylogenies. Identifying the evolutionary relationships among SE isolates from mouse, poultry, environmental, and clinical isolates, along with patterns of genetic diversity, advances understanding of SE and the role mice may play in SE contamination and spread among poultry population. Our data was able to identify SE isolates from different farms or years of collection. Moreover, the annotations of clade-defining SNPs provided information about possible protein functions among these SE isolates from each subgroup. Clade-defining or farm-unique biomarkers were useful for rapid detection and outbreak investigations.
BrucellaPeptide Cross-Reactive MHC I Presentation Activates SIINFEKL-Specific TCR Expressing T Cells
Authors: Harms Jerome S. , Khan Mike , Hall Cherisse , Splitter Gary A. , Homan E. Jane , Bremel Robert D. , Smith Judith A. 
Published: April 2018

ABSTRACTBrucella sppare intracellular pathogenic bacteria remarkable in their ability to escape immune surveillance and therefore inflict a state of chronic disease within the host. To enable further immune response studies,Brucellawere engineered to express the well characterized chicken ovalbumin (OVA). Surprisingly, we found that CD8 T cells bearing T cell receptors (TCR) nominally specific for the OVA peptide SIINFEKL (OT-1) reacted to parentalBrucella-infected targets as well as OVA-expressingBrucellavariants in cytotoxicity assays. Furthermore, splenocytes fromBrucellaimmunized mice produced IFN-γ and exhibited cytotoxicity in response to SIINFEKL-pulsed target cells. To determine if the SIINFEKL-reactive OT-1 TCR could be cross-reacting toBrucellapeptides, we searched theBrucellaproteome using an algorithm to generate a list of near-neighbor nonamer peptides that would bind to H2Kb. Selecting fiveBrucellapeptide candidates, along with controls, we verified that several of these peptides mimicked SIINFEKL resulting in T cell activation through the “SIINFEKL-specific” TCR. Activation was dependent on peptide concentration as well as sequence. Our results underscore the complexity and ubiquity of cross-reactivity in T cell recognition. This cross-reactivity may enable microbes such asBrucellato escape immune surveillance by presenting peptides similar to the host, and may also lead to the activation of autoreactive T cells.
Vitexin altersStaphylococcus aureussurface hydrophobicity to interfere with biofilm formation
Authors: Das Manash C. , Das Antu , Samaddar Sourabh , Daware Akshay Vishnu , Ghosh Chinmoy , Acharjee Shukdeb , Sandhu Padmani , Jawed Junaid Jibran , De Utpal C. , Majumdar Subrata , Gupta Sujoy K. Das , Akhter Yusuf , Bhattacharjee Surajit 
Published: April 2018

AbstractBacterial surface hydrophobicity is one of the determinant biophysical parameters of bacterial aggregation for being networked to form biofilm. Phytoconstituents like vitexin have long been in use for their antibacterial effect. The present work is aimed to characterise the effect of vitexin onS. aureussurface hydrophobicity and corresponding aggregation to form biofilm. We have found that vitexin shows minimum inhibitory concentration at 252 μg/ml againstS. aureus.Vitexin reduces cell surface hydrophobicity and membrane permeability at sub-MIC dose of 126 μg/ml. Thein silicobinding analysis showed higher binding affinity of vitexin with surface proteins ofS. aureus.Down regulation ofdltA,icaAB and reduction in membrane potential under sub-MIC dose of vitexin, explains reducedS. aureussurface hydrophobicity. Vitexin has substantially reduced the intracellular adhesion of planktonic cells to form biofilm through interference of EPS formation, motility and subsequent execution of virulence. This was supported by the observation that vitexin down regulates the expression oficaAB andagrAC genes ofS. aureus.In addition, vitexin also found to potentiate antibiofilm activity of sub-MIC dose of gentamicin and azithromycin. Furthermore, CFU count, histological examination of mouse tissue and immunomodulatory study justifies thein vivoprotective effect of vitexin fromS. aureusbiofilm associated infection. Finally it can be inferred that, vitexin has the ability to modulateS. aureuscell surface hydrophobicity which can further interfere biofilm formation of the bacteria.ImportanceThere has been substantial information known about role of bacterial surface hydrophobicity during attachment of single planktonic bacterial cells to any surface and the subsequent development of mature biofilm. This study presents the effect of flavone phytoconstituent vitexin on modulation of cell surface hydrophobicity in reducing formation of biofilm. Our findings also highlight the ability of vitexin in reducingin vivo S. aureusbiofilm which will eventually outcompete the correspondingin vitroantibiofilm effect. Synergistic effect of vitexin on azithromycin and gentamicin point to a regime where development of drug tolerance may be addressed. Our findings explore one probable way of overcoming drug tolerance through application of vitexin in addressing the issue ofS. aureusbiofilm through modulation of cell surface hydrophobicity.
TP53I11 Suppresses Extracellular Matrix-independent Survival and Mesenchymal Transition in Mammary Epithelial Cells
Authors: Xiao Tongqian , Zhang Hai , Zhou Yuanshuai , Geng Junsa , Xu Zhongjuan , Liang Yu , Qiao Hong , Suo Guangli 
Published: April 2018

AbstractExtracellular matrix (ECM)-independent survival is an essential prerequisite for tumor metastasis and a hallmark of epithelial cancer stem cells and epithelial-mesenchymal transition (EMT). We found that, in MCF10A and MDA-MB-231 cells, loss of TP53I11 (Tumor Protein P53 Inducible Protein 11) enhanced the ECM-independent survival and suppressed glucose starvation induced cell death by increasing the activation of AMPK that confer cells metabolic flexibility to survive under stress conditions. We show here that, TP53I11 enhanced glycolysis and promoted proliferation of MCF10A and MDA-MB-231 cells in normal culture, but exerted negative effect on EMT, cell migration and invasion, and its overexpression suppressed tumor progression and metastasis of MDA-MB-231 cells in vivo. Considering cancer cells also are confronted with the hostile environment such as nutrient scarcity during tumorigenesis and metastasis, our findings suggested that the disruption of metabolic flexibility by TP53I11 through inhibiting AMPK activation resulted in the suppression of tumorigenesis and metastasis of breast cancer.
MicroRNA-205 affects mouse granulosa cell apoptosis and estradiol synthesis by targeting CREB1
Authors: Zhang Pengju , Wang Jun , Lang Hongyan , Wang Weixia , Liu Xiaohui , Liu Haiyan , Tan Chengcheng , Li Xintao , Zhao Yumin , Wu Xinghong 
Published: April 2018

ABSTRACTMicroRNAs-205 (miR-205), were reportedly to be involved in various physiological and pathological processes, but its biological function in follicular atresia remain unknown. In this study, we investigated the expression of miR-205 in mouse granulosa cells (mGCs), and explored its functions in primary mGCs using a serial of in vitro experiments. The result of qRT-PCR demonstrated that miR-205 expression was significantly increased in early atretic follicles (EAF), and progressively atretic follicles (PAF) compared to healthy follicles (HF). Our results also revealed that overexpression of miR-205 in mGCs significantly promoted apoptosis, caspas-3/9 activities, and inhibited estrogen E2 release, and cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1, a key gene in E2 production) expression. Bioinformatics and luciferase reporter assays revealed that the gene of cyclic AMP response element (CRE)-binding protein 1 (CREB1) was a potential target of miR-205. qRT-PCR and western blot assays revealed that overexpression of miR-205 inhibited the expression of CREB1 in mGCs. Importantly, CREB1 upregulation partially rescued the effects of miR-205 on apoptosis, caspase-3/9 activities, E2 production and CYP19A1 expression in mGCs. Our results indicate that miR-205 may play an important role in ovarian follicular development and provide new insights into follicular atresia.