51 research outputs found
Structural Annotation of Mycobacterium tuberculosis Proteome
Of the ∼4000 ORFs identified through the genome sequence of Mycobacterium tuberculosis (TB) H37Rv, experimentally determined structures are available for 312. Since knowledge of protein structures is essential to obtain a high-resolution understanding of the underlying biology, we seek to obtain a structural annotation for the genome, using computational methods. Structural models were obtained and validated for ∼2877 ORFs, covering ∼70% of the genome. Functional annotation of each protein was based on fold-based functional assignments and a novel binding site based ligand association. New algorithms for binding site detection and genome scale binding site comparison at the structural level, recently reported from the laboratory, were utilized. Besides these, the annotation covers detection of various sequence and sub-structural motifs and quaternary structure predictions based on the corresponding templates. The study provides an opportunity to obtain a global perspective of the fold distribution in the genome. The annotation indicates that cellular metabolism can be achieved with only 219 folds. New insights about the folds that predominate in the genome, as well as the fold-combinations that make up multi-domain proteins are also obtained. 1728 binding pockets have been associated with ligands through binding site identification and sub-structure similarity analyses. The resource (http://proline.physics.iisc.ernet.in/Tbstructuralannotation), being one of the first to be based on structure-derived functional annotations at a genome scale, is expected to be useful for better understanding of TB and for application in drug discovery. The reported annotation pipeline is fairly generic and can be applied to other genomes as well
Genomic Characterization of Haemophilus parasuis SH0165, a Highly Virulent Strain of Serovar 5 Prevalent in China
Haemophilus parasuis can be either a commensal bacterium of the porcine respiratory tract or an opportunistic pathogen causing Glässer's disease, a severe systemic disease that has led to significant economical losses in the pig industry worldwide. We determined the complete genomic sequence of H. parasuis SH0165, a highly virulent strain of serovar 5, which was isolated from a hog pen in North China. The single circular chromosome was 2,269,156 base pairs in length and contained 2,031 protein-coding genes. Together with the full spectrum of genes detected by the analysis of metabolic pathways, we confirmed that H. parasuis generates ATP via both fermentation and respiration, and possesses an intact TCA cycle for anabolism. In addition to possessing the complete pathway essential for the biosynthesis of heme, this pathogen was also found to be well-equipped with different iron acquisition systems, such as the TonB system and ABC-type transport complexes, to overcome iron limitation during infection and persistence. We identified a number of genes encoding potential virulence factors, such as type IV fimbriae and surface polysaccharides. Analysis of the genome confirmed that H. parasuis is naturally competent, as genes related to DNA uptake are present. A nine-mer DNA uptake signal sequence (ACAAGCGGT), identical to that found in Actinobacillus pleuropneumoniae and Mannheimia haemolytica, followed by similar downstream motifs, was identified in the SH0165 genome. Genomic and phylogenetic comparisons with other Pasteurellaceae species further indicated that H. parasuis was closely related to another swine pathogenic bacteria A. pleuropneumoniae. The comprehensive genetic analysis presented here provides a foundation for future research on the metabolism, natural competence and virulence of H. parasuis
Nonmedical Use of Xtampza® ER and Other Oxycodone Medications in Adults Evaluated for Substance Abuse Treatment: Real-World Data from the Addiction Severity Index-Multimedia Version (ASI-MV®)
Jody L Green, Rebekkah S Robbins, Taryn Dailey-Govoni, Stephen F Butler Inflexxion, A Division of Integrated Behavioral Health, Irvine, CA, USACorrespondence: Jody L GreenInflexxion, A Division of Integrated Behavioral Health, 2 Park Plaza, Suite 1200, Irvine, CA, 82614, USATel +1 303 618 9044Email [email protected]: The purpose of this study was to evaluate real-world data related to past 30-day nonmedical use (NMU) and routes of administration of Xtampza® ER and comparator oxycodone medications in the US as captured within the Addiction Severity Index-Multimedia Version® (ASI-MV®).Methods: Data were collected from July 2016 through December 2019 from 647 centers located in 44 states using the ASI-MV, a clinical instrument used to evaluate substance use and treatment planning. Demographic characteristics were assessed using Pearson’s chi-square test for categorical data and quarterly NMU rates were calculated. Distribution of route of administration was studied using a proportional reporting ratio (PRR) analysis.Results: Of 192,810 assessments, 42,279 (21.9%) indicated past 30-day NMU of at least one prescription opioid, including Xtampza ER (N=73, 0.2%), other oxycodone ER (n=3802, 9.0%) and oxycodone IR (n=14,579, 34.5%). All quarterly Xtampza ER NMU rates per 100 ASI-MV assessments were significantly lower than those for other oxycodone ER and oxycodone IR. Overall, quarterly Xtampza ER NMU drug utilization adjusted rates were significantly lower than quarterly rates observed for other oxycodone ER NMU but not consistently significantly lower than oxycodone IR NMU. Although not all statistically significant, all ratios from the PRR analysis were less than 1.0, indicating that rates of use of any alternate route, any non-oral route, snorting, and injecting were higher for other oxycodone ER and oxycodone IR than for Xtampza ER.Conclusion: Xtampza ER had significantly lower rates of NMU than other oxycodone ER products and oxycodone IR products, as well as significantly lower rates of non-oral NMU than oxycodone IR products, in a population of individuals seeking substance abuse treatment. Understanding risks associated with different opioid medications is important for prescribers as they manage risks of opioid misuse and abuse with effective pain therapy.Keywords: pain management, analgesic, opioid, drug abuse, substance abuse treatment, real-world dat
Influence of Transmural Pressure and Cytoskeletal Structure on NF-κB Activation in Respiratory Epithelial Cells
Dietary Supplementation of Usnic Acid, an Antimicrobial Compound in Lichens, Does Not Affect Rumen Bacterial Diversity or Density in Reindeer
Cardiovascular flukes (Trematoda: Spirorchiidae) in Caretta caretta Linnaeus, 1758 from the Mediterranean Sea
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