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

An assessment of technology-based service encounters & network security on the e-health care systems of medical centers in Taiwan

<p>Abstract</p> <p>Background</p> <p>Enhancing service efficiency and quality has always been one of the most important factors to heighten competitiveness in the health care service industry. Thus, how to utilize information technology to reduce work load for staff and expeditiously improve work efficiency and healthcare service quality is presently the top priority for every healthcare institution. In this fast changing modern society, e-health care systems are currently the best possible way to achieve enhanced service efficiency and quality under the restraint of healthcare cost control. The electronic medical record system and the online appointment system are the core features in employing e-health care systems in the technology-based service encounters.</p> <p>Methods</p> <p>This study implemented the Service Encounters Evaluation Model, the European Customer Satisfaction Index, the Attribute Model and the Overall Affect Model for model inference. A total of 700 copies of questionnaires from two authoritative southern Taiwan medical centers providing the electronic medical record system and the online appointment system service were distributed, among which 590 valid copies were retrieved with a response rate of 84.3%. We then used SPSS 11.0 and the Linear Structural Relationship Model (LISREL 8.54) to analyze and evaluate the data.</p> <p>Results</p> <p>The findings are as follows: (1) Technology-based service encounters have a positive impact on service quality, but not patient satisfaction; (2) After experiencing technology-based service encounters, the cognition of the service quality has a positive effect on patient satisfaction; and (3) Network security contributes a positive moderating effect on service quality and patient satisfaction.</p> <p>Conclusion</p> <p>It revealed that the impact of electronic workflow (online appointment system service) on service quality was greater than electronic facilities (electronic medical record systems) in technology-based service encounters. Convenience and credibility are the most important factors of service quality in technology-based service encounters that patients demand. Due to the openness of networks, patients worry that transaction information could be intercepted; also, the credibility of the hospital involved is even a bigger concern, as patients have a strong sense of distrust. Therefore, in the operation of technology-based service encounters, along with providing network security, it is essential to build an atmosphere of psychological trust.</p

Portrait of a Pathogen: The Mycobacterium tuberculosis Proteome In Vivo

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a facultative intracellular pathogen that can persist within the host. The bacteria are thought to be in a state of reduced replication and metabolism as part of the chronic lung infection. Many in vitro studies have dissected the hypothesized environment within the infected lung, defining the bacterial response to pH, starvation and hypoxia. While these experiments have afforded great insight, the picture remains incomplete. The only way to study the combined effects of these environmental factors and the mycobacterial response is to study the bacterial response in vivo.We used the guinea pig model of tuberculosis to examine the bacterial proteome during the early and chronic stages of disease. Lungs were harvested thirty and ninety days after aerosol challenge with Mtb, and analyzed by liquid chromatography-mass spectrometry. To date, in vivo proteomics of the tubercle bacillus has not been described and this work has generated the first large-scale shotgun proteomic data set, comprising over 500 unique protein identifications. Cell wall and cell wall processes, and intermediary metabolism and respiration were the two major functional classes of proteins represented in the infected lung. These classes of proteins displayed the greatest heterogeneity indicating important biological processes for establishment of a productive bacterial infection and its persistence. Proteins necessary for adaptation throughout infection, such as nitrate/nitrite reduction were found at both time points. The PE-PPE protein class, while not well characterized, represented the third most abundant category and showed the most consistent expression during the infection.Cumulatively, the results of this work may provide the basis for rational drug design - identifying numerous Mtb proteins, from essential kinases to products involved in metal regulation and cell wall remodeling, all present throughout the course of infection

Protective Role of Catechin on d-Galactosamine Induced Hepatotoxicity Through a p53 Dependent Pathway

Objective of this study was to obtain a better understanding of the mechanism responsible for the d-galactosamine (d-GalN) induced hepatotoxicity and to study the effect of catechin against d-GalN induced hepatotoxicity. Catechin 50 and 100 mg/kg b.wt was administered for 1 week by oral route. Liver damage was induced by intra-peritoneal administration of 400 mg/kg b.wt d-galactosamine on the last day of catechin treatment. At the end of treatment all animals were killed and liver enzyme levels were estimated. Dissected hepatic samples were used for histopathology, RNA isolation, expression studies of Bax, Bcl-2 and p53 mRNA levels and mitochondrial membrane potential studies. We found that increases in the liver enzyme activity and decrease in antioxidant enzyme activity by d-GalN were significantly restricted by oral pretreatment with catechin. Disruption of mitochondrial membrane potential, up regulation of p53, Bax and down regulation of Bcl-2 mRNA levels in the liver of d-GalN intoxicated rats were effectively prevented by pretreatment with catechin