Automated Screening for Three Inborn Metabolic Disorders: A Pilot Study

Background: Inborn metabolic disorders (IMDs) form a large group of rare, but often serious, metabolic disorders. Aims: Our objective was to construct a decision tree, based on classification algorithm for the data on three metabolic disorders, enabling us to take decisions on the screening and clinical diagnosis of a patient. Settings and Design: A non-incremental concept learning classification algorithm was applied to a set of patient data and the procedure followed to obtain a decision on a patient’s disorder. Materials and Methods: Initially a training set containing 13 cases was investigated for three inborn errors of metabolism. Results: A total of thirty test cases were investigated for the three inborn errors of metabolism. The program identified 10 cases with galactosemia, another 10 cases with fructosemia and the remaining 10 with propionic acidemia. The program successfully identified all the 30 cases. Conclusions: This kind of decision support systems can help the healthcare delivery personnel immensely for early screening of IMDs

Sequences within the Spinach curly top virus virion sense promoter are necessary for vascular-specific expression of virion sense genes

AbstractSequences necessary for activity of the Spinach curly top virus virion sense promoter have been identified within an 84 bp region upstream of two transcription start sites located at nt 252 and 292. RNAs initiating at these sites are expressed at equivalent levels in SCTV-infected Arabidopsis and from promoter-reporter constructs. The promoter is capable of directing expression of all three virion sense genes, although not to the same degree. While CP and V3 expression are similar, expression of V2 is elevated. The promoter is active in transient leaf infusion assays in the absence of C2. In Nicotiana benthamiana plants the promoter is active in vascular tissue and under no conditions did we detect promoter activity in the mesophyll. This is in contrast to begomoviruses where the virion sense promoter is dependent on AL2, a positional homolog of C2, and the promoter is functional in both vascular and mesophyll tissue

IL-12 p40 GENE EXPRESSION: INHIBITORY PATHWAYS AND INFLAMMATORY BOWEL DISEASE

The IL-12 family of heterodimeric cytokines, comprising IL-12, IL-23 and IL-27, is an integral component of the inflammatory response. The IL-12 p40 subunit, which is part of both IL-12 and IL-23, is expressed specifically in macrophages and dendritic cells in response to microbial stimuli which signal through toll-like receptors (TLRs) and nucleotide-oligomerization-binding domain (NOD) proteins. Dysregulated expression of IL-12 p40 could lead to prolonged, unresolved inflammation manifesting into chronic inflammatory disorders such as inflammatory bowel disease (IBD). Understandably, IL-12 p40 expression is tightly regulated. We have demonstrated the requirement of a complex comprising nuclear factor of activated T cells (NFAT) and interferon regulatory factor 8 (IRF8) in IL-12 p40 gene transcriptional regulation. Subsequently, IRF8 was shown to be a target for an important anti-inflammatory pathway activated by carbon monoxide (CO) and heme oxygenase-1 (HO-1) in murine IBD. This dissertation explored two molecular mechanisms of IL-12 p40 inhibition - targeting the transcription factor NFAT using a novel cell-permeable inhibitory peptide and phosphoinositide 3-kinase (PI3K) mediated inhibition of IL-12. Firstly, VIVIT peptide which prevents the nuclear translocation of NFAT was employed to examine the role of NFAT in macrophage gene expression. We observed that NFAT inhibition attenuated the expression of inflammatory cytokines including IL-12, IL-23 and TNF. Secondly, we studied PI3K mediated inhibition of IL-12 and characterized immune responses and macrophage defects in PI3K p110δ mutant mice which spontaneously develop IBD. We observed that the PI3K mutant mice recapitulate certain aspects of human IBD, including a profound increase in several proinflammatory cytokines in the intestinal mucosa and in macrophages, such as IL-12, IL-23, IL-17, TNF and IFN-γ. Furthermore, macrophages from PI3K p110δ mutant mice were defective in IL-10 and C5a mediated inhibition of IL-12 p40.Thus, the expression of proinflammatory cytokines is coordinately regulated by transcription factors (such as NFAT and IRF8) and signaling molecules (such as PI3K), and mechanisms limiting inflammation are crucial for maintenance of immune homeostasis. Manipulation of such inhibitory pathways is a potential therapeutic approach for treating chronic inflammatory disorders

A report on Industrial test services under the COMPAC program from 2002-2003

This report highlights the test services offered between March 2002 to August 2003 under the COMPAC program to various industries engaged in plastics, fibre composites, adhesives etc. It presents the range of materials tested and types of-tests carried out as well as various industries served

Dynamics of the fecal microbiome in patients with recurrent and nonrecurrent Clostridium difficile infection

Comparison of diversity in the fecal microbiota in patients with C. difficile infection (CDI). Comparison of the microbial diversity (inverse Simpson index λ) in a severe and non-severe samples in nonrecurrent, recurrent, and reinfected patients (Kruskal–Wallis test, p = 0.040), b C. difficile positive versus negative samples (not significant), c patients with or without prior antibiotic exposure (not significant) and d with or without a history of prior CDI (not significant). (PDF 173 kb

Development and validation of RP HPLC method for determination of metformin and sitagliptin in bulk and pharmaceutical dosage form

A simple and rapid reversed phase-high performance liquid chromatographic method was developed for simultaneous determination of Metformin and Sitagliptin in Tablet Dosage form. The elution was done with a mobile phase of Water: Methanol (60:40) on Intersil-BDS C18 column (250 × 4.6 mm, 5 μm particle size). The wavelength detector was set at 258 nm. Retention times for Metformin and Sitagliptin were around 2.869 min, 3.942 min respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated according to the respect of linearity, ranges, precision, accuracy, repeatability, reproducibility, detection and quantification limits. Linear ranges were established between 20-80 μg/mL for both the drug. The LOD and LOQ for Metformin were found to be 0.663, 1.92 and for Sitagliptin were found to be 0.405, 1.228 respectively. The described High Performance Liquid Chromatography method was successfully employed for the analysis of pharmaceutical formulations containing combined dosage for

Isolation and characterization of lytic bacteriophages of Salmonella Typhimurium and their therapeutic application

Salmonella Typhimurium is an important bacterial pathogen of gastroenteritis revealing multidrug resistance and has zoonotic implication. In an approach towards alternatives to antibiotics, lytic bacteriophages were isolated against Salmonella Typhimurium from sewage effluent using double agar overlay method. The isolated bacteir ohages, viz. fST1, fST2, fST3, fST4 and fST5 were characterized microbiologically and revealed host range 85–92% individually and 100% collectively within the genus. Biophysical characterization revealed that the phages were stable at 16°, 37°, 42°C and pH 4, 7 and 9 for 3h, supporting their therapeutic application. Electron microscopic examination of the fST1 showed icosahedral head (52.5nm), contractile tail (220–250nm) belonging to the family Myoviridae and order Caudovirales. Further, molecular characterization of fST1 revealed 38kb nucleic acid and digested by restriction endonucleases i.e., EcoRI, Bam HI and Hae III. The therapeutic application of the isolated phage cocktail was ascertained in Swiss albino mice models by infecting the control and treatment groups with 3×108 cfu/ml of the organism intramuscularly and orally. Following challenge the treatment group administered with 3×109 pfu/ml of phage mixture showed significant decrease in number of colony forming units of bacteria in vivo

A Novel Loom for Alacrity of Protected Lawsuit dealings using Cloud Computing Environment

This paper suggest a well-organized information system for facilitate the litigation procedures Information System courts. The purpose is to decrease the duration of processing cases in courts. The aspiration is to save the time and effort of judges and lawyer. In addition, we make use of the advantages of electronic systems and reducing traffic especially in developed countries. Advanced Encryption Standard is used to encrypt all the manipulated data for each case. All read document are encrypted to attain secure information system Litigation process. This is because the big data for all cases will be stored on cloud environment

Patronin-mediated minus end growth is required for dendritic microtubule polarity.

Microtubule minus ends are thought to be stable in cells. Surprisingly, in Drosophila and zebrafish neurons, we observed persistent minus end growth, with runs lasting over 10 min. In Drosophila, extended minus end growth depended on Patronin, and Patronin reduction disrupted dendritic minus-end-out polarity. In fly dendrites, microtubule nucleation sites localize at dendrite branch points. Therefore, we hypothesized minus end growth might be particularly important beyond branch points. Distal dendrites have mixed polarity, and reduction of Patronin lowered the number of minus-end-out microtubules. More strikingly, extra Patronin made terminal dendrites almost completely minus-end-out, indicating low Patronin normally limits minus-end-out microtubules. To determine whether minus end growth populated new dendrites with microtubules, we analyzed dendrite development and regeneration. Minus ends extended into growing dendrites in the presence of Patronin. In sum, our data suggest that Patronin facilitates sustained microtubule minus end growth, which is critical for populating dendrites with minus-end-out microtubules