Comparative Evaluation of High Protein against Normal Protein Diet in Combination with Carbamates against Organophosphorus Intoxication in Rats

The relative efficacy of an isocaloric high (HPD) containing 59 per cent protein, in comparison to a conventional diet containing 21 per cent protein as applied in the alleviation of toxicity of diisopropyl phosphorofluoridate (DFP) and methyl isopropyl phosphonofluoridate (sarin), has been reported. In combination with well-known prophylactics like carbamates and cholinolytics like atropine against nerve gas toxicity, HPD appears to be superior to the conventional diet as studied by survival time measurements. Apart from carbamates, atropine and mecamylamine, HPD may be treated as an additional prophylactic agent to guard against the toxicity of DFP and sarin, which are being used as war chemicals

Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy.

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM. METHODS: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and studied after 4, 8, 16, and 20 week after induction of type 1 diabetes mellitus (T1DM). Induction of diabetes was followed by echocardiographic measurements, glycemic and hemoglobulin A1c profiling, immunoblot, qPCR, enzyme activity assays, and immunohistochemistry (IHC) analysis of DPPI, ISPs, and inflammatory markers. Fibrosis was determined from left ventricular heart by Serius Red staining and qPCR. Apoptosis was determined by TUNEL assay and immunoblot analysis. RESULTS: In the diabetic WT mice, DPPI expression increased along with ISP activation, and DPPI accumulated abundantly in the left ventricle mainly from infiltrating neutrophils. In diabetic DPPI-knockout (DPPI-KO) mice, significantly decreased activation of ISPs, myocyte apoptosis, fibrosis, and cardiac function was improved compared to diabetic WT mice. In addition, DPPI-KO mice showed a decrease in overall inflammatory status mediated by diabetes induction which was manifested by decreased production of pro-inflammatory cytokines like TNF-α, IL-1β and IL-6. CONCLUSION: This study elucidates a novel role of ISPs in potentiating the immunological responses that lead to the pathogenesis of DCM in T1DM. To the best of our knowledge, this is the first study to report that DPPI expression and activation promotes the inflammation that enhances myocyte apoptosis and contributes to the adverse cardiac remodeling that subsequently leads to DCM

Hexanitrohexaazaisowurtzitane or CL-20 in India: Synthesis and Characterisation

Hexanitrohexaazaisowurtzitane (HNIW) more commonly called CL-20, the highest density and the most powerful real world explosive, has been made with very high yield and a high product purity. CL-20 is thoroughly characterised by spectral data (IR, NMR and mass) along with electron spectroscopy for chemical analysis (ESCA) and X-ray diffractogram. Furthermore, small-scale sensitivity tests have also been carried out

Process Standardization for the Manufacture of Shrikhand Spread

Purpose: Shrikhand Spread, a unique sweetened fermented Indian milk product is made by separation of whey from dahi, the Indian counterpart of Western yoghurt, followed by addition of sugar. Production of dahi employing traditional method involved undefined mixed starter cultures, uncontrolled fermentation and longer production time resulting in wide variation in its chemical and microbiological qualities. In order to cater to a product with desirable properties like lower post-acidification, higher flavour profile, firm body and lower syneresis coupled with shorter production time, conjugated application of yoghurt cultures and dahi cultures were tried. Since the shelf-life of dahi is limited, conversion into shrikhand spread may be used as a tool to extend the shelf-life and therefore the market reach towards commercialization into the global market as a potential functional food.Design/Methodology/Approach: Different batches of dahi were made from homogenized (Stage I - 2500 psi, Stage II - 500 psi) and pasteurized (74-78 °C/16-19 Sec) milk, pre-adjusted to 3.15-3.20% fat and 11.40% snf with diverse starter combinations selected upon the extent of post acidification, volatile acid production, syneresis and rheological characteristics. Homogenized, pasteurized and regulated milk was further subjected to a heat-treatment (90°C/10 min) and seeded with selected starter combinations to obtain firm curd intended for shrikhand spread manufacture. Shelf-life of shrikhand spread was evaluated in terms of chemical and microbiological criteria upto 7 days of storage at 8±1°C.Findings: Starter combination of eXactDahi 2+YoFlex Express 1.0 at an incubation temperature-time combination of 45°C/5h was found most suitable for producing dahi with smooth body, higher volatile acidity and low syneresis. Utilization of dahi obtained employing the above starter combination for the manufacture shrikhand spread was suggested and the product was found to retain its goodness when stored for 7 days at 8±1°C. Originality/Value: Conjugated use of yoghurt cultures with dahi cultures was suggested to overcome the drawbacks of traditional process of dahi manufacture suitable for conversion into shrikhand spread. This dahi was found capable of enhancing its dietetic value in addition

Longitudinal borehole functionality in 15 rural Ghanaian towns from three groundwater quality clusters

OBJECTIVE: In sub-Saharan Africa, 45% of the rural population uses boreholes (BHs). Despite recent gains in improved water access and coverage, parallel use of unimproved sources persists. Periodic infrastructure disrepair contributes to non-exclusive use of BHs. Our study describes functionality of BHs in 2014, 2015, and 2016 in 15 rural towns in the Eastern Region of Ghana sourced from three groundwater quality clusters (high iron, high salinity, and control). We also assess factors affecting cross-sectional and longitudinal functionality using logistic regression. RESULTS: BH functionality rates ranged between 81 and 87% and were similar across groundwater quality clusters. Of 51 BHs assessed in all three years, 34 (67%) were consistently functional and only 3 (6%) were consistently broken. There was a shift toward proactive payment for water over the course of the study in the control and high-salinity clusters. Payment mechanism, population served, presence of nearby alternative water sources, and groundwater quality cluster were not significant predictors of cross-sectional or longitudinal BH functionality. However, even in the high iron cluster, where water quality is poor and no structured payment mechanism for water exists, BHs are maintained, showing that they are important community resources

Id1 regulates angiogenesis through transcriptional repression of thrombospondin-1

AbstractId proteins are helix-loop-helix transcription factors that regulate tumor angiogenesis. In order to identify downstream effectors of Id1 involved in the regulation of angiogenesis, we performed PCR-select subtractive hybridization on wild-type and Id1 knockout mouse embryo fibroblasts (MEFs). Here we demonstrate that thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, is a target of transcriptional repression by Id1. We also show that Id1-null MEFs secrete an inhibitor of endothelial cell migration, which is completely inactivated by depletion of TSP-1. Furthermore, in vivo studies revealed decreased neovascularization in matrigel assays in Id1-null mice compared to their wild-type littermates. This decrease was completely reversed by a TSP-1 neutralizing antibody. We conclude that TSP-1 is a major target for Id1 effects on angiogenesis

BLM and RMI1 alleviate RPA inhibition of topoIIIα decatenase activity

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα. Complex formation between BLM, TopoIIIα, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species-specific interactions between RPA and BLM-TopoIIIα-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIα and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIα activity, promoting decatenation in the presence of RPA

Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

BACKGROUND: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. RESULTS: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. CONCLUSION: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix–loop–helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has been shown to be upregulated in oesophageal squamous cell carcinoma (ESCC). However, the prognostic implications of Id proteins in ESCC have not been reported. We examined the expression of the Id proteins in ESCC cell lines and clinical ESCC specimens and found that Id protein expressions were dysregulated in both the ESCC cell lines and specimens. By correlating the expression levels of Id proteins and the clinicopathological data of our patient cohort, we found that M1 stage tumours had significantly higher nuclear Id-1 expression (P=0.012) while high nuclear Id-1 expression could predict development of distant metastasis within 1 year of oesophagectomy (P=0.005). In addition, high levels of Id-2 expression in both cytoplasmic and nuclear regions predicted longer patient survival (P=0.041). Multivariate analysis showed that high-level expression of Id-2 in both cytoplasmic and nuclear regions and lower level of nuclear Id-1 expression were independent favourable predictors of survival in our ESCC patients. Our results suggest that Id-1 may promote distant metastasis in ESCC, and both Id-1 and Id-2 may be used for prognostication for ESCC patients