A quantitative framework for estimating water resources in India

While issues related to water attract considerable attention in all spheres of life in India, very little quantitative information is available on the water budget of the country. There are primarily two reasons for this lacuna: first, the dearth of information on the variables associated with hydrology, and second, the absence of an easily accessible quantitative framework to put these variables in perspective. In this article, we discuss a framework that has been assembled to address both these issues. At the core of the framework is a hydrological routing model (HYDRA) that has been used to study the water balance of basins on various scales, ranging from a few square kilometres to continents. The basic data needed for implementing the framework are a suitable digital elevation model (DEM) and data on precipitation and evapotranspiration. Available discharge data can be used to validate the performance of the model. We demonstrate the viability of the framework by applying it to the hydrology of the Mandovi river on the western slopes of the Sahyadris; it is typical of the rivers along the Indian west coast. Most of the catchment area of the river is in Goa, but parts of the river also flow through Karnataka and Maharashtra. We use a 30" -resolution (∼ 1 km) DEM (GLOBE) and HYDRA to show that the model output mimics the observed discharge well, providing indirect validation for the surface run-off and sub-surface drainage values on which no data are available

Gold Nanoparticles with Self-Assembled Cysteine Monolayer Coupled to Nitrate Reductase in Polypyrrole Matrix Enhanced Nitrate Biosensor

We have developed here a novel, highly sensitive and selective nitrate (NO– 3) biosensor by covalent immobilization of nitrate reductase (NaR) in self-assembled monolayer (SAM) of cysteine on gold nanoparticles (GNP)-polypyrrole (PPy) modified platinum electrode. Incorporation of GNP in highly microporous PPy matrix was confirmed by morphological scanning electron microscope (SEM) images. The electrochemical behavior of the NaR modified electrode exhibited the characteristic reversible redox peaks at the potential, –0.76 and –0.62 V versus Ag/AgCl. Further, the GNP-PPy nanocomposite enhanced the current response by 2-fold perhaps by enhancing the immobilization of NaR and also direct electron transfer between the deeply buried active site and the electrode surface. The common biological interferences like ascorbic acid, uric acid were not interfering with the NO– 3 measurement at low concentration levels. This biosensor showed a wide linear range of response over the concentration of NO– 3 from 1 μM to 1 mM, with higher sensitivity of 84.5 nA μM–1 and a detection limit of 0.5 μM. Moreover, the NO– 3 level present in the nitrate-rich beetroot juice and the NO– 3 release from the lipopolysaccharide treated human breast cancer cells were estimated

In vivo Bioimaging as a Novel Strategy to Detect Doxorubicin-Induced Damage to Gonadal Blood Vessels

INTRODUCTION: Chemotherapy may induce deleterious effects in normal tissues, leading to organ damage. Direct vascular injury is the least characterized side effect. Our aim was to establish a real-time, in vivo molecular imaging platform for evaluating the potential vascular toxicity of doxorubicin in mice. METHODS: Mice gonads served as reference organs. Mouse ovarian or testicular blood volume and femoral arterial blood flow were measured in real-time during and after doxorubicin (8 mg/kg intravenously) or paclitaxel (1.2 mg/kg) administration. Ovarian blood volume was imaged by ultrasound biomicroscopy (Vevo2100) with microbubbles as a contrast agent whereas testicular blood volume and blood flow as well as femoral arterial blood flow was imaged by pulse wave Doppler ultrasound. Visualization of ovarian and femoral microvasculature was obtained by fluorescence optical imaging system, equipped with a confocal fiber microscope (Cell-viZio). RESULTS: Using microbubbles as a contrast agent revealed a 33% (P<0.01) decrease in ovarian blood volume already 3 minutes after doxorubicin injection. Doppler ultrasound depicted the same phenomenon in testicular blood volume and blood flow. The femoral arterial blood flow was impaired in the same fashion. Cell-viZio imaging depicted a pattern of vessels' injury at around the same time after doxorubicin injection: the wall of the blood vessels became irregular and the fluorescence signal displayed in the small vessels was gradually diminished. Paclitaxel had no vascular effect. CONCLUSION: We have established a platform of innovative high-resolution molecular imaging, suitable for in vivo imaging of vessels' characteristics, arterial blood flow and organs blood volume that enable prolonged real-time detection of chemotherapy-induced effects in the same individuals. The acute reduction in gonadal and femoral blood flow and the impairment of the blood vessels wall may represent an acute universal doxorubicin-related vascular toxicity, an initial event in organ injury

Caspase-dependent and -independent suppression of apoptosis by monoHER in Doxorubicin treated cells

Doxorubicin (DOX) is an antitumour agent for different types of cancer, but the dose-related cardiotoxicity limits its clinical use. To prevent this side effect we have developed the flavonoid monohydroxyethylrutoside (monoHER), a promising protective agent, which did not interfere with the antitumour activity of DOX. To obtain more insight in the mechanism underlying the selective protective effects of monoHER, we investigated whether monoHER (1 mM) affects DOX-induced apoptosis in neonatal rat cardiac myocytes (NeRCaMs), human endothelial cells (HUVECs) and the ovarian cancer cell lines A2780 and OVCAR-3. DOX-induced cell death was effectively reduced by monoHER in heart, endothelial and A2780 cells. OVCAR-3 cells were highly resistant to DOX-induced apoptosis. Experiments with the caspase-inhibitor zVAD-fmk showed that DOX-induced apoptosis was caspase-dependent in HUVECs and A2780 cells, whereas caspase-independent mechanisms seem to be important in NeRCaMs. MonoHER suppressed DOX-dependent activation of the mitochondrial apoptotic pathway in normal and A2780 cells as illustrated by p53 accumulation and activation of caspase-9 and -3 cleavage. Thus, monoHER acts by suppressing the activation of molecular mechanisms that mediate either caspase-dependent or -independent cell death. In light of the current work and our previous studies, the use of clinically achievable concentrations of monoHER has no influence on the antitumour activity of DOX whereas higher concentrations as used in the present study could influence the antitumour activity of DOX

Anti-inflammatory agents and monoHER protect against DOX-induced cardiotoxicity and accumulation of CML in mice

Cardiac damage is the major limiting factor for the clinical use of doxorubicin (DOX). Preclinical studies indicate that inflammatory effects may be involved in DOX-induced cardiotoxicity. Nɛ-(carboxymethyl) lysine (CML) is suggested to be generated subsequent to oxidative stress, including inflammation. Therefore, the aim of this study was to investigate whether CML increased in the heart after DOX and whether anti-inflammatory agents reduced this effect in addition to their possible protection on DOX-induced cardiotoxicity. These effects were compared with those of the potential cardioprotector 7-monohydroxyethylrutoside (monoHER)

Down-Regulation of HtrA1 Activates the Epithelial-Mesenchymal Transition and ATM DNA Damage Response Pathways

Expression of the serine protease HtrA1 is decreased or abrogated in a variety of human primary cancers, and higher levels of HtrA1 expression are directly related to better response to chemotherapeutics. However, the precise mechanisms leading to HtrA1 down regulation during malignant transformation are unclear. To investigate HtrA1 gene regulation in breast cancer, we characterized expression in primary breast tissues and seven human breast epithelial cell lines, including two non-tumorigenic cell lines. In human breast tissues, HtrA1 expression was prominent in normal ductal glands. In DCIS and in invasive cancers, HtrA1 expression was greatly reduced or lost entirely. HtrA1 staining was also reduced in all of the human breast cancer cell lines, compared with the normal tissue and non-tumorigenic cell line controls. Loss of HtrA1 gene expression was attributable primarily to epigenetic silencing mechanisms, with different mechanisms operative in the various cell lines. To mechanistically examine the functional consequences of HtrA1 loss, we stably reduced and/or overexpressed HtrA1 in the non-tumorigenic MCF10A cell line. Reduction of HtrA1 levels resulted in the epithelial-to-mesenchymal transition with acquisition of mesenchymal phenotypic characteristics, including increased growth rate, migration, and invasion, as well as expression of mesenchymal biomarkers. A concomitant decrease in expression of epithelial biomarkers and all microRNA 200 family members was also observed. Moreover, reduction of HtrA1 expression resulted in activation of the ATM and DNA damage response, whereas overexpression of HtrA1 prevented this activation. Collectively, these results suggest that HtrA1 may function as a tumor suppressor by controlling the epithelial-to-mesenchymal transition, and may function in chemotherapeutic responsiveness by mediating DNA damage response pathways

Использование принципа клиентоориентированности при формировании стратегии развития предприятий

Материалы межвуз. науч. конф. студентов, магистрантов и аспирантов, Гомель, 15 мая 2008 г