Embelia ribes extract reduces high fat diet and low dose streptozotocin-induced diabetic nephrotoxicity in rats

Nephropathy associated with type 2 diabetes is the single most common cause of end-stage renal disease. The aim of the present study was to evaluate the preventive effect of ethanolic extract of Embelia ribes fruit (EER) against high fat diet (HFD) and low dose streptozotocin (STZ)-induced diabetic nephrotoxicity in Wistar rats. HFD-fed and low dose STZ (35 mg/kg, i.p)-induced diabetic rats were treated with EER (100 and 200 mg/kg/day) for 21 days while continuing on HFD. Preventive effects of EER were demonstrated by significant reduction (p< 0.01) in body weight gain, fasting blood glucose, blood pressure, serum lactate dehydrogenase (LDH), creatinine, alkaline phosphatase (ALP), total cholesterol and triglyceride levels, while elevation in serum albumin and total protein levels. Insulin sensitizing effects were seen during oral glucose tolerance testing. Further, EER treatment significantly (p< 0.01) decreased the kidney thiobarbituric acid-reactive substance (TBARS) levels, while increasing the superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels in diabetic rats. Histological studies of kidney also supported the experimental findings. Taken together, our data suggest that EER attenuates renal injury in type 2 diabetic rats, possibly by improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, blood pressure lowering, and inhibition of lipid peroxidation process

Dynamic interactions between foreign institutional investment flows and stock market returns: The case of India

There has been a marked increase in the magnitude of Foreign Institutional Investments (FIIs) into India since the 1990s, resulting in increased forex reserves and liquidity and a higher-valued Indian capital market. However, such investment is more volatile than other types of flows, causing disruptive effects in the form of sudden stops (for example, the crash of the Indian stock market on January 21, 2008). This study empirically examines the dynamic relationship between FIIs and Indian stock market returns. It also analyses the effects of FIIs on Indian capital market returns, using data from January, 2004 through September, 2012. The analysis employs a Cross Correlation Function (CCF) approach, a Granger Causality Test and Vector Auto Regression after dividing the data into two parts: Pre Global financial crisis and Post Global financial crisis periods. The results of the CCF suggest bi-directional causality between FIIs and Nifty returns, whereas the Granger Causality Test and the VAR analysis suggest uni-directional causality running Nifty returns to FIIs

The Role of PILJ and Its Structural Domains in the Localization and Function of the CHP Chemosensory System in Pseudomonas Aeruginosa

Bacteria detect environmental signals using membrane-bound methyl-accepting chemotaxis proteins (MCPs), which are part of a larger complex of chemosensory proteins. Pseudomonas aeruginosa has four functionally distinct chemosensory protein complexes. The Chp chemosensory system regulates type IV pili mediated twitching motility and intracellular levels of cAMP by modulating the activity of an adenylate cyclase, CyaB. The Chp system is also proposed to be involved in type IV pili mediated directional twitching motility towards phosphatidylethanolamine (PE). PilJ is the only MCP predicted to be associated with the Chp system. In this study we investigated different domains of PilJ in order to decipher their roles in signal transduction and localization of the Chp chemosensory system. Our results show that both the periplasmic and transmembrane domains are involved in signal transduction. A PilJ periplasmic domain mutant (PilJΔ74-273) showed a partial but significant decrease in cAMP levels highlighting the importance of this domain in regulation of this phenotype. However, when sufficient intracellular cAMP is provided, twitching motility occurs in the presence or absence of PE independent of the periplasmic domain. To maintain the inner membrane localization while assaying the role of the transmembrane domains of PilJ, Tsr-PilJ chimeric proteins were used. These fusion proteins showed impaired signal transduction. Through localization studies, we discovered that the role of the PilJ transmembrane domains is not limited to signal transduction. Using fluorescence microscopy, an examination of the intracellular localization of C-terminus truncations of PilJ revealed that the second transmembrane domain plays a role in polar localization of PilJ. This is the first report where the localization of a MCP is impacted by a domain other than the cytoplasmic domain. Determining the internal localization cues for this MCP was important as MCPs are reported to be instrumental in chemosensory cluster formation and localization. Indeed, PilJ is needed for PilI foci formation as demonstrated by fluorescence microscopy studies. Taken together, these studies suggest that the PilJ transmembrane domains are important for both signal transduction and localization. Establishing the importance of PilJ for the potential nucleation of the Chp system paves the path for future work to identify potential partners that would directly or indirectly control the polar localization of PilJ

Women Entrepreneurship in India: A Case Study of Rink’s Creation of Rinku Lakdawala

The recent advances in technology and the modern Automation world demand the able administration and initiations from the educated women class and dynamic women entrepreneurs, who absolutely vouch for accidental to the economic growth of nations. It is the order  of the day where concept of  women entrepreneurship programs have to be devised to analysis the market failures and at the same time to abode the afire civic problems by adding  a new dimension of Women entrepreneurship for all SMEs’ and advance policies. Entrepreneurship is the basic activity that entails a core basic understanding “Made On Own”. In country like India, the business domain and working scenarios are dominated by menfolk only, but women with dynamic changes in the environment, have realized the criticality of survival and coming in par with the men. Women are becoming more assertive, powerful and standing for their rights, freedom and equality in the business domain. They enter small business and entrepreneurial activities that enriches their life for money earning and getting recognition in the society as well. The paper entails the importance of woman entrepreneurship through a case study where her entrepreneurial skills help her to get an identity for herself and be respectful in the eyes of the society. Woman is not confined to home based business, they are equally equipped to work in the mainstream of the business whether it a service or manufacturing unit. Mrs. Rinku Lakdawala of Rink’s Creation is a great role model to follow where she kept no stones unturned to make herself successful in Textile Industry. Keywords: Women Entrepreneurship, Challenges, Factors, Innovation

XENOBIOTIC REGULATION OF THE ATP BINDING CASSETTE TRANSPORTER ABCB6 AND ITS SIGNIFICANCE TO HEPATIC HEME HOMEOSTASIS

Heme is indispensable for mammalian life. It is an essential component of numerous heme proteins, with functions including oxygen transport and storage, energy metabolism, drug and steroid metabolism and signal transduction. Under normal physiological conditions intracellular free heme levels are extremely low because increased levels of free heme are cytotoxic and accordingly, heme biosynthesis is tightly regulated. Although, 5-aminolevulinic acid synthase (ALAS) mediated regulation of heme synthesis is considered the key step in heme biosynthesis, recent reports have identified a second regulatory step in heme biosynthesis mediated by the mitochondrial ATP binding cassette transporter b6 (Abcb6). Abcb6 expression is directly related to enhanced de novo porphyrin biosynthesis, and Abcb6 overexpression activates the expression of genes important for heme biosynthesis. Thus, Abcb6 represents a previously unrecognized rate-limiting step in heme biosynthesis. The dissertation outlines the progress made since its initiation in understanding the mechanism(s) that regulate Abcb6 expression and the significance of Abcb6 expression to cellular heme homeostasis. Exposure to therapeutic drugs and environmental contaminants leads to an increase in heme demand to compensate for the increased expression of the heme-dependent cytochrome P450s (P450s) detoxifying enzymes. Cells respond to this increasing heme demand by increasing heme synthesis. Thus, exposure to environmental contaminants serves as an optimal in vivo and in vitro model system to study mechanisms that regulate heme synthesis. In this model, Abcb6 expression was induced in response to exposure to xenobiotics [polyaromatic hydrocarbons (PAHs), 1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and pregnenolone 16alpha -carbonitrile (PCN)] suggesting a co-ordinate induction of Abcb6 to support the increased heme synthesis. Increased Abcb6 expression in response to cellular heme demands was mediated by the xenobiotic sensing nuclear receptors aryl-hydrocarbon receptor (AhR), the constitutive androstane receptor (CAR), and the pregnane-X receptor (PXR). Exposure to environmental contaminants also leads to the generation of oxidative stress, a primary mechanism by which these compounds cause cellular damage. Cells respond to this increased oxidative stress by activating anti-oxidant defense mechanisms, whose principal components include hemo-proteins (such as catalase, superoxide dismutase, etc). Arsenic, an environmental contaminant and a major hazard following occupational exposure exerts its chronic toxicity through the generation of reactive oxygen species. Of importance, exposure to arsenic also activates the antioxidant defense mechanism. Thus, exposure to arsenic serves as a good model system to evaluate in vivo and in vitro oxidative stress response. In this model system, sodium arsenite induced Abcb6 expression in a dose-dependent manner both in mice fed sodium arsenite in drinking water and in cells exposed to sodium arsenite in vitro. Arsenite-induced Abcb6 expression was transcriptionally regulated but was not mediated by the redox sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2). The significance of Abcb6 expression to cellular heme homeostasis under conditions of heme demand was evaluated in vitro by both gain of function (cells engineered to overexpress Abcb6) and loss of function (cells where endogenous Abcb6 expression was knocked down using Abcb6 specific ShRNA) analysis. Loss of Abcb6 expression in these in vitro model systems significantly compromises the ability of cells to respond to increased heme demand and the ability to protect against oxidative stress following exposure to environmental contaminants. To understand the significance of Abcb6 function to heme homeostasis in vivo, we generated mice carrying homozygous deletion of the Abcb6 allele (Abcb6 null mice). Abcb6 null animals appear phenotypically normal with a trend towards decreased hepatic heme levels, although, the decreased heme levels did not appear to be statistically significant. Interestingly however, Abcb6 null mice demonstrate genotypic changes that suggest a role for Abcb6 in lipid and cholesterol homeostasis. Abcb6 null mice have increased fasting serum cholesterol and increased accumulation of androstone metabolites. Abcb6 null mice also show decreased expression and activity of a specific set of P450s suggesting a role for Abcb6 in drug metabolism and disposition. Mitochondrial ABC transporters are difficult to study because of the two-membrane architecture of mitochondria, problems associated with analyzing transport process, and the high abundance of other ATPases and carriers/transporters. Thus, the development of an in vitro system with pure and active protein is a prerequisite toward understanding the mechanistic relationships between ATP binding and hydrolysis and coupling of these events to translocation of substrates across the lipid membranes. Towards this end, we developed an in vitro liposomal transport system with pure and active Abcb6 protein. Reconstitution of Abcb6 into liposomes allowed biochemical characterization of the ATPase including (i) substrate stimulated ATPase activity (ii) transport kinetics of its proposed endogenous substrate coproporphyrinogen III and (iii) transport kinetics of substrates identified using a HTS assay. In summary, this dissertation provides insight into the mechanisms that regulate Abcb6 expression in response to increasing heme demand and the in vitro significance of Abcb6 to cellular heme homeostasis. Development of the Abcb6-null mice suggests that loss of Abcb6 does not severely affect heme-dependent functions in the liver probably because of the activation of compensatory mechanisms that balance the loss of Abcb6. More interestingly, Abcb6-null mice show a phenotype that is characteristic of the deficiency of a protein that is involved in cholesterol and lipid homeostasis. Development of the Abcb6-null mice and the development of an in vitro system with purified Abcb6 should serve as useful tools to understand the transport function of Abcb6 and its role in normal and patho-physiology

Characterization of Groundnut (Arachis hypogaea L.) Germplasm in Relation to Major Foliar Pests and Diseases

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Microalgae and Its Use in Nutraceuticals and Food Supplements

Microalgae are a large diverse group of microorganisms comprising photoautotrophic protists and prokaryotic cyanobacteria—also called as blue-green algae. These microalgae form the source of the food chain for more than 70% of the world’s biomass. It contains higher nutritional values, with rapid growth characteristics. Microalgae are autotrophic organisms and extensively desired for use in nutraceuticals and as supplement in diet. Many microalgal species are documented for health benefits, by strengthening immune system and by increasing the nutritional constitution of body. In this chapter the major economically important species like Spirulina, Chlorella, Haematococcus, and Aphanizomenon are described with reference to its importance as nutraceuticals and food

An Exploratory study of factors related to Consumer Behaviour towards purchase of Fruits and Vegetables from different Retail Formats

The purpose of this study is to identify the variant consumer behaviour aspects in purchasing of the perishable products especially like fruits and vegetables in context with Asian consumers keeping the main focus towards developing retail markets especially in Indian context. Different channels of retailing and their formats with Foreign Direct Investment will help the global retail giants to enter the markets by identifying diverse purchasing factors related to fruits and vegetables as it forms the staple product of consumption irrespective of the demographical, physiological, socio – economic variables across the countries or their individual states.&nbsp

A Novel Flow Cytometric HTS Assay Reveals Functional Modulators of ATP Binding Cassette Transporter ABCB6

ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6’s ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity