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Gandhi T.K.,Massachusetts Institute of Technology | Gandhi T.K.,Defence Institute of Physiology and Allied science | Ganesh S.,Dr Shroffs Charity Eye Hospital | Sinha P.,Massachusetts Institute of Technology
Psychological Science | Year: 2014

The factors contributing to the development of spatial imagery skills are not well understood. Here, we consider whether visual experience shapes these skills. Although differences in spatial imagery between sighted and blind individuals have been reported, it is unclear whether these differences are truly due to visual deprivation or instead are due to extraneous factors, such as reduced opportunities for the blind to interact with their environment. A direct way of assessing vision's contribution to the development of spatial imagery is to determine whether spatial imagery skills change soon after the onset of sight in congenitally blind individuals. We tested 10 children who gained sight after several years of congenital blindness and found significant improvements in their spatial imagery skills following sight-restoring surgeries. These results provide evidence of vision's contribution to spatial imagery and also have implications for the nature of internal spatial representations. © The Author(s) 2014.


Sharma N.K.,Defence Institute of Physiology and Allied science | Sethy N.K.,Defence Institute of Physiology and Allied science | Bhargava K.,Defence Institute of Physiology and Allied science
Journal of Proteomics | Year: 2013

Hypoxia is one of the major stressors at high altitude. Exposure to hypobaric hypoxia induces several adverse consequences to the structural and functional integrity of brain. In an attempt to understand the proteome modulation, we used 2-DE coupled with MALDI-TOF/TOF for cortex and hippocampus exposed to short-term temporal (0, 3, 6, 12 and 24. h) hypobaric hypoxia. This enabled us in the identification of 88 and 73 hypoxia responsive proteins in cortex and hippocampus respectively. We further compared the proteomes of both the regions and identified 37 common proteins along with 49 and 32 specific proteins for cortex and hippocampus respectively. We observed significant up-regulation of glycolytic enzymes like Gapdh, Pgam1, Eno1 and malate-aspartate shuttle enzymes Mdh1 and Got1in cortex as compared to hippocampus deciphering efficient use of energy producing substrates. This was coupled with concomitant increase in expression of antioxidant enzymes like Sod1, Sod2 and Pebp1 in cortex to neutralize the hypoxia-induced reactive oxygen species (ROS) generation. Our comparative proteomics studies demonstrate that efficient use of energy generating pathways in conjugation with abundance of antioxidant enzymes makes cortex less vulnerable to hypoxia than hippocampus. © 2013 Elsevier B.V.


Kumar M.S.Y.,Defence Institute of Physiology and Allied science | Dutta R.,Defence Institute of Physiology and Allied science | Prasad D.,Defence Institute of Physiology and Allied science | Misra K.,Defence Institute of Physiology and Allied science
Food Chemistry | Year: 2011

A novel environmentally friendly technique, subcritical water extraction (SWE) was employed for the extraction of antioxidant compounds from Seabuckthorn leaves (SBT). Antioxidant activity of the extracts was evaluated using commonly accepted chemical assays. Also, present study reports the cytoprotective and antioxidant properties of SBT against tertiary-butyl hydroperoxide (tert-BOOH) induced oxidative stress in murine macrophages (Raw 264.7). Exposure of cells to tert-BOOH resulted, increase in cytotoxicity, reactive oxygen species (ROS) production and decrease in mitochondrial membrane potential, which is responsible for fall in intracellular antioxidant levels. Pretreatment of cells with SBT extracts inhibited cytotoxicity, ROS production and maintained antioxidants levels similar to that of control cells. The chemical composition of the SWE extracts studied showed total phenol content (76.07-93.72 mg/g GAE) and total flavonoid content (47.06-66.03 mg/g rutin). Further, some of its phenolic constituents; (1) Quercetin-3-galactoside, (2) Kaempferol and (3) Isorhamnetin were quantified by RP-HPLC. © 2011 Elsevier Ltd. All rights reserved.


Hota K.B.,Defence Institute of High Altitude Research | Hota S.K.,Defence Institute of High Altitude Research | Srivastava R.B.,Defence Institute of High Altitude Research | Singh S.B.,Defence Institute of Physiology and Allied science
Journal of Cerebral Blood Flow and Metabolism | Year: 2012

Oxygen sensing in hypoxic neurons has been classically attributed to cytochrome c oxidase and prolyl-4-hydroxylases and involves stabilization of transcription factors, hypoxia-inducible factor-1α (Hif-1α) and nuclear factor erythroid 2-related factor 2 (Nrf2) that mediate survival responses. On the contrary, release of cytochrome c into the cytosol during hypoxic stress triggers apoptosis in neuronal cells. We, here advocate that the redox state of neuroglobin (Ngb) could regulate both Hif-1α and Nrf2 stabilization and cytochrome c release during hypoxia. The hippocampal regions showing higher expression of Ngb were less susceptible to global hypoxia-mediated neurodegeneration. During normoxia, Ngb maintained cytochrome c in the reduced state and prevented its release from mitochondria by using cellular antioxidants. Greater turnover of oxidized cytochrome c and increased utilization of cellular antioxidants during acute hypoxia altered cellular redox status and stabilized Hif-1α and Nrf2 through Ngb-mediated mechanism. Chronic hypoxia, however, resulted in oxidation and degradation of Ngb, accumulation of ferric ions and release of cytochrome c that triggered apoptosis. Administration of N-acetyl-cysteine during hypoxic conditions improved neuronal survival by preventing Ngb oxidation and degradation. Taken together, these results establish a role for Ngb in regulating both the survival and apoptotic mechanisms associated with hypoxia. © 2012 ISCBFM All rights reserved.


Srivastava M.,Defence Institute of Physiology and Allied science | Khurana P.,Defence Institute of Physiology and Allied science | Sugadev R.,Defence Institute of Physiology and Allied science
BMC Research Notes | Year: 2012

Background: The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs) in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD) rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used 'Gene Ontology semantic similarity score' to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal) and disease (cancer) sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results: Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95) identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1-4). Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1), chemotherapy/drug resistance biomarkers (panel 2), hypoxia regulated biomarkers (panel 3) and lung extra cellular matrix biomarkers (panel 4). Conclusions: Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3), HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1/SAG, AIB1 and AZIN1) are significantly down regulated. All down regulated genes in this panel were highly up regulated in most other types of cancers. These panels of proteins may represent signature biomarkers for lung cancer and will aid in lung cancer diagnosis and disease monitoring as well as in the prediction of responses to therapeutics. © 2012 Srivastava et al.; licensee BioMed Central Ltd.


Manickam M.,Defence Institute of Physiology and Allied science | Tulsawani R.,Defence Institute of Physiology and Allied science
PLoS ONE | Year: 2014

Janus activated kinase/signal transducers and activators of transcription (JAK/STATs) pathway are associated with various neuronal functions including cell survival and inflammation. In the present study, it is hypothesized that protective action of aqueous extract of Hippophae rhamnoides in hippocampal neurons against hypoxia is mediated via JAK/STATs. Neuronal cells exposed to hypoxia (0.5% O2) display higher reactive oxygen species with compromised antioxidant status compared to unexposed control cells. Further, these cells had elevated levels of pro-inflammatory cytokines; tumor necrosis factor α and interleukin 6 and nuclear factor kappa B. Moreover, the expression of JAK1 was found to be highly expressed with phosphorylation of STAT3 and STAT5. Cells treated with JAK1, STAT3 and STAT5 specific inhibitors resulted in more cell death compared to hypoxic cells. Treatment of cells with extract prevented oxidative stress and inflammatory response associated with hypoxia. The extract treated cells had more cell survival than hypoxic cells with induction of JAK1 and STAT5b. Cells treated with extract having suppressed JAK1 or STAT3 or STAT5 expression showed reduced cell viability than the cell treated with extract alone. Overall, the findings from these studies indicate that the aqueous extract of Hippophae rhamnoides treatment inhibited hypoxia induced oxidative stress by altering cellular JAK1, STAT3 and STAT5 levels thereby enhancing cellular survival response to hypoxia and provide a basis for possible use of aqueous extract of Hippophae rhamnoides in facilitating tolerance to hypoxia. © 2014 Manickam, Tulsawani.


Jain S.,Defence Institute of Physiology and Allied science | Singh S.N.,Defence Institute of Physiology and Allied science
South African Journal of Botany | Year: 2013

Hoodia gordonii (family: Apocynaceae) is used traditionally by the Khoi-San tribes to control hunger. It has become extremely popular and has triggered commercial interest due to its appetite suppressant property. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced by the herb. Effect of organic solvent extract of H. gordonii on food intake and body weight of male Sprague Dawley rats was monitored at three different doses 50, 100 and 150. mg/kg body weight, given orally for five days. Subsequently, the dose of 100. mg/kg body weight was selected for further studies on the regulatory hormones and biochemical variables. Dose-dependent reduction in food intake (12-26%) was observed at a dose of 100 and 150. mg/kg body weight (p. <0.05). Appetite suppression persisted for 6. h and food intake was restored within 24. h after stopping of the treatment. There was an increase in liver glycogen stores, activity of mitochondrial CPT-1 and thyroid hormones in treated animals. The circulating levels of NPY and IGF-1 were decreased with marginal increase in leptin and CCK, in case of treated rats. There was no change in blood glucose and insulin levels were not affected significantly. The hormonal and metabolic changes due to treatment with the H. gordonii extract may be responsible for its anorectic activity. © 2013 Elsevier B.V.


Ashraf M.Z.,Defence Institute of Physiology and Allied science | Gupta N.,Defence Institute of Physiology and Allied science
International Journal of Biochemistry and Cell Biology | Year: 2011

Scavenger receptors are modified lipoprotein binding receptors, expressed on the surface of a variety of cells including endothelial, macrophages and platelets. The most extensively studied class B scavenger receptors comprise of CD36 and SR-BI and have been found to bind to native and modified LDL. Interaction of modified LDL to CD36 accelerates foam cell formation, the key step in atherosclerotic plaque deposition. Recently scavenger receptors have also been implicated in thrombosis. Platelet CD36 serves as a sensor of oxidative stress and modulator of platelet reactivity under hyperlipidemic conditions thus, inducing prothrombotic signals. In contrast, targeting platelet SR-BI corresponds to reduce platelet hyperreactivity in hyperlipidemia suggesting that targeting these receptors could be a promising strategy for the treatment of atherothrombotic disorders. © 2011 Elsevier Ltd.


Tulsawani R.,Defence Institute of Physiology and Allied science
Food and Chemical Toxicology | Year: 2010

Hippophae rhamnoides, is a high altitude plant, possesses immunomodulatory, anti-oxidant, anti-bacterial and adaptogenic activity and is widely used in treatment of various diseases. The present study was designed to ascertain the safety of aqueous extract of H. rhamnoides fruit when administered by gavage to rats for 90. days. Four groups of animals, each consisting of 15 males and 15 females, were adminstered 0, 100, 250, or 500. mg/kg extract, in a single dose/day. There were no treatment related change in mean body weight, organ/body weight ratio, histological, hematological and biochemical parameters studied in rats of either sex administered with extract at any dose evaluated. However, a significant increase in plasma glucose levels was observed in animals supplemented with 250 or 500. mg/kg extract, which returned to normal after a 2-week withdrawal of treatment. These results indicate no adverse effects of extract at a dose of 100. mg/kg body weight/day in rats administered for 90-days. Based on the findings of this study, the NOAEL was 100. mg/kg body weight/day of aqueous fruit extract of seabuckthorn in rats. © 2010 Elsevier Ltd.


Gupta N.,Defence Institute of Physiology and Allied science | Ashraf M.Z.,Defence Institute of Physiology and Allied science
Seminars in Thrombosis and Hemostasis | Year: 2012

There are several genetic and acquired risk factors for venous thromboembolism. Exposure to high altitude (HA), either during air travel, ascension of mountains, or while engaging in sports activities, has been observed to result in a hypercoagulable state, thus predisposing to thromboembolic events. Although several previous studies have suggested that conditions present at HAs contribute to establish a prothrombotic milieu, published reports are contradictory and the exact underlying mechanism remains poorly understood. Results from HA studies also show that environmental conditions at HA such as hypoxia, dehydration, hemoconcentration, low temperature, use of constrictive clothing as well as enforced stasis due to severe weather, would support the occurrence of thrombotic disorders. The three leading factors of Virchow triad, that is, venous stasis, hypercoagulability, and vessel-wall injury, all appear to be present at HA. In synthesis, the large list of environmental variables suggests that a single cause of HA-induced thromboembolic disorders (TED) may not exist, so that this peculiar phenomenon should be seen as a complex or multifactorial trait. Further investigation is needed to understand the risk of TED at HA as well as the possible underlying mechanisms. © 2012 by Thieme Medical Publishers, Inc.

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