A new rat model for the study of obesity

The currently used raL models of obesity and diabetes are derived from either Zucker or from Koletsky rats. Recently, we identified a spontaneous obese rat from out Wistar colony which is maintained as an inbred stock for the past 75 years. Initially, one of the male progeny in a litter was observed to have abnormal body weight for its age. The parents of this ral were identified, the progeny selectively bred, and a colony has been developed. This is designated as WNIN-0b. The colony is maintained by mating heterozygous animals (+/ob), as the homozygous (ob/ob) were found to be infertile. The trait is carried as an autosomal recessive mutation and the colony is currenfly in F7 generation.Obesity is visible in these mutants around 35 days of age. They are hyperphagic and reach a body weight of 500—600 g by 105 days of age. “Kinky” tail is characteristic of this mutant and this is visible around 50-60 days. Sexual maturity is delayed in female obese mutants, as judged by the day of vaginal opening. The animals are cuglyccmic and show hyperinsulinaemia, hypertriglyceridaemia, arid hypercholesterolemia. Another mutant showing hyperglycemia is also obtained fromthe obese colony. Unlike earlier models which are essentially derived from a randomAbred stock, this is the first report of a rat obese model, developed spontaneously from an inbred strain

Study experiences and the post-study intentions of female international undergraduate students

The number of female international students is increasing exponentially, and whilst international study may engender many benefits and challenges, little is known about their intentions once they complete their studies. This article reviews the literature on female international students with specific focus on exploring post-study intentions. A scoping review of four electronic databases was completed. After applying criteria to determine suitability, 30 publications were included in the final review. Analysis revealed three key foci: (1) the rationale for studying internationally; (2) the study experience; and (3) post-study intentions. The literature illustrates that an international study experience has the potential to be a powerful transformative opportunity if positive experiences outweigh the negatives. The findings also indicate that the post-study intentions of female international students are under-researched. The article contends that attention should be given to supporting the needs of this group, with a view to maximizing post-study opportunities

Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis.

Endocytic transport necessitates the generation of membrane tubules and their subsequent fission to transport vesicles for sorting of cargo molecules. The endocytic recycling compartment, an array of tubular and vesicular membranes decorated by the Eps15 homology domain protein, EHD1, is responsible for receptor and lipid recycling to the plasma membrane. It has been proposed that EHD dimers bind and bend membranes, thus generating recycling endosome (RE) tubules. However, recent studies show that molecules interacting with CasL-Like1 (MICAL-L1), a second, recently identified RE tubule marker, recruits EHD1 to preexisting tubules. The mechanisms and events supporting the generation of tubular recycling endosomes were unclear. Here, we propose a mechanism for the biogenesis of RE tubules. We demonstrate that MICAL-L1 and the BAR-domain protein syndapin2 bind to phosphatidic acid, which we identify as a novel lipid component of RE. Our studies demonstrate that direct interactions between these two proteins stabilize their association with membranes, allowing for nucleation of tubules by syndapin2. Indeed, the presence of phosphatidic acid in liposomes enhances the ability of syndapin2 to tubulate membranes in vitro. Overall our results highlight a new role for phosphatidic acid in endocytic recycling and provide new insights into the mechanisms by which tubular REs are generated.journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov't2013 Jun2013 04 17importe

Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

<p>Abstract</p> <p>Background</p> <p>11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet) on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats.</p> <p>Methods</p> <p>Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype) were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided <it>ad libitum</it>. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat.</p> <p>Results</p> <p>Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα), the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα), a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes.</p> <p>Conclusions</p> <p>This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly contribute to visceral fat loss in these obese rats. Studying the role of various nutrients on the regulation of 11β-HSD1 activity and expression will help in the evolving of dietary approaches to treat obesity and insulin resistance.</p

Optimum dose of nitrogen and potassium for ginger in Wynad, Kerala

Study on nutrient requirement of ginger in Wynad, Kerala showed the positive effect of higher, doses of Nand K on the yield. Among the 16 levels of Nand K, 3 combinations viz., 150 kg N, 50 kg K; 150 kg N, 100 kg K and 75 kg N, 150 kg K ha-1 were found to be significantly superior with respect to yield. Among the vegetative characters, plant height was found to be significantly influenced by nitrogen. The optimum dose of Nand K derived from the quadratic equation was 144 kg and 109 kg ha-1 respectively. &nbsp

Motometrics: A Toolbox for Annotation and Efficient Analysis of Motor Evoked Potentials

Stimulating the nervous system and measuring muscle response offers a unique opportunity to interrogate motor system function. Often, this is performed by stimulating motor cortex and recording muscle activity with electromyography; the evoked response is called the motor evoked potential (MEP). To understand system dynamics, MEPs are typically recorded through a range of motor cortex stimulation intensities. The MEPs increase with increasing stimulation intensities, and these typically produce a sigmoidal response curve. Analysis of MEPs is often complex and analysis of response curves is time-consuming. We created an MEP analysis software, called Motometrics, to facilitate analysis of MEPs and response curves. The goal is to combine robust signal processing algorithms with a simple user interface. Motometrics first enables the user to annotate data files acquired from the recording system so that the responses can be extracted and labeled with the correct subject and experimental condition. The software enables quick visual representations of entire datasets, to ensure uniform quality of the signal. It then enables the user to choose a variety of response curve analyses and to perform near real time quantification of the MEPs for quick feedback during experimental procedures. This is a modular open source tool that is compatible with several popular electrophysiological systems. Initial use indicates that Motometrics enables rapid, robust, and intuitive analysis of MEP response curves by neuroscientists without programming or signal processing expertise

Corrigendum: Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy

Novel substituted methylenedioxy lignan suppresses proliferation of cancer cells by inhibiting telomerase and activation of c-myc and caspases leading to apoptosis

Conventional solvent fractionation and bioactivity based target assays were used to identify a new anti-cancer molecule from Phyllanthus urinaria, a herbal medicinal plant used in South India. At each step of the purification process the different fractions that were isolated were tested for specific anti-proliferative activity by assays measuring the inhibition of [3H]thymidine incorporation, and trypan blue drug exclusion. The ethyl acetate fraction that contained the bioactivity was further purified and resolved by HPLC on a preparative column. The purity of each of the fractions and their bioactivity were checked. Fraction 3 demonstrated a single spot on TLC and showed maximum anti-proliferative activity. This fraction was further purified and the structure was defined as 7′-hydroxy-3′,4′,5,9,9′-pentamethoxy-3,4-methylene dioxy lignan using NMR and mass spectrometry analysis. The pure compound and the crude ethyl acetate fraction which showed anti-proliferative activities were examined for ability to target specific markers of apoptosis like bcl2, c-myc and caspases and for effects on telomerase. Four specific cancer cell lines HEp2, EL-1 monocytes, HeLa and MCP7 were used in this study. The results indicate that 7′-hydroxy-3′,4′,5,9,9′-pentamethoxy-3,4-methylene dioxy lignan was capable of inhibiting telomerase activity and also could inhibit bcl2 and activate caspase 3 and caspase 8 whose significance in the induction of apoptosis is well known. We believe that this compound could serve as a valuable chemotherapeutic drug after further evaluations

Histidine Hydrogen-Deuterium Exchange Mass Spectrometry for Probing the Microenvironment of Histidine Residues in Dihydrofolate Reductase

Histidine Hydrogen-Deuterium Exchange Mass Spectrometry (His-HDX-MS) determines the HDX rates at the imidazole C(2)-hydrogen of histidine residues. This method provides not only the HDX rates but also the pK(a) values of histidine imidazole rings. His-HDX-MS was used to probe the microenvironment of histidine residues of E. coli dihydrofolate reductase (DHFR), an enzyme proposed to undergo multiple conformational changes during catalysis.Using His-HDX-MS, the pK(a) values and the half-lives (t(1/2)) of HDX reactions of five histidine residues of apo-DHFR, DHFR in complex with methotrexate (DHFR-MTX), DHFR in complex with MTX and NADPH (DHFR-MTX-NADPH), and DHFR in complex with folate and NADP+ (DHFR-folate-NADP+) were determined. The results showed that the two parameters (pK(a) and t(1/2)) are sensitive to the changes of the microenvironment around the histidine residues. Although four of the five histidine residues are located far from the active site, ligand binding affected their pK(a), t(1/2) or both. This is consistent with previous observations of ligand binding-induced distal conformational changes on DHFR. Most of the observed pK(a) and t(1/2) changes could be rationalized using the X-ray structures of apo-DHFR, DHFR-MTX-NADPH, and DHFR-folate-NADP+. The availability of the neutron diffraction structure of DHFR-MTX enabled us to compare the protonation states of histidine imidazole rings.Our results demonstrate the usefulness of His-HDX-MS in probing the microenvironments of histidine residues within proteins