Body weight lowering effect of glucose-dependent insulinotropic polypeptide and glucagon-like peptide receptor agonists is more efficient in RAMP1/3 KO than in WT mice

The glucose-dependent insulinotropic polypeptide (GIPR) and glucagon-like peptide (GLP-1R) receptor agonists are insulin secretagogues that have long been shown to improve glycemic control and dual agonists have demonstrated successful weight loss in the clinic. GIPR and GLP-1R populations are located in the dorsal vagal complex where receptor activity-modifying proteins (RAMPs) are also present. According to recent literature, RAMPs not only regulate the signaling of the calcitonin receptor, but also that of other class B G-protein coupled receptors, including members of the glucagon receptor family such as GLP-1R and GIPR. The aim of this study was to investigate whether the absence of RAMP1 and RAMP3 interferes with the action of GIPR and GLP-1R agonists on body weight maintenance and glucose control. To this end, WT and RAMP 1/3 KO mice were fed a 45% high fat diet for 22 weeks and were injected daily with GLP-1R agonist (2 nmol/kg/d; NN0113-2220), GIPR agonist (30 nmol/kg/d; NN0441-0329) or both for 3 weeks. While the mono-agonists exerted little to no body weight lowering and anorectic effects in WT or RAMP1/3 KO mice, but at the given doses, when both compounds were administered together, they synergistically reduced body weight, with a greater effect observed in KO mice. Finally, GLP-1R and GIP/GLP-1R agonist treatment led to improved glucose tolerance, but the absence of RAMPs resulted in an improvement of the HOMA-IR score. These data suggest that RAMPs may play a crucial role in modulating the pharmacological actions of GLP-1 and GIP receptors

Head and Neck Lymphomas: Tip of the Iceberg?

ABSTRACT Background: Lymphomas comprise around 5% of all head and neck neoplasms and is the second most common extra nodal non hodgkin's lymphoma (NHL). However there is sporadic data on this entity from the subcontinent and hence we undertook this study. Methodology: This retrospective observational study was conducted at a tertiary care oncology center in India on diagnosed cases of NHL between January 2007 and December 2013. All patients were diagnosed based on histopathology and immunohistochemistry. Staging work up was done in all patients. Patients were considered as primary Head and Neck lymphomas if there was head and neck as the predominant site with or without regional lymph node involvement. Results: A total of 39 patients were studied. The age at presentation ranged from 29 to 78 years. The most common site of presentation was oral cavity (26%; n=10), followed by parotid and thyroid (18% each; n=7), eye (12%, n=5), maxilla (8%; n=3), paranasal sinuses (8%; n-=3) cheek (8%, n=3), and nasal cavity (2%, n=1). 41% (n=16) cases were in stage I, 43% (n=17) in stage II, 3% (n=1) in stage III, and 13% (n=5) were in stage IV. Most common histology was DLBCL (71%; n=28), followed by plasmablastic (10%; n=4), marginal zone (8%, n=3), mantle cell (3%; n=1), follicular lymphomas (5%; n=2), and NK/T cell lymphoma (3%; n=1). Most of the patients were of low risk (67%; n=26), followed by intermediate (23%; n=9), and high risk (10%; n=4). Patients were treated with anthracycline based chemotherapy +/-radiotherapy. In this study, stage I and stage II patients had a better prognosis and overall survival, median OS 28 months and 11 months, respectively. In stage III and IV, it was 7 and 3 months, respectively. According to site, the best median overall survival was seen with parotid (27 m), paranasal sinus (26m), and oral cavity (23 m), followed by thyroid (18 m) nasal cavity (17 m), maxilla (11 m), eye (8 m), and cheek (7 m)

An Alpha-Catulin Homologue Controls Neuromuscular Function through Localization of the Dystrophin Complex and BK Channels in Caenorhabditis elegans

The large conductance, voltage- and calcium-dependent potassium (BK) channel serves as a major negative feedback regulator of calcium-mediated physiological processes and has been implicated in muscle dysfunction and neurological disorders. In addition to membrane depolarization, activation of the BK channel requires a rise in cytosolic calcium. Localization of the BK channel near calcium channels is therefore critical for its function. In a genetic screen designed to isolate novel regulators of the Caenorhabditis elegans BK channel, SLO-1, we identified ctn-1, which encodes an α-catulin homologue with homology to the cytoskeletal proteins α-catenin and vinculin. ctn-1 mutants resemble slo-1 loss-of-function mutants, as well as mutants with a compromised dystrophin complex. We determined that CTN-1 uses two distinct mechanisms to localize SLO-1 in muscles and neurons. In muscles, CTN-1 utilizes the dystrophin complex to localize SLO-1 channels near L-type calcium channels. In neurons, CTN-1 is involved in localizing SLO-1 to a specific domain independent of the dystrophin complex. Our results demonstrate that CTN-1 ensures the localization of SLO-1 within calcium nanodomains, thereby playing a crucial role in muscles and neurons

Effects of biofertilizer containing N-fixer, P and K solubilizers and AM fungi on maize growth: A greenhouse trial.

An in vitro study was undertaken to evaluate the compatibility of indigenous plant growth promoting rhizobacteria (PGPR) with commonly used inorganic and organic sources of fertilizers in tea plantations. The nitrogenous, phosphatic and potash fertilizers used for this study were urea, rock phosphate and muriate of potash, respectively. The organic sources of fertilizers neem cake, composted coir pith and vermicompost were also used. PGPRs such as nitrogen fixer; Azospirillum lipoferum, Phosphate Solubilizing Bacteria (PSB); Pseudomonas putida, Potassium Solubilizing Bacteria (KSB); Burkholderia cepacia and Pseudomonas putida were used for compatibility study. Results were indicated that PGPRs preferred the coir pith and they proved their higher colony establishment in the formulation except Azospirillum spp. that preferred vermicompost for their establishment. The optimum dose of neem cake powder

Dynamic cumulative residual Renyi’s entropy

Recently, cumulative residual entropy (CRE) has been found to be a new measure of information that parallels Shannon’s entropy (see Rao et al. [Cumulative residual entropy: A new measure of information, IEEE Trans. Inform. Theory. 50(6) (2004), pp. 1220–1228] and Asadi and Zohrevand [On the dynamic cumulative residual entropy, J. Stat. Plann. Inference 137 (2007), pp. 1931–1941]). Motivated by this finding, in this paper, we introduce a generalized measure of it, namely cumulative residual Renyi’s entropy, and study its properties.We also examine it in relation to some applied problems such as weighted and equilibrium models. Finally, we extend this measure into the bivariate set-up and prove certain characterizing relationships to identify different bivariate lifetime modelsCochin University of Science and TechnologyStatistics, Vol. 46, No. 1, February 2012, 41–5

On bounds of some dynamic information divergence measures

In this paper, we obtain certain bounds for some dynamic information divergences measures viz. Renyi’s divergence of order αand Kerridge’s inaccuracy, using likelihood ratio ordering. The results are also extended to weighted models and theoretical examples are given to supplement the results

Characterizations of bivariate models using dynamic Kullback–Leibler discrimination measures

In this paper, the residual Kullback–Leibler discrimination information measure is extended to conditionally specified models. The extension is used to characterize some bivariate distributions. These distributions are also characterized in terms of proportional hazard rate models and weighted distributions. Moreover, we also obtain some bounds for this dynamic discrimination function by using the likelihood ratio order and some preceding results.Cochin University of Science and TechnologyStatistics and Probability Letters 81 (2011) 1594–159

Characterizations of Bivariate Models Using Some Dynamic Conditional Information Divergence Measures

In this article, we study some relevant information divergence measures viz. Renyi divergence and Kerridge’s inaccuracy measures. These measures are extended to conditionally specifiedmodels and they are used to characterize some bivariate distributions using the concepts of weighted and proportional hazard rate models. Moreover, some bounds are obtained for these measures using the likelihood ratio orderCochin University of Science and TechnologyCommunications in Statistics—Theory and Methods, 43: 1939–1948, 201