Steroids Up-Regulate p66Shc Longevity Protein in Growth Regulation by Inhibiting Its Ubiquitination

p66Shc, an isoform of Shc adaptor proteins, mediates diverse signals, including cellular stress and mouse longevity. p66Shc protein level is elevated in several carcinomas and steroid-treated human cancer cells. Several lines of evidence indicate that p66Shc plays a critical role in steroid-related carcinogenesis, and steroids play a role in its elevated levels in those cells without known mechanism.In this study, we investigated the molecular mechanism by which steroid hormones up-regulate p66Shc protein level. In steroid-treated human prostate and ovarian cancer cells, p66Shc protein levels were elevated, correlating with increased cell proliferation. These steroid effects on p66Shc protein and cell growth were competed out by the respective antagonist. Further, actinomycin D and cyclohexamide could only partially block the elevated p66Shc protein level by steroids. Treatment with proteasomal inhibitors, but not lysosomal protease inhibitor, resulted in elevated p66Shc protein levels, even higher than that by steroids. Using prostate cancer cells as a model, immunoprecipitation revealed that androgens and proteasomal inhibitors reduce the ubiquitinated p66Shc proteins.The data collectively indicate that functional steroid receptors are required in steroid up-regulation of p66Shc protein levels in prostate and ovarian cancer cells, correlating with cell proliferation. In these steroid-treated cells, elevated p66Shc protein level is apparently in part due to inhibiting its ubiquitination. The results may lead to an impact on advanced cancer therapy via the regulation of p66Shc protein by up-regulating its ubiquitination pathway

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

A jig for holding components for electroplating

A jig for holding a component to be selectively electroplated, which comprises a body (3), having at the inner side of its top a groove (7) to house a gasket (2) at lesat two perpendicular stems (9) being provided at the periphery of the said body (3), one end of the said stems being fixed to a T shape shield which is consisting of a horizontal rod (10) to which is fixed a perpendicular rod (11), the said rod (11) having at its one end a disc (12) of a desired size which tightly preses against the said groove (7) (not shown in fig.1) of the said body (3), a component (1) being placed between the said disc (12) and the said gasket (2), the said component (1) alongwith the said disc (12) and siad gasket (2) being placed in the said groove (7) the bottom portion of the said body (3) having a slot (8) provided with an opening to enable a metalic pin (5a) which matches with the hhole of the said component (1), to be electroplated, characterised in that the exposed portion of a metallic pin (5) being covered with the material such as herein described amp;which can withstand the temperature and pressure employed during the electroplating process, non corrosive and does not react with the content of the elctorplating bath and also used for making the body (3)

Electrochemical machining of an integrally bladed wheel - An example of useful corrosion

Machining of an integrally bladed stainless steel wheel by high rate anodic dissolution is discussed. The use of sodium chloride leads to spark-free machining but suffers from the disadvantage of heavily reduced blade profile. Sodium nitrate, on the other hand, leads to a sharp profile but has a tendency to spark. A method of overcoming the problem of sparking is discussed. Design of tool in relation to the machining of integrally bladed wheel is described

An improved process for the manufacture of a tool for electrochemical machining of materials and the tool so manufactured

An improved process for the manufacture of a tool which is used as a cathode in electrochemical machining of materials which comprises machining a metal piece having adequate electrical conductivity,to provide a hollow tube with a cross section similar to that of the profile of the material to be electrochemically machined,characterised in that drilling a hole near the edge of the hollow tube such that the hole extends to the entire length of the tube for uniform supply of electrolyte throughout the electrochemical machining,milling the ouside surface of the tube to the desired shape and size,slotting the surface of the said milled tube,insulating the inner surface of the said tube with an insulator pressure tube having a cross section similar to the inner profile of the tube,moulding the outside surface of the tube,with an insulator which may be same or different than that used for insulating the inner surface of the tube to get the tool

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Not AvailableAfrican swine fever virus (ASFV) belongs to the genus of virus of the Asfaviridae family. ASFV infection causes hemorrhage and high death rate hence increased loss to the swine community. It is a complex infectious disease of swine, which constitutes devastating impacts on animal health and the economy of the pig farmers. It has been confirmed that virus infections has been spreading in swine population for many years. In this study, the evolutionary epidemiology analysis of ASF virus from the geographical regions Africa, Europe, and Asia, respectively were retrieved from GenBank for the analysis. The nucleotide gene sequences of the viral protein p72 encoded by B646L gene published during 1960-2020 was taken in to study. The Bayesian skyline model with uncorrelated randomized clock model was employed to reconstruct the evolutionary history of the virus, to identify virus population demographics. Results of the analysis suggested that ASFV exhibited a high evolutionary rate, as the divergence caused reduction in the population in the recent years. The B646L gene of ASFV had an evolutionary rate of 4.13 X 10-6 substitution/site/year and the tMRCA as 3.15 x 105 with 95 percent HPD range in years (2.4 x 104 to 1.23 x 106) was obtained. In conclusion, the evolutionary study of ASFV with p72 protein from the ASFV of the B646L genes indicated that they evolved at a faster rate and plays a major role in the evolutionary process. Further, this study may help in designing or developing vaccines to control the spread of the disease.Not Availabl

Design of an Automated Dispenser Unit

This paper presents our work on developing an automated micro positioner and a low cost disposable dispenser module having a disposable dispenser core. The dispenser core is made up of Polydimethylsiloxane (PDMS). Once the user specifies the dispensing location in the Graphical User Interface (GUI), the movement of the micropositioner is automatic. The design, fabrication and characterization results of the dispenser module are also presented. The dispensing experiments are performed with Di-Ethanol Amine as the working reagent. The minimum dispensed volume achieved is about 4 nL

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Not AvailableCOVID-19 is the deadliest pandemic, with over 18.2 million people infected with the SARS-CoV-2 virus by August 2, 2021 resulting in human deaths and economic losses. A number of countries have formulated control measures in order to prevent the spread of the virus. However, it is unknown when the outbreak will subside in different countries around the world. The role of predicting the COVID-19 trend is extremely difficult. Indian government has made disease outbreak analysis a priority in order to implement necessary healthcare measures to reduce the impact of this deadly pandemic on human health and country’s economics. The time series data for COVID-19 disease was collected from the website www.covid19india.org and were analyzed using a periodic regression model using the data from 22nd Janaury March 2020 to 01st Febraury 2021 the estimated number of cases until 27 July, 2021 was predicted to develop a stochastic model using periodic regression and were documented in top 10 highly infected states in India. The analysis revealed a increasing pattern for the number of reporting cases in the early days of prediction and decreasing trend for the number of reporting cases in the later days of prediction, which could decrease in future days in Karnataka, West Bengal, Uttar Pradesh, Telangana, Bihar and Haryana states. However, in Madhya Pradesh, Andhra Pradesh, Maharashtra and Tamil Nadu states showed a rapid phase of rise in disease incidence, which is likely to infect a larger population and suggests the disease's pandemic existence over a duration. Our model emphasizes the importance of ongoing and continuous efforts that are in place in all states to minimize occurrence of new cases of infections, so as to potentially improving India's economic wealth with the available resourcesNot Availabl