Investigation of the role of microRNAs in Spinocerebellar Ataxia type 3

Spinocerebellar Ataxia Type 3 (SCA3) is an inherited, neurodegenerative disorder belonging to the group of polyglutamine repeat disorders. It is caused by CAG repeat expansions in the ATXN3 gene leading to expanded polyglutamine repeats in the ATXN3 protein. The expanded ATXN3 protein forms intranuclear inclusions in neuronal cells ultimately leading to neuronal death. MicroRNAs are endogenously produced, small, non-coding RNAs that play a role in post-transcriptional regulation of gene expression. MicroRNA mediated regulation of gene expression is associated with several processes such as the development of organisms, maintenance of homeostasis as well as with several human disorders such as cancer and neurodegenerative diseases. The present study demonstrates the ability of specific microRNAs to target the expression of the proteins ATXN3, MID1 and DNAJB1 which play important roles in the pathogenic mechanisms in SCA3. The microRNAs hsa-miR-32 and hsa-miR-181c were found to target and reduce ATXN3 expression, while hsa-miR-216a-5p, hsa-miR-374a-5p, hsa-miR-542a-3p target and reduce the expression of MID1. Profiling of gene and microRNA expression in iPSC-derived neurons from SCA3 patients and controls revealed that in SCA3 neurons, hsa-miR-370 and hsa-miR-543 that target the expression of the neuroprotective DNAJB1 chaperone are upregulated, while the target DNAJB1 mRNA and protein are downregulated. Similarly, DNAJB1 mRNA level was found to be downregulated in a transgenic SCA3 mouse model suggesting that the miRNA mediated reduction in the neuroprotective DNAJB1 might contribute to the pathogenesis observed in SCA3. These results demonstrate the two sided role of microRNAs in the pathogenesis of SCA3 by targeting the expression of neurotoxic proteins such as ATXN3, MID1 as well as neuroprotective proteins such as DNAJB1. The findings of this study might contribute towards miRNA based therapeutic strategies such as enhancing miRNA targeting of neurotoxic proteins and preventing miRNA targeting of neuroprotective proteins

METHOD DEVELOPMENT AND VALIDATION BY GC-MS FOR QUANTIFICATION OF 1-CHLOROETHYL CYCLOHEXYL CARBONATE AS A GENOTOXIC IMPURITY IN CANDESARTAN CILEXETIL DRUG SUBSTANCE

Objective: Candesartan Cilexetil is an Angiotension II receptor antagonist used mainly for the treatment of hypertension. The synthesis process of Candesartan uses 1-Chloroethyl Cyclohexyl Carbonate (CECC), which is potential genotoxic impurity as per the EMEA guideline. The method development and later validation activity was proposed and performed for the analysis of 1-Chloroethyl Cyclohexyl Carbonate (CECC) in Candesartan Cilexetil drug substance. Based on daily dose basis evaluation limit required was 0.49 µg/mL (i. e. 49 µg/g). Methods: The development activity was conducted by Gas chromatography technique with Mass spectrometer as detector. DB-5 make Agilent J&W column with length 50 meter, internal diameter 0.32 mm, film thickness 0.52 µm was used. Phase of DB-5 is 5% phenyl, 95% dimethyl polysiloxane and is an intermediate polarity phase with very good selectivity for polar compounds. Hexane was selected as diluent considering the selective solubility of CECC.  Results: Validation activity was planned and completed based on the International Conference on Harmonization (ICH) guidelines. The LOD and LOQ values were found to be 0.70 and 2.11 µg/g (i. e. 0.007 and 0.021 µg/mL) for CECC. Method very sensitive as method was related to genotoxic impurity. Also accuracy results were well in the range of 99 to 105 %. Linearity curve showed correlation coefficient of 0.99997. Conclusion: From validation data it was confirmed that the method is specific, precise, accurate, linear and sensitive for the required purpose. During the same activity three commercial batches were analyzed. Validation data as well as commercial batch data was enough to prove the method suitability

Survey on Various Trust Management Issues in Cloud Environments

Over the past few years, trust management has been one of the hot topics especially in the area of cloud computing. Well-known benefits resulting from cloud computing adoption, several issues have emerged during its evolution: most of them relate to security, privacy and trust management. In particular, its proliferation has placed even more attention to trust management, representing one of the key challenges in the adoption of cloud computing technologies. This paper proposes a survey of existing trust management models addressing collaboration agreements in cloud computing scenarios. Main limitations of current approaches are outlined and possible improvements are traced, as well as a future research path

Secure Data Storage on Cloud through Networking

Security, privacy issue and data protection is always one of the major issue which reduces the growth and make slow the speed of rising new technologies in the field of cloud computing. The advent of an advanced model should not negotiate with the required functionalities and capabilities present in the current model. Here to avoid risk and threaten are reduced in the new model the features are improved. In this paper, a survey of the different security risks that pose a threat to the cloud is presented. This paper is a survey more specific to the different security issues that has emanated due to the nature of the service delivery models of a cloud computing system

Modelling the Encroachment of Farmhouse Culture on Private Village Pastures and Its Environmental Fall-Out in Northern Western Ghats, India

Tropical India harbours numerous pasturelands across small landholdings ranging up to few hectares which are covered with grass that is suitable as fodder. These grazing lands are commonly known as ‘Gairan’ in urbanised northern Western Ghats mountain tract in Western India). Such grasslands comprise about 20% of the total area of a village (Jodha, 1986), support livestock and supplement the agro-economy of the village. These pasturelands are being replaced by fenced ‘farmhouses’ of the urban elite, resulting in land use changes that caused drastic qualitative and quantitative changes in terms of area, fodder species composition and livestock they support (Patwardhan et al., 2003). The study area has faced large changes in the last few decades with increases in the area under settlement by 240%s as well as a decrease in the area of agriculture land and grasslands-scrub vegetation by 31 % and 39 % respectively (Nalavade, 2003). The present paper documents socio-cultural, economic and environmental changes in private village pastures across the Mumbai-Pune urban belt

Whittle Index Based User Association in Dense Millimeter Wave Networks

We address the problem of user association in a dense millimeter wave (mmWave) network, in which each arriving user brings a file containing a random number of packets and each time slot is divided into multiple mini-slots. This problem is an instance of the restless multi-armed bandit problem, and is provably hard to solve. Using a technique introduced by Whittle, we relax the hard per-stage constraint that each arriving user must be associated with exactly one mmWave base station (mBS) to a long-term constraint and then use the Lagrangian multiplier technique to convert the problem into an unconstrained problem. This decouples the process governing the system into separate Markov Decision Processes at different mBSs. We prove that the problem is Whittle indexable, present a scheme for computing the Whittle indices of different mBSs, and propose an association scheme under which, each arriving user is associated with the mBS with the smallest value of the Whittle index. Using extensive simulations, we show that the proposed Whittle index based scheme outperforms several user association schemes proposed in prior work in terms of various performance metrics such as average cost, delay, throughput, and Jain's fairness index.Comment: 16 pages, 7 figure

Biometric Data Security using Recursive Visual Cryptography

Recursive Visual cryptography takes the idea from the basic scheme of Visual cryptography to hide multiple secrets recursively in the single image. This paper proposes a scheme of recursive creation of shares using the basic scheme and embedding secrets into the shares. This results levels of share creation i.e. n- secrets equals n/2 levels. This paper also provides  secured authentication for the user, using the Biometric authentication Thus the proposed paper is implemented in any of the real time applications. Keywords:Recursive Visual Cryptography, Embedding secrets, Biometric authentication, Levels of share

Anaesthesia management in a patient of interstitial lung disease with pulmonary hypertension for emergency laparotomy

We report the anesthaetic management of a patient with known case of interstitial lung disease (ILD) with profound fibrotic changes and bullae with severe pulmonary hypertension (PH) posted for exploratory laparotomy for cecal volvulus. Emergency exploratory laparotomy was done under combined spinal-epidural anaesthesia to avoid intra-operative and post-operative pulmonary complications associated with general anaesthesia and mechanical ventilation

Study of oxidative stress and C-Reactive protein in type-2 diabetes mellitus

Background: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion and insulin action or both. T2DM is associated with chronic low grade inflammation, possibly through a pathway involving a cytokine-mediated acute-phase response to infection and other inflammatory processes. authors aim to study C-reactive protein (CRP) which is an acute-phase reactant produced primarily in the liver hepatocytes. Oxidative stress levels in newly diagnosed T2M patients were analysed with respect to malondialdehyde (MDA) and nitric oxide (NO).Methods: Case-control study comprising of aged-sex matched subjects: newly diagnosed T2DM cases (n=30) and controls (n=30). The serum samples of subjects were analysed for levels of MDA by Buege and Aust method, while NO levels by Cortas and Wakid’s kinetic cadmium reduction method using spectrophotometer. CRP levels were analysed by using turbidimetry. Statistical analysis was done using Mini-tab 17 software with 95% confidence interval.Results: Serum levels of MDA, NO and CRP in newly diagnosed T2DM patients were significantly increased as compared to healthy controls.Conclusions:  Authors concluded that the oxidative stress and inflammation plays a pivotal role in the aetiology of hyperglycemia in T2DM. Oxidative stress and inflammatory markers might help prognosis of T2DM in hyperglycemic individuals with the help of which precautionary measure can be taken to reduce the rate of disease progression. Treatment involving anti-oxidant and anti-inflammatory medications might help to rescue vital organs from damage