The role of VIF in overcoming the APOBEC3G block to HIV-1 replication

This project focuses on the Virus Infectivity Factor protein of HIV-1 and its relief of the block to virus replication exerted by the APOBEC3G component of the innate immune response. Virus Infectivity Factor (vif) is an accessory gene of HIV, deletion of which leads to large drops in virus infectivity. This decrease in infectivity was found to be due to APOBEC3G, an inhibitor of HIV replication which is constitutively expressed in peripheral blood mononuclear cells (PBMCs), the natural host cells for HIV in humans. Vif is indispensable to block the inhibitory effects of APOBEC3G thereby allowing normal viral replication to continue inside the host. This recognition of the critical role played by Vif in the viral replication cycle has centred studies on characterising the interactions of Vif with both APOBEC3G as well as other virus encoded proteins. Stimulation of proteasomal degradation of APOBEC3G is currently believed to be the primary anti-APOBEC3G effect induced by Vif. However recent reports, particularly those showing that Vif remains able to block the inhibitory actions of degradation resistant APOBEC3G, question the validity of this hypothesis. The recognition that both APOBEC3G and Vif become incorporated into HIV particles through an interaction with the precursor of the virion structural proteins, Pr55GAG has raised the possibility that they may compete with each other for this incorporation. Using techniques such as mammalian two-hybrid assays, sucrose gradient analysis of GAG virus-like particles (VLPs) and confocal imaging, the interactions of these proteins with Pr55GAG have been analyzed and the results obtained indicate that Vif competes with APOBEC3G for Pr55GAG binding leading to its displacement and exclusion from the budding HIV virions. This potentially important pathway for Vif activity and its significance in the development of novel antiretroviral drugs in the future will be discussed

Association of serum uric acid-creatinine ratio with microalbuminuria and glycemic status (HbA1c) as an early indicator of diabetic nephropathy

Background: The serum uric acid is a good predictor of renal injury in both diabetes patients and non-diabetes. Creatinine is the marker to detect the renal function. Aim of our study was to assess the correlation of the serum uric acid to creatinine ratio with the Microalbuminuria and glycemic status (HbA1c) in diabetes mellitus patients.Methods: It is analytical observational study conducted in urban tertiary care hospital attached to medical college between July to august 2019 after obtaining the ethics clearance. Participants aged between 18 to 60 years with type 2 diabetes mellitus and healthy controls were included in present study. The patients with diabetic nephropathy with grade 3 and above and non-diabetes patients with history of ischemic heart disease, advanced hypertension, Chronic or acute kidney disease, liver disease, known case of hyperuricemia/gout, alcoholics, acute febrile illness, urinary tract infection, cancer were excluded from present study.Results: Total of 131 individuals were included in present study that fulfilled inclusion criteria. The mean age of the participants was 56.70±11.9 with 64 females and male 67 (male: female ratio of 1). Among 131 participants, 60 were with T2DM and 71 were normal control. Our study showed a significant strength of association between the UACr with the urine MAU (r=0.760, p<0.001), where-as the SAU was associated with MAU excretion in urine (0.52, p<0.001). The UACr was also significantly associated with the HbA1c (r=0.25, p=0.01).Conclusions: Urine microalbuminuria and HbA1c were significantly correlated with the ratio of uric acid to creatinine in the serum. The serum uric acid creatinine ratio (UACr) is a good predictor for predicting renal damage in patients with diabetes mellitus at an early stage of illness

The role of VIF in overcoming the APOBEC3G block to HIV-1 replication

This project focuses on the Virus Infectivity Factor protein of HIV-1 and its relief of the block to virus replication exerted by the APOBEC3G component of the innate immune response. Virus Infectivity Factor (vif) is an accessory gene of HIV, deletion of which leads to large drops in virus infectivity. This decrease in infectivity was found to be due to APOBEC3G, an inhibitor of HIV replication which is constitutively expressed in peripheral blood mononuclear cells (PBMCs), the natural host cells for HIV in humans. Vif is indispensable to block the inhibitory effects of APOBEC3G thereby allowing normal viral replication to continue inside the host. This recognition of the critical role played by Vif in the viral replication cycle has centred studies on characterising the interactions of Vif with both APOBEC3G as well as other virus encoded proteins. Stimulation of proteasomal degradation of APOBEC3G is currently believed to be the primary anti-APOBEC3G effect induced by Vif. However recent reports, particularly those showing that Vif remains able to block the inhibitory actions of degradation resistant APOBEC3G, question the validity of this hypothesis. The recognition that both APOBEC3G and Vif become incorporated into HIV particles through an interaction with the precursor of the virion structural proteins, Pr55GAG has raised the possibility that they may compete with each other for this incorporation. Using techniques such as mammalian two-hybrid assays, sucrose gradient analysis of GAG virus-like particles (VLPs) and confocal imaging, the interactions of these proteins with Pr55GAG have been analyzed and the results obtained indicate that Vif competes with APOBEC3G for Pr55GAG binding leading to its displacement and exclusion from the budding HIV virions. This potentially important pathway for Vif activity and its significance in the development of novel antiretroviral drugs in the future will be discussed.EThOS - Electronic Theses Online ServiceUniversity of WarwickOverseas Research Students Awards Scheme (ORSAS)GBUnited Kingdo

SLA Driven Load Balancing For Web Applications in Cloud Computing Environment

Cloud computing is an emerging topic in the field of parallel and distributed computing. Many IT giants suchas IBM, Sun, Amazon, Google, and Microsoft are promoting and offering various storage and computeclouds. Clouds provide services such as high performance computing, storage, and application hosting.Cloud providers are expected to ensure Quality of Service (QoS) through a Service Level Agreement (SLA)between the provider and the consumer. In this research, we develop a heterogeneous test bed compute cloudand investigate adaptive management of resources for Web applications to satisfy a SLA that enforcesspecific response time requirements. We develop a system on top of EUCALYTPUS framework that activelymonitors the response time of the computed resources assign to a Web application and dynamicallyallocates the resources required by the application to satisfy the specific response time requirements.Keywords: Eucalyptus, SLA, QOS, Virtualization, Minimum Response Time

Molecular docking study to elucidate the anti-pruritic mechanism of selected natural ligands by desensitizing TRPV3 ion channel in Psoriasis: An in silico approach

578-583Psoriasis is a chronic immune-mediated inflammatory skin disease, in which pruritus is a common feature and also affects the social well-being of individuals with psoriasis significantly. The transient receptor potential cation channel, subfamily V, member 3 (TRPV3) is believed to be involved in hypersensation and generation of itching in the case of psoriasis. The purpose of the present study was to find out suitable anti-pruritic agents and to establish the mechanism of actions of those anti-pruritic agents with the help of molecular docking studies, through which they can alleviate the itching and hypersensitivity problems in psoriasis. An extensive literature survey, pertaining to natural ligands having reported antipsoriatic activity was carried out. The crystal structure of the TRPV3 receptor was retrieved from rcsb.org. 3D structures of selected eleven natural ligands were prepared and optimized by ChemSketch free version 2015. Computational protein- ligand docking studies were carried out by AutoDock 4.2 simulator using the Lamarckian genetic algorithm. In this study, Hypericin showed a higher binding affinity (-8.09 kcal/mol) and fitted into the active pocket of TRPV3. Results revealed that Hypericin might be the candidates to be employed as an anti-pruritic agent in the case of psoriasis to desensitize the TRPV3 ion channel

Real-time model-based control of single pass tangential flow filtration for production of monoclonal antibodies

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A bioinformatic approach to establish P38α MAPK inhibitory mechanism of selected natural products in psoriasis

165-171In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38α mitogen-activated protein kinases (P38α MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38α MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38α MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (−9.00 and −8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action

Voice Based Digit Writer For Physically Challenged

A new concept of pen is coming now that is Automatic Pen Writer with Voice recognition. Voice Controlled Robot (VCR) is a mobile robot. The robot’s action can be controlled by the user through mobile phone by giving specific person’s voice commands. The robot will receive the voice commands from the person through the microphones and then the robot will execute the actual work. This project is specially made for physically challenged students who can not to write the exams like others. In this project the voice message will be recorded using the application in the mobile phone, and then the voice that is recorded will be sent to Arduino board by the help of Bluetooth. Through which the instructions will be sent to the robot. The robot writer will function based on the received Voice command

Novel quantum mechanics based engineering approach enables transaminase to convert bulky ketone substrates

Amine transaminases (ATAs) are being used in the production of chiral amines as an alternative to chemical synthesis to reduce cost and inadequate stereoselectivity. Yet, ATAs are enzymes, difficult to engineer because of the unique structural architecture of the active site that limits bulkier substrates, example Sitagliptin. However, in recent yearscombination of computational techniques and protein engineering has evolved enzymesto acceptbulkier substrates as shown for (R) 1 and more recently (S)-selective ATAs2. In this study, we have used the(S)-selective ATA from Chromobacterium violaceum to expand its substrate scope towards bulky ketones using a novel quantum mechanics (QM) based engineering framework. The framework predicts hotspots by analyzing the E-S molecular dynamics (MD) and QM simulations using novel methods developed in-house. To mention a few, path predictor, which predicts the path taken by the substrate to enter the active site, a grid based per residue energy profiling and atomistic motional correlations of the active site residues and QM based alanine scanning method. Please click Additional Files below to see the full abstract