IMPACT OF DELETERIOUS NON-SYNONYMOUS SINGLE NUCLEOTIDE POLYMORPHISMS OF CYTOKINE GENES ON NON-CLASSICAL HYDROGEN BONDS PREDISPOSING TO CARDIOVASCULAR DISEASE: AN IN SILICO APPROACH

  Objective: Cardiovascular disease (CVD) is a leading cause of death worldwide. Malfunctioning of genes that are responsible for several inflammatory processes is the major cause for its initiation. Cytokine genes are one such group of genes that are involved in the development of CVD. Hence, the prediction of potential point mutations in these genes is important for diagnostic purposes. Such mutations result in altered protein structure and function when compared to neutral ones.Methods: In this study, interleukin factor 6 (IL6), tumor necrosis factor α (TNF-α), interleukin factor 4 (IL4), and interferon gamma have been analyzed using sorting intolerant from tolerant and PolyPhen 2.0 tools.Results: Several single nucleotide polymorphisms (SNPs), in IL6, TNF-α, and IL4, are found to be potentially deleterious. In addition, bond analysis has also been performed on these SNPs. It has been predicted that L119P and R196H of IL6 as well as K87T and T181N of TNF-α are potential ns-SNP's that may cause structural and functional variations in the corresponding proteins. The hydrogen and Cation-Pi bond analysis performed in this study provides molecular-based evidence that support the predicted deleterious potential of such SNPs for these CVD candidate genes along with other conventional in silico tools.Conclusion: The study testifies the importance of adopting a computational approach to narrow down potential point mutants for disease predictions

External Auditor Dealing With Deep Cyber Security of Open Networks

We focus on how you can release major updates to that customer as much as possible, and we suggest a new model called Cloud Storage Audit with verifiable outsourcing for major updates. Within this model, major updates can be outsourced safely to authorized parties, so the important thing throughout the customer is that downloading the update is being saved very little. Moreover, the design gives us the ability to verify the validity of the encrypted secret keys issued by the OA. Specifically, we employ external auditors in current general audit designs; allow it to act as a delegated party in our position, and is also responsible for secure audits and major key updates to resist key detection. When the cloud downloads new files, the client should download the encrypted password only in OA. The licensed party maintains the encrypted secret key from the client for cloud storage audit and updates the encrypted status every time. The client downloads the encrypted password to the authorized authority and encrypts it exactly as it would like to upload new files to the cloud. In our design, only the agriculture authority should keep the encrypted form of the customer's secret key. In our design, only the agriculture authority should keep the encrypted form of the customer's secret key. We formalize the meaning and type of security in this form

To Assess Numerous Procedures in combination with a Neural learning plan to semantically classify short texts

In OSNs, information filtering can also be used for a unlike, more aware, principle. This is appropriate to the statement that in OSNs there is the leeway of redistribution or mentions other posts on fastidious public/private areas, called in general walls. Information filtering can as a result be used to give users the facility to repeatedly control the messages written on their own walls, by filtering out unwanted messages. We deem that this is a key OSN service that has not been present so far. We suggest a scheme agree to OSN users to have a straight control on the messages position on their walls. This is attain through a supple rule-based system, that allows users to modify the filtering decisive factor to be practical to their walls, and a Machine Learning-based soft classifier automatically labelling messages in hold up of content-based filtering

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addresse

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Computational Profiling of Deleterious Non-Synonymous SNP’s in HFE

Liver cirrhosis describes a condition where scar tissue gradually replaces healthy cells in liver. The main causes are sustained, excessive alcohol consumption, viral hepatitis B and C, and fatty liver disease - however, there are other possible causes. Hemochromatosis is most common form of iron overload disease. Three types of hemochromatosis are primary hemochromatosis, also called hereditary hemochromatosis; secondary hemochromatosis; and neonatal hemochromatosis. The HFE gene helps regulate the amount of iron absorbed from food and inherited genetic defects or mutation in HFE [C282Y] cause primary hemochromatosis. Computational approach is sought to determine other similar mutations in this gene. In-silico tools such as SIFT, Polyphen 2.0, and PROVEAN were employed to determine the various deleterious ns-SNPs of HFE that may influence cystic fibrosis

Evaluation of arjunolic acid against Brucella melitenis and in vitro cytotoxic study of lung adenocarcinomic cell line (A549)

510-513Brucellosis, a neglected tropical disease of zoonotic nature, is caused by the genus Brucella, specifically by Brucella abortus and B. melitensis in cattle and humans, respectively. Arjunolic acid (AA) is a triterpenoid, isolated from Terminalia arjuna (Roxb.) Wight & Arn., a medicinally important plant, used to treat various diseases in the Indian system of medicine. Here, we tried to evaluate AA for its antibacterial activity against Brucella and the in vitro cytotoxicity assay on human lung adenocarcinomic alveolar basal epithelial cell line (A549). Also, we assessed the synergistic effect of arjunolic acid and aquatic extract of Tarenna asiatica (L.) Kuntze ex K.Schum. (syn. Chomelia asiatica) leaves against B. melitensis. AA displayed a considerable antibacterial activity [zone of inhibition (9 mm) with a minimum inhibitory concentration of 30 μg/mL] against B. melitensis. The rate of cell death for the cancer cells was 82% at 100 μg/mL concentration of AA which indicates significant membrane disruption by AA in cancer cells. The estimated IC50 of AA against the A549 cell line was 139.90 μg/mL. The highest synergistic activity was exhibited by combination of arjunolic acid and AqE of T. asiatica at the concentration of 1:1, respectively forming a zone of inhibition measuring 10 mm

Evaluation of arjunolic acid against Brucella melitenis and in vitro cytotoxic studyof lung adenocarcinomic cell line (A549)

Brucellosis, a neglected tropical disease of zoonotic nature, is caused by the genus Brucella, specifically by Brucellaabortus and B. melitensis in cattle and humans, respectively. Arjunolic acid (AA) is a triterpenoid, isolated from Terminaliaarjuna (Roxb.) Wight & Arn., a medicinally important plant used to treat various diseases in the Indian system of medicine.Here, we tried to evaluate AA for its antibacterial activity on Brucella and the in vitro cytotoxicity assay on human lungadenocarcinomic alveolar basal epithelial cell line (A549). Also, we assessed the synergistic effect of arjunolic acid andTarenna asiatica (L.) Kuntze ex K.Schum. on B. melitensis. AA displayed a considerable antibacterial activity [zone ofinhibition (9 mm) with a minimum inhibitory concentration of 30 μg/mL] against B. melitensis. The rate of cell death for thecancer cells were at 100 μg/mL concentration of AA was 82% which indicates that AA shows significant membranedisruption to cancer cells. The estimated IC50 of AA against the A549 cell line was 139.90 μg/mL. The highest synergisticactivity was exhibited forming a zone of inhibition measuring 10mm when arjunolic acid and AqE of T. asiatica was addedin the concentration of 1:1, respectively