Abberent expression analysis of LMNA gene in hutchinson-gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is caused by de novo dominant point mutations of the genes encoding nuclear lamina proteins, leading towards premature aging. A protein sequence is subjected to mutations in nature which can affect the function and folding pattern of the protein by different ways. Mutations involved in HGPS were identified and were substituted in the seed sequence retrieved from the UniProt database to get the mutated versions. Tertiary structure of the Lamin A protein was previously unpredicted so was performed for all the mutated as well as for the seed protein to analyze the effects of mutations on the protein structure, folding and interactions. All the predicted models were refined and validated through multiple servers for multiple parameters. The validated 3D structure of seed protein was then successfully submitted to the Protein Model Database and was assigned with the PMDB ID PM0077829. All the predicted structures were superimposed with a root mean square deviation value of 7.0 Å and a high Dali Z-score of 1.9. It was observed that mutations affected physiochemical properties as well as instability index and thus is affecting the domains in specific and the whole structure in general. It was further analyzed that HGPS is the result of affected Lamin a protein interactions with other integral and binding proteins in the inner nuclear membrane affecting the link in between the nuclear membrane and the network of the lamina

In Silico Characterization of Genetic Alterations Associated with Mal De Meleda

Mal de Meleda (MDM) is an autosomal recessive skin disorder majorly caused by mutations in the ARS gene encoding SLURP-1 protein secreted by Keratinocytes. A number of genetic alterations have already been reported in SLURP1 associated with MDM, theoretically proposed to affect the integrity of the downstream product. There are a no reports available to the best of our knowledge, which characterize the effect of respective mutations at the protein structural level, which is the focus of this study. The protein sequence of SLURP1 was obtained from the UniProt database and the disease associated alterations were retrieved and mined from the literature resources. Domain analysis showed that the protein belongs to the Ly6/uPAR superfamily, has antitumor activity and is also a marker of late skin differentiation. Complete tertiary structure of SLURP1 was predicted as shown in figure 4, for further structural analysis as was not previously determined and was submitted to the PMDB after systematic evaluation and validation (PMDB ID: PM0077826). Structural abnormalities in the protein due to mutations were explored through comparative structural analysis along with interspecies conservation of the respective residue through phylogenetic analysis. It is expected that this systematic structural analysis will enhance our understanding about the disease mechanism and will also help to develop better diagnosis and designing treatment strategies in the near future against MDM and other relevant disorders

Assessing performance of the Healthcare Access and Quality Index, overall and by select age groups, for 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019

Health-care needs change throughout the life course. It is thus crucial to assess whether health systems provide access to quality health care for all ages. W measured the Healthcare Access and Quality (HAQ) Index overall and for select age groups in 204 locations from 1990 to 2019. For GBD 2019, HAQ Index construction methods were updated to use the arithmetic mean of scaled mortality-to-incidence ratios (MIRs) and risk-standardised death rates (RSDRs) for 32 causes of death that should not occur in the presence of timely, quality health care. Across locations and years, MIRs and RSDRs were scaled from 0 (worst) to 100 (best) separately, putting the HAQ Index on a different relative scale for each age group. We estimated absolute convergence for each group on the basis of whether the HAQ Index grew faster in absolute terms between 1990 and 2019 in countries with lower 1990 HAQ Index scores than countries with higher 1990 HAQ Index scores and by Socio-demographic Index (SDI) quintile. Interpretation Although major gaps remain across levels of social and economic development, convergence in the young group is an encouraging sign of reduced disparities in health-care access and quality. However, divergence in the working and post-working groups indicates that health-care access and quality is lagging at lower levels of social and economic development. To meet the needs of ageing populations, health systems need to improve health-care access and quality for working-age adults and older populations while continuing to realise gains among the young