Estimativa da taxa de pico de fluxo expiratório em jovens indianos / Estimation of peak expiratory flow rate in young Indians

INTRODUÇÃO: O pico de fluxo expiratório (PFE) é comumente usado para monitorar a progressão de doenças respiratórias, pois fornece boas informações sobre o estado das vias aéreas. Uma boa quantidade de pesquisas está sendo feita em todo o mundo para estabelecer uma equação de previsão local. A força-tarefa conjunta da Sociedade Torácica Americana e da Sociedade Respiratória Europeia promoveu pesquisas a esse respeito. Na Índia, os dados derivados da população caucasiana ainda são usados para o PFE. OBJETIVO: Estudar a relação dos parâmetros do PFE e os dados antropométricos como idade, altura, peso, índice de massa corporal (IMC), área de superfície corporal (ASC) e estabelecer uma equação de regressão para jovens adultos indianos. MÉTODOS: PFE foi feito em 1000 sujeitos de 15-25 anos da região metropolitana de Mumbai. O coeficiente de correlação de Pearson foi usado para entender a relação dos parâmetros antropométricos e PFE. A análise de regressão multivariada foi feita para estabelecer uma equação de predição. (Alfa 5%) RESULTADOS: Idade e todos os parâmetros antropométricos foram correlacionados com PFE. O pico de fluxo expiratório médio da população masculina foi de 515 ml / seg, enquanto a feminina foi de 399 ml / seg. Para o PFE, a maior correlação foi observada com a ASC seguida de altura, peso e idade, enquanto o IMC apresentou o menor coeficiente de correlação. TPFE teve a melhor significância com a idade, ASC, altura e IMC. Teve menos significado com o peso. No sexo feminino, a TPFE teve a melhor significância com altura, peso, IMC e idade. CONCLUSÃO: Existem diferenças de gênero na TPFE. Portanto, equações específicas de gênero são necessárias para a estimativa da TPFE

INTRODUCTION: Peak expiratory flow rate (PEFR) is commonly used to monitor the progression of respiratory diseases as it gives good information about the status of airways. A good amount of research is going across the world to establish a local prediction equation. The joint task force of the American thoracic society and European Respiratory Society has promoted research in this regard. In India, data derived from the Caucasian population are still used for PEFR. OBJECTIVE: To verify the relationship between PEF levels and the variables age, sex, anthropometric and body surface area, and establish the regression equation for young Indian adults. METHODS: A cross-sectional observational study was conducted in 15-25 years aged 1000 subjects from the Metropolitan region of Mumbai. Pearson's correlation coefficient was used to understand the relation of anthropometric parameters and PEFR. Multivariate regression analysis was done for establishing a prediction equation (Alpha 5%). RESULTS: Age and all anthropometric parameters were correlated with PEFR. The mean PEFR of the male population was 515 ml/sec, whereas, for females, it was 399 ml/sec, for PEFR highest correlation was observed with BSA (.696) followed by weight (.667), height (.630), age (.504) whereas BMI shown lowest correlation coefficient (.445). PEFR had the best significance with age, BSA, Height, and BMI. It had less significance with weight. In females, PEFR had the best significance with Height, weight, BMI, and Age. CONCLUSION: Gender-wise differences exist in PEFR. Hence gender-specific equations are needed for the estimation of PEFR.

14-3-3γ Prevents Centrosome Amplification and Neoplastic Progression.

More than 80% of malignant tumors show centrosome amplification and clustering. Centrosome amplification results from aberrations in the centrosome duplication cycle, which is strictly coordinated with DNA-replication-cycle. However, the relationship between cell-cycle regulators and centrosome duplicating factors is not well understood. This report demonstrates that 14-3-3γ localizes to the centrosome and 14-3-3γ loss leads to centrosome amplification. Loss of 14-3-3γ results in the phosphorylation of NPM1 at Thr-199, causing early centriole disjunction and centrosome hyper-duplication. The centrosome amplification led to aneuploidy and increased tumor formation in mice. Importantly, an increase in passage of the 14-3-3γ-knockdown cells led to an increase in the number of cells containing clustered centrosomes leading to the generation of pseudo-bipolar spindles. The increase in pseudo-bipolar spindles was reversed and an increase in the number of multi-polar spindles was observed upon expression of a constitutively active 14-3-3-binding-defective-mutant of cdc25C (S216A) in the 14-3-3γ knockdown cells. The increase in multi-polar spindle formation was associated with decreased cell viability and a decrease in tumor growth. Our findings uncover the molecular basis of regulation of centrosome duplication by 14-3-3γ and inhibition of tumor growth by premature activation of the mitotic program and the disruption of centrosome clustering.

14-3-3γ-Mediated transport of plakoglobin to the cell border is required for the initiation of desmosome assembly in vitro and in vivo.

The regulation of cell-cell adhesion is important for the processes of tissue formation and morphogenesis. Here, we report that loss of 14-3-3γ leads to a decrease in cell-cell adhesion and a defect in the transport of plakoglobin and other desmosomal proteins to the cell border in HCT116 cells and cells of the mouse testis. 14-3-3γ binds to plakoglobin in a PKCµ-dependent fashion, resulting in microtubule-dependent transport of plakoglobin to cell borders. Transport of plakoglobin to the border is dependent on the KIF5B-KLC1 complex. Knockdown of KIF5B in HCT116 cells, or in the mouse testis, results in a phenotype similar to that observed upon 14-3-3γ knockdown. Our results suggest that loss of 14-3-3γ leads to decreased desmosome formation and a decrease in cell-cell adhesion in vitro, and in the mouse testis in vivo, leading to defects in testis organization and spermatogenesis.

Generation of HIV-1 based bi-cistronic lentiviral vectors for stable gene expression and live cell imaging.

The study of protein-protein interactions, protein localization, protein organization into higher order structures and organelle dynamics in live cells, has greatly enhanced the understanding of various cellular processes. Live cell imaging experiments employ plasmid or viral vectors to express the protein/proteins of interest fused to a fluorescent protein. Unlike plasmid vectors, lentiviral vectors can be introduced into both dividing and non dividing cells, can be pseudotyped to infect a broad or narrow range of cells, and can be used to generate transgenic animals. However, the currently available lentiviral vectors are limited by the choice of fluorescent protein tag, choice of restriction enzyme sites in the Multiple Cloning Sites (MCS) and promoter choice for gene expression. In this report, HIV-1 based bi-cistronic lentiviral vectors have been generated that drive the expression of multiple fluorescent tags (EGFP, mCherry, ECFP, EYFP and dsRed), using two different promoters. The presence of a unique MCS with multiple restriction sites allows the generation of fusion proteins with the fluorescent tag of choice, allowing analysis of multiple fusion proteins in live cell imaging experiments. These novel lentiviral vectors are improved delivery vehicles for gene transfer applications and are important tools for live cell imaging in vivo.