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S G Roy

Publications and source records attributed to S G Roy.

10 recordsLinked to original sources

Regulation of alpha-smooth muscle actin gene expression in myofibroblast differentiation from rat lung fibroblasts.

Myofibroblasts express alpha-smooth muscle actin and have a phenotype intermediate between fibroblasts and smooth muscle cells. Their emergence can be induced by cytokines such as transforming growth factor beta; but the regulatory mechanism for induction of alpha-smooth muscle actin gene expression in myofibroblast differentiation has not been determined. To examine this mechanism at the level of the alpha-smooth muscle actin promoter, rat lung fibroblasts were transfected with varying lengths of the alpha-smooth muscle actin promoter linked to the chloramphenicol acetyl transferase reporter gene and treated with transforming growth factor beta1. The results show that the shortest inducible promoter was 150 base pairs long, suggesting the presence in this region of cis-elements of potential importance in transforming growth factor beta1 induced myofibroblast differentiation. Transfection of "decoy" oligonucleotides corresponding to sequences for four suspected regulatory factors demonstrated that only the transforming growth factor beta control element is involved in the regulation of transforming growth factor beta1-induced alpha-smooth muscle actin expression in myofibroblast differentiation. Consistent with this conclusion is the finding that a mutation in the transforming growth factor beta control element caused a significant reduction in promoter activity. These observations taken together show that alpha-smooth muscle actin promoter regulation during myofibroblast differentiation is uniquely different from that in smooth muscle cells and other cell lines. Since myofibroblasts play a key role in wound contraction and synthesis of extracellular matrix, clarification of this differentiation mechanism should provide new insight into fibrogenesis and suggest future novel strategies for modulation of wound healing and controlling fibrosis.

Actins↗

Regulation of beta-catenin levels and localization by overexpression of plakoglobin and inhibition of the ubiquitin-proteasome system.

beta-Catenin and plakoglobin (gamma-catenin) are closely related molecules of the armadillo family of proteins. They are localized at the submembrane plaques of cell-cell adherens junctions where they form independent complexes with classical cadherins and alpha-catenin to establish the link with the actin cytoskeleton. Plakoglobin is also found in a complex with desmosomal cadherins and is involved in anchoring intermediate filaments to desmosomal plaques. In addition to their role in junctional assembly, beta-catenin has been shown to play an essential role in signal transduction by the Wnt pathway that results in its translocation into the nucleus. To study the relationship between plakoglobin expression and the level of beta-catenin, and the localization of these proteins in the same cell, we employed two different tumor cell lines that express N-cadherin, and alpha- and beta-catenin, but no plakoglobin or desmosomal components. Individual clones expressing various levels of plakoglobin were established by stable transfection. Plakoglobin overexpression resulted in a dose-dependent decrease in the level of beta-catenin in each clone. Induction of plakoglobin expression increased the turnover of beta-catenin without affecting RNA levels, suggesting posttranslational regulation of beta-catenin. In plakoglobin overexpressing cells, both beta-catenin and plakoglobin were localized at cell-cell junctions. Stable transfection of mutant plakoglobin molecules showed that deletion of the N-cadherin binding domain, but not the alpha-catenin binding domain, abolished beta-catenin downregulation. Inhibition of the ubiquitin-proteasome pathway in plakoglobin overexpressing cells blocked the decrease in beta-catenin levels and resulted in accumulation of both beta-catenin and plakoglobin in the nucleus. These results suggest that (a) plakoglobin substitutes effectively with beta-catenin for association with N-cadherin in adherens junctions, (b) extrajunctional beta-catenin is rapidly degraded by the proteasome-ubiquitin system but, (c) excess beta-catenin and plakoglobin translocate into the nucleus.

3T3 Cells↗

Role of stress fibers in the association of intermediate filaments with microtubules in fibroblast cells.

The association between intermediate filaments (IF) and microtubules (MT) has been demonstrated by several experiments using MT inhibitors and by microinjecting specific antibodies. The actin cytoskeleton has recently been assigned a role in this process of drug induced IF collapse. However, this was not found to be true in large cells with irregular morphology. For instance, in early passage diploid fibroblasts of human origin and in armadillo cell lines, where the cells are large, irregular in shape and exhibit prominent stress fibers (SF), depolymerization of MT with nocodazole did not lead to collapse of IF. Instead, the IF formed bundles of coils that seemed to associate with the SF. Disintegration of the SF with cytochalasin B led to the collapse of the IF. It appears that the actin organization in such large cells with extensive SF, is not as contractile as in typical spindle shaped fibroblasts which have relatively less stable actin organization. The stable SF may actually prevent IF collapse.

Actin Cytoskeleton↗

Regulation of cytoplasmic microtubule complex organisation in somatic cell hybrids.

Regulation of cytoplasmic microtubule complex (CMTC) organization was studied in cultured human fibroblasts and mouse macrophages by somatic cell fusion. The heterokaryons stained with antitubulin antibody had fibroblast-like CMTC even 72 hours after fusion. There was no change in CMTC pattern when more than one macrophage had fused with one fibroblast. However, the macrophage CMTC was expressed in heterokaryons when the former were located at the periphery of the heterokaryon. To evaluate the role of existing CMTC in determining the CMTC of heterokaryons, the heterokaryons were treated with nocodazole to depolymerize the CMTC and then allowed to recover. The resultant CMTC was fibroblast like.

Animals↗

Reconstruction of Indian life tables for 1901-1981 and projections for 1981-2001.

"An attempt has been made to reconstruct life tables for India from 1901-11 to 1971-81 and to project for the decades 1981-91 and 1991-2001 by adopting a Brass relational model. The earlier actuarial life tables seem to have been based on a British model of sex differentials in mortality leading to higher life expectancies for females--not in tune with Indian experience. Consistency has been attained in this study by taking recourse to mortality patterns obtained from the Sample Registration System."

Asia↗

Estimating child mortality and modelling its age pattern for India.

"Using data [for India] on proportions of children dead...estimates of infant and child mortality are...obtained by Sullivan and Trussell modifications of [the] Brass basic method. The estimate of child survivorship function derived after logit smoothing appears to be more reliable than that obtained by the Census Actuary. The age pattern of childhood mortality is suitably modelled by [a] Weibull function defining the probability of surviving from birth to a specified age and involving two parameters of level and shape. A recently developed linearization procedure based on [a] graphical approach is adopted for estimating the parameters of the function."

Age Factors↗

Demography of sterilization: Indian experience.

Using program statistics and a few local studies, the paper examines the prevalence of sterilization in India and makes demographic analysis of the performance. Major points of note are that the prevalence rates expressed in terms of currently married women showed irregular fluctuations across time and the age pattern of acceptance hardly agreed with that of the married population. The selectivity of high fertility couples for sterilization had been fairly high, resulting in a low fertility impact. Estimates of births averted due to the program were derived by using a computerized microsimulation model CONVERSE. It appears that the path of fertility changes was not smooth in the last decade and the impact has been, as a rule, greatest 2 years after acceptance.

Age Factors↗

Developing model schedules of female proportions single for India.

The Indian Census provides marital status data cross classified by sex and age. There are, however, several limitations in the general state of information and the quality of data on marital status. For instance, the ratios proportions single in corresponding age groups in 2 consecutive censuses have been found to exceed unity in the absence of any significant migration. In the present study, the authors adjust the the schedules of proportions single for 1901-1971 with a logit linear model. In spite of the serious nature of errors in the data, the model appears to work well. In assessing its quality, the technique is applied to more accurate Japanese data, and found to have an extremely good fit. A comparison with the Coale-McNeil nuptiality model reveals that for the Indian situation the logit model may be more appropriate.

Asia↗