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Interplay between telomere length and telomerase in human leukocyte differentiation and aging.

Blood leukocytes derive from bone marrow hematopoietic stem cells and differentiate into multiple types of mature cells that include granulocytes, monocytes, mast cells of myeloid lineage, and T and B lymphocytes of lymphoid lineage. Their distinctive paths of differentiation and unique roles in immune response provide a model for comparative analysis of biological parameters, such as telomere length and telomerase activity, in different types of leukocytes. Age has also been associated with the decline in immune functions and with the attrition of telomere length in leukocytes. This review will summarize recent progress in the study of telomere length and telomerase expression in leukocytes during differentiation and aging. In addition, I will attempt to shed new light on the roles of telomere and telomerase in leukocyte function and potential clinical interventions.

Cell Differentiation↗

Advancing the expectancy concept via the interplay between theory and research.

Four papers from a 2001 Research Society on Alcoholism symposium on expectancy theory and research are summarized. The symposium contributors describe recent advances in expectancy theory and discuss their implications for assessment and for understanding the processes of development and change in the behavioral domain of alcohol use. First, findings are integrated across the diverse domains in which the expectancy concept has been applied. Second, the implications of expectancy theory for the measurement of expectancy structure and process are examined. Third, research and theory regarding alcohol expectancy development and change are presented, with an emphasis on the role of expectancies as mediators of known antecedents of drinking. Finally, an experimental procedure for investigating the causal role of expectancies is described, together with its implications for theory testing and prevention or intervention programming. Collectively, the symposium contributions demonstrate the utility of an integrated expectancy theory for the generation of innovative research operations and new insights regarding behavior development and change. Consistent with the notion of consilience, expectancy theory has demonstrated a convergence of findings across different levels of analysis, as well as across different operations, methods, and research designs.

Alcohol Drinking↗

Transcriptional regulation of vascular endothelial growth factor by estradiol and tamoxifen in breast cancer cells: a complex interplay between estrogen receptors alpha and beta.

Vascular endothelial growth factor (VEGF) is a potent angiogenic and prognostic factor for many tumors, including those of endocrine-responsive tissues such as the breast and uterus. Recent studies indicate that 17beta-estradiol (E(2)) modulates VEGF expression in breast and uterine cells, involving transcriptional activation through estrogen receptor (ER) alpha. However, molecular mechanisms of VEGF regulation mediated by the two ER subtypes and the potential role of ERbeta in the control of breast cancer angiogenesis have not yet been investigated. In transient transfection assays using the VEGF(-2275/+54) promoter-luciferase construct, E(2) (1 nM) increased transcription activity in MCF-7 cells (either untransfected or cotransfected with ERalpha) and it increased transcription activity in MDA-MB-231 cells cotransfected with ERalpha or ERbeta (1.8- and 2-fold induction, respectively). The positive effect was abolished when MCF-7 cells were treated with pure antiestrogen ICI 182,780 or the agonist/antagonist tamoxifen (1 micro M). To identify response elements involved in this transcriptional regulation, MCF-7 or MDA-MB-231 cells were transfected with several deletion constructs of the VEGF promoter. Deletion of 1.2-2.3 kb upstream to the transcription start in the VEGF promoter abrogated E(2)-dependent transcription in these cells. This region contains an imperfect estrogen-responsive element (ERE), ERE1520, and one activator protein 1 site. Transfection of MCF-7 cells (ERalpha) with the ERE1520-luciferase construct conferred transcriptional activity with 1 nM E(2) (1.9-fold induction). Also, the imperfect ERE formed a complex with ERalpha or ERbeta proteins in gel shift assay using MCF-7 or MDA-MB-231 nuclear extracts. In contrast to ERalpha, ERbeta could transactivate VEGF reporter construct in MDA-MB-231 cells, in the presence of E(2) or tamoxifen, suggesting different transactivational mechanisms between ERalpha and ERbeta in the presence of tamoxifen. Interestingly, E(2) inhibited VEGF transcription in MCF-7 cells transfected with ERbeta or MDA-MB-231 cells cotransfected with ERalpha and ERbeta, suggesting that heterodimerization of ERalpha/ERbeta has the ability to inhibit E(2)-induced VEGF expression in breast cancer cells. These results demonstrate that VEGF is a target gene for ERalpha and ERbeta in breast cancer cells; it remains to be determined whether ERalpha and ERbeta expression in breast biopsies correlates with VEGF expression and vascular density.

Breast Neoplasms↗

Toward a reconciliation of "assimilation" and "pluralism": the interplay of acculturation and ethnic retention.

"The reconciliation between ¿assimilation' and ¿pluralism' is sought to help prevent further polarization among immigration researchers and is based mainly on two arguments. First, if assimilation and acculturation are distinguished, acculturation has proceeded more quickly than assimilation in both ¿old' and ¿new' immigrations. This reconciles traditional assimilationist theory with current pluralist--or ethnic retention--theory, which admits that acculturation (and accommodation) are occurring but without assimilation. Second, the reconciliation can also be advanced by the recognition that the researchers of the old and new immigrations have studied different generations of newcomers and have approached their research with ¿outsider' and ¿insider' values, respectively." The geographical focus is on the United States.

Acculturation↗

Interplay between the molecular signals that control vertebrate limb development.

Vertebrate limbs display three obvious axes of asymmetry. These three axes are referred to as proximal-distal (Pr-D; shoulder to digit tips), anterior-posterior (A-P; thumb to little finger), and dorsal-ventral (D-V; back of hand to palm). At a molecular level, it is now possible to define the signals that control patterning of each of the three axes of the developing limb. These signals do not work in isolation though but rather their activity must be integrated such that the various limb elements are coordinately formed with relation to these three axes. This review will provide an overview of the intricate medley amongst the molecular signals that serve to establish and coordinate patterning information along the three primary axes of the limb.

Animals↗