Fascin,an actin-bundling protein,modulates colonic epithelial cell invasiveness and differentiation in vitro

In epithelial tissue, cell-matrix and cell-cell adhesive interactions have important roles in the normal organization and stabilization of the cell layer. The malignant conversion of epithelial cells involves alterations in the expression and function of these adhesion systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Fascin is an actin-crosslinking protein that is found in the core actin bundles of cell-surface spikes and projections that are implicated in cell motility. We demonstrate that fascin is not detectable in normal colonic epithelium, but is dramatically up-regulated in colorectal adenocarcinoma. To test the hypothesis that fascin could participate in tumor invasive behavior, we developed a cell culture model to examine the effect of fascin expression on the adhesive interactions, invasiveness, and differentiation of colonic epithelial cells. We report marked effects on the organization of cell-surface protrusions, actin cytoskeleton, and focal adhesions in the absence of alterations in the protein levels of the major components of these structures. These effects correlate with alterations in cell movements on two-dimensional matrix, and increased invasiveness in three-dimensional matrix. The cells also show increased proliferation and decreased capacity for normal glandular differentiation in collagen gels. We propose that up-regulation of fascin, by promoting the formation of protrusive, actin-based, cell-motility structures, could be a significant component in the acquisition of invasive phenotype in colonic carcinoma.     

TGF-beta signaling regulates CD8+ T cell responses to high- and low-affinity TCR interactions

Absence of transforming growth factor-beta (TGF-beta) signaling to T cells in mice results in an increase in T cell numbers, an activated CD44 high, CD69-, CD25- T cell phenotype and a T cell-mediated injury to many organs. It is not known if such T cell activation in the absence of TGF-beta signaling is spontaneous or due to aberrant T cell responses to a physiological stimulus. We used adoptive transfer of CD8+ T cells from mice double transgenic for the OT-1 TCR and the TGF-beta1-dominant negative transgene [OT-dominant-negative receptor (DNR)] to investigate the role of TGF-beta in regulating CD8+ T cell activation in vivo. The activation and expansion of single-transgenic OT and double-transgenic OT-DNR cells to oral antigens, high-affinity and low-affinity peptides were indistinguishable. Activation with high-affinity peptide and CFA however resulted in greater expansion of OT-DNR cells in comparison to OT cells. Low-affinity peptide and adjuvant did not result in OT cell activation or expansion but results in up-regulation of CD44 on OT-DNR cells. These data show that TGF-beta functions in vivo to limit the scale of CD8+ T cell expansion after high-affinity peptide-MHC interactions. TGF-beta also limits T cell activation to the highest affinity peptide-MHC interactions. The increase in T cell number and activation present in TGF-beta-deficient and TGF-beta DNR-expressing mice may be due to the loss of these two phenomena.     

Beyond Food Promotion: A Systematic Review on the Influence of the Food Industry on Obesity-Related Dietary Behaviour among Children

An increased consumption of energy-dense, nutrient-poor food and beverages as a result of a changing obesogenic environment contributes substantially to the increasing prevalence of childhood overweight and obesity. This paper reviews the nature and extent of food industry influences which expose children to commercial influences and thus might affect unhealthy dietary behaviour and finally contributes to obesity. A systematic search of nine electronic databases (including PubMed, PsycINFO, EconLit) and reference lists of original studies and reviews using key search terms identified 1900 articles. Of these only thirty-six articles met the inclusion and quality criteria. A narrative synthesis of the reviewed studies revealed six key obesogenic environments by which the food industry possibly influences obesity-related dietary behaviours in young children. These were schools, retailers, mass media “television”, mass media “internet”, home and promotional campaigns. Identifying these obesogenic environments is critical for monitoring and controlling the food industry, the development of effective environmental-level interventions to prevent childhood overweight and obesity and to identify knowledge gaps to be addressed in future research to support informed decisions of policy makers.     

Stroke and aphasia quality of life scale in Kannada-evaluation of reliability,validity and internal consistency

Background:

Quality of life (QoL) dwells in a person''s overall well-being. Recently, QoL measures have become critical and relevant in stroke survivors. Instruments measuring QoL of individuals with aphasia are apparently rare in the Indian context. The present study aimed to develop a Kannada instrument to measure the QoL of people with aphasia. Study objectives were to validate Stroke and aphasia quality of life-39 (SAQOL-39) into Kannada, to measure test–retest reliability and internal consistency.

Materials and Methods:

The original English instrument was modified considering socio-cultural differences among native English and Kannada speakers. Cross-linguistic adaptation of SAQOL-39 into Kannada was carried out through forward–backward translation scheme. The scale was administered on 32 people from Karnataka (a state in India) having aphasia. For a direct understanding of the subject''s QoL, scores were categorized into QoL severity levels. Item reliability of the Kannada version was examined by measuring Cronbach''s alpha. Test–retest reliability was examined by calculating the intraclass correlation coefficient (ICC).

Results:

Kannada SAQOL-39 showed good acceptability with minimum missing data and excellent test–retest reliability (ICC = 0.8). Value of Cronbach''s α observed for four items modified in the original version was 0.9 each and the mean α of all Kannada items was 0.9, demonstrating high internal consistency.

Conclusions:

The present study offers a valid, reliable tool to measure QoL in Kannada-speaking individuals with aphasia. This tool is useful in a cross-center, cross-national comparison of QoL data from people with aphasia. This instrument also permits direct translation into other Indian languages as the items are culturally validated to the Indian population. This study promotes future research using the Kannada SAQOL-39.