The galectin family of lectins regulates multiple biologic functions, such as development, inflammation, immunity, and cancer. One common function of several galectins is the ability to trigger T cell death. However, differences among the death pathways triggered by various galectins with regard to glycoprotein receptors, intracellular death pathways, and target cell specificity are not well understood. Specifically, galectin-9 and galectin-1 both kill thymocytes, peripheral T cells, and T cell lines; however, we have found that galectin-9 and galectin-1 require different glycan ligands and glycoprotein receptors to trigger T cell death. The two galectins also utilize different intracellular death pathways, as galectin-9, but not galectin-1, T cell death was blocked by intracellular Bcl-2, whereas galectin-1, but not galectin-9, T cell death was blocked by intracellular galectin-3. Target cell susceptibility also differed between the two galectins, as galectin-9 and galectin-1 killed different subsets of murine thymocytes. To define structural features responsible for distinct activities of the tandem repeat galectin-9 and dimeric galectin-1, we created a series of bivalent constructs with galectin-9 and galectin-1 carbohydrate recognition domains connected by different peptide linkers. We found that the N-terminal carbohydrate recognition domain and linker peptide contributed to the potency of these constructs. However, we found that the C-terminal carbohydrate recognition domain was the primary determinant of receptor recognition, death pathway signaling, and target cell susceptibility. Thus, carbohydrate recognition domain specificity, presentation, and valency make distinct contributions to the specific effects of different galectins in initiating T cell death.Cell death is an essential factor in T cell development, which regulates selection of functional T cells during development in the thymus, as well as elimination of activated T cells after microbial infection or other exposure to antigen (1, 2). A number of distinct T cell death pathways have been described, including those triggered by members of the galectin family of vertebrate lectins (3-5). Galectin-1 was the first family member described to induce death of developing thymocytes and activated peripheral T cells, and the galectin-1 T cell death pathway is the best characterized to date. Specific glycoprotein receptors involved in galectin-1 death and specific types of O-and N-glycan ligands required for galectin-1 death have been identified, and galectin-1 has been shown to trigger a novel intracellular death pathway (6 -14). Other galectins have also been reported to trigger death of T cell lines and various T cell subsets, including galectin-2, galectin-3, galectin-8, and galectin-9 (15-19). Relatively little is known about the glycoprotein receptors, glycan ligands, and intracellular death pathways used by these galectins. However, our laboratory has found that galectin-1 and galectin-3 kill different subsets of thymocytes, and use distinct sets...

Aims-Prior studies find that stress contributes to problem drinking while social support can buffer its effects. However, these studies are largely confined to middle class and general populations. We extend what is known by examining how the unique stressors and forms of social support experienced by women in poverty impact alcohol problems over a 4-year time period.Design and Participants-This prospective study used GEE transition modeling and 4 annual waves of survey data from 392 American mothers receiving Temporary Assistance for Needy Families (TANF) in a large Northern California county.Measurements-We examined the effects of neighborhood disorder, stressful life events and economic hardship on psychological distress and problem drinking over time, and whether social support moderated these relationships for women in poverty.Findings-Neighborhood disorder and stressful life events significantly increased the risk for problem drinking, largely through their effect on psychological distress. We found little evidence, however, that social support buffers poor women from the effects of these stressors.Conclusions-Women in poverty are exposed to severe, chronic stressors within their communities and immediate social networks which increase vulnerability to psychological distress and problem drinking. The finding that social support does not buffer stress among these women may reflect their high level of exposure to stressors, as well as the hardships and scarce resources within their networks. If the "private safety net" of the social network fails to provide a strong buffer, more effective environmental interventions that reduce exposure to stressors may be needed to prevent alcohol problems in poor women's lives. KeywordsPoverty; women; alcohol problems; stress; social support There is a long tradition of research addressing the role of stress in alcohol problems. On the whole, researchers report significant associations between stress and alcohol use and problems, and that this relationship is partly influenced by social resources for managing stress [1][2][3][4]. While some studies find that moderate drinking is associated with reduced stress [5][6][7] NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript excessive drinking and alcohol problems have been linked to elevated stress-especially chronic stress-and to psychological distress [1,[8][9][10]. Social support, a resource widely studied in relation to stress and health, has been shown to play a role in problem drinking through its direct associations with anxiety, depression and distress [11,12]. It has also been found to promote positive coping responses to stress [13], and to improve treatment retention and recovery from alcohol problems [14][15][16]. Still other studies document a stress-buffering role for social support [17] -that the impact of stressors on alcohol consumption can be reduced in the presence of high levels of support [2,4]-although this finding is not uniformly born out in the literature (see: [9,18]).Mo...

Passing medical marijuana laws does not seem to directly affect the views of young people in medical marijuana states. However, there is a national trend toward young people taking more permissive views about marijuana independent of any effects within states.