Mechanisms of Arsenic Detoxification and Resistance

Arsenic is a ubiquitous environmental toxic substance. As a consequence of continual exposure to arsenic, nearly every organism, from Escherichia coli to humans have evolved arsenic detoxification pathways. One of the pathways is extrusion of arsenic from inside the cells, thereby conferring resistance. The R773 arsRDABC operon in E. coli encodes an ArsAB efflux pump that confers resistance to arsenite. ArsA is the catalytic subunit of the pump, while ArsB forms the oxyanion conducting pathway. ArsD is an arsenite metallochaperone that binds arsenite and transfers it to ArsA. The interaction of ArsA and ArsD allows for resistance to As(III) at environmental concentrations. The interaction between ArsA ATPase and ArsD metallochaperone was examined. A quadruple mutant in the arsD gene encoding a K2A/K37A/K62A/K104A ArsD is unable to interact with ArsA. An error-prone mutagenesis approach was used to generate random mutations in the arsA gene that restored interaction with the quadruple arsD mutant in yeast two-hybrid assays. Three such mutants encoding Q56R, F120I and D137V ArsA were able to restore interaction with the quadruple ArsD mutant. Structural models generated by in silico docking suggest that an electrostatic interface favors reversible interaction between ArsA and ArsD. Mutations in ArsA that propagate changes in hydrogen bonding and salt bridges to the ArsA-ArsD interface also affect their interactions. The second objective was to examine the mechanism of arsenite resistance through methylation and subsequent volatilization. Microbial ArsM (As(III) S-adenosylmethyltransferase) catalyzes the formation of trimethylarsine as the volatile end product. The net result is loss of arsenic from cells. The gene for CrArsM from the eukaryotic green alga Chlamydomonas reinhardtii was chemically synthesized and expressed in E. coli. The purified protein catalyzed the methylation of arsenite into methyl-, dimethyl- and trimethyl products. Synthetic purified CrArsM was crystallized in an unliganded form. Biochemical and biophysical studies conducted on CrArsM sheds new light on the pathways of biomethylation. While in microbes ArsM detoxifies arsenic, the human homolog, hAS3MT, converts inorganic arsenic into more toxic and carcinogenic forms. An understanding of the enzymatic mechanism of ArsM will be critical in deciphering its parallel roles in arsenic detoxification and carcinogenesis.

Using structural equation modeling to assess two theoretical models that explain dropout

This study evaluated the relative fit of both Finn's (1989) Participation-Identification and Wehlage, Rutter, Smith, Lesko and Fernandez's (1989) School Membership models of high school completion to a sample of 4,597 eighth graders taken from the National Educational Longitudinal Study of 1988, (NELS:88), utilizing structural equation modeling techniques. This study found support for the importance of educational engagement as a factor in understanding academic achievement. The Participation-Identification model was particularly well fitting when applied to the sample of high school completers, dropouts (both overall and White dropouts) and African-American students. This study also confirmed the contribution of school environmental factors (i.e., size, diversity of economic and ethnic status among students) and family resources (i.e., availability of learning resources in the home and parent educational level) to students' educational engagement. Based on these findings, school social workers will need to be more attentive to utilizing macro-level interventions (i.e., community organization, interagency coordination) to achieve the organizational restructuring needed to address future challenges. The support found for the Participation-Identification model supports a shift in school social workers' attention from reactive attempts to improve the affective-interpersonal lives of students to proactive attention to their academic lives. The model concentrates school social work practices on the central mission of schools, which is educational engagement. School social workers guided by this model would be encouraged to seek changes in school policies and organization that would facilitate educational engagement. ^

Influence of religious coping on the substance use and HIV risk behaviors of recent Latino immigrants

This study examines the influence of acculturative stress on substance use and HIV risk behaviors among recent Latino immigrants. The central hypothesis of the study is that specific religious coping mechanisms influence the relationship that acculturative stress has on the substance use and HIV-risk behaviors of recent Latino immigrants. Within the Latino culture religiosity is a pervasive force, guiding attitudes, behaviors, and even social interactions. When controlling for education and socioeconomic status, Latinos have been found to use religious coping mechanisms more frequently than their Non-Latino White counterparts. In addition, less acculturated Latinos use religious coping strategies more frequently than those with higher levels of acculturation. Given its prominent role in Latino culture, it appears probable that this mechanism may prove to be influential during difficult life transitions, such as those experienced during the immigration process. This study examines the moderating influence of specific religious coping mechanisms on the relationship between acculturative stress and substance use/HIV risk behaviors of recent Latino immigrants. Analyses for the present study were conducted with wave 2 data from an ongoing longitudinal study investigating associations between pre-immigration factors and health behavior trajectories of recent Latino immigrants. Structural equation and zero-inflated Poisson modeling were implemented to test the specified models and examine the nature of the relationship among the variables. Moderating effects were found for negative religious coping. Higher levels of negative religious coping strengthened an inverse relationship between acculturative stress and substance use. Results also indicated direct relationships between religious coping mechanisms and substance use. External and positive religious coping were inversely related to substance use. Negative religious coping was positively related to substance use. This study aims to contribute knowledge of how religious coping influence's the adaptation process of recent Latino immigrants. Expanding scientific understanding as to the function and effect of these coping mechanisms could lead to enhanced culturally relevant approaches in service delivery among Latino populations. Furthermore this knowledge could inform research about specific cognitions and behaviors that need to be targeted in prevention and treatment programs with this population.