Intestinal Growth and in Vitro Transport of Glucose in the Rapidly Growing Rat

Author Institution: National Institute for Occupational Safety and Health ; Department of Physiology, Marshall University School of MedicineWe examined the in vitro transport and utilization of glucose by the intestinal epithelium in rats during the period of rapid growth between 8 and 12 weeks of age. The dry weight per centimeter in length of jejunum increased in direct proportion to body weight during this interval. The absorption of glucose at the mucosal surface (per unit length of gut) did not change with growth. In contrast, the serosal secretion of glucose decreased indicating the utilization of glucose was elevated. It was further shown that the increase in glucose usage was highly correlated with the increase in intestinal dry weight that occurred during the four week interval. The data indicate the increase in intestinal tissue with growth did not result in a corresponding increase in the capacity of the intestinal epithelium to absorb glucose. We attributed the discrepancy in the transport of glucose at the mucosal and serosal surfaces to increased diversion of absorbed glucose for metabolism by intestinal tissue

Molecular Mechanisms of Homolog-Independent DNA Repair During C. Elegans Meiosis

Meiosis is the specialized cell division by which most sexually reproducing organisms generate haploid gametes such as sperm and eggs. Meiotic cells of diploid organisms contain four copies of the genome: two homologous chromosomes as well as identical replicates of each homolog called sister chromatids. Although DNA damage threatens genomic stability, meiotic cells intentionally induce DNA double-strand breaks (DSBs) across the genome. Most studies of meiotic DSB repair have focused on how a limited subset of DSBs are resolved with the homologous chromosome as crossovers, which are required for accurate meiotic chromosome segregation. The remaining DSBs that are not repaired with the homologous chromosome have been long hypothesized in metazoans to be repaired using the sister chromatid. The perfect identity shared by sister chromatids, however, has precluded testing of this model by sequencing approaches. To directly detect the long-hypothesized homolog-independent recombination events during metazoan meiosis, I developed an ‘intersister/intrachromatid repair assay’ (ICR assay) in the nematode Caenorhabditis elegans which enables the direct detection of homolog-independent crossover and noncrossover recombination during meiosis. Using the ICR assay, I demonstrate that the sister chromatid or same DNA molecule can indeed be engaged to repair DSBs as crossovers or noncrossovers, and that intersister/intrachromatid repair is the sole recombination pathway utilized in late meiotic prophase I. Additionally, using the ICR assay in conjunction with cytological and functional DSB repair assays, I show that the highly conserved structural maintenance of chromosomes 5/6 complex (SMC-5/6) and tumor suppressor BRCA1 (BRC-1) restrict intersister crossover recombination and error-prone repair during meiotic prophase I. Finally, I investigated how meiotic DNA repair is impacted during germline aging. Utilizing a computational image analysis pipeline I developed, I find that sperm depletion causes reduced DSB induction, while processes associated with germline aging contribute to DNA repair defects in aged germlines. Moreover, I identify the ubiquitin ligase-like protein UEV-2 as a putative regulator of DNA repair defects during aging. Taken together, my thesis work illuminates mechanisms regulating metazoan intersister/intrachromatid meiotic recombination and defines pathways balancing efficiency and accuracy of DNA repair in the immortal germline

Good Dog! Applications of Dog Science

Each year 6 to 8 million pet dogs enter shelters, and unfortunately, many are returned to shelters, or euthanized, due to behavioral problems. Many behavioral problems can be alleviated if dogs get exercise; however, some owners cannot provide dogs sufficient exercise. Further, some dogs may be physically unable to exercise. One possible solution is to provide dogs with mental exercise. We are currently developing a series of touchscreen computer tasks with the hope that they provide mental stimulation and can be made available to owners via a tablet application. As of now, a few dogs in our lab have learned to effectively use the touch screen. In the near future, we hope such touch screen tasks will transfer over into an application that will serve as an effective program to minimize the amount of behavioral problems, and hence, the number of dogs sent to, returned to, and euthanized in shelters

Applying new biotechnologies to the study of occupational cancer--a workshop summary.

As high-throughput technologies in genomics, transcriptomics, and proteomics evolve, questions arise about their use in the assessment of occupational cancers. To address these questions, the National Institute for Occupational Safety and Health, the National Cancer Institute, the National Institute of Environmental Health Sciences, and the American Chemistry Council sponsored a workshop 8-9 May 2002 in Washington, DC. The workshop brought together 80 international specialists whose objective was to identify the means for best exploiting new technologies to enhance methods for laboratory investigation, epidemiologic evaluation, risk assessment, and prevention of occupational cancer. The workshop focused on identifying and interpreting markers for early biologic effect and inherited modifiers of risk

Cytogenetic analysis of an exposed-referent study: perchloroethylene-exposed dry cleaners compared to unexposed laundry workers

<p>Abstract</p> <p>Background</p> <p>Significant numbers of people are exposed to tetrachloroethylene (perchloroethylene, PCE) every year, including workers in the dry cleaning industry. Adverse health effects have been associated with PCE exposure. However, investigations of possible cumulative cytogenetic damage resulting from PCE exposure are lacking.</p> <p>Methods</p> <p>Eighteen dry cleaning workers and 18 laundry workers (unexposed controls) provided a peripheral blood sample for cytogenetic analysis by whole chromosome painting. Pre-shift exhaled air on these same participants was collected and analyzed for PCE levels. The laundry workers were matched to the dry cleaners on race, age, and smoking status. The relationships between levels of cytological damage and exposures (including PCE levels in the shop and in workers' blood, packyears, cumulative alcohol consumption, and age) were compared with correlation coefficients and t-tests. Multiple linear regressions considered blood PCE, packyears, alcohol, and age.</p> <p>Results</p> <p>There were no significant differences between the PCE-exposed dry cleaners and the laundry workers for chromosome translocation frequencies, but PCE levels were significantly correlated with percentage of cells with acentric fragments (R²= 0.488, p < 0.026).</p> <p>Conclusions</p> <p>There does not appear to be a strong effect in these dry cleaning workers of PCE exposure on persistent chromosome damage as measured by translocations. However, the correlation between frequencies of acentric fragments and PCE exposure level suggests that recent exposures to PCE may induce transient genetic damage. More heavily exposed participants and a larger sample size will be needed to determine whether PCE exposure induces significant levels of persistent chromosome damage.</p

Priorities for development of research methods in occupational cancer.

Occupational cancer research methods was identified in 1996 as 1 of 21 priority research areas in the National Occupational Research Agenda (NORA). To implement NORA, teams of experts from various sectors were formed and given the charge to further define research needs and develop strategies to enhance or augment research in each priority area. This article is a product of that process. Focus on occupational cancer research methods is important both because occupational factors play a significant role in a number of cancers, resulting in significant morbidity and mortality, and also because occupational cohorts (because of higher exposure levels) often provide unique opportunities to evaluate health effects of environmental toxicants and understand the carcinogenic process in humans. Despite an explosion of new methods for cancer research in general, these have not been widely applied to occupational cancer research. In this article we identify needs and gaps in occupational cancer research methods in four broad areas: identification of occupational carcinogens, design of epidemiologic studies, risk assessment, and primary and secondary prevention. Progress in occupational cancer will require interdisciplinary research involving epidemiologists, industrial hygienists, toxicologists, and molecular biologists