We have identified miss-sense mutations in keratin 8 in a subset of patients with inflammatory bowel disease (Crohn disease and ulcerative colitis). Inflammatory bowel diseases are a group of disorders that are polygenic in origin and involve intestinal epithelial breakdown. We investigated the possibility that these keratin mutations might contribute to the course of the disease by adversely affecting the keratin filament network that provides mechanical support to cells in epithelia. The mutations (Gly62 to Cys, Ile63 to Val and Lys464 to Asn) all lie outside the major mutation hotspots associated with severe disease in epidermal keratins, but using a combination of in vitro and cell culture assays we show that they all have detrimental effects on K8/K18 filament assembly in vitro and in cultured cells. The G62C mutation also gives rise to homodimer formation on oxidative stress to cultured intestinal epithelial cells, and homodimers are known to be polymerization incompetent. Impaired keratin assembly resulting from the K8 mutations found in some inflammatory bowel disease patients would be predicted to affect the maintenance and re-establishment of mechanical resilience in vivo, as required during keratin cytoskeleton remodeling in cell division and differentiation, which may lead to epithelial fragility in the gut. Simple epithelial keratins may thus be considered as candidates for genes contributing to a risk of inflammatory bowel disease.

Whilst the importance of mutations in a wide range of keratins in skin fragility disorders is now well established, there is much less evidence for simple epithelial keratin involvement in disease. Some simple epithelial keratin mutations have been reported in liver cirrhosis and pancreatitis patients, and recently mutations in the simple epithelial keratin K8 were identified in a group of patients with inflammatory bowel disease (Crohn disease or ulcerative colitis). In comparison with the mutations seen in epidermal keratins, these simple epithelial mutations would be predicted to have mild consequences, although analysis shows that they do have a distinct effect. This review article discusses the evidence that these mutations are a predisposing factor for inflammatory bowel disease.

In an attempt to better understand the reproductive cycle of adult male loggerhead sea turtles, several techniques were used to assess their reproductive activity, including plastron-softness analysis, ultrasonography, laparoscopy, testicular biopsy samples, and measuring testosterone levels. Stress levels were evaluated on a subset of turtles by measuring testosterone and corticosterone concentrations after capture and before release. A total of 40 adult males were captured in the Port Canaveral shipping channel in April of 2006 and 2007. Four turtles were classified as reproductively inactive based on laparoscopic examination, histology of the testes, and testosterone levels. The relative area of plastron softness was significantly lower for the inactive males compared to the active males. Ultrasonography proved to be a promising tool, as we were able to visualize both the testes and epididymides on the turtles examined. Furthermore, we found no statistical difference in epididymal duct diameters measured by ultrasonography and during laparoscopy, suggesting that ultrasonography could be used successfully as a substitute for laparoscopic surgery. Finally, testosterone levels separated into 2 distinct groups, with concentrations of the inactive males below 5 ng ml -1 , and concentrations of the active males reaching 188 ng ml -1. We conclude that in order to reduce stress levels due to capture and handling, especially during laparoscopy, ultrasonography and plastron analysis could be used together as a way to determine the reproductive activity of adult males in the field. The results from this study also suggest that not all adult males participate in mating activity each year.