Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's disease (AD) patients and cognitively normal age and gender-matched controls, we have for the first time examined changes in the 3D nuclear telomeric architecture of buccal cells among levels of AD severity based on five 3D parameters: i) telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data indicate that matched controls have significantly different 3D telomere profiles compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct profiles were also evident for each AD severity group. An increase in telomere number and aggregation concomitant with a decrease in telomere length from normal to severe AD defines the individual stages of the disease (p < 0.0001).

To assess whether demographic declines of Arctic species at the southern limit of their range will be gradual or punctuated, we compared large-scale environmental patterns including sea ice dynamics to ringed seal (Pusa hispida) reproduction, body condition, recruitment, and stress in Hudson Bay from 2003 to 2013. Aerial surveys suggested a gradual decline in seal density from 1995 to 2013, with the lowest density occurring in 2013. Body condition decreased and stress (cortisol) increased over time in relation to longer open water periods. The 2010 open water period in Hudson Bay coincided with extremes in large-scale atmospheric patterns (North Atlantic Oscillation, Arctic Oscillation, El Nino-Southern Oscillation) resulting in the earliest spring breakup and the latest ice formation on record. The warming event was coincident with high stress level, low ovulation rate, low pregnancy rate, few pups in the Inuit harvest, and observations of sick seals. Results provide evidence of changes in the condition of Arctic marine mammals in relation to climate mediated sea ice dynamics. We conclude that although negative demographic responses of Hudson Bay seals are occurring gradually with diminishing sea ice, a recent episodic environmental event played a significant role in a punctuated population decline.

Baleen from three adult male whales (North Atlantic right, bowhead and blue) contains regularly spaced areas of high testosterone content suggestive of annual testosterone cycles. Patterns in glucocorticoids (cortisol and corticosterone) show potential relationships with breeding-related stress as well as with entanglement in fishing gear and possible disease episodes.

The functional role of INSL3 and its receptor RXFP2 in carcinogenesis is largely unknown. We have previously demonstrated (pro-)cathepsin-L as a target of INSL3 in human thyroid cancer cells facilitating penetration of tumor cells through elastin matrices. We demonstrate the expression of RXFP2 in human thyroid tissues and in mouse follicular thyroid epithelial cells using Cre-recombinase transgene driven by Rxfp2 promoter. Recombinant and secreted INSL3 increased the motility of thyroid carcinoma (TC) cells in an autocrine/paracrine manner. This effect required the presence of RXFP2. We identified S100A4 as a novel INSL3 target molecule and showed that S100A4 facilitated INSL3-induced enhanced motility. Stable transfectants of the human follicular TC cell line FTC-133 expressing and secreting bioactive human INSL3 displayed enhanced anchorageindependent growth in soft agar assays. Xenotransplant experiments in nude mice showed that INSL3, but not EGFP-mock transfectants, developed fast-growing and highly vascularized xenografts. We used human umbilical vein endothelial cells in capillary tube formation assays to demonstrate increased 2-dimensional tube formations induced by recombinant human INSL3 and human S100A4 comparable to the effect of vascular endothelial growth factor used as positive control. We conclude that INSL3 is a powerful and multifunctional promoter of tumor growth and angiogenesis in human thyroid cancer cell xenografts. INSL3 actions involve RXFP2 activation and the secretion of S100A4 and (pro-)cathepsin-L.Comprising 1% of all malignancies, thyroid cancer is the most common carcinoma of endocrine glands and displays the highest increase in incidence of all malignancies in the United States over the time interval 1975-2000 (http://seer. cancer.gov/csr/1975_2004/; www.cancer.ca). 1 There are 4 types of thyroid carcinoma (TC) that comprise >98% of all thyroid malignancies: papillary (PTC), follicular (FTC), anaplastic, undifferentiated (UTC) and medullary TC (MTC). We showed previously that the insulin-like peptide hormone, insulin-like peptide 3 (INSL3) and a novel INSL3 splice form are present in human hyperplastic thyroid adenoma and thyroid cancer. 2 INSL3 is a member of the relaxin family and signals through the type C leucine-rich repeat G proteincoupled receptor RXFP2, also named GREAT and LGR8. [3][4][5][6][7] Activation of RXFP2 causes an increase in cAMP levels and, via the actions of the small G-proteins Ga s and Ga oB , activates and negatively modulates adenylate cyclase activity, respectively, which affects cAMP-response element transcriptional activity. [8][9][10] Deletion of the gene for INSL3 or the INSL3 receptor causes impaired transabdominal testis descent and cryptorchidism in rodents and boys. [11][12][13][14] Both INSL3 and the homologous peptide relaxin are found in tumor tissues but little information is currently available on the functional role of both the INSL3-RXFP2 and the relaxin-RXFP1 system in cancer cells. 15 In prostate cancer, increasing evidence from cell an...