SUMMARY A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs). Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs coopted into hormone-responsive regulatory elements distributed throughout the genome.

Purpose: Epigenetic alterations including changes to cellular DNA methylation levels contribute to carcinogenesis and may serve as powerful biomarkers of the disease. This investigation sought to determine whether hypomethylation at the long interspersed nuclear elements (LINE1), reflective of the level of global DNA methylation, in peripheral blood-derived DNA is associated with increased risk of bladder cancer.Experimental Design: LINE1 methylation was measured from blood-derived DNA obtained from participants of a population-based incident case-control study of bladder cancer in New Hampshire. Bisulfite-modified DNA was pyrosequenced to determine LINE1 methylation status; a total of 285 cases and 465 controls were evaluated for methylation.Results: Being in the lowest LINE1 methylation decile was associated with a 1.8-fold increased risk of bladder cancer [95% confidence interval (95% CI), 1.12-2.90] in models controlling for gender, age, and smoking, and the association was stronger in women than in men (odds ratio, 2.48; 95% CI, 1.19-5.17 in women; and odds ratio, 1.47; 95% CI, 0.79-2.74 in men). Among controls, women were more likely to have lower LINE1 methylation than men (P = 0.04), and levels of arsenic in the 90th percentile were associated with reduced LINE1 methylation (P = 0.04).Conclusions: LINE1 hypomethylation may be an important biomarker of bladder cancer risk, especially among women.

No abstract

No abstract

The let-7 family of microRNAs are important regulatory molecules in lung cancer. One downstream target of let-7 is the RAS gene family, including KRAS, an important oncogene in the etiology and clinical outcome of lung adenocarcinoma. Recently, a SNP in the let-7 binding region of the KRAS 3' UTR was identified (termed LCS6). This functional polymorphism alters let-7 binding, resulting in both increased KRAS expression and decreased let-7 exposure. Further, this SNP has been reported as a risk trait for lung cancer risk among low-moderate smokers. Given the functionality of LCS6, we tested the hypothesis that this SNP is associated with the occurrence of KRAS mutation as well as patient survival. Here, we report there is no association between the LCS6 KRAS polymorphism and KRAS mutation. Further, we find no association between the LCS6 polymorphism and lung cancer survival. These unexpected findings imply that this newly reported KRAS-LCS6 polymorphism will have limited clinical utility for NSCLC.

In vertebrates, the positioning of the internal organs relative to the midline is asymmetric and evolutionarily conserved. A number of molecules have been shown to play critical roles in left-right patterning. Using representational difference analysis to identify genes that are differentially expressed on the left and right sides of the chick embryo, we cloned chick Claudin-1, an integral component of epithelial tight junctions. Here, we demonstrate that retroviral overexpression of Claudin-1, but not Claudin-3, on the right side of the chick embryo between HH stages 4 and 7 randomizes the direction of heart looping. This effect was not observed when Claudin-1 was overexpressed on the left side of the embryo. A small, but reproducible, induction of Nodal expression in the perinodal region on the right side of the embryo was noted in embryos that were injected with Claudin-1 retroviral particles on their right sides. However, no changes in Lefty, Pitx2 or cSnR expression were observed. In addition, Flectin expression remained higher in the left dorsal mesocardial folds of embryos with leftwardly looped hearts resulting from Claudin-1 overexpression on the right side of the embryo. We demonstrated that Claudin-1's C-terminal cytoplasmic tail is essential for this effect: mutation of a PKC phosphorylation site in the Claudin-1 C-terminal cytoplasmic domain at threonine-206 eliminates Claudin-1's ability to randomize the direction of heart looping. Taken together, our data provide evidence that appropriate expression of the tight junction protein Claudin-1 is required for normal heart looping and suggest that phosphorylation of its cytoplasmic tail is responsible for mediating this function. q

Objective: 1) To determine the most frequent needs in a group of family caregivers of individuals with spinal cord injury in Neiva Colombia; 2) to describe caregivers' psychosocial functioning; and 3) to examine the relationship between caregiver needs and caregiver psychosocial functioning. Design: Cross-sectional. Participants/Methods: 37 caregivers completed a caregiver needs questionnaire composed of 27 questions (1-5 scale) and 9 subscales (emotional, information, economic, community, and household support, respite, physical health, sleep, and psychological health). The Patient Health Questionnaire (PHQ-9) was used to measure caregiver depression, the Zarit Burden Interview (ZBI) measured stress, the Interpersonal Support Evaluation List Short Version (ISEL-12) measured social support, and the Satisfaction With Life Scale (SWLS) was used to assess satisfaction with life. Results: Information, economic, emotional, community support, and respite needs were most frequently reported among this group of Colombian caregivers. Forty-three percent of the family caregivers reported some level of depression, 68% reported being overwhelmed by their caretaking responsibilities, and 43% reported dissatisfaction with their lives. Information, emotional, economic, physical, sleep, and psychological needs were positively correlated with depression and burden. Those with more household, physical, sleep, economic, and psychological needs had less satisfaction with life and social support. Caregivers with more community and respite needs had less social support, while those with more emotional needs had less satisfaction with life. Caregivers with more respite needs had more burden and those with more household needs had more depression.Conclusion: Approximately half of the sample reports some level of burden, depression, or being dissatisfied with life. Psychosocial functioning was related to various family needs. Further longitudinal research is needed to determine whether caregivers with more needs report worse psychosocial functioning or if those with worse psychosocial functioning report more needs.

This study modified the MAS to assess attitudes toward persons with disabilities in Colombia. The adequate reliability and fit of the factor structure of the Spanish MAS suggests that it holds promise to help researchers investigate attitudes toward persons with disabilities in Latin America, an important topic to the global disability community.