Widespread Presence of Human BOULE Homologs among Animals and Conservation of Their Ancient Reproductive Function

Sex-specific traits that lead to the production of dimorphic gametes, sperm in males and eggs in females, are fundamental for sexual reproduction and accordingly widespread among animals. Yet the sex-biased genes that underlie these sex-specific traits are under strong selective pressure, and as a result of adaptive evolution they often become divergent. Indeed out of hundreds of male or female fertility genes identified in diverse organisms, only a very small number of them are implicated specifically in reproduction in more than one lineage. Few genes have exhibited a sex-biased, reproductive-specific requirement beyond a given phylum, raising the question of whether any sex-specific gametogenesis factors could be conserved and whether gametogenesis might have evolved multiple times. Here we describe a metazoan origin of a conserved human reproductive protein, BOULE, and its prevalence from primitive basal metazoans to chordates. We found that BOULE homologs are present in the genomes of representative species of each of the major lineages of metazoans and exhibit reproductive-specific expression in all species examined, with a preponderance of male-biased expression. Examination of Boule evolution within insect and mammalian lineages revealed little evidence for accelerated evolution, unlike most reproductive genes. Instead, purifying selection was the major force behind Boule evolution. Furthermore, loss of function of mammalian Boule resulted in male-specific infertility and a global arrest of sperm development remarkably similar to the phenotype in an insect boule mutation. This work demonstrates the conservation of a reproductive protein throughout eumetazoa, its predominant testis-biased expression in diverse bilaterian species, and conservation of a male gametogenic requirement in mice. This shows an ancient gametogenesis requirement for Boule among Bilateria and supports a model of a common origin of spermatogenesis

Mapping the Archaeology of Somaliland: Religion, Art, Script, Time, Urbanism, Trade and Empire

FdA – Publicaties zonder aanstelling Universiteit LeidenHeritage of Indigenous People

Changes in Health for the Uninsured After Reaching Age-eligibility for Medicare

BACKGROUND: Uninsured adults in late middle age are more likely to have a health decline than individuals with private insurance. OBJECTIVE: To determine how health and the risk of future adverse health outcomes changes after the uninsured gain Medicare. DESIGN: Prospective cohort study. PARTICIPANTS: Participants (N = 3,419) in the Health and Retirement Study who transitioned from private insurance or being uninsured to having Medicare coverage at the 1996, 1998, 2000, or 2002 interview. MEASUREMENTS: We analyzed risk-adjusted changes in self-reported overall health and physical functioning during the transition period to Medicare (t(−2) to t(0)) and the following 2 years (t(0) to t(2)). RESULTS: Between the interview before age 65 (t(−2)) and the first interview after reaching age 65 (t(0)), previously uninsured individuals were more likely than those who had private insurance to have a major decline in overall health (adjusted relative risk [ARR] 1.46; 95% confidence interval [CI] 1.03 to 2.04) and to develop a new physical difficulty affecting mobility (ARR 1.24; 95% CI 0.96 to 1.56) or agility (ARR 1.33; 95% CI 1.12 to 1.54). Rates of improvement were similar between the 2 groups. During the next 2 years (t(0) to t(2)), adjusted rates of declines in overall health and physical functioning were similar for individuals who were uninsured and those who had private insurance before gaining Medicare. CONCLUSIONS: Gaining Medicare does not lead to immediate health benefits for individuals who were uninsured before age 65. However, after 2 or more years of continuous coverage, the uninsured no longer have a higher risk of adverse health outcomes

Calcium handling by vascular myocytes in hypertension

Calcium ions (Ca2+) trigger the contraction of vascular myocytes and the level of free intracellular Ca2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca2+ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extracellular Ca2+ and intracellular Ca2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca2+ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1) the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca2+ channel activity in hypertension; 2) Ca2+ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3) intracellular Ca2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca2+ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Ca2+ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca2+ channel function and/or an increase in Ca2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertensio