A Highly Conserved Poc1 Protein Characterized in Embryos of the Hydrozoan Clytia hemisphaerica: Localization and Functional Studies

Poc1 (Protein of Centriole 1) proteins are highly conserved WD40 domain-containing centriole components, well characterized in the alga Chlamydomonas, the ciliated protazoan Tetrahymena, the insect Drosophila and in vertebrate cells including Xenopus and zebrafish embryos. Functions and localizations related to the centriole and ciliary axoneme have been demonstrated for Poc1 in a range of species. The vertebrate Poc1 protein has also been reported to show an additional association with mitochondria, including enrichment in the specialized “germ plasm” region of Xenopus oocytes. We have identified and characterized a highly conserved Poc1 protein in the cnidarian Clytia hemisphaerica. Clytia Poc1 mRNA was found to be strongly expressed in eggs and early embryos, showing a punctate perinuclear localization in young oocytes. Fluorescence-tagged Poc1 proteins expressed in developing embryos showed strong localization to centrioles, including basal bodies. Anti-human Poc1 antibodies decorated mitochondria in Clytia, as reported in human cells, but failed to recognise endogenous or fluorescent-tagged Clytia Poc1. Injection of specific morpholino oligonucleotides into Clytia eggs prior to fertilization to repress Poc1 mRNA translation interfered with cell division from the blastula stage, likely corresponding to when neosynthesis normally takes over from maternally supplied protein. Cell cycle lengthening and arrest were observed, phenotypes consistent with an impaired centriolar biogenesis or function. The specificity of the defects could be demonstrated by injection of synthetic Poc1 mRNA, which restored normal development. We conclude that in Clytia embryos, Poc1 has an essentially centriolar localization and function

Demographic and biologic influences on survival in whites and blacks: 40 years of follow-up in the Charleston heart study

BACKGROUND: In the United States, life expectancy is significantly lower among blacks than whites. We examined whether socioeconomic status (SES) and cardiovascular disease (CVD) risk factors may help explain this disparity. METHODS: Forty years (1961 through 2000) of all-cause mortality data were obtained on a population-based cohort of 2,283 subjects in the Charleston Heart Study (CHS). We examined the influence of SES and CVD risk factors on all-cause mortality. RESULTS: Complete data were available on 98% of the original sample (647 white men, 728 white women, 423 black men, and 443 black women). After adjusting for SES and CVD risk factors, the hazard ratios (HRs) for white ethnicity were 1.14 (0.98 to 1.32) among men and 0.90 (0.75 to 1.08) among women, indicating that the mortality risk was 14% greater for white men and 10% lower for white women compared to their black counterparts. However the differences were not statistically significant. CONCLUSION: While there are marked contrasts in mortality among blacks and whites in the CHS, the differences can be largely explained by SES and CVD risk factors. Continued focus on improving and controlling cardiovascular disease risk factors may reduce ethnic disparities in survival

Population-attributable risk of coronary heart disease risk factors during long-term follow-up: the Malmö Preventive Project.

Aims To calculate the population-attributable risk (PAR) of coronary events (CE) from 10 risk factors, during long-term follow-up. Methods We used both case-cohort and case-control analyses for calculation of PAR in relation to 10 baseline risk factors. First CE (fatal or nonfatal, n = 3072) in 22 444 males and 10 902 females was recorded during a mean follow-up of 20 years by use of national registers. Results Using a Cox regression analysis in a case-cohort design, smoking (prevalence in men 49%, women 37%) was the strongest risk factor, RR 2.29 (95% CI 2.09-2.52; PAR 39%), followed by hypercholesterolaemia, RR 1.70 (95% CI 1.56-1.86; PAR 18%), and diabetes, RR 1.67 (95% CI 1.41-1.99; PAR 3%). For women the strongest risk factors were smoking, RR 3.16 (95% CI 2.50-3.98; PAR 44%), diabetes, RR 2.59 (95% CI 1.78-3.76; PAR 6%), and hypertension, RR 2.47 (95% CI 1.94-3.14; PAR 23%). In men, smoking was the strongest predictor both after 10 years [RR 2.69 (95% CI 2.23-3.24)] and 20 years [RR 2.45 (95% CI 2.15-2.79)], followed by hypercholesterolaemia (RR 2.16-1.63), hypertension (RR 2.04-1.51), and diabetes (RR 1.85 -1.47). The case-control design gave very similar results. Total PAR varied from 74% (fully adjusted Cox regression, case-control, in men) to 116% in women (case-cohort). Conclusion Smoking is the most important long-term risk factor for CE in both genders, based on data from a population with a high proportion of smokers. Ten measured variables explained almost all variation in risk and could be used as a basis for intervention programmes

Tetrahymena

Basal bodies comprise nine symmetric triplet microtubules that anchor forces produced by the asymmetric beat pattern of motile cilia. The ciliopathy protein Poc1 stabilizes basal bodies through an unknown mechanism. In poc1∆ cells, electron tomography reveals subtle defects in the organization of intertriplet linkers (A-C linkers) that connect adjacent triplet microtubules. Complete triplet microtubules are lost preferentially near the posterior face of the basal body. Basal bodies that are missing triplets likely remain competent to assemble new basal bodies with nine triplet microtubules, suggesting that the mother basal body microtubule structure does not template the daughter. Our data indicate that Poc1 stabilizes basal body triplet microtubules through linkers between neighboring triplets. Without this stabilization, specific triplet microtubules within the basal body are more susceptible to loss, probably due to force distribution within the basal body during ciliary beating. This work provides insights into how the ciliopathy protein Poc1 maintains basal body integrity