Cohesin Is Dispensable for Centromere Cohesion in Human Cells

BACKGROUND: Proper regulation of the cohesion at the centromeres of human chromosomes is essential for accurate genome transmission. Exactly how cohesion is maintained and is then dissolved in anaphase is not understood. PRINCIPAL FINDINGS: We have investigated the role of the cohesin complex at centromeres in human cells both by depleting cohesin subunits using RNA interference and also by expressing a non-cleavable version of the Rad21 cohesin protein. Rad21 depletion results in aberrant anaphase, during which the sister chromatids separate and segregate in an asynchronous fashion. However, centromere cohesion was maintained before anaphase in Rad21-depleted cells, and the primary constrictions at centromeres were indistinguishable from those in control cells. Expression of non-cleavable Rad21 (NC-Rad21), in which the sites normally cleaved by separase are mutated, resulted in delayed sister chromatid resolution in prophase and prometaphase, and a blockage of chromosome arm separation in anaphase, but did not impede centromere separation. CONCLUSIONS: These data indicate that cohesin complexes are dispensable for sister cohesion in early mitosis, yet play an important part in the fidelity of sister separation and segregation during anaphase. Cleavage at the separase-sensitive sites of Rad21 is important for arm separation, but not for centromere separation

Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase

Meiotic crossovers are produced when programmed double-strand breaks (DSBs) are repaired by recombination from homologous chromosomes (homologues). In a wide variety of organisms, meiotic HORMA-domain proteins are required to direct DSB repair towards homologues. This inter-homologue bias is required for efficient homology search, homologue alignment, and crossover formation. HORMA-domain proteins are also implicated in other processes related to crossover formation, including DSB formation, inhibition of promiscuous formation of the synaptonemal complex (SC), and the meiotic prophase checkpoint that monitors both DSB processing and SCs. We examined the behavior of two previously uncharacterized meiosis-specific mouse HORMA-domain proteins-HORMAD1 and HORMAD2-in wild-type mice and in mutants defective in DSB processing or SC formation. HORMADs are preferentially associated with unsynapsed chromosome axes throughout meiotic prophase. We observe a strong negative correlation between SC formation and presence of HORMADs on axes, and a positive correlation between the presumptive sites of high checkpoint-kinase ATR activity and hyper-accumulation of HORMADs on axes. HORMADs are not depleted from chromosomes in mutants that lack SCs. In contrast, DSB formation and DSB repair are not absolutely required for depletion of HORMADs from synapsed axes. A simple interpretation of these findings is that SC formation directly or indirectly promotes depletion of HORMADs from chromosome axes. We also find that TRIP13 protein is required for reciprocal distribution of HORMADs and the SYCP1/SC-component along chromosome axes. Similarities in mouse and budding yeast meiosis suggest that TRIP13/Pch2 proteins have a conserved role in establishing mutually exclusive HORMAD-rich and synapsed chromatin domains in both mouse and yeast. Taken together, our observations raise the possibility that involvement of meiotic HORMA-domain proteins in the regulation of homologue interactions is conserved in mammals

A 'snip' in time: what is the best age to circumcise?

<p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p

Two views of self-rated general health status

Global self-evaluations of health have proven to be sensitive predictors of morbidity and mortality. Yet researchers have only a limited understanding of how these self-evaluations are reached. This research compares two interpretations of self-rated health, as reflecting either a spontaneous assessment of one's health status and related practices, or an aspect of one's enduring self-concept. Using longitudinal data from successive waves of the National Population Health Survey in Canada (Statistics Canada, 1994-95, 1996-97, NPHS public use microdata documentation. Ottawa, Ontario: Statistics Canada; n=7505), our analysis tests a model of change in self-rated health as predicted by respondents' baseline physical and mental health symptoms, social support, leisure physical activity, smoking, body mass index, and 2-yr changes in these characteristics. As in past research, self-rated health was sensitive to improvement or decline in these predictors. Much of the explained variance, however, was unique to respondents' self-rated health 2 yr earlier. Moreover, the effect of several predictors on respondents' self-rated health varied according to whether respondents intended to improve specific health-related behaviours in the future. These findings suggest that self-rated health is not only a spontaneous assessment of one's health status and related practices; like a self-concept, self-rated health may be regulated by efforts to achieve one's relatively important health-related goals.Self-rated health Health determinants Self-concept Longitudinal Canada

Perceived control in relation to socioeconomic and behavioral resources for health

Perceived control is a personality characteristic that contributes to well-being, but few studies have attempted to integrate the functions of perceived control with those of other determinants of health. This research tested two hypotheses about the functions of perceived control: (a) individual differences in perceived control would account for socioeconomic differences in self-rated health status; (b) performance of health-related behaviors would account for the health benefits of perceived control. Using data from adult, nonproxy respondents in the National Population Health Survey of Canada (1995; n=11,110), confirmatory factor analysis supported a measurement model of self-rated health status composed of two correlated factors: physical health (i.e., chronic conditions, restricted activities, self-rated general health, physical functional capacity) and mental health (i.e., distress, depression). Structural equation modeling supported the first hypothesis, but not the second, regarding perceived control as a determinant of self-rated physical and mental health. Health-related behaviors partially mediated age differences in self-rated health, but different behaviors functioned in this way for men than for women. The findings suggest that psychological process, that of perceiving control over life events, underlies social inequality in health. Health-related behaviors appear not to serve as the primary mechanism through which perceived control influences healthSocioeconomic status Perceived control Health behaviors Health status National Population Health Survey of Canada