Age-dependent loss of cohesion protection in human oocytes.

Aneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis as a common cause. We found that loss of a specific pool of the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon. Our data indicate that SGO2 preserves sister chromatid cohesion in meiosis by protecting a "cohesin bridge" between sister chromatids. In human oocytes, SGO2 localizes to both sub-centromere cups and the pericentromeric bridge, which spans the sister chromatid junction. SGO2 normally colocalizes with cohesin; however, in meiosis II oocytes from older women, SGO2 is frequently lost from the pericentromeric bridge and sister chromatid cohesion is weakened. MPS1 and BUB1 kinase activities maintain SGO2 at sub-centromeres and the pericentromeric bridge. Removal of SGO2 throughout meiosis I by MPS1 inhibition reduces cohesion protection, increasing the incidence of single chromatids at meiosis II. Therefore, SGO2 deficiency in human oocytes can exacerbate the effects of maternal age by rendering residual cohesin at pericentromeres vulnerable to loss in anaphase I. Our data show that impaired SGO2 localization weakens cohesion integrity and may contribute to the increased incidence of aneuploidy observed in human oocytes with advanced maternal age.

An evaluation of experiences and views of Scottish leadership training opportunities amongst primary care professionals.

AIM: To determine experiences of leadership training of six primary care professions in Scotland and consider future development. METHODS: A questionnaire on previous leadership course attendance and future intentions was distributed to community pharmacists, general dental practitioners, general practitioners, practice nurses, practice managers and optometrists. Analysis comprised descriptive statistics for closed questions and management of textual data. RESULTS: Formal leadership training participation was fairly low except for practice managers. Leadership was perceived to facilitate development of staff, problem-solving and team working. Preference for future delivery was similar across the six professions with e-modules and small group learning being preferred. Time and financial pressures to undertake courses were common barriers for professionals. CONCLUSION: Leadership is key to improve quality, safety and efficiency of care and help deliver innovative services and transformative change. To date, leadership provision for primary care professionals has typically been patchy, uni-disciplinary in focus and undertaken outwith work environments. Future development must reflect needs of busy primary care professionals and the reality of team working to deliver integrated services at local level.