Switching yeast from meiosis to mitosis: double-strand break repair, recombination and synaptonemal complex

Background:

When Saccharomyces cerevisiae cells that have begun meiosis are transferred to mitotic growth conditions (‘return-to-growth’, RTG), they can complete recombination at high meiotic frequencies, but undergo mitotic cell division and remain diploid. It was not known how meiotic recombination intermediates are repaired following RTG. Using molecular and cytological methods, we investigated whether the usual meiotic apparatus could repair meiotically induced DSBs during RTG, or whether other mechanisms are invoked when the developmental context changes.

Results:

Upon RTG, the rapid disappearance of meiotic features—double-strand breaks in DNA (DSBs), synaptonemal complex (SC), and SC related structures—was striking. In wild-type diploids, the repair of meiotic DSBs during RTG was quick and efficient, resulting in homologous recombination. Kinetic analysis of double-strand breakage and recombination indicated that meiotic DSB formation precedes the commitment to meiotic levels of recombination. DSBs were repaired in RTG in dmc1, but not rad51 mutants, hence repair did not occur by the usual meiotic mechanism which requires the Dmc1 gene product. In haploids, DSBs were also repaired quickly and efficiently upon RTG, showing that DSB repair did not require the presence of a homologous chromosome. In all strains examined, SC and related structures were not required for DSB repair or recombination following RTG.

Conclusions:

At least two pathways of DSB repair, which differ from the primary meiotic pathway(s), can occur during RTG: One involving interhomologue recombination, and another involving sister-chromatid exchange. DSB formation precedes commitment to recombination. SC elements appear to prevent sister chromatid exchange in meiosis.

     

The antiatherogenic effect of allicin: possible mode of action.

OBJECTIVE: Garlic (Allium sativum) has been suggested to affect several cardiovascular risk factors. Its antiatherosclerotic properties are mainly attributed to allicin that is produced upon crushing of the garlic clove. Most previous studies used various garlic preparations in which allicin levels were not well defined. In the present study, we evaluated the effects of pure allicin on atherogenesis in experimental mouse models. METHODS AND RESULTS: Daily dietary supplement of allicin, 9 mg/kg body weight, reduced the atherosclerotic plaque area by 68.9 and 56.8% in apolipoprotein E-deficient and low-density lipoprotein (LDL) receptor knockout mice, respectively, as compared with control mice. LDL isolated from allicin-treated groups was more resistant to CuSO(4)-induced oxidation ex vivo than LDL isolated from control mice. Incubation of mouse plasma with (3)H-labeled allicin showed binding of allicin to lipoproteins. By using electron spin resonance, we demonstrated reduced Cu(2+) binding to LDL following allicin treatment. LDL treatment with allicin significantly inhibited both native LDL and oxidized LDL degradation by isolated mouse macrophages. CONCLUSIONS: By using a pure allicin preparation, we were able to show that allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages.     

Nutrient Intake following Vertical Banded Gastroplasty or Gastric Bypass

Background: This study explored eating habits, nutrient intake, and blood vitamin and mineral levels to determine whether severely obese subjects (BMI 40-50 kg m⁻²) post-vertical banded gastroplasty (VBG) or gastric bypass Roux-en-Y (GBR) are at risk of developing compounded under-nutrition. Methods: A dietary follow-up of 36 VBG and 19 GBR was maintained for 18 months via 7-day food intake diaries and 24-h recalls. Food intake was analysed for energy and nutrient composition and for its relative amount to recommended dietary allowances (RDA). Results: Weight loss was greatest during the first 6 months, continued at a slower rate for the next 6 months, nearly ceasing thereafter. The results following GBR were not substantially different from those following VBG 18 months postoperatively. The median weight loss at 1 year postoperatively was 48, 46, 48 and 36 kg; expressed as residual excess body weight: 0.2, 16, 13 and 22% for GBR Men, Women, VBG Men, Women, respectively. According to the classification proposed by Reinhold, all subjects achieved excellent treatment outcomes 18 months postoperatively. Despite the relatively low reported energy intake (20-50% below RDA), no correlation was found between rate of weight loss and energy intake at 6 months postoperatively. The intake of most vitamins and minerals was below 50% of RDA during the 18 months follow-up. The increase in energy intake did not improve the level of the nonenergy-contributing nutrients. Compliance to multivitamin and mineral supplement intake deteriorated with time. Conclusion: The low to within-normal range of blood vitamin and mineral levels 12 months postoperatively suggests the slow development of subclinical nutritional deficiency which could jeopardize the subjects' long-term health status.     

The associations between reflective ability and communication skills among medical students

ObjectivesAssess associations between medical students’ reflective ability demonstrated in written narratives, and communication skills demonstrated later in simulated-patient breaking bad news interactions.MethodsWe analyzed 66 medical students’ reflective ability, using ‘REFLECT’ rubric and four newly developed parameters: Noticing Explanations provided to patients, Noticing Emotions, Remoteness/Connectedness in their writing, and mentioning Self-Emotions. ‘BAS’ and ‘SPIKES’ questionnaires measured students’ communication skills. Spearman and Chi-square tests examined correlations among all variables. Multiple regressions examined associations between reflective ability and demographic variables with communication skills.ResultsSignificant positive correlations between students’ reflective ability, measured by REFLECT and three of the new parameters, and global communication skill scores. Reflective ability of Noticing Explanations in writing was associated with ability to tailoring information to patients’ needs and address emotions.ConclusionsHigh reflective ability may improve communication skills. Specifically, ability to notice explanations to patients may enhance later capability to tailor information to patients and address emotions empathically.Practice implicationsEncourage educational interventions enhancing reflective ability; specifically observation and detailed writing about how explanations are given to patients and patients’ reactions to them. This process may help students develop competency to share and tailor difficult information sensitively—a critical skill when communicating bad news.     

The elephant in the room: talking race in medical education

The deaths of black men and women while in police custody, rising anti-immigrant sentiment and rhetoric in high-income countries, and the continued health disparities experienced by Indigenous communities globally have brought race and racism to the forefront of public discourse in recent years. In a context where academic health science centres are increasingly called to be “socially accountable,” ignoring the larger social context of race and racism is something that medical education institutions can little afford to do. However, many such institutions have largely remained silent on the issue of race and racism, both within and outside of healthcare. Most medical education continues to emphasize a primarily biological understanding of race. We argue that a different approach is needed. Highlighting the social construction of race is an essential starting point for educators and trainees to tackle racialized health disparities in our clinics and to challenge racism in our classrooms, educational and research institutions, and communities.     

Preserving fertility when choosing chemotherapy regimens – the role of gonadotropin-releasing hormone agonists

Introduction: The late effects of cancer treatment have recently gained a worldwide ubiquitous interest among reproductive endocrinologists, oncologists, and all health care providers. Despite many publications on this subject, there are many equivocal issues necessitating summary. The case for and against using GnRH-agonist for fertility preservation is summarized with the rationale that preventing ovarian failure may be better than treating it.

Areas covered: We searched Medline in the last 10 years using terms: ‘fertility preservation’, ‘female chemotherapy’, ‘Gonadotropin-releasing hormone (GnRH) analogues’, ‘GnRH agonists’ ‘gonadotoxicity’, and ‘cancer treatment’. We included mainly publications from the past 7 years, but did not exclude previous, commonly referenced publications. Here, we summarize the various methods available for fertility preservation and minimizing chemotherapy induced gonadotoxicity.

Expert opinion: Until now, 20 studies (15 retrospective and 5 randomized controlled trial) have reported on 2038 patients treated with GnRH-a in parallel to chemotherapy, showing a significant decrease in premature ovarian failure (POF) rate in survivors versus 8 studies reporting on 509 patients, with negative results. Patients treated with GnRH-a in parallel to chemotherapy preserved their cyclic ovarian function in 91% of cases as compared to 41% of controls, with a pregnancy rate of 19 – 71% in the treated patients. Furthermore, over 10 recent meta-analyses have concluded that GnRH-a are beneficial and may decrease the risk of POF in survivors. Because most of the methods involving ovarian or egg cryopreservation are not yet clinically established and unequivocally successful, these young patients deserve to be informed with all the various modalities to minimize gonadal damage and preserve ovarian function and future fertility. Combining the various modalities for a specific patient may increase the odds of preservation of future fertility.