Meiosis initiation: a story of two sexes in all creatures great and small

Meiosis facilitates diversity across individuals and serves as a major driver of evolution. However, understanding how meiosis begins is complicated by fundamental differences that exist between sexes and species. Fundamental meiotic research is further hampered by a current lack of human meiotic cells lines. Consequently, much of what we know relies on data from model organisms. However, contextualising findings from yeast, worms, flies and mice can be challenging, due to marked differences in both nomenclature and the relative timing of meiosis. In this review, we set out to combine current knowledge of signalling and transcriptional pathways that control meiosis initiation across the sexes in a variety of organisms. Furthermore, we highlight the emerging links between meiosis initiation and oncogenesis, which might explain the frequent re-expression of normally silent meiotic genes in a variety of human cancers

A Feasibility Study of the WHO Digital Mental Health Intervention Step-by-Step to Address Depression Among Chinese Young Adults

Background: Chinese young adults experience barriers to mental health treatment, including the lack of treatment providers and stigma around treatment seeking. Evidence-based digital mental health interventions are promising and scalable alternatives to face-to-face treatment for this population, but lack rigorous evidence to support scale-up in China. Aim: The study was a feasibility study for a large-scale RCT of Step-by-Step, a behavioral activation-based, mental health intervention to address depression and anxiety symptoms in Chinese young adults. It sought to assess feasibility of recruitment and of delivery of Step-by-Step in a University setting, to assess acceptability of the intervention, and to examine potential effectiveness. Method: An uncontrolled, feasibility trial was conducted to assess the feasibility and acceptability of Chinese Step-by-Step for Chinese University students with elevated depressive symptoms (PHQ-9 scores at or above 10) in Macao, China. Data was collected at two different time points (i.e., baseline and 8-weeks after baseline), administered via questionnaires embedded in an interventional mobile application. Participation rate and dropout rate were measured. Depressive and anxiety symptom severity, well-being, and self-defined stress were assessed. Satisfaction with the program was assessed using qualitative interviews. Results: A total of 173 students were screened, 22.0% (n = 38) were eligible, and 63.2% of them (n = 24) started the intervention. The dropout rate by post-test was 45.8%. Results from completers showed that Step-by-Step was potentially effective in reducing depressive and anxiety symptom severity, and self-defined stress. Students were generally satisfied with the program, but also offered suggestions for continued improvement. Qualitative feedback was reported within the RE-AIM framework, covering recruitment, effectiveness, adoption, implementation, and maintenance. Amendments to the program were made according to the feedback (e.g., adding notification for new session, modify the time zone). Conclusion: A minimally guided Step-by-Step protocol and the study procedure were successfully pilot tested for use for Chinese University students. The intervention was acceptable and no adverse events were reported. The results support the potential effectiveness and feasibility of a large-scale evaluation of the program

A protocol for a type 1 effectiveness-implementation randomized controlled trial of the WHO digital mental health intervention Step-by-Step to address depression among Chinese young adults in Macao (SAR), China

Background Among Chinese college students, the burden of depression is considerably high, affecting up to 30 % of the population. Despite this burden, few Chinese students seek mental health treatment. In addition, depression is highly comorbid with other mental health disorders, such as anxiety. Scalable, transdiagnostic, evidence-based interventions are needed for this population. Objective The study will evaluate the effectiveness of a World Health Organization transdiagnostic digital mental health intervention, Step-by-Step, to reduce depressive and anxiety symptoms and improve well-being compared with enhanced care as usual and its implementation in a Chinese university community. Methods A type 1 effectiveness-implementation two-arm, parallel, randomized controlled trial will be conducted. The two conditions are 1) the 5-session Step-by-Step program with minimal guidance by trained peer-helpers and 2) psychoeducational information on depression and anxiety and referrals to local community services. A total of 334 Chinese university students will be randomized with a 1:1 ratio to either of the two groups. Depression, anxiety, wellbeing, and client defined problems will be assessed at pre-intervention, post-intervention, and 3-month follow-up. Endline qualitative interviews and focus group discussions will be conducted to explore SbS implementation among service users, university staff, and stakeholders. Data will be analysed based on the intent-to-treat principle. Discussion Step-by-Step is an innovative approach to address common mental health problems in populations with sufficient digital literacy. It is a promising intervention that can be embedded to scale mental health services within a university setting. It is anticipated that after successful evaluation of the program and its implementation in the type 1 hybrid design RCT study, Step-by-Step can be scaled and maintained as a low-intensity treatment in universities, and potentially extended to other populations within the Chinese community. Trial registration ChiCTR2100050214

Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.

Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines and patient-derived tumor organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast cancer development through downregulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring of NELF-E-associated chromatin partners as a function of EMT and a co-option of NELF-E with the key EMT transcription factor SLUG. Accordingly, loss of NELF-E leads to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identify the histone acetyltransferase, KAT2B, as a key functional target of NELF-E-SLUG. Genetic and pharmacological inactivation of KAT2B ameliorate the expression of EMT markers, phenocopying NELF ablation. Elevated expression of NELF-E and KAT2B is associated with poorer prognosis in breast cancer patients, highlighting the clinical relevance of our findings. Taken together, we uncover a crucial role of the NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis

Cancer and meiotic gene expression: Two sides of the same coin?

Meiosis increases genetic diversity in offspring by generating genetically unique haploid gametes with reshuffled chromosomes. This process requires a specialized set of meiotic proteins, which facilitate chromosome recombination and segregation. However, re-expression of meiotic proteins in mitosis can have catastrophic oncogenic consequences and aberrant expression of meiotic proteins is a common occurrence in human tumors. Mechanistically, re-activation of meiotic genes in cancer promotes oncogenesis likely because cancers—conversely to healthy mitosis—are fueled by genetic instability which promotes tumor evolution, and evasion of immune response and treatment pressure. In this review, we explore similarities between meiotic and cancer cells with a particular focus on the oncogenic activation of meiotic genes in cancer. We emphasize the role of histones and their modifications, DNA methylation, genome organization, R-loops and the availability of distal enhancers

A WHO digital intervention to address depression among young Chinese adults: a type 1 effectiveness-implementation randomized controlled trial

Abstract Common mental disorders among young people are rising globally. Current university-based interventions are inadequate to address the need for evidence-based interventions. We investigated the effectiveness and implementation of Step-by-Step (SbS), a WHO digital intervention to address depression, among Chinese university students with depressive symptoms. In this paper, we report a type 1 hybrid effectiveness-implementation randomized controlled trial conducted between September 2021 and September 2022. The control condition was enhanced treatment as usual (ETAU, psychoeducation). The primary outcome was improvement in depression symptoms. Secondary outcomes were improvements in psychological well-being, anxiety symptoms, and self-identified psychosocial problems. Effectiveness of the intervention was evaluated using generalized linear mixed models. Implementation outcomes were evaluated by thematic analysis of participant interviews. A total of 371 participants were enrolled to two treatment conditions in a 1:1 ratio. SbS resulted in a greater reduction in depressive symptoms at posttreatment (p = 0.004, Hedges’ g = 0.35), but no significant difference between SbS and ETAU was observed at three-month follow-up (p = 0.179, Hedges’ g = 0.16). The treatment effect was larger among those who adhered to the treatment (Hedges’ gs = 0.59 and 0.30). Subjective well-being also improved for SbS at both time points (Hedges’ gs = 0.31 and 0.30). In addition, SbS resulted in more improvement in anxiety symptoms at posttreatment (p = 0.029, Hedges’ g = 0.26), but not at three-month follow-up (p = 0.265, Hedges’ g = 0.13). The qualitative results demonstrated that the intervention was well-implemented as a self-help mental health service, with minimal support from peer supporters. In conclusion, Step-by-Step, a digital intervention developed by WHO, was effective in reducing depressive symptoms in the short term and improving psychological well-being in a longer term. The sustained effect on depression needs further investigation. Improving uptake and engagement in the program is needed for its scale-up implementation as a university-based mental health service for Chinese young adults. Trial registration: ChiCTR2100050214