Meiosis produces haploid gametes through a succession of chromosomal events, including pairing, synapsis, and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO (small ubiquitin-like modifier)–modification and ubiquitin-proteasome systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin, and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpointlike process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.

No abstract

Our results demonstrated the contributory role of neuroactive steroid 3alpha, 5alpha-THP in the anti-anxiety effect of ethanol. It is speculated that ethanol-induced modulation of endogenous GABAergic neurosteroids, especially 3alpha, 5alpha-THP, might be crucial pertinent to the etiology of 'trait' anxiety (tension reduction) and ethanol abuse.

BackgroundTopical minoxidil has been used for almost 40 years to treat alopecia. There is growing evidence supporting off‐label use of low‐dose oral minoxidil.ObjectiveTo conduct a systematic review evaluating the use of oral minoxidil for all types of alopecia.MethodsA primary literature search was conducted using PubMed in May 2019, utilizing the search term “oral minoxidil AND (hair loss OR alopecia OR baldness)”. Reviews, non‐English studies, and articles concerning only topical minoxidil were excluded.ResultsTen articles were included for review comprising a total 19,218 patients (215 women and 19,003 men). Oral minoxidil dose ranged from 0.25 to 5 mg daily to twice daily. The strongest evidence existed for androgenetic alopecia and alopecia areata (AA), with 61–100% and 18–82.4% of patients demonstrating objective clinical improvement. Successful treatment of female pattern hair loss, chronic telogen effluvium, monilethrix, and permanent chemotherapy‐induced alopecia was also reported. The most common adverse effects with oral minoxidil included hypertrichosis and postural hypotension.ConclusionOral minoxidil is a safe and successful treatment of androgenic alopecia and AA. In addition to its therapeutic benefits, practical advantages over topical minoxidil stem from improved patient compliance.

No abstract