SMC complexes differentially compact mitotic chromosomes according to genomic context

Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes

Health sector reform and sexual and reproductive health services in Mongolia

Since its transition to democracy, Mongolia has undergone a series of reforms, both at national level and in the health sector. This paper examines the pace and scope of these reforms, the ways in which they have impacted on sexual and reproductive health services and their implications for the health workforce. Formerly pro-natalist, Mongolia has made significant advances in contraceptive use, women's education and reductions in maternal mortality. However, rising adolescent pregnancy and sexually transmitted infections, and persisting high levels of abortion, remain challenges. The implementation of the National Reproductive Health Programme has targeted skills development, outreach and the provision of resources. Innovative adolescent-friendly health services have engaged urban youth, and the development of family group practices has created incentives to provide primary medical care for marginalised communities, including sexual and reproductive health services. The Health Sector Strategic Masterplan offers a platform for coordinated development in health, but is threatened by a lack of consensus in both government and donor communities, competing health priorities and the politicisation of emerging debates on fertility and abortion. With previous gains in sexual and reproductive health vulnerable to political change, these tensions risk the exacerbation of existing disparities and the development by default of a two-tiered health care system

Design, Synthesis, and Biological Evaluation of 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4′-pyridyl)carboxamido]morphinan Derivatives as Peripheral Selective μ Opioid Receptor Agents

Peripheral selective μ opioid receptor (MOR) antagonists could alleviate the symptoms of opioid-induced constipation (OIC) without compromising the analgesic effect of opioids. However, a variety of adverse effects were associated with them, partially due to their relatively low MOR selectivity. NAP, a 6β-<i>N</i>-4′-pyridyl substituted naltrexamine derivative, was identified previously as a potent and highly selective MOR antagonist mainly acting within the peripheral nervous system. The noticeable diarrhea associated with it prompted the design and synthesis of its analogues in order to study its structure–activity relationship. Among them, compound <b>8</b> showed improved pharmacological profiles compared to the original lead, acting mainly at peripheral while increasing the intestinal motility in morphine-pelleted mice (ED₅₀ = 0.03 mg/kg). The slight decrease of the ED₅₀ compared to the original lead was well compensated by the unobserved adverse effect. Hence, this compound seems to be a more promising lead to develop novel therapeutic agents toward OIC