Progesterone metabolism in T47Dco human breast cancer cells--II. Intracellular metabolic path of progesterone and synthetic progestins

We show here that progesterone added to the medium of proliferating T47Dco human breast cancer cells is metabolized with a half life of 2-4h. The final metabolic product, 5 alpha-pregnan-3 beta,6 alpha-diol-20-one, (P-metabolite) is released into the medium. This structure suggested that the intracellular metabolism of progesterone involves the enzymes 5 alpha-reductase, 3 beta-hydroxysteroid dehydrogenase, and 6 alpha-hydroxylase. To investigate this pathway, the cells were incubated with a variety of potential substrates. In addition to progesterone, only precursors with the 5 alpha-configuration served as substrates for the enzymes leading to P-metabolite formation. Some precursors with a 5 beta-configuration were also metabolized by T47Dco cells. This metabolism reflected activity by either 3 beta-hydroxysteroid dehydrogenase and/or 6 alpha-hydroxylase but, in contrast to progesterone metabolism, the rates were different and the products were often mixtures. In T47Dco and MCF-7 human breast tumor cells, the reduction at C-3 followed by 6 alpha-hydroxylation, appear to be the major, and possibly only, route of progesterone metabolism. In contrast, preliminary data suggest that in normal human breast epithelial cells, this is not an exclusive route. Androgens are partially subject to the same metabolic enzymes, but synthetic progestins are not metabolized by T47Dco during an 18 h incubation.     

Hymenolepis diminuta: Worm loss and worm weight loss in long-term infections of the rat

Infections of one and two Hymenolepis diminuta established in newly weaned rats continued to grow for the duration of the experiment (238 days), whereas infections of 5 worms per rat became asymptotic around Day 55 postinfection and remained at or below this level thereafter as shown by biomass and mean weight per worm measurements. Infections of 50 worms established in newly weaned rats became asymptotic around Day 28 postinfection and thereafter worms were lost from the rats. Initially the biomass fell with the loss of worms, but by Day 56 a new lower biomass persisted for the remainder of the infection period. This level was maintained, despite diminishing numbers of worms, due to the growth of surviving individuals to a weight exceeding the original weight at maturity by a factor of more than 2. Experiments using rats that were mature at the time of infection demonstrated that the same response occurred, but approximately 3 weeks earlier.     

Identification of Medically Actionable Secondary Findings in the 1000 Genomes

The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 secondary findings are associated with diseases that could inform medical follow-up, including cancer predisposition syndromes, cardiac conditions, and familial hypercholesterolemia. The majority of the identified medically actionable findings were in individuals from the European (5/379) and Americas (4/181) ancestry groups, with fewer findings in Asian (2/286) and African (1/246) ancestry groups. Our results suggest that medically relevant secondary findings can be identified in approximately 1% (12/1092) of individuals in a diverse reference sample. As clinical sequencing laboratories continue to implement the ACMG recommendations, our results highlight that at least a small number of potentially important secondary findings can be selected for return. Our results also confirm that understudied populations will not reap proportionate benefits of genomic medicine, highlighting the need for continued research efforts on genetic diseases in these populations.     

Children and marital satisfaction in a non-Western sample: having more children increases marital satisfaction among the Igbo people of Nigeria

Previous research has demonstrated that having more children decreases marital satisfaction among parents. However, the universality of these findings is limited since the vast majority of the studies have been conducted in Western countries. In the present study, 374 people from the Igbo ethnic group (Nigeria) were assessed for levels of marital satisfaction and the number of children. In contrast to almost all previous findings, we found a positive relationship between the number of children and marital satisfaction among parents. Number of children was the strongest predictor of marital satisfaction even when compared to other variables like wealth and education. Our results suggest that the negative relationship between the number of children and marital satisfaction is not culturally universal and probably only characterizes developed, individualistic Western countries. We discuss our findings from a sociocultural and evolutionary perspective.     

Where ichthyofaunal provinces meet: the fish fauna of the Lake Edward system,East Africa

Based on literature, museum collections and three recent expeditions, an annotated species list of the Lake Edward, East Africa, drainage system is presented, excluding the endemic haplochromines. A total of 34 non-Haplochromis species belonging to 10 families and 21 genera are recorded from the system. Three of these are endemic and two others have been introduced in the region. Six species are new records for the Lake Edward system. A species accumulation curve indicates that we probably covered most of the non-Haplochromis species in the area sampled during the recent expeditions, but undetected species might still be present in the Congolese part of the system, which is poorly sampled. A comparison of the species list with those of neighbouring basins confirmed the placement of the Lake Edward system within the east-coast ichthyofaunal province.     

Modelling ultraviolet exposures in a school environment.

A technique has been developed to represent erythemally effective ultraviolet radiation exposure within a school environment. The technique models the erythemally effective exposure onto a horizontal plane representation of a mapped school environment located in Hervey Bay (25 degrees S, 153 degrees E), Australia. The input parameters used to model the ultraviolet exposures received within the school playground included the measured sky view, ground albedo and standing surface albedo. Estimates of the erythemally effective ultraviolet exposure received within the school playground during morning tea and lunch time meal breaks during a winter and summer school day are presented. The influence of tree shade and building structure was found to vary significantly with solar zenith angle modelled over the winter and summer school meal break times with horizontal plane exposures predicted to vary from between 0 and 7 SED at different locations within the playground. The technique presented provides a method that can be followed to examine the effect of surrounding buildings and surface structures of real environments on the predicted horizontal plane ultraviolet exposure.