Patterns of nucleotide polymorphism distinguish temperate and tropical wild isolates of Caenorhabditis briggsae

Caenorhabditis briggsae provides a natural comparison species for the model nematode C. elegans, given their similar morphology, life history, and hermaphroditic mode of reproduction. Despite C. briggsae boasting a published genome sequence and establishing Caenorhabditis as a model genus for genetics and development, little is known about genetic variation across the geographic range of this species. In this study, we greatly expand the collection of natural isolates and characterize patterns of nucleotide variation for six loci in 63 strains from three continents. The pattern of polymorphisms reveals differentiation between C. briggsae strains found in temperate localities in the northern hemisphere from those sampled near the Tropic of Cancer, with diversity within the tropical region comparable to what is found for C. elegans in Europe. As in C. elegans, linkage disequilibrium is pervasive, although recombination is evident among some variant sites, indicating that outcrossing has occurred at a low rate in the history of the sample. In contrast to C. elegans, temperate regions harbor extremely little variation, perhaps reflecting colonization and recent expansion of C. briggsae into northern latitudes. We discuss these findings in relation to their implications for selection, demographic history, and the persistence of self-fertilization.     

Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease

Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis patient populations carry the major CF mutation (delta F508). Since different Jewish ethnic groups tended to live as closed isolates until recent times, high frequencies of specific mutations are expected among the remainder cystic fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence the severity of the disease. It is therefore expected that different mutations will be associated with either severe or mild phenotype. Direct genomic sequencing of exons included in the two nucleotide-binding folds of the putative CFTR protein was performed on 119 Israeli cystic fibrosis patients from 97 families. One sequence alteration which is expected to create a termination at residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57 (60%) are of Ashkenazi origin. Together with the delta F508 (23% in this group), G542X, N1303K, and 1717-1G----A mutations, the identification of 92% of cystic fibrosis chromosomes of Ashkenazi origin becomes possible. Patients homozygous for the W1282X mutation (n = 16) and patients heterozygous for the delta F508 and W1282X mutations (n = 22) had similarly severe disease, reflected by pancreatic insufficiency, high incidence of meconium ileus (37% and 27%, respectively), early age at diagnosis, poor nutritional status, and variable pulmonary function. In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in the Ashkenazi Jewish patient population in Israel. This nonsense mutation is associated with presentation of severe disease.     

Beyond the Biomedical: Community Resources for Mental Health Care in Rural Ethiopia

BackgroundThe focus of discussion in addressing the treatment gap is often on biomedical services. However, community resources can benefit health service scale-up in resource-constrained settings. These assets can be captured systematically through resource mapping, a method used in social action research. Resource mapping can be informative in developing complex mental health interventions, particularly in settings with limited formal mental health resources.MethodWe employed resource mapping within the Programme for Improving Mental Health Care (PRIME), to systematically gather information on community assets that can support integration of mental healthcare into primary care in rural Ethiopia. A semi-structured instrument was administered to key informants. Community resources were identified for all 58 sub-districts of the study district. The potential utility of these resources for the provision of mental healthcare in the district was considered.ResultsThe district is rich in community resources: There are over 150 traditional healers, 164 churches and mosques, and 401 religious groups. There were on average 5 eddir groups (traditional funeral associations) per sub-district. Social associations and 51 micro-finance institutions were also identified. On average, two traditional bars were found in each sub-district. The eight health centres and 58 satellite clinics staffed by Health Extension Workers (HEWs) represented all the biomedical health services in the district. In addition the Health Development Army (HDA) are community volunteers who support health promotion and prevention activities.DiscussionThe plan for mental healthcare integration in this district was informed by the resource mapping. Community and religious leaders, HEWs, and HDA may have roles in awareness-raising, detection and referral of people with mental illness, improving access to medical care, supporting treatment adherence, and protecting human rights. The diversity of community structures will be used to support rehabilitation and social reintegration. Alcohol use was identified as a target disorder for community-level intervention.     

Skeletal development in the African elephant and ossification timing in placental mammals

We provide here unique data on elephant skeletal ontogeny. We focus on the sequence of cranial and post-cranial ossification events during growth in the African elephant (Loxodonta africana). Previous analyses on ossification sequences in mammals have focused on monotremes, marsupials, boreoeutherian and xenarthran placentals. Here, we add data on ossification sequences in an afrotherian. We use two different methods to quantify sequence heterochrony: the sequence method and event-paring/Parsimov. Compared with other placentals, elephants show late ossifications of the basicranium, manual and pedal phalanges, and early ossifications of the ischium and metacarpals. Moreover, ossification in elephants starts very early and progresses rapidly. Specifically, the elephant exhibits the same percentage of bones showing an ossification centre at the end of the first third of its gestation period as the mouse and hamster have close to birth. Elephants show a number of features of their ossification patterns that differ from those of other placental mammals. The pattern of the initiation of the ossification evident in the African elephant underscores a possible correlation between the timing of ossification onset and gestation time throughout mammals.     

Carl von Hess

Ohne Zusammenfassung     

Development of in vitro embryo production systems for red deer (Cervus elaphus). Part 3. In vitro fertilisation using sheep serum as a capacitating agent and the subsequent birth of calves

The following experiments investigated the use of sheep serum (SS) as a capacitating agent for red deer (Cervus elaphus) sperm during in vitro fertilisation. Red deer oocytes were collected at slaughter and matured in vitro for 24h in TCM-199 supplemented with 10% foetal calf serum, 10 microg ml(-1) FSH and LH, and 1microg ml(-1) of oestradiol. Fertilisation medium was IVF-SOF modified to contain 5mM Ca(2+) and no glucose. Experiment 1 investigated the addition of heparin, BSA (8 mg ml(-1)) or 20% SS. All oocytes were penetrated when IVF-SOF was supplemented with SS compared to 10 and 0% penetration when either heparin or BSA was present (P<0.01). However, 43.8% of these oocytes were polyspermic when the medium contained SS. In Experiment 2, the effect of sperm concentration on penetration rates during in vitro fertilisation was investigated. Total sperm penetration and monospermic penetration rates increased with increased sperm concentrations in a log linear manner (P<0.001) and both approached an asymptote at 0.4 x 10(6) sperm ml(-1) with 93.6 and 77% for total and monospermic penetration, respectively. Polyspermic fertilisation also increased with increasing sperm concentrations (P<0.05) but was variable (range 3.5+/-4.2 to 42.3+/-10.6%), especially at the lower sperm concentrations. Experiment 3 investigated the viability of these oocytes after transfer into red deer recipients. Fifteen 2- and 4-cell embryos were transferred into the oviducts of synchronized recipients 28 h post in vitro insemination. An additional fourteen embryos (8-10 cell) were transferred into synchronised recipients after 48 h of in vitro culture in either SOFaaBSA (n=10) or on red deer epithelial oviduct monolayers (n=4). Five (33% 5/15) of the recipients that received 2- and 4-cell embryos were pregnant at Day 45 (verified by ultrasonography) and four recipients subsequently calved. One recipient receiving an embryo cultured in SOFaaBSA was pregnant at Day 45 and subsequently calved. The birth of five normal calves indicate that full developmental competence of red deer oocytes matured and fertilised in vitro can be achieved by the techniques described.