Failure of testicular development associated with a rearrangement of 9p24.1 proximal to the SNF2 gene

In 46,XY individuals, testes are determined by the activity of the SRY gene (sex-determining region Y), located on the short arm of the Ychromosome. The other genetic components of the cascade that leads to testis formation are unknown and may be located on the Xchromosome or on the autosomes. Evidence for the existence of several loci associated with failure of male sexual development is indicated by reports of 46,XY gonadal dysgenesis associated with structural abnormalities of the Xchromosome or of autosomes (chromosomes9, 10, 11 and 17). In this report, we describe the investigation of a child presenting with multiple congenital abnormalities, mental retardation and partial testicular failure. The patient had a homogeneous de novo 46,XY,inv dup(9)(pter→p24.1::p21.1 →p23.3::p24.1→qter) chromosome complement. No deletion was found by either cytogenetic or molecular analysis. The SRY gene and DSS region showed no abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent in situ hybridisation data indicated that the distal breakpoint of the duplicated fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest that a gene involved in normal testicular development and/or maintenance is present at this position on chromosome 9. Received: 20 January 1997 / Accepted: 5 November 1997     

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.     

Revealing Invisible Water: Moisture Recycling as an Ecosystem Service

An ecosystem service is a benefit derived by humanity that can be traced back to an ecological process. Although ecosystem services related to surface water have been thoroughly described, the relationship between atmospheric water and ecosystem services has been mostly neglected, and perhaps misunderstood. Recent advances in land-atmosphere modeling have revealed the importance of terrestrial ecosystems for moisture recycling. In this paper, we analyze the extent to which vegetation sustains the supply of atmospheric moisture and precipitation for downwind beneficiaries, globally. We simulate land-surface evaporation with a global hydrology model and track changes to moisture recycling using an atmospheric moisture budget model, and we define vegetation-regulated moisture recycling as the difference in moisture recycling between current vegetation and a hypothetical desert world. Our results show that nearly a fifth of annual average precipitation falling on land is from vegetation-regulated moisture recycling, but the global variability is large, with many places receiving nearly half their precipitation from this ecosystem service. The largest potential impacts for changes to this ecosystem service are land-use changes across temperate regions in North America and Russia. Likewise, in semi-arid regions reliant on rainfed agricultural production, land-use change that even modestly reduces evaporation and subsequent precipitation, could significantly affect human well-being. We also present a regional case study in the Mato Grosso region of Brazil, where we identify the specific moisture recycling ecosystem services associated with the vegetation in Mato Grosso. We find that Mato Grosso vegetation regulates some internal precipitation, with a diffuse region of benefit downwind, primarily to the south and east, including the La Plata River basin and the megacities of Sao Paulo and Rio de Janeiro. We synthesize our global and regional results into a generalized framework for describing moisture recycling as an ecosystem service. We conclude that future work ought to disentangle whether and how this vegetation-regulated moisture recycling interacts with other ecosystem services, so that trade-offs can be assessed in a comprehensive and sustainable manner.     

Care of the diabetic child in the community.

Brief admission of the new diabetic child and of a parent to an enlightened hospital for stabilisation, preliminary education, and familiarisation with hospital and community staff is well worth while. The greater the demand for constant control of the highest quality, the greater the need for a close understanding of the psychosocial factors concerned and for clinical skill. The nature of the home and the family relationships should in theory be available from the child''s general practitioner at the time of the first referral since he has so much information about the whole family. With the virtual disappearance, however, of mutual consultation in the patient''s home in many places, the opportunity for oral communication has declined, and availability on the telephone is not always easy. The busy general practitioner (far less an unknown physician from a deputising service without access to the records) has little time to write a comprehensive letter. In practice a relatively small hospital-based mobile team of specially experienced sisters who are keen to communicate in the home, the GP''s surgery, and the school makes a major contribution to the diabetic care of a young population vulnerable to major handicap in what should be the prime of life. Their cost effectiveness may be difficult to prove but it is not at all in doubt--especially when the sisters as in this area deal in the community with a wider range of chronic illnesses and handicaps in children.     

Lower Neighborhood Socioeconomic Status Associated with Reduced Diversity of the Colonic Microbiota in Healthy Adults

In the United States, there are persistent and widening socioeconomic gaps in morbidity and mortality from chronic diseases. Although most disparities research focuses on person-level socioeconomic-status, mounting evidence suggest that chronic diseases also pattern by the demographic characteristics of neighborhoods. Yet the biological mechanisms underlying these associations are poorly understood. There is increasing recognition that chronic diseases share common pathogenic features, some of which involve alterations in the composition, diversity, and functioning of the gut microbiota. This study examined whether socioeconomic-status was associated with alpha-diversity of the colonic microbiota. Forty-four healthy adults underwent un-prepped sigmoidoscopy, during which mucosal biopsies and fecal samples were collected. Subjects’ zip codes were geocoded, and census data was used to form a composite indicator of neighborhood socioeconomic-status, reflecting household income, educational attainment, employment status, and home value. In unadjusted analyses, neighborhood socioeconomic-status explained 12–18 percent of the variability in alpha-diversity of colonic microbiota. The direction of these associations was positive, meaning that as neighborhood socioeconomic-status increased, so did alpha-diversity of both the colonic sigmoid mucosa and fecal microbiota. The strength of these associations persisted when models were expanded to include covariates reflecting potential demographic (age, gender, race/ethnicity) and lifestyle (adiposity, alcohol use, smoking) confounds. In these models neighborhood socioeconomic-status continued to explain 11–22 percent of the variability in diversity indicators. Further analyses suggested these patterns reflected socioeconomic variations in evenness, but not richness, of microbial communities residing in the sigmoid. We also found indications that residence in neighborhoods of higher socioeconomic-status was associated with a greater abundance of Bacteroides and a lower abundance of Prevotella, suggesting that diet potentially underlies differences in microbiota composition. These findings suggest the presence of socioeconomic variations in colonic microbiota diversity. Future research should explore whether these variations contribute to disparities in chronic disease outcomes.     

Methimazole and generation of oxygen radicals by monocytes: potential role in immunosuppression.

A study was conducted investigating the possibility that the immunosuppressive action of methimazole (the active metabolite of the antithyroid drug carbimazole) might be due to an effect on the production of oxygen radicals by monocytes. Techniques comprised measurement of luminol dependent chemoluminescence in monocytes and a spectrophotometric assay for production of hydrogen peroxide. The results showed definite inhibition of formation of oxygen radicals by resting and stimulated monocytes, which may explain the immunosuppressive action of the drug in Graves'' disease. The findings also suggest that the formation of oxygen radicals and the initiation of the immune response may be closely related.     

Views,landmarks, and routes: how do desert ants negotiate an obstacle course?

The Australian desert ant Melophorus bagoti often follows stereotypical routes through a cluttered landscape containing both distant panoramic views and obstacles (plants) to navigate around. We created an artificial obstacle course for the ants between a feeder and their nest. Landmarks comprised natural objects in the landscape such as logs, branches, and tussocks. Many ants travelled stereotypical routes home through the obstacle course in training, threading repeatedly the same gaps in the landmarks. Manipulations altering the relations between the landmarks and the surrounding panorama, however, affected the routes in two major ways. Both interchanging the positions of landmarks (transpositions) and displacing the entire landmark set along with the starting position of the ants (translations) (1) reduced the stereotypicality of the route, and (2) increased turns and meanders during travel. The ants might have used the entire panorama in view-based travel, or the distal panorama might prime the identification and use of landmarks en route. Despite the large data set, both options (not mutually exclusive) remain viable.     

Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer-induced Osteolysis

The cannabinoid type 2 receptor (CB2) has previously been implicated as a regulator of tumor growth, bone remodeling, and bone pain. However, very little is known about the role of the skeletal CB2 receptor in the regulation of osteoblasts and osteoclasts changes associated with breast cancer. Here we found that the CB2-selective agonists HU308 and JWH133 reduced the viability of a variety of parental and bone-tropic human and mouse breast cancer cells at high micromolar concentrations. Under conditions in which these ligands are used at the nanomolar range, HU308 and JWH133 enhanced human and mouse breast cancer cell-induced osteoclastogenesis and exacerbated osteolysis, and these effects were attenuated in cultures obtained from CB2-deficient mice or in the presence of a CB2 receptor blocker. HU308 and JWH133 had no effects on osteoblast growth or differentiation in the presence of conditioned medium from breast cancer cells, but under these circumstances both agents enhanced parathyroid hormone-induced osteoblast differentiation and the ability to support osteoclast formation. Mechanistic studies in osteoclast precursors and osteoblasts showed that JWH133 and HU308 induced PI3K/AKT activity in a CB2-dependent manner, and these effects were enhanced in the presence of osteolytic and osteoblastic factors such as RANKL (receptor activator of NFκB ligand) and parathyroid hormone. When combined with published work, these findings suggest that breast cancer and bone cells exhibit differential responses to treatment with CB2 ligands depending upon cell type and concentration used. We, therefore, conclude that both CB2-selective activation and antagonism have potential efficacy in cancer-associated bone disease, but further studies are warranted and ongoing.