Fstl1 Antagonizes BMP Signaling and Regulates Ureter Development

Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in developing ureter and antagonizes BMP signaling activity. Mouse embryos carrying disrupted Fstl1 gene displayed prominent hydroureter arising from proximal segment and ureterovesical junction defects. These defects were associated with significant reduction in ureteric epithelial cell proliferation at E15.5 and E16.5 as well as absence of subepithelial ureteral mesenchymal cells in the urinary tract at E16.5 and E18.5. At the molecular level, increased BMP signaling was found in Fstl1 deficient ureters, indicated by elevated pSmad1/5/8 activity. In vitro study also indicated that Fstl1 can directly bind to ALK6 which is specifically expressed in ureteric epithelial cells in developing ureter. Furthermore, Sonic hedgehog (SHH) signaling, which is crucial for differentiation of ureteral subepithelial cell proliferation, was also impaired in Fstl1-/- ureter. Altogether, our data suggest that Fstl1 is essential in maintaining normal ureter development by antagonizing BMP signaling

Impact of Integrated Services on HIV Testing: A Nonrandomized Trial among Kenyan Family Planning Clients.

The impact of integrated reproductive health and HIV services on HIV testing and counseling (HTC) uptake was assessed among 882 Kenyan family planning clients using a nonrandomized cohort design within six intervention and six "comparison" facilities. The effect of integration on HTC goals (two tests over two years) was assessed using conditional logistic regression to test four "integration" exposures: a training and reorganization intervention; receipt of reproductive health and HIV services at recruitment; a functional measure of facility integration at recruitment; and a woman's cumulative exposure to functionally integrated care across different facilities over time. While recent receipt of HTC increased rapidly at intervention facilities, achievement of HTC goals was higher at comparison facilities. Only high cumulative exposure to integrated care over two years had a significant effect on HTC goals after adjustment (aOR 2.94, 95%CI 1.73-4.98), and programs should therefore make efforts to roll out integrated services to ensure repeated contact over time

Genetic approaches to human renal agenesis/hypoplasia and dysplasia

Congenital abnormalities of the kidney and urinary tract are frequently observed in children and represent a significant cause of morbidity and mortality. These conditions are phenotypically variable, often affecting several segments of the urinary tract simultaneously, making clinical classification and diagnosis difficult. Renal agenesis/hypoplasia and dysplasia account for a significant portion of these anomalies, and a genetic contribution to its cause is being increasingly recognized. Nevertheless, overlap between diseases and challenges in clinical diagnosis complicate studies attempting to discover new genes underlying this anomaly. Most of the insights in kidney development derive from studies in mouse models or from rare, syndromic forms of human developmental disorders of the kidney and urinary tract. The genes implicated have been shown to regulate the reciprocal induction between the ureteric bud and the metanephric mesenchyme. Strategies to find genes causing renal agenesis/hypoplasia and dysplasia vary depending on the characteristics of the study population available. The approaches range from candidate gene association or resequencing studies to traditional linkage studies, using outbred pedigrees or genetic isolates, to search for structural variation in the genome. Each of these strategies has advantages and pitfalls and some have led to significant discoveries in human disease. However, renal agenesis/hypoplasia and dysplasia still represents a challenge, both for the clinicians who attempt a precise diagnosis and for the geneticist who tries to unravel the genetic basis, and a better classification requires molecular definition to be retrospectively improved. The goal appears to be feasible with the large multicentric collaborative groups that share the same objectives and resources

(S)-2-acetoxy-5-undecanone, female sex pheromone of the raspberry cane midge, Resseliella theobaldi (Barnes)

The raspberry cane midge, Resseliella theobaldi, is a widespread pest of cultivated red raspberry in Europe. Pheromone-baited traps could provide a much-needed, accurate means to monitor the pest. Volatiles collected separately from virgin female and male midges were analyzed by gas chromatography (GC) coupled to mass spectrometry (MS) to reveal four female-specific components. In analyses by GC coupled to electroantennographic (EAG) recording from the antennae of a male midge, at least three of these components elicited responses. Based on its GC retention indices and mass spectrum, we propose that the major component is 2-acetoxy-5-undecanone and confirm this by synthesis of the racemic compound in seven steps and 63% yield from 4-pentenoic acid. The three minor components were each present at approximately 30% of the major component and were identified as 2-undecanone, (S)-2-acetoxyundecane, and (S)-2-undecanol by comparison of GC retention times and mass spectra with those of synthetic standards. GC analyses of the female-produced volatiles on an enantioselective column showed that only one enantiomer of 2-acetoxy-5-undecanone was present, and this was found to be the S-enantiomer by hydrolytic kinetic resolution of an epoxide intermediate in the synthesis and also by enantioselective hydrolysis of the racemic acetate with a lipase enzyme. The two enantiomers were also separated by high-performance liquid chromatography on an enantioselective column for field tests. In two field trapping tests, (S)-2-acetoxy-5-undecanone was highly attractive to male R. theobaldi; the R-enantiomer was not attractive. The racemic compound was just as attractive as the S-enantiomer, and addition of the three minor components in racemic form at two different loads did not affect catches. The pheromone could be dispensed from both rubber septa and polyethylene vials for at least 1 month under field conditions, but the former was preferred as it gave more uniform release. 2-Acetoxy-5-undecanone belongs to a new group of pheromone structures in the Cecidomyiidae, most others being mono- or diesters

PHOTOCHEMISTRY OF FORMALDEHYDE

Author Institution: School of Chemistry, University of BristolThe $HO_{x}$ family (OH and $HO_{2}$) is central to the photochemistry of the atmosphere. Recent measurement campaigns have revealed $HO_{x}$ concentrations much greater than predicted by models using only water, methane and ozone chemistry. Formaldehyde is now recognized as an important source of $HO_{x}$ in the upper troposphere. The photodissociation of formaldehyde by sunlight can occur through two distinct and competing channels: $H_{2}CO + h\nu \rightarrow H_{2} + CO H_{2}CO + h\nu \rightarrow HCO + H$ The second channel produces radicals that, after subsequent reaction with $O_{2}$, form $HO_{x}$. This project investigates the $HO_{x}$ production from the photochemistry of formaldehyde. To achieve this high resolution absorption cross section data for formaldehyde and formaldehyde quantum yields for the production of HCO are needed over a wavelength range and conditions of temperature and pressure appropriate to the upper troposphere. The data are then introduced into atmospheric models to predict the importance of formaldehyde in the upper tropospheric region