Gene identification for the cblD defect of vitamin B12 metabolism

Background Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine. Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementation analysis. One of these defects, the cblD defect, can cause isolated methylmalonic aciduria, isolated homocystinuria, or both. Affected persons present with multisystem clinical abnormalities, including developmental, hematologic, neurologic, and metabolic findings. The gene responsible for the cblD defect has not been identified. Methods We studied seven patients with the cblD defect, and skin fibroblasts from each were investigated in cell culture. Microcell-mediated chromosome transfer and refined genetic mapping were used to localize the responsible gene. This gene was transfected into cblD fibroblasts to test for the rescue of adenosylcobalamin and methylcobalamin synthesis. Results The cblD gene was localized to human chromosome 2q23.2, and a candidate gene, designated MMADHC (methylmalonic aciduria, cblD type, and homocystinuria), was identified in this region. Transfection of wild-type MMADHC rescued the cellular phenotype, and the functional importance of mutant alleles was shown by means of transfection with mutant constructs. The predicted MMADHC protein has sequence homology with a bacterial ATP-binding cassette transporter and contains a putative cobalamin binding motif and a putative mitochondrial targeting sequence. Conclusions Mutations in a gene we designated MMADHC are responsible for the cblD defect in vitamin B12 metabolism. Various mutations are associated with each of the three biochemical phenotypes of the disorder

Foreign capital and gender differences in promotions: Evidence from large Brazilian manufacturing firms

This paper examines whether there exists obstacles hindering women's ascension in the largest firms of the Brazilian manufacturing industry. In particular, we check whether gender matters in the time it takes to get a promotion to a managerial position. Once we control for covariate-dependent censoring, we find significant evidence that foreign-owned firms feature less gender differences in promotions than domestic firms. The same applies in other dimensions of career progress, namely, wage growth and promotion likelihood. It turns out that wage gains after promotion contribute to generating wage differential between males and females only within domestic firms. This is consistent with statistical discrimination and with the self-selection that results from employees optimally choosing which jobs to apply for. Jobs in domestic firms offer more flexibility in terms of hours per week, whereas multinationals compete for the most career-concerned workers

Evaluation of Long-Term Phosphorus Fertilizer Placement Effect on Soil Phosphorus and Crop Yield

Phosphorus (P) accumulation in soil with long-term P fertilizer placements can result in a potentially large available reserve of this nutrient for subsequent crop production. This study investigated the effect of phosphorus fertilizer management (placement: broadcast versus deep band) after ten years on soil P, and yield response of crop rotation. Field studies were conducted for a period of ten years in Manhattan, KS. Three treatments were evaluated: 1) control with no P fertilizer application and two fertilizer treatments (80 lb P2O5/a); 2) surface broadcast; and 3) deep band at approximately 4- to 6-in. depth. All treatments received strip-tillage. After ten years, soil samples were collected from the row at two sampling depths (0–3 and 3–6 in.), and the soil P and grain yield of 2015 were evaluated. The accumulation of large amounts of soil P was directly affected by P fertilizer placement. The broadcast P fertilizer placement increased the soil P by the resin method in the topsoil (0–3 in.) and deep band in the subsoil (3–6 in.). Broadcast and deep band placements had the same effect on grain yield of corn and soybean, however, the deep band showed an average lower grain yield for wheat than broadcast

On the nature of some SGRs and AXPs as rotation-powered neutron stars

We investigate the possibility that some SGRs/AXPs could be canonical rotation-powered pulsars using realistic NS structure parameters instead of fiducial values. We show that realistic NS parameters lowers the estimated value of the magnetic field and radiation efficiency, $L_X/\dot{E}_{\rm rot}$, with respect to estimates based on fiducial NS parameters. We show that nine SGRs/AXPs can be described as canonical pulsars driven by the NS rotational energy, for $L_X$ computed in the soft (2--10~keV) X-ray band. We compute the range of NS masses for which $L_X/\dot{E}_{\rm rot}<1$. We discuss the observed hard X-ray emission in three sources of the group of nine potentially rotation-powered NSs. This additional hard X-ray component dominates over the soft one leading to $L_X/\dot{E}_{\rm rot}>1$ in two of them. We show that 9 SGRs/AXPs can be rotation-powered NSs if we analyze their X-ray luminosity in the soft 2--10~keV band. Interestingly, four of them show radio emission and six have been associated with supernova remnants (including Swift J1834.9-0846 the first SGR observed with a surrounding wind nebula). These observations give additional support to our results of a natural explanation of these sources in terms of ordinary pulsars. Including the hard X-ray emission observed in three sources of the group of potential rotation-powered NSs, this number of sources with $L_X/\dot{E}_{\rm rot}<1$ becomes seven. It remains open to verification 1) the accuracy of the estimated distances and 2) the possible contribution of the associated supernova remnants to the hard X-ray emission.Comment: 11 pages, 14 figures, to appear in A&