In mammals, female development has traditionally been considered a default process in the absence of the testis-determining gene, Sry. Recently, it has been documented that the gene for R-spondin1 (RSPO1), a novel class of soluble activator for Wnt/beta-catenin signaling, is mutated in two Italian families with female-to-male (XX) sex reversal. To elucidate the role of Rspo1 as a candidate female-determining gene in a mouse model, we generated Rspo1-null (Rspo1(-/-)) mice and found that Rspo1(-/-) XX mice displayed masculinized features including pseudohermaphroditism in genital ducts, depletion of fetal oocytes, male-specific coelomic vessel formation and ectopic testosterone production in the ovaries. Thus, although Rspo1 is required to fully suppress the male differentiation program and to maintain germ cell survival during the development of XX gonads, the loss of its activity has proved to be insufficient to cause complete XX sex reversal in mice. Interestingly, these partial sex-reversed phenotypes of Rspo1(-/-) XX mice recapitulated those of previously described Wnt-4(-/-) XX mice. In accordance with this finding, the expression of Wnt-4 and its downstream genes was deregulated in early Rspo1(-/-) XX gonads, suggesting that Rspo1 may participate in suppressing the male pathway in the absence of Sry and maintaining oocyte survival through positively regulating Wnt-4 signaling.

Bone Morphogenetic Protein (BMP) signaling mediated by the receptor Wishful thinking (Wit) is essential for nervous system development in Drosophila. Mutants lacking wit function show defects in neuromuscular junction development and function, specification of neurosecretory phenotypes, and eclosion behavior that result in lethality. The ligand is Glass bottom boat, the Drosophila ortholog of mammalian BMP‐7, which acts as a retrograde signal through the Wit receptor. In order to identify transcriptional targets of the BMP pathway in the Drosophila nervous system, we have analyzed the gene expression profile of wit mutant larval central nervous system. Genes differentially expressed identified by microarray analysis have been verified by quantitative PCR and studied by in situ hybridization. Among the genes thus identified, we find solute transporters, neuropeptides, mitochondrial proteins, and novel genes. In addition, several genes are regulated by wit in an isoform‐specific manner that suggest regulation of alternative splicing by BMP signaling. Developmental Dynamics 239:2413–2425, 2010. © 2010 Wiley‐Liss, Inc.

The factors underlying psychological distress are multifactorial. Early intervention to treat subclinical anxiety and depression may prevent subsequent psychological distress.

A low level of personal accomplishment was relatively high among Japanese physicians compared with previous studies. Insufficient confidence in the psychological care of patients was associated with physician burnout rather than involvement in end-of-life care.

Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = −2.6626 to −0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels.