Analysis in Drosophila suggests that evolutionary changes in the spatial regulation of the transcription factor doublesex play a key role in the origin, diversification, and loss of sex-specific structures.

doublesex (dsx) encodes sex-specific transcription factors (DSX(F) in females and DSX(M) in males) that act at the bottom of the Drosophila somatic sex determination hierarchy. dsx, which is conserved among diverse taxa, is responsible for directing all aspects of Drosophila somatic sexual differentiation outside the nervous system. The role of dsx in the nervous system remainsminimally understood. Here, the mechanisms by which DSX acts to establish dimorphism in the central nervous system were examined. This study shows that the number of DSX-expressing cells in the central nervous system is sexually dimorphic during both pupal and adult stages. Additionally, the number of DSX-expressing cells depends on both the amount of DSX and the isoform present. One cluster of DSX-expressing neurons in the ventral nerve cord undergoes female-specific cell death that is DSX(F)-dependent. Another DSX-expressing cluster in the posterior brain undergoes more cell divisions in males than in females. Additionally, early in development, DSX(M) is present in a portion of the neural circuitry in which the male-specific product of fruitless (fru) is produced, in a region that has been shown to be critical for sex-specific behaviors. This study demonstrates that DSX(M) and FRU(M) expression patterns are established independent of each other in the regions of the central nervous system examined. In addition to the known role of dsx in establishing sexual dimorphism outside the central nervous system, the results demonstrate that DSX establishes sex-specific differences in neural circuitry by regulating the number of neurons using distinct mechanisms.

In pancreatic carcinoma patients with gastric outlet obstruction, duodenal stenting results in an earlier discharge from hospital and possibly improved survival.

BackgroundDrosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response.ResultsWe determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels.ConclusionsSubstantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors.

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Background: Drosophila melanogaster undergoes a complete metamorphosis, during which time the larval male and female forms transition into sexually dimorphic, reproductive adult forms. To understand this complex morphogenetic process at a molecular-genetic level, whole genome microarray analyses were performed.

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Transcription factor NF-B plays a key regulatory role in the cellular response to pro-inflammatory cytokines such as tumor necrosis factor-␣ (TNF). In the absence of TNF, NF-B is sequestered in the cytoplasm by inhibitory IB proteins. Phosphorylation of IB by the ␤-catalytic subunit of IKK, a multicomponent IB kinase, targets the inhibitor for proteolytic destruction and facilitates nuclear translocation of NF-B. This pathway is initiated by TNF-dependent phosphorylation of T loop serines in IKK␤, which greatly stimulates IB kinase activity. Prior in vitro mixing experiments indicate that protein serine/threonine phosphatase 2A (PP2A) can dephosphorylate these T loop serines and inactivate IKK, suggesting a negative regulatory role for PP2A in IKK signaling. Here we provided several in vivo lines of evidence indicating that PP2A plays a positive rather than a negative role in the regulation of IKK. First, TNF-induced degradation of IB is attenuated in cells treated with okadaic acid or fostriecin, two potent inhibitors of PP2A. Second, PP2A forms stable complexes with IKK in untransfected mammalian cells. This interaction is critically dependent on amino acid residues 121-179 of the IKK␥ regulatory subunit. Third, deletion of the PP2A-binding site in IKK␥ attenuates T loop phosphorylation and catalytic activation of IKK␤ in cells treated with TNF. Taken together, these data provide strong evidence that the formation of IKK⅐PP2A complexes is required for the proper induction of IB kinase activity in vivo.Insults to the immune system and various forms of cellular stress activate the transcription factor NF-B 3 and other dimeric members of the Rel polypeptide family (reviewed in Refs. 1 and 2). NF-B regulates the expression of multiple genes involved in the control of cell growth, division, and survival. A variety of stimuli can activate NF-B-mediated gene transcription, including tumor necrosis factor-␣ (TNF), interleukin-1, T and B cell mitogens, bacterial products, viral proteins, doublestranded RNA, as well as physical and chemical stress. Most of these agonists converge on a latent, cytoplasmic form of NF-B that associates with IB␣ or other members of the inhibitory IB family. Following cellular stimulation, IB␣ is phosphorylated, ubiquitinated, and degraded by the 26 S proteasome. In turn, NF-B is free to translocate to the nuclear compartment where it activates transcription units containing the B-binding site (1, 2).Phosphorylation of IB is catalyzed by a multicomponent protein kinase termed the IKK signalsome (3). Within the prototypic complex are two highly homologous IB kinase subunits, termed IKK␣ and IKK␤, which form homo-or heterodimers via their leucine zippers (4 -6). In response to various cell stimuli, IKK␣ and IKK␤ are activated by a mechanism involving phosphorylation of their respective T loops at Ser-176/Ser-180 and Ser-177/Ser-181 (7). T loop phosphorylation occurs via IKK subunit trans-autophosphorylation and/or the action of upstream kinases (3). In addition to phosphorylation of T loop ser...