The circadian clock controls many circadian outputs. Although a large number of transcripts are affected by the circadian oscillator, very little is known about their regulation and function. We show here that the Drosophila takeout gene, one of the output genes of the circadian oscillator, is regulated similarly to the circadian clock genes Clock (Clk) and cry. takeout RNA levels are at constant high levels in Clk JRK mutants. The circadian transcription factor PAR domain protein 1 (Pdp1ε) is a transcription factor that had previously been postulated to control clock output genes, particularly genes regulated similarly to Clk. In agreement with this, we show here that Pdp1ε is a regulator of takeout. Takeout levels are low in flies with reduced Pdp1ε and high in flies with increased amounts of Pdp1ε. Furthermore, flies with reduced or elevated Pdp1ε levels in the fat body display courtship defects, identifying Pdp1ε as an important transcriptional regulator in that tissue.fat body | courtship | clock | Drosophila G enetic and molecular analyses have yielded significant insight into the genes that constitute the core components of the Drosophila circadian clock (reviewed in refs. 1-3). It is regulated by two interlocked transcription/translation-based feedback loops, the period/timeless (per/tim) and Clock (Clk) loops (4). In addition, the regulation of the nuclear entry of proteins, their degradation rate, and phosphorylation state are crucial regulatory steps that are controlled by and contribute to the circadian clock. The per/tim cycle starts with the binding of CLK/CYC heterodimers to E-box promoter elements of the per and tim genes and their subsequent transcriptional activation. Eventually, the newly formed PER and TIM proteins will enter the nucleus and inhibit CLK/CYC action, thereby inhibiting the transcription of their own genes (5-7). Transcription of per and tim will resume once their protein levels have decreased sufficiently to release the inhibition of CLK/CYC. Rhythmic expression of Clock mRNA is regulated in the second loop, the Clock loop. CLK/CYC activate vrille (vri) and Pdp1ε, a transcriptional repressor and activator respectively, that have been shown to bind the Clock promoter competitively (8, 9). Although it was thought that this competition accounts for the oscillatory regulation of Clk mRNA, the fact that Clk mRNA levels are still high in Clk JRK mutants (4) and that the core oscillator is only minimally impacted in flies with increased or decreased PAR domain protein 1 (Pdp1ε) levels (depending on the allele/transgene and tissue examined) (10-12), indicate that an as yet unknown activator is required for Clk transcription. It has recently been demonstrated that CLK protein levels are constant in cells and that it is the phosphorylation state of the protein that determines its binding to DNA and its transcriptional activator function (7).Although locomotor activity is the best-characterized circadian output, the circadian clock regulates numerous other outputs such as sleep (13-16), n...

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IP-10 is a potential marker to identify latent TB infections that is expressed in large quantities and with good agreement with QFT-IT. The reasons for the discrepant results observed are discussed.

Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood–brain barrier (bbb) to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood–brain barrier is necessary and that male-specific factors in the bbb are physiologically required for normal male courtship behavior. Feminization of the bbb of adult males significantly reduces male courtship. We show that the bbb–specific G-protein coupled receptor moody and bbb–specific Go signaling in adult males are necessary for normal courtship. These data identify sex-specific factors and signaling processes in the bbb as important regulators of male mating behavior.

Male courtship behavior in Drosophila melanogaster is controlled by two main regulators, fruitless (fru) and doublesex (dsx). Their sex-specific expression in brain neurons has been characterized in detail, but little is known about the downstream targets of the sex-specific FRU and DSX proteins and how they specify the function of these neurons. While sexual dimorphism in the number and connections of fru and dsx expressing neurons has been observed, a majority of the neurons that express the two regulators are present in both sexes. This poses the question which molecules define the sex-specific function of these neurons. Signaling molecules are likely to play a significant role. We have identified a predicted G-protein coupled receptor (GPCR), CG4395, that is required for male courtship behavior. The courtship defect in the mutants can be rescued by expression of the wildtype protein in fru neurons of adult males. The GPCR is expressed in a subset of fru-positive antennal glomeruli that have previously been shown to be essential for male courtship. Expression of 4395-RNAi in GH146 projection neurons lowers courtship. This suggests that signaling through the CG4395 GPCR in this subset of fru neurons is critical for male courtship behavior.