The pigment-dispersing factor (PDF) is a neuropeptide controlling circadian behavioral rhythms in Drosophila, but its receptor is not yet known. From a large-scale temperature preference behavior screen in Drosophila, we isolated a P insertion mutant that preferred different temperatures during the day and night. This mutation, which we named han, reduced the transcript level of CG13758. We found that Han was expressed specifically in 13 pairs of circadian clock neurons in the adult brain. han null flies showed arrhythmic circadian behavior in constant darkness. The behavioral characteristics of han null mutants were similar to those of pdf null mutants. We also found that PDF binds specifically to S2 cells expressing Han, which results in the elevation of cAMP synthesis. Therefore, we herein propose that Han is a PDF receptor regulating circadian behavioral rhythm through coordination of activities of clock neurons.

Several transient receptor potential channels were recently found to be activated by temperature stimuli in vitro. Their physiological and behavioral roles are largely unknown. From a temperature-preference behavior screen of 27,000 Drosophila melanogaster P-insertion mutants, we isolated a gene, named pyrexia (pyx), encoding a new transient receptor potential channel. Pyx was opened by temperatures above 40 degrees C in Xenopus laevis oocytes and HEK293T cells. It was ubiquitously expressed along the dendrites of a subset of peripheral nervous system neurons and was more permeable to K(+) than to Na(+). Although some pyx alleles resulted in abnormal temperature preferences, pyx null flies did not have significantly different temperature preferences than wild-type flies. But 60% of pyx null flies were paralyzed within 3 min of exposure to 40 degrees C, whereas only 9% of wild-type flies were paralyzed by the same stimulus. From these findings, we propose that the primary in vivo role of Pyx is to protect flies from high-temperature stress.

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Objective: Integrin-associated protein (CD47) binds specifically to the inhibitory receptor signal-regulatory protein. This study was designed to evaluate the role of CD47 in natural killer (NK) cell-mediated cytotoxicity against cancer cells. Methods: Head-and-neck squamous cell carcinoma (HNSCC) cell lines were analyzed for the expression of CD47 and susceptibility to NK cell-mediated killing. Cytolytic activity was assessed by ⁵¹Cr-specific release assays and by measuring cytokine production. Results: HNSCC cell lines that had high CD47 expression showed lower levels of NK cytotoxicity than those with low CD47 expression. After pre-treating cells with neutralizing major histocompatibility complex (MHC) class I or anti-CD47 antibodies, NK cell-mediated cytotoxicity against HNSCC cell lines increased. In addition, when CD47 cDNA was transfected into Caco-2 cells, NK cell-mediated cytotoxicity decreased. Conclusion: These findings suggest that CD47 may play an inhibitory role in NK cell-mediated cytotoxicity against cancer cells, implying a possible mechanism of immune escape in human cancer.

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Fluorescent small molecules have become indispensable tools for biomedical research along with the rapidly developing optical imaging technology. We report here a neural stem cell specific boron-dipyrromethane (BODIPY) derivative compound of designation red 3 (CDr3), developed through a high throughput/content screening of in-house generated diversity oriented fluorescence library in stem cells at different developmental stages. This novel compound specifically detects living neural stem cells of both human and mouse origin. Furthermore, we identified its binding target by proteomic analysis as fatty acid binding protein 7 (FABP7), also known as brain lipid binding protein) which is highly expressed in neural stem cells and localized in the cytoplasm. CDr3 will be a valuable chemical tool in the study and applications of neural stem cells.

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