Sprouty Proteins Inhibit Receptor-mediated Activation of Phosphatidylinositol-specific Phospholipase C

PLCγ03B3 binds Spry1 and Spry2. Overexpression of Spry decreased PLCγ03B3 activity and IP3 and DAG production, whereas Spry-deficient cells yielded more IP3. Spry overexpression inhibited T-cell receptor signaling and Spry1 null T-cells hyperproliferated with TCR ligation. Through action of PLCγ03B3, Spry may influence signaling through multiple receptors

Hypothesis testing: discussion

Discussion on the papers by Zellner, Arnold and Siow, Aloysius, Posterior odds ratios for selected regression hypotheses and by Bernardo, José M., A Bayesian analysis of classical hypotheses testing, both of them part of a round table on Hypothesis testing held in the First International Congress on Bayesian Methods (Valencia, Spain, 28 May - 2 June 1979

SIRT1 Activates MAO-A in the Brain to Mediate Anxiety and Exploratory Drive

SIRT1 is a NAD+-dependent deacetylase that governs a number of genetic programs to cope with changes in the nutritional status of cells and organisms. Behavioral responses to food abundance are important for the survival of higher animals. Here we used mice with increased or decreased brain SIRT1 to show that this sirtuin regulates anxiety and exploratory drive by activating transcription of the gene encoding the monoamine oxidase A (MAO-A) to reduce serotonin levels in the brain. Indeed, treating animals with MAO-A inhibitors or selective serotonin reuptake inhibitors (SSRIs) normalized anxiety differences between wild-type and mutant animals. SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter. Both common and rare variations in the SIRT1 gene were shown to be associated with risk of anxiety in human population samples. Together these data indicate that SIRT1 mediates levels of anxiety, and this regulation may be adaptive in a changing environment of food availability.Leukemia & Lymphoma Society of America (Fellowship 5089-09)National Institutes of Health (U.S.)Paul F. Glenn FoundationNational Center for Research Resources (U.S.) (Grant UL1RR031990