Detection Of KOI-13.01 Using The Photometric Orbit

We use the KOI-13 transiting star-planet system as a test case for the recently developed BEER algorithm (Faigler & Mazeh 2011), aimed at identifying non-transiting low-mass companions by detecting the photometric variability induced by the companion along its orbit. Such photometric variability is generated by three mechanisms, including the beaming effect, tidal ellipsoidal distortion, and reflection/heating. We use data from three Kepler quarters, from the first year of the mission, while ignoring measurements within the transit and occultation, and show that the planet's ephemeris is clearly detected. We fit for the amplitude of each of the three effects and use the beaming effect amplitude to estimate the planet's minimum mass, which results in M_p sin i = 9.2 +/- 1.1 M_J (assuming the host star parameters derived by Szabo et al. 2011). Our results show that non-transiting star-planet systems similar to KOI-13.01 can be detected in Kepler data, including a measurement of the orbital ephemeris and the planet's minimum mass. Moreover, we derive a realistic estimate of the amplitudes uncertainties, and use it to show that data obtained during the entire lifetime of the Kepler mission, of 3.5 years, will allow detecting non-transiting close-in low-mass companions orbiting bright stars, down to the few Jupiter mass level. Data from the Kepler Extended Mission, if funded by NASA, will further improve the detection capabilities.Comment: Accepted to AJ on October 4, 2011. Kepler Q5 Long Cadence data will become publicly available on MAST by October 23. Comments welcome (V2: minor changes, to reflect proof corrections

Why is Behavioral Game a Game for Economists? : The concept of beliefs in equilibrium

The interdisciplinary exchange between economists and psychologists has so far been more active and fruitful in the modifications of Expected Utility Theory than in those of Game Theory. We argue that this asymmetry may be explained by economists' specific way of doing equilibrium analysis of aggregate-level outcomes in their practice, and by psychologists' reluctance to fully engage with such practice. We focus on the notion of belief that is embedded in economists' practice of equilibrium analysis, more specifically Nash equilibrium, and argue that its difference from the psychological counterpart is one of the factors that makes interdisciplinary exchange in behavioral game theory more difficult.Peer reviewe

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Diverse chemotypes drive biased signaling by cannabinoid receptors

Cannabinoid CB1 and CB2 receptors are members of the G protein-coupled receptor family, which is the largest class of membrane proteins in the human genome. As part of the endocannabinoid system, they have many regulatory functions in the human body. Their malfunction therefore triggers a diverse set of undesired conditions, such as pain, neuropathy, nephropathy, pruritus, osteoporosis, cachexia and Alzheimer’s disease. Although drugs targeting the system exist, the molecular and functional mechanisms involved are still poorly understood, preventing the development of better therapeutics with fewer undesired effects. One path toward the development of better and safer medicines targeting cannabinoid receptors relies on the ability of some compounds to activate a subset of pathways engaged by the receptor while sparing or even inhibiting the others, a phenomenon known as biased signaling. To take advantage of this phenomenon for drug development, a better profiling of the pathways engaged by the receptors is required. Using a BRET-based signaling detection platform, we systematically analyzed the primary signaling cascades activated by CB1 and CB2 receptors, including 9 G protein and 2 β-arrestin subtypes. Given that biased signaling is driven by ligand-specific distinct active conformations of the receptor, establishing a link between the signaling profiles elicited by different drugs and their chemotypes may help designing compounds that selectively activate beneficial pathways while avoiding those leading to undesired effects. We screened a selection of 35 structurally diverse ligands, including endocannabinoids, phytocannabinoids and synthetic compounds structurally similar or significantly different from natural cannabinoids. Our data show that biased signaling is a prominent feature of the cannabinoid receptor system and that, as predicted, ligands with different chemotypes have distinct signaling profiles. The study therefore allows for better understanding of cannabinoid receptors signaling and provides the information about tool compounds that can now be used to link signaling pathways to biological outcomes, aiding the design of improved therapeutics

Ebi/AP-1 Suppresses Pro-Apoptotic Genes Expression and Permits Long-Term Survival of Drosophila Sensory Neurons

Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1) is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box–like and WD40 repeats–containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1) and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration