Lithium promotes neural precursor cell proliferation: evidence for the involvement of the non-canonical GSK-3β-NF-AT signaling

Lithium, a drug that has long been used to treat bipolar disorder and some other human pathogenesis, has recently been shown to stimulate neural precursor growth. However, the involved mechanism is not clear. Here, we show that lithium induces proliferation but not survival of neural precursor cells. Mechanistic studies suggest that the effect of lithium mainly involved activation of the transcription factor NF-AT and specific induction of a subset of proliferation-related genes. While NF-AT inactivation by specific inhibition of its upstream activator calcineurin antagonized the effect of lithium on the proliferation of neural precursor cells, specific inhibition of the NF-AT inhibitor GSK-3β, similar to lithium treatment, promoted neural precursor cell proliferation. One important function of lithium appeared to increase inhibitory phosphorylation of GSK-3β, leading to GSK-3β suppression and subsequent NF-AT activation. Moreover, lithium-induced proliferation of neural precursor cells was independent of its role in inositol depletion. These findings not only provide mechanistic insights into the clinical effects of lithium, but also suggest an alternative therapeutic strategy for bipolar disorder and other neural diseases by targeting the non-canonical GSK-3β-NF-AT signaling

The low-temperature energy calibration system for the CUORE bolometer array

The CUORE experiment will search for neutrinoless double beta decay (0nDBD) of 130Te using an array of 988 TeO_2 bolometers operated at 10 mK in the Laboratori Nazionali del Gran Sasso (Italy). The detector is housed in a large cryogen-free cryostat cooled by pulse tubes and a high-power dilution refrigerator. The TeO_2 bolometers measure the event energies, and a precise and reliable energy calibration is critical for the successful identification of candidate 0nDBD and background events. The detector calibration system under development is based on the insertion of 12 gamma-sources that are able to move under their own weight through a set of guide tubes that route them from deployment boxes on the 300K flange down into position in the detector region inside the cryostat. The CUORE experiment poses stringent requirements on the maximum heat load on the cryostat, material radiopurity, contamination risk and the ability to fully retract the sources during normal data taking. Together with the integration into a unique cryostat, this requires careful design and unconventional solutions. We present the design, challenges, and expected performance of this low-temperature energy calibration system.Comment: To be published in the proceedings of the 13th International Workshop on Low Temperature Detectors (LTD), Stanford, CA, July 20-24, 200

Three-dimensional Magnetohydrodynamic Simulations of Buoyant Bubbles in Galaxy Clusters

We report results of 3D MHD simulations of the dynamics of buoyant bubbles in magnetized galaxy cluster media. The simulations are three dimensional extensions of two dimensional calculations reported by Jones & De Young (2005). Initially spherical bubbles and briefly inflated spherical bubbles all with radii a few times smaller than the intracluster medium (ICM) scale height were followed as they rose through several ICM scale heights. Such bubbles quickly evolve into a toroidal form that, in the absence of magnetic influences, is stable against fragmentation in our simulations. This ring formation results from (commonly used) initial conditions that cause ICM material below the bubbles to drive upwards through the bubble, creating a vortex ring; that is, hydrostatic bubbles develop into "smoke rings", if they are initially not very much smaller or very much larger than the ICM scale height. Even modest ICM magnetic fields with beta = P_gas/P_mag ~ 10^3 can influence the dynamics of the bubbles, provided the fields are not tangled on scales comparable to or smaller than the size of the bubbles. Quasi-uniform, horizontal fields with initial beta ~ 10^2 bifurcated our bubbles before they rose more than about a scale height of the ICM, and substantially weaker fields produced clear distortions. On the other hand, tangled magnetic fields with similar, modest strengths are generally less easily amplified by the bubble motions and are thus less influential in bubble evolution. Inclusion of a comparably strong, tangled magnetic field inside the initial bubbles had little effect on our bubble evolution, since those fields were quickly diminished through expansion of the bubble and reconnection of the initial field.Comment: 20 pages, 12 figures. Accepted for publication in The Astrophysical Journa

Systematic study of X-ray Cavities in the brightest galaxy of the Draco Constellation NGC 6338

We present results based on the systematic analysis of currently available Chandra archive data on the brightest galaxy in the Draco constellation NGC 6338, in order to investigate the properties of the X-ray cavities. In the central ~6 kpc, at least a two and possibly three, X-ray cavities are evident. All these cavities are roughly of ellipsoidal shapes and show a decrement in the surface brightness of several tens of percent. In addition to these cavities, a set of X-ray bright filaments are also noticed which are spatially coincident with the H{\alpha} filaments over an extent of 15 kpc. The H{\alpha} emission line filaments are perpendicular to the X- ray cavities. Spectroscopic analysis of the hot gas in the filaments and cavities reveal that the X-ray filaments are cooler than the gas contained in the cavities. The emission line ratios and the extended, asymmetric nature of the H{\alpha} emission line filaments seen in this system require a harder ionizing source than that produced by star formation and/or young, massive stars. Radio emission maps derived from the analysis of 1.4 GHz VLA FIRST survey data failed to show any association of these X-ray cavities with radio jets, however, the cavities are filled by radio emission. The total power of the cavities is 17\times 1042 erg s-1 and the ratio of the radio luminosity to cavity power is ~ 10-4, implying that most of the jet power is mechanical.Comment: The paper contains 12 figures and 3 tables, Accepted 2011 December 7 for publication in MNRA

Alcohol-related expectancies are associated with the D2 dopamine receptor and GABAa receptor B3 subunit genes

Molecular genetic research has identified promising markers of alcohol dependence, including alleles of the D2 dopamine receptor (DRD2) and the GABAA receptor ￢3 subunit (GABRB3) genes. Whether such genetic risk manifests itself in stronger alcohol-related outcome expectancies, or in difficulty resisting alcohol, is unknown. In the present study, A1+ (A1A1 and A1A2 genotypes) and A1- (A2A2 genotype) alleles of the DRD2 and G1+ (G1G1 and G1 non-G1 genotypes) and G1- (non-G1 non-G1 genotype) alleles of the GABRB3 were determined in a group of 56 medically-ill patients diagnosed with alcohol dependence. Mood-related Alcohol Expectancy (AE) and Drinking Refusal Self-Efficacy (DRSE) were assessed using the Drinking Expectancy Profile (Young and Oei, 1996). Patients with the DRD2 A1+ allele, compared to those with the DRD2 A1- allele, reported lower DRSE in situations of social pressure (p=. 009). Similarly, lower DRSE was reported under social pressure by patients with the GABRB3 G1+ allele when compared to those with the GABRB3 G1- allele (p=.027). Patients with the GABRB3 G1+ allele also revealed reduced DRSE in situations characterized by negative affect than patients with the GABRB3 G1- alleles (p=. 037). Patients carrying the GABRB3 G1+ allele showed stronger AE relating to negative affective change (for example, increased depression) than their GABRB3 G1- counterparts (p=. 006). Biological influence in the development of some classes of cognitions is hypothesized. The clinical implications, particularly with regard to patient-treatment matching and the development of an integrated psychological and pharmacogenetic approach are discussed

Synthetic Observations of Simulated AGN Jets: X-ray Cavities

Observations of X-ray cavities formed by powerful jets from AGN in galaxy cluster cores are widely used to estimate the energy output of the AGN. Using methods commonly applied to observations of clusters, we conduct synthetic X-ray observations of 3D MHD simulated jet-ICM interactions to test the reliability of measuring X-ray cavity power. These measurements are derived from empirical estimates of the enthalpy content of the cavities and their implicit ages. We explore how such physical factors as jet intermittency and observational conditions such as orientation of the jets with respect to the line of sight impact the reliability of observational measurements of cavity enthalpy and age. An estimate of the errors in these quantities can be made by directly comparing "observationally" derived values with "actual" values from the simulations. In our tests, cavity enthalpy derived from observations was typically within a factor of two of the simulation values. Cavity age and, therefore, cavity power are sensitive to the accuracy of the estimated inclination angle of the jets. Cavity age and power estimates within a factor of two of the actual values are possible given an accurate inclination angle.Comment: 34 pages, 14 figures, accepted for publication in Ap