Intra-accumbens baclofen, but not muscimol, increases second order instrumental responding for food reward in rats

Stimulation of either GABA(A) or GABA(B) receptors within the nucleus accumbens shell strongly enhances food intake in rats. However the effects of subtype-selective stimulation of GABA receptors on instrumental responses for food reward are less well characterized. Here we contrast the effects of the GABA(A) receptor agonist muscimol and GABA(B) receptor agonist baclofen on instrumental responding for food using a second order reinforcement schedule. Bilateral intra-accumbens administration of baclofen (220-440 pmol) stimulated responding but a higher dose (660 pmol) induced stereotyped oral behaviour that interfered with responding. Baclofen (220-660 pmol) also stimulated intake of freely available chow. Muscimol (220-660 pmol) was without effect on responding for food on this schedule but did stimulate intake of freely available chow. Unilateral administration of either baclofen or muscimol (220 pmol) induced similar patterns of c-fos immunoreactivity in several hypothalamic sites but differed in its induction in the central nucleus of the amygdala. We conclude that stimulation of GABA(A) or GABA(B) receptors in the nucleus accumbens shell of rats produces clearly distinguishable effects on operant responding for food

Psychoses in relation to the exercising of the reproductive function in women

The essence of the biological life of woman is a series of sexual adjustments dependent upon the changes that occur in the actual seximl organs and the closely related endocrines. Coincident with this is her psychological relation to her human and material environment, which must, pari-passu, seek to harmonise with the corresponding physical adjustment. During the actual functioning of the sexual organs the adjustments, both physical and psychical, are dynamic in nature and far-reaching in effect. The actual mental attitude to pregnancy is a complex and individual one, with but one common factor, fear, in the background of the mind. Adjustments require the display or redistribution of energy, consequently in a brain below the average germinally, or, from disease, faulty, inadequate adjustments may arise. These reactions constitute the mental disorders which characterise the active period of the reproductive functioning

Star Formation at the Twilight of the Dark Ages: Which Stars Reionized the Universe?

We calculate the global star formation rate density (SFRD) from z ~ 30-3 using a semi-analytic model incorporating the hierarchical assembly of dark matter halos, gas cooling via atomic hydrogen, star formation, supernova feedback, and suppression of gas collapse in small halos due to the presence of a photoionizing background. We compare the results with the predictions of simpler models based on the rate of dark matter halo growth and a fixed ratio of stellar-to-dark mass, and with observational constraints on the SFRD at 3 < z < 6. We also estimate the star formation rate due to very massive, metal-free Pop III stars using a simple model based on the halo formation rate, calibrated against detailed hydrodynamic simulations of Pop III star formation. We find that the total production rate of hydrogen-ionizing photons during the probable epoch of reionization (15 < z < 20) is approximately equally divided between Pop II and Pop III stars, and that if reionization is late (less than about 15, close to the lower limit of the range allowed by the WMAP results), then Pop II stars alone may be able to reionize the Universe.Comment: submitted to ApJ

Non-linear Stochastic Galaxy Biasing in Cosmological Simulations

We study the biasing relation between dark-matter halos or galaxies and the underlying mass distribution, using cosmological $N$-body simulations in which galaxies are modelled via semi-analytic recipes. The nonlinear, stochastic biasing is quantified in terms of the mean biasing function and the scatter about it as a function of time, scale and object properties. The biasing of galaxies and halos shows a general similarity and a characteristic shape, with no galaxies in deep voids and a steep slope in moderately underdense regions. At \sim 8\hmpc, the nonlinearity is typically \lsim 10 percent and the stochasticity is a few tens of percent, corresponding to $\sim 30$ percent variations in the cosmological parameter $\beta=\Omega^{0.6}/b$. Biasing depends weakly on halo mass, galaxy luminosity, and scale. The time evolution is rapid, with the mean biasing larger by a factor of a few at $z\sim 3$ compared to $z=0$, and with a minimum for the nonlinearity and stochasticity at an intermediate redshift. Biasing today is a weak function of the cosmological model, reflecting the weak dependence on the power-spectrum shape, but the time evolution is more cosmology-dependent, relecting the effect of the growth rate. We provide predictions for the relative biasing of galaxies of different type and color, to be compared with upcoming large redshift surveys. Analytic models in which the number of objects is conserved underestimate the evolution of biasing, while models that explicitly account for merging provide a good description of the biasing of halos and its evolution, suggesting that merging is a crucial element in the evolution of biasing.Comment: 27 pages, 21 figures, submitted to MNRA

TTC5 is required to prevent apoptosis of acute myeloid leukemia stem cells

Using a screening strategy, we identified the tetratricopeptide repeat (TPR) motif protein, Tetratricopeptide repeat domain 5 (TTC5, also known as stress responsive activator of p300 or Strap) as required for the survival of human acute myeloid leukemia (AML) cells. TTC5 is a stress-inducible transcription cofactor known to interact directly with the histone acetyltransferase EP300 to augment the TP53 response. Knockdown (KD) of TTC5 induced apoptosis of both murine and human AML cells, with concomitant loss of clonogenic and leukemia-initiating potential; KD of EP300 elicited a similar phenotype. Consistent with the physical interaction of TTC5 and EP300, the onset of apoptosis following KD of either gene was preceded by reduced expression of BCL2 and increased expression of pro-apoptotic genes. Forced expression of BCL2 blocked apoptosis and partially rescued the clonogenic potential of AML cells following TTC5 KD. KD of both genes also led to the accumulation of MYC, an acetylation target of EP300, and the form of MYC that accumulated exhibited relative hypoacetylation at K148 and K157, residues targeted by EP300. In view of the ability of excess cellular MYC to sensitize cells to apoptosis, our data suggest a model whereby TTC5 and EP300 cooperate to prevent excessive accumulation of MYC in AML cells and their sensitization to cell death. They further reveal a hitherto unappreciated role for TTC5 in leukemic hematopoiesis

The nature of the ISM in galaxies during the star-formation activity peak of the Universe

We combine a semi-analytic model of galaxy formation, tracking atomic and molecular phases of cold gas, with a three-dimensional radiative-transfer and line tracing code to study the sub-mm emission from atomic and molecular species (CO, HCN, [CI], [CII], [OI]) in galaxies. We compare the physics that drives the formation of stars at the epoch of peak star formation (SF) in the Universe (z = 2.0) with that in local galaxies. We find that normal star-forming galaxies at high redshift have much higher CO-excitation peaks than their local counterparts and that CO cooling takes place at higher excitation levels. CO line ratios increase with redshift as a function of galaxy star-formation rate, but are well correlated with H2 surface density independent of redshift. We find an increase in the [OI]/[CII] line ratio in typical star-forming galaxies at z = 1.2 and z = 2.0 with respect to counterparts at z = 0. Our model results suggest that typical star-forming galaxies at high redshift consist of much denser and warmer star-forming clouds than their local counterparts. Galaxies belonging to the tail of the SF activity peak at z = 1.2 are already less dense and cooler than counterparts during the actual peak of SF activity (z = 2.0). We use our results to discuss how future ALMA surveys can best confront our predictions and constrain models of galaxy formation.Comment: 19 pages, 14 figures, accepted for publication in MNRA

Hierarchical Bayesian inference of the Initial Mass Function in Composite Stellar Populations

The initial mass function (IMF) is a key ingredient in many studies of galaxy formation and evolution. Although the IMF is often assumed to be universal, there is continuing evidence that it is not universal. Spectroscopic studies that derive the IMF of the unresolved stellar populations of a galaxy often assume that this spectrum can be described by a single stellar population (SSP). To alleviate these limitations, in this paper we have developed a unique hierarchical Bayesian framework for modelling composite stellar populations (CSPs). Within this framework we use a parameterized IMF prior to regulate a direct inference of the IMF. We use this new framework to determine the number of SSPs that is required to fit a set of realistic CSP mock spectra. The CSP mock spectra that we use are based on semi-analytic models and have an IMF that varies as a function of stellar velocity dispersion of the galaxy. Our results suggest that using a single SSP biases the determination of the IMF slope to a higher value than the true slope, although the trend with stellar velocity dispersion is overall recovered. If we include more SSPs in the fit, the Bayesian evidence increases significantly and the inferred IMF slopes of our mock spectra converge, within the errors, to their true values. Most of the bias is already removed by using two SSPs instead of one. We show that we can reconstruct the variable IMF of our mock spectra for signal-to-noise ratios exceeding $\sim$75.Comment: Accepted for publication in MNRAS, 16 pages, 8 figure

Source, Path and Site Effects on Loma Prieta Strong Motions

The amplitudes of strong ground motions from the Loma Prieta earthquake recorded in the San Francisco and Oakland areas exceeded the levels predicted by standard empirical attenuation relations. Preliminary analysis of accelerograms having known trigger times suggests that the elevation of ground motion amplitudes in the distance range of approximately 40 to 100 km was due to critical reflections from the base of the crust. These reflections were large and occurred at relatively close range because of the deep focal depth of the earthquake and the strong velocity gradient at the base of the crust, and were enhanced by rupture directivity. These motions were further amplified, presumably by impedance contrast effects, at soft soil sites in San Francisco and Oakland. The effect of the critical reflections in amplifying peak accelerations of the Loma Prieta earthquake in the San Francisco and Oakland regions was as large as the effect of soft soil site conditions