Clozapine Increases Nestin Concentration in the Adult Male Rat Hippocampus: A Preliminary Study

Patients with schizophrenia, and rodent models of the disease, both exhibit suppressed neurogenesis, with antipsychotics possibly enhancing neurogenesis in pre-clinical models. Nestin, a cytoskeletal protein, is implicated in neuronal differentiation and adult neurogenesis. We hy-pothesized that schizophrenia pathogenesis involves nestin downregulation; however, few studies have related nestin to schizophrenia. We assessed nestin protein concentration, prepulse inhibition (PPI), and social interaction in the MK-801 model of schizophrenia, with or without antipsychotic (clozapine) treatment. Adult male Sprague–Dawley rats were intraperitoneally administered saline or MK-801 (0.1 mg/kg) to produce a schizophrenia-like phenotype, with concomitant subcutaneous injections of vehicle or clozapine (5 mg/kg). PPI was assessed on days 1, 8, and 15, and social interaction was assessed on day 4. Hippocampus tissue samples were dissected for Western blotting of nestin concentration. MK-801 alone did not alter nestin concentration, while clozapine alone enhanced hippocampal nestin concentration; this effect was not apparent in animals with MK-801 and clozapine co-administration. MK-801 also produced schizophrenia-like PPI disruptions, some of which were reversed by clozapine. Social interaction deficits were not detected in this model. This is the first report of clozapine-induced enhancements of hippocampal nestin concentration that might be mediated by NMDA receptors. Future studies will explore the impact of neurodevelopmental nestin concentration on symptom onset and antipsychotic treatment

Cannabis Vapor Exposure Alters Neural Circuit Oscillatory Activity in a Neurodevelopmental Model of Schizophrenia: Exploring the Differential Impact of Cannabis Constituents

Cannabis use is highly prevalent in patients with schizophrenia and worsens the course of the disorder. To understand how exposure to cannabis changes schizophrenia-related oscillatory disruptions, we investigated the impact of administering cannabis vapor containing either Δ9-tetrahydrocannabinol (THC) or balanced THC/cannabidiol (CBD) on oscillatory activity in the neonatal ventral hippocampal lesion (NVHL) rat model of schizophrenia. Male Sprague Dawley rats underwent lesion or sham surgeries on postnatal day 7. In adulthood, electrodes were implanted targeting the cingulate cortex (Cg), the prelimbic cortex (PrLC), the hippocampus (HIP), and the nucleus accumbens (NAc). Local field potential recordings were obtained after rats were administered either the THC-only cannabis vapor (8-18% THC/0% CBD) or the Balanced THC:CBD cannabis vapor (4-11% THC/8.5-15.5% CBD) in a cross-over design with a 2-week wash-out period between exposures. Compared to controls, NVHL rats had reduced baseline gamma power in the Cg, HIP, and NAc, and reduced HIP-Cg high-gamma coherence. THC-only vapor exposure broadly suppressed oscillatory power and coherence, even beyond the baseline reductions observed in NHVL rats. Balanced THC:CBD vapor, however, did not suppress oscillatory power and coherence, and in some instances enhanced power. For NVHL rats, THC-only vapor normalized the baseline HIP-Cg high-gamma coherence deficits. NHVL rats demonstrated a 20 ms delay in HIP theta to high-gamma phase coupling, which was not apparent in the PrLC and NAc after both exposures. In conclusion, cannabis vapor exposure has varying impacts on oscillatory activity in NVHL rats, and the relative composition of naturally occurring cannabinoids may contribute to this variability

The Impact of Sex, Circadian Disruption, and the Clock\u3csup\u3e∆19/∆19\u3c/sup\u3e Genotype on Alcohol Drinking in Mice

Shift work is associated with increased alcohol drinking, more so in males than females, and is thought to be a coping mechanism for disrupted sleep cycles. However, little is presently known about the causal influence of circadian rhythm disruptions on sex differences in alcohol consumption. In this study, we disrupted circadian rhythms in female and male mice using both environmental (i.e., shifting diurnal cycles) and genetic (i.e., Clock∆19/∆19 mutation) manipulations, and measured changes in alcohol consumption and preference using a two-bottle choice paradigm. Alcohol consumption and preference, as well as food and water consumption, total caloric intake, and weight were assessed in adult female and male Clock∆19/∆19 mutant mice or wild-type (WT) litter-mates, housed under a 12-hour:12-hour light:dark (L:D) cycle or a shortened 10-hour:10-hour L:D cycle. Female WT mice (under both light cycles) increased their alcohol consumption and preference over time, a pattern not observed in male WT mice. Compared to WT mice, Clock∆19/∆19 mice displayed increased alcohol consumption and preference. Sex differences were not apparent in Clock∆19/∆19 mice, with or without shifting diurnal cycles. In conclusion, sex differences in alcohol consumption patterns are evident and increase with prolonged access to alcohol. Disrupting circadian rhythms by mutating the Clock gene greatly increases alcohol consumption and abolishes sex differences present in WT animals

Place field repetition and spatial learning in a multicompartment environment

Recent studies have shown that place cells in the hippocampus possess firing fields that repeat in physically similar, parallel environments. These results imply that it should be difficult for animals to distinguish parallel environments at a behavioral level. To test this, we trained rats on a novel odor-location task in an environment with four parallel compartments which had previously been shown to yield place field repetition. A second group of animals was trained on the same task, but with the compartments arranged in different directions, an arrangement we hypothesised would yield less place field repetition. Learning of the odor-location task in the parallel compartments was significantly impaired relative to learning in the radially arranged compartments. Fewer animals acquired the full discrimination in the parallel compartments compared to those trained in the radial compartments, and the former also required many more sessions to reach criterion compared to the latter. To confirm that the arrangement of compartments yielded differences in place cell repetition, in a separate group of animals we recorded from CA1 place cells in both environments. We found that CA1 place cells exhibited repeated fields across four parallel local compartments, but did not do so when the same compartments were arranged radially. To confirm that the differences in place field repetition across the parallel and radial compartments depended on their angular arrangement, and not incidental differences in access to an extra-maze visual landmark, we repeated the recordings in a second set of rats in the absence of the orientation landmark. We found, once again, that place fields showed repetition in parallel compartments, and did not do so in radially arranged compartments. Thus place field repetition, or lack thereof, in these compartments was not dependent on extra-maze cues. Together, these results imply that place field repetition constrains spatial learning. © 2015 Wiley Periodicals, Inc

Self-similar scaling and evolution in the galaxy cluster X-ray Luminosity-Temperature relation

We investigate the form and evolution of the X-ray luminosity-temperature (LT) relation of a sample of 114 galaxy clusters observed with Chandra at 0.1<z<1.3. The clusters were divided into subsamples based on their X-ray morphology or whether they host strong cool cores. We find that when the core regions are excluded, the most relaxed clusters (or those with the strongest cool cores) follow an LT relation with a slope that agrees well with simple self-similar expectations. This is supported by an analysis of the gas density profiles of the systems, which shows self-similar behaviour of the gas profiles of the relaxed clusters outside the core regions. By comparing our data with clusters in the REXCESS sample, which extends to lower masses, we find evidence that the self-similar behaviour of even the most relaxed clusters breaks at around 3.5keV. By contrast, the LT slopes of the subsamples of unrelaxed systems (or those without strong cool cores) are significantly steeper than the self-similar model, with lower mass systems appearing less luminous and higher mass systems appearing more luminous than the self-similar relation. We argue that these results are consistent with a model of non-gravitational energy input in clusters that combines central heating with entropy enhancements from merger shocks. Such enhancements could extend the impact of central energy input to larger radii in unrelaxed clusters, as suggested by our data. We also examine the evolution of the LT relation, and find that while the data appear inconsistent with simple self-similar evolution, the differences can be plausibly explained by selection bias, and thus we find no reason to rule out self-similar evolution. We show that the fraction of cool core clusters in our (non-representative) sample decreases at z>0.5 and discuss the effect of this on measurements of the evolution in the LT relation.Comment: 21 pages, 15 figures. Submitted to MNRAS. Comments welcom

Economic sustainability modeling provides decision support for assessing hybrid poplar-based biofuel development in California

Biofuels are expected to play a major role in meeting California's long-term energy needs, but many factors influence the commercial viability of the various feedstock and production technology options. We developed a spatially explicit analytic framework that integrates models of plant growth, crop adoption, feedstock location, transportation logistics, economic impact, biorefinery costs and biorefinery energy use and emissions. We used this framework to assess the economic potential of hybrid poplar as a feedstock for jet fuel production in Northern California. Results suggest that the region has sufficient suitable croplands (2.3 million acres) and nonarable lands (1.5 million acres) for poplar cultivation to produce as much as 2.26 billion gallons of jet fuel annually. However, there are major obstacles to such large-scale production, including, on nonarable lands, low poplar yields and broad spatial distribution and, on croplands, competition with existing crops. We estimated the production cost of jet fuel to be $4.40 to$5.40 per gallon for poplar biomass grown on nonarable lands and $3.60 to$4.50 per gallon for biomass grown on irrigated cropland; the current market price is $2.12 per gallon. Improved poplar yields, use of supplementary feedstocks at the biorefinery and economic supports such as carbon credits could help to overcome these barriers

New constraints on dark energy from the observed growth of the most X-ray luminous galaxy clusters

We present constraints on the mean matter density, Omega_m, the normalization of the density fluctuation power spectrum, sigma_8, and the dark-energy equation-of-state parameter, w, obtained from measurements of the X-ray luminosity function of the largest known galaxy clusters at redshifts z<0.7, as compiled in the Massive Cluster Survey (MACS) and the local BCS and REFLEX galaxy cluster samples. Our analysis employs an observed mass-luminosity relation, calibrated by hydrodynamical simulations, including corrections for non-thermal pressure support and accounting for the presence of intrinsic scatter. Conservative allowances for all known systematic uncertainties are included, as are standard priors on the Hubble constant and mean baryon density. We find Omega_m=0.28 +0.11 -0.07 and sigma_8=0.78 +0.11 -0.13 for a spatially flat, cosmological-constant model, and Omega_m=0.24 +0.15 -0.07, sigma_8=0.85 +0.13 -0.20 and w=-1.4 +0.4 -0.7 for a flat, constant-w model. Future work improving our understanding of redshift evolution and observational biases affecting the mass--X-ray luminosity relation have the potential to significantly tighten these constraints. Our results are consistent with those from recent analyses of type Ia supernovae, cosmic microwave background anisotropies, the X-ray gas mass fraction of relaxed galaxy clusters, baryon acoustic oscillations and cosmic shear. Combining the new X-ray luminosity function data with current supernova, cosmic microwave background and cluster gas fraction data yields the improved constraints Omega_m=0.269 +- 0.016, sigma_8=0.82 +- 0.03 and w=-1.02 +- 0.06. (Abridged)Comment: Submitted to MNRAS. 15 pages, 15 figures. v2: Improved modeling of the mass-luminosity relation, including additional systematic allowances for evolution in the scatter and non-thermal pressure support. Constraints are somewhat weaker, but overall conclusions are unchanged

The Observed Growth of Massive Galaxy Clusters I: Statistical Methods and Cosmological Constraints

(Abridged) This is the first of a series of papers in which we derive simultaneous constraints on cosmological parameters and X-ray scaling relations using observations of the growth of massive, X-ray flux-selected galaxy clusters. Our data set consists of 238 clusters drawn from the ROSAT All-Sky Survey, and incorporates extensive follow-up observations using the Chandra X-ray Observatory. Here we describe and implement a new statistical framework required to self-consistently produce simultaneous constraints on cosmology and scaling relations from such data, and present results on models of dark energy. In spatially flat models with a constant dark energy equation of state, w, the cluster data yield Omega_m=0.23 +- 0.04, sigma_8=0.82 +- 0.05, and w=-1.01 +- 0.20, marginalizing over conservative allowances for systematic uncertainties. These constraints agree well and are competitive with independent data in the form of cosmic microwave background (CMB) anisotropies, type Ia supernovae (SNIa), cluster gas mass fractions (fgas), baryon acoustic oscillations (BAO), galaxy redshift surveys, and cosmic shear. The combination of our data with current CMB, SNIa, fgas, and BAO data yields Omega_m=0.27 +- 0.02, sigma_8=0.79 +- 0.03, and w=-0.96 +- 0.06 for flat, constant w models. For evolving w models, marginalizing over transition redshifts in the range 0.05-1, we constrain the equation of state at late and early times to be respectively w_0=-0.88 +- 0.21 and w_et=-1.05 +0.20 -0.36. The combined data provide constraints equivalent to a DETF FoM of 15.5. Our results highlight the power of X-ray studies to constrain cosmology. However, the new statistical framework we apply to this task is equally applicable to cluster studies at other wavelengths.Comment: 16 pages, 7 figures. v4: final version (typographic corrections). Results can be downloaded at https://www.stanford.edu/group/xoc/papers/xlf2009.htm

The Observed Growth of Massive Galaxy Clusters III: Testing General Relativity on Cosmological Scales

This is the third of a series of papers in which we derive simultaneous constraints on cosmological parameters and X-ray scaling relations using observations of the growth of massive, X-ray flux-selected galaxy clusters. Our data set consists of 238 clusters drawn from the ROSAT All-Sky Survey, and incorporates extensive follow-up observations using the Chandra X-ray Observatory. Here we present improved constraints on departures from General Relativity (GR) on cosmological scales, using the growth index, gamma, to parameterize the linear growth rate of cosmic structure. Using the method of Mantz et al. (2009a), we simultaneously and self-consistently model the growth of X-ray luminous clusters and their observable-mass scaling relations, accounting for survey biases, parameter degeneracies and systematic uncertainties. We combine the cluster growth data with gas mass fraction, SNIa, BAO and CMB data. This combination leads to a tight correlation between gamma and sigma_8. Consistency with GR requires gamma~0.55. Under the assumption of self-similar evolution and constant scatter in the scaling relations, and for a flat LCDM model, we measure gamma(sigma_8/0.8)^6.8=0.55+0.13-0.10, with 0.79<sigma_8<0.89. Relaxing the assumptions on the scaling relations by introducing two additional parameters to model possible evolution in the normalization and scatter of the luminosity-mass relation, we obtain consistent constraints on gamma that are only ~20% weaker than those above. Allowing the dark energy equation of state, w, to take any constant value, we simultaneously constrain the growth and expansion histories, and find no evidence for departures from either GR or LCDM. Our results represent the most robust consistency test of GR on cosmological scales to date. (Abridged)Comment: Accepted for publication in MNRAS. 11 pages, 5 figures, 1 table. New figure added: Fig. 4 shows the tight constraints on gamma from the cluster growth data alone compared with those from the other data sets combined

The prospects for constraining dark energy with future X-ray cluster gas mass fraction measurements

We examine the ability of a future X-ray observatory to constrain dark energy via measurements of the cluster X-ray gas mass fraction, fgas. We find that fgas measurements for a sample of ~500 hot, X-ray bright, dynamically relaxed clusters, to a precision of ~5 per cent, can be used to constrain dark energy with a Dark Energy Task Force (DETF) figure of merit of 15-40, with the possibility of boosting these values by 40 per cent or more by optimizing the redshift distribution of target clusters. Such constraints are comparable to those predicted by the DETF for other leading, planned dark energy experiments. A future fgas experiment will be preceded by a large X-ray or SZ survey that will find hot, X-ray luminous clusters out to high redshifts. Short `snapshot' observations with the new X-ray observatory should then be able to identify a sample of ~500 suitably relaxed systems. The redshift, temperature and X-ray luminosity range of interest has already been partially probed by existing X-ray cluster surveys which allow reasonable estimates of the fraction of clusters that will be suitably relaxed for fgas work. Our analysis uses a Markov Chain Monte Carlo method which fully captures the relevant degeneracies between parameters and facilitates the incorporation of priors and systematic uncertainties in the analysis. We explore the effects of such uncertainties for scenarios ranging from optimistic to pessimistic. We conclude that the fgas experiment will provide tight constraints on the mean matter and dark energy densities, with a peak sensitivity for dark energy work at redshifts midway between those of supernovae and baryon acoustic oscillation/weak lensing/cluster number counts experiments. In combination, these experiments should enable a precise measurement of the evolution of dark energy. (Abridged)Comment: Accepted for publication in MNRAS. 16 pages, 6 figures, 4 tables. Predicted cluster redshift distribution consistent with the observed evolution of massive clusters reported by Mantz et al 2008 (arXiv:0709.4294). Additional discussion included. Conclusions unchange