The collaborative cross strains and their founders vary widely in cocaine-induced behavioral sensitization

Cocaine use and overdose deaths attributed to cocaine have increased significantly in the United States in the last 10 years. Despite the prevalence of cocaine use disorder (CUD) and the personal and societal problems it presents, there are currently no approved pharmaceutical treatments. The absence of treatment options is due, in part, to our lack of knowledge about the etiology of CUDs. There is ample evidence that genetics plays a role in increasing CUD risk but thus far, very few risk genes have been identified in human studies. Genetic studies in mice have been extremely useful for identifying genetic loci and genes, but have been limited to very few genetic backgrounds, leaving substantial phenotypic, and genetic diversity unexplored. Herein we report the measurement of cocaine-induced behavioral sensitization using a 19-day protocol that captures baseline locomotor activity, initial locomotor response to an acute exposure to cocaine and locomotor sensitization across 5 exposures to the drug. These behaviors were measured in 51 genetically diverse Collaborative Cross (CC) strains along with their inbred founder strains. The CC was generated by crossing eight genetically diverse inbred strains such that each inbred CC strain has genetic contributions from each of the founder strains. Inbred CC mice are infinitely reproducible and provide a stable, yet diverse genetic platform on which to study the genetic architecture and genetic correlations among phenotypes. We have identified significant differences in cocaine locomotor sensitivity and behavioral sensitization across the panel of CC strains and their founders. We have established relationships among cocaine sensitization behaviors and identified extreme responding strains that can be used in future studies aimed at understanding the genetic, biological, and pharmacological mechanisms that drive addiction-related behaviors. Finally, we have determined that these behaviors exhibit relatively robust heritability making them amenable to future genetic mapping studies to identify addiction risk genes and genetic pathways that can be studied as potential targets for the development of novel therapeutics

Quantum Physics Exploring Gravity in the Outer Solar System: The Sagas Project

We summarise the scientific and technological aspects of the SAGAS (Search for Anomalous Gravitation using Atomic Sensors) project, submitted to ESA in June 2007 in response to the Cosmic Vision 2015-2025 call for proposals. The proposed mission aims at flying highly sensitive atomic sensors (optical clock, cold atom accelerometer, optical link) on a Solar System escape trajectory in the 2020 to 2030 time-frame. SAGAS has numerous science objectives in fundamental physics and Solar System science, for example numerous tests of general relativity and the exploration of the Kuiper belt. The combination of highly sensitive atomic sensors and of the laser link well adapted for large distances will allow measurements with unprecedented accuracy and on scales never reached before. We present the proposed mission in some detail, with particular emphasis on the science goals and associated measurements.Comment: 39 pages. Submitted in abridged version to Experimental Astronom

Environmental heterogeneity modulates the effect of biodiversity on the spatial variability of grassland biomass

Plant productivity varies due to environmental heterogeneity, and theory suggests that plant diversity can reduce this variation. While there is strong evidence of diversity effects on temporal variability of productivity, whether this mechanism extends to variability across space remains elusive. Here we determine the relationship between plant diversity and spatial variability of productivity in 83 grasslands, and quantify the effect of experimentally increased spatial heterogeneity in environmental conditions on this relationship. We found that communities with higher plant species richness (alpha and gamma diversity) have lower spatial variability of productivity as reduced abundance of some species can be compensated for by increased abundance of other species. In contrast, high species dissimilarity among local communities (beta diversity) is positively associated with spatial variability of productivity, suggesting that changes in species composition can scale up to affect productivity. Experimentally increased spatial environmental heterogeneity weakens the effect of plant alpha and gamma diversity, and reveals that beta diversity can simultaneously decrease and increase spatial variability of productivity. Our findings unveil the generality of the diversity-stability theory across space, and suggest that reduced local diversity and biotic homogenization can affect the spatial reliability of key ecosystem functions

Search for the Chiral Magnetic Effect in Au+Au collisions at sNN=27\sqrt{s_{_{\rm{NN}}}}=27 GeV with the STAR forward Event Plane Detectors

A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at $\sqrt{s_{_{\rm{NN}}}}=27$ GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity $|\eta|<1.0$ and at forward rapidity $2.1 < |\eta|<5.1$. We compare the results based on the directed flow plane ($\Psi_1$) at forward rapidity and the elliptic flow plane ($\Psi_2$) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to $\Psi_1$ than to $\Psi_2$, while a flow driven background scenario would lead to a consistent result for both event planes[1,2]. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.Comment: main: 8 pages, 5 figures; supplementary material: 2 pages, 1 figur

ATHENA detector proposal — a totally hermetic electron nucleus apparatus proposed for IP6 at the Electron-Ion Collider

ATHENA has been designed as a general purpose detector capable of delivering the full scientific scope of the Electron-Ion Collider. Careful technology choices provide fine tracking and momentum resolution, high performance electromagnetic and hadronic calorimetry, hadron identification over a wide kinematic range, and near-complete hermeticity. This article describes the detector design and its expected performance in the most relevant physics channels. It includes an evaluation of detector technology choices, the technical challenges to realizing the detector and the R&amp;D required to meet those challenges

Distinct neuropathologic phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1

The proteins ClC-6 and ClC-7 are expressed in the endosomal-lysosomal system. Because Clcn6-deficient mice display some features of neuronal ceroid lipofuscinosis (NCL), CLCN6 may be a candidate gene for novel forms of NCL. Using landmarks of disease progression from NCL mouse models as a guide, we examined neuropathologic alterations in the central nervous system of Clcn6, Clcn7, andgl mice. gl mice bear a mutation in Ostm1, the beta-subunit critical for Clcn7 function. Severely affected Clcn7 and gl mice have remarkably similar neuropathologic phenotypes, with pronounced reactive changes and neuron loss in the thalamocortical system, similar to findings in early-onset forms of NCL. In contrast, Clcn6 mice display slowly progressive, milder neuropathologic features with very little thalamic involvement or microglial activation. These findings detail for the first time the markedly different neuropathologic consequences of mutations in these two CLC genes. Clcn7 and gl mice bear a close resemblance to the progressive neuropathologic phenotypes of early onset forms of NCL, whereas the distinct phenotype of Clcn6-deficient mice suggests that this gene could be a candidate for a later-onset form of mild neurologic dysfunction with some NCL-like features

Tn5530 from Burkholderia cepacia strain 2a encodes a chloride channel protein essential for the catabolism of 2,4-dichlorophenoxyacetic acid

Chloride channel proteins (ClC) are found in living systems where they transport chloride ions across cell membranes. Recently, the structure/function of two prokaryotic ClC has been determined but little is known about the role of these proteins in the microbial metabolism of chlorinated compounds. Here we show that transposon Tn5530 from Burkholderia cepacia strain 2a encodes a ClC protein (BcClC) which is responsible for expelling Cl- ions generated during the catabolism of 2,4-dichlorophenoxyacetic acid (a chlorinated herbicide). We found that BcClC has the ability to transport Cl- ions across reconstituted proteoliposome membranes. We created two mutants in which the intrachannel glutamate residue of the protein, known to be responsible for opening and closing the channel (i.e. gating), was changed in order to create constitutively open and closed forms. We observed that cells carrying the closed-channel protein accumulated Cl- ions intracellularly leading to a decrease in intracellular pH, cell stasis and death. Further, we established that BcClC has the same gating mechanism as that reported for the ClC protein from Salmonella typhimurium. Our results show that the physiological role of ClC is to maintain cellular homeostasis which can be impaired by the catabolism of chlorinated compounds

Opposing community assembly patterns for dominant and jonnondominant plant species in herbaceous ecosystems globally

Biotic and abiotic factors interact with dominant plants—the locally most frequent or with the largest coverage—and nondominant plants differently, partially because dominant plants modify the environment where nondominant plants grow. For instance, if dominant plants compete strongly, they will deplete most resources, forcing nondominant plants into a narrower niche space. Conversely, if dominant plants are constrained by the environment, they might not exhaust available resources but instead may ameliorate environmental stressors that usually limit nondominants. Hence, the nature of interactions among nondominant species could be modified by dominant species. Furthermore, these differences could translate into a disparity in the phylogenetic relatedness among dominants compared to the relatedness among nondominants. By estimating phylogenetic dispersion in 78 grasslands across five continents, we found that dominant species were clustered (e.g., co-dominant grasses), suggesting dominant species are likely organized by environmental filtering, and that nondominant species were either randomly assembled or overdispersed. Traits showed similar trends for those sites (<50%) with sufficient trait data. Furthermore, several lineages scattered in the phylogeny had more nondominant species than expected at random, suggesting that traits common in nondominants are phylogenetically conserved and have evolved multiple times. We also explored environmental drivers of the dominant/nondominant disparity. We found different assembly patterns for dominants and nondominants, consistent with asymmetries in assembly mechanisms. Among the different postulated mechanisms, our results suggest two complementary hypotheses seldom explored: (1) Nondominant species include lineages adapted to thrive in the environment generated by dominant species. (2) Even when dominant species reduce resources to nondominant ones, dominant species could have a stronger positive effect on some nondominants by ameliorating environmental stressors affecting them, than by depleting resources and increasing the environmental stress to those nondominants. These results show that the dominant/nondominant asymmetry has ecological and evolutionary consequences fundamental to understand plant communities