Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline

Rationale: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. Objective: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. Methods: Attentional function in mice haploinsufficient for Map2k7 (Map2k7+/− mice) was investigated using the five-choice serial reaction time task (5-CSRTT). Results: Once stable performance had been achieved, Map2k7+/− mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline—a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia—signs of improvement in attentional performance were detected. Conclusions: Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline

Model of a fluid at small and large length scales and the hydrophobic effect

We present a statistical field theory to describe large length scale effects induced by solutes in a cold and otherwise placid liquid. The theory divides space into a cubic grid of cells. The side length of each cell is of the order of the bulk correlation length of the bulk liquid. Large length scale states of the cells are specified with an Ising variable. Finer length scale effects are described with a Gaussian field, with mean and variance affected by both the large length scale field and by the constraints imposed by solutes. In the absence of solutes and corresponding constraints, integration over the Gaussian field yields an effective lattice gas Hamiltonian for the large length scale field. In the presence of solutes, the integration adds additional terms to this Hamiltonian. We identify these terms analytically. They can provoke large length scale effects, such as the formation of interfaces and depletion layers. We apply our theory to compute the reversible work to form a bubble in liquid water, as a function of the bubble radius. Comparison with molecular simulation results for the same function indicates that the theory is reasonably accurate. Importantly, simulating the large length scale field involves binary arithmetic only. It thus provides a computationally convenient scheme to incorporate explicit solvent dynamics and structure in simulation studies of large molecular assemblies

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

Baseline diet quality of predominantly minority children and adolescents from households characterized by low socioeconomic status in the Childhood Obesity Prevention and Treatment Research (COPTR) Consortium

Background: The Healthy Eating Index (HEI-2010) is a measure of diet quality that examines conformance with the Dietary Guidelines for Americans. The objectives of this study were to estimate baseline diet quality of predominantly low-income minority children using the HEI-2010 and to identify the most important HEI components to target for dietary intervention. Methods: Two or three baseline 24 h dietary recalls were collected in-person or over telephone between May 2012 and June 2014 from 1,745 children and adolescents from four randomized clinical trials in the Childhood Obesity Prevention and Treatment Research (COPTR) Consortium. Nine adequacy and three moderation food components were calculated and averaged to determine overall HEI scores. The overall HEI-2010 scores were categorized as ≥81, 51-80, or ≤ 50 based on the HEI-2005 classification. For each study, mean overall and component HEI scores were estimated using linear regression models. Results: Mean (95% CI) overall HEI scores ranged from 47.9 (46.8, 49.0) to 64.5 (63.6, 65.4). Only 0.3 to 8.1% of children and adolescents had HEI-2010 score ≥ 81. The average component score for green and beans was less than 30% of maximum score for all trials. In contrast, the average component score for protein, dairy (except for IMPACT), and empty calories (except forIMPACT) was more than 80% of maximum score. Conclusions: Based on HEI-2010 scores, few children and adolescents consumed high quality diets. Dietary interventions for children and adolescents should focus on improving intakes of green vegetables and beans. Clinical trial registry numbers: GROW study (clinical trial # NCT01316653); NET-Works study (clinical trial #NCT01606891); Stanford Goals (clinical trial #NCT01642836); IMPACT (clinical trial # NCT01514279)

Giant magnetothermopower of magnon-assisted transport in ferromagnetic tunnel junctions

We present a theoretical description of the thermopower due to magnon-assisted tunneling in a mesoscopic tunnel junction between two ferromagnetic metals. The thermopower is generated in the course of thermal equilibration between two baths of magnons, mediated by electrons. For a junction between two ferromagnets with antiparallel polarizations, the ability of magnon-assisted tunneling to create thermopower $S_{AP}$ depends on the difference between the size $\Pi_{\uparrow, \downarrow}$ of the majority and minority band Fermi surfaces and it is proportional to a temperature dependent factor $(k_{B}T/\omega_{D})^{3/2}$ where $\omega_{D}$ is the magnon Debye energy. The latter factor reflects the fractional change in the net magnetization of the reservoirs due to thermal magnons at temperature $T$ (Bloch's $T^{3/2}$ law). In contrast, the contribution of magnon-assisted tunneling to the thermopower $S_P$ of a junction with parallel polarizations is negligible. As the relative polarizations of ferromagnetic layers can be manipulated by an external magnetic field, a large difference $\Delta S = S_{AP} - S_P \approx S_{AP} \sim - (k_B/e) f (\Pi_{\uparrow},\Pi_{\downarrow}) (k_BT/\omega_{D})^{3/2}$ results in a magnetothermopower effect. This magnetothermopower effect becomes giant in the extreme case of a junction between two half-metallic ferromagnets, $\Delta S \sim - k_B/e$.Comment: 9 pages, 4 eps figure

Theory of Supersolidity

After reviewing some experimental facts, and early theories, I sketch the Hartree-Fock description of Boson solids, emphasizing the contrast with the Fermion case in that the natural solution is a product of local wave-functions. I then investigate the Boson Hubbard model to demonstrate that the local functions are not orthogonal and exemplify a novel state of matter which has superflow but not ODLRO, below a cooperative thermal transition. I then discuss whether or not these ideas actually apply to solid He

Implementation of a pharmacogenomics consult service to support the INGENIOUS trial

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding

A community-based, multi-level, multi-setting, multi-component intervention to reduce weight gain among low socioeconomic status Latinx children with overweight or obesity: The Stanford GOALS randomised controlled trial

Background: There are few long-term studies of interventions to reduce in low socioeconomic status children with overweight or obesity. The Stanford GOALS trial evaluated a 3-year, community-based, multi-level, multi-setting, multi-component (MMM) systems intervention, to reduce weight gain among low socioeconomic status, Latinx children with overweight or obesity. Methods: We did a two-arm, parallel group, randomised, open-label, active placebo-controlled trial with masked assessment over 3 years. Families from low-income, primarily Latinx communities in Northern California, CA, USA, with 7–11-year-old children with overweight or obesity were randomly assigned to a MMM intervention or a Health Education (HE) comparison intervention. The MMM intervention included home environment changes and behavioural counselling, community after school team sports, and reports to primary health-care providers. The primary outcome was child BMI trajectory over three years. Secondary outcomes included one- and two-year changes in BMI. This trial is registered with ClinicalTrials.gov NCT01642836. Findings: Between July 13, 2012, and Oct 3, 2013, 241 families were recruited and randomly assigned to MMM (n=120) or HE (n=121). Children's mean age was 9·5 (SD 1·4) years, 134 (56%) were female and 107 (44%) were male, and 236 (98%) were Latinx. 238 (99%) children participated in year 1, 233 (97%) in year 2, and 227 (94%) in year 3 of follow-up assessments. In intention-to-treat analysis, over 3 years, the difference between intervention groups in BMI trajectory was not significant (mean adjusted difference −0·25 [95% CI −0·90 to 0·40] kg/m2; Cohen's d=0.10; p=0·45). Children in the MMM intervention group gained less BMI over 1 year than did children in the HE intervention group (−0·73 [–1·07 to −0·39] kg/m2, d=0.55); the same was true over 2 years (−0·63 [–1·13 to −0·14] kg/m2; d =0.33). No differential adverse events were observed. Interpretation: The MMM intervention did not reduce BMI gain versus HE over 3 years but the effects over 1 and 2 years in this rigorous trial show the promise of this systems intervention approach for reducing weight gain and cardiometabolic risk factors in low socioeconomic status communities. Funding: US National Institutes of Health

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm