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

Positive selection in glycolysis among Australasian stick insects

Background: The glycolytic pathway is central to cellular energy production. Selection on individual enzymes within glycolysis, particularly phosphoglucose isomerase (Pgi), has been associated with metabolic performance in numerous organisms. Nonetheless, how whole energy-producing pathways evolve to allow organisms to thrive in different environments and adopt new lifestyles remains little explored. The Lanceocercata radiation of Australasian stick insects includes transitions from tropical to temperate climates, lowland to alpine habitats, and winged to wingless forms. This permits a broad investigation to determine which steps within glycolysis and what sites within enzymes are the targets of positive selection. To address these questions we obtained transcript sequences from seven core glycolysis enzymes, including two Pgi paralogues, from 29 Lanceocercata species. Results: Using maximum likelihood methods a signature of positive selection was inferred in two core glycolysis enzymes. Pgi and Glyceraldehyde 3-phosphate dehydrogenase (Gaphd) genes both encode enzymes linking glycolysis to the pentose phosphate pathway. Positive selection among Pgi paralogues and orthologues predominately targets amino acids with residues exposed to the protein’s surface, where changes in physical properties may alter enzyme performance. Conclusion: Our results suggest that, for Lancerocercata stick insects, adaptation to new stressful lifestyles requires a balance between maintaining cellular energy production, efficiently exploiting different energy storage pools and compensating for stress-induced oxidative damag

What do near-term observations tell us about long-term developments in greenhouse gas emissions? A letter

Long-term scenarios developed by integrated assessment models are used in climate research to provide an indication of plausible long-term emissions of greenhouse gases and other radiatively active substances based on developments in the global energy system, land-use and the emissions associated with these systems The phenomena that determine these long-term developments (several decades or even centuries) are very different than those that operate on a shorter time-scales (a few years) Nevertheless, in the literature, we still often find direct comparisons between short-term observations and long-term developments that do not take into account the differing dynamics over these time scales In this letter, we discuss some of the differences between the factors that operate in the short term and those that operate in the long term We use long-term historical emissions trends to show that short-term observations are very poor indicators of long-term future emissions developments Based on this, we conclude that the performance of long-term scenarios should be evaluated against the appropriate, corresponding long-term variables and trends The research community may facilitate this by developing appropriate data sets and protocols that can be used to test the performance of long-term scenarios and the models that produce the

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

Argon plasma treatment techniques on steel and effects on diamond-like carbon structure and delamination

Copyright © 2011 Elsevier B.V. All rights reserved.We demonstrate alteration in diamond-like carbon (DLC) film structure, chemistry and adhesion on steel, related to variation in the argon plasma pretreatment stage of plasma enhanced chemical vapour deposition. We relate these changes to the alteration in substrate structure, crystallinity and chemistry due to application of an argon plasma process with negative self bias up to 600 V. Adhesion of the DLC film to the substrate was assessed by examination of the spallated fraction of the film following controlled deformation. Films with no pretreatment step immediately delaminated. At 300 V pretreatment, the spallated fraction is 8.2%, reducing to 1.2% at 450 V and 0.02% at 600V. For bias voltages below 450V the adhesion enhancement is explained by a reduction in carbon contamination on the substrate surface, from 59at.% with no treatment to 26at.% at 450V, concurrently with a decrease in the surface roughness, Rq, from 31.5nm to 18.9nm. With a pretreatment bias voltage of 600V a nanocrystalline, nanostructured surface is formed, related to removal of chromium and relaxation of stress; X-ray diffraction indicates this phase is incipient at 450V. In addition to improving film adhesion, the nanotexturing of the substrate prior to film deposition results in a DLC film that shows an increase in sp3/sp2 ratio from 1.2 to 1.5, a reduction in surface roughness from 31nm to 21nm, and DLC nodular asperities with reduced diameter and increased uniformity of size and arrangement. These findings are consistent with the substrate alterations due to the plasma pretreatment resulting in limitation of surface diffusion in the growth process. This suggests that in addition to deposition phase processes, the parameters of the pretreatment process need to be considered when designing diamond-like carbon coatings.This work is partially supported by the Technology Strategy Board, reference BD266E

Children’s rights in their oral health care: How responsive are oral health professionals to children’s rights

Research on children’s rights in oral health care is lacking, and this study aims to partially fill this gap. In 2015, we conducted research in one region of New Zealand using video methods to explore the rights of 22 children during a specific oral health treatment, the placement of stainless steel crowns. Our findings show that many children did not receive a professional standard of care, there were gaps in the delivery and standard of care, and there were numerous examples of children’s rights’ violations. At the same time, however, some of the children’s dental practitioners’ (CDPs) actions may have been acceptable practice within the profession if children’s rights have not yet fully been embedded into the practice of oral health care workers. We conclude with a discussion of the implications of our findings and suggestions for a more rights based standard of oral health care

Psychometric assessment of the short-form Child Perceptions Questionnaire: an international collaborative study.

OBJECTIVE: To examine the factor structure and other psychometric characteristics of the most commonly used child oral-health-related quality-of-life (OHRQoL) measure (the 16-item short-form CPQ11-14 ) in a large number of children (N = 5804) from different settings and who had a range of caries experience and associated impacts. METHODS: Secondary data analyses used subnational epidemiological samples of 11- to 14-year-olds in Australia (N = 372), New Zealand (three samples: 352, 202, 429), Brunei (423), Cambodia (244), Hong Kong (542), Malaysia (439), Thailand (220, 325), England (88, 374), Germany (1055), Mexico (335) and Brazil (404). Confirmatory factor analysis (CFA) was used to examine the factor structure of the CPQ11-14 across the combined sample and within four regions (Australia/NZ, Asia, UK/Europe and Latin America). Item impact and internal reliability analysis were also conducted. RESULTS: Caries experience varied, with mean DMFT scores ranging from 0.5 in the Malaysian sample to 3.4 in one New Zealand sample. Even more variation was noted in the proportion reporting only fair or poor oral health; this was highest in the Cambodian and Mexican samples and lowest in the German sample and one New Zealand sample. One in 10 reported that their oral health had a marked impact on their life overall. The CFA across all samples revealed two factors with eigenvalues greater than 1. The first involved all items in the oral symptoms and functional limitations subscales; the second involved all emotional well-being and social well-being items. The first was designated the 'symptoms/function' subscale, and the second was designated the 'well-being' subscale. Cronbach's alpha scores were 0.72 and 0.84, respectively. The symptoms/function subscale contained more of the items with greater impact, with the item 'Food stuck in between your teeth' having greatest impact; in the well-being subscale, the 'Felt shy or embarrassed' item had the greatest impact. Repeating the analyses by world region gave similar findings. CONCLUSION: The CPQ11-14 performed well cross-sectionally in the largest analysis of the scale in the literature to date, with robust and mostly consistent psychometric characteristics, albeit with two underlying factors (rather than the originally hypothesized four-factor structure). It appears to be a sound, robust measure which should be useful for research, practice and policy

Structural Determinants and Children's Oral Health: A Cross-National Study

Much research on children's oral health has focused on proximal determinants at the expense of distal (upstream) factors. Yet, such upstream factors-the so-called structural determinants of health-play a crucial role. Children's lives, and in turn their health, are shaped by politics, economic forces, and social and public policies. The aim of this study was to examine the relationship between children's clinical (number of decayed, missing, and filled teeth) and self-reported oral health (oral health-related quality of life) and 4 key structural determinants (governance, macroeconomic policy, public policy, and social policy) as outlined in the World Health Organization's Commission for Social Determinants of Health framework. Secondary data analyses were carried out using subnational epidemiological samples of 8- to 15-y-olds in 11 countries ( N = 6,648): Australia (372), New Zealand (three samples; 352, 202, 429), Brunei (423), Cambodia (423), Hong Kong (542), Malaysia (439), Thailand (261, 506), United Kingdom (88, 374), Germany (1498), Mexico (335), and Brazil (404). The results indicated that the type of political regime, amount of governance (e.g., rule of law, accountability), gross domestic product per capita, employment ratio, income inequality, type of welfare regime, human development index, government expenditure on health, and out-of-pocket (private) health expenditure by citizens were all associated with children's oral health. The structural determinants accounted for between 5% and 21% of the variance in children's oral health quality-of-life scores. These findings bring attention to the upstream or structural determinants as an understudied area but one that could reap huge rewards for public health dentistry research and the oral health inequalities policy agenda

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02