Class I HDAC Inhibition Blocks Cocaine-Induced Plasticity Through Targeted Changes in Histone Methylation

Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the acetylation of histone tails, but little is known about the functional specificity of different HDAC isoforms in the development and maintenance of cocaine-induced plasticity, and prior studies of HDAC inhibitors report conflicting effects on cocaine-elicited behavioral adaptations. Here, we demonstrate that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior, an effect mediated in part via a chromatin-mediated suppression of GABAA receptor subunit expression and inhibitory tone on NAc neurons. Our findings suggest a novel mechanism by which prolonged and selective HDAC inhibition can alter behavioral and molecular adaptations to cocaine and inform the development of novel therapeutics for cocaine addiction

Human-made structures, vegetation, and weather influence ferruginous hawk breeding performance

Studies of anthropogenic impacts on wildlife may produce inconclusive or biased results if they fail to account for natural sources of variation in breeding performance and do not use probabilistic sampling at a scale functional for management. We used stratified random sampling and generalized linear mixed models to test hypotheses on relationships of daily nest survival rate (DSR) and fledgling production with anthropogenic and environmental factors that influence reproduction in the ferruginous hawk (Buteo regalis). We conducted the study across ferruginous hawk range in Wyoming, USA, 2010–2012. We performed extensive field surveys of prey, vegetation, and nest substrates, and used spatially explicit data to quantify weather, and the most widespread forms of anthropogenic infrastructure (i.e., roads, oil and gas well pads) in ferruginous hawk territories. We found strong evidence that DSR and productivity were greater for nests on anthropogenic structures (i.e., artificial nest platforms, gas condensation tanks, abandoned windmill platforms, power poles) compared to natural substrates (i.e., trees, cliffs, rock outcrops). Additionally, ferruginous hawks produced more fledglings at territories with greater shrub cover and fewer severe storms during the June brood‐rearing period. Amount of oil and gas development and prey was not associated with either measure of breeding performance. Our results suggest that artificial nest platforms are an effective tool to improve breeding success of ferruginous hawks and nesting on anthropogenic structures does not constitute an ecological trap for this species. Although ferruginous hawks nested in some areas with very little vegetative cover, territories with greater amounts of shrub cover produced more fledglings. The negative impact of severe spring storms on fledgling production illustrates the importance of including future weather scenarios in management planning for this species because storms are predicted to increase in frequency and intensity as a result of climate change. Published 2015. This article is a U.S. Government work and is in the public domain in the USA

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV

Phylogenetic Analysis of Pelecaniformes (Aves) Based on Osteological Data: Implications for Waterbird Phylogeny and Fossil Calibration Studies

) were also assessed. The antiquity of these taxa and their purported status as stem members of extant families makes them valuable for studies of higher-level avian diversification. (sister taxon to Phalacrocoracidae). These relationships are invariant when ‘backbone’ constraints based on recent avian phylogenies are imposed.Relationships of extant pelecaniforms inferred from morphology are more congruent with molecular phylogenies than previously assumed, though notable conflicts remain. The phylogenetic position of the Plotopteridae implies that wing-propelled diving evolved independently in plotopterids and penguins, representing a remarkable case of convergent evolution. Despite robust support for the placement of fossil taxa representing key calibration points, the successive outgroup relationships of several “stem fossil + crown family” clades are variable and poorly supported across recent studies of avian phylogeny. Thus, the impact these fossils have on inferred patterns of temporal diversification depends heavily on the resolution of deep nodes in avian phylogeny

What do general practitioners know about ADHD? Attitudes and knowledge among first-contact gatekeepers: systematic narrative review

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood disorder with international prevalence estimates of 5 % in childhood, yet significant evidence exists that far fewer children receive ADHD services. In many countries, ADHD is assessed and diagnosed in specialist mental health or neuro-developmental paediatric clinics, to which referral by General (Family) Practitioners (GPs) is required. In such ‘gatekeeper’ settings, where GPs act as a filter to diagnosis and treatment, GPs may either not recognise potential ADHD cases, or may be reluctant to refer. This study systematically reviews the literature regarding GPs’ views of ADHD in such settings. Methods: A search of nine major databases was conducted, with wide search parameters; 3776 records were initially retrieved. Studies were included if they were from settings where GPs are typically gatekeepers to ADHD services; if they addressed GPs’ ADHD attitudes and knowledge; if methods were clearly described; and if results for GPs were reported separately from those of other health professionals. Results: Few studies specifically addressed GP attitudes to ADHD. Only 11 papers (10 studies), spanning 2000–2010, met inclusion criteria, predominantly from the UK, Europe and Australia. As studies varied methodologically, findings are reported as a thematic narrative, under the following themes: Recognition rate; ADHD controversy (medicalisation, stigma, labelling); Causes of ADHD; GPs and ADHD diagnosis; GPs and ADHD treatment; GP ADHD training and sources of information; and Age, sex differences in knowledge and attitudes. Conclusions: Across times and settings, GPs practising in first-contact gatekeeper settings had mixed and often unhelpful attitudes regarding the validity of ADHD as a construct, the role of medication and how parenting contributed to presentation. A paucity of training was identified, alongside a reluctance of GPs to become involved in shared care practice. If access to services is to be improved for possible ADHD cases, there needs to be a focused and collaborative approach to training

Use of group records of feed intake to select for feed efficiency in rabbit

Models for genetic evaluation of feed efficiency (FE) for animals housed in groups when they are either fed ad libitum (F) or on restricted (R) feeding were implemented. Definitions of FE on F included group records of feed intake (¯FI_F) and individual records of growth rate (GF) and metabolic weight (MF). Growth rate (GR) as FE measurement on R was used. Data corresponded to 5,336 kits from a rabbit sire line, from 1,255 litters in 14 batches and 667 cages. A five-trait mixed model (also with metabolic weight on R, MR) was implemented including, for each trait, the systematic effects of batch, body weight at weaning, parity order and litter size; and the random effects of litter, additive genetic and individual. A Bayesian analysis was performed. Conditional traits such as ¯FI_F |M_F,G_F and G_F |M_F,¯FI_F were obtained from elements of additive genetics ( ( ¯FI_F |M_F,G_F )_g and ( G_F |M_F,¯FI_F )_g ) or phenotypic (( ¯FI_F |M_F,G_F )_p and ( G_F |M_F,¯FI_F )_p ) (co)variance matrices. In the first case, heritabilities were low (0.07 and 0.06 for ( ¯FI_F |M_F,G_F )_g and ( G_F |M_F,¯FI_F )_g, respectively) but null genetic correlation between the conditional and conditioning traits is guaranteed. In the second case, heritabilities were higher (0.22 and 0.16 for ( ¯FI_F |M_F,G_F )_p and ( G_F |M_F,¯FI_F )_p, respectively) but the genetic correlation between ( ¯FI_F |M_F,G_F )_p and G_F was moderate (0.58). Heritability of GR was low (0.08). This trait was negatively correlated with ( G_F |M_F,¯FI_F )_p and ( G_F |M_F,¯FI_F )_gof animals on F, which indicate a different genetic background. The correlation between GR and GF was also low to moderate (0.48) and the additive variance of GF was almost 4 times that of GR, suggesting the presence of a substantial genotype by feeding regimen interaction.info:eu-repo/semantics/acceptedVersio

Quantitative conversations: the importance of developing rapport in standardised interviewing

© 2014, The Author(s). When developing household surveys, much emphasis is understandably placed on developing survey instruments that can elicit accurate and comparable responses. In order to ensure that carefully crafted questions are not undermined by ‘interviewer effects’, standardised interviewing tends to be utilised in preference to conversational techniques. However, by drawing on a behaviour coding analysis of survey paradata arising from the 2012 UK Poverty and Social Exclusion Survey we show that in practice standardised survey interviewing often involves extensive unscripted conversation between the interviewer and the respondent. Whilst these interactions can enhance response accuracy, cooperation and ethicality, unscripted conversations can also be problematic in terms of survey reliability and the ethical conduct of survey interviews, as well as raising more basic epistemological questions concerning the degree of standardisation typically assumed within survey research. We conclude that better training in conversational techniques is necessary, even when applying standardised interviewing methodologies. We also draw out some theoretical implications regarding the usefulness of the qualitative–quantitative dichotomy

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets