Expression analysis of novel striatal-enriched genes in Huntington disease

Selective degeneration of striatal neurons is a pathologic hallmark of Huntington disease (HD). The exact mechanism(s) behind this specific neurodegeneration is still unknown. Expression studies of diseased human post-mortem brain, as well as different mouse models exhibiting striatal degeneration, have demonstrated changes in the expression of many important genes with a large proportion of changes being observed in the striatal-enriched genes. These investigations have raised questions about how enrichment of particular transcripts in the striatum can lead to its selective vulnerability to neurodegeneration. Monitoring the expression changes of striatal-enriched genes during the course of the disease may be informative about their potential involvement in selective degeneration. In this study, we analyzed a Serial Analysis of Gene Expression (SAGE) database (www.mouseatlas.org) and compared the mouse striatum to 18 other brain regions to generate a novel list of striatal-enriched transcripts. These novel striatal-enriched transcripts were subsequently evaluated for expression changes in the YAC128 mouse model of HD, and differentially expressed transcripts were further examined in human post-mortem caudate samples. We identified transcripts with altered expression in YAC128 mice, which also showed consistent expression changes in human post-mortem tissue. The identification of novel striatal-enriched genes with altered expression in HD offers new avenues of study, leading towards a better understanding of specific pathways involved in the selective degeneration of striatal neurons in H

Identification and Characterization of Genes Required for Compensatory Growth in Drosophila

To maintain tissue homeostasis, some organs are able to replace dying cells with additional proliferation of surviving cells. Such proliferation can be localized (e.g., a regeneration blastema) or diffuse (compensatory growth). The relationship between such growth and the growth that occurs during development has not been characterized in detail. Drosophila melanogaster larval imaginal discs can recover from extensive damage, producing normally sized adult organs. Here we describe a system using genetic mosaics to screen for recessive mutations that impair compensatory growth. By generating clones of cells that carry a temperature-sensitive cell-lethal mutation, we conditionally ablate patches of tissue in the imaginal disc and assess the ability of the surviving sister clones to replace the lost tissue. We have used this system together with a modified whole-genome resequencing (WGS) strategy to identify several mutations that selectively compromise compensatory growth. We find specific alleles of bunched (bun) and Ribonucleoside diphosphate reductase large subunit (RnrL) reduce compensatory growth in the imaginal disc. Other genes identified in the screen, including two alleles of Topoisomerase 3-alpha (Top3α), while also required for developmental growth, appear to have an enhanced requirement during compensatory growth. Compensatory growth occurs at a higher rate than normal growth and may therefore have features in common with some types of overgrowth. Indeed, the RnrL allele identified compromises both these types of altered growth and mammalian ribonucleotide reductase and topoisomerases are targets of anticancer drugs. Finally, the approach we describe is applicable to the study of compensatory growth in diverse tissues in Drosophila

Near-infrared [Fe II] emission from supernova remnants and the supernova rate of starburst galaxies

In an effort to better calibrate the supernova rate of starburst galaxies as determined from near-IR [Fe II] features, we report on a [Fe II] 1.644 microns line-imaging survey of a sample of 42 optically-selected SNRs in M33. A wide range of [Fe II] luminosities are observed within our sample (from less than 6 to 695 L_sun). Our data suggest that the bright [Fe II] SNRs are entering the radiative phase and that the density of the local ISM largely controls the amount of [Fe II] emission. We derive the following relation between the [Fe II] 1.644 microns line luminosity of radiative SNRs and the electronic density of the postshock gas, n_e: L_[Fe II] (L_sun) ~ 1.1 n_e (cm^-3). We also find a correlation in our data between L_[Fe II] and the metallicity of the shock-heated gas, but the physical interpretation of this result remains inconclusive, as our data also show a correlation between the metallicity and n_e. The dramatically higher level of [Fe II] emission from SNRs in the central regions of starburst galaxies is most likely due to their dense environments, although metallicity effects might also be important. The typical [Fe II]-emitting lifetime of a SNR in the central regions of starburst galaxies is found to be of the order of 10^4 yr. On the basis of these results, we provide a new empirical relation allowing the determination of the current supernova rate of starburst galaxies from their integrated near-IR [Fe II] luminosity.Comment: 13 pages, 5 figures; accepted for publication in MNRA

Acceptability of Treatments and Services for Individuals with Hoarding Behaviors

Objective To explore the acceptability of currently available treatments and services for individuals who self-report hoarding behaviors. Method Between 10/2013 and 8/2014, participants were invited to complete an online survey that provided them descriptions of eleven treatments and services for hoarding behaviors and asked them to evaluate their acceptability using quantitative (0 [not at all acceptable]−10 [completely acceptable]) Likert scale ratings. The a priori definition of acceptability for a given resource was an average Likert scale score of six or greater. Two well-validated self-report measures assessed hoarding symptom severity: the Saving Inventory-Revised and the Clutter Image Rating Scale. Results Two hundred and seventy two participants who self-reported having hoarding behaviors completed the questionnaire. Analyses focused on the 73% of responders (n=203) who reported clinically significant hoarding behaviors (i.e., Saving Inventory-Revised scores of ≥40). The three most acceptable treatments were individual cognitive behavioral therapy (6.2±3.1 on the Likert scale), professional organizing service (6.1±3.2), and use of a self-help book (6.0±3.0). Conclusion In this sample of individuals with self-reported clinically significant hoarding behaviors (n=203), only 3 out of 11 treatments and services for hoarding were deemed acceptable using an a priori score. While needing replication, these findings indicate the need to design more acceptable treatments and services to engage clients and maximize treatment outcomes for hoarding disorder

First use of Re:View – a tool to combine assessment tasks, marking criteria and graduate attributes

In order to improve clarity of the link between assessment tasks and graduate attributes to students, Re:View was introduced across three undergraduate biochemistry subjects. Re:View is an on-line assessment tool which provides a direct visual link between graduate attributes and marking criteria. It also provides students with an easy to access portal to retrieve their grade and assessor feedback on assessment tasks. Our aim was to improve the second and third year biochemistry student laboratory based learning experience by developing and clarifying the link between assessment tasks, marking criteria and graduate attributes, using ReView as the assessment tool. Marking criteria for laboratory based assessments across three biochemistry subjects were available to the students, and their assessments were marked against rubrics of criterion referenced marking criteria using Re:View. Student opinion was canvassed via anonymous feedback surveys and focus groups. Student opinion showed Re:View was of benefit to align marking criteria with graduate attributes and provided easy access to feedback which could be used to improve future work. With the use of Re:View we have clarified the link between assessment tasks and marking criteria and enhanced student engagement with laboratory based assessment tasks, which has improved their written assessment performance

Risk of Childhood Cancers Associated with Residence in Agriculturally Intense Areas in the United States

Background: The potential for widespread exposure to agricultural pesticides through drift during application raises concerns about possible health effects to exposed children living in areas of high agricultural activity. Objectives: We evaluated whether residence in a county with greater agricultural activity was associated with risk of developing cancer in children \u3c 15 years of age. Methods: Incidence data for U.S. children 0–14 years of age diagnosed with cancer between 1995 and 2001 were provided by member registries of the North American Association of Central Cancer Registries. We determined percent cropland for each county using agricultural census data, and used the overall study distribution to classify agriculturally intense counties. We estimated odds ratios and 95% confidence intervals for all ages and 5-year age groups for total cancers and selected cancer sites using logistic regression. Results: Our study results showed statistically significant increased risk estimates for many types of childhood cancers associated with residence at diagnosis in counties having a moderate to high level of agricultural activity, with a remarkably consistent dose–response effect seen for counties having ≥ 60% of the total county acreage devoted to farming. Risk for different cancers varied by type of crop. Conclusions: Although interpretation is limited by the ecologic design, in this study we were able to evaluate rarer childhood cancers across a diverse agricultural topography. The findings of this exploratory study support a continued interest in the possible impact of long-term, low-level pesticide exposure in communities located in agriculturally intense areas

The theory of planned behaviour predicts self-reports of walking, but does not predict step count

Objectives This paper compares multiple measures of walking in two studies, and the second study compares how well Theory of Planned Behaviour (TPB) constructs perform in predicting these different measures. Methods In Study 1, 41 participants wore a New Lifestyles NL-2000 pedometer for 1 week. Subsequently, participants completed a questionnaire containing measures of the TPB constructs and two self-report measures of walking, followed by two interview measures of walking. For Study 2, 200 RAF trainee aircraftsmen wore pedometers for 2 weeks. At the end of each week, participants completed the questionnaire and interview measures of walking. Results Both studies found no significant association between questionnaire measures of walking and pedometer measures. In Study 1, the interview measures produced significant, large correlations with the pedometer measure, but these relationships were markedly weaker in the second study. TPB variables were found to explain 22% of variance in intention to walk in Study 1 and 45% of the variance in Study 2. In Study 2, prediction of subsequent measures of behaviour was found to be weak, except when using a single-item measure of walking. Conclusions Recall of walking is poor, and accurate measurement by self-report is problematic. Although the TPB predicts intentions to walk well, it does not predict actual amount of walking, as assessed by pedometer. Possible reasons for these findings include the unique nature of walking as an activity primarily used to facilitate higher order goals. The use of single-item measures may exaggerate the effectiveness of the TPB model for walking, and possibly other forms of physical activity.</p

The opposites task: Using general rules to test cognitive flexibility in preschoolers

A brief narrative description of the journal article, document, or resource. Executive functions play an important role in cognitive development, and during the preschool years especially, children's performance is limited in tasks that demand flexibility in their behavior. We asked whether preschoolers would exhibit limitations when they are required to apply a general rule in the context of novel stimuli on every trial (the "opposites" task). Two types of inhibitory processing were measured: response interference (resistance to interference from a competing response) and proactive interference (resistance to interference from a previously relevant rule). Group data show 3-year-olds have difficulty inhibiting prepotent tendencies under these conditions, whereas 5-year-olds' accuracy is near ceiling in the task. (Contains 4 footnotes and 1 table.

Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder

Background: cognitive behavioural therapy (CBT), including exposure and ritual prevention, is a first-line treatment for obsessive-compulsive disorder (OCD), but few reliable predictors of CBT outcome have been identified. Based on research in animal models, we hypothesized that individual differences in basolateral amygdala-ventromedial prefrontal cortex (BLA-vmPFC) communication would predict CBT outcome in patients with OCD. Methods: we investigated whether BLA-vmPFC resting-state functional connectivity (rs-fc) predicts CBT outcome in patients with OCD. We assessed BLA-vmPFC rs-fc in patients with OCD on a stable dose of a selective serotonin reuptake inhibitor who then received CBT and in healthy control participants. Results: we included 73 patients with OCD and 84 healthy controls in our study. Decreased BLA-vmPFC rs-fc predicted a better CBT outcome in patients with OCD and was also detected in those with OCD compared with healthy participants. Additional analyses revealed that decreased BLA-vmPFC rs-fc uniquely characterized the patients with OCD who responded to CBT. Limitations: we used a sample of convenience, and all patients were receiving pharmacological treatment for OCD. Conclusion: in this large sample of patients with OCD, BLA-vmPFC functional connectivity predicted CBT outcome. These results suggest that future research should investigate the potential of BLA-vmPFC pathways to inform treatment selection for CBT across patients with OCD and anxiety disorders

Reductions in C-reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training

BACKGROUND: Reductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases. Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle. The aim of this investigation was to determine the effects of 12 months of progressive resistance training (PRT) on systemic inflammation, and whether reductions in systemic inflammation were associated with changes in body composition. We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass. METHODS: Participants (n = 103) were randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C-reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle mass and total fat mass were determined using bioelectrical impedance. RESULTS: Twelve months of PRT tended to reduce CRP compared to sham exercise (β = −0.25, p = 0.087). Using linear mixed-effects models, the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass (p = 0.04) and tended to be stronger for total fat mass (p = 0.07) following PRT when compared to sham-exercise. Using univariate regression models, stratified by group allocation, reductions in CRP were associated with increases in skeletal muscle mass (p = 0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in the sham-exercise group (p = 0.87 and p = 0.32, respectively). CONCLUSIONS: We have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass. Furthermore, reductions in CRP were associated with reductions in adiposity, but only when associated with PRT. Lifestyle interventions aimed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations