Predicting specificity in bZIP coiled-coil protein interactions

We present a method for predicting protein-protein interactions mediated by the coiled-coil motif. When tested on interactions between nearly all human and yeast bZIP proteins, our method identifies 70% of strong interactions while maintaining that 92% of predictions are correct. Furthermore, cross-validation testing shows that including the bZIP experimental data significantly improves performance. Our method can be used to predict bZIP interactions in other genomes and is a promising approach for predicting coiled-coil interactions more generally

Approachability to a Human in Gilts Divergently Selected for Feed Efficiency

The objective of this study was to evaluate approachability of gilts divergently selected for residual feed intake (RFI) to a novel human. Twenty low-RFI and 19 high-RFI gilts were tested using a human approach test. Testing occurred over two consecutive weeks between 1300 and 1900 hours. Gilts were tested individually within a 4.9 x 2.4 m test arena. Throughout the test, latency to first enter, duration of time spent, and frequency of entrances within 1 m and 0.5 m of the human were recorded. These results suggest that divergent selection for RFI did not alter gilt approach behavior to a novel human

Effects of Genetic Selection for Residual Feed Intake on Behavioral Reactivity of Castrated Male Pigs to Novel Stimuli Tests

Increasing feed efficiency in swine is important for increasing sustainable food production and profitability for producers; therefore, this is often selected for at breeding. Residual feed intake (RFI) can be used for the genetic selection of pigs for feed efficiency. In our selection project, low-RFI pigs consume less feed for equal weight gain compared to their less efficient, high-RFI counterparts. However, little is known about how feed efficiency influences the pig\u27s behavioral reactivity toward fear-eliciting stimuli. In this study, behavioral reactivity of pigs divergently selected for RFI was evaluated using human approach- (HAT) and novel object tests (NOT). Forty low-RFI (more feed efficient) and 40 high-RFI (less feed efficient) castrated male pigs (barrows; 46.5 ± 8.6 kg) from 8th generation Yorkshire RFI selection lines were randomly selected and evaluated once using HAT and once using NOT over a four week period utilizing a crossover experimental design. Each pig was individually tested within a 4.9 × 2.4 m test arena for 10 min; behavior was evaluated using live and video observations. The test arena floor was divided into four zones; zone 1 being oral, nasal, and/or facial contact with the human (HAT) or orange traffic cone (NOT) and zone 4 being furthest from the human or cone and included the point where the pig entered the arena. During both HAT and NOT, low-RFI pigs crossed fewer zones (P \u3c 0.0001), had fewer head movements (P ≤ 0.02), defecated less frequently (P ≤ 0.03), displayed a shorter duration of freezing (P = 0.05), and froze less frequently (HAT: low-RFI = 4.9 ± 0.65 vs. high-RFI = 7.5 ± 0.96; NOT: low-RFI = 4.7 ± 0.66 vs. high-RFI = 7.2 ± 0.96; P \u3c 0.0001) compared to high-RFI pigs. During HAT, low-RFI pigs also attempted to escape less frequently (low-RFI = 0.4 ± 0.14 vs. high-RFI = 1.1 ± 0.30; P = 0.001) compared to high-RFI pigs. In contrast, compared to the high-RFI pigs, low-RFI pigs took 48 s longer during HAT and 52 s longer during NOT to approach zone 1 (P ≤ 0.04). These results indicate that low-RFI pigs had decreased behavioral reactivity during HAT and NOT compared to high-RFI pigs. This may suggest that reducing a pig\u27s behavioral reactivity is an important component of improving feed efficiency; however, it may have implications for animal handling and facility design

Methods for the evaluation of the Jamie Oliver Ministry of Food program, Australia.

BACKGROUND: Community-based programs aimed at improving cooking skills, cooking confidence and individual eating behaviours have grown in number over the past two decades. Whilst some evidence exists to support their effectiveness, only small behavioural changes have been reported and limitations in study design may have impacted on results.This paper describes the first evaluation of the Jamie Oliver Ministry of Food Program (JMoF) Australia, in Ipswich, Queensland. JMoF Australia is a community-based cooking skills program open to the general public consisting of 1.5 hour classes weekly over a 10 week period, based on the program of the same name originating in the United Kingdom. METHODS/DESIGN: A mixed methods study design is proposed. Given the programmatic implementation of JMoF in Ipswich, the quantitative study is a non-randomised, pre-post design comparing participants undergoing the program with a wait-list control group. There will be two primary outcome measures: (i) change in cooking confidence (self-efficacy) and (ii) change in self-reported mean vegetable intake (serves per day). Secondary outcome measures will include change in individual cooking and eating behaviours and psycho-social measures such as social connectedness and self-esteem. Repeated measures will be collected at baseline, program completion (10 weeks) and 6 months follow up from program completion. A sample of 250 participants per group will be recruited for the evaluation to detect a mean change of 0.5 serves a day of vegetables at 80% power (0.5% significance level). Data analysis will assess the magnitude of change of these variables both within and between groups and use sub group analysis to explore the relationships between socio-demographic characteristics and outcomes.The qualitative study will be a longitudinal design consisting of semi-structured interviews with approximately 10-15 participants conducted at successive time points. An inductive thematic analysis will be conducted to explore social, attitudinal and behavioural changes experienced by program participants. DISCUSSION: This evaluation will contribute to the evidence of whether cooking programs work in terms of improving health and wellbeing and the underlying mechanisms which may lead to positive behaviour change. TRIAL REGISTRATION: Australian and New Zealand Trial registration number: ACTRN12611001209987

Amelioration of Binge Eating by Nucleus Accumbens Shell Deep Brain Stimulation in Mice Involves D2 Receptor Modulation

Hedonic overconsumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity (Wise, 2012). Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive–compulsive disorder, and addiction, may also be effective in ameliorating binge eating. Therefore, we examined the ability of DBS of the NAS to block this behavior in mice. c-Fos immunoreactivity was assessed as a marker of DBS-mediated neuronal activation. NAS DBS was found to reduce binge eating and increased c-Fos levels in this region. DBS of the dorsal striatum had no influence on this behavior, demonstrating anatomical specificity for this effect. The dopamine D2 receptor antagonist, raclopride, attenuated the action of DBS, whereas the D1 receptor antagonist, SCH-23390, was ineffective, suggesting that dopamine signaling involving D2 receptors underlies the effect of NAS DBS. To determine the potential translational relevance to the obese state, chronic NAS DBS was also examined in diet-induced obese mice and was found to acutely reduce caloric intake and induce weight loss. Together, these findings support the involvement of the mesolimbic dopamine pathways in the hedonic mechanisms contributing to obesity, and the efficacy of NAS DBS to modulate this system

Rats can predict aversiveness of Active Pharmaceutical Ingredients.

Taste is crucial for patient acceptability and compliance with prescribed medicines, in particular with pediatric patients. Evaluating the taste of new active pharmaceutical ingredients (APIs) is therefore essential to put in place adequate taste-masking techniques, if needed, which will lead to acceptable palatable formulations. Thus, there is an urgent need to develop and optimize taste assessment methods that could be used at different stages of the drug development process. The aim of this study was to investigate the suitability of the rat brief-access taste aversion (BATA) model as a screening tool for assessment of APIs aversiveness that could predict human taste responses. Presently, the taste intensity of nine marketed APIs known to have different levels of bitter intensity (quinine hydrochloride dihydrate, 6-n-propylthiouracil, sildenafil citrate, diclofenac sodium, ranitidine hydrochloride, caffeine citrate, isoniazid, telbivudine and paracetamol) was investigated at different overlapping concentrations with two in vivo taste assessment methods: the rat BATA model and human taste panels with the intention of determining the drugs' concentrations to produce half of the maximal rating. Overall there was a strong correlation (R2?=?0.896) between rats IC50 and humans EC50 values. This correlation verifies the BATA model as a rapid and reliable tool for quantitative assessment of API aversiveness. A comparable ranking order was obtained mainly for high and medium aversive compounds, whereas it was less aligned for weakly aversive compounds. It was nonetheless possible to propose a classification of poor taste intensity determined in rats that would predict human taste tolerability

CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids

Mutations in the colony stimulating factor 1 receptor