Metabolic adaptation allows Amacr-deficient mice to remain symptom-free despite low levels of mature bile acids

Bile acids play multiple roles in the physiology of vertebrates; they facilitate lipid absorption, serve as signaling molecules to control carbohydrate and lipid metabolism, and provide a disposal route for cholesterol. Unexpectedly, the α-methylacyl-CoA racemase (Amacr) deficient mice, which are unable to complete the peroxisomal cleavage of C27-precursors to the mature C24-bile acids, are physiologically asymptomatic when maintained on a standard laboratory diet. The aim of this study was to uncover the underlying adaptive mechanism with special reference to cholesterol and bile acid metabolism that allows these mice to have a normal life span. Intestinal cholesterol absorption in Amacr −/− mice is decreased resulting in a 2-fold increase in daily cholesterol excretion. Also fecal excretion of bile acids (mainly C27-sterols) is enhanced 3-fold. However, the body cholesterol pool remains unchanged, although Amacr-deficiency accelerates hepatic sterol synthesis 5-fold. Changes in lipoprotein profiles are mainly due to decreased phospholipid transfer protein activity. Thus Amacr-deficient mice provide a unique example of metabolic regulation, which allows them to have a normal lifespan in spite of the disruption of a major metabolic pathway. This metabolic adjustment can be mainly explained by setting cholesterol and bile acid metabolism to a new balanced level in the Amacr-deficient mouse.     

Using Conjoint Analysis to Weight Broiler Welfare Variables Based on Slaughterhouse Data

The Council of the European Union adopted the welfare directive for broiler chickens in 2007 (Commission of the European Communities, 2007). The directive defines minimum demands and objectives for broiler production ranging from stocking density to welfare. This study found that the level of nonhuman animal welfare can be determined, for example, with welfare indexes that have different weight values for welfare variables. A total of 20 poultry experts from slaughterhouses, the feed industry, administration, and research received simulated data on 24 flocks. This included data for 5 welfare variables based on postmortem meat inspection information on commercial flocks and based on literature: mortality during rearing, foot-pad score, and the incidence of ascites, dermatitis, and cachexia in routine meat inspection. The experts ranked these flocks from the worst to the best according to animal welfare. Conjoint analysis weighted the relative importance of the welfare variables for broiler welfare. The study based relative importance for broiler welfare on 20 expert opinions: 24.6% for mortality, 35.9% for foot-pad score, 19.7% for the incidence of ascites, 15.7% for the incidence of dermatitis, and 4.1% for the incidence of cachexia. In the future, an index for broiler welfare evaluation could be developed based on the results of this study.     

Microscopy Image Browser: A Platform for Segmentation and Analysis of Multidimensional Datasets

Understanding the structure–function relationship of cells and organelles in their natural context requires multidimensional imaging. As techniques for multimodal 3-D imaging have become more accessible, effective processing, visualization, and analysis of large datasets are posing a bottleneck for the workflow. Here, we present a new software package for high-performance segmentation and image processing of multidimensional datasets that improves and facilitates the full utilization and quantitative analysis of acquired data, which is freely available from a dedicated website. The open-source environment enables modification and insertion of new plug-ins to customize the program for specific needs. We provide practical examples of program features used for processing, segmentation and analysis of light and electron microscopy datasets, and detailed tutorials to enable users to rapidly and thoroughly learn how to use the program.     

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients.     

Effects of environmental factors on the phytoplankton community in the Gulf of Finland – unattended high frequency measurements and multivariate analyses

We studied life history and secondary production of Cheumatopsyche spp. (Trichoptera: Hydropsychidae) in StroublesCreek, a 3rd order stream near Blacksburg, Virginia to compare lifehistories and production dynamics in two reaches with differentland-uses. The upstream reach was influenced by agriculturalactivities and more annual degree-days accumulated in this sectionof the stream. The downstream reach was surrounded by forest,received less thermal input than the upstream reach, and showedlittle evidence of human disturbance. Differences between the twosites included a shift in dominant taxa and changes in voltinismand production of hydropsychids. Cheumatopsyche pettiti(Banks) was dominant at the upstream site, while C. pettitiand Cheumatopsyche oxa Ross were both abundant downstream.Cheumatopsyche larvae and other aquatic insects had higherdensities at the forested downstream site. C. pettiti wasbivoltine at the upstream site, but C. pettiti and C. oxa were partially bivoltine downstream, with a small summergeneration overlapping with continuous emergence of overwinteringlarvae. Cheumatopsyche production at the two sites inStroubles Creek was higher than in forested, low-order streams ofNorth America, but similar to some values obtained at streams inagricultural areas and large rivers. Production was higher at thedownstream site, but the superior bivoltinism at the upstream sitecounterbalanced, to some extent, the increase in larval densitythat caused higher production downstream. The adjustment in lifehistory and production dynamics, in the two reaches, showed theecological plasticity of Cheumatopsyche and the importance ofhydropsychids in the energy flow of moderately disturbedstreams.