7α-Hydroxylation of 26-hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid by cytochrome P-450 in pig liver microsomes

AbstractPig liver microsomes were found to catalyze the 7α-hydroxylation of several potential bile acid precursors besides cholesterol. 26-Hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid were all efficiently converted into the 7α-hydroxylated products. Two cytochrome P-450 fractions showing 7α-hydroxylase activity could be isolated. One fraction catalyzed 7α-hydroxylation of 26-hydroxycholesterol. 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7α-hydroxylation of cholesterol in addition to the other substrates. 26-Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7α-hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P-450 catalyzing 7α-hydroxylation of 26-hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid. The results indicate that this cytochrome P-450 is different from that catalyzing 7α-hydroxylation of cholesterol

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits

Funder: H2020 European Research Council; doi: http://dx.doi.org/10.13039/100010663Funder: Research Foundation FlandersFunder: Universiteit Gent; doi: http://dx.doi.org/10.13039/501100004385Funder: Marguerite-Marie DelacroixFunder: Autistica; doi: http://dx.doi.org/10.13039/100011706Funder: Riksbankens Jubileumsfond; doi: http://dx.doi.org/10.13039/501100004472; Grant(s): NHS14-1802:1Funder: K.F. Hein FondsFunder: Scott Family Junior Research FellowshipAbstract: Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

USB complete : Everything you need to develop custom USB peripherals

Amerika Serikatxviii, 523 p.; 25 cm

USB complete: the developer's guide

Now in its fifth edition, bridges the gap between the technical specifications and the real world of designing and programming devices that connect over the Universal Serial Bus (USB). Readers will learn how to select the appropriate USB speed, device class, and hardware for a device; communicate with devices using Visual C# and Visual Basic; use standard host drivers to access devices, including devices that perform vendor-defined tasks; save power with USB's built-in power-conserving protocols; and create robust designs using testing and debugging tools. This fully revised edition also incl