Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1α : modulation by p38 MAPK

The transcriptional coactivator PPAR gamma coactivator 1 α (PGC-1α) is a key regulator of metabolic processes such as mitochondrial biogenesis and respiration in muscle and gluconeogenesis in liver. Reduced levels of PGC-1α in humans have been associated with type II diabetes. PGC-1α contains a negative regulatory domain that attenuates its transcriptional activity. This negative regulation is removed by phosphorylation of PGC-1α by p38 MAPK, an important kinase downstream of cytokine signaling in muscle and β-adrenergic signaling in brown fat. We describe here the identification of p160 myb binding protein (p160MBP) as a repressor of PGC-1α. The binding and repression of PGC-1α by p160MBP is disrupted by p38 MAPK phosphorylation of PGC-1α. Adenoviral expression of p160MBP in myoblasts strongly reduces PGC-1α's ability to stimulate mitochondrial respiration and the expression of the genes of the electron transport system. This repression does not require removal of PGC-1α from chromatin, suggesting that p160MBP is or recruits a direct transcriptional suppressor. Overall, these data indicate that p160MBP is a powerful negative regulator of PGC-1α function and provide a molecular mechanism for the activation of PGC-1α by p38 MAPK. The discovery of p160MBP as a PGC-1α regulator has important implications for the understanding of energy balance and diabetes

FlyBase 101 – the basics of navigating FlyBase

FlyBase (http://flybase.org) is the leading database and web portal for genetic and genomic information on the fruit fly Drosophila melanogaster and related fly species. Whether you use the fruit fly as an experimental system or want to apply Drosophila biological knowledge to another field of study, FlyBase can help you successfully navigate the wealth of available Drosophila data. Here, we review the FlyBase web site with novice and less-experienced users of FlyBase in mind and point out recent developments stemming from the availability of genome-wide data from the modENCODE project. The first section of this paper explains the organization of the web site and describes the report pages available on FlyBase, focusing on the most popular, the Gene Report. The next section introduces some of the search tools available on FlyBase, in particular, our heavily used and recently redesigned search tool QuickSearch, found on the FlyBase homepage. The final section concerns genomic data, including recent modENCODE (http://www.modencode.org) data, available through our Genome Browser, GBrowse

Neutron to proton ratios of quasiprojectile and midrapidity emission in the 64^{64}Zn + 64^{64}Zn reaction at 45 MeV/nucleon

Simultaneous measurement of both neutrons and charged particles emitted in the reaction $^{64}$Zn + $^{64}$Zn at 45 MeV/nucleon allows comparison of the neutron to proton ratio at midrapidity with that at projectile rapidity. The evolution of N/Z in both rapidity regimes with increasing centrality is examined. For the completely re-constructed midrapidity material one finds that the neutron-to-proton ratio is above that of the overall $^{64}$Zn + $^{64}$Zn system. In contrast, the re-constructed ratio for the quasiprojectile is below that of the overall system. This difference provides the most complete evidence to date of neutron enrichment of midrapidity nuclear matter at the expense of the quasiprojectile

National critical incident reporting systems relevant to anaesthesia: a European survey

Background Critical incident reporting is a key tool in the promotion of patient safety in anaesthesia. Methods We surveyed representatives of national incident reporting systems in six European countries, inviting information on scope and organization, and intelligence on factors determining success and failure. Results Some systems are government-run and nationally conceived; others started out as small, specialty-focused initiatives, which have since acquired a national reach. However, both national co-ordination and specialty enthusiasts seem to be necessary for an optimally functioning system. The role of reporting culture, definitional issues, and dissemination is discussed. Conclusions We make recommendations for others intending to start new systems and speculate on the prospects for sharing patient safety lessons relevant to anaesthesia at European leve

‘I had to pop a wheelie and pay extra attention in order not to fall:’ embodied experiences of two wheelchair tennis athletes transgressing ableist and gendered norms in disability sport and university spaces

When bodies move in certain contexts, it can mean very different things for different people. In our society, some bodies are more valued than others, and detrimentally, this can mean that certain types of bodies are ostracised and segregated to the outskirts of production economies and society. Dis/ability sport spaces, able-bodied sports spaces and able-bodied university spaces have been an under-researched area when considering how the body moves throughout these spaces for elite wheelchair athletes taking part in university courses. To learn more, this paper drew on feminist poststructuralism and new materialist perspectives and shared an insight into how two athletes with dis/abilities transgressed abled and gendered norms in different spaces and how they positioned themselves as athletic bodies and disabled bodies in these spaces. Employing a post-critical ethnographic design, we found that dependent on the space a dis/abled body is in constant flux as to when it feels marginalised and different (typically able-bodied spaces) and when it feels included, valued, and strong (typically dis/abled spaces). Significantly, the materiality of the institutional structures of universities, founded upon historic aesthetics of beauty dictated the physical spaces the athletes entered and created spaces of exclusion based on capitalist and ableist ideologies

Functional characterization of a melon alcohol acyl-transferase gene family involved in the biosynthesis of ester volatiles. Identification of the crucial role of a threonine residue for enzyme activity

Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT). We demonstrate here that, in Charentais melon (Cucumis melo var. cantalupensis), AAT are encoded by a gene family of at least four members with amino acid identity ranging from 84% (Cm-AAT1/Cm-AAT2) and 58% (Cm-AAT1/Cm-AAT3) to only 22% (Cm-AAT1/Cm-AAT4). All encoded proteins, except Cm-AAT2, were enzymatically active upon expression in yeast and show differential substrate preferences. Cm-AAT1 protein produces a wide range of short and long-chain acyl esters but has strong preference for the formation of E-2-hexenyl acetate and hexyl hexanoate. Cm-AAT3 also accepts a wide range of substrates but with very strong preference for producing benzyl acetate. Cm-AAT4 is almost exclusively devoted to the formation of acetates, with strong preference for cinnamoyl acetate. Site directed mutagenesis demonstrated that the failure of Cm-AAT2 to produce volatile esters is related to the presence of a 268-alanine residue instead of threonine as in all active AAT proteins. Mutating 268-A into 268-T of Cm-AAT2 restored enzyme activity, while mutating 268-T into 268-A abolished activity of Cm-AAT1. Activities of all three proteins measured with the prefered substrates sharply increase during fruit ripening. The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. The data presented in this work suggest that the multiplicity of AAT genes accounts for the great diversity of esters formed in melon

Predicting patterns of service utilization within children\u27s mental health agencies

Background: Some children with mental health (MH) problems have been found to receive ongoing care, either continuously or episodically. We sought to replicate patterns of MH service use over extended time periods, and test predictors of these patterns. Methods: Latent class analyses were applied to 4 years of visit data from five MH agencies and nearly 6000 children, 4-to 13-years-old at their first visit. Results: Five patterns of service use were identified, replicating previous findings. Overall, 14% of cases had two or more episodes of care and 23% were involved for more than 2 years. Most children (53%) were seen for just a few visits within a few months. Two patterns represented cases with two or more episodes of care spanning multiple years. In the two remaining patterns, children tended to have just one episode of care, but the number of sessions and length of involvement varied. Using discriminant function analyses, we were able to predict with just over 50% accuracy children\u27s pattern of service use. Severe externalizing behaviors, high impairment, and high family burden predicted service use patterns with long durations of involvement and frequent visits. Conclusions: Optimal treatment approaches for children seen for repeated episodes of care or for care lasting multiple years need to be developed. Children with the highest level of need (severe pathology, impairment, and burden) are probably best served by providing high intensity services at the start of care