1,095 research outputs found

    Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice.

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    Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism

    Flight test and analyses of the B-1 structural mode control system at supersonic flight conditions

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    A practical structural mode control system (SMCS) that could be turned on at takeoff and be left on for the entire flight was demonstrated. The SMCS appears to be more effective in damping the key fuselage bending modes at supersonic speeds than at the design point of Mach 0.85 (for fixed gains). The SMCS has an adverse effect on high frequency symmetric modes; however, this adverse effect did not make the system unstable and does not appear to affect ride quality performance. The vertical ride quality analyses indicate that the basic configuration without active systems is satisfactory for long term exposure. If clear air turbulence were to be encountered, indications are that the SMCS would be very effective in reducing the adverse accelerations. On the other hand, lateral ride quality analyses indicate that the aircraft with the SMCS on does not quite meet the long term exposure criteria, but would be satisfactory for shot term exposure at altitude. Again, the lateral SMCS was shown to be very effective in reducing peak lateral accelerations

    A Pilot Randomised Control Trial of Digitally-Mediated Social Stories for Children on the Autism Spectrum

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    Social stories is a widely used intervention for children on the autism spectrum, particularly within an educational context. To date, systematic reviews and meta analyses of the research evaluating social stories has produced mixed results, often due to a lack of methodological rigour and variability in the development and delivery of the social stories. To address the gap in methodological rigour, a pilot Randomised Control Trial (RCT) was conducted, incorporating a social stories intervention group (n = 9 children on the autism spectrum) and an attentional control group who received a poem (n = 6 children on the autism spectrum) using a digital platform to address variability. Digitally-mediated social stories were found to be effective in producing beneficial changes in behaviour outcomes, which were sustained at a six-week follow up.</p

    Evaluation of a Brazilian fuel alcohol yeast strain for Scotch whisky fermentations

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    Traditionally, distilling companies in Scotland have employed a very limited number of yeast strains in the production of alcohol for Scotch whiskies. Recent changes such as the decline in availability of brewers’ yeast as a secondary yeast strain and the availability of yeast in different formats (e.g., dried and cream yeast as alternatives to compressed yeast) have promoted interest in alternative Scotch whisky distilling yeasts. In previous work, we investigated different strains of yeasts, specifically Brazilian yeasts which had been isolated from and used in fuel alcohol distilleries. One of the Brazilian yeasts (CAT 1) showed a comparable fermentation performance and superior stress tolerance compared with a standard commercial Scotch whisky distilling yeast (M Type). The Brazilian CAT 1 yeast isolate was further assessed in laboratory scale fermentations and subsequent new make spirit was subjected to sensory analyses. The spirits produced using the Brazilian strain had acceptable flavour profiles and exhibited no sensory characteristics that were atypical of Scotch whisky new make spirit. This study highlights the potential of exploiting yeast biodiversity in traditional Scotch whisky distillery fermentation processes

    Piloting a digitally-mediated social story intervention for autistic children led by teachers within naturalistic school settings

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    BackgroundSocial stories (SS) are widely used within the autism community. However, research into their effectiveness is mixed at best and mainly relies on single case study designs. Additional support from the researcher is also often provided, raising questions as to the use and effectiveness of SS within usual school settings.MethodSeventeen school teachers developed and delivered personalised digitally-mediated SS with 22 autistic children (aged 5-11yrs) over a 4-week intervention period. Data was collected during a baseline period (1 week), throughout the 4-week intervention phase and at 6-week follow-up to consider changes in child behaviour, understanding and anxiety. A new assessment framework to evaluation treatment fidelity according to Gray’s 10 Criteria was also developed.ResultsWith the support of a new SS app teachers were able to carry out SS interventions with a high degree of fidelity within their usual school settings. Behavioural data showed significant improvements from baseline to week 4 for all measures relating to the goals of the intervention (including a reduction in anxiety and an increase in understanding), some of which were still present at follow-up.ConclusionThis study has demonstrated that technology can be used to support teachers to develop and deliver SS interventions to autistic children within school settings. Such technology can now be used to facilitate much needed future, larger, controlled studies within this area. Implications for practice are discussed

    Comparative Approaches to Studying Strategy: Towards an Evolutionary Account of Primate Decision Making

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    How do primates, humans included, deal with novel problems that arise in interactions with other group members? Despite much research regarding how animals and humans solve social problems, few studies have utilized comparable procedures, outcomes, or measures across different species. Thus, it is difficult to piece together the evolution of decision making, including the roots from which human economic decision making emerged. Recently, a comparative body of decision making research has emerged, relying largely on the methodology of experimental economics in order to address these questions in a cross-species fashion. Experimental economics is an ideal method of inquiry for this approach. It is a well-developed method for distilling complex decision making involving multiple conspecifics whose decisions are contingent upon one another into a series of simple decision choices. This allows these decisions to be compared across species and contexts. In particular, our group has used this approach to investigate coordination in New World monkeys, Old World monkeys, and great apes (including humans), using identical methods. We find that in some cases there are remarkable continuities of outcome, as when some pairs in all species solved a coordination game, the Assurance game. On the other hand, we also find that these similarities in outcomes are likely driven by differences in underlying cognitive mechanisms. New World monkeys required exogenous information about their partners’ choices in order to solve the task, indicating that they were using a matching strategy. Old World monkeys, on the other hand, solved the task without exogenous cues, leading to investigations into what mechanisms may be underpinning their responses (e.g., reward maximization, strategy formation, etc.). Great apes showed a strong experience effect, with cognitively enriched apes following what appears to be a strategy. Finally, humans were able to solve the task with or without exogenous cues. However, when given the chance to do so, they incorporated an additional mechanism unavailable to the other primates - language - to coordinate outcomes with their partner. We discuss how these results inform not only comparative psychology, but also evolutionary psychology, as they provide an understanding of the evolution of human economic behavior, and the evolution of decision making more broadly

    Activation of hepatic glutaminase by spermine

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    Homocysteine Metabolism in ZDF (Type 2) Diabetic Rats

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    Mild hyperhomocysteinemia is a risk factor for many diseases, including cardiovascular disease. We determined the effects of insulin resistance and of type 2 diabetes on homocysteine (Hcy) metabolism using Zucker diabetic fatty rats (ZDF/Gmi fa/fa and ZDF/Gmi fa/?). Plasma total Hcy was reduced in ZDF fa/fa rats by 24% in the pre-diabetic insulin-resistant stage, while in the frank diabetic stage there was a 59% reduction. Hepatic activities of several enzymes that play a role in the removal of Hcy: cystathionine β-synthase (CBS), cystathionine γ-lyase, and betaine:Hcy methyltransferase (BHMT) were increased as was methionine adenosyltransferase. CBS and BHMT mRNA levels and the hepatic level of S-adenosylmethionine were also increased in the ZDF fa/fa rats. Studies with primary hepatocytes showed that Hcy export and the transsulfuration flux in cells from ZDF fa/fa rats were particularly sensitive to betaine. Interestingly, liver betaine concentration was found to be significantly lower in the ZDf fa/fa rats at both 5 and 11 weeks. These results emphasize the importance of betaine metabolism in determining plasma Hcy levels in type 2 diabetes

    Generous Leaders and Selfish Underdogs: Pro-Sociality in Despotic Macaques

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    Actively granting food to a companion is called pro-social behavior and is considered to be part of altruism. Recent findings show that some non-human primates behave pro-socially. However, pro-social behavior is not expected in despotic species, since the steep dominance hierarchy will hamper pro-sociality. We show that some despotic long-tailed macaques do grant others access to food. Moreover, their dominance hierarchy determines pro-social behavior in an unexpected way: high-ranking individuals grant, while low-ranking individuals withhold their partner access to food. Surprisingly, pro-social behavior is not used by subordinates to obtain benefits from dominants, but by dominants to emphasize their dominance position. Hence, Machiavellian macaques rule not through “fear above love”, but through “be feared when needed and loved when possible”
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