274 research outputs found

    Measurement of Receptor-Activated Phosphoinositide Turnover in Rat Brain: Nonequivalence of Inositol Phosphate and CDP-Diacylglycerol Formation

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    Two methods for the measurement of receptor-activated phosphoinositide turnover were evaluated for their degree of correspondence in slices of rat brain; they involved the Li + -dependent accumulations of either [ 3 H]-inositol-labeled inositol phosphates or [ 3 H]cytidine-labeled CDP-diacylglycerol. In contrast to the expectation that the ratio of these two responses would remain approximately constant, varying degrees of correspondence were obtained. The two extremes are exemplified by carbachol, which elicited large increases in both inositol phosphate and CDP-diacylglycerol labeling, and endothelin, which gave a robust inositol phosphate response with little or no accumulation of 3 H-CDP-diacylglycerol. No instance of the presence of the latter response in the absence of 3 H-inositol phosphate accumulation was observed. Measurement of 3 H-CDP-diacylglycerol accumulation thus may add additional insight into the regulation of phosphoinositide turnover and the complex actions of Li + .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66135/1/j.1471-4159.1993.tb03258.x.pd

    Keeping it liminal. The Mondiali Antirazzisti (Anti-racist World Cup) as a multifocal interaction ritual

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    © 2013 Taylor & Francis. This paper examines how social mixing and celebration of diversity can be enabled through sports festivals marked by their carnivalesque atmosphere. Our analysis draws on a longitudinal ethnographic study of the Mondiali Antirazzisti (Anti-racist World Cup), a non-competitive football tournament and intercultural festival featuring the yearly participation of hardcore football fans (ultras), migrant groups, third-sector associations and other informal groups. We consider how the multifocal ritual form of the event helps to create a liminal space in which discrimination and stereotypes can be temporarily challenged. The sources of collective effervescence are multiplied by placing sport games within a wider range of other leisure and cultural activities, thus promoting internal diversity and the inclusion of outsiders. Additionally, social boundaries are also blurred by not emphasising the competitive dimension of the sporting activities, making sporting categorisations more fluid, and breaking down the separation between protagonists and spectators. Nonetheless, considering the transient character of liminality, we also investigate problems and limitations implied by the pursuit of these objectives. It is concluded that, despite a certain degree of self-referentiality, the festival fosters the spreading of anti-discriminatory cultures by enhancing the participants’ reflexivity and feeding their commitment in generating spin-off activities in different local contexts

    Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

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    <p>Abstract</p> <p>Background</p> <p>The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the <it>myelin protein zero (MPZ) </it>gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P<sub>0</sub>) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P<sub>0</sub>ex) is known, while the transmembrane and intracellular structure is unknown.</p> <p>Findings</p> <p>One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with Déjérine-Sottas syndrome.</p> <p>Conclusions</p> <p>The phenotypic variation caused by different missense mutations in the <it>MPZ </it>gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and Déjérine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.</p

    Predicting Phospholipidosis Using Machine Learning

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    Phospholipidosis is an adverse effect caused by numerous cationic amphiphilic drugs and can affect many cell types. It is characterized by the excess accumulation of phospholipids and is most reliably identified by electron microscopy of cells revealing the presence of lamellar inclusion bodies. The development of phospholipidosis can cause a delay in the drug development process, and the importance of computational approaches to the problem has been well documented. Previous work on predictive methods for phospholipidosis showed that state of the art machine learning methods produced the best results. Here we extend this work by looking at a larger data set mined from the literature. We find that circular fingerprints lead to better models than either E-Dragon descriptors or a combination of the two. We also observe very similar performance in general between Random Forest and Support Vector Machine models.</p

    ICT-based system to predict and prevent falls (iStoppFalls): results from an international multicenter randomized controlled trial

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    Background: Falls and fall-related injuries are a serious public health issue. Exercise programs can effectively reduce fall risk in older people. The iStoppFalls project developed an Information and Communication Technology-based system to deliver an unsupervised exercise program in older people’s homes. The primary aims of the iStoppFalls randomized controlled trial were to assess the feasibility (exercise adherence, acceptability and safety) of the intervention program and its effectiveness on common fall risk factors. Methods: A total of 153 community-dwelling people aged 65+ years took part in this international, multicentre, randomized controlled trial. Intervention group participants conducted the exercise program for 16 weeks, with a recommended duration of 120 min/week for balance exergames and 60 min/week for strength exercises. All intervention and control participants received educational material including advice on a healthy lifestyle and fall prevention. Assessments included physical and cognitive tests, and questionnaires for health, fear of falling, number of falls, quality of life and psychosocial outcomes. Results: The median total exercise duration was 11.7 h (IQR = 22.0) over the 16-week intervention period. There were no adverse events. Physiological fall risk (Physiological Profile Assessment, PPA) reduced significantly more in the intervention group compared to the control group (F1,127 = 4.54, p = 0.035). There was a significant three-way interaction for fall risk assessed by the PPA between the high-adherence (>90 min/week; n = 18, 25.4 %), low-adherence (n = 53, 74.6 %) and control group (F2,125 = 3.12, n = 75, p = 0.044). Post hoc analysis revealed a significantly larger effect in favour of the high-adherence group compared to the control group for fall risk (p = 0.031), postural sway (p = 0.046), stepping reaction time (p = 0.041), executive functioning (p = 0.044), and quality of life (p for trend = 0.052). Conclusions: The iStoppFalls exercise program reduced physiological fall risk in the study sample. Additional subgroup analyses revealed that intervention participants with better adherence also improved in postural sway, stepping reaction, and executive function

    Jography: Exploring meanings, experiences and spatialities of recreational road-running

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    Jogging is a relatively under-researched mobile practice with much existing literature focusing on ‘serious’ and competitive running. In this paper, we provide an account of some of the movements, meanings and experiences that together help produce the practice of jogging in the south-western English city of Plymouth. Drawing upon participant diaries and interviews, we uncover rich detail about how joggers ascribe not one but a number of meanings to their practice. Some of these are positive, some are negative; some complement each other and some compete with each other. We also consider how the experiences of joggers can be shaped by their ongoing need to develop tactics capable of enabling them to negotiate space with non-joggers. This is in some contrast to more competitive running that occurs in the separated space of an athletics track. Our sense is that better awareness of the meanings and experiences of jogging will be of value if the advertised health and sustainability benefits of the practice are to be more effectively encouraged and promoted

    The medical threat of mamba envenoming in sub-Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and antivenomics profiling of available antivenoms

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    Mambas (genus Dendroaspis) are among the most feared of the medically important elapid snakes found in sub-Saharan Africa, but many facets of their biology, including the diversity of venom composition, remain relatively understudied. Here, we present a reconstruction of mamba phylogeny, alongside genus-wide venom gland transcriptomic and high-resolution top-down venomic analyses. Whereas the green mambas, D. viridis, D. angusticeps, D. j. jamesoni and D. j. kaimosae, express 3FTx-predominant venoms, black mamba (D. polylepis) venom is dominated by dendrotoxins I and K. The divergent terrestrial ecology of D. polylepis compared to the arboreal niche occupied by all other mambas makes it plausible that this major difference in venom composition is due to dietary variation. The pattern of intrageneric venom variability across Dendroaspis represented a valuable opportunity to investigate, in a genus-wide context, the variant toxicity of the venom, and the degree of paraspecific cross-reactivity between antivenoms and mamba venoms. To this end, the immunological profiles of the five mamba venoms were assessed against a panel of commercial antivenoms generated for the sub-Saharan Africa market. This study provides a genus-wide overview of which available antivenoms may be more efficacious in neutralising human envenomings caused by mambas, irrespective of the species responsible. The information gathered in this study lays the foundations for rationalising the notably different potency and pharmacological profiles of Dendroaspis venoms at locus resolution. This understanding will allow selection and design of toxin immunogens with a view to generating a safer and more efficacious pan-specific antivenom against any mamba envenomation
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