Reduced levels of dopamine and altered metabolism in brains of HPRT knock-out rats: a new rodent model of Lesch-Nyhan Disease

Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of-function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPRT activity disrupts brain function. As the rat is the preferred rodent experimental model for studying neurobiology and diseases of the brain, we used genetically-modified embryonic stem cells to generate an HPRT knock-out rat. Male HPRT-deficient rats were viable, fertile and displayed normal caged behaviour. However, metabolomic analysis revealed changes in brain biochemistry consistent with disruption of purine recycling and nucleotide metabolism. Broader changes in brain biochemistry were also indicated by increased levels of the core metabolite citrate and reduced levels of lipids and fatty acids. Targeted MS/MS analysis identified reduced levels of dopamine in the brains of HPRT-deficient animals, consistent with deficits noted previously in human LND patients and HPRT knock-out mice. The HPRT-deficient rat therefore provides a new experimental platform for future investigation of how HPRT activity and disruption of purine metabolism affects neural function and behaviour

An evaluation of primary care led dementia diagnostic services in Bristol

© 2014 Dodd et al. Background: Typically people who go to see their GP with a memory problem will be initially assessed and those patients who seem to be at risk will be referred onto a memory clinic. The demographic forces mean that memory services will need to expand to meet demand. An alternative may be to expand the role of primary care in dementia diagnosis and care. The aim of this study was to contrast patient, family member and professional experience of primary and secondary (usual) care led memory services. Methods: A qualitative, participatory study. A topic guide was developed by the peer and professional panels. Data were collected through peer led interviews of people with dementia, their family members and health professionals. Results: Eleven (21%) of the 53 GP practices in Bristol offered primary care led dementia services. Three professional panels were held and were attended by 9 professionals; nine carers but no patients were involved in the three peer panels. These panels identified four main themes: GPS rarely make independent dementia diagnosis; GPS and memory nurses work together; patients and carers generally experience a high quality diagnostic service; an absence of post diagnostic support. Evidence relating to these themes was collected through a total of 46 participants took part; 23 (50%) in primary care and 23 (50%) in the memory service. Conclusions: Patients and carers were generally satisfied with either primary or secondary care led approaches to dementia diagnosis. Their major concern, shared with many health care professionals, was a lack of post diagnostic support

Post-traumatic glenohumeral cartilage lesions: a systematic review

<p>Abstract</p> <p>Background</p> <p>Any cartilage damage to the glenohumeral joint should be avoided, as these damages may result in osteoarthritis of the shoulder. To understand the pathomechanism leading to shoulder cartilage damage, we conducted a systematic review on the subject of articular cartilage lesions caused by traumas where non impression fracture of the subchondral bone is present.</p> <p>Methods</p> <p>PubMed (MEDLINE), ScienceDirect (EMBASE, BIOBASE, BIOSIS Previews) and the COCHRANE database of systematic reviews were systematically scanned using a defined search strategy to identify relevant articles in this field of research. First selection was done based on abstracts according to specific criteria, where the methodological quality in selected full text articles was assessed by two reviewers. Agreement between raters was investigated using percentage agreement and Cohen's Kappa statistic. The traumatic events were divided into two categories: 1) acute trauma which refers to any single impact situation which directly damages the articular cartilage, and 2) chronic trauma which means cartilage lesions due to overuse or disuse of the shoulder joint.</p> <p>Results</p> <p>The agreement on data quality between the two reviewers was 93% with a Kappa value of 0.79 indicating an agreement considered to be 'substantial'. It was found that acute trauma on the shoulder causes humeral articular cartilage to disrupt from the underlying bone. The pathomechanism is said to be due to compression or shearing, which can be caused by a sudden subluxation or dislocation. However, such impact lesions are rarely reported. In the case of chronic trauma glenohumeral cartilage degeneration is a result of overuse and is associated to other shoulder joint pathologies. In these latter cases it is the rotator cuff which is injured first. This can result in instability and consequent impingement which may progress to glenohumeral cartilage damage.</p> <p>Conclusion</p> <p>The great majority of glenohumeral cartilage lesions without any bony lesions are the results of overuse. Glenohumeral cartilage lesions with an intact subchondral bone and caused by an acute trauma are either rare or overlooked. And at increased risk for such cartilage lesions are active sportsmen with high shoulder demand or athletes prone to shoulder injury.</p

Agreement between pedometer and accelerometer in measuring physical activity in overweight and obese pregnant women

<p>Abstract</p> <p>Background</p> <p>Inexpensive, reliable objective methods are needed to measure physical activity (PA) in large scale trials. This study compared the number of pedometer step counts with accelerometer data in pregnant women in free-living conditions to assess agreement between these measures.</p> <p>Methods</p> <p>Pregnant women (n = 58) with body mass index ≥25 kg/m²at median 13 weeks' gestation wore a GT1M Actigraph accelerometer and a Yamax Digi-Walker CW-701 pedometer for four consecutive days. The Spearman rank correlation coefficients were determined between pedometer step counts and various accelerometer measures of PA. Total agreement between accelerometer and pedometer step counts was evaluated by determining the 95% limits of agreement estimated using a regression-based method. Agreement between the monitors in categorising participants as active or inactive was assessed by determining Kappa.</p> <p>Results</p> <p>Pedometer step counts correlated moderately (r = 0.36 to 0.54) with most accelerometer measures of PA. Overall step counts recorded by the pedometer and the accelerometer were not significantly different (medians 5961 vs. 5687 steps/day, p = 0.37). However, the 95% limits of agreement ranged from -2690 to 2656 steps/day for the mean step count value (6026 steps/day) and changed substantially over the range of values. Agreement between the monitors in categorising participants to active and inactive varied from moderate to good depending on the criteria adopted.</p> <p>Conclusions</p> <p>Despite statistically significant correlations and similar median step counts, the overall agreement between pedometer and accelerometer step counts was poor and varied with activity level. Pedometer and accelerometer steps cannot be used interchangeably in overweight and obese pregnant women.</p

Kerteszia subgenus of Anopheles associated with the Brazilian Atlantic rainforest:current knowledge and future challenges

Background: The Atlantic rainforest ecosystem, where bromeliads are abundant, provides an excellent environment for Kerteszia species, because these anophelines use the axils of those plants as larval habitat. Anopheles (K.) cruzii and Anopheles (K.) bellator are considered the primary vectors of malaria in the Atlantic forest. Although the incidence of malaria has declined in some areas of the Atlantic forest, autochthonous cases are still registered every year, with Anopheles cruzii being considered to be a primary vector of both human and simian Plasmodium. Methods: Recent publications that addressed ecological aspects that are important for understanding the involvement of Kerteszia species in the epidemiology of malaria in the Atlantic rainforest in the Neotropical Region were analysed. Conclusion: The current state of knowledge about Kerteszia species in relation to the Atlantic rainforest ecosystem was discussed. Emphasis was placed on ecological characteristics related to epidemiological aspects of this group of mosquitoes. The main objective was to investigate biological aspects of the species that should be given priority in future studie

Historical Temperature Variability Affects Coral Response to Heat Stress

Coral bleaching is the breakdown of symbiosis between coral animal hosts and their dinoflagellate algae symbionts in response to environmental stress. On large spatial scales, heat stress is the most common factor causing bleaching, which is predicted to increase in frequency and severity as the climate warms. There is evidence that the temperature threshold at which bleaching occurs varies with local environmental conditions and background climate conditions. We investigated the influence of past temperature variability on coral susceptibility to bleaching, using the natural gradient in peak temperature variability in the Gilbert Islands, Republic of Kiribati. The spatial pattern in skeletal growth rates and partial mortality scars found in massive Porites sp. across the central and northern islands suggests that corals subject to larger year-to-year fluctuations in maximum ocean temperature were more resistant to a 2004 warm-water event. In addition, a subsequent 2009 warm event had a disproportionately larger impact on those corals from the island with lower historical heat stress, as indicated by lower concentrations of triacylglycerol, a lipid utilized for energy, as well as thinner tissue in those corals. This study indicates that coral reefs in locations with more frequent warm events may be more resilient to future warming, and protection measures may be more effective in these regions

Rapid Evolution of Coral Proteins Responsible for Interaction with the Environment

Christian R. Voolstra is with King Abdullah University of Science and Technology, Shinichi Sunagawa is with the European Molecular Biology Laboratory, Mikhail V. Matz is with UT Austin, Till Bayer is with King Abdullah University of Science and Technology, Manuel Aranda is with King Abdullah University of Science and Technology, Emmanuel Buschiazzo is with University of California Merced, Michael K. DeSalvo is with University of California San Francisco, Erika Lindquist is with the Department of Energy Joint Genome Institute, Alina M. Szmant is with University of North Carolina Wilmington, Mary Alice Coffroth is with State University of New York at Buffalo, Mónica Medina is with University of California Merced.Background -- Corals worldwide are in decline due to climate change effects (e.g., rising seawater temperatures), pollution, and exploitation. The ability of corals to cope with these stressors in the long run depends on the evolvability of the underlying genetic networks and proteins, which remain largely unknown. A genome-wide scan for positively selected genes between related coral species can help to narrow down the search space considerably. Methodology/Principal Findings -- We screened a set of 2,604 putative orthologs from EST-based sequence datasets of the coral species Acropora millepora and Acropora palmata to determine the fraction and identity of proteins that may experience adaptive evolution. 7% of the orthologs show elevated rates of evolution. Taxonomically-restricted (i.e. lineage-specific) genes show a positive selection signature more frequently than genes that are found across many animal phyla. The class of proteins that displayed elevated evolutionary rates was significantly enriched for proteins involved in immunity and defense, reproduction, and sensory perception. We also found elevated rates of evolution in several other functional groups such as management of membrane vesicles, transmembrane transport of ions and organic molecules, cell adhesion, and oxidative stress response. Proteins in these processes might be related to the endosymbiotic relationship corals maintain with dinoflagellates in the genus Symbiodinium. Conclusion/Relevance -- This study provides a birds-eye view of the processes potentially underlying coral adaptation, which will serve as a foundation for future work to elucidate the rates, patterns, and mechanisms of corals' evolutionary response to global climate change.This work was supported by DEB-1054766 to M.V.M. and National Science Foundation grants IOS-0644438 and OCE-0313708 to M.M., and by a Collaborative Travel Fund to C.R.V. made by King Abdullah University of Science and Technology (KAUST). The work conducted by the U.S. Department of Energy Joint Genome Institute is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o