3,139 research outputs found

    Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

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    Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

    Coalescent-based genome analyses resolve the early branches of the euarchontoglires

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    Despite numerous large-scale phylogenomic studies, certain parts of the mammalian tree are extraordinarily difficult to resolve. We used the coding regions from 19 completely sequenced genomes to study the relationships within the super-clade Euarchontoglires (Primates, Rodentia, Lagomorpha, Dermoptera and Scandentia) because the placement of Scandentia within this clade is controversial. The difficulty in resolving this issue is due to the short time spans between the early divergences of Euarchontoglires, which may cause incongruent gene trees. The conflict in the data can be depicted by network analyses and the contentious relationships are best reconstructed by coalescent-based analyses. This method is expected to be superior to analyses of concatenated data in reconstructing a species tree from numerous gene trees. The total concatenated dataset used to study the relationships in this group comprises 5,875 protein-coding genes (9,799,170 nucleotides) from all orders except Dermoptera (flying lemurs). Reconstruction of the species tree from 1,006 gene trees using coalescent models placed Scandentia as sister group to the primates, which is in agreement with maximum likelihood analyses of concatenated nucleotide sequence data. Additionally, both analytical approaches favoured the Tarsier to be sister taxon to Anthropoidea, thus belonging to the Haplorrhine clade. When divergence times are short such as in radiations over periods of a few million years, even genome scale analyses struggle to resolve phylogenetic relationships. On these short branches processes such as incomplete lineage sorting and possibly hybridization occur and make it preferable to base phylogenomic analyses on coalescent methods

    Assessment of interprofessional competence in undergraduate health professions education: protocol for a systematic review of self-report instruments

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    Background Health practitioners from different professions, and with differing competencies, need to collaborate to provide quality care. Competencies in interprofessional working need developing in undergraduate educational preparation. This paper reports the protocol for a systematic review of self-report instruments to assess interprofessional learning in undergraduate health professionals’ education. Methods We will search PubMed, Web of Science, CINAHL and ERIC from January 2010 onwards. A combination of search terms for interprofessional learning, health professions, psychometric properties, assessment of learning and assessment tools will be used. Two reviewers will independently screen all titles, abstracts and full-texts. Potential conflicts will be resolved through discussion. Quantitative and mixed-methods studies evaluating interprofessional learning in undergraduate health professions education (e.g. medicine, nursing, occupational and physical therapy, pharmacy and psychology) will be included. Methodological quality of each reported instrument, underpinning theoretical frameworks, and the effects of reported interventions will be assessed. The overall outcome will be the effectiveness of instruments used to assess interprofessional competence. Primary outcomes will be the psychometric properties (e.g. reliability, discriminant and internal validity) of instruments used. Secondary outcomes will include time from intervention to assessment, how items relate to specific performance/competencies (or general abstract constructs) and how scores are used (e.g. to grade students, to improve courses or research purposes). Quantitative summaries in tabular format and a narrative synthesis will allow recommendations to be made on the use of self-report instruments in practice. Discussion Many studies use self-report questionnaires as tools for developing meaningful interprofessional education activities and assessing students’ interprofessional competence. This systematic review will evaluate both the benefits and limitations of reported instruments and help educators and researchers (i) choose the most appropriate existing self-report instruments to assess interprofessional competence and (ii) inform the design and conduct of interprofessional competency assessment using self-report instruments. Systematic review registration Open Science Framework [https://osf.io/vrfjn]

    Molecular identification of adenoviruses associated with respiratory infection in Egypt from 2003 to 2010.

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    BACKGROUND: Human adenoviruses of species B, C, and E (HAdV-B, -C, -E) are frequent causative agents of acute respiratory infections worldwide. As part of a surveillance program aimed at identifying the etiology of influenza-like illness (ILI) in Egypt, we characterized 105 adenovirus isolates from clinical samples collected between 2003 and 2010. METHODS: Identification of the isolates as HAdV was accomplished by an immunofluorescence assay (IFA) and confirmed by a set of species and type specific polymerase chain reactions (PCR). RESULTS: Of the 105 isolates, 42% were identified as belonging to HAdV-B, 60% as HAdV-C, and 1% as HAdV-E. We identified a total of six co-infections by PCR, of which five were HAdV-B/HAdV-C co-infections, and one was a co-infection of two HAdV-C types: HAdV-5/HAdV-6. Molecular typing by PCR enabled the identification of eight genotypes of human adenoviruses; HAdV-3 (n = 22), HAdV-7 (n = 14), HAdV-11 (n = 8), HAdV-1 (n = 22), HAdV-2 (20), HAdV-5 (n = 15), HAdV-6 (n = 3) and HAdV-4 (n = 1). The most abundant species in the characterized collection of isolates was HAdV-C, which is concordant with existing data for worldwide epidemiology of HAdV respiratory infections. CONCLUSIONS: We identified three species, HAdV-B, -C and -E, among patients with ILI over the course of 7 years in Egypt, with at least eight diverse types circulating

    Doubling of marine dinitrogen-fixation rates based on direct measurements

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    Biological dinitrogen fixation provides the largest input of nitrogen to the oceans, therefore exerting important control on the ocean’s nitrogen inventory and primary productivity. Nitrogen-isotope data fromocean sediments suggest that the marine-nitrogen inventory has been balanced for the past 3,000 years (ref. 4). Producing a balanced marine-nitrogenbudget based on direct measurements has proved difficult, however, with nitrogen loss exceeding the gain from dinitrogen fixation by approximately 200 TgNyr-1 (refs 5, 6). Here we present data from the Atlantic Ocean and show that the most widely used method of measuring oceanic N2-fixation rates underestimates the contribution of N2-fixing microorganisms (diazotrophs) relative to a newly developed method. Using molecular techniques to quantify the abundance of specific clades of diazotrophs in parallel with rates of 15N2 incorporation into particulate organic matter, we suggest that the difference between N2-fixation rates measured with the established method and those measured with the new method8 can be related to the composition of the diazotrophic community. Our data show that in areas dominated by Trichodesmium, the established method underestimatesN2-fixation rates by an averageof 62%. We also find that the newly developed method yields N2-fixation rates more than six times higher than those from the established method when unicellular, symbiotic cyanobacteria and c-proteobacteria dominate the diazotrophic community. On the basis of average areal rates measured over the Atlantic Ocean, we calculated basin-wide N2-fixation rates of 14+/-1TgNyr-1 and 24+/-1TgNyr-1 for the established and new methods, respectively. If our findings can be extrapolated to other ocean basins, this suggests that the global marine N2-fixation rate derived from direct measurements may increase from 103+/-8TgNyr-1 to 177+/-8TgNyr-1, and that the contribution of N2 fixers other than Trichodesmium is much more significant than was previously thought

    Environmental and diagenetic controls on the morphology and calcification of the Ediacaran metazoan Cloudina

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    Abstract Cloudina is a globally distributed Ediacaran metazoan, with a tubular, funnel-in-funnel form built of thin laminae (ca. 1–10 μm). To what degree local environmental controlled morphology, and whether early diagenesis controlled the degree of calcification of Cloudina, is debated. Here we test these hypotheses by considering assemblages from four, coeval localities from the Upper Omkyk Member, Nama Group, Namibia, from inner ramp to mid-ramp reef across the Zaris Subbasin. We show that sinuosity of the Cloudina tube is variable between sites, as is the relative thickness of the tube wall, suggesting these features were environmentally controlled. Walls are thickest in high-energy reef settings, and thinnest in the low-energy, inner ramp. While local diagenesis controls preservation, all diagenetic expressions are consistent with the presence of weakly calcified, organic-rich laminae, and lamina thicknesses are broadly constant. Finally, internal ‘cements’ within Cloudina are found in all sites, and pre-date skeletal breakage, transport, as well as syn-sedimentary botryoidal cement precipitation. Best preservation shows these to be formed by fine, pseudomorphed aragonitic acicular crystals. Sr concentrations and Mg/Ca show no statistically significant differences between internal Cloudina cements and botryoidal cements, but we infer all internal cements to have precipitated when Cloudina was still in-situ and added considerable mechanical strength, but may have formed post-mortem or in abandoned parts of the skeleton

    Effect of Cavtratin, a Caveolin-1 Scaffolding Domain Peptide, on Oligodendroglial Signaling Cascades

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    Caveolin and caveolin containing rafts are involved in the signaling of growth factors in various cell types. Previous reports of our lab indicated a co-localization of caveolin and the high affinity nerve growth factor (NGF) receptor tyrosine kinase A (TrkA). Mutual effects have been observed among which a caveolin-1 knock-down resulted in an impairment of the NGF signaling cascade rather than in an increase of activity as expected from other growth factor reports. On the other hand, an over-expression of caveolin-1 impaired the NGF stimulated activity of p42/44 mitogen activated protein kinases (MAPK). In this study, we used a caveolin-1 scaffolding domain (CSD) peptide (cavtratin) of which an inhibitory effect on growth factor receptors was reported. Our data showed that cavtratin suppresses the NGF-induced phosphorylation of TrkA as well as the activation of MAPK in porcine oligodendrocytes significantly

    Sequentially based analysis versus image based analysis of Intima Media Thickness in common carotid arteries studies - Do major IMT studies underestimate the true relations for cardio- and cerebrovascular risk?

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    <p>Abstract</p> <p>Background</p> <p>Image-based B-mode ultrasound has gained popularity in major studies as a non-invasive method of measuring cardio- and cerebrovascular risk factors. However, none of the major studies appears to have paid sufficient attention to the variation in end diastolic wall process. By using sequentially based analyses (SBA) of Intima-Media Thickness (IMT), the general purpose of this study was to show that the current image based (ECG tracked) analysis (IBA) has some major variations and might underestimate the true relations for cardiovascular events and stroke for IMT measurement.</p> <p>Method</p> <p>The study group consisted of 2500 healthy male subjects aged between 35 to 55 years. 4 sequences (300 images) were analyzed per subject. 750,000 images were analysed throughout the course of this study.</p> <p>Results</p> <p>IBA showed significantly lower mean, maximal, and minimal values for IMT in CCA than for SBA. The correlation analysis between IBA and SBA with the cardio- and cerebrovascular risk factors showed a higher correlation of SBA for all risk factors. The Pearson coefficient was 0.81, p < 0.01, for SBA versus Framingham CHD risk level (FCRL) and 0.49, p = 0.01, for IBA versus FCRL.</p> <p>Conclusion</p> <p>IBA did not measure the true maximal values of the IMT in this study. Together with the correlation analysis, this indicates that IBA might underestimate the true relations for IMT and risk factors.</p
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