47 research outputs found

    Stem cell‐derived enteroid cultures as a tool for dissecting host‐parasite interactions in the small intestinal epithelium.

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    Toxoplasma gondii and Cryptosporidium spp. can cause devastating pathological effects in humans and livestock, and in particular to young or immunocompromised individuals. The current treatment plans for these enteric parasites are limited due to long drug courses, severe side effects, or simply a lack of efficacy. The study of the early interactions between the parasites and the site of infection in the small intestinal epithelium has been thwarted by the lack of accessible, physiologically relevant, and species-specific models. Increasingly, 3D stem cell-derived enteroid models are being refined and developed into sophisticated models of infectious disease. In this review we shall illustrate the use of enteroids to spearhead research into enteric parasitic infections, bridging the gap between cell line cultures and in vivo experiments

    Early Energy Deficit in Huntington Disease: Identification of a Plasma Biomarker Traceable during Disease Progression

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    Huntington disease (HD) is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD have not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance (1H NMR) spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. 1H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA), valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide

    Towards a framework for attention cueing in instructional animations: Guidelines for research and design

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    This paper examines the transferability of successful cueing approaches from text and static visualization research to animations. Theories of visual attention and learning as well as empirical evidence for the instructional effectiveness of attention cueing are reviewed and, based on Mayer’s theory of multimedia learning, a framework was developed for classifying three functions for cueing: (1) selection—cues guide attention to specific locations, (2) organization—cues emphasize structure, and (3) integration—cues explicate relations between and within elements. The framework was used to structure the discussion of studies on cueing in animations. It is concluded that attentional cues may facilitate the selection of information in animations and sometimes improve learning, whereas organizational and relational cueing requires more consideration on how to enhance understanding. Consequently, it is suggested to develop cues that work in animations rather than borrowing effective cues from static representations. Guidelines for future research on attention cueing in animations are presented

    Bovine cryptosporidiosis: impact, host-parasite interaction and control strategies

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    International audienceAbstractGastrointestinal disease caused by the apicomplexan parasite Cryptosporidium parvum is one of the most important diseases of young ruminant livestock, particularly neonatal calves. Infected animals may suffer from profuse watery diarrhoea, dehydration and in severe cases death can occur. At present, effective therapeutic and preventative measures are not available and a better understanding of the host–pathogen interactions is required. Cryptosporidium parvum is also an important zoonotic pathogen causing severe disease in people, with young children being particularly vulnerable. Our knowledge of the immune responses induced by Cryptosporidium parasites in clinically relevant hosts is very limited. This review discusses the impact of bovine cryptosporidiosis and describes how a thorough understanding of the host–pathogen interactions may help to identify novel prevention and control strategies

    Control of style-of-faulting on spatial pattern of earthquake-triggered landslides

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    Predictive mapping of susceptibility to earthquake-triggered landslides (ETLs) commonly uses distance to fault as spatial predictor, regardless of style-of-faulting. Here, we examined the hypothesis that the spatial pattern of ETLs is influenced by style-of-faulting based on distance distribution analysis and Fry analysis. The Yingxiu–Beichuan fault (YBF) in China and a huge number of landslides that ruptured and occurred, respectively, during the 2008 Wenchuan earthquake permitted this study because the style-of-faulting along the YBF varied from its southern to northern parts (i.e. mainly thrust-slip in the southern part, oblique-slip in the central part and mainly strike-slip in the northern part). On the YBF hanging-wall, ETLs at 4.4–4.7 and 10.3–11.5 km from the YBF are likely associated with strike- and thrust-slips, respectively. On the southern and central parts of the hanging-wall, ETLs at 7.5–8 km from the YBF are likely associated with oblique-slips. These findings indicate that the spatial pattern of ETLs is influenced by style-of-faulting. Based on knowledge about the style-of-faulting and by using evidential belief functions to create a predictor map based on proximity to faults, we obtained higher landslide prediction accuracy than by using unclassified faults. When distance from unclassified parts of the YBF is used as predictor, the prediction accuracy is 80%; when distance from parts of the YBF, classified according to style-of-faulting, is used as predictor, the prediction accuracy is 93%. Therefore, mapping and classification of faults and proper spatial representation of fault control on occurrence of ETLs are important in predictive mapping of susceptibility to ETLs

    Current methods in structural proteomics and its applications in biological sciences

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    Identifying dementia in Down syndrome with the Severe Impairment Battery, Brief Praxis Test and Dementia Scale for People with Learning Disabilities

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    BackgroundIndividuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer's disease. However, many measures regularly used for the detection of dementia in the general population are not suitable for individuals with DS due in part to floor effects. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT) and Dementia Scale for People with Learning Disabilities (DLD), have been used in clinical trials and other research with this population. Validity research is limited, particularly regarding the use of such tools for detection of prodromal dementia in the DS population. The current project presents baseline cross-sectional SIB, BPT and DLD performance in order to characterise their predictive utility in discriminating normal cognition, possible dementia and probable dementia in adult DS.MethodBaseline SIB, BPT and DLD performances from 100 individuals (no dementia = 68, possible dementia = 16 & probable dementia = 16) were examined from a longitudinal cohort of aging individuals with DS. Receiver operating characteristic curves investigated the accuracy of these measures in relation to consensus dementia diagnoses, diagnoses which demonstrated high percent agreement with the examining neurologist's independent diagnostic impression.ResultsThe SIB and BPT exhibited fair discrimination ability for differentiating no/possible versus probable dementia [area under the curve (AUC) = 0.61 and 0.66, respectively]. The DLD exhibited good discrimination ability for differentiating no versus possible/probable dementia (AUC = 0.75) and further demonstrated better performance of the DLD Cognitive subscale compared with the DLD Social subscale (AUC = 0.77 and 0.67, respectively).ConclusionsResults suggest that the SIB, BPT and DLD are able to reasonably discriminate consensus dementia diagnoses in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. The general performance of these measures suggests that further work in the area of test development is needed to improve on the AUCs for dementia status discrimination in this unique population. At present, however, the current findings suggest that the DLD may be the best option for reliable identification of prodromal dementia in this population, reinforcing the importance of including informant behaviour ratings in assessment of cognition for adults with DS

    Anticipating engagement: pre-service teachers' perceptions of virtual worlds

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    Engagement has become a significant driver in the choice of resources that teachers utilise at both university and K-12 level. Educators and governments recognise that increasingly, students are being pushed away from school due to a lack of engagement at a time when the need to have a skilled and educated society is ever more pressing. Information communication technologies (ICTs) are often used as a means to provide engagement. With the now ubiquitous presence of ICTs in classrooms, homes and workplaces, the need to develop high quality learning experiences with ICTs is increasingly apparent. Virtual worlds are an ICT that, when first encountered, offer what appears to be a highly engaging environment especially for young adults and children. Many virtual worlds have some level of game features such as multiple paths, user-level control, interaction, visuals, risk-taking, rules and goals (Baranauskas et al. 2001; Crookall et al. 1987; Gredler 1996). Malone (1980) suggests that there are four factors of games that contribute to the level of engagement; challenge, fantasy, complexity and control. However, for students at university, these features can possibly act as a motivator or as a deterrent. Most adult students have expectations about what they believe a learning experience should be. Due to the connection they make with games and having fun, games are not traditionally linked to serious learning
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