155 research outputs found
Decreased function of survival motor neuron protein impairs endocytic pathways
This document is the Accepted Manuscript version. The final, definitive version is available online at https://doi.org/10.1073/pnas.1600015113.Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death.Peer reviewedFinal Accepted Versio
Transanal total mesorectal excision: a pure NOTES approach for selected patients
Background: The concept of natural orifice transluminal endoscopic surgery (NOTES) has stimulated the development of various βincisionlessβ procedures. One of the most popular is the transanal approach for rectal lesions. The aims of this study were to report how we standardized NOTES technique for transanal mesorectal excision without abdominal assistance, discuss the difficulties and surgical outcomes of this technique and report its feasibility in a small group of selected patients. Methods: Three consecutive female patients underwent transanal NOTES rectal resection without transabdominal laparoscopic assistance for rectal lesions. Functional results were assessed with the Fecal Incontinence Quality of Life scale and the Wexner score. Results: The technical steps are described in details and complemented with a video. All procedures were completed without transabdominal laparoscopic help. The mesorectal plane was entirely dissected without any disruption, and distal and circumferential margins were tumor-free. No major complications were observed. Functional results show a significant impairment after surgery with improvement at 6 months to levels near those of the preoperative period. Conclusions: The performance and publication of NOTES procedures are subject to much discussion. Despite the small number of patients, this procedure appears feasible and can be accomplished maintaining fecal continence and respecting oncologic principles
An empirical analysis of the determinants of mobile instant messaging appropriation in university learning
Published ArticleResearch on technology adoption often profiles device usability (such as
perceived usefulness) and user dispositions (such as perceived ease of use) as the
prime determinants of effective technology adoption. Since any process of technology
adoption cannot be conceived out of its situated contexts, this paper argues
that any pre-occupation with technology acceptance from the perspective of device
usability and user dispositions potentially negates enabling contexts that make
successful adoption a reality. Contributing to contemporary debates on technology
adoption, this study presents flexible mobile learning contexts comprising cost
(device cost and communication cost), device capabilities (portability, collaborative
capabilities), and learner traits (learner control) as antecedents that enable the
sustainable uptake of emerging technologies. To explore the acceptance and
capacity of mobile instant messaging systems to improve student performance, the
study draws on these antecedents, develops a factor model and empirically tests it
on tertiary students at a South African University of Technology. The study
involved 223 national diploma and bachelorβs degree students and employed partial
least squares for statistical analysis. Overall, the proposed model displayed a good
fit with the data and rendered satisfactory explanatory power for studentsβ acceptance
of mobile learning. Findings suggest that device portability, communication
cost, collaborative capabilities of device and learner control are the main drivers of
flexible learning in mobile environments. Flexible learning context facilitated by learner control was found to have a positive influence on attitude towards mobile
learning and exhibited the highest path coefficient of the overall model. The study
implication is that educators need to create varied learning opportunities that
leverage learner control of learning in mobile learning systems to enhance flexible
mobile learning. The study also confirmed the statistical significance of the original
Technology Acceptance Model constructs
Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects
Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species
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