Genomic organization and alternative splicing of the human and mouse RPTPρ genes

BACKGROUND: Receptor protein tyrosine phosphatase rho (RPTPρ, gene symbol PTPRT) is a member of the type IIB RPTP family. These transmembrane molecules have been linked to signal transduction, cell adhesion and neurite extension. The extracellular segment contains MAM, Ig-like and fibronectin type III domains, and the intracellular segment contains two phosphatase domains. The human RPTPρ gene is located on chromosome 20q12-13.1, and the mouse gene is located on a syntenic region of chromosome 2. RPTPρ expression is restricted to the central nervous system. RESULTS: The cloning of the mouse cDNA, identification of alternatively spliced exons, detection of an 8 kb 3'-UTR, and the genomic organization of human and mouse RPTPρ genes are described. The two genes are comprised of at least 33 exons. Both RPTPρ genes span over 1 Mbp and are the largest RPTP genes characterized. Exons encoding the extracellular segment through the intracellular juxtamembrane 'wedge' region are widely spaced, with introns ranging from 9.7 to 303.7 kb. In contrast, exons encoding the two phosphatase domains are more tightly clustered, with 15 exons spanning ∼ 60 kb, and introns ranging in size from 0.6 kb to 13.1 kb. Phase 0 introns predominate in the intracellular, and phase 1 in the extracellular segment. CONCLUSIONS: We report the first genomic characterization of a RPTP type IIB gene. Alternatively spliced variants may result in different RPTPρ isoforms. Our findings suggest that RPTPρ extracellular and intracellular segments originated as separate modular proteins that fused into a single transmembrane molecule during a later evolutionary period

An Anatomy Massive Open Online Course as a Continuing Professional Development Tool for Healthcare Professionals

Massive open online courses (MOOCs) remain a novel and under-evaluated learning tool within anatomical and medical education. This study aimed to provide valuable information by using an anatomy MOOC to investigate the demographic profile, patterns of engagement and self-perceived benefits to healthcare professionals. A 21-item survey aimed at healthcare professionals was embedded into the Exploring Anatomy: The Human Abdomen MOOC, in April 2016. The course attracted 2711 individual learners with 94 of these completing the survey, and 79 of those confirming they worked full- or part-time as healthcare professionals. Variations in use across healthcare profession (allied healthcare professional, nurse or doctor) were explored using a Fisher’s exact test to calculate significance across demographic, motivation and engagement items; one-way ANOVA was used to compare self-perceived benefits. Survey data revealed that 53.2% were allied healthcare professionals, 35.4% nurses and 11.4% doctors. Across all professions, the main motivation for enrolling was to learn new things in relation to their clinical practice, with a majority following the prescribed course pathway and utilising core, and clinically relevant, material. The main benefits were in relation to improving anatomy knowledge, which enabled better support for patients. This exploratory study assessing engagement and self-perceived benefits of an anatomy MOOC has shown a high level of ordered involvement, with some indicators suggesting possible benefits to patients by enhancing the subject knowledge of those enrolled. It is suggested that this type of learning tool should be further explored as an approach to continuing professional, and interprofessional, education

Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III

<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA type I, II and III) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (<it>SMN1</it>). <it>SMN2 </it>is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two <it>SMN2 </it>copies while most SMA type II patients carry three <it>SMN2 </it>copies and SMA III patients have three or four <it>SMN2 </it>copies. The <it>SMN1 </it>gene produces a full-length transcript (FL-SMN) while <it>SMN2 </it>is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA.</p> <p>Methods</p> <p>In this study we performed quantification of the <it>SMN2 </it>gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively) by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the <it>SMN1 </it>gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker.</p> <p>Results</p> <p>Comparison of the <it>SMN2 </it>copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III) and presence of four copies of the <it>SMN2 </it>gene. In both asymptomatic cases we found an increased number of <it>SMN2 </it>copies in the healthy carriers and a biallelic <it>SMN1 </it>absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls.</p> <p>Conclusions</p> <p>We suggest that the <it>SMN2 </it>gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.</p

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

Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

Environmental sustainability assessment of ready-made baby foods: Meals, menus and diets

Although there is a growing body of literature on the environmental impacts of food, virtually none of the studies has addressed baby foods. Therefore, this work explored the life cycle environmental impacts of different ready-made baby foods, both at the level of individual meals and their combinations within a weekly menu. Twelve different meals were considered, based on baby food products available on the UK market, spanning breakfast, lunch and dessert. Menus following four different diets – omnivorous, vegetarian, pescatarian and dairy-free – were also evaluated. The results showed that, on average, lunch meals had the highest impacts and desserts the lowest. Breakfast has either intermediate (wet porridge) or low (dry porridge) impacts. Among the lunch meals, spaghetti Bolognese and salmon risotto had the highest impacts and among the desserts, strawberry, raspberry and banana as well as apple, pear and banana purees had the lowest. The key hotspots across the meals were raw materials and packaging. Meals with more meat and cream were found to have higher impacts. Manufacturing also played a significant role for global warming potential as well as depletion of fossil resources and the ozone layer due to the fossil fuels used in the process. When the impacts were analysed per mass of baby food consumed weekly, the dairy-free diet had higher impacts than the other three, but the difference among them was relatively small. The trends changed when nutritional value was taken into account, with the dairy-free diet exhibiting considerably higher impacts per unit of energy content. In that case, the pescatarian diet became the best option for most impacts. There was little difference between the omnivore and vegetarian diets. It is expected that these results will be of interest to baby food manufacturers and consumers, helping them to make more informed manufacturing and purchasing decisions