Phocine Distemper Virus in Seals, East Coast, United States, 2006

: Phocine Distemper Virus in Seal

Impact of Tumour Epithelial Subtype on Circulating MicroRNAs in Breast Cancer Patients

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45). Three miRNAs of interest were then quantified in the circulation(n = 166) and tissue (n = 100) of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes .2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of miRNAs, and highlights divergent miRNA profiles between tissue and blood samples from breast cancer patients

Leveraging accessible tourism development through mega-events, and the disability-attitude gap

Able-bodied, and increasingly people with disabilities, represent a key audience for mega-events; occasions that act as crucibles where social problems endemic to host destinations can be exposed and tackled through targeted social policy. Drawing on the social model of disability, the paper examines how Japan utilised Tokyo 2020 as a field configuring event to disrupt systems of ableist thinking and tackle physical and attitudinal barriers restricting Persons with Disabilities (PwD) to accessible tourism. Qualitative evidence reveals national commitments to relegitimise, improve accessibility for - and acceptance toward - PwD in Japanese society, through transformations to the built environment, national awareness, and educational campaigns in the build up to Tokyo 2020. An over-emphasis on physical as opposed to social structural change mean negative attitudes often persist, where disability remains stigmatised, leading to PwD immobility and social exclusion. Our policy recommendations and managerial implications, alongside research directions attend to this disability-attitude gap

Hookworm infection, anaemia and genetic variability of the New Zealand sea lion

Hookworms are intestinal blood-feeding nematodes that parasitize and cause high levels of mortality in a wide range of mammals, including otariid pinnipeds. Recently, an empirical study showed that inbreeding (assessed by individual measures of multi-locus heterozygosity) is associated with hookworm-related mortality of California sea lions. If inbreeding increases susceptibility to hookworms, effects would expectedly be stronger in small, fragmented populations. We tested this assumption in the New Zealand sea lion, a threatened otariid that has low levels of genetic variability and high hookworm infection rates. Using a panel of 22 microsatellites, we found that average allelic diversity (5.9) and mean heterozygosity (0.72) were higher than expected for a small population with restricted breeding, and we found no evidence of an association between genetic variability and hookworm resistance. However, similar to what was observed for the California sea lion, homozygosity at a single locus explained the occurrence of anaemia and thrombocytopenia in hookworm-infected pups (generalized linear model, F = 11.81, p < 0.001) and the effect was apparently driven by a particular allele (odds ratio = 34.95%; CI: 7.12–162.41; p < 0.00001). Our study offers further evidence that these haematophagus parasites exert selective pressure on otariid blood-clotting processes

Emerging and recurring diseases in cetaceans worldwide and the role of environmental stressors. Scientific Committee Document SC/60/DW5, International Whaling Commission, June 2008, Santiago, Chile

Emerging and recurring infectious diseases known or suspected to have the potential to significantly impact cetacean populations, and possible synergistic effects of environmental factors are reviewed. Cetacean morbilliviruses and papillomaviruses and brucellosis may affect population densities through high mortality rates or interference with reproduction. Evidence is available for the role of environmental factors in the emergence/recurrence and severity of at least six infectious conditions i.e. lobomycosis, toxoplasmosis, tattoo skin disease, generalized bacterial infections, miscellaneous skin diseases and morbillivirus epizootics. Other micro-parasites of potential importance include rhabdo-, herpes- and parainfluenza-viruses as well as Helicobacter spp., Streptococcus spp., Salmonella spp. and Mycobacterium marinum. The population impact and aetiology of newly emerging skin diseases in South America are unknown and represent a cause of concern

How do event zones influence visitor behaviour and engagement with host destinations? A longitudinal study of the Cambridge half marathon (2017–2020)

This work identifies important influencing factors that affect event visitor behaviour in and beyond event zones, utilising a four-year, mixed-method, longitudinal study (n=6212) of the Cambridge Half Marathon (2017–2020). We counter a commonly held view that visitors naturally spill out into local cultural and business precincts, arguing that event zones represent cities within cities that spatially segregate visitors from the host destination; only 7% of the sample engaged in longer and deeper cultural stays. Quantitative data reveals statistically significant demographic and tripographic factors that increase the likelihood of visitors venturing beyond the event zone, whilst qualitative data reveals the behavioural and organisational factors that encourage or discourage engagement. Managerial tactics and strategies for encouraging visitors to venture beyond event zones, across host destinations, to optimise local economic benefits across the host destination are presented

CERKL-associated retinal dystrophy: Genetics, Phenotype and Natural History

PURPOSE: To analyze the clinical characteristics, natural history, and genetics of CERKL-associated retinal dystrophy in the largest series to date. DESIGN: Multicenter retrospective cohort study. SUBJECTS: 47 patients (37 families) with likely disease-causing CERKL variants METHODS: Review of clinical notes, ophthalmic images, and molecular diagnosis from two international centres. MAIN OUTCOME MEASURES: Visual function, retinal imaging and characteristics were evaluated and correlated. RESULTS: The mean age at the first visit was 29.6 + 13.9 years and the mean follow-up time was 9.1 + 7.4 years. The most frequent initial symptom was central vision loss (40%) and the most common retinal feature was well-demarcated areas of macular atrophy (57%). Seventy percent of the participants had double-null genotypes and 64% had electrophysiological assessment. Amongst the latter, 53% showed similar severity of rod and cone dysfunction, 27% revealed a rod-cone, 10% a cone-rod, and 10% a macular dystrophy dysfunction pattern. Patients without double-null genotypes tended to have fewer pigment deposits and included a higher proportion of older patients with a relatively mild electrophysiological phenotype. Longitudinal analysis showed that over half of the cohort lost 15 ETDRS letters or more in at least one eye during the first 5 years of follow up. CONCLUSIONS: The phenotype of CERKL-retinal dystrophy is broad, encompassing isolated macular disease to severe retina-wide involvement, with a range of functional phenotypes, generally not fitting in the rod-cone/cone-rod dichotomy. Disease onset is often earlier, with more severe retinal degenerative changes and photoreceptor dysfunction, in nullizygous cases

Quantifying the hydration structure of sodium and potassium ions: taking additional steps on Jacob's Ladder

The ability to reproduce the experimental structure of water around the sodium and potassium ions is a key test of the quality of interaction potentials due to the central importance of these ions in a wide range of important phenomena. Here, we simulate the Na+ and K+ ions in bulk water using three density functional theory functionals: (1) the generalized gradient approximation (GGA) based dispersion corrected revised Perdew, Burke, and Ernzerhof functional (revPBE-D3) (2) the recently developed strongly constrained and appropriately normed (SCAN) functional (3) the random phase approximation (RPA) functional for potassium. We compare with experimental X-ray diffraction (XRD) and X-ray absorption fine structure (EXAFS) measurements to demonstrate that SCAN accurately reproduces key structural details of the hydration structure around the sodium and potassium cations, whereas revPBE-D3 fails to do so. However, we show that SCAN provides a worse description of pure water in comparison with revPBE-D3. RPA also shows an improvement for K+, but slow convergence prevents rigorous comparison. Finally, we analyse cluster energetics to show SCAN and RPA have smaller fluctuations of the mean error of ion-water cluster binding energies compared with revPBE-D3