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The aim of this study was to investigate whether early-English education benefits the perception of English phonetic contrasts that are known to be perceptually confusable for Dutch native speakers, comparing Dutch pupils who were enrolled in an early-English programme at school from the age of four with pupils in a mainstream programme with English instruction from the age of 11, and English-Dutch early bilingual children. Children were 4-5-year-olds (start of primary school), 8-9-year-olds, or 11-12-year-olds (end of primary school). Children were tested on four contrasts that varied in difficulty /b/-/s/ (easy), /k/-/ɡ/ (intermediate), /f/-/θ/ (difficult), /ɛ/-/æ/ (very difficult). Bilingual children outperformed the two other groups on all contrasts except /b/-/s/. Early-English pupils did not outperform mainstream pupils on any of the contrasts. This shows that early-English education as it is currently implemented is not beneficial for pupils' perception of non-native contrasts.Dinosaur fossils from the Middle Jurassic are rare globally, but the Isle of Skye (Scotland, UK) preserves a varied dinosaur record of abundant trace fossils and rare body fossils from this time. Here we describe two new tracksites from Rubha nam Brathairean (Brothers' Point) near where the first dinosaur footprint in Scotland was found in the 1980s. These sites were formed in subaerially exposed mudstones of the Lealt Shale Formation of the Great Estuarine Group and record a dynamic, subtropical, coastal margin. These tracksites preserve a wide variety of dinosaur track types, including a novel morphotype for Skye Deltapodus which has a probable stegosaur trackmaker. Additionally, a wide variety of tridactyl tracks shows evidence of multiple theropods of different sizes and possibly hints at the presence of large-bodied ornithopods. Overall, the new tracksites show the dinosaur fauna of Skye is more diverse than previously recognized and give insight into the early evolution of major dinosaur groups whose Middle Jurassic body fossil records are currently sparse.Sclerotinia stem rot is an economically important disease of canola (Brassica napus) and is caused by the fungal pathogen Sclerotinia sclerotiorum. This study evaluated the differential gene expression patterns of S. sclerotiorum during disease development on two canola lines differing in susceptibility to this pathogen. Sequencing of the mRNA libraries derived from inoculated petioles and mycelium grown on liquid medium generated approximately 164 million Illumina reads, including 95 million 75-bp-single reads, and 69 million 50-bp-paired end reads. Overall, 36% of the quality filter-passed reads were mapped to the S. sclerotiorum reference genome. On the susceptible line, 1301 and 1214 S. sclerotiorum genes were differentially expressed at early (8-16 hours post inoculation (hpi)) and late (24-48 hpi) infection stages, respectively, while on the resistant line, 1311 and 1335 genes were differentially expressed at these stages, respectively. CPYPP ic50 Gene ontology (GO) categories associated with cell wall degradation, detoxification of host metabolites, peroxisome related activities like fatty acid ß-oxidation, glyoxylate cycle, oxidoreductase activity were significantly enriched in the up-regulated gene sets on both susceptible and resistant lines. Quantitative RT-PCR of six selected DEGs further validated the RNA-seq differential gene expression analysis. The regulation of effector genes involved in host defense suppression or evasion during the early infection stage, and the expression of effectors involved in host cell death in the late stage of infection provide supporting evidence for a two-phase infection model involving a brief biotrophic phase during early stages of infection. The findings from this study emphasize the role of peroxisome related pathways along with cell wall degradation and detoxification of host metabolites as the key mechanisms underlying pathogenesis of S. sclerotiorum on B. napus.Dantrolene has been demonstrated to be neuroprotective for multiple neurodegenerative diseases. However, dantrolene's limited penetration into the CNS hampers its effectiveness as a neuroprotective agent. Here, we studied whether the intranasal administration of dantrolene provided better penetration into the brain than the commonly used oral approach. C57BL/6 mice, aged 2-4 months, received a single dose of either intranasal or oral dantrolene (5mg/kg). Inhibition of dantrolene clearance from the brain was examined by co-administration with P-gp/BCRP inhibitors, nimodipine or elacridar. The concentration of dantrolene in the brain and plasma was measured at 10, 20, 30, 50, 70, 120, 150 and 180 minutes after administration. Separate cohorts of mice were given intranasal dantrolene (5mg/kg) or vehicle, 3 times/ week, for either 3 weeks or 4 months, to examine potential adverse side effects on olfaction and motor coordination, respectively. We found that Dantrolene concentrations were sustained in the brain after intranasal administration for 180 min, while concentrations fell to zero at 120 min for oral administration. Chronic use of intranasal dantrolene did not impair olfaction or motor function in these mice. Blood brain barrier pump inhibitors did not further increase dantrolene peak concentrations in the brain. Our results suggested that Intranasal administration of dantrolene is an effective route to increase its concentration and duration in the brain compared to the oral approach, without any obvious side effects on olfaction or motor function.BACKGROUND AND PURPOSE We hypothesized that admission insular infarcts could be associated with early neurological deterioration (END) in acute minor stroke with large vessel occlusion. METHODS Using acute and follow-up diffusion-weighted imaging (DWI), we assessed insular involvement including the percent insular ribbon infarction (PIRI) scores and follow-up lesion patterns in acute minor stroke (NIHSS ≤5) with MCA/ICA occlusion. Follow-up lesion patterns were classified as swelling, new lesions, or infarct growth. END was defined as any increase in the NIHSS score. RESULTS Among 166 patients (age 66±12 y, 60.8% male), 82 (49.4%) had insular lesions on baseline DWI, and 64 (38.6%) had PIRI scores ≥2. On follow-up DWI, infarct growths, new lesions, and swelling were observed in 34.9%, 69.9%, and 29.5% of patients. Infarct growths were significantly more frequent in patients with insular infarcts (43.9%), especially those with a PIRI score of 2 (54.8%), than in patients without insular infarcts (p = 0.02). While END was not significantly different in patients with and without insular lesions, insular lesions were independently associated with infarct growths (OR 2.
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