In all groups, the N1-P2 amplitude at channel C4 (right hemisphere) reflected a change in ART but not in RFT. Behaviorally, 6-year olds and adults predominately utilized RFT cues (classified /ba/(wa) as /ba/) during phonetic judgments, as opposed to 4-5-year olds which utilized both cues equally. Our findings suggest that both ART and RFT
are encoded in the auditory cortex, but an N1-P2 shift toward the vertex following age 4-5 indicates a shift toward an adult-like weighting strategy, such that, to utilize Saracatinib RFT to a greater extent. (c) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Background Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic
studies has been restricted due to insufficient sample sizes and phenotype heterogeneity.
Methods We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11 009 unrelated controls from the UK. We Adriamycin clinical trial replicated the most promising signals in an independent set of up to 7473 cases and 42 938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent.
Findings We identified five genome-wide significant loci (binomial during test p <= 5.0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1.12 [95% CI 1.08-1.16]; p=7.24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense
polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects.
Interpretation Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.”
“Brain-derived neurotrophic factor (BDNF) is highly expressed in the hippocampus of many species, including humans.