Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

Seven new loci associated with age-related macular degeneration

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P <5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P <5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

'Changing attitudes with a little imagination': Imagined contact effects on young children's intergroup bias

The current research tested a recent development in social psychology, namely 'imagined contact', among young children (n = 123, 5 to 10 years). Children imagined interacting with a physically disabled child, or did not take part in this activity (the control group). Compared with the control group, children who engaged in 'imagined contact' subsequently showed reduced intergroup bias in their general attitude and ratings of warmth and competence. Imagined contact also led to more positive intended friendship behavior towards the disabled, but only among 5 – 6 year olds. This provides partial support for our hypothesis that younger children, perhaps as a result of their lack of outgroup experience, are more likely to benefit from imagined contact. Implications for the development of attitudes towards the disabled, imagined contact theory and the development of classroom-based prejudice-reduction techniques based on imagined contact are discussed.

Holocene “turn-on” and evolution of the Southern Great Barrier Reef: Revisiting reef cores from the Capricorn Bunker Group

Extensive drilling of the Great Barrier Reef (GBR) in the 70s and 80s illuminated the main factors controlling reef growth during the Holocene. However, questions remain about: (1) the precise nature and timing of reef "turnon" or initiation, (2) whether consistent spatio-temporal patterns occur in the bio-sedimentologic response of the reef to Holocene sea-level rise then stability, and (3) how these factors are expressed in the context of the different evolutionary states (juvenile-mature-senile reefs). Combining 21 new C14-AMS and 146 existing recalibrated radiocarbon and U/Th ages, we investigated the detailed spatial and temporal variations in sedimentary facies and coralgal assemblages in fifteen cores across four reefs (Wreck, Fairfax, One Tree and Fitzroy) from the Southern GBR. Our newly defined facies and assemblages record distinct chronostratigraphic patterns in the cores, displaying both lateral zonation across the different reefs and shallowing upwards sequences, characterised by a transition from deep (Porites/faviids) to shallow (Acropora/Isopora) coral types. The revised reef accretion curves show a significant lag period, ranging from 0.7-2 ka, between flooding of the antecedent Pleistocene substrate and Holocene reef turn-on. This lag period and dominance of more environmentally tolerant early colonizers (e.g., domal Porites and faviids), suggests initial conditions that were unfavourable for coral growth. We contend that higher input of fine siliciclastic material from regional terrigenous sources, exposure to hydrodynamic forces and colonisation in deeper waters are the main factors influencing initially reduced growth and development. All four reefs record a time lag and we argue that the size and shape of the antecedent platform is most important in determining the duration between flooding and recolonisation of the Holocene reef. Finally, our study of Capricorn Bunker Group Holocene reefs suggests that the size and shape of the antecedent substrate has a greater impact on reef evolution and final evolutionary state (mature vs. senile), than substrate depth alone.