Probing the Neural Basis of Perceptual Phenomenology with the Touch-Induced Visual Illusion

Using the touch-induced visual illusion we examine whether the brain regions involved in coding sensory information are dissociable from those that contain decision information. Activity in the intraparietal sulcus, as measured by functional magnetic resonance imaging, was associated with the illusion suggesting a sensory coding role whereas activity in the middle occipital gyrus differentially modulated activity according to the decisions made by subjects consistent with their reported perceptual phenomenology.     

Protoporphyrins Enhance Oligomerization and Enzymatic Activity of HtrA1 Serine Protease

High temperature requirement protein A1 (HtrA1), a secreted serine protease of the HtrA family, is associated with a multitude of human diseases. However, the exact functions of HtrA1 in these diseases remain poorly understood. We seek to unravel the mechanisms of HtrA1 by elucidating its interactions with chemical or biological modulators. To this end, we screened a small molecule library of 500 bioactive compounds to identify those that alter the formation of extracellular HtrA1 complexes in the cell culture medium. An initial characterization of two novel hits from this screen showed that protoporphyrin IX (PPP-IX), a precursor in the heme biosynthetic pathway, and its metalloporphyrin (MPP) derivatives fostered the oligomerization of HtrA1 by binding to the protease domain. As a result of the interaction with MPPs, the proteolytic activity of HtrA1 against Fibulin-5, a specific HtrA1 substrate in age-related macular degeneration (AMD), was increased. This physical interaction could be abolished by the missense mutations of HtrA1 found in patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Furthermore, knockdown of HtrA1 attenuated apoptosis induced by PPP-IX. These results suggest that PPP-IX, or its derivatives, and HtrA1 may function as co-factors whereby porphyrins enhance oligomerization and the protease activity of HtrA1, while active HtrA1 elevates the pro-apoptotic actions of porphyrin derivatives. Further analysis of this interplay may shed insights into the pathogenesis of diseases such as AMD, CARASIL and protoporphyria, as well as effective therapeutic development.     

The Footprint of Continental-Scale Ocean Currents on the Biogeography of Seaweeds

Explaining spatial patterns of biological organisation remains a central challenge for biogeographic studies. In marine systems, large-scale ocean currents can modify broad-scale biological patterns by simultaneously connecting environmental (e.g. temperature, salinity and nutrients) and biological (e.g. amounts and types of dispersed propagules) properties of adjacent and distant regions. For example, steep environmental gradients and highly variable, disrupted flow should lead to heterogeneity in regional communities and high species turnover. In this study, we investigated the possible imprint of the Leeuwin (LC) and East Australia (EAC) Currents on seaweed communities across ~7,000 km of coastline in temperate Australia. These currents flow poleward along the west and east coasts of Australia, respectively, but have markedly different characteristics. We tested the hypothesis that, regional seaweed communities show serial change in the direction of current flow and that, because the LC is characterised by a weaker temperature gradient and more un-interrupted along-shore flow compared to the EAC, then coasts influenced by the LC have less variable seaweed communities and lower species turnover across regions than the EAC. This hypothesis was supported. We suggest that this pattern is likely caused by a combination of seaweed temperature tolerances and current-driven dispersal. In conclusion, our findings support the idea that the characteristics of continental-scale currents can influence regional community organisation, and that the coupling of ocean currents and marine biological structure is a general feature that transcends taxa and spatial scales.     

Rapid isolation of moderate and highly polymorphic DNA fragments mapping close to WT (Wilms' tumour) and AN2 (aniridia) on chromosome 11

Summary Genes implicated in the development of Wilms' tumour (WT) and aniridia (AN2) have been localised to a subregion of band p13 on chromosome 11 by molecular and cytogenetic characterisation of WAGR syndrome patients carrying variable constitutional deletions. Polymorphic markers for the region would be valuable for linkage analysis in the familial forms of both Wilms' tumour and aniridia, as well as for studying somatic rearrangements of chromosome 11 in a variety of tumour types. Here we describe the isolation and characterisation of three frequently polymorphic arbitrary DNA fragments that map proximal to the AN2 and WT loci.     

Interauterine Transfusion: 101 Consecutive Cases treated at Queen Charlotte's Maternity Hospital

Intrauterine transfusion was performed or attempted in 101 cases during a period of four and a half years. After exclusion of six cases, for reasons detailed in the text, 95 cases are considered in detail. Intrauterine transfusion was successfully performed in 93 of these, with a mean of 2·8 transfusions each. Forty-four babies (46·3%) survived and all but one are so far developing normally.