Ethanol impairs Rho GTPase signaling and differentiation of cerebellar granule neurons in a rodent model of fetal alcohol syndrome

Developmental exposure to ethanol impairs fetal brain development and causes fetal alcohol syndrome. Although the cerebellum is one of the most alcohol-sensitive brain areas, signaling mechanisms underlying the deleterious effects of ethanol on developing cerebellar granule neurons (CGNs) are largely unknown. Here we describe the effects of in vivo ethanol exposure on neurite formation in CGNs and on the activation of Rho GTPases (RhoA and Rac1), regulators of neurite formation. Exposure of 7-day-old rat pups to ethanol for 3 h moderately increased blood alcohol concentration (BAC) (∼40 mM) and inhibited neurite formation and Rac1 activation in CGNs. Longer exposure to ethanol for 5 h resulted in higher BAC (∼80 mM), induced apoptosis, inhibited Rac1, and activated RhoA. Studies demonstrated a regulatory role of Rho GTPases in differentiation of cerebellar neurons, and indicated that ethanol-associated impairment of Rho GTPase signaling might contribute to brain defects observed in fetal alcohol syndrome. Received 16 July 2006; received after revision 12 September 2006; accepted 13 October 2006     

Prolactin inducible protein in cancer, fertility and immunoregulation: structure, function and its clinical implications

Prolactin inducible protein (PIP) is a 17- kDa single polypeptide chain, known by various names due to its versatile nature and function in human reproductive and immunological systems. It is expressed in several exocrine tissues such as the lacrimal, salivary, and sweat glands. Its expression is up regulated by prolactin and androgens, and estrogens down regulate it. Due to its over-expression in metastatic breast and prostate cancer, presently PIP is considered as a prognostic biomarker. Moreover, its aspartyl-proteinase nature suggests its role in tumor progression. PIP has unique features because it is small in size and plays multiple important functions. Its ability to bind potentially with CD4-T cell receptor, immunoglobulin G (IgG), actin, zinc α2-glycoprotein (ZAG), fibronectin and enamel pellicle, reveals its important biological functions. This is the first comprehensive review on the structure and functional analysis of PIP and its clinical applications. Received 04 August 2008; received after revision 09 September 2008; accepted 15 September 2008     

Hot-corrosion behavior of Cr_2O_3–CNT-coated ASTM-SA213-T22 steel in a molten salt environment at 700°C

The present work investigates the hot-corrosion behavior of carbon nanotube(CNT)-reinforced chromium oxide coatings on boiler steel in a molten salt(Na_2SO_4–60 wt%V_2O_5) environment at 700°C under cyclic conditions. The coatings were deposited via the high-velocity oxygen fuel process. The uncoated and coated steel samples were subjected to hot corrosion in a silicon tube furnace at 700°C for 50 cycles. The kinetics of the corrosion behavior was analyzed through mass-gain measurements after each cycle. The corrosion products were analyzed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray analysis techniques. The results revealed that uncoated steel suffered spallation of scale because of the formation of nonprotective Fe_2O_3 scale. The coated steel samples exhibited lower mass gains with better adhesiveness of oxide scale with the steel alloy until the end of exposure. The CNT-reinforced coatings were concluded to provide better corrosion resistance in the hot-corrosion environment because of the uniform dispersion of CNTs in the coating matrix and the formation of protective chromium oxides in the scale.     

Discovery of a magma chamber and faults beneath a Mid-Atlantic Ridge hydrothermal field

Crust at slow-spreading ridges is formed by a combination of magmatic and tectonic processes, with magmatic accretion possibly involving short-lived crustal magma chambers. The reflections of seismic waves from crustal magma chambers have been observed beneath intermediate and fast-spreading centres, but it has been difficult to image such magma chambers beneath slow-spreading centres, owing to rough seafloor topography and associated seafloor scattering. In the absence of any images of magma chambers or of subsurface near-axis faults, it has been difficult to characterize the interplay of magmatic and tectonic processes in crustal accretion and hydrothermal circulation at slow-spreading ridges. Here we report the presence of a crustal magma chamber beneath the slow-spreading Lucky Strike segment of the Mid-Atlantic Ridge. The reflection from the top of the magma chamber, centred beneath the Lucky Strike volcano and hydrothermal field, is approximately 3 km beneath the sea floor, 3-4 km wide and extends up to 7 km along-axis. We suggest that this magma chamber provides the heat for the active hydrothermal vent field above it. We also observe axial valley bounding faults that seem to penetrate down to the magma chamber depth as well as a set of inward-dipping faults cutting through the volcanic edifice, suggesting continuous interactions between tectonic and magmatic processes.     

Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain

Molecular processes that govern pathogenic features of erythrocyte invasion and cytoadherence in malaria are reliant on Plasmodium-specific Duffy-binding-like domains (DBLs). These cysteine-rich modules recognize diverse host cell-surface receptors during pathogenesis. DBLs of parasite erythrocyte-binding proteins mediate invasion, and those from the antigenically variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) have been implicated in cytoadherence. The simian and human malarial parasites, P. knowlesi and P. vivax, invade human erythrocytes exclusively through the host DARC receptor (Duffy antigen receptor for chemokines). Here we present the crystal structure of the P. knowlesi DBL domain (Pkalpha-DBL), which binds to DARC during invasion of human erythrocytes. Pkalpha-DBL retains the overall fold observed in DBLs from P. falciparum erythrocyte-binding antigen (EBA)-175 (ref. 4). Mapping the residues that have previously been implicated in binding highlights a fairly flat but exposed site for DARC recognition in subdomain 2 of Pkalpha-DBL; this is in sharp contrast to receptor recognition by EBA-175 (ref. 4). In Pkalpha-DBL, the residues that contact DARC and the clusters of residues under immune pressure map to opposite surfaces of the DBL, and suggest a possible mechanism for immune evasion by P. vivax. Our comparative structural analysis of Pkalpha-DBL and P. falciparum EBA-175 provides a framework for the understanding of malaria parasite DBLs, and may affect the development of new prophylactic and therapeutic strategies.     

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).