The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD)

<p>Abstract</p> <p>Background</p> <p>Although polymorphisms of <it>PRNP</it>, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s) modulating susceptibility to prion disease. Ribosomal protein SA (<it>RPSA</it>), also called 37 kDa laminin receptor precursor (LRP)/67 kDa laminin receptor (LR), acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR.</p> <p>Methods</p> <p>To identify other susceptibility genes involved in prion disease, we performed genetic analysis of <it>RPSA</it>. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD) patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on <it>RPSA </it>by direct sequencing or restriction fragment length polymorphism (RFLP) analysis.</p> <p>Results</p> <p>We observed four single nucleotide polymorphisms (SNPs), including -8T>C (rs1803893) in the 5'-untranslated region (UTR) of exon 2, 134-32C>T (rs3772138) in the intron, 519G>A (rs2269350) in the intron and 793+58C>T (rs2723) in the intron on the <it>RPSA</it>. The 519G>A (at codon 173) is located in the direct PrP binding site. The genotypes and allele frequencies of the <it>RPSA </it>polymorphisms showed no significant differences between the controls and sporadic CJD patients.</p> <p>Conclusion</p> <p>These results suggest that these <it>RPSA </it>polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of <it>RPSA </it>gene with sporadic CJD.</p

Mediterranean Thermohaline Response to Large-Scale Winter Atmospheric Forcing in a High-Resolution Ocean Model Simulation

Large-scale circulation anomalies over the North Atlantic and Euro-Mediterranean regions described by dominant climate modes, such as the North Atlantic Oscillation (NAO), the East Atlantic pattern (EA), the East Atlantic/Western Russian (EAWR) and the Mediterranean Oscillation Index (MOI), significantly affect interannual-to-decadal climatic and hydroclimatic variability in the Euro-Mediterranean region. However, whereas previous studies assessed the impact of such climate modes on air–sea heat and freshwater fluxes in the Mediterranean Sea, the propagation of these atmospheric forcing signals from the surface toward the interior and the abyss of the Mediterranean Sea remains unexplored. Here, we use a high-resolution ocean model simulation covering the 1979–2013 period to investigate spatial patterns and time scales of the Mediterranean thermohaline response to winter forcing from NAO, EA, EAWR and MOI. We find that these modes significantly imprint on the thermohaline properties in key areas of the Mediterranean Sea through a variety of mechanisms. Typically, density anomalies induced by all modes remain confined in the upper 600 m depth and remain significant for up to 18–24 months. One of the clearest propagation signals refers to the EA in the Adriatic and northern Ionian seas: There, negative EA anomalies are associated to an extensive positive density response, with anomalies that sink to the bottom of the South Adriatic Pit within a ~ 2-year time. Other strong responses are the thermally driven responses to the EA in the Gulf of Lions and to the EAWR in the Aegean Sea. MOI and EAWR forcing of thermohaline properties in the Eastern Mediterranean sub-basins seems to be determined by reinforcement processes linked to the persistency of these modes in multiannual anomalous states. Our study also suggests that NAO, EA, EAWR and MOI could critically interfere with internal, deep and abyssal ocean dynamics and variability in the Mediterranean Sea

Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model

Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group") or water (sFlt-1 "positive control") until weaning. The mFc group ("negative control") received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis.Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes.Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model