Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events

Toll-like receptors (TLRs) are pattern recognition receptors of innate immunity. TLRs initiate inflammatory pathways that may exacerbate chronic inflammatory diseases like atherosclerosis. En face laser scanning confocal microscopy (LSCM) of isolated aortic segments revealed the distribution of intimal TLR2 expression and the atheroprotective outcomes resulting from a TLR2 deficiency. TLR2 expression was restricted to endothelial cells in regions of disturbed blood flow, such as the lesser curvature region, in atherosclerosis-prone, low-density lipoprotein receptor–deficient (LDLr−/−) mice. Diet-induced hyperlipidemia in LDLr−/− mice increased this regional endothelial TLR2 expression. Bone marrow (BM) reconstitution of LDLr−/− and LDLr−/−TLR2−/− mice created chimeric mice with green fluorescent protein (GFP) expression in BM-derived cells (BMGFP+). Lesser curvature BMGFP+ leukocyte accumulation, lipid accumulation, foam cell generation and endothelial cell injury were all increased by hyperlipidemia, whereas hyperlipidemic double mutant BMGFP+LDLr−/−TLR2−/− mice had reduced BMGFP+ leukocyte accumulation, lipid accumulation, foam cells, and endothelial cell injury. This is the first report of in vivo site-specific expression of endothelial cell TLR2. Expression of this receptor on endothelial cells contributed to early atherosclerotic processes in lesion-prone areas of the mouse aorta

Minimal change prion retinopathy: Morphometric comparison of retinal and brain prion deposits in Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the \u27cellular\u27 prion protein (Pr

Impacto de la formalización minera sobre el uso y defensa del territorio comunal de las CC.NN. Boca Inambari y Tres Islas, Madre de Dios

Analiza los efectos del estancamiento del proceso de formalización minera sobre las comunidades nativas Boca Inambari y Tres Islas en el departamento de Madre de Dios, Perú. Plantea que el estancamiento de la formalización minera en Madre de Dios, la incomunicación intersectorial de las entidades de decisión respecto al potencial de formalización de las Comunidades Nativas, así como las interdicciones, y los engaños de algunos consultores, han desestimulado el afán de las comunidades para ordenar sus actividades y las han conducido a asumir alternativas para subsistir. En consecuencia, identifica los efectos del estancamiento del proceso de formalización sobre el uso de otros recursos naturales diferentes al oro y sobre la soberanía territorial comunal; y caracteriza las estrategias alternativas de subsistencia de las comunidades nativas frente a las interdicciones contra la minería.Tesi

Assessment of the Red Cell Proteome of Young Patients with Unexplained Hemolytic Anemia by Two-Dimensional Differential In-Gel Electrophoresis (DIGE)

Erythrocyte cytosolic protein expression profiles of children with unexplained hemolytic anemia were compared with profiles of close relatives and controls by two-dimensional differential in-gel electrophoresis (2D-DIGE). The severity of anemia in the patients varied from compensated (i.e., no medical intervention required) to chronic transfusion dependence. Common characteristics of all patients included chronic elevation of reticulocyte count and a negative workup for anemia focusing on hemoglobinopathies, morphologic abnormalities that would suggest a membrane defect, immune-mediated red cell destruction, and evaluation of the most common red cell enzyme defects, glucose-6-phosphate dehydrogenase and pyruvate kinase deficiency. Based upon this initial workup and presentation during infancy or early childhood, four patients classified as hereditary nonspherocytic hemolytic anemia (HNSHA) of unknown etiology were selected for proteomic analysis. DIGE analysis of red cell cytosolic proteins clearly discriminated each anemic patient from both familial and unrelated controls, revealing both patient-specific and shared patterns of differential protein expression. Changes in expression pattern shared among the four patients were identified in several protein classes including chaperons, cytoskeletal and proteasome proteins. Elevated expression in patient samples of some proteins correlated with high reticulocyte count, likely identifying a subset of proteins that are normally lost during erythroid maturation, including proteins involved in mitochondrial metabolism and protein synthesis. Proteins identified with patient-specific decreased expression included components of the glutathione synthetic pathway, antioxidant pathways, and proteins involved in signal transduction and nucleotide metabolism. Among the more than 200 proteins identified in this study are 21 proteins not previously described as part of the erythrocyte proteome. These results demonstrate the feasibility of applying a global proteomic approach to aid characterization of red cells from patients with hereditary anemia of unknown cause, including the identification of differentially expressed proteins as potential candidates with a role in disease pathogenesis

Examples of protein expression patterns where one or both parents are intermediate between the levels measured in the patient sample and those measured in the controls (see also <b>Table 3</b>).

<p>Shown are Graphs (in normalized volume) for both replicates run per indicated sample in experimental set HA09 (A), HA19 (B), HA21 (C, left panel: patient lower expressing, right panel: patient higher expressing) and HA24 (D, left panel: patient lower expressing, right panel: patient higher expressing). Numbers (#) refer to Spot ranks in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034237#pone-0034237-t003" target="_blank">Table 3</a>.</p

Sample characterization (Blood Parameters and Enzyme Assays).

**<p>blood transfusion prior to drawing blood: HA09 42 days, HA24 37 days.</p><p>m: male.</p><p>f: female.</p><p>UI: International Unit.</p><p>G6PD: Glucose -6- Phosphate Dehydrogenase.</p><p>TPI: Triose Phosphate Isomerase.</p><p>GPI: Glucose Phosphate Isomerase.</p><p>ND: No Data.</p><p>The complete panel of enzyme assays performed on all samples in this study including controls can be found in Supplementary <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034237#pone-0034237-t001" target="_blank">Table 1</a>.</p

Principal Component Analysis was calculated by Same Spots software.

<p>Dot plot of all spots included in analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034237#pone-0034237-t002" target="_blank">Table 2</a>) shows that in all four experimental sets (HA09, HA19, HA21 and HA24), replicate samples group closely together and patient samples differ significantly from both familial and unrelated control samples.</p