HIV-1 Capture and Transmission by Dendritic Cells: The Role of Viral Glycolipids and the Cellular Receptor Siglec-1

Dendritic cells (DCs) are essential in order to combat invading viruses and trigger antiviral responses. Paradoxically, in the case of HIV-1, DCs might contribute to viral pathogenesis through trans-infection, a mechanism that promotes viral capture and transmission to target cells, especially after DC maturation. In this review, we highlight recent evidence identifying sialyllactose-containing gangliosides in the viral membrane and the cellular lectin Siglec-1 as critical determinants for HIV-1 capture and storage by mature DCs and for DC-mediated trans-infection of T cells. In contrast, DC-SIGN, long considered to be the main receptor for DC capture of HIV-1, plays a minor role in mature DC-mediated HIV-1 capture and trans-infection.

Sphingomyelinase D/Ceramide 1-Phosphate in Cell Survival and Inflammation

Sphingolipids are major constituents of biological membranes of eukaryotic cells. Many studies have shown that sphingomyelin (SM) is a major phospholipid in cell bilayers and is mainly localized to the plasma membrane of cells, where it serves both as a building block for cell architecture and as a precursor of bioactive sphingolipids. In particular, upregulation of (C-type) sphingomyelinases will produce ceramide, which regulates many physiological functions including apoptosis, senescence, or cell differentiation. Interestingly, the venom of some arthropodes including spiders of the genus Loxosceles, or the toxins of some bacteria such as Corynebacterium tuberculosis, or Vibrio damsela possess high levels of D-type sphingomyelinase (SMase D). This enzyme catalyzes the hydrolysis of SM to yield ceramide 1-phosphate (C1P), which promotes cell growth and survival and is a potent pro-inflammatory agent in different cell types. In particular, C1P stimulates cytosolic phospholipase A2 leading to arachidonic acid release and the subsequent formation of eicosanoids, actions that are all associated to the promotion of inflammation. In addition, C1P potently stimulates macrophage migration, which has also been associated to inflammatory responses. Interestingly, this action required the interaction of C1P with a specific plasma membrane receptor, whereas accumulation of intracellular C1P failed to stimulate chemotaxis. The C1P receptor is coupled to Gi proteins and activates of the PI3K/Akt and MEK/ERK1-2 pathways upon ligation with C1P. The proposed review will address novel aspects on the control of inflammatory responses by C1P and will highlight the molecular mechanisms whereby C1P exerts these actions.

Crystal structure and phase transition studies in perovskite-type oxides using powder-diffraction techniques and symmetry-mode analysis : SrLnMRuO6 (Ln=La,Pr,Nd; M=Zn,Co,Mg,Ni,Fe) and ALn2CuTi2O9 (A=Ca,Ba; Ln=La,Pr,Nd,Sm)

La tesis se ha centrado en la síntesis y caracterización estructural de materiales tipo perovskita: SrLnMRuO6 (Ln=La,Pr,Nd; M=Zn,Co,Mg,Ni,Fe) y ALn2CuTi2O9 (A=Ca,Ba; Ln=La,Pr,Nd,Sm). El estudio de las estructuras de los materiales se ha realizado mediante el análisis de los patrones de difracción en polvo de rayos-X, sincrotrón y/o neutrones. En el refinamiento por el método de Rietveld de las estructuras se han sustituido las coordenadas atómicas (el método más común), por coordenadas colectivas: las amplitudes de los modos que describen la distorsión de la fase prototipo. Los resultados generales para la serie SrLnMRuO6 (Ln=La,Pr,Nd; M=Zn,Co,Mg,Ni) a temperatura ambiente se ha recogido en un diagrama en el que se han indicado las amplitudes de los modos que transforman de acuerdo a las irreps en función del factor de tolerancia, ya que todos ellos cristalizan en la misma fase monoclínica (P21/n); y a temperaturas altas se ha construido un diagrama de fase. Los materiales SrLnFeRuO6 ( Ln=La,Pr,Nd) y CaLn2CuTi2O9 cristalizan en la fase ortorrómbica Pbnm a temperatura ambiente; mientras que BaLn2CuTi2O9 tienen una estructura más simétrica, I4/mcm. A altas temperaturas se han identificado las transiciones de fase inducidas por el cambio de temperatura.A temperaturas bajas se han analizado las estructuras magnéticas de algunos de los compuestos mediante difracción de neutrones.

Genetics of Type III Bartter Syndrome in Spain, Proposed Diagnostic Algorithm

9 p.

Evaluation of Alpha 1-Antitrypsin and the Levels of mRNA Expression of Matrix Metalloproteinase 7, Urokinase Type Plasminogen Activator Receptor and COX-2 for the Diagnosis of Colorectal Cancer

8 p.

Mechanisms Responsible for the Trophic Effect of Beta-Adrenoceptors on the I-to Current Density in Type 1 Diabetic Rat Cardiomyocytes

Background/Aims: In diabetic ventricular myocytes, transient outward potassium current (I-to) amplitude is severely reduced because of the impaired catecholamine release that characterizes diabetic autonomic neuropathy. Sympathetic nervous system exhibits a trophic effect on I-to since incubation of myocytes with noradrenaline restores current amplitude via beta-adrenoceptor (beta AR) stimulation. Here, we investigate the intracellular signalling pathway though which incubation of diabetic cardiomyocytes with the beta AR agonist isoproterenol recovers I-to amplitude to normal values. Methods: Experiments were performed in ventricular myocytes isolated from streptozotocin-diabetic rats. I-to current was recorded by using the patch-clamp technique. Kv4 channel expression was determined by immunofluorescence. Protein-protein interaction was determined by coimmunoprecipitation. Results: Stimulation of beta AR activates first a G alpha s protein, adenylyl cyclase and Protein Kinase A. PKA-phosphorylated receptor then switches to the G alpha i protein. This leads to the activation of the beta AR-Kinase-1 and further receptor phosphorylation and arrestin dependent internalization. The internalized receptor-arrestin complex recruits and activates cSrc and the MAPK cascade, where Ras, c-Raf1 and finally ERK1/2 mediate the increase in Kv4.2 and Kv4.3 protein abundance in the plasma membrane. Conclusion: beta(2)AR stimulation activates a G alpha s and G alpha i protein dependent pathway where the ERK1/2 modulates the Ito current amplitude and the density of the Kv4.2 and Kv4.2 channels in the plasma membrane upon sympathetic stimulation in diabetic heart.