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Several genes have been related to late-onset Alzheimer's disease (LOAD). Phospholipases A2 (PLA2) influence the processing and secretion of the amyloid precursor protein, which gives rise to the beta-amyloid peptide, the major component of the amyloid plaque in AD. Hence, in the present study, polymorphisms of three genes encoding PLA2 enzymes group (cytosolic PLA2: BanI cPLA2 polymorphism; calcium-independent PLA2: AvrII iPLA2 polymorphism; PAFAH: Val279Phe PAFAH polymorphism) were analysed in a case-control sample using 58 patients with LOAD and 107 matched healthy controls. There was a genotypic association between the BanI cPLA2 polymorphism and LOAD (χ2=6.25, 2df, p=0.04), however there was no allelic association. There were no associations between AvrII iPLA2 and Val279Phe PAFAH polymorphisms and LOAD. These data suggest that the BanI cPLA2 polymorphism may play a role in the susceptibility for LOAD in our Brazilian sample.Vários genes têm sido investigados como fatores de risco para o desenvolvimento da doença de Alzheimer (DA) de início tardio. As fosfolipases A2 (PLA2) influenciam o processamento e secreção da proteína precursora do amilóide, que dá origem ao peptídeo meta-amilóide, o principal componente da placa amilóide na DA. Assim, no presente estudo, foram analisados três polimorfismos genéticos que codificam enzimas do grupo das PLA2 (PLA2 citosólica: polimorfismo BanI cPLA2; PLA2 cálcio-independente: polimorfismo AvrII iPLA2; PAFAH: polimorfismo Val279Phe PAFAH) em 58 pacientes com DA de início tardio e 107 controles saudáveis pareados. Houve associação genotípica entre o polimorfismo BanI cPLA2 e DA de início tardio (χ2=6,25, 2df, p=0,04); no entanto não foi observada associação alélica. Não houve associação entre os polimorfismos AvrII iPLA2 e Val279Phe PAFAH com a doença. Tais dados sugerem que o polimorfismo BanI cPLA2 pode estar envolvido como fator de susceptibilidade para DA de início tardio em nossa amostra brasileira.

Endothelial colony-forming cells (ECFCs) are the only endothelial progenitor cells (EPCs) that are capable of acquiring a mature endothelial phenotype. ECFCs are mainly mobilized from bone marrow to promote vascularization and represent a promising tool for cell-based therapy of severe ischemic diseases. Vascular endothelial growth factor (VEGF) stimulates the proliferation of peripheral blood-derived ECFCs (PB-ECFCs) through oscillations in intracellular Ca2+ concentration ([Ca2+]i). VEGF-induced Ca2+ spikes are driven by the interplay between inositol-1,4,5-trisphosphate (InsP3)-dependent Ca2+ release and store-operated Ca2+ entry (SOCE). The therapeutic potential of umbilical cord blood-derived ECFCs (UCB-ECFCs) has also been shown in recent studies. However, VEGF-induced proliferation of UCB-ECFCs is faster compared with their peripheral counterpart. Unlike PB-ECFCs, UCB-ECFCs express canonical transient receptor potential channel 3 (TRPC3) that mediates diacylglycerol-dependent Ca2+ entry. The present study aimed at investigating whether the higher proliferative potential of UCB-ECFCs was associated to any difference in the molecular underpinnings of their Ca 2+ response to VEGF. We found that VEGF induces oscillations in [Ca2+]i that are patterned by the interaction between InsP3-dependent Ca2+ release and SOCE. Unlike PB-ECFCs, VEGF-evoked Ca2+ oscillations do not arise in the absence of extracellular Ca2+ entry and after pharmacological (with Pyr3 and flufenamic acid) and genetic (by employing selective small interference RNA) suppression of TRPC3. VEGF-induced UCB-ECFC proliferation is abrogated on inhibition of the intracellular Ca2+ spikes. Therefore, the Ca 2+ response to VEGF in UCB-ECFCs is shaped by a different Ca 2+ machinery as compared with PB-ECFCs, and TRPC3 stands out as a promising target in EPC-based treatment of ischemic pathologies.

In the framework of an extensive study aimed at evaluating the wettability and the interfacial characteristics of different metal-ceramic systems for joining, the behaviour of ZrB2 in contact with liquid Ag and its alloys (Cu, Ti, Zr) has been studied. ZrB2 specimens, sintered pure or with different sintering aids by HIP have been used. The wetting and joining experiments have been performed by the sessile drop technique under controlled atmospheres. Contact angles and drop dimensions have been measured by using an in-house developed procedure (ASTRA©) allowing these data to be recorded in real time. Joining tests have also been made with the Ti-Al-V alloy. The dependence of the wetting characteristics and the interfacial reactions have been reported as a function of time, compositions of the ceramic and of the alloy involved. Interfacial structures and reaction products in both specimens resulting from wetting tests and joining processes have been analysed by SEM, EDS, XRD and microindentation tests. In some specimens the interfacial morphologies show the presence of interfacial reaction layers and of different bulk phases which are interpreted in terms of the relevant phase-diagrams and with respect to the final characteristics of the joint.

Engagement of killer cell inhibitory receptors (KIRs) with their MHC class I ligands inhibits T and NK lymphocyte activation. In humans, killer cell activatory receptors (KARs) are highly homologous to KIRs, interact with an identical set of MHC class I molecules, and are encoded by individual genes belonging to the Ig-like superfamily. In contrast to KIRs, engagement of KARs leads to T and NK cell activation. We identified a set of disulfide-linked dimers selectively associated with KARs. KAR-associated polypeptides (KARAPs) are phosphorylated on tyrosine and serine residues. Reconstitution of KAR cell surface expression in the absence of KARAPs correlates with the failure of KAR to transduce any detectable activation signals. These results indicate that KARs are included in a multimeric complex with phosphorylated KARAPs and define a novel set of polypeptides that are likely to be involved in the control of lymphocyte activation upon MHC class I recognition.