The Structure and Regulation of Human Muscle α-Actinin

SummaryThe spectrin superfamily of proteins plays key roles in assembling the actin cytoskeleton in various cell types, crosslinks actin filaments, and acts as scaffolds for the assembly of large protein complexes involved in structural integrity and mechanosensation, as well as cell signaling. α-actinins in particular are the major actin crosslinkers in muscle Z-disks, focal adhesions, and actin stress fibers. We report a complete high-resolution structure of the 200 kDa α-actinin-2 dimer from striated muscle and explore its functional implications on the biochemical and cellular level. The structure provides insight into the phosphoinositide-based mechanism controlling its interaction with sarcomeric proteins such as titin, lays a foundation for studying the impact of pathogenic mutations at molecular resolution, and is likely to be broadly relevant for the regulation of spectrin-like proteins

Atherosclerotic carotid disease and cardiovascular risk in HIV-Infected patients

Introduction Although survival has been improved in HIV-infected patients, the risk for atherosclerotic diseases has increased. Objective To evaluate the effect of HIV infection on atherosclerosis in asymptomatic patients. Subjects and methods Study design: observational, prospective case-control study, including 124 consecutive male and female HIV-infected patients, older than 18 year (HIV-group). Results were compared with 130 healthy volunteers of same gender and age (Control-group). Study protocol: Clinical evaluation followed by ultrasound exam of carotids for carotid intimal-medial thickness (CIMT) measurement. The presence of atherosclerosis plaques was recorded. Statistical analysis: Chi-square test and linear regression analysis. Significance level: p < 0.05. Result Age (HIV-group:43.87 ± 11.31 vs Control-group: 42.9 ± 11.54, p = 0.324) was similar in both groups. There was 52.00% male in HIV-group and 54.00% in Control group. Atherosclerotic plaque was identified in 30.64% of the patients HIV and in 3.84% of the control (p < 0.001). Surprisingly, 22% of HIV-infected patients, classified at low risk score Freminghan, presented plaques in the carotid arteries. For controls, there was an increase of 0.068 mm in the CIMT for each one-year increase in age (OR: 1.068; CI95%: 1.03–1.107; p < 0.001). The presence of HIV increased this increment for tenfold (OR: 10.7; CI95%: 3.58–31.76; p < 0.001). There was an interaction between age and HIV-infection to increase CIMT (p < 0.001). Conclusions Our results indicated that: 1- patients with HIV are at higher risk for atherosclerosis in the carotid artery than control individuals. 2- The effect of age on risk for atherosclerosis occurs in both groups, however it is more remarkable in HIV-infected patients

The initial stage of OH adsorption on Ni(111)

The adsorption of OH on Ni(111) has been investigated by a combination of density functional theory and classical molecular dynamics. At low coverage, the adsorption is strong, the adsorbate carries almost unit negative charge, and interacts strongly with water. Because of their high charges, adsorbed OH species repel each other, and adsorption becomes less favorable with increasing coverage. Adsorption on Ni(111) is contrasted with that on Pt(111).Fil: Juarez, Fernanda. Universitat Ulm; AlemaniaFil: Salmazo, Debora. Université de Strasbourg; FranciaFil: Savinova, Elena R.. Universitat Ulm; AlemaniaFil: Quaino, Paola Monica. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Programa de Electroquímica Aplicada e Ingeniería Electroquímica; ArgentinaFil: Belletti, Gustavo Daniel. Universidad Nacional del Litoral. Instituto de Química Aplicada del Litoral. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Química Aplicada del Litoral.; ArgentinaFil: Santos, Elizabeth del Carmen. Universidad Nacional del Litoral. Instituto de Química Aplicada del Litoral. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Química Aplicada del Litoral.; ArgentinaFil: Schmickler, Wolfgang. Universitat Ulm; Alemani

Preparation and structural characterization of vulcanized natural rubber nanocomposites containing nickel-zinc ferrite nanopowders

Single-phase polycrystalline mixed nickel-zinc ferrites belonging to Ni0.5Zn0.5Fe2O4 were prepared on a nanometric scale (mean crystallite size equal to 14.7 nm) by chemical synthesis named the modified poliol method. Ferrite nanopowder was then incorporated into a natural rubber matrix producing nanocomposites. The samples were investigated by means of infrared spectroscopy, X-ray diffraction, scanning electron microscopy and magnetic measurements. The obtained results suggest that the base concentration of nickel-zinc ferrite nanoparticles inside the polymer matrix volume greatly influences the magnetic properties of nanoconnposites. A small quantity of nanoparticles, less than 10 phr, in the nanocomposite is sufficient to produce a small alteration in the semi-crystallinity of nanocomposites observed by X-ray diffraction analysis and it produces a flexible magnetic composite material with a saturation magnetization, a coercivity field and an initial magnetic permeability equal to 3.08 emu/g, 99.22 Oe and 9.42 X 10(-5) respectively.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Binding and structural analyses of potent inhibitors of the human Ca2+/calmodulin dependent protein kinase kinase 2 (CAMKK2) identified from a collection of commercially-available kinase inhibitors.

Calcium/Calmodulin-dependent Protein Kinase Kinase 2 (CAMKK2) acts as a signaling hub, receiving signals from various regulatory pathways and decoding them via phosphorylation of downstream protein kinases - such as AMPK (AMP-activated protein kinase) and CAMK types I and IV. CAMKK2 relevance is highlighted by its constitutive activity being implicated in several human pathologies. However, at present, there are no selective small-molecule inhibitors available for this protein kinase. Moreover, CAMKK2 and its closest human homolog, CAMKK1, are thought to have overlapping biological roles. Here we present six new co-structures of potent ligands bound to CAMKK2 identified from a library of commercially-available kinase inhibitors. Enzyme assays confirmed that most of these compounds are equipotent inhibitors of both human CAMKKs and isothermal titration calorimetry (ITC) revealed that binding to some of these molecules to CAMKK2 is enthalpy driven. We expect our results to advance current efforts to discover small molecule kinase inhibitors selective to each human CAMKK