Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes

We determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosclerosis. Eight genotypic groups of mice were studied (AI, LCAT, CETP, LCAT/AI, CETP/AI, LCAT/CETP, LCAT/AI/CETP, and non-transgenic) after four months on an atherogenic diet. The extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. The relative influence (R²) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. Whereas apo AI (R² = 0.22, P < 0.001) and CETP (R² = 0.13, P < 0.01) expression reduced lesion size, the LCAT (R² = 0.16, P < 0.005) and LCAT/AI (R² = 0.13, P < 0.003) genotypes had the opposite effect. Logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo AI transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. These results show that apo AI overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of LCAT when both transgenes were co-expressed. On the other hand, CETP expression was sufficient to eliminate the deleterious effect of LCAT and LCAT/AI overexpression. Therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while CETP expression can change specific athero genic scenarios.39139

Fractional Wave-diffusion Equation With Periodic Conditions

We study a time-space fractional wave-diffusion equation with periodic conditions using Laplace transforms and Fourier series and presenting its solution in terms of three-parameter Mittag-Leffler functions. As a particular case we recover a recent result. We also present some graphics associated with particular values of the parameters. © 2012 American Institute of Physics.5312Caputo, M., Carcione, J.M., Hysteresis cycles and fatigue criteria using anelastic models based on fractional derivatives (2011) Rheol. Acta, 50 (2), pp. 107-115. , 10.1007/s00397-010-0524-zMainardi, F., Spada, G., Creep, relaxation and viscosity properties for basic fractional models in rheology (2011) Eur. Phys. J. Spec. Top., 193, pp. 133-160. , 10.1140/epjst/e2011-01387-1, e-print arXiv:cond-mat.mtrl.sci1110.3400v1Mainardi, F., Mura, A., Pagnini, G., The M-Wright function in time-fractional diffusion processes: A tutorial survey (2010) Int. J. Differ. Equations, 2010, p. 104505. , 10.1155/2010/104505, e-print arXiv:org/abs/1004.2950(2011) Fractional Dynamics, Recent Advances, , J. Klafter, S. C. Lim, R. Metzler, edited by and (World Scientific, Singapore, )Costa, F.S., Fractional thermal systems (2011) International Conference on Multimedia Technology (ICMT), , E. Capelas de Oliveira, Hangzhou, China, 26-28 JulyOliveira, E., Costa, F.S., Vaz, J., The fractional Schrödinger equation for delta potentials (2010) J. Math. Phys., 51, p. 123517. , 10.1063/1.3525976Oliveira, E., Vaz, J., Tunneling in fractional quantum mechanics (2011) J. Phys. A: Math. Theor., 44, p. 185303. , 10.1088/1751-8113/44/18/185303Machado, J.T., Kiryakova, V., Mainardi, F., Recent history of fractional calculus (2011) Nonlinear Sci. Number. Simul., 16, pp. 1140-1153. , 10.1016/j.cnsns.2010.05.027Podlubny, I., (1999) Fractional Differential Equations, , (Academic, San Diego, )Kilbas, A.A., Srivastava, H.M., Trujillo, J.J., (2006) Theory and Applications of Fractional Differential Equations, 204. , J. Van Mill, and Mathematics Studies, edited by (Elsevier, Amsterdam, )Zhang, H., Liu, F., The fundamental solutions of the space, space-time Riesz fractional partial differential equations with periodic conditions (2007) Numer. Math. J. Chin. Univ., 16, pp. 181-192Prabhakar, T.R., A singular integral equation with generalized Mittag-Leffler function in the kernel (1971) Yokohama Math. J., 19, pp. 7-25Samko, S.G., Kilbas, A.A., Marichev, O.I., (1993) Fractional Integrals and Derivatives: Theory and Applications, , (Gordon and Breach, New York, )Mainardi, F., Luchko, Y., Pagnini, G., The fundamental solution of the space-time fractional diffusion equation (2001) Fract. Calc. & Appl. Anal., 4 (2), pp. 153-192. , e-print arXiv:cond-mat.stat.mech/0702419v1Camargo, R., Charnet, R., de Oliveira, E., On the fractional Green function (2009) J. Math. Phys., 50, p. 043514. , 10.1063/1.311948

The Fractional Schrödinger Equation For Delta Potentials

The fractional Schrödinger equation is solved for the delta potential and the double delta potential for all energies. The solutions are given in terms of Fox's H-function. © 2010 American Institute of Physics.5112Rangarajan, G., Ding, M., (2000) Phys. Lett. A, 273, p. 322. , 10.1016/S0375-9601(00)00518-1Mainardi, F., (1996) Appl. Math. Lett., 9, p. 23. , 10.1016/0893-9659(96)00089-4Duan, J.S., (2005) J. Math. Phys., 46, p. 013504. , 10.1063/1.1819524Figueiredo Camargo, R., Capelas de Oliveira, E., Vaz, J., (2009) J. Math. Phys., 50, p. 123518. , 10.1063/1.3269587Laskin, N., (2000) Phys. Lett. A, 268, p. 298. , 10.1016/S0375-9601(00)00201-2Laskin, N., (2000) Phys. Rev. E, 62, p. 3135. , 10.1103/PhysRevE.62.3135(1995) Lévy Flights and Related Topics in Physics, 450. , M.F.Shlesinger, G.M.Zaslavsky, U.Frisch, edited by and, Lecture Notes in Physics, (Springer, New York)Guo, X., Xu, M., (2006) J. Math. Phys., 47, p. 082104. , 10.1063/1.2235026Laskin, N., (2000) Chaos, 10, p. 780. , 10.1063/1.1050284Naber, M., (2004) J. Math. Phys., 45, p. 3339. , 10.1063/1.1769611Jeng, M., Xu, S.-L.-Y., Hawkins, E., Schwarz, J.M., (2010) J. Math. Phys., 51, p. 062102. , 10.1063/1.3430552Dong, J., Xu, M., (2007) J. Math. Phys., 48, p. 072105. , 10.1063/1.2749172Butzer, P.L., Westphal, U., (2000) Applications of Fractional Calculus in Physics, pp. 1-85. , R.Hilfer, and, "An introduction to fractional calculus," in, edited by (World Scientific, Singapore)Riesz, M., (1948) Acta Math., 81, p. 1. , 10.1007/BF02395016Gradshteyn, I.S., Ryzhik, I.M., (2007) Table of Integrals, Series, and Products, , 7th ed. (Academic Press, NY)Gasiorowicz, S., (2003) Quantum Physics, , 3rd ed. (Wiley, NY)Scott, T.C., Babb, J.F., Dalmano, A., Morgan, J.D., (1993) J. Chem. Phys., 99, p. 2841. , 10.1063/1.465193Mathai, A.M., Saxena, R.K., Haubold, H.J., (2009) The H-Function, , (Springer, NY)Braaksma, B.L.J., (1962) Compos. Math., 15, p. 239. , 2013, 1964Kilbas, A.A., Srivastava, H.M., Trujillo, J.J., (2006) Theory and Applications of Fractional Differential Equations, , (Elsevier, Amsterdam)Oberhettinger, F., (1974) Tables of Mellin Transforms, , (Springer-Verlag, Berlin)Churchill, R.V., (1960) Complex Variables and Applications, , (McGraw-Hill, NY)Podlubny, I., (1998) Fractional Differential Equations, , (Academic Press, San Diego

Labyrinthine fístulae in chronic otitis media with cholesteatoma

The chronic otitis media with cholesteatoma (COMC) may evoluate to intracranial and extra cranial complications, including the labyrithine fístulae. In this study, we present the evolution of our patients with labyrinthine fístulae. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: Ten out 82 patients with COMC had labyrinthine fístulae and underwent surgery from January/2001 to April/2002. They were assessed by clinical exam, computed tomography scans, and pre and postoperative audiogram. RESULTS: Hearing loss, otorrhea, tinnitus and dizziness were present in 100%, 90%,80%, and 40% of the cases. In one patient the fístulae was seen only in the coronal CT-scan, in another patient the fístulae was not seen neither in coronal nor axial images. Among the patients who had tinnitus, 66% referred improvement of this complaint after surgery. DISCUSSION: in the cases without invasion of the perilymphatic space, we noticed a tendency of improvement of the postoperative audiogram pattern and clinical outcome. In the extensive fístulae, on the other hand, there were no clinical changes. CONCLUSION: The CT-scan remains the best exam to assess the COMC with 90% of sensitivity for labyrinthine fístulae. In the stage II we had a good postoperative outcome.A otite média crônica colesteatomatosa (OMCC) pode cursar com complicações intra e/ou extracranianas, entre elas a fístula labiríntica. Neste trabalho, mostramos a incidência e a evolução dos casos de fístula labiríntica decorrentes da OMCC em nosso serviço. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Dez pacientes com fístula labiríntica, do total de 82 pacientes com OMCC, foram submetidos à cirurgia no período de janeiro de 2001 a abril de 2002 e avaliados através de exame otorrinolaringológico completo, tomografia computadorizada e audiometria pré e pós-operatória. RESULTADOS: Perda auditiva, otorréia, zumbido e vertigem estavam presentes em 100%, 90%, 80% e 40% dos casos respectivamente na avaliação clínica pré-operatória. Em um paciente a fístula aparecia apenas nos cortes tomográficos coronais e tivemos um caso de falso-negativo. Dos pacientes com zumbido, 66% apresentaram melhora deste quadro no pós-operatório. DISCUSSÃO: Nos casos de fístula sem invasão do espaço perilinfático (até grau II), notamos uma tendência de melhora dos quadros clínico e audiométrico após a cirurgia. Nas fístulas extensas, por outro lado, o resultado audiométrico se manteve inalterado. CONCLUSÃO: A tomografia continua sendo o exame de escolha para os quadros de OMCC com sensibilidade de 90% para fístulas labirínticas. Nas fístulas grau II a cirurgia apresenta bom resultado funcional.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de Otorrinolaringologia e Distúrbios da Comunicação HumanaSciEL

Plasma Lipases And Lipid Transfer Proteins Increase Phospholipid But Not Free Cholesterol Transfer From Lipid Emulsion To High Density Lipoproteins

Background: Plasma lipases and lipid transfer proteins are involved in the generation and speciation of high density lipoproteins. In this study we have examined the influence of plasma lipases and lipid transfer protein activities on the transfer of free cholesterol (FC) and phospholipids (PL) from lipid emulsion to human, rat and mouse lipoproteins. The effect of the lipases was verified by incubation of labeled (3H-FC, 14C-PL) triglyceride rich emulsion with human plasma (control, post-heparin and post-heparin plus lipase inhibitor), rat plasma (control and post-heparin) and by the injection of the labeled lipid emulsion into control and heparinized functionally hepatectomized rats. Results: In vitro, the lipase enriched plasma stimulated significantly the transfer of 14C-PL from emulsion to high density lipoprotein (p&lt;0.001) but did not modify the transfer of 3H-FC. In hepatectomized rats, heparin stimulation of intravascular lipolysis increased the plasma removal of 14C-PL and the amount of 14C-PL found in the low density lipoprotein density fraction but not in the high density lipoprotein density fraction. The in vitro and in vivo experiments showed that free cholesterol and phospholipids were transferred from lipid emulsion to plasma lipoproteins independently from each other. The incubation of human plasma, control and control plus monoclonal antibody anti-cholesteryl ester transfer protein (CETP), with 14C-PL emulsion showed that CETP increases 14C-PL transfer to human HDL, since its partial inhibition by the anti-CETP antibody reduced significantly the 14C-PL transfer (p&lt;0.05). However, comparing the nontransgenic (no CETP activity) with the CETP transgenic mouse plasma, no effect of CETP on the 14C-PL distribution in mice lipoproteins was observed. Conclusions: It is concluded that: 1-intravascular lipases stimulate phospholipid transfer protein mediated phospholipid transfer, but not free cholesterol, from triglyceride rich particles to human high density lipoproteins and rat low density lipoproteins and high density lipoproteins; 2-free cholesterol and phospholipids are transferred from triglyceride rich particles to plasma lipoproteins by distinct mechanisms, and 3 - CETP also contributes to phospholipid transfer activity in human plasma but not in transgenic mice plasma, a species which has high levels of the specific phospholipid transfer protein activity.219Backer, G., Bacquer, D., Konitzer, M., Epidemiological aspects of high density lipoprotein cholesterol (1998) Atherosclerosis, 137, pp. S1-S6Stein, O., Stein, Y., Atheroprotective mechanisms of HDL (1999) Atherosclerosis, 144, pp. 285-301Tall, A.R., Plasma lipid transfer proteins (1995) Annu Rev Biochem, 64, pp. 235-257Hesler, B., Tall, A.R., Swenson, T.L., Weech, P.K., Marcel, Y.L., Milne, R.W., Monoclonal antibody to the Mr 74000 cholesterol ester transfer protein neutralize all of the cholesterol ester and triglyceride transfer activities in human plasma (1988) J Biol Chem, 263, pp. 5020-5023Swenson, T.L., Brocia, R.W., Tall, A.R., Plasma cholesteryl ester transfer protein has binding sites for neutral lipids and phospholipids (1988) J Biol Chem, 263, pp. 5150-5157Lagrost, L., Athias, A., Gambert, P., Lallemant, C., Comparative study of phospholipid transfer activities mediated by cholesteryl ester transfer protein and phospholipid transfer protein (1994) J Lipid Res, 35, pp. 825-835Tato, F., Vega, G.L., Grundy, S.M., Determinants of plasma HDL-cholesterol in hypertriglyceridemic patients (1997) Arterioscler Thromb Vasc Biol, 17, pp. 56-63Tall, A.R., Forester, L.R., Bongiovanni, G.L., Facilitation of phosphatidylcholine transfer into HDL lipoproteins by an apolipoprotein in the density 1.20-1.26 g/ml fraction of plasma (1983) J Lipid Res, 24, pp. 277-289Albers, J.J., Tollefson, J.H., Chen, C.H., Steinmetz, A., Isolation and characterization of human plasma lipid transfer proteins (1984) Arteriosclerosis, 4, pp. 49-58Guyard-Dangremont, V., Desrumaux, C., Gambert, P., Lallemant, C., Lagrost, L., Phospholipid and cholesteryl ester transfer activities in plasma from 14 vertebrate species. Relation to atherogenesis susceptibility (1998) Comp Biochem Physiol Biochem Mol Biol, 120, pp. 517-525Tall, A.R., Krumholz, S., Olivecrona, T., Deckelbaum, R.J., Plasma phospholipid transfer protein enhances transfer and exchange of phospholipids between VLDL and HDL lipoproteins during lipolysis (1985) J Lipid Res, 26, pp. 842-851Nishida, H.I., Nishida, T., Phospholipid transfer protein mediates transfer of not only phosphatidylcholine but also cholesterol from phosphatidylcholine-cholesterol vesicles to high density lipoproteins (1997) J Biol Chem, 272, pp. 6959-6964Lagrost, L., Desrumaux, C., Masson, D., Deckert, V., Gambert, P., Structure and function of the plasma phospholipid transfer protein (1998) Curr Opin Lipidol, 9, pp. 203-209Albers, J.J., Tu, A.Y., Paigen, B., Chen, H., Cheung, M.C., Marcovina, S.M., Transgenic mice expressing human phospholipid transfer protein have increased HDL/non-HDL cholesterol ratio (1996) Int J Clin Lab Res, 26, pp. 262-267Foger, B., Santamarina-Fojo, S., Shamburek, R.D., Parrot, C.L., Talley, G.D., Brewer Jr., H.B., Plasma phospholipid transfer protein. Adenovirus-mediated overexpression in mice leads to decreased plasma high density lipoprotein (HDL) and enhanced hepatic uptake of phospholipids and cholesteryl esters from HDL (1997) J Biol Chem, 272, pp. 27393-27400Redgrave, T.G., Small, D.M., Quantitation of the transfer of surface phospholipid of chylomicrons to the HDL lipoprotein fraction during the catabolism of chylomicrons in the rat (1979) J Clin Invest, 64, pp. 162-171Tall, A.R., Green, P.H., Glickman, R.M., Riley, J.W., Metabolic fate of chylomicron phospholipids and apoproteins in the rat (1979) J Clin Invest, 64, pp. 977-989Tall, A.R., Blum, C.B., Forester, G.P., Nelson, C.A., Changes in the distribution and composition of plasma HDL liproteins after ingestion of fat (1982) J Biol Chem, 257, pp. 198-207Groot, H., Scheek, L.M., Effects of fat ingestion on HDL profiles in human sera (1984) J Lipid Res, 25, pp. 684-692Brunzell, J.D., Familial lipoprotein lipase deficiency and other causes of the chylomicronemia syndrome (1995) Metabolic & Molecular Bases of Inherited Disease, pp. 1913-1932. , Scriver, CR, Beaudet, AL, Sly, WS, ed, McGraw-Hill Inc, New York, 7th edBijvoet, S., Gagne, S.E., Moorjani, S., Gagne, C., Henderson, H.E., Fruchart, J.C., Dallongeville, J., Hayden, M.R., Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency (1996) J Lipid Res, 37, pp. 640-650Kuusi, T., Ehnholm, C., Viikari, J., Harkonen, R., Vartiainen, E., Puska, P., Taskinen, M.-R., Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia (1989) J Lipid Res, 30, pp. 1117-1126Liu, S., Jirik, F.R., LeBoeuf, R.C., Henderson, H., Castellani, L.W., Lusis, A.J., Ma, Y., Kirk, E., Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase (1994) J Biol Chem, 269, pp. 11417-11424Weinstock, P.H., Bisgaier, C.L., Aalto-Setala, K., Radner, H., Ramakrishnan, R., Levak-Frank, S., Essenburg, A.D., Breslow, J.L., Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes (1995) J Clin Invest, 96, pp. 2555-2568Applebaum-Bowden, D., Kobayashi, J., Kashyap, V.S., Brown, D.R., Berard, A., Meyn, S., Parrott, C., Santamarina-Fojo, S., Hepatic lipase gene therapy in hepatic lipase-deficient mice. Adenovirus-mediated replacement of a lipolytic enzyme to the vascular endothelium (1996) J Clin Invest, 97, pp. 799-805Gillett, M.P., Vieira, E.M., Dimenstein, R., The phospholipase activities present in preheparin mouse plasma are inhibited by antiserum to hepatic lipase (1993) Int J Biochem, 25, pp. 449-453Ha, Y.C., Barter, P.J., Differences in plasma cholesteryl ester transfer activity in sixteen vertebrate species (1982) Comp Biochem Physiol B, 71, pp. 265-269Clee, S.M., Zhang, H., Bissada, N., Miao, L., Ehrenborg, E., Benlian, P., Shen, G.X., Hayden, M.R., Relationship between lipoprotein lipase and HDL lipoprotein cholesterol in mice: Modulation by cholesteryl ester transfer protein and dietary status (1997) J Lipid Res, 38, pp. 2079-2089Oliveira, H.C.F., Hirata, M.H., Redgrave, T.G., Maranhão, R.C., Competition between chylomicrons and their remnants for plasma removal: A study with artificial emulsion models of chylomicrons (1988) Biochim Biophys Acta, 958, pp. 211-217Nakandakare, E.R., Lottenberg, S.A., Oliveira, H.C.F., Bertolami, M.C., Vasconcelos, K.S., Sperotto, G., Quintão, E.C., Simultaneous measurements of chylomicron lipolysis and remnant removal using a doubly labeled artificial lipid emulsion: Studies in normolipidemic and hyperlipidemic subjects (1994) J Lipid Res, 35, pp. 143-152Jiao, S., Cole, T.G., Kitchens, R.T., Pfleger, B., Schonfeld, G., Genetic heterogeneity of lipoproteins in inbred strains of mice: Analysis by gel-permeation chromatography (1990) Metabolism, 39, pp. 155-160Ehnholm, C., Kuusi, T., Preparation, characterization and measurement of hepatic lipase (1986) Methods Enzymol, 129, pp. 716-738Oliveira, H.C.F., Quintão, E.C., 'In vitro' cholesteryl ester bidirectional flow between high-density lipoproteins and triglyceride-rich emulsions: Effects of particle concentration and composition, cholesteryl ester transfer activity and oleic acid (1996) J Biochem Biophys Methods, 32, pp. 45-57Huff, M.W., Miller, D.B., Wolf, B.M., Connelly, P.W., Sawyez, C.G., Uptake of hypertriglyceridemic VLDL and their remnants by HepG2 cells: The role of lipoprotein lipase, hepatic triglyceride lipase, and cell surface proteoglycans (1997) J Lipid Res, 38, pp. 1318-1333Marques-Vidal, P., Jauhiainen, M., Metso, J., Ehnholm, C., Transformation of HDL2 particles by hepatic lipase and phospholipid transfer protein (1997) Atherosclerosis, 133, pp. 87-96Murdoch, S.J., Breckenridge, W.C., Effect of lipid transfer proteins on lipoprotein lipase induced transformation of VLDL and HDL (1996) Biochim Biophys Acta, 1303, pp. 222-232Murdoch, S.J., Breckenridge, W.C., Influence of lipoprotein lipase and hepatic lipase on the transformation of VLDL and HDL during lipolysis of VLDL (1995) Atherosclerosis, 118, pp. 193-212Patsch, J.R., Gotto Jr., A.M., Olivercrona, T., Eisenberg, S., Formation of HDL2-like particles during lipolysis of VLDL in vitro (1978) Proc Natl Acad Sci USA, 75, pp. 4519-4523Gillett, M.P., Costa, E.M., Owen, J.S., The phospholipase activities present in preheparin mouse plasma are inhibited by antiserum to hepatic lipase (1980) Biochim Biophys Acta, 617, pp. 237-244Peterson, J., Bengtsson-Olivecrona, G., Olivecrona, T., Mouse preheparin plasma contains high levels of hepatic lipase with low affinity for heparin (1986) Biochim Biophys Acta, 87, pp. 865-870O'Meara, N.M., Cabana, V.G., Lukens, J.R., Loharikar, B., Forte, T.M., Polonsky, K.S., Getz, G.S., Heparin-induced lipolysis in hypertriglyceridemic subjects results in the formation of atypical HDL particle (1994) J Lipid Res, 35, pp. 2178-219

Kinase Inhibitor Profile For Human Nek1, Nek6, And Nek7 And Analysis Of The Structural Basis For Inhibitor Specificity

Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Ä262-1258)-(T162A), Isogranulatimide for hNek6(S206A), and GSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the respective hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by molecular docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors.20111761191Rubin, G.M., Yandell, M.D., Wortman, J.R., Gabor Miklos, G.L., Nelson, C.R., Hariharan, I.K., Fortini, M.E., Fleischmann, W., Comparative genomics of the eukaryotes (2000) Science, 287, pp. 2204-2215Johnson, L.N., Lowe, E.D., Noble, M.E., Owen, D.J., The Eleventh Datta Lecture. The structural basis for substrate recognition and control by protein kinases (1998) FEBS Lett., 430, pp. 1-11Hanks, S.K., Eukaryotic protein kinases (1991) Curr. Opin. Struct. 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Cell Sci., 125, pp. 4423-4433Meirelles, G.V., Perez, A.M., Souza, E.E., Basei, F.L., Papa, P.F., Melo Hanchuk, T.D., Cardoso, V.B., Kobarg, J., "Stop Ne(c)king around": How systems biology can help to characterize the functions of Nek family kinases from cell cycle regulation to DNA damage response (2014) World J. Biol. Chem., 5, pp. 141-160Fry, A.M., Mayor, T., Meraldi, P., Stierhof, Y.D., Tanaka, K., Nigg, E.A., C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2 (1998) J. Cell Biol., 141, pp. 1563-1574Quarmby, L.M., Mahjoub, M.R., Caught nek-ing: Cilia and centrioles (2005) J. Cell Sci., 118, pp. 5161-5169Meirelles, G.V., Silva, J.C., Mendonça, Y.A., Ramos, C.H., Torriani, I.L., Kobarg, J., Human Nek6 is a monomeric mostly globular kinase with an unfolded short N-terminal domain (2011) BMC Struct. 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mHealth in urology

Introduction: Smartphones are increasingly playing a role in healthcare and previous studies assessing medical applications (apps) have raised concerns about lack of expert involvement and low content accuracy. However, there are no such studies in Urology. We reviewed Urology apps with the aim of assessing the level of participation of healthcare professionals (HCP) and scientific Urology associations in their development. Material and Methods: A systematic search was performed on PubMed, Apple's App Store and Google's Play Store, for Urology apps, available in English. Apps were reviewed by three graders to determine the app's platform, target customer, developer, app type, app category, price and the participation of a HCP or a scientific Urology association in the development. Results: The search yielded 372 apps, of which 150 were specific for Urology. A fifth of all apps had no HCP involvement (20.7%) and only a third had been developed with a scientific Urology association (34.7%). The lowest percentage of HCP (13.4%) and urological association (1.9%) involvement was in apps designed for the general population. Furthermore, there was no contribution from an Urology society in "Electronic Medical Record" nor in "Patient Information" apps. A limitation of the study is that only Android and iOS apps were reviewed. Conclusions: Despite the increasing Mobile Health (mHealth) market, this is the first study that demonstrates the lack of expert participation in the design of Urology apps, particularly in apps designed for the general public. Until clear regulation is enforced, the urological community should help regulate app development. Maintaining a register of certified apps or issuing an official scientific seal of approval could improve overall app quality. We propose that urologists become stakeholders in mHealth, shaping future app design and promoting peer-review app validation