IKAP/Elp1 Is Required In Vivo for Neurogenesis and Neuronal Survival, but Not for Neural Crest Migration

Familial Dysautonomia (FD; Hereditary Sensory Autonomic Neuropathy; HSAN III) manifests from a failure in development of the peripheral sensory and autonomic nervous systems. The disease results from a point mutation in the IKBKAP gene, which encodes the IKAP protein, whose function is still unresolved in the developing nervous system. Since the neurons most severely depleted in the disease derive from the neural crest, and in light of data identifying a role for IKAP in cell motility and migration, it has been suggested that FD results from a disruption in neural crest migration. To determine the function of IKAP during development of the nervous system, we (1) first determined the spatial-temporal pattern of IKAP expression in the developing peripheral nervous system, from the onset of neural crest migration through the period of programmed cell death in the dorsal root ganglia, and (2) using RNAi, reduced expression of IKBKAP mRNA in the neural crest lineage throughout the process of dorsal root ganglia (DRG) development in chick embryos in ovo. Here we demonstrate that IKAP is not expressed by neural crest cells and instead is expressed as neurons differentiate both in the CNS and PNS, thus the devastation of the PNS in FD could not be due to disruptions in neural crest motility or migration. In addition, we show that alterations in the levels of IKAP, through both gain and loss of function studies, perturbs neuronal polarity, neuronal differentiation and survival. Thus IKAP plays pleiotropic roles in both the peripheral and central nervous systems

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Evaluation of localization strategies with the meshless method of approximate particular solutions.

En el presente trabajo, se evalúan varios esquemas de localización con  el Método de Soluciones Particulares Aproximadas (MAPS). Este método sin malla utiliza soluciones particulares de una ecuación auxiliar de Poisson no homogénea para aproximar la variable dependiente. Problemas de difusión con condiciones de frontera tipo Dirichlet y Neumann son abordados para evaluar el desempeño de la formulación local mediante el uso de vecindades en forma de cruz, cruz alargada y circular. Los resultados obtenidos con las vecindades en forma de cruz muestran una mayor estabilidad con respecto al parámetro de forma. Las estrategias de localización muestran un mejor desempeño en problemas con condiciones de frontera de Dirichlet, mientras que la formulación global obtiene mejores resultados en problemas de difusión con condiciones de frontera de Neumann

Caracterización epidemiológica y virológica de la rinotraqueítis infecciosa bovina en Colombia

IP 1115-07-018-95epidemiologica y virologica de la rinotraquetis infecciosabovina en Colombia / Juan Carlos Zapata J...(et;al.) En: Caracterizacion epidemiologica y virologica de larinotraquetis:informe especial;ARTICULOS DE REVISTA : Espectro clinico y epidemioligico de larinotraqueitis infecciosa bovina /;J.J.Arboleda..(et al.) En : Revista Colombiana de CienciasPecuarias. Vol.9, no. 1y2 (1996) -- El herpesvirus;Bovino -1 : estructura,replicacion y latencia / J.D. Rodas..(etal.) En: Revista Colombiana de Ciencias;Pecuarias. Vol. 9, no. 1y2 (1996) -- Estandarizacion de latecnica de Elisa para rinotraqueitis infecciosa;bovina (RIB) y determinacin de la prevalencia de la infeccionenel hato blanco orejinegro (BON) de Antioquia;/ JD Rodas..(et al) En: Revista Colombiana de Ciencias Pecuarias. Vol. 9,no. 1y2 (1996) --Estandarizacion de;una prueba de Elisa para la deteccion de anticuerpos contra elherpesvirusBovino-1 (HBV-1) en suero lacteo /;J.D. Rodas..(et al.) En: Revista Colombiana de Ciencias Pecuarias. Vol. 9,no. 1y2 (1996) --Estandarizacin de;una tecnica de reaccion en cadena de la polimerasa (PCR) paraladetecciondel herpes virus bovino-1 (HVB-1);en semen / J.D. Rodas..(et al.) En: Revista Colombiana deCiencias Pecuarias. Vol. 9, no.1y2 (1996) --;Evaluacion del tratamiento de semen bovino con anticuerposespecificos contra la rinotraquetis infecciosa;bovina (RIB) : ensayos preliminares / J.D. Rodas..(et al.)En:Revista Colombiana de Ciencias Pecuarias. Vol.;9, no. 1y2 (1996) -- Encuesta virologica de herpesvirusbovino-1(HVB-1) enla Feria de Ganados de Medellin /;M. Restrepo..(et al.) En: Revista Colombiana de Ciencias Pecuarias. Vol. 9, no. 1y2 (1996) --Estandarizacion d;la tecnica ELISA en leche entera para la deteccion de anticuerpos contra el herpesvirus Bovino-1 (HVB-1) /;J.C. Palacio...(et al.) En: Revista Colombiana de CienciasPecuarias. Vol.10, no. 2 (1997) -- Caracterizacio

Cyclic and heteroclinic flows near general static spherically symmetric black holes

We investigate the Michel-type accretion onto a static spherically symmetric black hole. Using a Hamiltonian dynamical approach, we show that the standard method employed for tackling the accretion problem has masked some properties of the fluid flow. We determine new analytical solutions that are neither transonic nor supersonic as the fluid approaches the horizon(s); rather, they remain subsonic for all values of the radial coordinate. Moreover, the three-velocity vanishes and the pressure diverges on the horizon(s), resulting in a flow-out of the fluid under the effect of its own pressure. This is in favor of the earlier prediction that pressure-dominant regions form near the horizon. This result does not depend on the form of the metric and it applies to a neighborhood of any horizon where the time coordinate is timelike. For anti-de Sitter-like f(R) black holes we discuss the stability of the critical flow and determine separatrix heteroclinic orbits. For de Sitter-like f(R) black holes, we construct polytropic cyclic, non-homoclinic, physical flows connecting the two horizons. These flows become non-relativistic for Hamiltonian values higher than the critical value, allowing for a good estimate of the proper period of the flow