Asparagine requirement in Plasmodium berghei as a target to prevent malaria transmission and liver infections

The proteins of Plasmodium, the malaria parasite, are strikingly rich in asparagine. Plasmodium depends primarily on host haemoglobin degradation for amino acids and has a rudimentary pathway for amino acid biosynthesis, but retains a gene encoding asparagine synthetase (AS). Here we show that deletion of AS in Plasmodium berghei (Pb) delays the asexual-and liver-stage development with substantial reduction in the formation of ookinetes, oocysts and sporozoites in mosquitoes. In the absence of asparagine synthesis, extracellular asparagine supports suboptimal survival of PbAS knockout (KO) parasites. Depletion of blood asparagine levels by treating PbASKO-infected mice with asparaginase completely prevents the development of liver stages, exflagellation of male gametocytes and the subsequent formation of sexual stages. In vivo supplementation of asparagine in mice restores the exflagellation of PbASKO parasites. Thus, the parasite life cycle has an absolute requirement for asparagine, which we propose could be targeted to prevent malaria transmission and liver infections.

Nonequilibrium statistical mechanics of one-dimensional turbulence

The method of statistical mechanics is applied to the study of the one-dimensional model of turbulence proposed in an earlier paper. The closure problem is solved by the variational approach which has been developed for the three-dimensional case, yielding two integral equations for two unknown functions. By solving the two integral equations, the Kolmogorov k���5/3 law is derived and the (one-dimensional) Kolmogorov constant Ko is evaluated, obtaining Ko=0.55, which is in good agreement with the result of numerical experiments on one-dimensional turbulence.

Variational approach to the closure problem of turbulence theory

A new method is proposed to solve the closure problem of turbulence theory and to drive the Kolmogorov law in an Eulerian framework. Instead of using complex Fourier components of velocity field as modal parameters, a complete set of independent real parameters and dynamic equations are worked out to describe the dynamic states of a turbulence. Classical statistical mechanics is used to study the statistical behavior of the turbulence. An approximate stationary solution of the Liouville equation is obtained by a perturbation method based on a Langevin-Fokker-Planck (LFP) model. The dynamic damping coefficient eta of the LFP model is treated as an optimum control parameter to minimize the error of the perturbation solution; this leads to a convergent integral equation for eta to replace the divergent response equation of Kraichnan's direct-interaction (DI) approximation, thereby solving the closure problem without appealing to a Lagrangian formulation. The Kolmogorov constant Ko is evaluated numerically, obtaining Ko = 1.2, which is compatible with the experimental data given by Gibson and Schwartz, (1963).

Influencia del GSD en la orientaci��n de un bloque fotogram��trico

Direcciones de correo electr��nico de las autoras: Edurne Ortiz de Elguea (txintxe1989@holmail.com) y Priscila Garc��a (pelukina06@hotmail.com).

La estructura y propiedades magn��ticos de las nanopart��culas de Fe50Ni50 obtenidas mediante el m��todo de explosi��n el��ctrica de hilo

[Es]Actualmente ninguna ��rea cient��fica es ajena a la revoluci��n de la nanociencia; las nanopart��culas atraen el inter��s de muchos investigadores desde el punto de vista de la ciencia fundamental y para sus aplicaciones tecnol��gicas. Las nanopart��culas ofrecen la posibilidad de fabricar sensores que sean capaces de detectar desde un virus hasta concentraciones de substancias pat��genas que no pueden ser detectadas por los m��todos convencionales. Hoy en d��a existes 82 tratamientos contra el c��ncer basadas en la utilizaci��n de nanopart��culas y los materiales composite con nanopart��culas se utilizan como medio de protecci��n frente la radiaci��n del rango de microondas. En la rama de ciencias ambientales, las nanopart��culas met��licas sirven como materiales anticontaminantes. En este trabajo se ha estudiado la estructura y las propiedades magn��ticas de las nanopart��culas de FeNi preparadas mediante el m��todo de explosi��n el��ctrica de hilo. Con la t��cnica de Rayos���X(DRX) se ha determinado que las nanopart��culas se cristalizan en un sistema c��bico FCC con un par��metro de celda de 3.596 ��, tambi��n, se ha obtenido el tama��o de dominio coherente que es de 35 nm. La muestra se ha sometido a un programa de temperatura controlada para seguir la evoluci��n de la estructura cristalina y del tama��o del cristal, tanto en atm��sfera oxidante como en vac��o. Para el aprendizaje de los microscopios utilizados en este trabajo, se ha asistido al curso ���Fundamentos de microscopia electr��nica de barrido y microan��lisis��� impartido por SGIker de la UPV/EHU. Se han empleado los microscopios electr��nicos SEM y TEM para obtener im��genes de gran resoluci��n de la muestra y analizar su contenido elemental. Partiendo de las im��genes sacadas por el SEM se ha calculado el valor medio del tama��o de las part��culas de la muestra, 58 nm. Mediante el Mastersizer 2000 se ha medido el tama��o de las part��culas y/o agregados por m��todo de difracci��n l��ser, disgregando la muestra todo lo posible hasta conseguir el tama��o medio que se aproxime al de una sola part��cula, 100nm. Por ��ltimo, para la caracterizaci��n magn��tica se ha servido del VSM que mide el momento magn��tico de una muestra cuando ��sta vibra en presencia de un campo magn��tico est��tico, consiguiendo una imanaci��n de saturaci��n de 125 emu/g. Hemos fabricado y caracterizado las nanopart��culas magn��ticas de hierro-n��quel y los resultados obtenidos han sido enviados a un congreso especializado de ciencia de materiales (ISMANAM - 2013, Italia).

Localizaci��n gr��fica de los expedientes patrimoniales de Vitoria en el AHPA

Direcciones de correo electr��nico de las autoras: amaya999@hotmail.com ; nagores@hotmail.es

New Oncogenic Drivers in Hepatocellular Carcinoma: Role of the RNA Binding Protein Hu antigen R

156 p. : graf.

GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus

Background: Type-1 cannabinoid receptors (CB1R) are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that participates in homeostatic and behavioral functions including food intake. Although CB1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. Methodology/Principal Findings: Light and electron microscopy techniques were used to analyze CB1R distribution in the VMH of CB1R-WT, CB1R-KO and conditional mutant mice bearing a selective deletion of CB1R in cortical glutamatergic (Glu-CB1R-KO) or GABAergic neurons (GABA-CB1R-KO). At light microscopy, CB1R immunolabeling was observed in the VMH of CB1R-WT and Glu-CB1R-KO animals, being remarkably reduced in GABA-CB1R-KO mice. In the electron microscope, CB1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB1R immunopositive profiles and CB1R density in terminals making asymmetric or symmetric synapses in CB1R-WT mice. Furthermore, the proportion of CB1R immunopositive terminals/preterminals in CB1R-WT and Glu-CB1R-KO mice was reduced in GABA-CB1R-KO mutants. CB1R density was similar in all animal conditions. Finally, the percentage of CB1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB1R-KO mutants relative to CB1R-WT mice, indicating that CB1R was distributed in cortical and subcortical excitatory synaptic terminals. Conclusions/Significance: Our anatomical results support the idea that the VMH is a relevant hub candidate in the endocannabinoid-mediated modulation of the excitatory and inhibitory neurotransmission of cortical and subcortical pathways regulating essential hypothalamic functions for the individual's survival such as the feeding behavior.

Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis

Pannexin1 (Panx1) is a plasma membrane channel permeable to relatively large molecules, such as ATP. In the central nervous system (CNS) Panx1 is found in neurons and glia and in the immune system in macrophages and T-cells. We tested the hypothesis that Panx1-mediated ATP release contributes to expression of Experimental Autoimmune Encephalomyelitis (EAE), an animal model for multiple sclerosis, using wild-type (WT) and Panx1 knockout (KO) mice. Panx1 KO mice displayed a delayed onset of clinical signs of EAE and decreased mortality compared to WT mice, but developed as severe symptoms as the surviving WT mice. Spinal cord inflammatory lesions were also reduced in Panx1 KO EAE mice during acute disease. Additionally, pharmacologic inhibition of Panx1 channels with mefloquine (MFQ) reduced severity of acute and chronic EAE when administered before or after onset of clinical signs. ATP release and YoPro uptake were significantly increased in WT mice with EAE as compared to WT non-EAE and reduced in tissues of EAE Panx1 KO mice. Interestingly, we found that the P2X7 receptor was upregulated in the chronic phase of EAE in both WT and Panx1 KO spinal cords. Such increase in receptor expression is likely to counterbalance the decrease in ATP release recorded from Panx1 KO mice and thus contribute to the development of EAE symptoms in these mice. The present study shows that a Panx1 dependent mechanism (ATP release and/or inflammasome activation) contributes to disease progression, and that inhibition of Panx1 using pharmacology or gene disruption delays and attenuates clinical signs of EAE.

Distribuci��n de "coxiella burnetii" en los rumiantes dom��sticos y en la fauna silvestre de la Comunidad Atut��noma Vasca. Evaluaci��ndel efecto del tratamiento antibi��tico y de la vacunaci��n en el control de la fiebre Q en reba��os ovinos naturalmente infectados

243 p. : il.

TWEAK/Fn14 Signaling Is Required for Liver Regeneration after Partial Hepatectomy in Mice

Background & Aims: Pro-inflammatory cytokines are important for liver regeneration after partial hepatectomy (PH). Expression of Fibroblast growth factor-inducible 14 (Fn14), the receptor for TNF-like weak inducer of apoptosis (TWEAK), is induced rapidly after PH and remains elevated throughout the period of peak hepatocyte replication. The role of Fn14 in post-PH liver regeneration is uncertain because Fn14 is expressed by liver progenitors and TWEAK-Fn14 interactions stimulate progenitor growth, but replication of mature hepatocytes is thought to drive liver regeneration after PH. Methods: To clarify the role of TWEAK-Fn14 after PH, we compared post-PH regenerative responses in wild type (WT) mice, Fn14 knockout (KO) mice, TWEAK KO mice, and WT mice treated with anti-TWEAK antibodies. Results: In WT mice, rare Fn14(+) cells localized with other progenitor markers in peri-portal areas before PH. PH rapidly increased proliferation of Fn14(+) cells; hepatocytic cells that expressed Fn14 and other progenitor markers, such as Lgr5, progressively accumulated from 12-8 h post-PH and then declined to baseline by 96 h. When TWEAK/Fn14 signaling was disrupted, progenitor accumulation, induction of pro-regenerative cytokines, hepatocyte and cholangiocyte proliferation, and over-all survival were inhibited, while post-PH liver damage and bilirubin levels were increased. TWEAK stimulated proliferation and increased Lgr5 expression in cultured liver progenitors, but had no effect on either parameter in cultured primary hepatocytes. Conclusions: TWEAK-FN14 signaling is necessary for the healthy adult liver to regenerate normally after acute partial hepatectomy.

Caracterizaci��n de los dep��sitos fluviales del r��o Ebro en la cuenca de Miranda de Ebro (Burgos)

[ES] La evoluci��n fluvial del r��o Ebro ha sido analizada de forma desigual, siendo m��s numerosas las investigaciones centradas en su curso medio y bajo. En este trabajo se describe el sistema de terrazas fluviales elaborado por el r��o Ebro a su paso por la Cuenca de Miranda de Ebro (��lava ��� Burgos). Se han reconocido cinco niveles de terrazas (T1-T5) mediante su an��lisis estratigr��fico, morfol��gico y sedimentol��gico. Las terrazas se sit��an a unas alturas que oscilan entre los 68 y los 5 m sobre el nivel actual del r��o Ebro. El relleno sedimentario de los niveles m��s elevados (T1-T4) est�� compuesto por gravas polig��nicas bien clasificadas y muy redondeadas con presencia puntual de niveles de arenas; mientras que el nivel m��s bajo (T5) est�� constituido enteramente por part��culas finas. Los resultados apuntan hacia variaciones de caudal y aportes sedimentarios, en relaci��n con las oscilaciones clim��ticas cuaternarias, como los factores que gobiernan la evoluci��n fluvial en la Cuenca de Miranda de Ebro, en coherencia con los modelos de evoluci��n propuestos para otros puntos de la cuenca hidrogr��fica