Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D-1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia.

Recognition of Membrane-Bound Fusion-Peptide/MPER Complexes by the HIV-1 Neutralizing 2F5 Antibody : Implications for Anti-2F5 Immunogenicity

13 p.

Structural Basis for Feed-Forward Transcriptional Regulation of Membrane Lipid Homeostasis in Staphylococcus aureus

11 p.

Development of catalytic methane reforming systems integrating hydrogen selective PdCu membrane modules

En la presente tesis doctoral se ha estudiado la integración del proceso de producción de hidrógeno con su purificación mediante el empleo de membranas selectivas de hidrógeno. La producción de hidrógeno se realiza empleando catalizadores no convencionales de níquel soportado sobre magnesia y alúmina en un reactor catalítico. Se analiza la actividad de los catalizadores y la producción de hidrógeno mediante distintos procesos con metano como son la oxidación parcial catalítica (OPC), OPC húmeda y reformadoLa purificación de hidrógeno se realiza en un módulo provisto de una membrana selectiva de hidrógeno de PdCu depositado en un soporte poroso cerámico. Una vez optimizada su preparación mediante deposición no electrolítica se caracterizan. Para ello se determina su permeabilidad a distintas temperaturas y realizando ciclos térmicos en atmósferas inerte y de hidrógeno, que puede fragilizar el metal. Una vez preparados los catalizadores y las membranas se integran los dos sistemas y se determinan los parámetros de operación óptimos como la presión de la línea de alimentación y el caudal de gas de arrastre en el módulo de membrana. Ambos parámetros se optimizan para lograr la máxima recuperación de hidrógeno en el módulo de membrana. Por últimos se realizan ensayos completos de producción y purificación, que permiten observar el rendimiento del sistema y también el efecto que los compuestos de la mezcla compleja alimentada a las membranas tienen en su comportamiento. Para concluir la integración de procesos se realizan ensayos añadiendo azufre de forma que el sistema sea más similar al proceso real. Esto permite también analizar el efecto del azufre tanto en los catalizadores como en las membranas.

Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1

Dynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G), bundle signaling element (BSE) and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH) domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL). Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.

Membrane activities of Dynamin-related protein 1 (DRP1) and BCL2-related Ovarian Killer (BOK)

311 p.

Low Effort L-i Nuclear Fusion Plasma Control Using Model Predictive Control Laws

One of the main problems of fusion energy is to achieve longer pulse duration by avoiding the premature reaction decay due to plasma instabilities. The control of the plasma inductance arises as an essential tool for the successful operation of tokamak fusion reactors in order to overcome stability issues as well as the new challenges specific to advanced scenarios operation. In this sense, given that advanced tokamaks will suffer from limited power available from noninductive current drive actuators, the transformer primary coil could assist in reducing the power requirements of the noninductive current drive sources needed for current profile control. Therefore, tokamak operation may benefit from advanced control laws beyond the traditionally used PID schemes by reducing instabilities while guaranteeing the tokamak integrity. In this paper, a novel model predictive control (MPC) scheme has been developed and successfully employed to optimize both current and internal inductance of the plasma, which influences the L-H transition timing, the density peaking, and pedestal pressure. Results show that the internal inductance and current profiles can be adequately controlled while maintaining the minimal control action required in tokamak operation.