Developmental critical period in genetic redox dysregulation: animal and human studies in schizophrenia

Converging evidence favors an abnormal susceptibility to oxidative stress in schizophrenia. Decreased levels of glutathione (GSH), the major cellular antioxidant and redox regulator, was observed in cerebrospinal-fluid and prefrontal cortex of patients. Importantly, abnormal GSH synthesis of genetic origin was observed: Two case-control studies showed an association with a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease associated genotypes (35% of patients) correlated with decreased GCLC protein, GCL activity and GSH content. Similar GSH system anomalies were observed in early psychosis patients. Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. In pharmacological and knock-out (KO) models, GSH deficit induces anomalies analogous to those reported in patients. (a) morphology: spine density and GABA-parvalbumine immunoreactivity (PV-I) were decreased in anterior cingulate cortex. KO mice showed delayed cortical PV-I at PD10. This effect is exacerbated in mice with increased DA from PD5-10. KO mice exhibit cortical impairment in myelin and perineuronal net known to modulate PV connectivity. (b) physiology: In cultured neurons, NMDA response are depressed by D2 activation. In hippocampus, NMDA-dependent synaptic plasticity is impaired and kainate induced g-oscillations are reduced in parallel to PV-I. (c) cognition: low GSH models show increased sensitivity to stress, hyperactivity, abnormal object recognition, olfactory integration and social behavior. In a clinical study, GSH precursor N-acetyl cysteine (NAC) as add on therapy, improves the negative symptoms and decreases the side effects of antipsychotics. In an auditory oddball paradigm, NAC improves the mismatched negativity, an evoked potential related to pre-attention and to NMDA receptors function. In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysregulation of GSH synthesis combined with environmental insults in early development represent a major risk factor contributing to the development of schizophrenia

Proyecto de diseño de las instalaciones de climatización y eléctrica de un local destinado a tareas de laboratorio y oficinas para una industria cerámica

El objetivo del presente proyecto será el definir, en su totalidad, las instalaciones de climatización/ventilación y eléctrica, de un local destinado a realizar las tareas de laboratorio de resistencia de materiales y oficinas para una industria cerámica. Esta iniciativa nace como una necesidad de este tipo de empresas a ofrecer unos productos de mayor calidad que la competencia, bastante dura en la zona donde se encuentran. Aún y la existencia de laboratorios homologados que ofrecen este tipo de servicios, se cree necesario este tipo de instalaciones, basados en la investigación de nuevos materiales y/o productos, pudiendo así ofrecer al cliente las máximas garantías de calidad de los productos finales obtenidos.

An expression of mixed animal model equations to account for different means and variances in the base population

This paper presents a general expression to predict breeding values using animal models when the base population is selected, i.e. the means and variances of breeding values in the base generation differ among individuals. Rules for forming the mixed model equations are also presented. A numerical example illustrates the procedure.

Mitochondrial DNA damage and animal longevity: insights from comparative studies

Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur, even under physiological conditions. Aging, in this chemical context, could be viewed as an entropic process, the result of chemical side reactions that chronically and cumulatively degrade the function of biological systems. Mitochondria are a main source of reactive oxygen species (ROS) and chemical sidereactions in healthy aerobic tissues and are the only known extranuclear cellular organelles in animal cells that contain their own DNA (mtDNA). ROS can modify mtDNA directly at the sugar-phosphate backbone or at the bases, producing many different oxidatively modified purines and pyrimidines, as well as single and double strand breaks and DNA mutations. In this scenario, natural selection tends to decrease the mitochondrial ROS generation, the oxidative damage to mtDNA, and the mitochondrial mutation rate in long-lived species, in agreement with the mitochondrial oxidative stress theory of aging.

The Rein-Deer Drawn from the living Animal

Stockton 1789

El modelo político italiano. Un laboratorio: de la tercera vía a la globalización

Italia, uno de los laboratorios socio-políticos de la postguerra, vive hoy una profunda crisis de sistema. La quiebra del Estado social clientelar, el declive de la democracia de los partidos y el fin del sistema de economía mixta han puesto en cuestión el modelo de Estado y de sociedad construido por los partidos populares surgidos de la resistencia. La crisis de este laboratorio se ha visto agravada por la desaparición de la escena política de las denominadas dos iglesias de Italia, el partido católico y el comunista, los cuales estructuraron durantes años la identidad de los italianos e impulsaron la modernización económica. En un contexto de metamorfosis social y política ha irrumpido un movimiento nacionalpopulista, que ha tomado forma política en actores políticos ajenos a los principios constituyentes de 1948, como el partido xénofo y segregacionista de la Lega Norte y la alianza política Forza Italia. La actual dialéctica del proceso de modernización capitalista, globalización económico-financiera verus comunitarismos étnicos-regionales, ha afectado de lleno a la sociedad italiana. El objetivo de este libro no es otro que el de aportar algo de luz a la crisis de este laboratorio, caracterizado por la dialéctica que se estableció entre la defensa de una tercera vía socio-política por parte de uno de los partidos comunistas más importantes de la postguerra y el proceso de modernización capitalista, el cual tiene sus últimas manifestaciones en la quiebra del Estado social y en la globalización económica.

Assessment of the discrimination of animal fat by FT_Raman spectroscopy

In recent years, there has been an increased attention towards the composition of feeding fats. In the aftermath of the BSE crisis all animal by-products utilised in animal nutrition have been subjected to close scrutiny. Regulation requires that the material belongs to the category of animal by-products fit for human consumption. This implies the use of reliable techniques in order to insure the safety of products. The feasibility of using rapid and non-destructive methods, to control the composition of feedstuffs on animal fats has been studied. Fourier Transform Raman spectroscopy has been chosen for its advantage to give detailed structural information. Data were treated using chemometric methods as PCA and PLS-DA which have permitted to separate well the different classes of animal fats. The same methodology was applied on fats from various types of feedstock and production technology processes. PLS-DA model for the discrimination of animal fats from the other categories presents a sensitivity and a specificity of 0.958 and 0.914, respectively. These results encourage the use of FT-Raman spectroscopy to discriminate animal fats.

Työminäkuva strategiaprosessissa. Case: Teknillinen korkeakoulu - Tietoliikenneohjelmistojen ja multimedian laboratorio

Tutkimuksen tavoitteena on selvittää työminäkuvan ja strategiaprosessin välistä yhteyttä laadullisen tutkimuksen keinoin. Tutkimus on luonteeltaan fenomenografinen eli se keskittyy selvittämään, miten ihmiset kokevat maailman ilmiöineen. Aineiston hankinnassa on hyödynnetty triangulaatiota eli ilmiötä tarkastellaan kolmen aineiston valossa. Aineistoa on kerätty haastatteluin, osallistuvalla havainnoinnilla sekä tutustumalla valmiisiin dokumentteihin, ja analysoitu koodaten ja luokitellen. Koska työntekijän ammatillinen identiteetti vaikuttaa hänen tapaansa ratkaista ongelmia ja tehdä päätöksiä, voidaan tutkimustuloksiin perustuen sanoa, että työminäkuva heijastuu strategiaprosesissa näkyvään ajatteluun ja käyttäytymiseen. Tulokset osoittavat myös, että strateginen työskentely kehittää työminäkuvaa edelleen. Resurssiperusteisen strategianmuodostuksen teoriaa soveltaen voidaan todeta olevan kyse jatkuvasta prosessissa, jossa kehitystä tapahtuu sekä organisaatio- että yksilötasolla