Una propuesta de la biología de sistemas para el estudio de enfermedades raras

El grupo de Bases Moleculares de la Proliferación Celular de la Universidad de Málaga estudia patologías muy poco convencionales. Su poca incidencia en la población, menos de cinco casos por cada diez mil habitantes, las convierten hoy en un gran reto para la ciencia y la investigació

Aminooxi análogos de histidina: una posible estrategia para modular la histidina descarboxilasa humana.

Congreso anual de la Sociedad Española de Bioquímica y Biología MolecularLa histamina (Hia) es una amina biógena implicada en procesos fisiológicos esenciales (respuesta inmune, neurotransmisión y otros). El desequilibrio de su metabolismo juega un destacado papel en muchas patologías. El control de los efectos adversos de Hia se ejerce únicamente modulando sus receptores (H1R-H4R). En células humanas, Hia se sintetiza por descarboxilación de la L-His, en la reacción dependiente de piridoxal 5-fosfato (PLP) que cataliza la histidina decarboxilasa (HDC, EC 4.1.1.22). La baja tasa de expresión y la inestabilidad de HDC han dificultado su caracterización estructural y funcional, y por tanto el desarrollo de estrategias basadas en su inhibición. Nuestra experiencia derivada de estudios in silico (modelado y dinámica molecular) y experimentales con HDC, nos permitió abordar la búsqueda de nuevas posibilidades. Mediante tecnología de “barrido virtual” dedujimos que un inhibidor competitivo efectivo debería ser aquel capaz de enlazarse eficientemente con el PLP formando una estructura similar al intermediario PLP-substrato. Debería también conservar el grupo imidazol para reforzar la afinidad por el sitio catalítico. Ambas características podían conseguirse utilizando el compuesto 4(5)-aminooximetilimidazol (O-IMHA). Esta hipótesis se ha contrastado experimentalmente sobre extractos de HDC humana purificada. Hemos comprobado que O-IMHA es capaz de formar una PLP-oxima en el centro catalítico de la enzima humana. Los resultados indican que O-IMHA puede constituir una cabeza de síntesis prometedora de inhibidores de HDC. Aprovechando el conocimiento actual sobre la estructura de la enzima proponemos las configuraciones más probables del aducto en el sitio catalítico y podremos desarrollar nuevos derivados con potencial traslacional. SAF2011-26518 y CVI-06585. CIBERER (ISCIII)Universidad de Málaga. Campus Internacional Andalucia Tec

Polyamines and other biogenic amines at the molecular basis of low prevalence diseases

Ponencia Invitada en el 3rd International Conference on PolyaminesBiogenic amines are amino acid-derived compounds involved in the most important physiological functions: cell proliferation and differentiation, immunity, neurotransmission and neuroendocrine system, fertility. Diseases are the result of unrecovered alterations in the balance of, at least, one of our physiological network modules. In addition to the most common diseases, there are described more than 6000 low prevalent/rare diseases (RD), most of them related to the any of the physiological processes mentioned above. Thus, the pleitropy of biogenic amines suggest they must be involved in wide spectrum of human RDs. Putative solutions for these orphan patients need efforts to integrate useful molecular, clinical and pharmacological information from other similar, but more prevalent pathologies. The major aim of our group is to contribute to this relational and integrative effort (Reyes-Palomares et al., 2013, PMID: 23437198). Arginine-derived polyamines (putrescine, spermidine and spermine) are absolutely required for cell proliferation. Thus, polyamine overproduction is related to cancer proliferation and progression, including rare neoplasias (i.e.: neuroblastoma). Polyamine synthesis also is a clear target to fight against protozoan infections (rare diseases in Europe). Impaired polyamine synthesis has been related to epithelial pathologies as psoriasis and hairless phenotypes. It is proven that spermine synthase deficit is in the origin of Snyder-Robinson syndrome (Pegg, 2014, PMID:24395705). Histamine is derived from histidine. It is considered a neurotransmitter and immune mediator also having roles in cell life and death equilibrium. In a recent review, using text-mining technologies, we locate more than 25 immune, inflammatory, neurological and neuroendocrine rare pathologies having histamine (and other biogenic amines, as serotonin and dopamine) as relevant elements in their origins and/or evolution (Pino-Ángeles et al., 2012, PMID: 22435405). In addition, we should also consider the histamine role played in malignant pathologies as mastocytosis, rare gastrointestinal carcinomas and fertility (Sánchez-Jiménez et al., 2013, PMID: 22435405). The gaps in our knowledge still are considerable (specially at the level of membrane-related biomolecular interactions), and further integrative efforts (including in silico-assisted approaches) are claimed to fill them, as this information may contribute to development of new and more efficient strategies of prevention and therapy for many biomedical problems (both prevalent and rare diseases), of course, after the appropriate pre-clinical validation and clinical trial phases. Funded by Ministerio de Economía y Competitividad (Grant SAF2011-26518 and contract from AMER Consortium, CDTI), Plan Andaluz de Investigación y Desarrollo (CVI-06585). CIBERER is an initiative of Instituto de Salud Carlos III.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Funded by Ministerio de Economía y Competitividad (Grant SAF2011-26518 and contract from AMER Consortium, CDTI), Plan Andaluz de Investigación y Desarrollo (CVI-06585). CIBERER is an initiative of Instituto de Salud Carlos III

The Spanish Long-term Care System. ENEPRI Research Report No. 88, 15 June 2010

Launched in January 2009, ANCIEN is a research project that runs for a 44-month period and involves 20 partners from EU member states. The project principally concerns the future of long-term care (LTC) for the elderly in Europe and addresses two questions in particular: 1) How will need, demand, supply and use of LTC develop? 2) How do different systems of LTC perform? This case study on Spain is part of the first stage in the project aimed at collecting the basic data and necessary information to portray long-term care in each country of the EU. It will be followed by analysis and projections of future scenarios on long-term care needs, use, quality assurance and system performance. State-of-the-art demographic, epidemiologic and econometric modelling will be used to interpret and project needs, supply and use of long-term care over future time periods for different LTC systems

Network perspective of histamine related diseases

Histamine is the most pleiotropic biogenic amine. Produced and stored by a limited set of cells—histaminergic neurons, enterochromaffin-like cells, and mast cells—it broadcasts intercellular communication signals to a wide variety of cell types through its tissue-specific receptors. The many molecular interactions of these receptors and other mediators result in complex cellular networks whose alteration result in disease. Therefore, complex diseases map to modules of these cellular networks in the diseasomes. In this communication, we survey the histamine cellular networks to map the histamine diseasome, presenting a network view of the pleiotropy of histamine and its role in several complex diseases.A.A. Moya is a CIBERER fellow. The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)]. This communication has the support of a travel grant "Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech"

Implementación de servicios de infraestructura tecnológica en sistema operativo gnu/linux zentyal server 6.2

El presente corresponde a la implementación y puesta en marcha de servicios de infraestructura tecnológica de un empresa/organización, utilizando el sistema operativo Zentyal 6.2, la cual es un OS GNU/Linux basado en Ubuntu; el propósito específico es implementar servicios de dominio, DNS, DHCP, cortafuegos, VPN, servicios de compartición de impresora, archivos en red y conexión por Proxy no Transparente, todo ello bajo el control del OS descrito.La instalación de los paquetes de servicios (software de terceros) se realizó con ayuda del asistente en Zentyal6.2; Se configura las interfaces de red para servicios de dominio grupo12.com, DHCP (ZonaVerde/LAN) y DNS(dinámico), en donde el DNS permite identificar IPv4 del dominio configurado; El cortafuegos requirió IPv4 de los sitios a “DENEGAR” toda vez que no se acepta reglas por dominio, lo cual se hizo necesario identificar previamente las IPs de dominios para las pruebas; El VPN requirió la creación de un servidor VPN y de certificados para cliente y servidor, así como un clienteVPN para la conexión por un túnel desde cliente hasta el servidor; O.S.Zentyal6.2. ha integrado adecuadamente el software de terceros para lograr las solucionesIT deseadas en una empresa/cliente, la cual, responde a lo esperado frente a implementación de servicios de los sistemas de seguridad de la infraestructura de red

Autophagy and polyglutamine diseases

AbstractIn polyglutamine diseases, an abnormally elongated polyglutamine tract results in protein misfolding and accumulation of intracellular aggregates. The length of the polyglutamine expansion correlates with the tendency of the mutant protein to aggregate, as well as with neuronal toxicity and earlier disease onset. Although currently there is no effective cure to prevent or slow down the progression of these neurodegenerative disorders, increasing the clearance of mutant proteins has been proposed as a potential therapeutic approach. The ubiquitin–proteasome system and autophagy are the two main degradative pathways responsible for eliminating misfolded and unnecessary proteins in the cell. We will review some of the studies that have proposed autophagy as a strategy to reduce the accumulation of polyglutamine-expanded protein aggregates and protect against mutant protein neurotoxicity. We will also discuss some of the currently known mechanisms that induce autophagy, which may be beneficial for the treatment of these and other neurodegenerative disorders

A role for antizyme inhibitor 2 in the biosynthesis and content of serotonin and histamine in mouse mast cells

Polyamines (putrescine, spermidine and spermine; PAs) are essential for the majority of living cells. Antizymes and antizyme inhibitors are key regulatory proteins of PA levels by affecting ornithine decarboxylase and PA uptake. In addition to PAs, mast cells (MC) synthesize and store in their granules histamine (Hia) and serotonin (5-HT), which are critical for their function. Our previous studies have indicated a metabolic interplay among PAs, Hia and 5-HT in this cell type. For instance, we showed that PAs affect Hia synthesis during early stages of IL-3-induced bone marrow cell differentiation into bone marrow derived MCs (BMMCs) and demonstrated that PAs are present in MC secretory granules and are important for granule homeostasis, including Hia storage and 5-HT levels. A few years ago, a novel antizyme inhibitor (AZIN2) was described whose expression is restricted to a few tissues and cell types including brain, testis and MCs. In MCs, it was recently proposed that AZIN2 could act as a local regulator of PA biosynthesis in association with 5-HT-containing granules and with 5-HT release following MC activation. To gain insight into the role of AZIN2 in the biosynthesis and storage of 5-HT and also Hia, we have generated BMMCs from both wild-type and transgenic mice with severe Azin2 hypomorphism, and have analyzed the content of PAs, 5-HT and Hia, and some elements of their metabolisms. Spermine and 5-HT levels were reduced in Azin2 hypomorphic BMMCs compared with wild-type controls, whereas the amount of Hia was increased. Accordingly, the level of tryptophan hydroxylase 1 (the key enzyme for 5-HT biosynthesis) was reduced and the amount of enzymatic activity of histidine decarboxylase (the enzyme responsible for Hia biosynthesis) was increased in Azin2 hypomorphic BMMCs. Taken together, our results show evidence that AZIN2 has an important role in the regulation of 5-HT and Hia biosynthesis and storage in MCsUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work was supported by SAF2011-26518 (MINECO, Spain) and P10-CVI-6585 and Bio-267 (Junta de Andalucia, Spain). CIBERER is an iniciative of Instituto de Salud Carlos III (Spain)

A role for antizyme inhibitor 2 in the biosynthesis and content of histamine and serotonin in mouse mast cells

Polyamines (putrescine, spermidine and spermine; PAs) are required for the survival of the majority of living cells. Antizymes and antizyme inhibitors are key regulatory proteins of PA levels by affecting ornithine decarboxylase, the rate-limiting biosynthetic enzyme, and PA uptake. In addition to PA, mast cells (MC) synthesize and store in their granules the biogenically active amines histamine (Hia) and serotonin (5-HT), which are of critical importance for their function. Previously, we have performed several studies in this cell type regarding the interplay between the metabolisms of PAs and Hia and 5-HT. Our results showed that PAs affect Hia synthesis during early stages of IL-3-induced bone marrow cell differentiation into bone marrow derived MCs (BMMCs) and demonstrated that PAs are present in MC secretory granules and are important for granule homeostasis, including Hia storage and 5-HT levels. A few years ago, a novel antizyme inhibitor (AZIN2) was described. In contrast to AZIN1, AZIN2 expression is restricted to a few tissues and cell types including brain, testis and MCs. In MCs, it was recently described that AZIN2 could act as a local regulator of PA biosynthesis in association with the 5-HT granule content and release. At present, our aim is to gain further insight into the role of AZIN2 in the biosynthesis, storage and release of both Hia and 5-HT. In this study, we have generated BMMCs from both wild-type and transgenic mice with severe Azin2 hypomorphism, and have analyzed the content of PAs, Hia and 5-HT, and some elements of their metabolisms. Both PAs and 5-HT levels were reduced in Azin2 hypomorphic BMMCs compared with wild-type controls, whereas the amount of Hia was increased. Accordingly, the level of tryptophan hydroxylase 1 (the key enzyme for 5-HT biosynthesis) was reduced and the amount of enzymatic activity of histidine decarboxylase (the enzyme responsible for histamine biosynthesis) was increased in Azin2 hypomorphic BMMCs. Taken together, our results show evidence that AZIN2 has an important role in the regulation of Hia and 5-HT biosynthesis and storage in MCs. Department of Molecular Biology and Biochemistry, and CIBER de Enfermedades Raras (CIBER-ER), Faculty of Sciences, University of Málaga, Málaga 29071, Spain. Corresponding author: I. Fajardo ([email protected]) This work was supported by SAF2011-26518 (MINECO, Spain) and P10-CVI-6585 and Bio-267 (Junta de Andalucia, Spain). CIBERER is an iniciative of Instituto de Salud Carlos III (Spain).Universidad de Málaga. Campus de Excelencia Internacional Andalucía-Tech. SAF2011-26518 (MINECO, Spain) and P10-CVI-6585 and Bio-267 (Junta de Andalucia, Spain. CIBERER is an iniciative of Instituto de Salud Carlos III (Spain)

Medición de emisiones contaminantes de vehículos con motor a gasolina, empleando prueba estática

Articulo de Investigación.The pollutant emissions of vehicles with gasoline engine are analyzed, carrying out a verification of polluting emissions with static test, which allows knowing the chemical composition of five combustion gases coming from the exhaust of cars: CO, CO, NOx and unburned hydrocarbons (HC) as well as excess oxygen (O2). Random tests of emissions of polluting gases of private vehicles will be carried out, taking as sample the vehicles that move to the facilities of the UAEM Nezahualcóyotl University Center. The results will be analyzed based on the criteria established in the pollutant emission standards established for the circulation of light automotive vehicles (NOM-041-SEMARNAT-2015, NOM 042-SEMARNAT-2003 and NOM-EM-167- SEMARNAT-2016 ). As a result of the investigation, the polluting emissions from car exhaust were measured, the relationship between the type of pollutant found, the possible causes or failures in the emission control systems of gasoline vehicles was established. The preventive maintenance strategieSecretaria de Investigación de la Universidad Autonoma del Estado de México, Proyectos UAEM con financiamiento