Laneratze enpresak Euskal Herrian : balio sozialaren kuantifikazioa

Gizartea eta hura inguratzen duenari enpresek garrantzia ematen hasi diren aldi baten bizi gara. Izan ere ez dugu pentsatzen dugun informazio beste eta ezin diogu berrikuntzak egunerokoak dituen egoera honi era onenean edota dauden baliabide onenekin aurre egin. Esate baterako ba al dakigu zein enpresa mota den mesedegarria administrazioarentzat eta ondorioz gizartearentzat? Eta zer diren Laneratze Enpresak? Zer den balio soziala? Kuantifikatu daitekeen? Eta erantzuna bai bada, nola? Sozietatearen erdiak baino gehiagok ez daki hauei zer erantzun, oraindik zalantza sortzen duten terminoak eta galderak direlako. Hori da lan honen erronka eta lan honen helburua, hauek argitzea, azaltzea, kontzeptuak benetan bereganatzea, praktikan jartzea eta horiengatik ondorio batzuk ateratzea. Hau da, Laneratze Enpresa eta balio sozialari buruzko teoria ikustea eta errealitatera eramatea aukeratutako Laneratze Enpresa bati aplikatuko zaion balio soziala kuantifikatzeko metodologia baten bitartez, horrela lortutako emaitzetatik zenbait ideia ondorioztatuko direlarik. Azken hori, lanaren ekarpenik nabarmenena eta lan eta ilusio gehien suposatu duena izan da: Laiene Jatetxea S.L. Laneratze Enpresari berak sortzen duen balio soziala kalkulatzea, SPOLY metodologiaren bitartez eta erakundearen zuzendariaren ezinbesteko laguntzaren bitartez. Zergatik izan da baliagarria analisi hau? Enpresa berarentzat eta bertako partaideentzat etorkizunean non edo nola hobetu behar duten ikusteko tresna izan delako, enpresak benetan sortzen duena kuantifikatzea ahalbidetu duelako; eta administrazioarentzat eta gizartearentzat, tipologia honetako enpresek eta balio sozialari garrantzia emateak eta ondorioz kalkulatzeak zer nolako onurak dakartzan ezagutarazteko ikerketa ona izan delako.

CGP37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger, protects neurons from excitotoxicity by blocking voltage-gated Ca2+ channels

Inhibition of the mitochondrial Na+/Ca2+ exchanger (NCLX) by CGP37157 is protective in models of neuronal injury that involve disruption of intracellular Ca2+ homeostasis. However, the Ca2+ signaling pathways and stores underlying neuroprotection by that inhibitor are not well defined. In the present study, we analyzed how intracellular Ca2+ levels are modulated by CGP37157 (10 mu M) during NMDA insults in primary cultures of rat cortical neurons. We initially assessed the presence of NCLX in mitochondria of cultured neurons by immunolabeling, and subsequently, we analyzed the effects of CGP37157 on neuronal Ca2+ homeostasis using cameleon-based mitochondrial Ca2+ and cytosolic Ca2+ ([Ca2+](i)) live imaging. We observed that NCLX-driven mitochondrial Ca2+ exchange occurs in cortical neurons under basal conditions as CGP37157 induced a decrease in [Ca-2](i) concomitant with a Ca2+ accumulation inside the mitochondria. In turn, CGP37157 also inhibited mitochondrial Ca2+ efflux after the stimulation of acetylcholine receptors. In contrast, CGP37157 strongly prevented depolarization-induced [Ca2+](i) increase by blocking voltage-gated Ca2+ channels (VGCCs), whereas it did not induce depletion of ER Ca2+ stores. Moreover, mitochondrial Ca2+ overload was reduced as a consequence of diminished Ca2+ entry through VGCCs. The decrease in cytosolic and mitochondrial Ca2+ overload by CGP37157 resulted in a reduction of excitotoxic mitochondrial damage, characterized here by a reduction in mitochondrial membrane depolarization, oxidative stress and calpain activation. In summary, our results provide evidence that during excitotoxicity CGP37157 modulates cytosolic and mitochondrial Ca2+ dynamics that leads to attenuation of NMDA-induced mitochondrial dysfunction and neuronal cell death by blocking VGCCs.

Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease

The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.

Paleobotánica del epipaleolítico y mesolítico vascos

Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas

Uros, genética, indígenas y colonos. A propósito de la Neolitización de Europa

El presente trabajo se ha preparado en el seno de los intereses de los proyectos de investigación: HAR2011-26364 “Las Comunidades humanas de la alta Cuenca del Ebro en la Transición Pleistoceno-Holoceno” del Ministerio de Ciencia e Innovación y CGL2009-12703-C03-03 “Geología, geocronología y paleobiología de los Yacimientos de la Sierra de Atapuerca” del Ministerio de Educación y Ciencia. Así mismo se encuadra en el trabajo del Grupo de Investigación en Prehistoria de la Universidad del País Vasco (UPV/EHU) IT-288-07/ UFI 11-09.

Arte medioambiental y ecología. Paradigmas de comprensión, interpretación y valoración de las relaciones entre arte y ecología (1960-2015)

549 pp. (Bibliogr. pp. 501-522) (Conclusiones pp. 467-483/ Conclusions pp. 484-497)

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

Combining rimonabant and fentanyl in a single entity: preparation and pharmacological results

Based on numerous pharmacological studies that have revealed an interaction between cannabinoid and opioid systems at the molecular, neurochemical, and behavioral levels, a new series of hybrid molecules has been prepared by coupling the molecular features of two well-known drugs, ie, rimonabant and fentanyl. The new compounds have been tested for their affinity and functionality regarding CB1 and CB2 cannabinoid and mu opioid receptors. In [S-35]-GTP.S (guanosine 5'-O-[gamma-thio] triphosphate) binding assays from the post-mortem human frontal cortex, they proved to be CB1 cannabinoid antagonists and mu opioid antagonists. Interestingly, in vivo, the new compounds exhibited a significant dual antagonist action on the endocannabinoid and opioid systems.

Parte de guerra del Batallón Euzko Indarra de ANV, firmado por el Comisario Político Bernabé Orbegozo y el Comisario General Luis Ruiz de Aguirre

Fecha: 18 de julio de 1937 / Unidad de ínstalación: Carpeta Rectorado - E-1 / Nº de pág.: 1 (Mecanografiada y firmas manuscritas)

Notificación de las posiciones ocupadas por el Batallón Euzko Indarra de ANV, firmada por ordén del Comisario político al Comisario General Luis Ruiz de Aguirre

Fecha: 19-7-1937 / Unidad de ínstalación: Carpeta Rectorado - E-2 / Nº de pág.: 1 (Mecanografiada y firma manuscrita del Delegado ayudante)

Inferring Population Genetic Structure in Widely and Continuously Distributed Carnivores: The Stone Marten (Martes foina) as a Case Study

The stone marten is a widely distributed mustelid in the Palaearctic region that exhibits variable habitat preferences in different parts of its range. The species is a Holocene immigrant from southwest Asia which, according to fossil remains, followed the expansion of the Neolithic farming cultures into Europe and possibly colonized the Iberian Peninsula during the Early Neolithic (ca. 7,000 years BP). However, the population genetic structure and historical biogeography of this generalist carnivore remains essentially unknown. In this study we have combined mitochondrial DNA (mtDNA) sequencing (621 bp) and microsatellite genotyping (23 polymorphic markers) to infer the population genetic structure of the stone marten within the Iberian Peninsula. The mtDNA data revealed low haplotype and nucleotide diversities and a lack of phylogeographic structure, most likely due to a recent colonization of the Iberian Peninsula by a few mtDNA lineages during the Early Neolithic. The microsatellite data set was analysed with a) spatial and non-spatial Bayesian individual-based clustering (IBC) approaches (STRUCTURE, TESS, BAPS and GENELAND), and b) multivariate methods [discriminant analysis of principal components (DAPC) and spatial principal component analysis (sPCA)]. Additionally, because isolation by distance (IBD) is a common spatial genetic pattern in mobile and continuously distributed species and it may represent a challenge to the performance of the above methods, the microsatellite data set was tested for its presence. Overall, the genetic structure of the stone marten in the Iberian Peninsula was characterized by a NE-SW spatial pattern of IBD, and this may explain the observed disagreement between clustering solutions obtained by the different IBC methods. However, there was significant indication for contemporary genetic structuring, albeit weak, into at least three different subpopulations. The detected subdivision could be attributed to the influence of the rivers Ebro, Tagus and Guadiana, suggesting that main watercourses in the Iberian Peninsula may act as semi-permeable barriers to gene flow in stone martens. To our knowledge, this is the first phylogeographic and population genetic study of the species at a broad regional scale. We also wanted to make the case for the importance and benefits of using and comparing multiple different clustering and multivariate methods in spatial genetic analyses of mobile and continuously distributed species.

Nombramiento de Luis Ruiz de Aguirre como Comisario Político de ANV, firmado por el jefe de operaciones del Ejército de Euzkadi

Fecha: 19-4-1937 / Unidad de ínstalación: Carpeta Rectorado - F-1 / Nº de pág.: 1 (mecanografiado y firma manuscrita)

Notificación de Leopoldo Gaspar a Luis Ruiz de Aguirre sobre el nombramiento de un comisario en el Regimiento de carros de combate

Fecha: 14-8-1937 / Unidad de ínstalación: Carpeta Rectorado - F-2 / Nº de pág.: 1 (mecanografiada y firma manuscrita)

Certificado del Delegado del Gobierno de Euzkadi en Bayona, Javier de Gortazar, expedido a Luis Ruiz de Aguirre, en el que se hace constar que forma parte del personal del Departamento de Agricultura del Gobierno de Euzkadi

Fecha: 1-9-1937 / Unidad de ínstalación: Carpeta Rectorado - F-3 / Nº de hojas: 1. Mecanografiado y firma manuscrita

Lymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.