Never-resting microglia: physiological roles in the healthy brain and pathological implications

Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic will review the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic will discuss the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the maintenance of the blood brain barrier; the regulation of adult neurogenesis and hippocampal learning; and neuronal survival, among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic will also summarize the current view of microglial nomenclature, phenotypes, origin and differentiation, sex differences, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state will be discussed. In conclusion, this Research Topic seeks to emphasize how the current research in neuroscience is challenged by never-resting microglia.

From the Cajal alumni Achucarro and Rio-Hortega to the rediscovery of never-resting microglia

Under the guidance of Ramon y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the twentieth century, Nicolas Achucarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pio del Rio-Hortega developed modifications of Achucarro's methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal's own views on cells that he thought belonged to the same class as oligodendroglia (the so called "third element" of the nervous system), leading to a long-standing discussion. It was only in 1924 that Rio-Hortega's observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely "resting," and their contribution as "activated" cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: "resting" microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal's school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their causal relationship to diseases.

Evaluación del proyecto de Madrid 2012 bajo un enfoque de mercado. Una exploración de posibilidades y mejoras

[ES] Desde que el 24 de abril de 1966 Madrid perdiera frente a Munich la votación para ser elegida como ciudad organizadora de los Juegos Olímpicos de 1972, la ciudad nunca había estado tan cerca de la organización de unas Olimpiadas.

El desarrollo exportador de las pymes industriales españolas participantes en un consorcio de exportación: un estudio de caso

[ES] Pese a los recientes esfuerzos realizados para dinamizarlos desde los organismos públicos competentes españoles, aún son relativamente pocos los consorcios de exportación realmente exitosos en España frente a los que ni llegan a constituirse o apenas sobreviven un tiempo. Por otra parte, también son escasos los estudios nacionales existentes en esta área. Este trabajo se centra en el análisis de las fases del proceso del desarrollo exportador de algunas pymes industriales españolas que participan en un consorcio de exportación, así como en los factores que influyen en la elección y funcionamiento de este mecanismo institucional colaborativo potencialmente eficaz para penetrar con mayor éxito en los mercados exteriores.

Ganadería, trasterminancia y trashumancia en los territorios vascos en el tránsito del medievo a la modernidad (siglos XV y XVI)

[ES] El presente artículo pretende aportar nuevos datos sobre la ganadería en los territorios vascos durante la Edad Moderna. Ante todo se trata de romper con falsos paradigmas que se han venido repitiendo durante largo tiempo, aportando datos inéditos. Los clásicos de la historiografía vasca siempre han recalcado el carácter rural y agrario de la economía vasca; a pesar de ello, actividades como la ganadería jamás han ocupado un espacio primordial como objeto de estudio entre los historiadores, que en muchos casos han aceptado las teorías de etnógrafos y antropólogos sin contrastarlas. La ganadería en tierras vascas siguió modelos cantábricos, que ya vienen siendo estudiados desde algunas décadas por los historiadores gallegos, asturianos o cántabros; escuelas que han establecido nuevas metodologías para el estudio de la ganadería, las cabañas predominantes, el régimen de explotación, su impacto económico, etc., y cuyo ejemplo desgraciadamente no ha sido secundado en el caso vasco.

Clasicismo e Ilustración: modelos sin nostalgia

Javier Alonso Aldama, Cirilo García Román e Idoia Mamolar Sánchez (eds)

Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study

Background: This study aimed to examine factors associated with treatment adherence in first-episode psychosis (FEP) patients followed up over 8 years, especially involuntary first admission and stopping cannabis use. Methods: This prospective, longitudinal study of FEP patients collected data on symptoms, adherence, functioning,and substance use. Adherence to treatment was the main outcome variable and was categorized as ‘good’ or ‘bad’. Cannabis use during follow-up was stratified as continued use, stopped use, and never used. Bivariate and logistic regression models identified factors significantly associated with adherence and changes in adherence over the 8-year follow-up period. Results: Of the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission, 74.4% bad adherence,and 52% cannabis use. Good adherence at baseline was associated with Global Assessment of Functioning score (p = 0.019), Hamilton Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001). Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always good, 25% improved from bad to good. Among the improved adherence group, 95.7% had involuntary first admission and 38.9% stopped cannabis use. In the subgroup of patients with bad adherence at baseline, involuntary first admission and quitting cannabis use during follow up were associated with improved adherence. Conclusions: The long-term association between treatment adherence and type of first admission and cannabis use in FEP patients suggest targets for intervention to improve clinical outcomes.

Determinants of self-reported smoking and misclassification during pregnancy, and analysis of optimal cut-off points for urinary cotinine: a cross-sectional study

10 p.

Functional analysis of cancer-associated EGFR mutants using a cellular assay with YFP-tagged EGFR intracellular domain

Background: The presence of EGFR kinase domain mutations in a subset of NSCLC patients correlates with the response to treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Although most EGFR mutations detected are short deletions in exon 19 or the L858R point mutation in exon 21, more than 75 different EGFR kinase domain residues have been reported to be altered in NSCLC patients. The phenotypical consequences of different EGFR mutations may vary dramatically, but the majority of uncommon EGFR mutations have never been functionally evaluated. Results: We demonstrate that the relative kinase activity and erlotinib sensitivity of different EGFR mutants can be readily evaluated using transfection of an YFP-tagged fragment of the EGFR intracellular domain (YFP-EGFR-ICD), followed by immunofluorescence microscopy analysis. Using this assay, we show that the exon 20 insertions Ins770SVD and Ins774HV confer increased kinase activity, but no erlotinib sensitivity. We also show that, in contrast to the common L858R mutation, the uncommon exon 21 point mutations P848L and A859T appear to behave like functionally silent polymorphisms. Conclusion: The ability to rapidly obtain functional information on EGFR variants of unknown relevance using the YFP-EGFR-ICD assay might prove important in the future for the management of NSCLC patients bearing uncommon EGFR mutations. In addition, our assay may be used to determine the response of resistant EGFR mutants to novel second-generation TKIs.

‘Terentius Culleo’, entre Boccaccio y Petrarca

Coordinardor: I. Ruiz Arzalluz. Editores: A. Martínez Sobrino, M. T. Muñoz García de Iturrospe, I. Ortigosa Egiraun, E. San Juan Manso. (Anejos de Veleia, Series Minor, 32)

Breaking the 400 ppm barrier: Physical and Social implications of the recent CO2 rise

6 p.

Rompiendo la barrera de las 400 ppm: implicaciones físicas y sociales del reciente aumento de CO2

6 p.

400 ppm-ko langa hautsi da: CO2-kontzentrazioaren igoeraren ondorio fisiko eta sozialak

6 p.

Reinventando los museos

Cap. 1. Museos en la posmodernidad : restos y desafíos. Iñaki Arrieta Urtizberea. Cap. 2. Never let a crisis go to waste. John Coppola. Cap. 3. Logique du don et biens communs : réinventer le musée. François Mairesse. Cap. 4. Procesos de hibridación: la evolución de las infraestructuras museísticas, gestión independiente y autogestión como reinvención del sistema del arte. Nekane Aramburu. Cap. 5. Patrimoine et musées du XXIe. Lieux de vie fédérateurs d’actions sociales. Lieux de vie créateurs d’innovation. Annette Viel. Cap. 6. El museo etnográfico: su prolongada adaptación a la crisis. Experiencias en Galicia. Xosé C. Sierra Rodríguez. Cap. 7. Reflexiones en torno a una “refundación”: El nuevo Museu Marítim de Barcelona. Olga López Miguel. Cap. 8. “El museu de todos, el museo para todos”: la accesibilidad como política. Carme Comas Camacho. Cap. 9. Pedagogía pública en participación a través de la construcción de un retrato transmedia de un territorio: caso de estudio en el Barco Museo Mater. Margarita León Guereño, Izaskun Suberbiola Garbizu, Lierni Gartzia Telleria, Josu Aramberri Miranda, José Miguel Correa Gorospe. Cap. 10. ¿Hacia una gestión de museos en red (MGMenRED)?: postcrisis, benchmarking y Euskal Hiria. Karmele Barandiaran e Igor Calzada.

Uptake and factors that influence the use of 'sit less, move more' occupational intervention strategies in Spanish office employees

Background: Little is known about the types of 'sit less, move more' strategies that appeal to office employees, or what factors influence their use. This study assessed the uptake of strategies in Spanish university office employees engaged in an intervention, and those factors that enabled or limited strategy uptake. Methods: The study used a mixed method design. Semi-structured interviews were conducted with academics and administrators (n = 12; 44 +/- 12 mean SD age; 6 women) at three points across the five-month intervention, and data used to identify factors that influenced the uptake of strategies. Employees who finished the intervention then completed a survey rating (n = 88; 42 +/- 8 mean SD age; 51 women) the extent to which strategies were used [never (1) to usually (4)]; additional survey items (generated from interviewee data) rated the impact of factors that enabled or limited strategy uptake [no influence (1) to very strong influence (4)]. Survey score distributions and averages were calculated and findings triangulated with interview data. Results: Relative to baseline, 67% of the sample increased step counts post intervention (n = 59); 60% decreased occupational sitting (n = 53). 'Active work tasks' and 'increases in walking intensity' were the strategies most frequently used by employees (89% and 94% sometimes or usually utilised these strategies); 'walk-talk meetings' and ` lunchtime walking groups' were the least used (80% and 96% hardly ever or never utilised these strategies). 'Sitting time and step count logging' was the most important enabler of behaviour change (mean survey score of 3.1 +/- 0.8); interviewees highlighted the motivational value of being able to view logged data through visual graphics in a dedicated website, and gain feedback on progress against set goals. 'Screen based work' (mean survey score of 3.2 +/- 0.8) was the most significant barrier limiting the uptake of strategies. Inherent time pressures and cultural norms that dictated sedentary work practices limited the adoption of 'walk-talk meetings' and ` lunch time walking groups'. Conclusions: The findings provide practical insights into which strategies and influences practitioners need to target to maximise the impact of 'sit less, move more' occupational intervention strategies.