The tumour microenvironment links complement system dysregulation and hypoxic signalling.

The complement system is an innate immune pathway typically thought of as part of the first line of defence against "non-self" species. In the context of cancer, complement has been described to have an active role in facilitating cancer-associated processes such as increased proliferation, angiogenesis and migration. Several cellular members of the tumour microenvironment express and/or produce complement proteins locally, including tumour cells. Dysregulation of the complement system has been reported in numerous tumours and increased expression of complement activation fragments in cancer patient specimens correlates with poor patient prognosis. Importantly, genetic or pharmacological targeting of complement has been shown to reduce tumour growth in several cancer preclinical models, suggesting that complement could be an attractive therapeutic target. Hypoxia (low oxygen) is frequently found in solid tumours and has a profound biological impact on cellular and non-cellular components of the tumour microenvironment. In this review, we focus on hypoxia since this is a prevailing feature of the tumour microenvironment that, like increased complement, is typically associated with poor prognosis. Furthermore, interesting links between hypoxia and complement have been recently proposed but never collectively reviewed. Here, we explore how hypoxia alters regulation of complement proteins in different cellular components of the tumour microenvironment, as well as the downstream biological consequences of this regulation

Cambio climático y política turística en España: diagnóstico del litoral mediterráneo español

El litoral mediterráneo español es una de las áreas de Europa donde pueden ser másevidentes los cambios en las condiciones climáticas durante las próximas décadas. Lasubida de temperaturas y el descenso de precipitaciones son factores que obligan a tomarmedidas de adaptación que reduzcan el disconfort térmico previsto y la escasez de recursosde agua convencional derivada de una disminución de las lluvias. La actividad turísticaes un sector vulnerable ante el cambio climático y sus riesgos asociados y ha de ir adaptándosea la nueva realidad climática prevista. Junto a los protocolos internacionales dereducción de emisiones de gases de efecto invernadero, se han puesto en marcha planesde adaptación al cambio climático, con medidas concretas para cada sector económico.Se analizan las políticas de adaptación al cambio climático desarrolladas en España enlos últimos años, con especial detalle en las regiones del litoral mediterráneo, por la granimportancia económica y territorial de la actividad turística en ellas y los preocupantesefectos que se señalan en los modelos de cambio climático para las próximas décadas enestos territorios

Reconstruction of thermal local signal from statistical downscaling (SD) through artificial neuronal network: detection of local patterns of change in Valencia Region (Spain) (1948-2011)

Para el área de la Comunidad Valenciana (España) se dispone de más de 300 series de temperatura diaria de las que sólo 3 cubren por completo el periodo 1948-2011, y una mayoría menos de la mitad de dicho periodo. El presente trabajo busca reconstruir todas las señales térmicas locales que faltan en el periodo completo 1948-2011 a partir del reanálisis NCEP/NCAR en dicho periodo. Para ello se realiza un downscaling estadístico con los datos observados por medio de una ANN. Ello ha permitido detectar patrones locales de cambio climático que han sido consistentes a lo largo del espacio y tiempo. Estos patrones señalan una tendencia mayor al calentamiento en las partes altas de los relieves y áreas de montaña, y menor en el fondo de los valles. El valor del estudio reside en la detección de las áreas potencialmente más vulnerables al cambio térmico, más que en una determinación exacta de una magnitud global de cambio térmico.For the area of Valencia (Spain) is available more than 300 daily temperature series of which only three cover completely the period from 1948 to 2011, and a majority less than half of that period. This work seeks to reconstruct all missing local thermal signals for the whole period 1948-2011 from the NCEP/NCAR reanalysis availability in that period. To do this, a statistical downscaling is performed with the observed data available through an ANN. This allowed us to detect local patterns of climate change that have been consistent over time and space. These patterns indicate substantially a greater warming tendency in the upper parts of the reliefs and mountain areas, and lower in the valley bottoms and lower lands. The value of the study lies primarily in identifying areas potentially more vulnerable to thermal change, rather than the accurate determination of a global magnitude of thermal change

Statistical downscaling and attribution of air temperature change patterns in the Valencia region (1948–2011)

This study is based on the statistical downscaling and spatial interpolation of high-resolution temperatures (90 m) over the 1948–2011 period performed for the Valencia Region (east Iberian Peninsula) after considering local topographical factors in the fine-scale distribution of temperatures. The objective was to detect the areas that were potentially more vulnerable to air temperature change. This allowed the detection of local climate change patterns, which were analyzed and found to be consistent in spatial and temporal terms. These patterns indicate a more marked warming tendency in higher parts of reliefs and their slopes. However, this tendency is less pronounced in bottoms of valleys and on coastal plains, particularly for minimum temperatures, while the tendency for increasing maximum temperatures becomes more generalised. These patterns seem to connect well with regional changes in pressure fields, wind frequency, precipitation patterns and sea surface temperature.This work has been made possible thanks to the Foundation ‘Centro de Estudios Ambientales del Mediterráneo’ (CEAM) located in Valencia, Spain, the University Institute ‘Instituto Interuniversitario de Geografía’ of the University of Alicante, the University Department ‘Departamento de Geografía’ of the University of Valencia and the Spanish Ministry of Economy and Competitiveness through Project no. CGL2011-30433-C02 (Termed)

Replication stress and chromatin context link ATM activation to a role in DNA replication

ATM-mediated signaling in response to DNA damage is a barrier to tumorigenesis. Here we asked whether replication stress could also contribute to ATM signaling. We demonstrate that, in the absence of DNA damage, ATM responds to replication stress in a hypoxia-induced heterochromatin-like context. In certain hypoxic conditions, replication stress occurs in the absence of detectable DNA damage. Hypoxia also induces H3K9me3, a histone modification associated with gene repression and heterochromatin. Hypoxia-induced replication stress together with increased H3K9me3 leads to ATM activation. Importantly, ATM prevents the accumulation of DNA damage in hypoxia. Most significantly, we describe a stress-specific role for ATM in maintaining DNA replication rates in a background of increased H3K9me3. Furthermore, the ATM-mediated response to oncogene-induced replication stress is enhanced in hypoxic conditions. Together, these data indicate that hypoxia plays a critical role in the activation of the DNA damage response, therefore contributing to this barrier to tumorigenesis

Spatial Planning Response to the Challenges of Climate Change Adaptation: An Analysis of Selected Instruments and Good Practices in Europe

The task of combining objectives, spatial planning instruments, and climate change adaptation targets is a complex endeavour that varies across countries. There is a call for a universal discussion on how spatial planning should respond to climate change challenges. To address this issue, this article delves into the approaches taken by Greece, Spain, Portugal, and Poland, aiming to explore how spatial planning instruments support climate change adaptation goals. The authors, based on a jointly extracted questionnaire, identified what they consider to be the most relevant examples of instruments to use to ensure the integration of spatial planning objectives and the response to climate challenges. The identified solutions are compared in detail. Three key spatial planning themes emerged in this study: investment in renewable energy, the development and preservation of green infrastructure, and the protection of coastal zones. This article examines the systemic solutions found in these countries, discusses the role of both classical and sectoral spatial planning instruments, and identifies the level of public authority responsible for key interventions. It shows that instruments developed at the supra-local level should support local authorities by providing them with legal and substantive arguments for developing solutions relevant to climate challenges.This work was funded by Fundação para a Ciência e a Tecnologia (FCT; Portugal) through the strategic projects UIDB/04292/2020 and UIDP/04292/2020 granted to Marine and Environmental Sciences Centre (MARE), and the project LA/P/0069/2020 granted to Associate Laboratory Aquatic Research Network (ARNET)

Competencias por el uso del agua en la provincia de Alicante: experiencias de gestión en la armonización de usos urbano-turísticos y agrícolas

La disponibilitat d’aigua en quantitat i qualitat és un factor decisiu per atendre les demandes urbanes, turístiques i agrícoles en territoris amb escassesa natural de recursos. A la província d’Alacant, a fi de garantir aquestes demandes s’ha recorregut a solucions hidràuliques tradicionals, com ara transvasaments i explotació d’aqüífers, unides a la utilització creixent de fonts no convencionals i a l’increment de l’eficiència de l’ús de l’aigua, com també a unes altres solucions basades en l’harmonització de diversos usos. S’analitzen els models més importants desenvolupats a Alacant per a l’harmonització d’usos de l’aigua urbanoturístics i agrícoles: la gestió col·lectiva d’aqüífers sobreexplotats (Junta Central d’Usuaris del Vinalopó) i els acords subscrits entre el medi urbà i els agricultors basats en l’intercanvi d’aigües depurades i aigües netes per utilitzar-les en el regadiu i els usos urbanoturístics, respectivament (Consorci d’Aigües de la Marina Baixa). Es posa de manifest la importància creixent de les aigües residuals regenerades per a l’harmonització d’usos urbanoturístics i agrícoles de l’aigua.Water availability in quantity and quality is a decisive factor to attend the urban, tourist and agricultural demands in areas with natural scarcity of resources. In the province of Alicante in order to ensure these demands, it has been resorted to hydraulic traditional solutions such as transfers and aquifers exploitation and new ones as growing use of non-conventional sources, increasing the efficiency of water use and others based on the harmonization of different uses. In this paper, it is analyzed the most important models developed in Alicante for harmonizing tourist and agricultural water uses: the collective management of overexploited aquifers (Junta Central de Usuarios del Vinalopó) and the agreements signed between urban areas and farmers based on the exchange of wastewater and clean water for its use in irrigation and tourism activities, respectively (Consorcio de Aguas de la Marina Baja). It is highlighted the growing importance of sewage regenerated for harmonizing tourist and agricultural water uses.La disponibilidad de agua en cantidad y calidad es un factor decisivo para atender las demandas urbanas, turísticas y agrícolas en territorios con escasez natural de recursos. En la provincia de Alicante, a fin de garantizar estas demandas se ha recurrido a soluciones hidráulicas tradicionales, como trasvases y explotación de acuíferos, unidas al creciente empleo de fuentes no convencionales y al incremento de la eficiencia del uso del agua, así como a otras basadas en la armonización de distintos usos. Se analizan los modelos más importantes desarrollados en Alicante para la armonización de usos del agua urbanoturísticos y agrícolas: la gestión colectiva de acuíferos sobreexplotados (Junta Central de Usuarios del Vinalopó) y los acuerdos suscritos entre el medio urbano y los agricultores basados en el intercambio de aguas depuradas y aguas limpias para su empleo en el regadío y los usos urbano-turísticos, respectivamente (Consorcio de Aguas de la Marina Baja). Se pone de manifiesto la importancia creciente de las aguas residuales regeneradas para la armonización de usos urbano-turísticos y agrícolas del agua

Algunas consideraciones sobre la masa (o masa no hay más que una)

This article presents sorne reasoned arguments against relativistic mass as a basic concept in Theory of Special Relativity. Relativistic mass limitations are examined and invariant mass is defended as the only one. Finally, a didactic proposal, consistent with the use of invariable mass, is presented in order to introducing rnass and energy concepts at Bachillerato

Abandono de terrazas de cultivo: recolonización vegetal y erosión en el sureste peninsular

[Resumen] El paisaje del sureste peninsular ha estado marcado, en los últimos decenios, por los cambios en los aprovechamientos de las laderas subáridas. Frente a concepciones lineales de los procesos erosivos que afectan a estos espacios, la metodología empleada y los resultados obtenidos evidencian la necesidad de abordar este tema con planteamientos puramente geográficos, donde se valora el papel de los factores abióticos y bióticos del medio, sin olvidar que ambos son decisivos en la comprensión y explicación del paisaje desde una visión antropocéntrica.[Abstract] In the last decades the southeast peninsular landscape has been affected by the changes in the used subarid slopes. Opposite to lineal conceptions of erosive processes in these areas, the employed methodology and the obtained resu1ts show the need to research this subject with purely geographic patterns in which the abiotic and biotic factors are valued without forgetting that both are decisives in the understanding and explication of the lanscape from an human perspectiv