Holocene landscapes in the Serra de Arga (NW Portugal)

El diagrama polínico obtenido permite conocer la dinámica de la vegetación y los cambios en el paisaje durante el Holoceno en el entorno de la Serra de Arga. Las fechas obtenidas, permiten situar el inicio de la secuencia en relación con el evento climático GH-8.2 registrado en las secuencias de hielo de Groenlandia. Tras esta fase de regresión se registra una recuperación del bosque correlacionable con el óptimo climático de Holoceno y en la cual se constata el predominio de los robledales. Tras un corto episodio en el que se produce un hiato sedimentario, la secuencia se reanuda en una fase de marcada deforestación tras la cual se registra un fuerte incremento de Pinus relacionado con la proliferación de plantaciones forestales.The pollen diagram obtained allow us to understand the dynamics of vegetation and landscape changes during the Holocene in the vicinity of the Serra de Arga. The dates obtained are used to place the beginning of the sequence in relation to GH-8.2 climate event recorded in Greenland ice cores. After this phase of regression there is a forest recovery coincident with the Holocene climatic optimum in which notes the predominance of oak. After a short episode in which there is a sedimentary hiatus, the sequence is resumed in a phase of marked deforestation after which records a sharp increase in Pinus associated with the proliferation of forest plantations.Fundação Calouste Gulbenkia

Mechanistic investigation into the selective anticancer cytotoxicity and immune system response of surface-functionalised, dichloroacetate-loaded, UiO-66 nanoparticles

The high drug loading and excellent biocompatibilities of metal-organic frameworks (MOFs) have led to their application as drug delivery systems (DDSs). Nanoparticle surface chemistry dominates both biostability and dispersion of DDSs while governing their interactions with biological systems, cellular and/or tissue targeting, and cellular internalisation, leading to a requirement for versatile and reproducible surface functionalisation protocols. Herein, we explore not only the effect of introducing different surface functionality to the biocompatible Zr-MOF UiO-66, but also the efficacy of three surface modification protocols: (i) direct attachment of biomolecules (folic acid, biotin) introduced as modulators of UiO-66 synthetic, (ii) our previously reported ‘’click-modulation” approach to covalently attach polymers (poly(ethylene glycol), poly-L-lactide, poly-N-isopropylacrylamide) to the surface of UiO-66 through click chemistry, and (iii) surface ligand exchange, to postsynthetically coordinate folic acid, biotin and heparin to UiO-66. The innovative use of a small molecule with metabolic anticancer activity, dichloroacetic acid (DCA), as a modulator during synthesis is described, and found to be compatible with all three protocols, yielding surface-coated, DCA-loaded (10-20% w/w) nanoMOFs (70-170 nm). External surface modification generally enhances stability and colloidal dispersion of UiO-66. Cellular internalisation routes and efficiencies of UiO-66 by HeLa cervical cancer cells can be tuned by surface chemistry, and anticancer cytotoxicity of DCA-loaded MOFs correlates with endocytosis efficiency and mechanisms. The MOFs with the most promising coatings (folic acid, poly(ethylene glycol), poly-L-lactide, and poly-N-isopropylacrylamide) were extensively tested for selectivity of anti-cancer cytotoxicity against MCF-7 breast cancer cells and HEK293 healthy kidney cells, as well as for cell proliferation and ROS production against J774 macrophages and peripheral blood lymphocytes (PBLs) isolated from the blood of human donors. DCA-loaded, folic acid modified UiO-66 selectively kills cancer cells without harming healthy ones or provoking immune system response in vitro, suggesting a significant targeting effect and great potential in anticancer drug delivery. The results provide mechanistic insight into the design and functionalisation of MOFs for drug delivery, and underline the availability of various in vitro techniques to potentially minimise early-stage in vivo animal studies, following the three Rs: reduction, refinement and replacement

By-catch associated with fisheries of Heterocarpus vicarius (Costa Rica) and Heterocarpus reedi (Chile) (Decapoda: Pandalidae): a six-year study (2004-2009)

artículo (arbitrado) -- Universidad de Costa Rica. Centro de Investigaciones en Ciencias del Mar y Limnología (CIMAR), 2013Growing concern about the quantity and diversity of by-catch species caught in the bottom trawling nets of crustacean fisheries led us to compare the quantity of by-catch recorded in Chilean and Costa Rican deep-water shrimp fisheries by year, latitude, and bathymetry. We analyzed catches from 2143 trawl hauls between 2004 and 2009 from the fisheries of the northern nylon shrimp,Heterocarpus vicarius, and the kolibri shrimp,Solenocera agassizii, off Costa Rica and the Chilean nylon shrimp, Heterocarpus reedi, off Chile. A catch index was estimated to determine the quantity of by-catch retained for each kilogram of shrimp. The by-catch associated with the shrimp fisheries of Costa Rica and Chile was mainly fishes and crustaceans; by-catch species diversity was considerably higher in Costa Rica compared to that of Chile. In Chile, catches of H. reediand by-catch were greater in the central and southern zone, whereas in Costa Rica, catches of shrimp (H. vicarius, S. agassizii) and by-catch were higher in the central zone. In terms of bathymetry, the largest catches of shrimp and by-catch came from the deep stratum (between 251 and 400 m) for both countries; the by-catch was noticeably larger in this stratum in Costa Rica. The catch index revealed that for every 1 kg of shrimp caught in Costa Rica, 5.7 kg of by-catch were caught; in Chile, this ratio was 1.1:1. However, the projected global by-catch was considerably higher for the fishery forH. reedithan for that ofH. vicarius,which is related to the landed volumes of the target species in Costa Rica and Chile. The encouraging results in the H. reedi-fishery concerning technical measures to reduce by-catch and discards rates should be also considered for Central American deep-water shrimp fisheries.The authors (PA and JCO) thank the Fondo de Investigación Pesquera (FIP) for funding the fishery assessment projects carried out off the central coast of Chile and for the availability of the data bases used to develop the present project. The researchers from Costa Rica (ISW, VNM and FVR) are thankful to the company The Rainbow Jewels, S.A., Puntarenas, for their ongoing support for monitoring the deepwater resources of Pacific Costa Rica. Likewise, thanks a lot to the captains (Rigo and Esteban: “Mecate”), crews of the shrimp trawlers ONUVA and SULTANA, and all the students who helped us with the collection and handling of the samples. Financial support was made available from the German company Ristic AG, Oberferrieden, the Costa Rican company The Rainbow Jewels S.A., Puntarenas, and the University of Costa Rica (projects V.I. No. 111-A4-508, V.I. No. 808-A9-536 and V.I. No. 808-A9-537). Additional funding was provided by the “Program University – Enterprise for Sustainable Development” (PUEDES) of the Council of Central American Universities (CSUCA), the German Society for Technical Cooperation (GTZ) and the University of Kassel, Germany. Furthermore, we are grateful for the logistic support provided by the Center of Marine Research and Limnology (CIMAR) and the School of Biology, University of Costa Rica. We are grateful to Ing. Álvaro De Caso for his collaboration with the statistical analysis of the fishery data. Danielle Barriga and Tayler Clarke revised and improved the English, which is greatly appreciated. Finally, we are thankful to Raquel Romero-Emilia, who helped us to prepare the final version of the figures.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-β1 and focal adhesion kinase activation

Neuroblastoma is a highly metastatic tumor that emerges from neural crest cell progenitors. Focal Adhesion Kinase (FAK) is a regulator of cell migration that binds to the receptor Neogenin-1 and is upregulated in neuroblastoma. Here, we show that Netrin-1 ligand binding to Neogenin-1 leads to FAK autophosphorylation and integrin β1 activation in a FAK dependent manner, thus promoting neuroblastoma cell migration. Moreover, Neogenin-1, which was detected in all tumor stages and was required for neuroblastoma cell migration, was found in a complex with integrin β1, FAK, and Netrin-1. Importantly, Neogenin-1 promoted neuroblastoma metastases in an immunodeficient mouse model. Taken together, these data show that Neogenin-1 is a metastasis-promoting protein that associates with FAK, activates integrin β1 and promotes neuroblastoma cell migration.This work was supported by the Comisión Nacional de Investigación Científica y Tecnológica [21130521]; Fondo Nacional de Desarrollo Científico y Tecnológico [1140697]; Fondo Nacional de Desarrollo Científico y Tecnológico [1180495]; Red Temática de Investigación Cooperativa en Cancer [RD12/0036/0027]; SAF [SAF2015-65175-R]; Red Temática de Investigación Cooperativa en Cancer [RD12/0036/0027]; PSG: Ministerio de Ciencia, Innovación y Universidades and FEDER funds (RTI2018-093596); JGC: Ministerio de Economía y Competitividad of Spain (PI17CIII/00013), Consejería de Educación, Juventud y Deporte, Comunidad de Madrid (P2017/BMD-3692), Fundación Oncohematología Infantil, AFANION, and Asociación Pablo Ugarte.S

Steppes, savannahs, forests and phytodiversity reservoirs during the Pleistocene in the Iberian Peninsula

A palaeobotanical analysis of the Pleistocene floras and vegetation in the Iberian Peninsula shows the existence of patched landscapes with Pinus woodlands, deciduous and mixed forests, parklands (savannah-like), shrublands, steppes and grasslands. Extinctions of Arctotertiary woody taxa are recorded during the Early and Middle Pleistocene, but glacial refugia facilitated the survival of a number of temperate, Mediterranean and Ibero-North African woody angiosperms. The responses of Iberian vegetation to climatic changes during the Pleistocene have been spatially and temporarily complex, including rapid changes of vegetation in parallel to orbital and suborbital variability, and situations of multi-centennial resilience or accommodation to climatic changes. Regional characteristics emerged as soon as for the Middle Pleistocene, if not earlier: Ericaceae in the Atlantic coast indicating wetter climate, thermo-mediterranean elements in the south as currently, and broad-leaf trees in the northeastern. Overall, steppe landscapes and open Pinus woodlands prevailed over many continental regions during the cold spells of the Late Pleistocene. The maintenance of a high phytodiversity during the glacials was linked to several refuge zones in the coastal shelves of the Mediterranean and intramountainous valleys. Northern Iberia, especially on coastal areas, was also patched with populations of tree species, and this is not only documented by palaeobotanical data (pollen, charcoal) but also postulated by phylogeographical models

Transcriptome profiling of grapevine seedless segregants during berry development reveals candidate genes associated with berry weight

Indexación: Web of Science; PubMedBackground Berry size is considered as one of the main selection criteria in table grape breeding programs. However, this is a quantitative and polygenic trait, and its genetic determination is still poorly understood. Considering its economic importance, it is relevant to determine its genetic architecture and elucidate the mechanisms involved in its expression. To approach this issue, an RNA-Seq experiment based on Illumina platform was performed (14 libraries), including seedless segregants with contrasting phenotypes for berry weight at fruit setting (FST) and 6–8 mm berries (B68) phenological stages. Results A group of 526 differentially expressed (DE) genes were identified, by comparing seedless segregants with contrasting phenotypes for berry weight: 101 genes from the FST stage and 463 from the B68 stage. Also, we integrated differential expression, principal components analysis (PCA), correlations and network co-expression analyses to characterize the transcriptome profiling observed in segregants with contrasting phenotypes for berry weight. After this, 68 DE genes were selected as candidate genes, and seven candidate genes were validated by real time-PCR, confirming their expression profiles. Conclusions We have carried out the first transcriptome analysis focused on table grape seedless segregants with contrasting phenotypes for berry weight. Our findings contributed to the understanding of the mechanisms involved in berry weight determination. Also, this comparative transcriptome profiling revealed candidate genes for berry weight which could be evaluated as selection tools in table grape breeding programs.http://bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-016-0789-

VALES V: a kinematic analysis of the molecular gas content in H-ATLAS galaxies at z ~ 0.03?0.35 using ALMA

We present Atacama Large Millimeter/submillimeter Array (ALMA) resolved observations of molecular gas in galaxies up to z = 0.35 to characterize the role of global galactic dynamics on the global interstellar medium properties. These observations consist of a sub-sample of 39 galaxies taken from the Valparaíso ALMA Line Emission Survey (VALES). From the CO(J = 1–0) emission line, we quantify the kinematic parameters by modelling the velocity fields. We find that the infrared (IR) luminosity increases with the rotational to dispersion velocity ratio (Vrot/σv, corrected for inclination). We find a dependence between Vrot/σv and the [C II]/IR ratio, suggesting that the so-called [C II] deficit is related to the dynamical state of the galaxies. We find that global pressure support is needed to reconcile the dynamical mass estimates with the stellar masses in our systems with low Vrot/σv values. The star formation rate (SFR) is weakly correlated with the molecular gas fraction (⁠fH2⁠) in our sample, suggesting that the release of gravitational energy from cold gas may not be the main energy source of the turbulent motions seen in the VALES galaxies. By defining a proxy of the ‘star formation efficiency’ (SFE) parameter as the SFR divided by the CO luminosity (SFE′ ≡ SFR/L′CO⁠), we find a constant SFE′ per crossing time (tcross). We suggest that tcross may be the controlling time-scale in which the star formation occurs in dusty z ∼ 0.03–0.35 galaxies

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field