Relación entre la evolución sedimentaria de la laguna de Gallocanta (Cordillera Ibérica, NE de España) y la historia de la vegetación de su cuenca durante el Cuaternario reciente

The analysis of the facies in the sediments from Gallocanta Lake allows the identification of three stages of sedimentation. The lowest stage related with the late Pleistocene corresponds with distal alluvial areas, the second stage reflects a shallow carbonated lake probably developed from the beginning of the Holocene to the Middle Age and, the last one corresponds to a saline-carbonated lake formed in the last centuries. In the alluvial facies the pollen concentration is very low. The following stages are related with different types of pollen assemblages. The stage of a shallow carbonated lake is associated with the development of a deciduous and evergreen Quercus forest in the basin and represents the maximum water depth, 4 to 10 meters, of the Gallocanta Lake. This period The last stage of saline-carbonated lake, dated at 1900 AD, coincides with the maximum phase of Olea cultivation contemporaneous with the decrease of the lake level. The depth of the water was between 0 and 2 m. The drying out of the Gallocanta lake coincides with the lake level lowering of other lakes in the Ebro basin suggesting a regional driving-factor (climatic and/or anthropic) as the main responsible for the observed desiccation of the last century

Anthropogenic influence in the Sado estuary (Portugal): a geochemical approach

Two areas of salt marsh in the Sado estuary – Faralhão, on the industrialized north margin and Malha da Costa, on the south bank, sheltered by a uninhabited sand spit – have been cored to study the geochemical signature of anthropogenic activity in recent (19th century onwards) intertidal sediments. Short cores were taken from each site from both the high and low marsh and were studied for texture, organic matter, pH, carbonates and geochemistry, including the heavy metals Cu, Pb and Zn. The marsh sediments are free of carbonate bioclasts and quite uniform in texture, consisting of acid to neutral clayey silt in addition to organic matter, which is higher in the top 20 cm. The vertical concentration profiles of heavy metals indicates enrichment in the top 30 cm of the sediment of the high marsh, in contrast with underlying high and low marsh sediment that has concentrations of metals at both studied sites similar to the Average Shale international reference/ continental crust sediments. The geochemical signal of anthropogenic influence in the marsh sediment was determined to have commenced from 1900-1920 using the sedimentation rates derived from 210Pb and 137Cs analyses. Spatial contrast in contamination levels was found within the estuary, with sediments of the Faralhão marsh showing higher enrichment factors of all metals. The anthropogenic increase of the supply of metal to the Sado estuary resulted from extensive exploitation of pyrite ore in the drainage basin until the1960’s; since that time, the sediments record a break in metal input, which resulted from a decline of the mining industry. However, in the marsh located closer to the industrial area (Faralhão) this break is followed by a local increase of heavy metal fluxes, which is interpreted as the result of intensification of anthropogenic influence. The comparison of metal concentrations in marsh sediments with target values established in quality guidelines indicates the studied area to be of environmental concern.Con el fin de estudiar el registro geoquímico de la actividad antrópica en sedimentos recientes (a partir del siglo XIX) e intermareales, han sido perforadas dos zonas de marisma en el Estuario del Sado- Faralhão, en el industrializado margen norte, y Malha da Costa, en la orilla sur, resguardada por una flecha litoral de arena no ocupada antrópicamente. Los pequeños sondeos realizados en cada punto de muestreo englobaron la marisma alta y baja. Fueron realizados análisis texturales, de contenido en materia orgánica, de pH, carbonatos y geoquímica, incluyendo los metales pesados Cu, Pb y Zn. Los sedimentos de marisma no muestran carbonato bioclástico y son bastante uniformes en la textura, consistiendo en limo arcilloso ácido a neutro junto con materia orgánica cuyo contenido es mayor en los 20 cm más superficiales. La concentración vertical de los perfiles de metales pesados indica un enriquecimiento en los 30 cm superficiales de la marisma alta, en contraste con los sedimentos subyacentes de marisma alta y baja que poseen concentraciones de metales similares a los referenciados internacionalmente para Average Shale / sedimentos de corteza continental. La señal geoquímica de la influencia antrópica en los sedimentos de marisma fue datada de 1900 a 1920 usando las tasas de sedimentación deducidas mediante 210Pb y 137Cs. Un contraste espacial en los niveles de contaminación fue encontrado en el interior del estuario: la marisma de Faralhão muestra valores con mayor enriquecimiento para todos los metales. El aporte antrópico de metales en el estuario de Sado resulta de la extensa explotación de pirita en la cuenca hasta 1960; a partir de ese momento los sedimentos registran una disminución en el aporte antropogénico de metales, consecuencia de la disminución del trabajo minero. Sin embargo, en la marisma cercana a la zona industrial (Faralhão) a esta interrupción le sigue un restablecimiento del flujo de metales pesados, interpretado como resultado del aumento de la influencia antrópica. La comparación de las concentraciones de metales en sedimentos de marisma con valores fijados establecidos en directrices de calidad sugiere una inquietud ambiental para el área de estudio

Leaf litter degradation in highly turbid transitional waters: preliminary results from litter-bag experiments in the Gironde Estuary

The rates of decomposition of oak (Quercus robur) leaves have been examined using litter bags in a very high turbidity macrotidal estuary, the Gironde Estuary (S.W. France). The first experiments show a marked decrease in the decomposition rate of oak leaves at the water-sediment interface (mud-contact: anoxic conditions, reduced physical fragmentation) in comparison to the water column. The results point out the impact of hydrodynamic conditions on leaf litter degradation in such fluvio-estuarine systems. Regarding the aquatic-terrestrial linkage, our observations suggest direct changes in leaf decomposition kinetics and then, a potential delay on the recycling and transport processes of coarse particulate organic matter, especially in a context of modification of the natural water flow, due to global and land use changes

Surgical management of giant pituitary neuroendocrine tumors: Meta-analysis and consensus statement on behalf of the EANS skull base section.

The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated. The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section. We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases. After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy

T Cells Enhance Stem-Like Properties and Conditional Malignancy in Gliomas

Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs) can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas). Many aspects of glioma CSCs (GSCs), however, have been characterized in non-physiological settings.We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade. Using this method, we examined stemness in human grade IV gliomas (GBM) before and after dendritic cell (DC) vaccine therapy. This was followed by gene expression, phenotypic and functional analysis of murine GL26 tumors recovered from nude, wild-type, or DC-vaccinated host brains.GSC similarity was specifically increased in post-vaccine GBMs, and correlated best to vaccine-altered gene expression and endogenous anti-tumor T cell activity. GL26 analysis confirmed immune alterations, specific acquisition of stem cell markers, specifically enhanced sensitivity to anti-stem drug (cyclopamine), and enhanced tumorigenicity in wild-type hosts, in tumors in proportion to anti-tumor T cell activity. Nevertheless, vaccine-exposed GL26 cells were no more tumorigenic than parental GL26 in T cell-deficient hosts, though they otherwise appeared similar to GSCs enriched by chemotherapy. Finally, vaccine-exposed GBM and GL26 exhibited relatively homogeneous expression of genes expressed in progenitor cells and/or differentiation.T cell activity represents an inducible physiological process capable of proportionally enriching GSCs in human and mouse gliomas. Stem-like gliomas enriched by strong T cell activity, however, may differ from other GSCs in that their stem-like properties may be disassociated from increased tumor malignancy and heterogeneity under specific host immune conditions

Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments.

We report a technique to selectively and continuously label the proteomes of individual cell types in coculture, named cell type-specific labeling using amino acid precursors (CTAP). Through transgenic expression of exogenous amino acid biosynthesis enzymes, vertebrate cells overcome their dependence on supplemented essential amino acids and can be selectively labeled through metabolic incorporation of amino acids produced from heavy isotope-labeled precursors. When testing CTAP in several human and mouse cell lines, we could differentially label the proteomes of distinct cell populations in coculture and determine the relative expression of proteins by quantitative mass spectrometry. In addition, using CTAP we identified the cell of origin of extracellular proteins secreted from cells in coculture. We believe that this method, which allows linking of proteins to their cell source, will be useful in studies of cell-cell communication and potentially for discovery of biomarkers

The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma

INTRODUCTION: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. METHODS: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. RESULTS: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. CONCLUSIONS: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas

FGFR1-Induced Epithelial to Mesenchymal Transition through MAPK/PLCγ/COX-2-Mediated Mechanisms

Tumour invasion and metastasis is the most common cause of death from cancer. For epithelial cells to invade surrounding tissues and metastasise, an epithelial-mesenchymal transition (EMT) is required. We have demonstrated that FGFR1 expression is increased in bladder cancer and that activation of FGFR1 induces an EMT in urothelial carcinoma (UC) cell lines. Here, we created an in vitro FGFR1-inducible model of EMT, and used this model to identify regulators of urothelial EMT. FGFR1 activation promoted EMT over a period of 72 hours. Initially a rapid increase in actin stress fibres occurred, followed by an increase in cell size, altered morphology and increased migration and invasion. By using site-directed mutagenesis and small molecule inhibitors we demonstrated that combined activation of the mitogen activated protein kinase (MAPK) and phospholipase C gamma (PLCγ) pathways regulated this EMT. Actin stress fibre formation was regulated by PLCγ activation, and was also important for the increase in cell size, migration and altered morphology. MAPK activation regulated migration and E-cadherin expression, indicating that combined activation of PLCγand MAPK is required for a full EMT. We used expression microarrays to assess changes in gene expression downstream of these signalling cascades. COX-2 was transcriptionally upregulated by FGFR1 and caused increased intracellular prostaglandin E2 levels, which promoted migration. In conclusion, we have demonstrated that FGFR1 activation in UC cells lines promotes EMT via coordinated activation of multiple signalling pathways and by promoting activation of prostaglandin synthesis