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

Late Holocene climatic oscillations traced by clay mineral assemblages and other palaeoceanographic proxies in Ria de Vigo (NW Spain)

This work aims to study recent climatic oscillations and their influence on sedimentation in the Ria de Vigo, a coastal embayment in Galicia, NW Spain. It is based on the study of clay mineral assemblages, in conjunction with other proxies (granulometric, geochemical, geochronological and microfaunal), in the core KSGX 24. A Benthic Foraminifera High Productivity (BFHP) proxy was used to determine changes in the flux of organic matter (OM) at the bottom of the study area. Total organic carbon (TOC) content is not a suitable proxy to estimate changes in the past supply of OM due to diagenetic processes.The sedimentation was finest in 3 sections: ~ 230–214 cm, ~ 185–73 cm and ~ 20–0 cm. These muddy sections are characterised, in general, by higher proportions of detrital minerals, concentrations of several chemical elements related to lithogenic sources and BFHP values. In addition, these sections are impoverished in carbonates, Ca, Sr and La when compared with the layers with the highest sand content.The clay mineral assemblage of the studied site, characterised by the dominance of illite, intermediate concentrations of kaolinite and minor amounts of smectite and chlorite, reveals the prevalence of a typical temperate humid climate in the last 3 ka BP, the estimated age for the core base. However, the quantities of illite and chlorite increase in the muddy layers. The characteristics of these muddy layers were interpreted as representing relatively cold climatic oscillations associated with the strengthening of northerly winds and the prevalence of an upwelling regime corresponding to wellknown periods, such as the first cold period of the Upper Holocene (~ 2.9 ka cal BP), the Dark Ages (between ~ 2.2 - 1.2 ka cal BP) and the Little Ice Age (~ 0.6 ka cal BP)

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