An in vitro L-band EPR study with whole human teeth in a surface coil resonator. Radiat

Abstract L-band EPR measurements were done in vitro on extracted human teeth with the objective to evaluate the feasibility of retrospective in vivo EPR dosimetry. In a recent study, the relative contributions of individual tooth components (enamel, crown dentin and root) to the total response of a whole tooth inside an L-band surface coil resonator was investigated. In the present work, the gamma-dose response curves were evaluated for di erent EPR signal evaluation methods, using 35 whole teeth with absorbed doses in the range 1-100 Gy. The paper reports on the ÿrst attempt to deconvolute the single composite L-band EPR line in components due to CO − 2 and native radicals. The L-band EPR spectrum of teeth could be approximated by combining powder-simulated spectra of orthorhombic and quasi-axial signals of the CO − 2 radical and an isotropic signal of the native radicals. Among the applied EPR signal evaluation methods, the evaluation by spectrum deconvolution revealed the lowest detection limit for absorbed dose. A detection limit of about 0:5 Gy was estimated for the currently available L-band equipment

Influencia del tamaño de la semilla de trigo y sus reservas proteicas : II- el rendimiento de grano del cultivo subsecuente

p.17-24Para probar que se pueden obtener aumentos de rendimiento utilizando semillas grandes, se seleccionaron lotes del cv. Cooperación Cabildo que provenían de una red de fertilización y presentaban un rango de entre 18 y 40 g las mil semillas, y entre 9 y 18 por ciento de proteína. Con ellas se sembraron tres ensayos en dos años. El rendimiento se correlacionó positivamente con el peso de mil granos y negativamente con el porcentaje de proteína. No se obtuvo correlación del rendimiento con el peso seco de las plántulas ni con el porcentaje de emergencia. Ese mayor rendimiento se debió al incremento del número de espigas por m2

Antibody-functionalized polymer-coated gold nanoparticles targeting cancer cells: an in vitro and in vivo study

Gold nanoparticles ( 3c5 nm) coated with plasma-polymerized allylamine were produced through plasma vapor deposition and bioconjugated with a monoclonal antibody targeting the epidermal growth factor receptor. The resulting nanoconjugates displayed an antibody loading of about 1.7 nmol mg -1 and efficiently target epidermal growth factor receptor overexpressing cell lines, as ascertained by ELISA and Western blot assays. The in vitro targeting properties were also confirmed in vivo, where a similar biodistribution profile of what was experienced for the unconjugated antibody was observed. Thanks to the possibility of doping the gold nanoparticles with radionuclides during plasma vapor deposition, the proposed functionalization strategy represents a very suitable platform for the in vivo cancer targeting with nanosized multifunctional particles. This journal is \ua9 2012 The Royal Society of Chemistry

The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action

<p>Abstract</p> <p>Background</p> <p>The incidence of melanoma is considerably increasing worldwide. Frequent failing of classical treatments led to development of novel therapeutic strategies aiming at managing advanced forms of this skin cancer. Additionally, the implication of the endocannabinoid system in malignancy is actively investigated.</p> <p>Methods</p> <p>We investigated the cytotoxicity of endocannabinoids and their hydrolysis inhibitors on the murine B16 melanoma cell line using a MTT test. Enzyme and receptor expression was measured by RT-PCR and enzymatic degradation of endocannabinoids using radiolabeled substrates. Cell death was assessed by Annexin-V/Propidium iodine staining. Tumors were induced in C57BL/6 mice by s.c. flank injection of B16 melanoma cells. Mice were injected i.p. for six days with vehicle or treatment, and tumor size was measured each day and weighted at the end of the treatment. Haematoxylin-Eosin staining and TUNEL assay were performed to quantify necrosis and apoptosis in the tumor and endocannabinoid levels were quantified by HPLC-MS. Tube formation assay and CD31 immunostaining were used to evaluate the antiangiogenic effects of the treatments.</p> <p>Results</p> <p>The <it>N</it>-arachidonoylethanolamine (anandamide, AEA), 2-arachidonoylglycerol and <it>N</it>- palmitoylethanolamine (PEA) reduced viability of B16 cells. The association of PEA with the fatty acid amide hydrolase (FAAH) inhibitor URB597 considerably reduced cell viability consequently to an inhibition of PEA hydrolysis and an increase of PEA levels. The increase of cell death observed with this combination of molecules was confirmed in vivo where only co-treatment with both PEA and URB597 led to decreased melanoma progression. The antiproliferative action of the treatment was associated with an elevation of PEA levels and larger necrotic regions in the tumor.</p> <p>Conclusions</p> <p>This study suggests the interest of targeting the endocannabinoid system in the management of skin cancer and underlines the advantage of associating endocannabinoids with enzymatic hydrolysis inhibitors. This may contribute to the improvement of long-term palliation or cure of melanoma.</p

Targeting the Lactate Transporter MCT1 in Endothelial Cells Inhibits Lactate-Induced HIF-1 Activation and Tumor Angiogenesis

Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1) pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs) thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1) that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2) and basic fibroblast growth factor (bFGF) expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities

Modeling Brain Resonance Phenomena Using a Neural Mass Model

Stimulation with rhythmic light flicker (photic driving) plays an important role in the diagnosis of schizophrenia, mood disorder, migraine, and epilepsy. In particular, the adjustment of spontaneous brain rhythms to the stimulus frequency (entrainment) is used to assess the functional flexibility of the brain. We aim to gain deeper understanding of the mechanisms underlying this technique and to predict the effects of stimulus frequency and intensity. For this purpose, a modified Jansen and Rit neural mass model (NMM) of a cortical circuit is used. This mean field model has been designed to strike a balance between mathematical simplicity and biological plausibility. We reproduced the entrainment phenomenon observed in EEG during a photic driving experiment. More generally, we demonstrate that such a single area model can already yield very complex dynamics, including chaos, for biologically plausible parameter ranges. We chart the entire parameter space by means of characteristic Lyapunov spectra and Kaplan-Yorke dimension as well as time series and power spectra. Rhythmic and chaotic brain states were found virtually next to each other, such that small parameter changes can give rise to switching from one to another. Strikingly, this characteristic pattern of unpredictability generated by the model was matched to the experimental data with reasonable accuracy. These findings confirm that the NMM is a useful model of brain dynamics during photic driving. In this context, it can be used to study the mechanisms of, for example, perception and epileptic seizure generation. In particular, it enabled us to make predictions regarding the stimulus amplitude in further experiments for improving the entrainment effect

Ionic strength dependence of localized contact formation between membranes: nonlinear theory and experiment.

Erythrocyte membrane surface or suspending phase properties can be experimentally modified to give either spatially periodic local contacts or continuous contact along the seams of interacting membranes. Here, for cells suspended in a solution of the uncharged polysaccharide dextran, the average lateral separation between localized contacts in spatially periodic seams at eight ionic strengths, decreasing from 0.15 to 0.065, increased from 0.65 to 3.4 micrometers. The interacting membranes and intermembrane aqueous layer were modeled as a fluid film, submitted to a disjoining pressure, responding to a displacement perturbation either through wave growth resulting in spatially periodic contacts or in perturbation decay, to give a plane continuous film. Measured changes of lateral contact separations with ionic strength change were quantitatively consistent with analytical predictions of linear theory for an instability mechanism dependent on the membrane bending modulus. Introduction of a nonlinear approach established the consequences of the changing interaction potential experienced by different parts of the membrane as the disturbance grew. Numerical solutions of the full nonlinear governing equations correctly identified the ionic strength at which the bifurcation from continuous seam to a stationary periodic contact pattern occurred and showed a decrease in lateral contact and wave crest separation with increasing ionic strength. The nonlinear approach has the potential to recognize the role of nonspecific interactions in initiating the localized approach of membranes, and then incorporate the contribution of specific molecular interactions, of too short a range to influence the beginning of perturbation growth. This new approach can be applied to other biological processes such as neural cell adhesion, phagocytosis, and the acrosome reaction