Description: Thermal stress affects organism performance differently depending on the ambient temperature to which they are acclimatized, which varies along latitudinal gradients. This study investigated whether differences in physiological responses to temperature are consistent with regional differences in temperature regimes for the stony coral Oculina patagonica . To resolve this question we experimentally assessed how colonies originating from four different locations characterized by 〉3°C variation in mean maximum annual temperature responded to warming from 20 to 32°C. We assessed plasticity in symbiont identity, density, and photosynthetic properties, together with changes in host tissue biomass. Results show that, without changes in the type of symbiont hosted by coral colonies, O. patagonica has limited capacity to acclimatize to future warming. We found little evidence of variation in overall thermal tolerance, or in thermal optima, in response to spatial variation in ambient temperature. Given that the invader O. patagonica is a relatively new member of the Mediterranean coral fauna our results also suggest that coral populations may need to remain isolated for a long period of time for thermal adaptation to potentially take place. Our study indicates that for O. patagonica , mortality associated with thermal stress manifests primarily through tissue breakdown under moderate but prolonged warming (which does not impair symbiont photosynthesis and, therefore, does not lead to bleaching). Consequently, projected global warming is likely to causes repeat incidents of partial and whole colony mortality and might drive a gradual range contraction of Mediterranean corals. This article is protected by copyright. All rights reserved.

Description: Hyperpolarized [1, 13 C]pyruvate was injected rapidly into haemolysates in which hydrolysis of nicotinamide adenine dinucleotide (phosphate) (NAD(P))/NAD(P)H had been inhibited with nicotinamide. Haemolysates provide a stable glycolytic system in which membrane permeability is not a flux-controlling step, and they enable the concentration of NADH to be adjusted experimentally while keeping the rest of the sample with the same composition as that of the cytoplasm of the cell (albeit diluted twofold at the time of injection of the [1, 13 C]pyruvate). We showed that the maximum amplitude of the 13 C NMR signal from the [1, 13 C] L -lactate, produced from [1, 13 C]pyruvate, and the time at which it occurred was dependent on NADH concentration, as predicted by enzyme-kinetic analysis. The main feature of such curves was dictated by the immediacy of the supply of the co-substrate of lactate dehydrogenase (LDH, EC 1.1.1.27), and we posit that this also pertains in vivo in various tissues including neoplasms. By constructing an appropriate mathematical model and by using a Markov-chain Monte Carlo approach, we fitted experimental data to estimate LDH and NADH concentrations. Experiments carried out with only endogenous NADH present enabled the estimation of its effective concentration in human RBCs; the ability to make this estimate is a special feature of the rapid-dissolution dynamic nuclear polarization method. We found an endogenous NADH concentration in human RBCs two to four times higher than previously reported. Copyright © 2014 John Wiley & Sons, Ltd. We measured lactate dehydrogenase and NADH concentrations in human erythrocytes by using 13 C NMR rapid-dissolution dynamic nuclear polarization. A detailed enzyme kinetic model was used in the description of the experimental system, and a Markov-chain Monte Carlo procedure yielded estimates of parameter values. We report new estimates of concentrations of LDH and NADH in human erythrocytes; the former was about three times lower than previously reported while the latter was about three times higher.

Description: Idiopathic CD4 + lymphocytopenia (ICL) is a rare immunodeficiency syndrome of unknown origin for which the increased risks of opportunistic infections and of malignancies have been well established but skin dysimmune diseases, including psoriasis, have been scarcely reported to now. We report herein the severe course of psoriasis in 4 patients with ICL, and show evidence for a defect in the skin recruitment of regulatory CD4 + FoxP3 + T cells. These data raise the apparent paradigm of the occurrence of a severe immunomediated disease together with a profound T-cell defect, a model which might also apply to other immune deficiencies associated with psoriasis. This article is protected by copyright. All rights reserved.

Description: Background:  Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have beenscarcelyreported. Objectives:  To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods:  A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention to treat analysis. Results:  We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n=24), adalimumab (7), etanercept (6), ustekinumab (3) or efalizumab (2). A 75% improvement of BSA or PASI index 12 to 14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events consisting of bacterial infection in 7 of them were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was pursued up to 48 weeks in 34% of flares. Conclusion:  Biologics show overall good short-term efficacy, but treatment switch due to lack of efficacy or side effects is frequently observed on a longer term, with one third of patients still receiving the drug after one year. The most significant safety concern consists of severe infections.

Description: Background:  Even though efficacy of biologics has been extensively studied in psoriasis vulgaris, studies in erythrodermic psoriasis, the most severe form of the disease, have beenscarcelyreported. Objectives:  To address the efficacy and safety of biologics in patients with erythrodermic psoriasis. Methods:  A multicentre national retrospective study was performed using the French Psoriasis Group network. Patients showing psoriasis involving at least 90% of body surface area (BSA), and in whom severity of the disease had been evaluated before and after 3 and/or 6 months of treatment with biologics, were enrolled in the study. Results were expressed using intention to treat analysis. Results:  We included 28 patients, representing 42 flares of erythrodermic psoriasis treated with infliximab (n=24), adalimumab (7), etanercept (6), ustekinumab (3) or efalizumab (2). A 75% improvement of BSA or PASI index 12 to 14 weeks after treatment onset was reached in 48% of flares treated with infliximab, in 50% of those treated with adalimumab and in 40% of those treated with etanercept. Twelve serious adverse events consisting of bacterial infection in 7 of them were observed. Biological treatment was discontinued for safety concern in 19% of cases. A given biologic was pursued up to 48 weeks in 34% of flares. Conclusion:  Biologics show overall good short-term efficacy, but treatment switch due to lack of efficacy or side effects is frequently observed on a longer term, with one third of patients still receiving the drug after one year. The most significant safety concern consists of severe infections.

Description: We used the disturbance resulting from a once in a 100-yr storm on the northwest Mediterranean coast to examine the extent of the disturbance, the tolerance thresholds to burial, and the medium-term response of the long-lived Posidonia oceanica seagrass. Sediment burial at 12 surveyed areas was particularly strong in shallow meadows, with 23% of their surfaces buried, on average, under more than 10 cm of sediment. In contrast, less than 5% of the meadow was affected at deeper locations. At three sites, we tracked short-term mortality along a gradient of sediment burial. Survival response to burial was clearly nonlinear, with a significant threshold at 4–5 cm, beyond which shoot mortality was 100%. To track medium-term potential recovery, we established permanent plots subject to three sediment burial levels (0–5, 5–10, and 〉 10 cm burial) in four meadows. Where the initial shoot mortality was 100%, we recorded no shoot recovery over the 4-yr period. In the remaining plots, where some shoots remained alive, we detected either further mortality or shoot recovery of 7% per year on average. Extreme storm events can result in sudden catastrophic losses of seagrass cover in shallow P. oceanica meadows. In the long term and due to the long return time of such storms, the species may still be able to recover despite its low recovery potential. However, added anthropogenic stressors, including climate change, may seriously test the ability of long-lived shallow seagrass ecosystems to resist high-intensity natural disturbances and may be critical for its persistence.

Description: This paper presents a comparative study between the oblique sounding results, the ITU Rec533 HF prediction model and the vertical sounding results of a transequatorial long haul link. The long haul link is a 12760km link between the Spanish Antarctic Station, SAS, located in the Livingston Island and the Ebro Observatory (OE) in Spain. The data was collected during three consecutive surveys (2009/10, 2010/11 and 2011/12). The ionospheric channel from the SAS to the OE is studied in terms of frequency availability as function of time using the measurements of an oblique incidence sounder (OIS) and measurements of several vertical incidence sounding stations (VIS) placed near the estimated radiopropagation path. The results obtained show promising correlations between VIS and OIS measurements, and led us think that the frequency of largest availability for this particular long haul radio link can be estimated from the VIS sounding measurements.

Description: Worldwide increase in seawater temperature represents one of the major threats affecting corals, which experience bleaching, and thereafter a significant decrease in photosynthesis and calcification. The impact of bleaching on coral physiology may be exacerbated when coupled with eutrophication, i.e., increasing plankton, inorganic nutrient concentrations, sedimentation and turbidity due to coastal urbanization. Whereas zooplankton provision (heterotrophy) may alleviate the negative consequences of thermal stress, inorganic nutrient supply may exacerbate them, which creates a paradox. Our experimental study aims to disentangle the effects of these two components of eutrophication on the physiological response of Turbinaria reniformis subject to normal and to a short-term temperature increase. Additionally, three different inorganic nutrient ratios were tested to assess the influence of nutrient stoichiometry on coral physiology: control (ambient SW 0.5 μ M N and 0.1 μ M P), N only (ambient + 2 μ M N) and N + P (ambient + 2 μ M N and + 0.5 μ M P). Our results show a deleterious effect of a 2 μ M nitrate enrichment alone (N) on coral photosynthetic processes under thermal stress as well as on calcification rates when associated with heterotrophy. On the contrary, a coupled nitrate and phosphorus enrichment (N + P) maintained coral metabolism and calcification during thermal stress and enhanced them when combined with heterotrophy. Broadly, our results shed light on the tight relationship existing between inorganic nutrient availability and heterotrophy. Moreover, it assesses the relevance of N: P stoichiometry as a determining factor for the health of the holobiont that may be adapted to specific nutrient ratios in its surrounding environment.

Description: Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc.

Description: ABSTRACT The Cerdanya valley in northeast Spain experiences intense cold air pooling which decouples the valley atmosphere from the regional circulation, especially in winter. This makes air temperature prediction a challenge. A network of 40 temperature sensors was installed in 2012 along seven elevational transects to collect hourly temperatures throughout the cold pool, enabling measurement of the detailed cold pool structure for the first time. Sensors were also installed in the upper Conflent valley to the northeast for comparison, where previous research has shown that there is reduced cold air pooling. Sensor data were validated against automatic weather station observations at two locations. Through calculation of hourly lapse rates in various elevation bands for 2 years, frequent inversions developing up to 1450 m are shown, and sometimes extending much higher than this, concentrating in winter. Case studies of two intense episodes in December 2012 and January 2013 show that model simulations, despite being able to simulate broad mechanisms of cold air pooling formation, underestimate the amount of cooling. This is due to over-enthusiastic simulation of a low level jet in the first case and mountain waves in the second. Solving these model problems has important consequences for the future ability to predict episodes of extreme low temperatures and associated hazards (frost, fog) in Cerdanya and mountain valleys elsewhere.