Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT) and monocyte (MAT) activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37%) and specificity (90%) of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P < 0.001) or MAT 10/22 (46%, P < 0.01) were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls

The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver

PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of the Thb gene, by which PPARα but not HNF4α transactivates. Intriguingly, we found that HNF4α enhanced PPARα/RXRα transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4α was physically interacting with RXRα. RT-PCR performed with RNA from liver-specific HNF4α-null mice confirmed the involvement of HNF4α in the PPARα-regulated induction of Thb by Wy14,643. Overall, we conclude that HNF4α enhances the PPARα-mediated activation of Thb gene expression in part through interaction with the obligate PPARα partner, RXRα

Fatal Disseminated Acanthamoeba lenticulata Acanthamebiasis in a Heart Transplant Patient

We report a fatal case of disseminated acanthamebiasis caused by Acanthamoeba lenticulata (genotype T5) in a 39-year-old heart transplant recipient. The diagnosis was based on skin histopathologic results and confirmed by isolation of the ameba from involved skin and molecular analysis of a partial 18S rRNA gene sequence (DF3)

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI<25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI<25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far

Examining techniques for measuring the effects of nutrients on mental performance and mood state

Purpose: Intake of specific nutrients has been linked to mental states and various indices of cognitive performance although the effects are often subtle and difficult to interpret. Measurement of so-called objective variables (e.g. reaction times) is often considered to be the gold standard for assessing outcomes in this field of research. It can, however, be argued that data on subjective experience (e.g. mood) are also important and may enrich existing objective data. The aim of this review is to evaluate methods for measuring mental performance and mood, considering the definition of subjective mood and the validity of measures of subjective experience. Methods: A multi-stakeholder expert group was invited by ILSI Europe to come to a consensus around the utility of objective and subjective measurement in this field, which forms the basis of the paper. Therefore, the present review reflects a succinct overview of the science but is not intended to be a systematic review. Results: The proposed approach extends the traditional methodology using standard ‘objective’ measurements to also include the consumers’ subjective experiences in relation to food. Specific recommendations include 1) using contemporary methods to capture transient mood states; 2) using sufficiently sensitive measures to capture effects of nutritional intervention; 3) considering the possibility that subjective and objective responses will occur over different time frames; and 4) recognition of the importance of expectancy and placebo effects for subjective measures. Conclusions: The consensus reached was that the most informative approach should involve collection and consideration of both objective and subjective data

The International Space Analogue Rock Store (ISAR): A key tool for future planetary exploration.

International audienceIn order to prepare the next in situ space missions we have created a " lithothèque " of analogue rocks for calibrating and testing future (and existing) space flight instruments. This rock collection is called the International Space Analogue Rockstore (ISAR) and is hosted in the CNRS and the Observatoire des Sciences de l'Univers en Region Centre (OSUC) in Orléans. For maximum science return, all instruments on a single mission should ideally be tested with the same suite of relevant analogue materials. The ISAR lithothéque aims to fulfill this role by providing suitable materials to instrument teams [1]. The lithothèque is accompanied by an online database of all relevant structural, textural, and geochemical data (www.isar.cnrs-orleans.fr).The data base will also be available during missions to aid interpretation of data obtained in situ. Mars is the immediate goal for MSL-2011 and the new international Mars 2018 mission. The lithothèque thus presently contains relevant Mars-analogue rock and mineral samples, a preliminary range of which is now available to the scientific community for instrument testing [2]. The preliminary group of samples covers a range of lithologies to be found on Mars, especially those in Noachain/Hesperian terrains where MSL will land (Gale Crater) and where the 2018 landing site will most likely be located. It includes a variety of basalts (tephrite, primitive basalt, silicified basalt; plus cumulates), komatiites, artificially synthesized martian basalts [3], volcanic sands, a banded iron formation, carbonates associated with volcanic lithologies and hydrothermalism, the clay Nontronite, and hydrothermal cherts. Some of the silicified volcanic sands contain traces of early life that are good analogues for potential martian life [4]. [1] Westall F. et al., LPI contribution 1608, 1346, 42nd LPSC, 2011; [2] Bost N. et al., in review (Icarus); [3] Bost N. et al., in review (Meteoritics); [4] Westall et al., 2011, Planetary and Space Science 59. ISAR Team: N. Bost, F. Westall, C; Ramboz, F. Foucher, D. Pullan, T. Zegers, B. Hoffman, F. Rull, J. Bridges, A; Steele, H. Amundsen, R. Barbieri, A. Hubert, B. Cavalazzi, J. Bridges, M. Viso, J. Vago, S. Petit, A. Meunier, I. Fleischer, G. Klingelhöfer, N. Arndt..

Hydrothermal, deuteric and acidic basalt alteration at the Skouriotissa Mine, Cyprus: relevance for Mars.

International audienceBasalts are the prevalent rock type on Mars and the products of aqueously altered basalts and hydrated minerals associated with basalts are of particular interest as possible tracers of a past, slightly more clement climate on the planet and/or magmatic processes [1,2]. Study of alteration processes of basalts on Earth that show some similarities to surface and subsurface processes occurring on Mars will help understand and interpret martian features. The Skouriotissa mine in Cyprus is an open pit copper mine (consisting of a very massive sulphide deposit, VMS) exposing the upper pillow basalt formation in the Troodos ophiolitic zone. The basalt has been altered by (1) hydrothermal and deuteritic processes and (2) acidic water (pH <5) associated with the mining working. We have analysed the mineralogical evolution of the basalt through different alteration facies (phyllosilicates, including Mg-smectite, vermiculite, nontronite, and zeolites), depending on the type of alteration. Similar mineralogical associations have been described on Noachian/early Hesperian Mars (e.g. [1,2.3]) and may have been formed by the same kinds of processes. These suites of rocks form part of the collection of Mars analogue rocks that is being prepared at the CNRS/Observatoire des Sciences de l'Univers en région Centre (OSUC) in Orléans to help calibrate present and future flight instruments (e.g. MSL, the international Mars- 2018 in situ mission). This collection is named International Space Analogue Rockstore (ISAR) and the relevant information is contained in the website: http://www.isar.cnars-orleans.fr [4,5]. [1] Bibring et al., 2006, Science 312; [2] Ehlmann et al., 2011, Nature 479; [3] Meunier et al., in prep. ; [4] Bost N. et al., in review (Icarus).[5] Bost N. et al., This Conference, abstract 1403