Detection of Ectodysplasin A and phenotypic characterization of its deficiency

Ectodysplasin A (EDA), a trimeric ligand of the TNF super-family, is implicated in the em- bryonic development of ectodermal appendages such as hairs, teeth, sweat glands and other types of glands. Inactivating mutations in the EDA gene located on the X-chromosome cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a disease characterized by the absence or malformation of structures derived from the ectoderm. Although EDA is synthetized as a membrane-bound protein, it can be cleaved and released in a soluble form, but it is not known whether soluble EDA can be detected. Stimulation of EDA receptor (EDAR) during development in EDA-deficient animals can cor- rect the phenotype of EDA deficiency. It is however unknown whether EDAR stimulation in adult mice might affect exocrine glands in the nasal cavity, eyes and ears. Objectives: 1. One aim was to develop a method for the detection of endogenous EDA. 2. A second aim was to localize exocrine glands in the nasal cavity, eyes and ears of wild- type and EDA-deficient adult mice and to evaluate the impact on these glands of a chronic, post-developmental stimulation of EDAR. Methods: 1. A sandwich ELISA was used to detect EDA in sera of different species (human, foetal calf, mouse). Serum pre-depletions were performed to address the nature of the signal detected. For this purpose, EDA-binding reagents distinct from the pair of anti-EDA antibodies used in the sandwich ELISA were used. 2. Adult EDA-deficient mice were treated for 12 weeks by intraperitoneal injections of an EDAR agonist. Localization, size and morphology of exocrine glands in the nasal cavity, eye and ear were monitored in histology sections. Results: Endogenous levels of circulating EDA were detected in human and bovine, but not in mouse sera. Pre-depletion on recombinant EDAR could remove about half of the signal, confirming the presence of receptor-binding competent EDA in the serum. A variety of exocrine glands were localized by histology in the nasal cavity, eyes and ears of WT and EDA-deficient mice. Differences were noticed across genotypes, but no obvious effect of treatment on the presence or morphology of these glands was detected. Importance: A clinical trial for the orphan disease XLHED based on neonatal administration of an EDAR agonist is currently on-going. In this context, the detection of endogenous EDA in serum is relevant. Indeed, this could be exploited to establish a diagnostic screen for EDA-deficiency

Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated

Dense molecular gas toward W49A: A template for extragalactic starbursts?

The HCN, HCO+, and HNC molecules are commonly used as tracers of dense star-forming gas in external galaxies, but such observations are spatially unresolved. Reliably inferring the properties of galactic nuclei and disks requires detailed studies of sources whose structure is spatially resolved. We compare the spatial distributions and abundance ratios of HCN, HCO+, and HNC in W49A, the most massive and luminous star-forming region in the Galactic disk, based on maps of a 2' (6.6 pc) field at 14" (0.83 pc) resolution of the J=4-3 transitions of HCN, H13CN, HC15N, HCO+, H13CO+, HC18O+ and HNC. The kinematics of the molecular gas in W49A appears complex, with a mixture of infall and outflow motions. Both the line profiles and comparison of the main and rarer species show that the main species are optically thick. Two 'clumps' of infalling gas appear to be at ~40 K, compared to ~100 K at the source centre, and may be ~10x denser than the rest of the outer cloud. Chemical modelling suggests that the HCN/HNC ratio probes the current gas temperature, while the HCN/HCO+ ratio and the deuterium fractionation were set during an earlier, colder phase of evolution. The data suggest that W49A is an appropriate analogue of an extragalactic star forming region. Our data show that the use of HCN/HNC/HCO+ line ratios as proxies for the abundance ratios is incorrect for W49A, suggesting the same for galactic nuclei. Our observed isotopic line ratios such as H13CN/H13CO+ approach our modeled abundance ratios quite well in W49A. The 4-3 lines of HCN and HCO+ are much better tracers of the dense star-forming gas in W49A than the 1-0 lines. Our observed HCN/HNC and HCN/HCO+ ratios in W49A are inconsistent with homogeneous PDR or XDR models, indicating that irradiation hardly affects the gas chemistry in W49A. Overall, the W49A region appears to be a useful template for starburst galaxies.Comment: Accepted by A&A; 17 pages, 15 figure

Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes

We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

Abundance and scarcity: classical theories of money, bank balance sheets and business models, and the British restriction of 1797‐1818.

The thesis looks through the lens of bank balance sheet accounting to investigate the structural change in the British banking system between 1780 and 1832, and how classical quantity theorists of money attempted to respond to the ensuing financialisation of the wartime economy with its growing reliance on credit funded with paper-based instruments (the ‘Vansittart system’ of war finance). The thesis combines contributions to three separate fields to construct a holistic historical example of the challenges faced by monetary economists when ‘modelling’ financial innovation, credit growth, ‘fringe’ banking, and agent incentives – at a time of radical experimentation: the suspension of the 80-year-old gold standard (“the Restriction”). First, critical text analysis of the history of economics argues that the 1809-10 debate between Ricardo and Bosanquet at the peak of the credit boom, bifurcated classical theory into two timeless competing policy paradigms advocating the ‘Scarcity’ or ‘Abundance’ of money relative to exchange transactions. The competing hypotheses regarding the role of money and credit are identified and the rest of the thesis examines the archival evidence for each. Second, the core of the thesis contributes to the historical literature on banking in relation to money by reconstructing a taxonomy of bank business models, their relationships with the London inter-bank settlement system, and their responses to the Restriction - drawing on some 17,000 mostly new data points collected from the financial records of London and Country banks. The final section contributes to the economic history of money by constructing aggregated views of total bank liabilities from the firm-level data, scaled to recently available British GDP estimates. These are examined to establish (with hindsight) the relative merits and lacuna of the competing theoretical hypotheses postulated by political economists. It was the period of deleveraging after 1810 that revealed the lacuna of both paradigms

H. Sarrasin (illustrateur non-identifié 18..-19..) : signature [1905]

H. Sarrasin (illustrateur non-identifié 18..-19..) : signature [1905

Les cloches républicaines : duo [illustration H. Sarrasin (18..-19..)]

Les cloches républicaines : duo ; (dédicace) “à Monsieur Gagey & à Madame Vindry” ; illustration H. Sarrasin (18..-19.. illustrateur non-identifié) ; poésie de A. Lallemand [Alfred Lallemand] ; musique de A. Scassola [Aristide Scassola] & Clavandier [Marius Clavandier (1873-1956)] ; Orgeret éditeur, Lyon, dépôt à Paris Labbé ; (signature datée) “René / Lyon 17” ; [intérieur : “chanson” ; cotage JMO394 ; Crevel frères imprimerie-gravure] ; verso catalogue ; incipit “Les cloches sonneront, dans un siècle prochain” ; datation (titre) : 1905 par dépôt BNF et cotage (Devriès et Lesure). Exemplaire avec au recto et en page 2, la signature datée et localisée de l’artiste non-identifié propriétaire (René N?, 1917, Lyon). (notice mise à jour 07/07/2017

Au pairs are rarely male: Norms on the gender perception of role names across English, French, and German.

A list of role names for future use in research on gender stereotyping was created and evaluated. In two studies, 126 role names were rated with reference to their gender stereotypicality by English-, French-, and German-speaking students of universities in Switzerland (French and German) and in the U.K. (English). Role names were either presented in specific feminine and masculine forms (Study 1) or in the masculine form (generic masculine) only (Study 2). The rankings of the stereotypicality ratings were highly reliable across languages and questionnaire versions, but the overall mean of the ratings was less strongly male if participants were also presented with the female versions of the role names and if the latter were presented on the left side of the questionnaires