The imperative of arachidonic acid in human reproduction.

We are presenting new evidence on essential fatty acids (EFA) in prenatal human development. We have demonstrated, for the first time, the detailed process of active selection of some fatty acids by the placenta (biomagnification) and rejection of others (bioreduction) and how this strategy is of supreme importance for understanding of the biology of human reproduction. The biomagnification process by the placenta is dominated by arachidonic acid (ArA) and its allies: di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid. Stearic acid is similarly bio-magnified which is likely to provide for the sn-1 position in membrane synthesis. In contrast there is a bioreduction of oleic, linoleic and all ω3 precursors for docosahexaenoic acid (DHA), including eicosapentaenoic acid (EPA). Although DHA is biomagnified, the amplification from mother to fetus is small compared to ArA. We report on the dominant compartmentalisation of ArA from mother to fetal plasma, cell membranes of red cells, mono-nuclear cells, endothelium and the placenta. We conclude that ArA and its allies, play a paramount role in the development of the products of conception. It is plausible that inadequate provision of ArA may be relevant to the neuro-vascular complications of prematurity and neurodevelopmental disorders associated with premature birth. We present evidence of ArA's universal role from an identical arachidonic acid-based strategy observed in contrasting cultures. The dominance of ArA in the prenatal and in post-natal nutritional provision by human milk makes a compelling case for re-evaluation of its role, especially in reproductive biology

Surface core level shifts of clean and oxygen covered Ir(111)

We present the results of high resolution core level photoelectron spectroscopy employed to investigate the electronic structure of clean and oxygen covered Ir(111) surface. Ir 4f7/2 core level spectra are shown to be very sensitive to the local atomic environment. For the clean surface we detected two distinct components shifted by 550meV, originated by surface and bulk atoms. The larger Gaussian width of the bulk component is explained as due to experimentally unresolved subsurface components. In order to determine the relevance of the phonon contribution we examined the thermal behaviour of the core level lineshape using the Hedin-Rosengren theory. From the phonon- induced spectral broadening we found the Debye temperature of bulk and surface atoms to be 298 and 181K, respectively, which confirms the softening of the vibrational modes at the surface. Oxygen adsorption leads to the appearance of new surface core level components at 200meV and +230meV, which are interpreted as due to first-layer Ir atoms differently coordinated with oxygen. The coverage dependence of these components demonstrates that the oxygen saturation corresponds to 0.38ML, in good agreement with recent density functional theory calculations

Epitaxial growth of ultrathin palladium films on Re{0001}

Ultrathin bimetallic layers create unusual magnetic and surface chemical effects through the modification of electronic structure brought on by low dimensionality, polymorphism, reduced screening, and epitaxial strain. Previous studies have related valence and core-level shifts to surface reactivity through the d-band model of Hammer and Nørskov, and in heteroepitaxial films this band position is determined by competing effects of coordination, strain, and hybridization of substrate and overlayer states. In this study we employ the epitaxially matched Pd on Re{0001} system to grow films with no lateral strain. We use a recent advancement in low-energy electron diffraction to expand the data range sufficiently for a reliable determination of the growth sequence and out-of-plane surface relaxation as a function of film thickness. The results are supported by scanning tunneling microscopy and X-ray photoemission spectroscopy, which show that the growth is layer-by-layer with significant core-level shifts due to changes in film structure, morphology, and bonding

Using quantitative single molecule localization microscopy to optimize multivalent HER2-targeting ligands

IntroductionThe progression-free survival of patients with HER2-positive metastatic breast cancer is significantly extended by a combination of two monoclonal antibodies, trastuzumab and pertuzumab, which target independent epitopes of the extracellular domain of HER2. The improved efficacy of the combination over individual antibody therapies targeting HER2 is still being investigated, and several molecular mechanisms may be in play: the combination downregulates HER2, improves antibody-dependent cell mediated cytotoxicity, and/or affects the organization of surface-expressed antigens, which may attenuate downstream signaling.MethodsBy combining protein engineering and quantitative single molecule localization microscopy (qSMLM), here we both assessed and optimized clustering of HER2 in cultured breast cancer cells.ResultsWe detected marked changes to the cellular membrane organization of HER2 when cells were treated with therapeutic antibodies. When we compared untreated samples to four treatment scenarios, we observed the following HER2 membrane features: (1) the monovalent Fab domain of trastuzumab did not significantly affect HER2 clustering; (2) individual therapy with either trastuzumab or (3) pertuzumab produced significantly higher levels of HER2 clustering; (4) a combination of trastuzumab plus pertuzumab produced the highest level of HER2 clustering. To further enhance this last effect, we created multivalent ligands using meditope technology. Treatment with a tetravalent meditope ligand combined with meditope-enabled trastuzumab resulted in pronounced HER2 clustering. Moreover, compared to pertuzumab plus trastuzumab, at early time points this meditope-based combination was more effective at inhibiting epidermal growth factor (EGF) dependent activation of several downstream protein kinases.DiscussionCollectively, mAbs and multivalent ligands can efficiently alter the organization and activation of the HER2 receptors. We expect this approach could be used in the future to develop new therapeutics

Autorità e potere nei Paesi musulmani : concetti e pratiche

Gli eventi riportati dalle cronache internazionali evidenziano il fermento culturale, sociale e politico che esiste oggi nei Paesi a maggioranza musulmana. Questi accadimenti nascono da tensioni politiche e socio-economiche e da dialettiche culturali che, da un lato, hanno delle specificit\ue0 nazionali, e, dall'altro, una natura precipua ma transnazionale. Essa si pu\uf2 spiegare attraverso il consenso che larghi strati delle popolazioni musulmane accordano a figure di autorit\ue0, istituzioni sociali o sistemi normativi e concettuali tradizionali che sono sopravvissuti nel corso dei secoli, adattandosi e rimodellandosi in base alle mutate condizioni storiche. Dalla coscienza della complessit\ue0 di questi apporti prende le mosse questo libro, che vuole mettere a fuoco la pluralit\ue0 che sostanzia il concetto stesso di \uabautorit\ue0\ubb. Le direttrici sottese dalla riflessione sono, quindi, necessariamente due: quella dell'eterogeneit\ue0, sia essa intesa in senso cronologico o geografico; e quella della continuit\ue0, che ha permesso la persistenza di categorie di pensiero, istituzioni e strutture sociali che hanno dato forme per certi versi simili alle civilt\ue0 del Vicino e Medio Oriente, al subcontinente indiano, ma anche, al di l\ue0 di queste, a parte dell'Africa subsahariana e alle isole del sudest asiatico

Aspetti dell'autorità nei Paesi musulmani: riflessioni e prospettive

This chapter outlines the scope of the volume, discussing key concepts around the concept of authority and power in different historical and regional contexts

International Trade Fair Report on 5 Leading European Countries, 1990-2006

Annual analysis based on certified data on international trade shows in Europe. Evaluation of the trend for 5 main countrie

Determining the Chemical Reactivity Trends of Pd/Ru(0001) Pseudomorphic Overlayers: Core-Level Shift Measurements and DFT Calculations

We have addressed the problem of determining a reliable experimental descriptor of surface chemical reactivity by measuring Pd and Ru 3d(5/2) core-level shifts of the Pd(n)/Ru(0001) pseudomorphic overlayer system (n = 0-3) by high resolution X-ray photoelectron spectroscopy. We find a linear relationship between the calculated theoretical changes of the d-band center position projected on each Ru and Pd atomic layer (which is, according to the Hammer and Norskov d-band model, a good theoretical descriptor of chemical reactivity) and the corresponding core-level shifts, both for the Ru atomic planes and for the Pd overlayers. Core-level shifts, therefore, should be considered as reliable experimental descriptors of chemical reactivity in the same sense (and with similar limitations) of the theoretical descriptor d-band center. Final-state effect contributions to the shifts do not obscure this trend