ABCC6 is a basolateral plasma membrane protein

RATIONALE:: ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein. OBJECTIVE:: In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment. METHODS AND RESULTS:: We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum. CONCLUSIONS:: Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation. © 2013 American Heart Association, Inc

Resonant scattering of positronium as a quasifree electron

In order to clarify the physics underlying the observations of the electronlike behavior of positronium (Ps) and its resonant scattering from CO2, we have measured the Ps+N2 total cross section and found it also to exhibit significant structure. Analysis of the resonances reveals that Ps is distorted in the collisions and classical trajectory Monte Carlo calculations indicate that the electron is on average closer to the target than the positron, which may in turn bind resonantly to the ensuing temporary negative ion. This description of the nature of Ps resonances agrees with long-standing theoretical predictions

Complete Break Up of Ortho Positronium (Ps)- Hydrogenic ion System

The dynamics of the complete breakup process in an Ortho Ps - He+ system including electron loss to the continuum (ELC) is studied where both the projectile and the target get ionized. The process is essentially a four body problem and the present model takes account of the two centre effect on the electron ejected from the Ps atom which is crucial for a proper description of the ELC phenomena. The calculations are performed in the framework of Coulomb Distorted Eikonal Approximation. The exchange effect between the target and the projectile electron is taken into account in a consistent manner. The proper asymptotic 3-body boundary condition for this ionization process is also satisfied in the present model. A distinct broad ELC peak is noted in the fully differential cross sections (5DCS) for the Ps electron corroborating qualitatively the experiment for the Ps - He system. Both the dynamics of the ELC from the Ps and the ejected electron from the target He+ in the FDCS are studied using coplanar geometry. Interesting features are noted in the FDCS for both the electrons belonging to the target and the projectile.Comment: 14 pages,7 figure

Measurement of the Spin-Dependence of the pbar-p Interaction at the AD-Ring

We propose to use an internal polarized hydrogen storage cell gas target in the AD ring to determine for the first time the two total spin-dependent pbar-p cross sections sigma_1 and sigma_2 at antiproton beam energies in the range from 50 to 450 MeV. The data obtained are of interest by themselves for the general theory of pbar-p interactions since they will provide a first experimental constraint of the spin-spin dependence of the nucleon-antinucleon potential in the energy range of interest. In addition, measurements of the polarization buildup of stored antiprotons are required to define the optimum parameters of a future, dedicated Antiproton Polarizer Ring (APR), intended to feed a double-polarized asymmetric pbar-p collider with polarized antiprotons. Such a machine has recently been proposed by the PAX collaboration for the new Facility for Antiproton and Ion Research (FAIR) at GSI in Darmstadt, Germany. The availability of an intense stored beam of polarized antiprotons will provide access to a wealth of single- and double-spin observables, thereby opening a new window on QCD spin physics.Comment: 51 pages, 23 figures, proposal submitted to the SPS committee of CER

EFFECT OF FERTILIZERS ON THE YIELD, PROTEIN CONTENT AND AMINO ACID COMPOSITION OF WINTER CEREALS

The effect of different fertilizers (nitrogen, phosphorus, potassium) and their combinations on the yield, raw protein content and amino acid composition were studied in field experiments. The levels of treatment were 200 kg/ha for nitrogen, 500-1000 kg/ha for phosphorus and potassium. Winter rye, triticale and wheat cultivar were grown in two subsequent years. Nitrogen fertilization in all cases increased the yield of grains and the raw protein content. The increase reached about 50% in average comparing with control samples grown without adding nitrogen fertilizers. Although there are significant differences between the different cereals studied, it can be generally stated that the increase in protein content is connected with a decrease in the essential to non-essential amino acid ratio. The decrease is higher if only nitrogen fertilizer is used and moderate if a combined treatment with nitrogen, phosphorus and potassium fertilizer is applied

Ageism and sexuality

Sexuality remains important throughout a person’s life, but sexual behavior does not receive the same levels of acceptance at all ages. Older people are challenged by ageist attitudes and perceptions that hinder their sexual expression. They are stereotyped as non-sexual beings who should not, cannot, and do not want to have sexual relationships. Expressing sexuality or engaging in sexual activity in later life is considered by many in society as immoral or perverted. False expectations for older people also stem from ideals of beauty, centralization of the biomedical perspective on sexuality of older adults, and the association of sex with reproduction. Unfortunately, older people internalize many ageist attitudes towards sexuality in later life and become less interested in sex and less sexually active. The following chapter explores attitudes towards sexuality in later life among the media, young people, older people themselves, and care providers. In order to enable older people to express their sexuality and sexual identity freely and fully, awareness of ageist perceptions must be raised and defeated

Interoperable AI: Evolutionary Race Towards Sustainable Knowledge Sharing

Article and Supplementary MaterialInternational audienceThe advancement and deployment of artificial intelligent agents brought numerous benefits in knowledge and data gathering and processing. However, one of the key challenges in deploying such agents in an open environment like the Web is their interoperability as they currently mostly run in silos. In this paper we report on a simulation and evaluation based on evolutionary agent-based modelling to empirically test how sustainable different strategies are for knowledge sharing in open multi-agent systems (MAS). Our results show the importance of translation-based approaches and the need for incentives to support these

Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers

Multidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic compartmentalization in lysosomes because of their hydrophobic weak base nature. We hence developed a novel photoactivation-based pharmacological Trojan horse approach to target and eradicate MDR cancer cells based on photo-rupture of IA-loaded lysosomes and tumor cell lysis via formation of reactive oxygen species. Illumination of IA-loaded cells resulted in lysosomal photodestruction and restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1 resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring parental cell sensitivity. Finally, in vivo application of this photodynamic therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in the chorioallantoic membrane model revealed selective destruction of tumors and their associated vasculature. These findings identify lysosomal sequestration of IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor cells via lysosomal photodestruction

Polarizing a stored proton beam by spin flip?

We discuss polarizing a proton beam in a storage ring, either by selective removal or by spin flip of the stored ions. Prompted by recent, conflicting calculations, we have carried out a measurement of the spin-flip cross section in low-energy electron-proton scattering. The experiment uses the cooling electron beam at COSY as an electron target. The measured cross sections are too small for making spin flip a viable tool in polarizing a stored beam. This invalidates a recent proposal to use co-moving polarized positrons to polarize a stored antiproton beam. (C) 2009 Elsevier B.V. All rights reserved