Investigations into metabolism, transport and function of sulfonated steroids in the porcine testicular-epididymal compartment

Sulfonated steroids have been traditionally regarded as inactive metabolites destined for excretion, as they are incapable of binding to classical nuclear steroid receptors. However, by the enzyme steroid sulfatase (STS) they may be converted into free steroids, which may be biologically active directly or after a few additional enzymatic reactions. Thus, as sulfonated steroids commonly circulate at relatively high concentrations, they may form an important pool of precursors for the local (intra-tissue) production of active free steroids. This so-called sulfatase pathway has received increased attention over recent years especially with respect to estrogen metabolism in human hormone-dependent breast cancer, where the intratumoral estrogen production from sulfonated precursors obviously has a much higher capacity in comparison to the de novo synthesis via free steroids. This study is composed of two parts of which the first one addresses the secretory patterns of free and sulfonated steroids in vivo, whereas in the second part the expression of STS and of the steroid sulfotransferases SULT1E1 (estrogen specific) and SULT2B1 (specific for beta-hydroxysteroids) was characterized in the testis and in different segments of the epididymis. Other subjects of the second part of this study were hydrolysis of steroid sulfates and the sulfonation of estrone (E1), dehydroepiandrosterone (DHEA) and pregnenolone (P5) in the tissues investigated. Concentrations of androstenedione, testosterone, pregnenolone sulfate (P5S), dehydroepiandrosterone sulfate (DHEAS), estrone-3-sulfate (E1S)and 17beta-estradiol-3-sulfate were performed in the Steroid Research & Mass Spectrometry Unit, Division of Pediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus-Liebig-University, Giessen (head: Prof. Dr. S. Wudy) applying liquid chromatography tandem mass spectrometry (LC-MS-MS). Moreover, 17beta-estradiol (E2) and E1 were measured by inhouse radioimmunoassays to cope with the low concentrations of free estrogens in boars. In order to get new information on the sulfonation of free steroids and the hydrolysis of steroid sulfates in the porcine testicular-epididymal compartment, subcellular fractions were prepared from tissue samples collected from the testis and from defined sites of the epididymis (EH1, EH2: proximal/distal part of epididymal head; EB1-4: epididymal body, from proximal to distal; ET1, ET2: proximal/distal part of epididymal tail) using differential centrifugation. STS and steroid sulfotransferase activities were measured based on the differential distribution of free and sulfonated steroids between an aqueous phase and an organic solvent, tert butyl-methylether. The immunostaining results were shown that SULTs 1E1 and 2B1, immunostaining was especially prominent in superficial epithelial protrusions. Sporadic staining of weaker intensity was also found in the muscular layer and in the vascular endothelium. With WB, a specific band of the expected molecular size (approx. 61 kDa) was found in the testis and all segments of the epididymis. These results show that STS is widely expressed in the porcine testicular-epididymal compartment, indicating a high potential for sulfatase pathways especially in Leydig cells and the epithelial cells of the rete testis and epididymis. The co-expression of STS with SULTs 1E1 and 2B1 in the epididymal epithelium and especially their colocalization in superficial protrusions are very intriguing. In the epididymal duct, apocrine secretion has been described to give rise to the formation of epididymosomes, small vesicles which are considered as vehicles for the transfer of certain molecules to the maturing sperm cells. Other intriguing findings are the virtual absence of a sulfonation of E1, DHEA and P5 in testicular cytosols as well as the absent or questionable detection of SULTs 1E1 and 2B1 in light of the high efflux of various steroid sulfates from the testis. A plausible explanation could be a significant use of sulfonated steroids as precursors/intermediates in porcine testicular steroidogenesis starting from cholesterol sulfate. The concept of a “sulfate pathway” of steroidogenesis would not only provide an explanation for the production of high amounts of steroid sulfates in the virtual absence of relevant steroid sulfotransferase activities but also for the high STS expression in Leydig cells. According to this concept, STS could play a crucial role in the control of the substrate flow through the steroidogenic enzyme cascade by mediating the transition of sulfonated precursors into the pool of free steroids, with the exact subcellular localization being of importance for the step of the enzyme cascade at which this transition(s) may occur. Thus, in order to corroborate this concept investigations into the utilization of sulfonated substrates by steroidogenic enzymes and on the subcellular localization of STS are necessary

Kaon-Nucleon Scattering Amplitudes and Z∗^*-Enhancements from Quark Born Diagrams

We derive closed form kaon-nucleon scattering amplitudes using the ``quark Born diagram" formalism, which describes the scattering as a single interaction (here the OGE spin-spin term) followed by quark line rearrangement. The low energy I=0 and I=1 S-wave KN phase shifts are in reasonably good agreement with experiment given conventional quark model parameters. For $k_{lab}> 0.7$ Gev however the I=1 elastic phase shift is larger than predicted by Gaussian wavefunctions, and we suggest possible reasons for this discrepancy. Equivalent low energy KN potentials for S-wave scattering are also derived. Finally we consider OGE forces in the related channels K$\Delta$, K$^*$N and K$^*\Delta$, and determine which have attractive interactions and might therefore exhibit strong threshold enhancements or ``Z$^*$-molecule" meson-baryon bound states. We find that the minimum-spin, minimum-isospin channels and two additional K$^*\Delta$ channels are most conducive to the formation of bound states. Related interesting topics for future experimental and theoretical studies of KN interactions are also discussed.Comment: 34 pages, figures available from the authors, revte

Evaluating Lifeworld as an emancipatory methodology

Disability research is conducted within a highly politicised ‘hotbed’ of competing paradigms and principles. New researchers, who want to work within the social model, are soon faced with complex and challenging methodological and philosophical dilemmas. The social model advocates research agendas that are focused on the emancipation and empowerment of disabled people but, in reality, these are rarely achieved. To be successful researchers need to engage with innovative and creative methodologies and to share their experiences of these within environments that welcome challenge and debate. This paper focuses on Lifeworld and assesses its value as a tool for emancipatory research. Using examples from a study with parents, whose children were in the process of being labelled as having autism, the paper illustrates how the principles that ‘underpin’ the methodology offered a supportive framework for a novice researcher

Transverse Spin at PHENIX: Results and Prospects

The Relativistic Heavy Ion Collider (RHIC), as the world's first and only polarized proton collider, offers a unique environment in which to study the spin structure of the proton. In order to study the proton's transverse spin structure, the PHENIX experiment at RHIC took data with transversely polarized beams in 2001-02 and 2005, and it has plans for further running with transverse polarization in 2006 and beyond. Results from early running as well as prospective measurements for the future will be discussed.Comment: 6 pages, 2 figures, presented at Transversity 2005, Como, Ital

Geomorphological significance of Ontario Lacus on Titan: Integrated interpretation of Cassini VIMS, ISS and RADAR data and comparison with the Etosha Pan (Namibia)

International audienceOntario Lacus is the largest lake of the whole southern hemisphere of Titan, Saturn's major moon. It has been imaged twice by each of the Cassini imaging systems (Imaging Science Subsystem (ISS) in 2004 and 2005, Visual and Infrared Mapping Spectrometer (VIMS) in 2007 and 2009 and Radar in 2009 and 2010). In this study, we take advantage of each imaging dataset to establish a global survey of Ontario Lacus' environment from 2005 to 2010. We perform a geomorphological mapping and interpretation of Ontario Lacus, mainly based on a joint analysis of VIMS and Radar SAR datasets, along with the T49 altimetric profile acquired in December 2008. The morphologies observed on Ontario Lacus are compared to landforms of a semi-arid terrestrial analog, which closely resembles Titan's lakes: the pans of the Etosha Basin, located in Namibia. From this comparison, we infer that Ontario Lacus is an extremely flat depression where liquids, only located in the darkest areas in the Radar data, cover topographic lows where the "alkanofer" would raise above the depression floor. The rest of the depression appears rather as a muddy flat surface likely composed of a thick coating of photon-absorbing materials, explaining its still rather dark appearance in the infrared and radar data. We also determined whether surface changes occurred during the 5 years time interval between 2005 and 2010. We found that the depression contour is constant at the resolution of ISS and VIMS data, both being consistent with the depression contour derived from the Radar data. Our interpretation, in which the liquids are located only in some parts of Ontario Lacus, agrees with the lack of significant change of the depression contour between 2007 (and 2005 with more uncertainties) and 2010

Decoupling of the S=1/2 antiferromagnetic zig-zag ladder with anisotropy

The spin-1/2 antiferromagnetic zig-zag ladder is studied by exact diagonalization of small systems in the regime of weak inter-chain coupling. A gapless phase with quasi long-range spiral correlations has been predicted to occur in this regime if easy-plane (XY) anisotropy is present. We find in general that the finite zig-zag ladder shows three phases: a gapless collinear phase, a dimer phase and a spiral phase. We study the level crossings of the spectrum,the dimer correlation function, the structure factor and the spin stiffness within these phases, as well as at the transition points. As the inter-chain coupling decreases we observe a transition in the anisotropic XY case from a phase with a gap to a gapless phase that is best described by two decoupled antiferromagnetic chains. The isotropic and the anisotropic XY cases are found to be qualitatively the same, however, in the regime of weak inter-chain coupling for the small systems studied here. We attribute this to a finite-size effect in the isotropic zig-zag case that results from exponentially diverging antiferromagnetic correlations in the weak-coupling limit.Comment: to appear in Physical Review

The mass-to-light ratio of rich star clusters

We point out a strong time-evolution of the mass-to-light conversion factor eta commonly used to estimate masses of unresolved star clusters from observed cluster spectro-photometric measures. We present a series of gas-dynamical models coupled with the Cambridge stellar evolution tracks to compute line-of-sight velocity dispersions and half-light radii weighted by the luminosity. We explore a range of initial conditions, varying in turn the cluster mass and/or density, and the stellar population's IMF. We find that eta, and hence the estimated cluster mass, may increase by factors as large as 3 over time-scales of 50 million years. We apply these results to an hypothetic cluster mass distribution function (d.f.) and show that the d.f. shape may be strongly affected at the low-mass end by this effect. Fitting truncated isothermal (Michie-King) models to the projected light profile leads to over-estimates of the concentration parameter c of delta c ~ 0.3 compared to the same functional fit applied to the projected mass density.Comment: 6 pages, 2 figures, to appear in the proceedings of the "Young massive star clusters", Granada, Spain, September 200

Shear-banding in a lyotropic lamellar phase, Part 1: Time-averaged velocity profiles

Using velocity profile measurements based on dynamic light scattering and coupled to structural and rheological measurements in a Couette cell, we present evidences for a shear-banding scenario in the shear flow of the onion texture of a lyotropic lamellar phase. Time-averaged measurements clearly show the presence of structural shear-banding in the vicinity of a shear-induced transition, associated to the nucleation and growth of a highly sheared band in the flow. Our experiments also reveal the presence of slip at the walls of the Couette cell. Using a simple mechanical approach, we demonstrate that our data confirms the classical assumption of the shear-banding picture, in which the interface between bands lies at a given stress $\sigma^\star$. We also outline the presence of large temporal fluctuations of the flow field, which are the subject of the second part of this paper [Salmon {\it et al.}, submitted to Phys. Rev. E]

Quantum cellular automata quantum computing with endohedral fullerenes

We present a scheme to perform universal quantum computation using global addressing techniques as applied to a physical system of endohedrally doped fullerenes. The system consists of an ABAB linear array of Group V endohedrally doped fullerenes. Each molecule spin site consists of a nuclear spin coupled via a Hyperfine interaction to an electron spin. The electron spin of each molecule is in a quartet ground state $S=3/2$. Neighboring molecular electron spins are coupled via a magnetic dipole interaction. We find that an all-electron construction of a quantum cellular automata is frustrated due to the degeneracy of the electronic transitions. However, we can construct a quantum celluar automata quantum computing architecture using these molecules by encoding the quantum information on the nuclear spins while using the electron spins as a local bus. We deduce the NMR and ESR pulses required to execute the basic cellular automata operation and obtain a rough figure of merit for the the number of gate operations per decoherence time. We find that this figure of merit compares well with other physical quantum computer proposals. We argue that the proposed architecture meets well the first four DiVincenzo criteria and we outline various routes towards meeting the fifth criteria: qubit readout.Comment: 16 pages, Latex, 5 figures, See http://planck.thphys.may.ie/QIPDDF/ submitted to Phys. Rev.