Epoxygenation of arachidonic acid by rat anterior pituitary microsomal fractions

AbstractMicrosomal fractions isolated from rat anterior pituitary glands catalyze the oxygenation of arachidonic acid. By a combination of Chromatographic and mass spectrometric techniques, we have identified epoxy-eicosatrienoic acids as reaction products and thus documented the presence of an NADPH-dependent arachidonic acid epoxygenase activity in rat adenohypophysis

CYP-13A12 of the nematode Caenorhabditis elegans is a PUFA-epoxygenase involved in behavioural response to reoxygenation

A specific behavioural response of Caenorhabditis elegans, the rapid increase of locomotion in response to anoxia/reoxygenation called the O2-ON response, has been used to model key aspects of ischaemia/reperfusion injury. A genetic suppressor screen demonstrated a direct causal role of CYP (cytochrome P450)-13A12 in this response and suggested that CYP-eicosanoids, which in mammals influence the contractility of cardiomyocytes and vascular smooth muscle cells, might function in C. elegans as specific regulators of the body muscle cell activity. In the present study we show that co-expression of CYP-13A12 with the NADPH-CYP-reductase EMB-8 in insect cells resulted in the reconstitution of an active microsomal mono-oxygenase system that metabolized EPA (eicosapentaenoic acid) and also AA (arachidonic acid) to specific sets of regioisomeric epoxy and hydroxy derivatives. The main products included 17,18-EEQ (17,18-epoxyeicosatetraenoic acid) from EPA and 14,15-EET (14,15-epoxyeicosatrienoic acid) from AA. Locomotion assays showed that the defective O2-ON response of C20-PUFA (polyunsaturated fatty acid)-deficient, Δ-12 and Δ-6 fatty acid desaturase mutants (fat-2 and fat-3 respectively) can be restored by feeding the nematodes AA or EPA, but not ETYA (eicosatetraynoic acid), a non-metabolizable AA analogue. Short-term incubation with 17,18-EEQ was sufficient to rescue the impaired locomotion of the fat-3 strain. The endogenous level of free 17,18-EEQ declined during anoxia and was rapidly restored in response to reoxygenation. On the basis of these results, we suggest that CYP-dependent eicosanoids such as 17,18-EEQ function as signalling molecules in the regulation of the O2-ON response in C. elegans. Remarkably, the exogenously administered 17,18-EEQ increased the locomotion activity under normoxic conditions and was effective not only with C20-PUFA-deficient mutants, but to a lesser extent also with wild-type worms

Role of CYP eicosanoids in the regulation of pharyngeal pumping and food uptake in Caenorhabditis elegans

Cytochrome P450 (CYP)-dependent eicosanoids comprise epoxy- and hydroxy-metabolites of long-chain PUFAs (LC-PUFAs). In mammals, CYP eicosanoids contribute to the regulation of cardiovascular and renal function. Caenorhabditis elegans produces a large set of CYP eicosanoids; however, their role in worm's physiology is widely unknown. Mutant strains deficient in LC-PUFA/eicosanoid biosynthesis displayed reduced pharyngeal pumping frequencies. This impairment was rescued by long-term eicosapentaenoic and/or arachidonic acid supplementation, but not with a nonmetabolizable LC-PUFA analog. Short-term treatment with 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), the most abundant CYP eicosanoid in C. elegans, was as effective as long-term LC-PUFA supplementation in the mutant strains. In contrast, 20-HETE caused decreased pumping frequencies. The opposite effects of 17,18-EEQ and 20-HETE were mirrored by the actions of neurohormones. 17,18-EEQ mimicked the stimulating effect of serotonin when added to starved worms, whereas 20-HETE shared the inhibitory effect of octopamine in the presence of abundant food. In wild-type worms, serotonin increased free 17,18-EEQ levels, whereas octopamine selectively induced the synthesis of hydroxy-metabolites. These results suggest that CYP eicosanoids may serve as second messengers in the regulation of pharyngeal pumping and food uptake in C. elegans

Constrained Supersymmetric Flipped SU(5) GUT Phenomenology

We explore the phenomenology of the minimal supersymmetric flipped SU(5) GUT model (CFSU(5)), whose soft supersymmetry-breaking (SSB) mass parameters are constrained to be universal at some input scale, $M_{in}$, above the GUT scale, $M_{GUT}$. We analyze the parameter space of CFSU(5) assuming that the lightest supersymmetric particle (LSP) provides the cosmological cold dark matter, paying careful attention to the matching of parameters at the GUT scale. We first display some specific examples of the evolutions of the SSB parameters that exhibit some generic features. Specifically, we note that the relationship between the masses of the lightest neutralino and the lighter stau is sensitive to $M_{in}$, as is the relationship between the neutralino mass and the masses of the heavier Higgs bosons. For these reasons, prominent features in generic $(m_{1/2}, m_0)$ planes such as coannihilation strips and rapid-annihilation funnels are also sensitive to $M_{in}$, as we illustrate for several cases with tan(beta)=10 and 55. However, these features do not necessarily disappear at large $M_{in}$, unlike the case in the minimal conventional SU(5) GUT. Our results are relatively insensitive to neutrino masses.Comment: 23 pages, 8 figures; (v2) added explanations and corrected typos, version to appear in EPJ

Radiative Corrections to Neutralino and Chargino Masses in the Minimal Supersymmetric Model

We determine the neutralino and chargino masses in the MSSM at one-loop. We perform a Feynman diagram calculation in the on-shell renormalization scheme, including quark/squark and lepton/slepton loops. We find generically the corrections are of order 6%. For a 20 GeV neutralino the corrections can be larger than 20%. The corrections change the region of $\mu,\ M_2,\ \tan\beta$ parameter space which is ruled out by LEP data. We demonstrate that, e.g., for a given $\mu$ and $\tan\beta$ the lower limit on the parameter $M_2$ can shift by 20 GeV.Comment: 11 pages, JHU-TIPAC-930030, PURD-TH-93-13, uses epsf.sty, 6 uuencoded postscript figures, added one sentence and a referenc

Lepton Flavour Violation in a Class of Lopsided SO(10) Models

A class of predictive SO(10) grand unified theories with highly asymmetric mass matrices, known as lopsided textures, has been developed to accommodate the observed mixing in the neutrino sector. The model class effectively determines the rate for charged lepton flavour violation, and in particular the branching ratio for $\mu -> e \gamma$, assuming that the supersymmetric GUT breaks directly to the constrained minimal supersymmetric standard model (CMSSM). We find that in light of the combined constraints on the CMSSM parameters from direct searches and from the WMAP satellite observations, the resulting predicted rate for $\mu -> e \gamma$ in this model class can be within the current experimental bounds for low $\tan \beta$, but that the next generation of $\mu -> e \gamma$ experiments would effectively rule out this model class if LFV is not detected.Comment: 23 page

Measurement of SUSY masses via cascade decays for SPS 1a

If R-parity conserving supersymmetry exists below the TeV-scale, new particles will be produced and decay in cascades at the LHC. The lightest supersymmetric particle will escape the detectors, thereby complicating the full reconstruction of the decay chains. In this paper we expand on existing methods for determining the masses of the particles in the cascade from endpoints of kinematical distributions. We perform scans in the mSUGRA parameter space to delimit the region where this method is applicable. From the examination of theoretical distributions for a wide selection of mass scenarios it is found that caution must be exerted when equating the theoretical endpoints with the experimentally obtainable ones. We provide analytic formulae for the masses in terms of the endpoints most readily available. Complications due to the composite nature of the endpoint expressions are discussed in relation to the detailed analysis of two points on the SPS 1a line. Finally we demonstrate how a Linear Collider measurement can improve dramatically on the precision of the masses obtained

Yukawa structure, flavour and CP violation in Supergravity

The hierarchical structure of fermion masses and mixings strongly suggests an underlying family symmetry. In supergravity any familon field spontaneously breaking this symmetry necessarily acquires an F-term which contributes to the soft trilinear couplings. We show, as a result, mu -> e gamma decay can receive large contributions from this source at the level of current experimental bounds and thus this channel may provide the first indication of supersymmetry and a clue to the structure of the soft breaking sector. Using the mercury EDM bounds we find strong bounds on the right handed down quark mixing angles that are inconsistent with models relating them to neutrino mixing angles and favour a near-symmetric form for the magnitude of the down quark mass matrix.Comment: Final version to appear in PRD. Improved discusion of several points, updated references, typos correcte

Chemical speciation modelling of groundwater in a shallow glacial sand aquifer part 1 General parameters

The aim of the work detailed in this report has been to gain a better understanding of the speciation chemistry controlling the aqueous chemical forms of elements and compounds normally present in groundwaters found at the BGS in situ migration experiment at Drigg, Cumbria. This will form the basis of future modelling studies designed to interpret in situ tracer experiments using 60Co in the presence of naturally occurring organic complexants. Total element concentrations in relevant samples were obtained using Inductively Coupled Plasma Optical Emission Spectroscopy. The aqueous speciation chemistry was modelled using the geochemical code PHREEQE in conjunction with the UWIST thermodynamic database. The natural chemical speciation of each sample was determined as was the sensitivity to changes in chemical parameters such as pH and oxidation-reduction potential (Eh). In addition, the possible solubility limiting phases were determined for elements of interest. The results show that for all non-transition metal elements, the major aqueous species is the free ion. However, for the transition metal elements, this is not the case. For manganese, the carbonate species is by far the most abundant. This reflects the different complexing abilities of transition elements as compared to other metals. In the given system, carbonate equilibria are likely to control the calcium solubility. Calculation predict that the precipitation of calcium carbonate (as calcite) from the aqueous phase is unlikely. Hence, it can be concluded that coprecipitation of Ba2+ and sr2+ will not occur. The speciation of aqueous iron is very sensitive to changes in pH and Eh. When the Eh is changed by only 11 Om V (from +227m V to + 117m V) the dominant aqueous species is changed from Fe(OHho to Fe2+. The total change in the concentration of Fe(OHho over this range is an order of magnitude. Fe(OHho is an aqueous species of potential interest because calculations suggest that species such as this may precipitate and coprecipitate with radionuclide species (e.g. Co, Ni). The formation of iron hydroxide leads to an increase in the number of surface sites available for sorption of charged species and a corresponding reduction -in their aqueous concentration. There is also an increased probability Of the formation of colloidal particles involving humic and fulvic substances. Changes in pH and Eh are both possible during the tracer test, where waters of differing compositions are likely to mix within the aquifer as a result of pumping. These will be modelled and presented in part II, along with predictions for the speciation of various radionuclides added to the groundwater

Chemical speciation modelling of groundwater in a shallow glacial sand aquifer. Part II, radionuclide speciation and effect of organics

The aims of the work detailed in this report are to gain understanding of the changes that occur in groundwater chemistry following the addition of a) the radionuclides 58C0 and 63Ni, and b) organic complexants. The analytical data used in these modelling studies is as for the first report in this series, and consists of inductively coupled plasma analyses for total element concentrations of three samples. For reasons that are detailed in the text (section 4.3) only two of the three samples were modelled using the PHREEQE geochemical code in conjunction with the UWCC thermodynamic database. Acetate and EDTA were used as analogues for the weakest and strongest binding expected by the natural organic matter present in the aquifer. The results show that at the measured pH, the major form of 58C0 will be the Co2+ ion. In the case of 63Ni, the major aqueous phase species is NiC03O. The speciation of cobalt is unaltered with changes in the pH or Eh, whereas nickel is pH sensitive. The formation of solid phase cobalt or nickel species is not predicted. The addition of 58C0 to the aquifer as a CcbH2EDTA is predicted to result in the dissociation of the complex and consequent formation of the free Co2+ and ZnEDTA2-. Acetate doesn ot perturb either the natural aqueous speciatiorn the speciationo f the added radionuclides. In contrast, using EDTA as an analogue for natural organic matter results in significant perturbations of both the natural speciation and the radionuclide speciation. It was found that 48% of the total iron, 92% of the total cobalt and 99% of the total nickel were complexed by EDTA with an EDTA concentration equivalent to the measured total organic carbon concentration of 3.5 and 2.5 mg dm-3 in sample 2 and 3 respectively