Nitric oxide inhibits enterocyte mitochondrial phospholipase D

AbstractMitochondrial damage is one of the prominent features of cell death in oxidative stress and related pathological conditions. Alteration in membrane lipid composition may be responsible for the mitochondrial damage. In this study, we have shown that intestinal mitochondria contain an active phospholipase D (PLD) which is activated by oxidants, Ca2+ or polyamines and this results in degradation of phosphatidylethanolamine (PE) and formation of phosphatidic acid (PA). This PLD activity is inhibited by nitric oxide (NO) which prevents the lipid alteration in mitochondria when exposed to these agents. This can be reversed by the NO scavenger, haemoglobin. This suggests that alteration of mitochondrial membrane lipid composition by activation of PLD in certain pathological condition such as oxidative stress may be prevented by the simultaneous presence of nitric oxide

Phenomenology of a Pseudo-Scalar Inflaton: Naturally Large Nongaussianity

Many controlled realizations of chaotic inflation employ pseudo-scalar axions. Pseudo-scalars \phi are naturally coupled to gauge fields through c \phi F \tilde{F}. In the presence of this coupling, gauge field quanta are copiously produced by the rolling inflaton. The produced gauge quanta, in turn, source inflaton fluctuations via inverse decay. These new cosmological perturbations add incoherently with the "vacuum" perturbations, and are highly nongaussian. This provides a natural mechanism to generate large nongaussianity in single or multi field slow-roll inflation. The resulting phenomenological signatures are highly distinctive: large nongaussianity of (nearly) equilateral shape, in addition to detectably large values of both the scalar spectral tilt and tensor-to-scalar ratio (both being typical of large field inflation). The WMAP bound on nongaussianity implies that the coupling, c, of the pseudo-scalar inflaton to any gauge field must be smaller than about 10^{2} M_p^{-1}.Comment: 45 pages, 7 figure

N=1* in 5 dimensions: Dijkgraaf-Vafa meets Polchinski-Strassler

One of the powerful techniques to analyze the 5 dimensional Super Yang Mills theory with a massive hypermultiplet (N=1*) is provided by the AdS/CFT correspondence. It predicts that, for certain special values of the hypermultiplet mass, this theory develops nonperturbative branches of the moduli space as well as new light degrees of freedom. We use the higher dimensional generalization of the matrix model/gauge theory correspondence and recover all the prediction of the supergravity analysis. We construct the map between the four dimensional holomorphic superpotential and the five dimensional action and explicitly show that the superpotential is flat along the nonperturbative branches. This is the first instance in which the Dijkgraaf-Vafa method is used to analyze intrinsically higher dimensional phenomena.Comment: 28 pages, Late

Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 and review of published literature

BACKGROUND: Bainbridge-Ropers syndrome (BRPS) is a recently described developmental disorder caused by de novo truncating mutations in the additional sex combs like 3 (ASXL3) gene. To date, there have been fewer than 10 reported patients. OBJECTIVES: Here, we delineate the BRPS phenotype further by describing a series of 12 previously unreported patients identified by the Deciphering Developmental Disorders study. METHODS: Trio-based exome sequencing was performed on all 12 patients included in this study, which found a de novo truncating mutation in ASXL3. Detailed phenotypic information and patient images were collected and summarised as part of this study. RESULTS: By obtaining genotype:phenotype data, we have been able to demonstrate a second mutation cluster region within ASXL3. This report expands the phenotype of older patients with BRPS; common emerging features include severe intellectual disability (12/12), poor/ absent speech (12/12), autistic traits (9/12), distinct face (arched eyebrows, prominent forehead, high-arched palate, hypertelorism and downslanting palpebral fissures), (9/12), hypotonia (12/12) and significant feeding difficulties (12) when young. DISCUSSION: Similarities in the patients reported previously in comparison with this cohort included their distinctive craniofacial features, feeding problems, absent/limited speech and intellectual disability. Shared behavioural phenotypes include autistic traits, hand-flapping, rocking, aggressive behaviour and sleep disturbance. CONCLUSIONS: This series expands the phenotypic spectrum of this severe disorder and highlights its surprisingly high frequency. With the advent of advanced genomic screening, we are likely to identify more variants in this gene presenting with a variable phenotype, which this study will explore

Metastable SUSY Breaking, de Sitter Moduli Stabilisation and K\"ahler Moduli Inflation

We study the influence of anomalous U(1) symmetries and their associated D-terms on the vacuum structure of global field theories once they are coupled to N=1 supergravity and in the context of string compactifications with moduli stabilisation. In particular, we focus on a IIB string motivated construction of the ISS scenario and examine the influence of one additional U(1) symmetry on the vacuum structure. We point out that in the simplest one-Kahler modulus compactification, the original ISS vacuum gets generically destabilised by a runaway behaviour of the potential in the modulus direction. In more general compactifications with several Kahler moduli, we find a novel realisation of the LARGE volume scenario with D-term uplifting to de Sitter space and both D-term and F-term supersymmetry breaking. The structure of soft supersymmetry breaking terms is determined in the preferred scenario where the standard model cycle is not stabilised non-perturbatively and found to be flavour universal. Our scenario also provides a purely supersymmetric realisation of Kahler moduli (blow-up and fibre) inflation, with similar observational properties as the original proposals but without the need to include an extra (non-SUSY) uplifting term.Comment: 38 pages, 8 figures. v2: references added, minor correction

Chiral Rings and Phases of Supersymmetric Gauge Theories

We solve for the expectation values of chiral operators in supersymmetric U(N) gauge theories with matter in the adjoint, fundamental and anti-fundamental representations. A simple geometric picture emerges involving a description by a meromorphic one-form on a Riemann surface. The equations of motion are equivalent to a condition on the integrality of periods of this form. The solution indicates that all semiclassical phases with the same number of U(1) factors are continuously connected.Comment: 55 page

Neutralino, axion and axino cold dark matter in minimal, hypercharged and gaugino AMSB

Supersymmetric models based on anomaly-mediated SUSY breaking (AMSB) generally give rise to a neutral wino as a WIMP cold dark matter (CDM) candidate, whose thermal abundance is well below measured values. Here, we investigate four scenarios to reconcile AMSB dark matter with the measured abundance: 1. non-thermal wino production due to decays of scalar fields ({\it e.g} moduli), 2. non-thermal wino production due to decays of gravitinos, 3. non-thermal wino production due to heavy axino decays, and 4. the case of an axino LSP, where the bulk of CDM is made up of axions and thermally produced axinos. In cases 1 and 2, we expect wino CDM to constitute the entire measured DM abundance, and we investigate wino-like WIMP direct and indirect detection rates. Wino direct detection rates can be large, and more importantly, are bounded from below, so that ton-scale noble liquid detectors should access all of parameter space for m_{\tz_1}\alt 500 GeV. Indirect wino detection rates via neutrino telescopes and space-based cosmic ray detectors can also be large. In case 3, the DM would consist of an axion plus wino admixture, whose exact proportions are very model dependent. In this case, it is possible that both an axion and a wino-like WIMP could be detected experimentally. In case 4., we calculate the re-heat temperature of the universe after inflation. In this case, no direct or indirect WIMP signals should be seen, although direct detection of relic axions may be possible. For each DM scenario, we show results for the minimal AMSB model, as well as for the hypercharged and gaugino AMSB models.Comment: 29 pages including 13 figure

Challenges and Obstacles for a Bouncing Universe in Brane Models

A Brane evolving in the background of a charged AdS black-hole displays in general a bouncing behaviour with a smooth transition from a contracting to an expanding phase. We examine in detail the conditions and consequences of this behaviour in various cases. For a cosmological-constant-dominated Brane, we obtain a singularity-free, inflationary era which is shown to be compatible only with an intermediate-scale fundamental Planck mass. For a radiation-dominated Brane, the bouncing behaviour can occur only for background-charge values exceeding those allowed for non-extremal black holes. For a matter-dominated Brane, the black-hole mass affects the proper volume or the expansion rate of the Brane. We also consider the Brane evolving in an asymmetric background of two distinct charged AdS black hole spacetimes being bounded by the Brane and find that, in the case of an empty critical Brane, bouncing behaviour occurs only if the black-hole mass difference is smaller than a certain value. The effects of a Brane curvature term on the bounce at early and late times are also investigated.Comment: 23 pages, Latex file, comments and references added, version to appear in Phys. Rev.

Rotating Black Branes in the presence of nonlinear electromagnetic field

In this paper, we consider a class of gravity whose action represents itself as a sum of the usual Einstein-Hilbert action with cosmological constant and an $U(1)$ gauge field for which the action is given by a power of the Maxwell invariant. We present a class of the rotating black branes with Ricci flat horizon and show that the presented solutions may be interpreted as black brane solutions with two event horizons, extreme black hole and naked singularity provided the parameters of the solutions are chosen suitably. We investigate the properties of the solutions and find that for the special values of the nonlinear parameter, the solutions are not asymptotically anti-deSitter. At last, we obtain the conserved quantities of the rotating black branes and find that the nonlinear source effects on the electric field, the behavior of spacetime, type of singularity and other quantities.Comment: 7 pages, 5 figures, to appear in EPJ

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change