Gaugino Anomaly Mediated SUSY Breaking: phenomenology and prospects for the LHC

We examine the supersymmetry phenomenology of a novel scenario of supersymmetry (SUSY) breaking which we call Gaugino Anomaly Mediation, or inoAMSB. This is suggested by recent work on the phenomenology of flux compactified type IIB string theory. The essential features of this scenario are that the gaugino masses are of the anomaly-mediated SUSY breaking (AMSB) form, while scalar and trilinear soft SUSY breaking terms are highly suppressed. Renormalization group effects yield an allowable sparticle mass spectrum, while at the same time avoiding charged LSPs; the latter are common in models with negligible soft scalar masses, such as no-scale or gaugino mediation models. Since scalar and trilinear soft terms are highly suppressed, the SUSY induced flavor and CP-violating processes are also suppressed. The lightest SUSY particle is the neutral wino, while the heaviest is the gluino. In this model, there should be a strong multi-jet +etmiss signal from squark pair production at the LHC. We find a 100 fb^{-1} reach of LHC out to m_{3/2}\sim 118 TeV, corresponding to a gluino mass of \sim 2.6 TeV. A double mass edge from the opposite-sign/same flavor dilepton invariant mass distribution should be visible at LHC; this, along with the presence of short-- but visible-- highly ionizing tracks from quasi-stable charginos, should provide a smoking gun signature for inoAMSB.Comment: 30 pages including 14 .eps figure

Chiral Modulations in Curved Space I: Formalism

The goal of this paper is to present a formalism that allows to handle four-fermion effective theories at finite temperature and density in curved space. The formalism is based on the use of the effective action and zeta function regularization, supports the inclusion of inhomogeneous and anisotropic phases. One of the key points of the method is the use of a non-perturbative ansatz for the heat-kernel that returns the effective action in partially resummed form, providing a way to go beyond the approximations based on the Ginzburg-Landau expansion for the partition function. The effective action for the case of ultra-static Riemannian spacetimes with compact spatial section is discussed in general and a series representation, valid when the chemical potential satisfies a certain constraint, is derived. To see the formalism at work, we consider the case of static Einstein spaces at zero chemical potential. Although in this case we expect inhomogeneous phases to occur only as meta-stable states, the problem is complex enough and allows to illustrate how to implement numerical studies of inhomogeneous phases in curved space. Finally, we extend the formalism to include arbitrary chemical potentials and obtain the analytical continuation of the effective action in curved space.Comment: 22 pages, 3 figures; version to appear in JHE

Neutralino versus axion/axino cold dark matter in the 19 parameter SUGRA model

We calculate the relic abundance of thermally produced neutralino cold dark matter in the general 19 parameter supergravity (SUGRA-19) model. A scan over GUT scale parameters reveals that models with a bino-like neutralino typically give rise to a dark matter density \Omega_{\tz_1}h^2\sim 1-1000, i.e. between 1 and 4 orders of magnitude higher than the measured value. Models with higgsino or wino cold dark matter can yield the correct relic density, but mainly for neutralino masses around 700-1300 GeV. Models with mixed bino-wino or bino-higgsino CDM, or models with dominant co-annihilation or A-resonance annihilation can yield the correct abundance, but such cases are extremely hard to generate using a general scan over GUT scale parameters; this is indicative of high fine-tuning of the relic abundance in these cases. Requiring that m_{\tz_1}\alt 500 GeV (as a rough naturalness requirement) gives rise to a minimal probably dip in parameter space at the measured CDM abundance. For comparison, we also scan over mSUGRA space with four free parameters. Finally, we investigate the Peccei-Quinn augmented MSSM with mixed axion/axino cold dark matter. In this case, the relic abundance agrees more naturally with the measured value. In light of our cumulative results, we conclude that future axion searches should probe much more broadly in axion mass, and deeper into the axion coupling.Comment: 23 pages including 17 .eps figure

Surfactant proteins SP-A and SP-D modulate uterine contractile events in ULTR myometrial cell line

Pulmonary surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules. However, there is extrapulmonary existence, especially in the amniotic fluid and at the feto-maternal interface. There is sufficient evidence to suggest that SP-A and SP-D are involved in the initiation of labour. This is of great importance given that preterm birth is associated with increased mortality and morbidity. In this study, we investigated the effects of recombinant forms of SP-A and SP-D (rhSP-A and rhSP-D, the comprising of trimeric lectin domain) on contractile events in vitro, using a human myometrial cell line (ULTR) as an experimental model. Treatment with rhSP-A or rhSP-D increased the cell velocity, distance travelled and displacement by ULTR cells. rhSP-A and rhSP-D also affected the contractile response of ULTRs when grown on collagen matrices showing reduced surface area. We investigated this effect further by measuring contractility-associated protein (CAP) genes. Treatment with rhSP-A and rhSP-D induced expression of oxytocin receptor (OXTR) and connexin 43 (CX43). In addition, rhSP-A and rhSP-D were able to induce secretion of GROα and IL-8. rhSP-D also induced the expression of IL-6 and IL-6 Ra. We provide evidence that SP-A and SP-D play a key role in modulating events prior to labour by reconditioning the human myometrium and in inducing CAP genes and pro-inflammatory cytokines thus shifting the uterus from a quiescent state to a contractile one

Increased dynamics in the 40-57 Ω-loop of the G41S variant of human cytochrome c promote its pro-apoptotic conformation

Thrombocytopenia 4 is an inherited autosomal dominant thrombocytopenia, which occurs due to mutations in the human gene for cytochrome c that results in enhanced mitochondrial apoptotic activity. The Gly41Ser mutation was the first to be reported. Here we report stopped-flow kinetic studies of azide binding to human ferricytochrome c and its Gly41Ser variant, together with backbone amide H/D exchange and 15N-relaxation dynamics using NMR spectroscopy, to show that alternative conformations are kinetically and thermodynamically more readily accessible for the Gly41Ser variant than for the wild-type protein. Our work reveals a direct conformational link between the 40-57 Ω-loop in which residue 41 resides and the dynamical properties of the axial ligand to the heme iron, Met80, such that the replacement of glycine by serine promotes the dissociation of the Met80 ligand, thereby increasing the population of a peroxidase active state, which is a key non-native conformational state in apoptosis

Impact of clerkship in the attitudes toward psychiatry among Portuguese medical students

<p>Abstract</p> <p>Background</p> <p>Given the shortage of human resources and the launching of a new Mental Health Plan, recruitment of psychiatrists is currently a major concern in Portugal, as well as in several other countries. Medical students' attitude toward psychiatry has been pointed as a predictor of recruitment. This study aims to evaluate the medical students' perception of psychiatry before and after a clerkship, and the impact on their intention to pursue psychiatry as a future specialty option.</p> <p>Methods</p> <p>Two self-report questionnaires were administered to all 6^thyear students in a medical school in Lisbon, before and after a 4-weeks full-time psychiatric clerkship, in order to evaluate attitudes toward psychiatry and intention to follow psychiatry in the future. Statistical analysis included Wilcoxon and Chi-square tests.</p> <p>Results</p> <p>153 students (60.8% female) filled in both questionnaires (no dropouts). After the clerkship, there was a significant improvement regarding the overall merits of psychiatry, efficacy, role definition and functioning of psychiatrists, use of legal powers to hospitalize patients and specific medical school factors. There was also a significant increase of students decided or considering the possibility to take a residency in psychiatry.</p> <p>However, perceptions of low prestige and negative pressure from family and peers regarding a future choice of psychiatry remained unchanged in about one-third of the students.</p> <p>Conclusions</p> <p>The results indicate clearly that the clerkship had a favorable overall impact on the student attitude towards psychiatry, as well as in the number of students considering a future career in psychiatry. Attitudes toward psychiatry seems a promising outcome indicator of the clerkship's quality, but further research is needed in order to assess its reliability as a sound predictor of recruitment.</p

Detection and characterisation of multi-drug resistance protein 1 (MRP-1) in human mitochondria

BACKGROUND: Overexpression of plasma membrane multi-drug resistance protein 1 (MRP-1) can lead to multidrug resistance. In this study, we describe for the first time the expression of mitochondrial MRP-1 in untreated human normal and cancer cells and tissues. METHODS: MRP-1 expression and subcellular localisation in normal and cancer cells and tissues was examined by differential centrifugation and western blotting, and immunofluorescence microscopy. Viable mitochondria were isolated and MRP-1 efflux activity measured using the calcein-AM functional assay. MRP-1 expression was increased using retroviral infection and specific overexpression confirmed by RNA array. Cell viability was determined by trypan blue exclusion and annexin V-propidium iodide labelling of cells. RESULTS: MRP-1 was detected in the mitochondria of cancer and normal cells and tissues. The efflux activity of mitochondrial MRP-1 was more efficient (55-64%) than that of plasma membrane MRP-1 (11-22%; P<0.001). Induced MRP-1 expression resulted in a preferential increase in mitochondrial MRP-1, suggesting selective targeting to this organelle. Treatment with a non-lethal concentration of doxorubicin (0.85 nM, 8 h) increased mitochondrial and plasma membrane MRP-1, increasing resistance to MRP-1 substrates. For the first time, we have identified MRP-1 with efflux activity in human mitochondria. CONCLUSION: Mitochondrial MRP-1 may be an exciting new therapeutic target where historically MRP-1 inhibitor strategies have limited clinical success

Wnt Signaling Is Required for Early Development of Zebrafish Swimbladder

10.1371/journal.pone.0018431PLoS ONE63

Pathogenic marine microbes influence the effects of climate change on a commercially important tropical bivalve

There is growing evidence that climate change will increase the prevalence of toxic algae and harmful bacteria, which can accumulate in marine bivalves. However, we know little about any possible interactions between exposure to these microorganisms and the effects of climate change on bivalve health, or about how this may affect the bivalve toxin-pathogen load. In mesocosm experiments, mussels, Perna viridis, were subjected to simulated climate change (warming and/or hyposalinity) and exposed to harmful bacteria and/or toxin-producing dinoflagellates. We found significant interactions between climate change and these microbes on metabolic and/or immunobiological function and toxin-pathogen load in mussels. Surprisingly, however, these effects were virtually eliminated when mussels were exposed to both harmful microorganisms simultaneously. This study is the first to examine the effects of climate change on determining mussel toxin-pathogen load in an ecologically relevant, multi-trophic context. The results may have considerable implications for seafood safety

Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses

Baculoviruses (BV) are DNA viruses that are pathogenic for insects. Although BV infect a range of mammalian cell types, they do not replicate in these cells. Indeed, the potential effects of these insect viruses on the immune responses of mammals are only just beginning to be studied. We show in this paper that a recombinant Autographa californica multiple nuclear polyhedrosis virus carrying a fragment of ovalbumin (OVA) on the VP39 capsid protein (BV-OVA) has the capacity to act as an adjuvant and vector of antigens in mice, thereby promoting specific CD4 and cytotoxic T cell responses against OVA. BV also induced in vivo maturation of dendritic cells and the production of inflammatory cytokines, thus promoting innate and adaptive immune responses. The OVA-specific response induced by BV-OVA was strong enough to reject a challenge with OVA-expressing melanoma cells (MO5 cells) and effectively prolonged survival of MO5 bearing mice. All these findings, together with the absence of pre-existing immunity to BV in humans and the lack of viral gene expression in mammalian cells, make BV a candidate for vaccination