Gene deficiency in activating Fcγ receptors influences the macrophage phenotypic balance and reduces atherosclerosis in mice

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fcγ receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fcγ receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in γ-chain (the common signaling subunit of activating Fcγ receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fcγ receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fcγ receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fcγ receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-κB activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fcγ receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fcγ receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fcγ receptor-mediated inflammatory responses could effectively suppress atherosclerosis

Chiral dynamics of kaon-nucleon interactions, revisited

The anti-kaon nucleon system close to threshold is analyzed in view of the new accurate DEAR kaonic hydrogen data. The calculations are performed using chiral SU(3) effective field theory in combination with non-perturbative schemes based on coupled channels. Several variants of such approaches are compared with experimental data and the differences in the results are discussed. Coulomb and isospin breaking effects turn out to be important and are both taken into account. The pole structure of the Lambda(1405) resonance close to the anti-kaon nucleon threshold is critically examined.Comment: 30 pages, 14 figures, 11 table

Cognitive Analytic Therapy in People with Learning Disability: An investigation into the common reciprocal roles found within this client group

Developments over the last twenty years have shown that, contrary to previous opinion, people with learning disabilities can benefit from psychotherapy (Sinason 1992; Kroese, Dagnan & Loumidia, 1997). Cognitive Analytic Therapy (CAT) has been adapted for use with a learning disability population (Ryle 2002). CAT collaboratively examines the Reciprocal Roles (RRs) a client plays in relationships. These are impacted by clients’ experiences of the world. The aim of this research is to identify which RRs may become apparent in working with people with learning disabilities. The therapy notes of participants (n=16) who had undergone CAT were examined and analysed using content analysis. Twenty-two different RRs were found. Four common Reciprocal Roles and two common idealised Reciprocal Roles were identified. Other observations about the data are presented. The limitations and clinical implications of the study are discussed

Screening of nuclear pairing in nuclear and neutron matter

The screening potential in the $^1S_0$ and $^3S_1$ pairing channels in neutron and nuclear matter in different approximations is discussed. It is found that the vertex corrections to the potential are much stronger in nuclear matter than in neutron matter.Comment: 11 pages, 8 figures, revtex4 styl

The nature of the Lambda(1405)

We present here some results supporting the nature of the $\Lambda(1405)$ resonance as dynamically generated from the meson baryon interaction in coupled channels and resulting from the superposition of two close-by poles. We find support for this picture in the $K^- p \to \pi^0 \pi^0 \Sigma^0$ reaction, which shows a different shape than the one obtained from the $\pi ^- p \to K^0 \pi \Sigma$ reaction. We also call the attention to the $K^- p \to \gamma \pi \Sigma$ with $\pi \Sigma$ in the $\Lambda(1405)$ region, which shows a narrow peak in the calculations around 1420 MeV. We also report on recent calculations of the radiative decay of the two $\Lambda(1405)$ states and on reactions to obtain information on these decay modes. Finally, we present results for the $pp\to p K^+\Lambda(1405)$ reaction recently measured at ANKE/COSY and compare them with theoretical results.Comment: Talk given at the NSTAR2007 Workshop, Bonn September 200

Pion Cloud Contribution to K+ Nucleus Scattering

A careful reanalysis is done of the contribution to $K^{+}$ nucleus scattering from the interaction of the kaon with the virtual pion cloud. The usual approximations made in the evaluation of the related kaon selfenergy are shown to fail badly. We also find new interaction mechanisms which provide appreciable corrections to the kaon selfenergy. Some of these contribute to the imaginary part below pion creation threshold. The inclusion of these new mechanisms in the inelastic part of the optical potential produces a significant improvement in the differential and total $K^{+}$ nuclear cross sections. Uncertainties remain in the dispersive part of the optical potential.Comment: 27 pages, 17 figures (not all of them included, please request them), report UG-DFM-2/9

Nuclear response functions in homogeneous matter with finite range effective interactions

The question of nuclear response functions in a homogeneous medium is examined. A general method for calculating response functions in the random phase approximation (RPA) with exchange is presented. The method is applicable for finite-range nuclear interactions. Examples are shown in the case of symmetric nuclear matter described by a Gogny interaction. It is found that the convergence of the results with respect to the multipole truncation is quite fast. Various approximation schemes such as the Landau approximation, or the Landau approximation for the exchange terms only, are discussed in comparison with the exact results.Comment: 9 pages, 9 figure

Vertical abundance stratification in the blue horizontal branch star HD135485

It is commonly believed that the observed overabundances of many chemical species relative to the expected cluster metallicity in blue horizontal branch (BHB) stars appear as a result of atomic diffusion in the photosphere. The slow rotation of BHB stars (with T_eff > 11,500K), typically v sin{i} < 10 km/s, is consistent with this idea. In this work we search for observational evidence of vertical chemical stratification in the atmosphere of HD135485. If this evidence exists, it will demonstrate the importance of atomic diffusion processes in the atmospheres of BHB stars. We undertake an extensive abundance stratification analysis of the atmosphere of HD135485, based on recently acquired high resolution and S/N CFHT ESPaDOnS spectra and a McDonald-CE spectrum. Our numerical simulations show that nitrogen and sulfur reveal signatures of vertical abundance stratification in the stellar atmosphere. It appears that the abundances of these elements increase toward the upper atmosphere. This fact cannot be explained by the influence of microturbulent velocity, because oxygen, carbon, neon, argon, titanium and chromium do not show similar behavior and their abundances remain constant throughout the atmosphere. It seems that the iron abundance may increase marginally toward the lower atmosphere. This is the first demonstration of vertical abundance stratification of metals in a BHB star.Comment: 8 pages, 5 figures, accepted to A&

Novel Antihypertensive Lactoferrin-Derived Peptides Produced by Kluyveromyces marxianus: Gastrointestinal Stability Profile and In Vivo Angiotensin I-Converting Enzyme (ACE) Inhibition

Novel antihypertensive peptides released by Kluyveromyces marxianus from bovine lactoferrin (LF) have been identified. K. marxianus LF permeate was fractionated by semipreparative high performance liquid chromatography and 35 peptides contained in the angiotensin I-converting enzyme (ACE)-inhibitory fractions were identified by using an ion trap mass spectrometer. On the basis of peptide abundance and common structural features, six peptides were chemically synthesized. Four of them (DPYKLRP, PYKLRP, YKLRP, and GILRP) exerted in vitro inhibitory effects on ACE activity and effectively decreased systolic blood pressure after oral administration to spontaneously hypertensive rats (SHRs). Stability against gastrointestinal enzymes suggested that the sequence LRP could contribute to the in vivo effects of parental peptides. Finally, there were reductions in circulating ACE activity and angiotensin II level in SHRs after either DPYKLRP or LRP intake, thus confirming ACE inhibition as the in vivo mechanism for their antihypertensive effect.This work was supported by grant AGL2010–21009 from ‘Ministerio de Educación y Ciencia - FEDER’, Consolider Ingenio 2010, Fun-C-Food, CSD2007–00063 and RETICS INVICTUS RD12/0014/0004 from ‘Instituto de Salud Carlos III’. A.G.-T. is the recipient of a predoctoral fellowship from ‘Ministerio de Educación y Ciencia’ (BES-2011–044424).Peer reviewe