Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

On the massive gluon propagator, the PT-BFM scheme and the low-momentum behaviour of decoupling and scaling DSE solutions

We study the low-momentum behaviour of Yang-Mills propagators obtained from Landau-gauge Dyson-Schwinger equations (DSE) in the PT-BFM scheme. We compare the ghost propagator numerical results with the analytical ones obtained by analyzing the low-momentum behaviour of the ghost propagator DSE in Landau gauge, assuming for the truncation a constant ghost-gluon vertex and a simple model for a massive gluon propagator. The asymptotic expression obtained for the regular or decoupling ghost dressing function up to the order ${\cal O}(q^2)$ is proven to fit pretty well the numerical PT-BFM results. Furthermore, when the size of the coupling renormalized at some scale approaches some critical value, the numerical PT-BFM propagators tend to behave as the scaling ones. We also show that the scaling solution, implying a diverging ghost dressing function, cannot be a DSE solution in the PT-BFM scheme but an unattainable limiting case.Comment: 16 pages, 2 figs., 2 tabs (updated version to be published in JHEP

IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

Chiral perturbation theory in a magnetic background - finite-temperature effects

We consider chiral perturbation theory for SU(2) at finite temperature $T$ in a constant magnetic background $B$. We compute the thermal mass of the pions and the pion decay constant to leading order in chiral perturbation theory in the presence of the magnetic field. The magnetic field gives rise to a splitting between $M_{\pi^0}$ and $M_{\pi^{\pm}}$ as well as between $F_{\pi^0}$ and $F_{\pi^{\pm}}$. We also calculate the free energy and the quark condensate to next-to-leading order in chiral perturbation theory. Both the pion decay constants and the quark condensate are decreasing slower as a function of temperature as compared to the case with vanishing magnetic field. The latter result suggests that the critical temperature $T_c$ for the chiral transition is larger in the presence of a constant magnetic field. The increase of $T_c$ as a function of $B$ is in agreement with most model calculations but in disagreement with recent lattice calculations.Comment: 24 pages and 9 fig

Holographic rho mesons in an external magnetic field

We study the rho meson in a uniform magnetic field eB using a holographic QCD-model, more specifically a D4/D8/Dbar8 brane setup in the confinement phase at zero temperature with two quenched flavours. The parameters of the model are fixed by matching to corresponding dual field theory parameters at zero magnetic field. We show that the up- and down-flavour branes respond differently to the presence of the magnetic field in the dual QCD-like theory, as expected because of the different electromagnetic charge carried by up- and down-quark. We discuss how to recover the Landau levels, indicating an instability of the QCD vacuum at eB = m_rho^2 towards a phase where charged rho mesons are condensed, as predicted by Chernodub using effective QCD-models. We improve on these existing effective QCD-model analyses by also taking into account the chiral magnetic catalysis effect, which tells us that the constituent quark masses rise with eB. This turns out to increase the value of the critical magnetic field for the onset of rho meson condensation to eB = 1.1 m_rho^2 = 0.67 GeV^2. We briefly discuss the influence of pions, which turn out to be irrelevant for the condensation in the approximation made.Comment: 26 pages, 10 .pdf figures, v2: version accepted for publication in JHE

Quasi-Normal Modes of Stars and Black Holes

Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

Mediterranean spotted fever: clinical and laboratory characteristics of 415 Sicilian children

BACKGROUND: Mediterranean spotted fever (MSF) is an acute febrile, zoonotic disease caused by Rickettsia conorii and transmitted to humans by the brown dogtick Rhipicephalus sanguineus. Nearly four hundred cases are reported every year (mainly from June to September) on the Italian island of Sicily. The aim of the study was to analyze the clinical and laboratory characteristics of patients with MSF and the efficacy of the drugs administered. METHODS: Our study was carried out on 415 children with MSF, during the period January 1997 – December 2004, at the "G. Di Cristina" Children's hospital in Palermo, Sicily, Italy. On admission patients' clinical history, physical and laboratory examination and indirect immunofluorescence antibody test (IFAT) for Rickettsia conorii were performed. Diagnosis was considered confirmed if the patients had an MSF diagnostic score greater than or equal to 25 according to the Raoult's scoring system. All patients were treated with chloramphenicol or with macrolides (clarithromycin or azithromycin). RESULTS: Fever, rash and tache noire were present in 386 (93%), 392 (94.5%) and 263 (63.4%) cases respectively. Eighteen (4.6%) children showed atypical exanthema. Chloramphenicol and newer macrolides all appeared to be effective and safe therapies. CONCLUSION: Clinical features of 415 children with MSF were similar to those reported by other authors except for a lower incidence of headache, arthralgia and myalgia and a higher frequency of epato-splenomegaly. Concerning therapy, clarithromycin can be considered a valid alternative therapy to tetracyclines or chloramphenicol especially for children aged < eight years

CD27− B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection

Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27−IgA+ and CD27−IgG+ B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27− cells from patients. Taken together, these results show that during HIV-1 infection, CD27− B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection

The Gaia-ESO Survey: Chromospheric Emission, Accretion Properties, and Rotation in γγ Velorum and Chamaeleon I

We use the fundamental parameters delivered by the GES consortium in the first internal data release to select the members of $\gamma$ Vel and Cha I among the UVES and GIRAFFE spectroscopic observations. A total of 140 $\gamma$ Vel members and 74 Cha I members were studied. We calculated stellar luminosities through spectral energy distributions, while stellar masses were derived by comparison with evolutionary tracks. The spectral subtraction of low-activity and slowly rotating templates, which are rotationally broadened to match the $v\sin i$ of the targets, enabled us to measure the equivalent widths (EWs) and the fluxes in the H$\alpha$ and H$\beta$ lines. The H$\alpha$ line was also used for identifying accreting objects and for evaluating the mass accretion rate ($\dot M_{\rm acc}$). The distribution of $v\sin i$ for the members of $\gamma$ Vel displays a peak at about 10 km s$^{-1}$ with a tail toward faster rotators. There is also some indication of a different $v\sin i$ distribution for the members of its two kinematical populations. Only a handful of stars in $\gamma$ Vel display signatures of accretion, while many more accretors were detected in the younger Cha~I. Accreting and active stars occupy two different regions in a $T_{\rm eff}$-flux diagram and we propose a criterion for distinguishing them. We derive $\dot M_{\rm acc}$ in the ranges $10^{-11}$-$10^{-9} M_\odot$yr$^{-1}$ and $10^{-10}$-$10^{-7} M_\odot$yr$^{-1}$ for $\gamma$ Vel and Cha I accretors, respectively. We find less scatter in the $\dot M_{\rm acc}-M_\star$ relation derived through the H$\alpha$ EWs, when compared to the H$\alpha$ $10\%W$ diagnostics, in agreement with other authors

Learning to Eat Vegetables in Early Life: The Role of Timing, Age and Individual Eating Traits

Vegetable intake is generally low among children, who appear to be especially fussy during the pre-school years. Repeated exposure is known to enhance intake of a novel vegetable in early life but individual differences in response to familiarisation have emerged from recent studies. In order to understand the factors which predict different responses to repeated exposure, data from the same experiment conducted in three groups of children from three countries (n = 332) aged 4–38 m (18.9±9.9 m) were combined and modelled. During the intervention period each child was given between 5 and 10 exposures to a novel vegetable (artichoke puree) in one of three versions (basic, sweet or added energy). Intake of basic artichoke puree was measured both before and after the exposure period. Overall, younger children consumed more artichoke than older children. Four distinct patterns of eating behaviour during the exposure period were defined. Most children were “learners” (40%) who increased intake over time. 21% consumed more than 75% of what was offered each time and were labelled “plate-clearers”. 16% were considered “non-eaters” eating less than 10 g by the 5th exposure and the remainder were classified as “others” (23%) since their pattern was highly variable. Age was a significant predictor of eating pattern, with older pre-school children more likely to be non-eaters. Plate-clearers had higher enjoyment of food and lower satiety responsiveness than non-eaters who scored highest on food fussiness. Children in the added energy condition showed the smallest change in intake over time, compared to those in the basic or sweetened artichoke condition. Clearly whilst repeated exposure familiarises children with a novel food, alternative strategies that focus on encouraging initial tastes of the target food might be needed for the fussier and older pre-school children