Alginate-coated chitosan nanogels differentially modulate class-A and class-B CpG-ODN targeting of dendritic cells and intracellular delivery.

UNLABELLED CpG-oligodeoxynucleotides (CpG-ODNs) interact with dendritic cells (DCs), but evidence is less clear for CpG-ODN admixed with or incorporated into vaccine delivery vehicles. We loaded alginate-coated chitosan-nanogels (Ng) with class-A or class-B CpG-ODN, and compared with the same CpG-ODNs free or admixed with empty Ng. Experiments were performed on both porcine and human blood DC subpopulations. Encapsulation of class-A CpG-ODN (loading into Ng) strongly reduced the CpG-ODN uptake and intracellular trafficking in the cytosol; this was associated with a marked deficiency in IFN-α induction. In contrast, encapsulation of class-B CpG-ODN increased its uptake and did not influence consistently intracellular trafficking into the nucleus. The choice of CpG-ODN class as adjuvant is thus critical in terms of how it will behave with nanoparticulate vaccine delivery vehicles. The latter can have distinctive modulatory influences on the CpG-ODN, which would require definition for different CpG-ODN and delivery vehicles prior to vaccine formulation. FROM THE CLINICAL EDITOR This basic science study investigates the role of class-A and class-B CpG-oligodeoxynucleotides loaded into alginate-coated chitosan nanogels, demonstrating differential effects between the two classes as related to the use of these nanoformulations as vaccine delivery vehicles.

Search for pair and single production of new heavy quarks that decay to a ℤ boson and a third-generation quark in pp collisions at √ s=8 TeV with the ATLAS detector

A search is presented for the production of new heavy quarks that decay to a Z boson and a third-generation Standard Model quark. In the case of a new charge +2/3 quark (T), the decay targeted is T → Zt, while the decay targeted for a new charge −1/3 quark (B) is B → Zb. The search is performed with a dataset corresponding to 20.3 fb−1 of pp collisions at √ s = 8TeV recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider. Selected events contain a high transverse momentum Z boson candidate reconstructed from a pair of oppositely charged same-flavor leptons (electrons or muons), and are analyzed in two channels defined by the absence or presence of a third lepton. Hadronic jets, in particular those with properties consistent with the decay of a b-hadron, are also required to be present in selected events. Different requirements are made on the jet activity in the event in order to enhance the sensitivity to either heavy quark pair production mediated by the strong interaction, or single production mediated by the electroweak interaction. No significant excess of events above the Standard Model expectation is observed, and lower limits are derived on the mass of vector-like T and B quarks under various branching ratio hypotheses, as well as upper limits on the agnitude of electroweak coupling parameters.

Measurement of the total cross section from elastic scattering in pp collisions at √s=7TeV with the ATLAS detector

A measurement of the total pp cross section at the LHC at √s = 7 TeV is presented. In a special run with high-β* beam optics, an integrated luminosity of 80 μb−1 was accumulated in order to measure the differential elastic cross section as a function of the Mandelstam momentum transfer variable t . The measurement is performed with the ALFA sub-detector of ATLAS. Using a fit to the differential elastic cross section in the |t | range from 0.01 GeV2 to 0.1 GeV2 to extrapolate to |t | →0, the total cross section, σtot(pp→X), is measured via the optical theorem to be: σtot(pp→X) = 95.35± 0.38 (stat.)± 1.25 (exp.)± 0.37 (extr.) mb, where the first error is statistical, the second accounts for all experimental systematic uncertainties and the last is related to uncertainties in the extrapolation to |t | → 0. In addition, the slope of the elastic cross section at small |t | is determined to be B = 19.73 ±0.14 (stat.) ±0.26 (syst.) GeV−2.

Flavor tagged time-dependent angular analysis of the B0s → J/ψΦ decay and extraction of Δ Γs and the weak phase Φs in ATLAS

A measurement of the B 0 s →J/ψϕ decay parameters, updated to include flavor tagging is reported using 4.9  fb −1 of integrated luminosity collected by the ATLAS detector from s √ =7  TeV pp collisions recorded in 2011 at the LHC. The values measured for the physical parameters are ϕ s 0.12±0.25(stat)±0.05(syst)  rad ΔΓ s 0.053±0.021(stat)±0.010(syst)  ps −1 Γ s 0.677±0.007(stat)±0.004(syst)  ps −1 |A ∥ (0)| 2 0.220±0.008(stat)±0.009(syst) |A 0 (0)| 2 0.529±0.006(stat)±0.012(syst) δ ⊥ =3.89±0.47(stat)±0.11(syst)  rad where the parameter ΔΓ s is constrained to be positive. The S -wave contribution was measured and found to be compatible with zero. Results for ϕ s and ΔΓ s are also presented as 68% and 95% likelihood contours, which show agreement with the Standard Model expectations.

Observation of an Excited B±c Meson State with the ATLAS Detector

A search for excited states of the B ± c meson is performed using 4.9  fb −1 of 7 TeV and 19.2  fb −1 of 8 TeV pp collision data collected by the ATLAS experiment at the LHC. A new state is observed through its hadronic transition to the ground state, with the latter detected in the decay B ± c →J/ψπ ± . The state appears in the m(B ± c π + π − )−m(B ± c )−2m(π ± ) mass difference distribution with a significance of 5.2 standard deviations. The mass of the observed state is 6842±4±5  MeV , where the first error is statistical and the second is systematic. The mass and decay of this state are consistent with expectations for the second S -wave state of the B ± c meson, B ± c (2S) .

The differential production cross section of the phi (1020) meson in sqrts = 7 TeV pp collisions measured with the ATLAS detector

Ameasurement is presented of the φ×BR(φ → K+K−) production cross section at √s = 7 TeV using pp collision data corresponding to an integrated luminosity of 383 μb−1, collected with theATLAS experiment at the LHC. Selection of φ(1020) mesons is based on the identification of charged kaons by their energy loss in the pixel detector. The differential cross section ismeasured as a function of the transverse momentum, pT,φ , and rapidity, yφ, of the φ(1020) meson in the fiducial region 500< pT,φ <1200MeV, |yφ| < 0.8, kaon pT,K > 230 MeV and kaon momentum pK < 800 MeV. The integrated φ(1020)-meson production cross section in this fiducial range is measured to be σφ×BR(φ → K+K−) = 570 ± 8 (stat) ± 66 (syst) ± 20 (lumi) μb.

Study of heavy-flavor quarks produced in association with top-quark pairs at s √ =7  TeV using the ATLAS detector

Using a sample of dilepton top-quark pair (tt ¯ ) candidate events, a study is performed of the production of top-quark pairs together with heavy-flavor (HF) quarks, the sum of tt ¯ +b+X and tt ¯ +c+X , collectively referred to as tt ¯  + HF . The data set used corresponds to an integrated luminosity of 4.7  fb −1 of proton-proton collisions at a center-of-mass energy of 7 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. The presence of additional HF (b or c ) quarks in the tt ¯ sample is inferred by looking for events with at least three b -tagged jets, where two are attributed to the b quarks from the tt ¯ decays and the third to additional HF production. The dominant background to tt ¯  + HF in this sample is tt ¯ +jet events in which a light-flavor jet is misidentified as a heavy-flavor jet. To determine the heavy- and light-flavor content of the additional b -tagged jets, a fit to the vertex mass distribution of b -tagged jets in the sample is performed. The result of the fit shows that 79 ± 14 (stat) ± 22 (syst) of the 105 selected extra b -tagged jets originate from HF quarks, 3 standard deviations away from the hypothesis of zero tt ¯  + HF production. The result for extra HF production is quoted as a ratio (R HF ) of the cross section for tt ¯  + HF production to the cross section for tt ¯ production with at least one additional jet. Both cross sections are measured in a fiducial kinematic region within the ATLAS acceptance. R HF is measured to be [6.2±1.1(stat)±1.8(syst)]% for jets with p T >25  GeV and |η|<2.5 , in agreement with the expectations from Monte Carlo generators.

Trichinella britovi in a red fox (Vulpes vulpes) from Portugal

Trichinellosis is one of the most important foodborne parasitic zoonoses, caused by nematodes of the genus Trichinella. Pigs and other domestic and wild animals, including red foxes (Vulpes vulpes), are sources of Trichinella infection for human beings. Trichinella britovi is the major agent of infection in sylvatic animals and the most important species circulating in the European wildlife. The present study aimed at assessing Trichinella spp. infection in red foxes from the North of Portugal. Forty-seven carcasses of wild red foxes shot during the official hunting season or killed in road accidents were obtained between November 2008 and March 2010. In order to identify the presence of Trichinella spp. larvae in red foxes, an individual artificial digestion was performed using approximately 30g of muscle samples. Larvae of Trichinella spp. were detected in one (2.1%) out of the 47 assessed foxes. After a multiplex polymerase chain reaction analysis, T. britovi was molecularly identified as the infecting species. The recognition of T. britovi in a red fox confirms that a sylvatic cycle is present in the North of Portugal and that the local prevalence of Trichinella infection in wildlife must not be ignored due to its underlying zoonotic risks.

Quantitative analysis of arachidonic acid, endocannabinoids, N-acylethanolamines and steroids in biological samples by LCMS/MS: Fit to purpose.

Arachidonic acid (5Z,8Z,11Z,14Z-eicosatetraenoic acid; C20:4) (arachidonate, AA) is a vital polyunsaturated omega-6 fatty acid (PUFA) without its presence the mammalian brain, muscles, and possibly other organs cannot develop or function [1] and [2]. AA fulfils numerous known and possibly yet unknown functions as integral part of mammalian phospholipid membranes and as free AA which also acts as a precursor of a variety of biologically active lipid mediators generally referred to as eicosanoids (e.g., prostaglandins, leukotrienes). A more recent class of eicosanoids is composed of the endogenous cannabinoids (endocannabinoids) 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (anandamide, AEA), which act on cannabinoid CB1 and CB2 receptors but also modulate ion channels and nuclear receptors [3] and [4]. In recent years, the role of endocannabinoids as prominent anti-inflammatory and neuromodulatory eicosanoids has been shown by numerous studies [5].

Retention in care of HIV-infected pregnant and lactating women starting art under Option B+ in rural Mozambique.

OBJECTIVE In 2013, Mozambique adopted Option B+, universal lifelong antiretroviral therapy (ART) for all pregnant and lactating women, as national strategy for prevention of mother-to-child transmission of HIV. We analyzed retention in care of pregnant and lactating women starting Option B+ in rural northern Mozambique. METHODS We compared ART outcomes in pregnant ("B+pregnant"), lactating ("B+lactating") and non-pregnant-non-lactating women of childbearing age starting ART after clinical and/or immunological criteria ("own health") between July 2013 and June 2014. Lost to follow-up was defined as no contact >180 days after the last visit. Multivariable competing risk models were adjusted for type of facility (type 1 vs. peripheral type 2 health center), age, WHO stage and time from HIV diagnosis to ART. RESULTS Over 333 person-years of follow-up (of 243 "B+pregnant", 65″B+lactating" and 317 "own health" women), 3.7% of women died and 48.5% were lost to follow-up. "B+pregnant" and "B+lactating" women were more likely to be lost in the first year (57% vs. 56.9% vs. 31.6%; p<0.001) and to have no follow-up after the first visit (42.4% vs. 29.2% vs. 16.4%; p<0.001) than "own health" women. In adjusted analyses, risk of being lost to follow-up was higher in "B+pregnant" (adjusted subhazard ratio [asHR]: 2.77; 95% CI: 2.18-3.50; p<0.001) and "B+lactating" (asHR: 1.94; 95% CI: 1.37-2.74; p<0.001). Type 2 health center was the only additional significant risk factor for loss to follow-up. CONCLUSIONS Retaining pregnant and lactating women in option B+ ART was poor; losses to follow-up were mainly early. The success of Option B+ for prevention of mother-to-child transmission of HIV in rural settings with weak health systems will depend on specific improvements in counseling and retention measures, especially at the beginning of treatment. This article is protected by copyright. All rights reserved.

Expression and biological activities of bovine interleukin 4: effects of recombinant bovine interleukin 4 on T cell proliferation and B cell differentiation and proliferation in vitro

Interleukin 4 (IL-4) is a pleotropic cytokine affecting a wide range of cell types in both the mouse and the human. These activities include regulation of the growth and differentiation of both T and B lymphocytes. The activities of IL-4 in nonprimate, nonmurine systems are not well established. Herein, we demonstrate in the bovine system that IL-4 upregulates production of IgM, IgG1, and IgE in the presence of a variety of costimulators including anti-IgM, Staphylococcus aureus cowan strain I, and pokeweed mitogen. IgE responses are potentiated by the addition of IL-2 to IL-4. Culture of bovine B lymphocytes with IL-4 in the absence of additional costimulators resulted in the increased surface expression of CD23 (low-affinity Fc epsilon RII), IgM, IL-2R, and MHC class II in a dose-dependent manner. IL-4 alone increased basal levels of proliferation of bulk peripheral blood mononuclear cells but in the presence of Con A inhibited proliferation. In contrast to the activities of IL-4 in the murine system, proliferation of TH1- and TH2-like clones was inhibited in a dose-dependent manner as assessed by antigen-or IL-2-driven in vitro proliferative responses. These observations are consistent with the role of IL-4 as a key player in regulation of both T and B cell responses.