IgG Fc N-glycosylation translates MHCII haplotype into autoimmune skin disease

The major histocompatibility complex haplotype represents the most prevalent genetic risk factor for the development of autoimmune diseases. However, the mechanisms by which major histocompatibility complex-associated genetic susceptibility translates into autoimmune disease are not fully understood. Epidermolysis bullosa acquisita is an autoimmune skin-blistering disease driven by autoantibodies to type VII collagen. Here, we investigated autoantigen-specific plasma cells, CD4(+) T cells, and IgG fraction crystallizable glycosylation in murine epidermolysis bullosa acquisita in congenic mouse strains with the disease-permitting H2s or disease-nonpermitting H2b major histocompatibility complex II haplotypes. Mice with an H2s haplotype showed increased numbers of autoreactive CD4(+) T cells and elevated IL-21 and IFN-gamma production, associated with a higher frequency of IgG autoantibodies with an agalactosylated, proinflammatory N-glycan moiety. Mechanistically, we show that the altered antibody glycosylation leads to increased ROS release from neutrophils, the main drivers of autoimmune inflammation in this model. These results indicate that major histocompatibility complex II-associated susceptibility to autoimmune diseases acuminates in a proinflammatory IgG fraction crystallizable N-glycosylation pattern and provide a mechanistic link to increased ROS release by neutrophils.Proteomic

Global Search for New Physics with 2.0/fb at CDF

Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak-scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with the standard model prediction. A model-independent approach (Vista) considers gross features of the data, and is sensitive to new large cross-section physics. Further sensitivity to new physics is provided by two additional algorithms: a Bump Hunter searches invariant mass distributions for "bumps" that could indicate resonant production of new particles; and the Sleuth procedure scans for data excesses at large summed transverse momentum. This combined global search for new physics in 2.0/fb of ppbar collisions at sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D Rapid Communication

Observation of Orbitally Excited B_s Mesons

We report the first observation of two narrow resonances consistent with states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+, \bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1}) = 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let

A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection

SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin cleavage site (FCS) of spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) and found that FCS inactivation markedly increased spike binding to human ACE2. After vaccination of mice, the MVA/SdFCS vaccine induced eightfold higher neutralizing antibodies compared with MVA/S, which expressed spike without FCS inactivation, and protected against the Beta variant. We next added nucleocapsid to the MVA/SdFCS vaccine (MVA/SdFCS-N) and tested its immunogenicity and efficacy via intramuscular (IM), buccal (BU), or sublingual (SL) routes in rhesus macaques. IM vaccination induced spike-specific IgG in serum and mucosae (nose, throat, lung, and rectum) that neutralized the homologous (WA-1/2020) and heterologous VOCs, including Delta, with minimal loss (<2-fold) of activity. IM vaccination also induced both spike- and nucleocapsid-specific CD4 and CD8 T cell responses in the blood. In contrast, the SL and BU vaccinations induced less spike-specific IgG in secretions and lower levels of polyfunctional IgG in serum compared with IM vaccination. After challenge with the SARS-CoV-2 Delta variant, the IM route induced robust protection, the BU route induced moderate protection, and the SL route induced no protection. Vaccine-induced neutralizing and non-neutralizing antibody effector functions positively correlated with protection, but only the effector functions correlated with early protection. Thus, IM vaccination with MVA/SdFCS-N vaccine elicited cross-reactive antibody and T cell responses, protecting against heterologous SARS-CoV-2 VOC more effectively than other routes of vaccination

Measurement of the ttbar Production Cross Section in ppbar collisions at sqrt s = 1.96 TeV in the All Hadronic Decay Mode

We report a measurement of the ttbar production cross section using the CDF-II detector at the Fermilab Tevatron. The analysis is performed using 311 pb-1 of ppbar collisions at sqrt(s)=1.96 TeV. The data consist of events selected with six or more hadronic jets with additional kinematic requirements. At least one of these jets must be identified as a b-quark jet by the reconstruction of a secondary vertex. The cross section is measured to be sigma(tbart)=7.5+-2.1(stat.)+3.3-2.2(syst.)+0.5-0.4(lumi.) pb, which is consistent with the standard model prediction.Comment: By CDF collaboratio

Search for charged Higgs bosons in decays of top quarks in p-pbar collisions at sqrt(s) = 1.96 TeV

7 pages, 2 figuresWe report the recent charged Higgs search in top quark decays in 2.2/fb CDF data. This is the first attempt to search for charged Higgs using fully reconstructed mass assuming H->c-sbar in small tan beta region. No evidence of a charged Higgs is observed in the CDF data, hence 95% upper limits are placed at B(t->H+b)We report on the first direct search for charged Higgs bosons decaying into cs̅ in tt̅ events produced by pp̅ collisions at √s=1.96  TeV. The search uses a data sample corresponding to an integrated luminosity of 2.2  fb-1 collected by the CDF II detector at Fermilab and looks for a resonance in the invariant mass distribution of two jets in the lepton+jets sample of tt̅ candidates. We observe no evidence of charged Higgs bosons in top quark decays. Hence, 95% upper limits on the top quark decay branching ratio are placed at B(t→H+b)< 0.1 to 0.3 for charged Higgs boson masses of 60 to 150  GeV/c2 assuming B(H+→cs̅ )=1.0. The upper limits on B(t→H+b) are also used as model-independent limits on the decay branching ratio of top quarks to generic scalar charged bosons beyond the standard model.Peer reviewe

Search for chargino-neutralino production in ppbar collisions at sqrt(s) = 1.96 TeV

We present the results of a search for associated production of the chargino and neutralino supersymmetric particles using up to 1.1 fb-1 of integrated luminosity collected by the CDF II experiment at the Tevatron ppbar collider at a center-of-mass energy of 1.96 TeV. The search is conducted by analyzing events with a large transverse momentum imbalance and either three charged leptons or two charged leptons of the same electric charge. The numbers of observed events are found to be consistent with standard model expectations. Upper limits on the production cross section are derived in different theoretical models. In one of these models a lower limit on the mass of the chargino is set at 129 GeV/c^2 at the 95% confidence level.Comment: To be submitted to Phys.Rev.Let

Comments and Reply on: &quot;Study of multi-muon events produced in pp̄ interactions at √s = 1.96 TeV&quot;; T. Aaltonen et al. (The CDF collaboration)

The European Physical Journal C-Particles and Fields-publishes scientific manuscripts of relevance to the scientific community following careful and strict peer reviewing and, whenever appropriate and necessary, through discussion with the authors, so as to optimise scientific content and style of presentation prior to publication. In some cases significant disagreement between authors and referees (and/or editors) of the journal cannot be resolved despite all efforts and best of intentions. While the journal-notwithstanding any appeals-retains the right to reject such manuscripts, the editors of this journal may decide, in cases deemed of exceptional interest and potential significance for the field, to accept the manuscript for publication, to amend it by &quot;comments&quot; of the editor(s) in charge and, if appropriate, by a &quot;reply&quot; of the authors of the commented manuscript. The present comment is on &quot;Study of multi-muon events produced in pp̄ interactions at √ = 1.96 TeV&quot;; T. Aaltonen et al. (The CDF Collaboration, Eur. Phys. J. C, 2010, doi:10.1140/epjc/s10052-010-1336-0. © 2010 The Author(s)