An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease

Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622/sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD

Photoproduction of D∗±D^{*\pm} mesons associated with a leading neutron

The photoproduction of $D^{*\pm} (2010)$ mesons associated with a leading neutron has been observed with the ZEUS detector in $ep$ collisions at HERA using an integrated luminosity of 80 pb$^{-1}$. The neutron carries a large fraction, {$x_L>0.2$}, of the incoming proton beam energy and is detected at very small production angles, {$\theta_n<0.8$ mrad}, an indication of peripheral scattering. The $D^*$ meson is centrally produced with pseudorapidity {$|\eta| 1.9$ GeV}, which is large compared to the average transverse momentum of the neutron of 0.22 GeV. The ratio of neutron-tagged to inclusive $D^*$ production is $8.85\pm 0.93({\rm stat.})^{+0.48}_{-0.61}({\rm syst.})\%$ in the photon-proton center-of-mass energy range {$130 <W<280$ GeV}. The data suggest that the presence of a hard scale enhances the fraction of events with a leading neutron in the final state.Comment: 28 pages, 4 figures, 2 table

Isolated tau leptons in events with large missing transverse momentum at HERA

A search for events containing isolated tau leptons and large missing transverse momentum, not originating from the tau decay, has been performed with the ZEUS detector at the electron-proton collider HERA, using 130 pb^-1 of integrated luminosity. A search was made for isolated tracks coming from hadronic tau decays. Observables based on the internal jet structure were exploited to discriminate between tau decays and quark- or gluon-induced jets. Three tau candidates were found, while 0.40 +0.12 -0.13 were expected from Standard Model processes, such as charged current deep inelastic scattering and single W-boson production. To search for heavy-particle decays, a more restrictive selection was applied to isolate tau leptons produced together with a hadronic final state with high transverse momentum. Two candidate events survive, while 0.20 +-0.05 events are expected from Standard Model processes.Comment: 28 pages, 4 figures, 3 tables, accepted by Phys. Lett. B. Updated with minor changes to the text requested by the journal refere

Search for contact interactions, large extra dimensions and finite quark radius in ep collisions at HERA

A search for physics beyond the Standard Model has been performed with high-Q^2 neutral current deep inelastic scattering events recorded with the ZEUS detector at HERA. Two data sets, e^+ p \to e^+ X and e^- p \to e^- X, with respective integrated luminosities of 112 pb^-1 and 16 pb^-1, were analyzed. The data reach Q^2 values as high as 40000 GeV^2. No significant deviations from Standard Model predictions were observed. Limits were derived on the effective mass scale in eeqq contact interactions, the ratio of leptoquark mass to the Yukawa coupling for heavy leptoquark models and the mass scale parameter in models with large extra dimensions. The limit on the quark charge radius, in the classical form factor approximation, is 0.85 10^-16 cm.Comment: 28 pages, 4 figures, accepted for publication in Physics Letters

Seasonal Influenza A Virus in Feces of Hospitalized Adults

In a cohort of hospitalized adults with seasonal influenza A in Hong Kong, viral RNA was frequently (47%) detected in stool specimens. Viable virus was rarely isolated. Viral RNA positivity had little correlation with gastrointestinal symptoms and outcomes. In vitro studies suggested low potential for seasonal influenza viruses to cause direct intestinal infections