α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease

A diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Searches for electroweak neutralino and chargino production in channels with Higgs, Z, and W bosons in pp collisions at 8 TeV

Searches for supersymmetry (SUSY) are presented based on the electroweak pair production of neutralinos and charginos, leading to decay channels with Higgs, Z, and W bosons and undetected lightest SUSY particles (LSPs). The data sample corresponds to an integrated luminosity of about 19.5 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV collected in 2012 with the CMS detector at the LHC. The main emphasis is neutralino pair production in which each neutralino decays either to a Higgs boson (h) and an LSP or to a Z boson and an LSP, leading to hh, hZ, and ZZ states with missing transverse energy (E-T(miss)). A second aspect is chargino-neutralino pair production, leading to hW states with E-T(miss). The decays of a Higgs boson to a bottom-quark pair, to a photon pair, and to final states with leptons are considered in conjunction with hadronic and leptonic decay modes of the Z and W bosons. No evidence is found for supersymmetric particles, and 95% confidence level upper limits are evaluated for the respective pair production cross sections and for neutralino and chargino mass values

The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse

The self-antigen α-synuclein (α-syn) was recently shown to be associated with Parkinson’s disease (PD). Here we mapped the T cell receptor (TCR) repertoire of α-syn-specific T cells from six PD patients. The self-antigen α-syn-specific repertoire was compared to the repertoire of T cells specific for pertussis (PT), as a representative foreign antigen that most individuals are exposed to, revealing that the repertoire for α-syn was as diverse as the repertoire for PT. The diversity of PT-specific clonotypes was similar between individuals with PD diagnosis and age-matched healthy controls. We found that the TCR repertoire was specific to each PD patient, and no shared TCRs among patients were defined, likely due to differences in HLA expression that select for different subsets of epitope-specific TCR rearrangements. This study provides the first characterization of α-syn-specific TCR clonotypes in individuals with PD. Antigen-specific TCRs can serve as immunotherapeutics and diagnostics, and means to track longitudinal changes in specific T cells, and disease progression

Activity of phosphorus of synthetic Fe-K-P compounds in superphosphate fertilizers as affected by pH and ionic strength Efeito do pH e da força iônica na atividade de fósforo oriundo de compostos sinteticos do tipo Fe-K-P de superfosfatos

The concentration of orthophosphate ions released from Fe-K-P compounds (Fe3KH8(PO4)6 .6H2O and Fe3KH14(PO4)8 .4H2O) present in superphosphates increases with pH, which initially suggests that the agronomic effectiveness of P fertilizers containing high amounts of these compounds would also increase with soil pH but studies considering activity, instead of concentration, are necessary. With this purpose, both compounds were synthesized under laboratory conditions, characterized by elemental chemical analysis, optical microscopy, X ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), and used in a solubility study. Solutions of 0.01, 0.05 and 0.1 mol L-1 NaCl with pH adjusted to 3.0, 4.0, 5.0, 5.5, 6.0, 6.5, 7.0 and 7.5 were prepared for the solubility study of H8-syn, H14-syn and a phosphate rock (PR) from Brazil. The orthophosphate activity as H2PO4- and HPO4(2-) was calculated in each situation as related to pH and ionic strength using software MINTEQ. The remaining precipitates after equilibrium were chemically analyzed and subjected to X ray, SEM and EDS. Results of chemical analysis and instrumental techniques confirmed the preparation method. The activity of orthophosphate ions of both compounds tended to decrease under increasing pH and/or ionic strength of the solution, which in turn suggests that an increase in the solution pH does not necessarily promote an increase in the P bioavailability for plant uptake. This can be important when evaluating agronomic data of P fertilizers with high contents of these two Fe-K-P compounds.<br>O aumento do pH da concentração de íons ortofosfatos liberados de compostos do tipo Fe-K-P (Fe3KH8(PO4)6 .6H2O e Fe3KH14(PO4)8 .4H2O), presentes em superfosfatos, evidenciam, inicialmente, que a eficiência agronômica de fertilizantes fosfatados, com elevadas quantidades destes, poderiam aumentar com o pH do solo; todavia, estudos que considerem atividades, em vez de concentração, são necessários. Com este propósito, ambos os compostos foram preparados em condições de laboratório (H8-sin e H14-sin), caracterizados por análise química elementar, microscopia óptica, raios X, microscopia eletrônica de varredura (MEV) e espectrometria de energia dispersiva (EDS), e utilizados em um estudo de solubilidade. Soluções de NaCl, nas concentrações de 0,01, 0,05 e 0,1 mol L-1 com o pH ajustado de 3 a 7,5, foram utilizadas no estudo de solubilidade envolvendo o H8-sin, H14-sin e um fosfato de rocha apatítico do Brasil. O programa MINTEQ foi utilizado para calcular a atividade dos ortofosfatos H2PO4- e HPO4(2-) em cada situação de pH e força iônica. O tipo de precipitado remanescente, quando atingido o equilíbrio, foi submetido à análise química elementar, raios X, MEV e EDS. As análises confirmaram que os métodos de preparo foram adequados para ambos os compostos. A atividade dos íons ortofosfatos oriundos da reação de hidrólise do H8-sin e H14-sin tendeu a diminuir com o aumento do pH e, ou, a força iônica da solução, o que mostra que um aumento da concentração em solução não necessariamente significa um aumento da biodisponibilidade de P às plantas. Estes dados poderão ser importantes para compreender a eficiência de fertilizantes fosfatados que contêm elevadas quantidades desses compostos