Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Caracterización del cáncer renal, relación del tamaño tumoral y el grado nuclear con la supervivencia

Introducción: el cáncer renal representa un 3 % de las neoplasias malignas del adulto. Objetivo: valorar los nuevos aspectos clínicos e histológicos que suponen las nuevas clasificaciones, caracterizar, de manera clínico-patológica, a los pacientes atendidos por cáncer renal, según criterios actualizados, describir algunas variables de interés, así como estimar la supervivencia general en cinco años de evolución, de los diferentes subtipos histológicos más frecuentes y su relación con el tamaño y grado nuclear. Método: investigación descriptiva y ambispectiva que se desarrolló en el Departamento de Anatomía Patológica del Hospital “Hermanos Ameijeiras”, con 112 pacientes atendidos por tumores malignos renales, durante el período comprendido entre los años 2004 y 2006. Las variables utilizadas fueron: las variables: tiempo de supervivencia, estado del paciente, grado nuclear y tamaño tumoral. Resultados: el tipo histológico más frecuentemente diagnosticado fue el carcinoma de células claras, con un total de 76 casos. El mayor porcentaje de casos, presentaban tamaño promedio entre 4 y 7 cm de diámetro. Se pudo apreciar que la mayoría de los casos se encontraban clasificados dentro del grado nuclear 2 de Fuhrman. Conclusiones: el carcinoma de células claras sigue siendo el de peor pronóstico de supervivencia. El tamaño del tumor y el grado nuclear presentaron diferencias significativas en cuanto a la supervivencia de los pacientes, al corresponder el peor comportamiento a los de mayor tamaño o grado nuclear

Hacia una psicología rural latinoamericana

El objetivo de este libro es abrir la discusión crítica sobre las especificidades, problemáticas y principales áreas de interés de la Psicología Rural, aspirando a convertirse en un material de referencia para psicólogos y psicólogas interesados en el área. En este sentido, y dada su voluntad de poner en discusión el ámbito de la Psicología Rural en sí mismo, posiblemente se trate del primer libro a nivel global en su tipo

Measurement of an excess in the yield of J/ψ at very low pT in Pb–Pb collisions at √sNN = 2.76 TeV

We report on the first measurement of an excess in the yield of J/ψ at very low transverse momentum (pT<0.3 GeV/c) in peripheral hadronic Pb-Pb collisions at sNN−−−√ = 2.76 TeV, performed by ALICE at the CERN LHC. Remarkably, the measured nuclear modification factor (RAA) of J/ψ in the rapidity range 2.5<y<4 reaches about 7 (2) in the pT range 0-0.3 GeV/c in the 70-90% (50-70%) centrality class. The J/ψ production cross section associated with the observed excess is obtained under the hypothesis that coherent photoproduction of J/ψ is the underlying physics mechanism. If confirmed, the observation of J/ψ coherent photoproduction in Pb-Pb collisions at impact parameters smaller than twice the nuclear radius opens new theoretical and experimental challenges and opportunities. In particular, coherent photoproduction accompanying hadronic collisions may provide insight into the dynamics of photoproduction and nuclear reactions, as well as become a novel probe of the Quark-Gluon Plasma

Centrality dependence of pion freeze-out radii in Pb-Pb collisions at √sNN = 2.76 TeV

We report on the measurement of freeze-out radii for pairs of identical-charge pions measured in Pb--Pb collisions at sNN−−−√=2.76 TeV as a function of collision centrality and the average transverse momentum of the pair kT. Three-dimensional sizes of the system (femtoscopic radii), as well as direction-averaged one-dimensional radii are extracted. The radii decrease with kT, following a power-law behavior. This is qualitatively consistent with expectations from a collectively expanding system, produced in hydrodynamic calculations. The radii also scale linearly with ⟨dNch/dη⟩1/3. This behaviour is compared to world data on femtoscopic radii in heavy-ion collisions. While the dependence is qualitatively similar to results at smaller sNN−−−√, a decrease in the Rout/Rside ratio is seen, which is in qualitative agreement with specific predictions from hydrodynamic models. The results provide further evidence for the production of a collective, strongly coupled system in heavy-ion collisions at the LHC

Measurement of transverse energy at midrapidity in Pb–Pb collisions at √sNN = 2.76 TeV

We report the transverse energy (ET) measured with ALICE at midrapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV as a function of centrality. The transverse energy was measured using identified single particle tracks. The measurement was cross checked using the electromagnetic calorimeters and the transverse momentum distributions of identified particles previously reported by ALICE. The results are compared to theoretical models as well as to results from other experiments. The mean ET per unit pseudorapidity (η), ⟨dET/dη⟩, in 0-5% central collisions is 1737 ± 6(stat.) ± 97(sys.) GeV. We find a similar centrality dependence of the shape of ⟨dET/dη⟩ as a function of the number of participating nucleons to that seen at lower energies. The growth in ⟨dET/dη⟩ at the LHC sNN−−−√ exceeds extrapolations of low energy data. We observe a nearly linear scaling of ⟨dET/dη⟩ with the number of quark participants. With the canonical assumption of a 1 fm/c formation time, we estimate that the energy density in 0-5% central Pb-Pb collisions at sNN−−−√ = 2.76 TeV is 12.3 ± 1.0 GeV/fm3\xspace and that the energy density at the most central 80 fm2 of the collision is at least 21.5 ± 1.7 GeV/fm3. This is roughly 2.3 times that observed in 0-5% central Au-Au collisions at sNN−−−√ = 200 GeV

Centrality dependence of the charged-particle multiplicity density at midrapidity in Pb–Pb collisions at √sNN = 5.02 TeV

The pseudorapidity density of charged particles (dNch/dη) at mid-rapidity in Pb-Pb collisions has been measured at a center-of-mass energy per nucleon pair of sNN−−−√ = 5.02 TeV. It increases with centrality and reaches a value of 1943±54 in |η|<0.5 for the 5% most central collisions. A rise in dNch/dη as a function of sNN−−−√ for the most central collisions is observed, steeper than that observed in proton-proton collisions and following the trend established by measurements at lower energy. The centrality dependence of dNch/dη as a function of the average number of participant nucleons, ⟨Npart⟩, calculated in a Glauber model, is compared with the previous measurement at lower energy. A constant factor of about 1.2 describes the increase in 2⟨Npart⟩⟨dNch/dη⟩ from sNN−−−√ = 2.76 TeV to sNN−−−√ = 5.02 TeV for all centrality intervals, within the measured range of 0-80% centrality. The results are also compared to models based on different mechanisms for particle production in nuclear collisions