The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

The CYGNO experiment, a directional detector with optical readout for Dark Matter search

The CYGNO experiment employs a gaseous Time Projection Chamber (TPC) in conjunction with Gas Electron Multipliers (GEMs) for amplification and optical readout. This configuration holds the potential to achieve precise 3D tracking down to O(1 keV) energies. The primary objective of this novel technique is to enable direct directional measurements of Dark Matter within our Galaxy. We assess the performance of the largest prototype, LIME, at Laboratori Nazionali del Gran Sasso (LNGS), including stability, energy response and resolution, using radioactive X-ray sources and Monte Carlo simulations. These findings will guide the fine-tuning of the CYGNO 04 demonstrator

Gating of a pH-Sensitive K2P Potassium Channel by an Electrostatic Effect of Basic Sensor Residues on the Selectivity Filter

K+ channels share common selectivity characteristics but exhibit a wide diversity in how they are gated open. Leak K2P K+ channels TASK-2, TALK-1 and TALK-2 are gated open by extracellular alkalinization. The mechanism for this alkalinization-dependent gating has been proposed to be the neutralization of the side chain of a single arginine (lysine in TALK-2) residue near the pore of TASK-2, which occurs with the unusual pKa of 8.0. We now corroborate this hypothesis by transplanting the TASK-2 extracellular pH (pHo) sensor in the background of a pHo-insensitive TASK-3 channel, which leads to the restitution of pHo-gating. Using a concatenated channel approach, we also demonstrate that for TASK-2 to open, pHo sensors must be neutralized in each of the two subunits forming these dimeric channels with no apparent cross-talk between the sensors. These results are consistent with adaptive biasing force analysis of K+ permeation using a model selectivity filter in wild-type and mutated channels. The underlying free-energy profiles confirm that either a doubly or a singly charged pHo sensor is sufficient to abolish ion flow. Atomic detail of the associated mechanism reveals that, rather than a collapse of the pore, as proposed for other K2P channels gated at the selectivity filter, an increased height of the energetic barriers for ion translocation accounts for channel blockade at acid pHo. Our data, therefore, strongly suggest that a cycle of protonation/deprotonation of pHo-sensing arginine 224 side chain gates the TASK-2 channel by electrostatically tuning the conformational stability of its selectivity filter

Sotaque e telejornalismo: representações de comunicadores de mídia nordestinos

RESUMO: Objetivo: descrever o conteúdo das representações sociais do comunicador de mídia nordestino acerca do seu sotaque. Métodos: a coleta de dados foi realizada em duas etapas. Na primeira, foi empregada a técnica de associação livre, na qual 50 universitários apresentaram o que pensavam diante da palavra "sotaque". Na segunda, por meio do Procedimento de Classificações Múltiplas (PCM), 25 comunicadores atuantes na Região Metropolitana do Recife classificaram as 15 palavras mais associadas pelos estudantes de duas maneiras, classificação livre e dirigida. Na classificação livre, os comunicadores agruparam as palavras segundo critérios por eles estabelecidos, enquanto que na classificação dirigida, as palavras foram classificadas de acordo com o grau de associação com o termo MEU SOTAQUE. A análise foi realizada utilizando-se métodos estatísticos multidimensionais, que permitiram construir a estruturação do campo das Representações Sociais. Resultados: três regiões delimitadas expressam a representação dos sujeitos sobre sotaque: Conceito, Identidade e Espaço. Na primeira, há seis categorias (engraçado, diferente, arrastado, matuto, preconceito, oxente), na segunda, as palavras são identidade, característica, língua, fala e cultura, próximas ao termo meu sotaque e, na terceira, região, regionalismo, nordeste e localidade. Identidade foi o termo mais relacionado ao termo MEU SOTAQUE, enquanto que os itens menos relacionados são os presentes na região conceito, exceto pelo termo oxente. Conclusão: o sotaque nordestino é tido como uma marca da identidade e cultura da região Nordeste. Os comunicadores suavizam características do falar nordestino durante o exercício profissional para se adequar ao padrão preconizado pelo mercado de trabalho sem perder a sua identidade

Solar Neutrino Detection Sensitivity in DARWIN via Electron Scattering

We detail the sensitivity of the proposed liquid xenon DARWIN observatory to solar neutrinos via elastic electron scattering. We find that DARWIN will have the potential to measure the fluxes of five solar neutrino components: pp, 7Be, 13N, 15O and pep. The precision of the 13N, 15O and pep components is hindered by the double-beta decay of 136Xe and, thus, would benefit from a depleted target. A high-statistics observation of pp neutrinos would allow us to infer the values of the electroweak mixing angle, sin2θw, and the electron-type neutrino survival probability, Pee, in the electron recoil energy region from a few keV up to 200 keV for the first time, with relative precision of 5% and 4%, respectively, with 10 live years of data and a 30 tonne fiducial volume. An observation of pp and 7Be neutrinos would constrain the neutrino-inferred solar luminosity down to 0.2%. A combination of all flux measurements would distinguish between the high- (GS98) and low-metallicity (AGS09) solar models with 2.1–2.5σ significance, independent of external measurements from other experiments or a measurement of 8B neutrinos through coherent elastic neutrino-nucleus scattering in DARWIN. Finally, we demonstrate that with a depleted target DARWIN may be sensitive to the neutrino capture process of 131Xe

A next-generation liquid xenon observatory for dark matter and neutrino physics

The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector