The RCK2 domain of the human BKCa channel is a calcium sensor

Large conductance voltage and Ca2+-dependent K+ channels (BKCa) are activated by both membrane depolarization and intracellular Ca2+. Recent studies on bacterial channels have proposed that a Ca2+-induced conformational change within specialized regulators of K+ conductance (RCK) domains is responsible for channel gating. Each pore-forming α subunit of the homotetrameric BKCa channel is expected to contain two intracellular RCK domains. The first RCK domain in BKCa channels (RCK1) has been shown to contain residues critical for Ca2+ sensitivity, possibly participating in the formation of a Ca2+-binding site. The location and structure of the second RCK domain in the BKCa channel (RCK2) is still being examined, and the presence of a high-affinity Ca2+-binding site within this region is not yet established. Here, we present a structure-based alignment of the C terminus of BKCa and prokaryotic RCK domains that reveal the location of a second RCK domain in human BKCa channels (hSloRCK2). hSloRCK2 includes a high-affinity Ca2+-binding site (Ca bowl) and contains similar secondary structural elements as the bacterial RCK domains. Using CD spectroscopy, we provide evidence that hSloRCK2 undergoes a Ca2+-induced change in conformation, associated with an α-to-β structural transition. We also show that the Ca bowl is an essential element for the Ca2+-induced rearrangement of hSloRCK2. We speculate that the molecular rearrangements of RCK2 likely underlie the Ca2+-dependent gating mechanism of BKCa channels. A structural model of the heterodimeric complex of hSloRCK1 and hSloRCK2 domains is discussed

Search for Pairs of Isolated Radio Pulsars - Components in Disrupted Binary Systems

We have developed a method for analyzing the kinematic association of isolated relativistic objects - possible remnants of disrupted close binary systems. We investigate pairs of fairly young radio pulsars with known proper motions and estimated distances (dispersion measures) that are spaced no more than 2-3 kpc apart. Using a specified radial velocity distribution for these objects, we have constructed 100-300 thousand trajectories of their possible motion in the Galactic gravitational field on a time scale of several million years. The probabilities of their close encounters at epochs consistent with the age of the younger pulsar in the pair are analyzed. When these probabilities exceed considerably their reference values obtained by assuming a purely random encounter between the pulsars under consideration, we conclude that the objects may have been gravitationally bound in the past. As a result, we have detected six pulsar pairs (J0543+2329/J0528+2200, J1453-6413/J1430-6623, J2354+6155/J2321+6024, J1915+1009/J1909+1102, J1832-0827/J1836-1008, and J1917+1353/J1926+1648) that are companions in disrupted binary systems with a high probability. Estimates of their kinematic ages and velocities at binary disruption and at the present epoch are provided

Galactic electrons and positrons at the Earth:new estimate of the primary and secondary fluxes

We analyse predictions of the CR lepton fluxes at the Earth of both secondary and primary origins, evaluate the theoretical uncertainties, and determine their level of consistency with respect to the available data. For propagation, we use a relativistic treatment of the energy losses for which we provide useful parameterizations. We compute the secondary components by improving on the method that we derived earlier for positrons. For primaries, we estimate the contributions from astrophysical sources (supernova remnants and pulsars) by considering all known local objects within 2 kpc and a smooth distribution beyond. We find that the electron flux in the energy range 5-30 GeV is well reproduced by a smooth distant distribution of sources with index $\gamma\sim 2.3-2.4$, while local sources dominate the flux at higher energy. For positrons, local pulsars have an important effect above 5-10 GeV. Uncertainties affecting the source modeling and propagation are degenerate and each translates into about one order of magnitude error in terms of local flux. The spectral shape at high energy is weakly correlated with the spectral indices of local sources, but more strongly with the hierarchy in their distance, age and power. Despite the large theoretical errors that we describe, our global and self-consistent analysis can explain all available data without over-tuning the parameters, and therefore without the need to consider any exotic physics. Though a \emph{standard paradigm} of Galactic CRs is well established, our results show that we can hardly talk about any \emph{standard model} of CR leptons, because of the very large theoretical uncertainties. Our analysis provides details about the impact of these uncertainties, thereby sketching a roadmap for future improvements.Comment: 34 pages, 14 figures. V2: few changes, results unchanged; matches the version accepted in Astron. Astrophy

Habitable Zones in the Universe

Habitability varies dramatically with location and time in the universe. This was recognized centuries ago, but it was only in the last few decades that astronomers began to systematize the study of habitability. The introduction of the concept of the habitable zone was key to progress in this area. The habitable zone concept was first applied to the space around a star, now called the Circumstellar Habitable Zone. Recently, other, vastly broader, habitable zones have been proposed. We review the historical development of the concept of habitable zones and the present state of the research. We also suggest ways to make progress on each of the habitable zones and to unify them into a single concept encompassing the entire universe.Comment: 71 pages, 3 figures, 1 table; to be published in Origins of Life and Evolution of Biospheres; table slightly revise