20 research outputs found
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 , 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