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

One blind and three targeted searches for (sub)millisecond pulsars

We conducted one blind and three targeted searches for millisecond and submillisecond pulsars. The blind search was conducted within 3deg of the Galactic plane and at longitudes between 20 and 110deg. It takes 22073 pointings to cover this region, and 5487 different positions in the sky. The first targeted search was aimed at Galactic globular clusters, the second one at 24 bright polarized and pointlike radiosources with steep spectra, and the third at 65 faint polarized and pointlike radiosources. The observations were conducted at the large radiotelescope of Nancay Observatory, at a frequency near 1400 MHz. Two successive backends were used, first a VLBI S2 system, second a digital acquisition board and a PC with large storage capacity sampling the signal at 50 Mb/s on one bit, over a 24-MHz band and in one polarization. The bandwidth of acquisition of the second backend was later increased to 48 MHz and the sampling rate to 100 Mb/s. The survey used the three successive setups, with respective sensitivities of 3.5, 2.2, and 1.7 mJy. The targeted-search data were obtained with the third setup and reduced with a method based on the Hough transform, yielding a sensitivity of 0.9 mJy. The processing of the data was done in slightly differed time by soft-correlation in all cases. No new short-period millisecond pulsars were discovered in the different searches. To better understand the null result of the blind survey, we estimate the probability of detecting one or more short-period pulsars among a given Galactic population of synthetic pulsars with our setup: 25% for the actual incomplete survey and 79% if we had completed the whole survey with a uniform nominal sensitivity of 1.7 mJy. The alternative of surveying a smaller, presumably more densely populated, region with a higher sensitivity would have a low return and would be impractical at a transit instrument. (abridged)Comment: accepted for publication in Astronomy & Astrophysic

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

Enhancement Effects of Martentoxin on Glioma BK Channel and BK Channel (α+β1) Subtypes

BACKGROUND: BK channels are usually activated by membrane depolarization and cytoplasmic Ca(2+). Especially,the activity of BK channel (α+β4) can be modulated by martentoxin, a 37 residues peptide, with Ca(2+)-dependent manner. gBK channel (glioma BK channel) and BK channel (α+β1) possessed higher Ca(2+) sensitivity than other known BK channel subtypes. METHODOLOGY AND PRINCIPAL FINDINGS: The present study investigated the modulatory characteristics of martentoxin on these two BK channel subtypes by electrophysiological recordings, cell proliferation and Ca(2+) imaging. In the presence of cytoplasmic Ca(2+), martentoxin could enhance the activities of both gBK and BK channel (α+β1) subtypes in dose-dependent manner with EC(50) of 46.7 nM and 495 nM respectively, while not shift the steady-state activation of these channels. The enhancement ratio of martentoxin on gBK and BK channel (α+β1) was unrelated to the quantitative change of cytoplasmic Ca(2+) concentrations though the interaction between martentoxin and BK channel (α+β1) was accelerated under higher cytoplasmic Ca(2+). The selective BK pore blocker iberiotoxin could fully abolish the enhancement of these two BK subtypes induced by martentoxin, suggesting that the auxiliary β subunit might contribute to the docking for martentoxin. However, in the absence of cytoplasmic Ca(2+), the activity of gBK channel would be surprisingly inhibited by martentoxin while BK channel (α+β1) couldn't be affected by the toxin. CONCLUSIONS AND SIGNIFICANCE: Thus, the results shown here provide the novel evidence that martentoxin could increase the two Ca(2+)-hypersensitive BK channel subtypes activities in a new manner and indicate that β subunit of these BK channels plays a vital role in this enhancement by martentoxin

On the simple random-walk models of ion-channel gate dynamics reflecting long-term memory

Several approaches to ion-channel gating modelling have been proposed. Although many models describe the dwell-time distributions correctly, they are incapable of predicting and explaining the long-term correlations between the lengths of adjacent openings and closings of a channel. In this paper we propose two simple random-walk models of the gating dynamics of voltage and Ca2+-activated potassium channels which qualitatively reproduce the dwell-time distributions, and describe the experimentally observed long-term memory quite well. Biological interpretation of both models is presented. In particular, the origin of the correlations is associated with fluctuations of channel mass density. The long-term memory effect, as measured by Hurst R/S analysis of experimental single-channel patch-clamp recordings, is close to the behaviour predicted by our models. The flexibility of the models enables their use as templates for other types of ion channel

Investigating Primary Cilia during Peripheral Nervous System Formation

The primary cilium plays a pivotal role during the embryonic development of vertebrates. It acts as a somatic signaling hub for specific pathways, such as Sonic Hedgehog signaling. In humans, mutations in genes that cause dysregulation of ciliogenesis or ciliary function lead to severe developmental disorders called ciliopathies. Beyond its role in early morphogenesis, growing evidence points towards an essential function of the primary cilium in neural circuit formation in the central nervous system. However, very little is known about a potential role in the formation of the peripheral nervous system. Here, we investigate the presence of the primary cilium in neural crest cells and their derivatives in the trunk of developing chicken embryos in vivo. We found that neural crest cells, sensory neurons, and boundary cap cells all bear a primary cilium during key stages of early peripheral nervous system formation. Moreover, we describe differences in the ciliation of neuronal cultures of different populations from the peripheral and central nervous systems. Our results offer a framework for further in vivo and in vitro investigations on specific roles that the primary cilium might play during peripheral nervous system formation

THE PROBLEM OF ATTITUDES TO HEALTH AND HEALTHY LIFESTYLE FIRST-YEAR STUDENTS

In article the attitudes towards health and a healthy lifestyle at first-year students are investigated. Problems of health are especially actual for our country as owing to the happening social transformations, the low level of culture of the attitude towards the health the prestige of a healthy lifestyle, especially at youth catastrophically falls. Results of research have important theoretical value for the analysis of a healthy lifestyle, psychological culture, the attitude towards health of student's youth, in particular, they testify to low levels of behavioural activity and uneasiness in relation to the health at respondents. The received results and the formulated conclusions allow to reflect more deeply and in details processes of change and deformation of a way of life and culture of health and can be used in educational process as textbooks and methodical grants in these subjects are generally focused on a statement of material and don't provide development by students of technologies of self-development, formation of personal vital philosophy, individual system of a healthy lifestyle