A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.Comment: Accepted by Physical Biology; includes a supplement and a supplementary mpeg movie can be found at http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp

Evidence for two classes of parsec-scale radio double source in active galactic nuclei

There is a group of powerful compact radio sources which have two almost equal flux density components on parsec scales. On the basis of multifrequency, multiepoch Very Long Base Interferometry (VLBI) observations, we conclude that there are two physically distinct classes among such sources. In one class the two components are probably 'minilobes' where oppositely directed jets terminate. Because of their intrinsic symmetry we believe the new name 'compact symmetric objects' best describes this class of object. We present detailed observations of the source 0108+388, showing that this source has properties consistent with this class, including a very small limit on relative internal motions of is ≤ 0.18/h^(-1) (c) (using H_0 = 100 h km s^(-1) Mp c^(-1) and q_0 = 0.5). We also detect a weak feature between the two main components which may be associated with the central engine in this source. We believe there exists another class of double source composed of core-jet sources in which a component in the jet is as bright as the component associated with the central engine. These sources are distinct from those of the first class in showing systematic differences in the properties of the two components. All these sources have small relative motions between the two main components (e.g., in 2021+614 we detect a motion of 0.13 h^(-1)(c) and in 0711+356 an upper limit of 0.4 h^(-1)(c)). The combination of large relative brightness for the secondary and the low velocities might be explained if the secondary is due to a bright standing shock in the jet. Alternatively, the bright secondary component might be due to a relativistic flow close to the line of sight at a point along a curving parsec-scale channel (as has been proposed for 4C 39.25)

Markarian 421's Unusual Satellite Galaxy

We present Hubble Space Telescope (HST) imagery and photometry of the active galaxy Markarian 421 and its companion galaxy 14 arcsec to the ENE. The HST images indicate that the companion is a morphological spiral rather than elliptical as previous ground--based imaging has concluded. The companion has a bright, compact nucleus, appearing unresolved in the HST images. This is suggestive of Seyfert activity, or possibly a highly luminous compact star cluster. We also report the results of high dynamic range long-slit spectroscopy with the slit placed to extend across both galaxies and nuclei. We detect no emission lines in the companion nucleus, though there is evidence for recent star formation. Velocities derived from a number of absorption lines visible in both galaxies indicate that the two systems are probably tidally bound and thus in close physical proximity. Using the measured relative velocities, we derive a lower limit on the MKN 421 mass within the companion orbit (R \sim 10 kpc) of 5.9 \times 10^{11} solar masses, and a mass-to-light ratio of >= 17. Our spectroscopy also shows for the first time the presence of H\alpha and [NII] emission lines from the nucleus of MKN 421, providing another example of the appearance of new emission features in the previously featureless spectrum of a classical BL Lac object. We see both broad and narrow line emission, with a velocity dispersion of several thousand km s^{-1} evident in the broad lines.Comment: LaTeX (aaspp4 style), 28 pages, 8 figures, to appear in AJ. Revised text from ref. comments; new & modified figures; new photometry included; minor corrections of typos. Color version of Fig. 1 to appear in Feb. 2000 Sky & Telescop

Kinematics of the Parsec-Scale Relativistic Jet in Quasar 3C 279: 1991-1997

We present results of long-term high-frequency VLBI monitoring of the relativistic jet in 3C 279, consisting of 18 epochs at 22 GHz from 1991 to 1997 and 10 epochs at 43 GHz from 1995 to 1997. Three major results of this study are apparent speeds measured for six superluminal components range from 4.8c to 7.5c (H0=70 km s-1Mpc-1, q0=0.1), variations in the total radio flux are due primarily to changes in the VLBI core flux, and the uniform-sphere brightness temperature of the VLBI core is ~1×1013 K at 22 GHz after 1995, one of the highest direct estimates of a brightness temperature. If the variability brightness temperature measured for 3C 279 by Lähteenmäki & Valtaoja is an actual value and not a lower limit, then the rest-frame brightness temperature of 3C 279 is quite high and limited by inverse Compton effects rather than equipartition. The parsec-scale morphology of 3C 279 consists of a bright, compact VLBI core, a jet component (C4) that moved from ~2 to ~3.5 mas from the core during the course of our monitoring, and an inner jet that extends from the core to a stationary component, C5, at ~1 mas from the core. Component C4 followed a curved path, and we reconstruct its three-dimensional trajectory using polynomial fits to its position versus time. Component C5 faded with time, possibly due to a previous interaction with C4 similar to interactions seen in simulations by Gómez et al. Components in the inner jet are relatively short lived and fade by the time they reach ~1 mas from the core. The components have different speeds and position angles from each other, but these differences do not match the differences predicted by the precession model of Abraham & Carrara. Although VLBI components were born about six months prior to each of the two observed γ-ray high states, the sparseness of the γ-ray data prevents a statistical analysis of possible correlations

A new small-bodied azhdarchoid pterosaur from the Lower Cretaceous of England and its implications for pterosaur anatomy, diversity and phylogeny

BACKGROUND: Pterosaurs have been known from the Cretaceous sediments of the Isle of Wight (southern England, United Kingdom) since 1870. We describe the three-dimensional pelvic girdle and associated vertebrae of a small near-adult pterodactyloid from the Atherfield Clay Formation (lower Aptian, Lower Cretaceous). Despite acknowledged variation in the pterosaur pelvis, previous studies have not adequately sampled or incorporated pelvic characters into phylogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: The new specimen represents the new taxon Vectidraco daisymorrisae gen. et sp. nov., diagnosed by the presence of a concavity posterodorsal to the acetabulum and the form of its postacetabular process on the ilium. Several characters suggest that Vectidraco belongs to Azhdarchoidea. We constructed a pelvis-only phylogenetic analysis to test whether the pterosaur pelvis carries a useful phylogenetic signal. Resolution in recovered trees was poor, but they approximately matched trees recovered from analyses of total evidence. We also added Vectidraco and our pelvic characters to an existing total-evidence matrix for pterosaurs. Both analyses recovered Vectidraco within Azhdarchoidea. CONCLUSIONS/ SIGNIFICANCE: The Lower Cretaceous strata of western Europe have yielded members of several pterosaur lineages, but Aptian pterosaurs from western Europe are rare. With a pelvis length of 40 mm, the new animal would have had a total length of c. 350 mm, and a wingspan of c. 750 mm. Barremian and Aptian pterodactyloids from western Europe show that small-bodied azhdarchoids lived alongside ornithocheirids and istiodactylids. This assemblage is similar in terms of which lineages are represented to the coeval beds of Liaoning, China; however, the number of species and specimens present at Liaoning is much higher. While the general phylogenetic composition of western European and Chinese communities appear to have been approximately similar, the differences may be due to different palaeoenvironmental and depositional settings. The western Europe pterodactyloid record may therefore be artificially low in diversity due to preservational factors

Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK.

OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose tolerance and diabetes), and its relationship to body mass index (BMI) and waist-hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK. MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI, waist circumference, and waist-hip ratio. METHODS: Population based samples of Chinese and European adults were recruited. Each subject had a standard WHO oral glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and 610 Europid subjects. The age adjusted prevalences of glucose intolerance in Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values < 0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3 cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v 0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared with Europids. In both Chinese and Europid adults, higher BMI, waist circumference, and waist-hip ratio were associated with glucose intolerance. CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women, despite lower BMIs, is similar to or higher than that in local Europid men and women and intermediate between levels found in China and those in Mauritius. It is suggested that an increase in mean BMI to the levels in the Europid population will be associated with a substantial increase in glucose intolerance in Chinese people

Zero modes, entropy bounds and partition functions

Some recent finite temperature calculations arising in the investigation of the Verlinde-Cardy relation are re-analysed. Some remarks are also made about temperature inversion symmetry.Comment: 12 pages, JyTe

VSOP and Ground-based VLBI Imaging of the TeV Blazar Markarian 421 at Multiple Epochs

We present thirty VLBI images of the TeV blazar Markarian 421 (1101+384) at fifteen epochs spanning the time range from 1994 to 1997, and at six different frequencies from 2.3 to 43 GHz. The imaged observations include a high-resolution 5 GHz VLBI Space Observatory Programme (VSOP) observation with the HALCA satellite on 1997 November 14; full-track VLBA observations from 1994 April, 1996 November, and 1997 May at frequencies between 5 and 43 GHz; six epochs of VLBA snapshot observations at frequencies between 2 and 15 GHz from Radio Reference Frame studies; and five geodetic VLBI observations at 2 and 8 GHz from the archive of the Washington VLBI Correlator Facility located at the U.S. Naval Observatory. The dense time coverage of the images allows us to unambiguously track components in the parsec-scale jet over the observed time range. We measure the speeds of three inner jet components located between 0.5 and 5 mas from the core (0.3 to 3 pc projected linear distance) to be 0.19 +/- 0.27, 0.30 +/- 0.07, and -0.07 +/- 0.07 c (H_{0}=65 km s^{-1} Mpc^{-1}). If the sole 43 GHz image is excluded, all measured speeds are consistent with no motion. These speeds differ from tentative superluminal speeds measured by Zhang & B\aa\aa th from three epochs of data from the early 1980's. Possible interpretations of these subluminal speeds in terms of the high Doppler factor demanded by the TeV variability of this source are discussed.Comment: 18 pages, including 7 figures, emulateapj.sty, accepted by The Astrophysical Journal; modified text describing Radio Reference Frame observation