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Kv2.1 channels play opposing roles in regulating membrane potential, Ca2+ channel function, and myogenic tone in arterial smooth muscle.
The accepted role of the protein Kv2.1 in arterial smooth muscle cells is to form K+ channels in the sarcolemma. Opening of Kv2.1 channels causes membrane hyperpolarization, which decreases the activity of L-type CaV1.2 channels, lowering intracellular Ca2+ ([Ca2+]i) and causing smooth muscle relaxation. A limitation of this model is that it is based exclusively on data from male arterial myocytes. Here, we used a combination of electrophysiology as well as imaging approaches to investigate the role of Kv2.1 channels in male and female arterial myocytes. We confirmed that Kv2.1 plays a canonical conductive role but found it also has a structural role in arterial myocytes to enhance clustering of CaV1.2 channels. Less than 1% of Kv2.1 channels are conductive and induce membrane hyperpolarization. Paradoxically, by enhancing the structural clustering and probability of CaV1.2-CaV1.2 interactions within these clusters, Kv2.1 increases Ca2+ influx. These functional impacts of Kv2.1 depend on its level of expression, which varies with sex. In female myocytes, where expression of Kv2.1 protein is higher than in male myocytes, Kv2.1 has conductive and structural roles. Female myocytes have larger CaV1.2 clusters, larger [Ca2+]i, and larger myogenic tone than male myocytes. In contrast, in male myocytes, Kv2.1 channels regulate membrane potential but not CaV1.2 channel clustering. We propose a model in which Kv2.1 function varies with sex: in males, Kv2.1 channels control membrane potential but, in female myocytes, Kv2.1 plays dual electrical and CaV1.2 clustering roles. This contributes to sex-specific regulation of excitability, [Ca2+]i, and myogenic tone in arterial myocytes
Selfgravity and QSO disks
It is well known that the outer parts of QSO accretion disks are prone to
selfgravity if heated solely by orbital dissipation. Such disks might be
expected to form stars rather than accrete onto the black hole. The arguments
leading to this conclusion are reviewed. Conversion of a part of the gas into
high-mass stars or stellar-mass black holes, and the release of energy in these
objects by fusion or accretion, may help to stabilize the remaining gas. If the
disk extends beyond a parsec, however, more energy is probably required for
stability than is available by turning half the gas into high-mass stars. Small
black holes are perhaps marginally viable energy sources, with important
implications (not pursued here) for the QSO spectral energy distribution, the
metallicity of the gas, microlensing of QSO disks, and perhaps
gravitational-wave searches. Other possible palliatives for selfgravity include
accretion driven by nonviscous torques that allow near-sonic accretion speeds
and hence lower surface densities for a given mass accretion rate. All such
modes of accretion face major theoretical difficulties, and in any case merely
postpone selfgravity. Alternatively, thin disks may not exist beyond a thousand
Schwarzshild radii or so (0.01 parsec), in which case QSOs must be fueled by
gas with small specific angular momentum.Comment: 16 pages, no figures; uses mn2e.cl
Human IgG/FcγR Interactions Are Modulated by Streptococcal IgG Glycan Hydrolysis
BACKGROUND: The human pathogen Streptococcus pyogenes produces an endoglycosidase, EndoS that hydrolyzes the chitobiose core of the asparagine-linked glycan on the heavy chain of human IgG. IgG-binding to Fc gamma receptors (FcgammaR) on leukocytes triggers effector functions including phagocytosis, oxidative burst and the release of inflammatory mediators. The interactions between FcgammaR and the Fc domain of IgG depend on the IgG glycosylation state. METHODOLOGY/PRINCIPAL FINDINGS: Here we show for the first time that EndoS hydrolyzes the heavy chain glycan of all four human IgG subclasses (IgG1-4), in purified form and in a plasma environment. An inactive form of EndoS, obtained by site-directed mutagenesis, binds IgG with high affinity, in contrast to wild type EndoS that only transiently interacts with IgG, as shown by Slot-blotting and surface plasmon resonance technology. Furthermore, EndoS hydrolysis of the IgG glycan influences the binding of IgG to immobilized soluble FcgammaR and to an erythroleukemic cell line, K562, expressing FcgammaRIIa. Incubation of whole blood with EndoS results in a dramatic decrease of IgG binding to activated monocytes as analyzed by flow cytometry. Moreover, the IgG bound to K562 cells dissociates when cells are treated with EndoS. Likewise, IgG bound to immobilized FcgammaRIIa and subsequently treated with EndoS, dissociates from the receptor as analyzed by surface plasmon resonance and Western blot. CONCLUSIONS/SIGNIFICANCE: We provide novel information about bacterial enzymatic modulation of the IgG/FcgammaR interaction that emphasizes the importance of glycosylation for antibody effector functions. Moreover, EndoS could be used as a biochemical tool for specific IgG N-glycan hydrolysis and IgG purification/detection, or as a potential immunosuppressing agent for treatment of antibody-mediated pathological processes
New Chiral Phases of Superfluid 3He Stabilized by Anisotropic Silica Aerogel
A rich variety of Fermi systems condense by forming bound pairs, including
high temperature [1] and heavy fermion [2] superconductors, Sr2RuO4 [3], cold
atomic gases [4], and superfluid 3He [5]. Some of these form exotic quantum
states having non-zero orbital angular momentum. We have discovered, in the
case of 3He, that anisotropic disorder, engineered from highly porous silica
aerogel, stabilizes a chiral superfluid state that otherwise would not exist.
Additionally, we find that the chiral axis of this state can be uniquely
oriented with the application of a magnetic field perpendicular to the aerogel
anisotropy axis. At suffciently low temperature we observe a sharp transition
from a uniformly oriented chiral state to a disordered structure consistent
with locally ordered domains, contrary to expectations for a superfluid glass
phase [6].Comment: 6 pages, 4 figure, and Supplementary Informatio
N-band Imaging of Seyfert Nuclei and the MIR-X-ray correlation
We present new mid-infrared (N-band) images of a sample of eight nearby
Seyfert galaxies. In all of our targets, we detect a central unresolved source,
which in some cases has been identified for the first time. In particular, we
have detected the mid-infrared emission from the active nucleus of NGC 4945,
which previously remained undetected at any wavelength but hard X-rays. We also
detect circumnuclear extended emission in the Circinus galaxy along its major
axis, and find marginal evidence for extended circumnuclear emission in NGC
3281.
The high spatial resolution (1.7") of our data allows us to separate the flux
of the nuclear point sources from the extended circumnuclear starburst (if
present). We complement our sample with literature data for a number of
non-active starburst galaxies, and relate the nuclear N-band flux to published
hard (2-10 kev) X-ray fluxes. We find tight and well-separated correlations
between nuclear N-band flux and X-ray flux for both Seyfert and starburst
nuclei which span over 3 orders of magnitude in luminosity. We demonstrate that
these correlations can be used as a powerful classification tool for galactic
nuclei.
For example, we find strong evidence against NGC 1808 currently harbouring an
active Seyfert nucleus based on its position in the mid-infrared-X-ray diagram.
On the other hand, we confirm that NGC 4945 is in fact a Seyfert 2 galaxy.Comment: 31 pages, incl. 4 figures, uses AASTex. Replaced with accepted
version after minor modifications. To appear in Ap
Shadowing of the Nascent Jet in NGC 4261 by a Line-Emitting Supersonic Accretion Disk
NGC 4261 (3C 270) is a low-luminosity radio galaxy with two symmetric
kiloparsec-scale jets. Earlier Hubble Space Telescope observations indicated
the presence of a hundred-parsec scale disk of cool dust and gas surrounding a
central, supermassive (\sim 4.9\times 10^8\msun) black hole. The recent
detection of free-free radio absorption by a small, geometrically-thin disk,
combined with earlier studies of the disk's large scale properties, provide the
strictest constraints to date on the nature of the accretion process in this
system. We show here that a supersonic disk, illuminated by the active galactic
nucleus (AGN), can not only account for the observed radio shadowing, but can
also produce the optical broad lines emitted from this region. Beyond a
critical radius , line cooling dominates over gravitational dissipation
and the gas is effectively cooled down to temperatures below K. Within
, however, heating due to the release of gravitational energy overwhelms
line cooling and the plasma is heated very quickly to a temperature close to
its virial value as it falls toward the central engine. The disk is
optically-thin to UV and X-ray radiation within , so the ionizing
radiation from the AGN is preferentially absorbed near , affecting the
disk structure significantly. To include the ensuing photoionization effect, we
have used the algorithm Cloudy with additional heating introduced by
gravitational dissipation to calculate the temperature profile and line
emission from the disk in a self-consistent manner. The results of our model
calculation are consistent with current multiwavelength observations of the
disk in this source.Comment: 28 pages, 9 figures. To appear in Ap
An integrative identification guide to the Hydrozoa (Cnidaria) of Bocas del Toro, Panama
This work is the first attempt to assess the biodiversity of the Hydrozoa in the Archipiélago de Bocas del Toro (Panamá, Caribbean Sea) using morphology and molecular taxonomy, and to produce field identification tools to help future identification and monitoring efforts in the area. We sampled, identified, vouchered, and barcoded 112 specimens of Hydrozoa from shallow coastal waters (0–22 m depth) in the Archipiélago de Bocas del Toro. The specimens belong to 70 taxa, of which 53 were identified at the species level, and 17 were identified at the genus or family level. We produced 64 sequences of the large ribosomal subunit of the mitochondrial RNA (mt lsu-rRNA, 16S), the genetic marker generally used for barcoding Hydrozoa. We updated the local checklist that now comprises 118 species, and produced 87 detailed taxon identification tables that display species descriptions augmented with pictures, geographic distribution (worldwide and in Bocas del Toro), GenBank accession numbers for the 16S mitochondrial gene, and a synopsis of the families they belong to
Effects of Green Tea Catechins and Theanine on Preventing Influenza Infection among Healthcare Workers: A Randomized Controlled Trial
<p>Abstract</p> <p>Background</p> <p>Experimental studies have revealed that green tea catechins and theanine prevent influenza infection, while the clinical evidence has been inconclusive. This study was conducted to determine whether taking green tea catechins and theanine can clinically prevent influenza infection.</p> <p>Methods</p> <p><b>Design, Setting, and Participants</b>: A randomized, double-blind, placebo-controlled trial of 200 healthcare workers conducted for 5 months from November 9, 2009 to April 8, 2010 in three healthcare facilities for the elderly in Higashimurayama, Japan.</p> <p><b>Interventions</b>: The catechin/theanine group received capsules including green tea catechins (378 mg/day) and theanine (210 mg/day). The control group received placebo.</p> <p><b>Main Outcome Measures</b>: The primary outcome was the incidence of clinically defined influenza infection. Secondary outcomes were (1) laboratory-confirmed influenza with viral antigen measured by immunochromatographic assay and (2) the time for which the patient was free from clinically defined influenza infection, i.e., the period between the start of intervention and the first diagnosis of influenza infection, based on clinically defined influenza infection.</p> <p>Results</p> <p>Eligible healthcare workers (n = 197) were enrolled and randomly assigned to an intervention; 98 were allocated to receive catechin/theanine capsules and 99 to placebo. The incidence of clinically defined influenza infection was significantly lower in the catechin/theanine group (4 participants; 4.1%) compared with the placebo group (13 participants; 13.1%) (adjusted OR, 0.25; 95% CI, 0.07 to 0.76, <it>P </it>= 0.022). The incidence of laboratory-confirmed influenza infection was also lower in the catechin/theanine group (1 participant; 1.0%) than in the placebo group (5 participants; 5.1%), but this difference was not significant (adjusted OR, 0.17; 95% CI, 0.01 to 1.10; <it>P </it>= 0.112). The time for which the patient was free from clinically defined influenza infection was significantly different between the two groups (adjusted HR, 0.27; 95% CI, 0.09 to 0.84; <it>P </it>= 0.023).</p> <p>Conclusions</p> <p>Among healthcare workers for the elderly, taking green tea catechins and theanine may be effective prophylaxis for influenza infection.</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01008020">NCT01008020</a></p
The structure and radiation spectra of illuminated accretion disks in AGN. II. Flare/spot model of X-ray variability
We discuss a model of X-ray variability of active galactic nuclei (AGN). We
consider multiple spots which originate on the surface of an accretion disk
following intense irradiation by coronal flares. The spots move with the disk
around the central black hole and eventually decay while new spots continuously
emerge. We construct time sequences of the spectra of the spotted disk and
compute the corresponding energy-dependent fractional variability amplitude. We
explore the dependence on the disk inclination and other model parameters. AGN
seen at higher inclination with respect to the observer, such as Seyfert 2
galaxies, are expected to have fractional variability amplitude of the direct
emission by a factor of a few higher than objects seen face on, such as the
Seyfert 1s.Comment: Astronomy and Astrophysics (in press
Extreme Slim Accretion Disks and Narrow Line Seyfert 1 Galaxies: the Nature of the soft X-ray Hump
We present a detailed model of an extreme slim disk (ESD) with a hot corona
around a massive black hole with dimensionless accretion rate \dotm in the
range 2.5\ll \dotm\leq 100. We assume that a fraction of the
gravitational energy is released in the hot corona and the rest is released in
the ESD. The energy equation of the ESD is dominated by advection and the
spectrum shows a broad ``hump'' caused by saturated Comptonization with
monochromatic luminosity given by . This relationship
enables us to estimate the black hole mass from the ESD luminosity. The
spectrum of the hot corona is sensitive to the parameter f\dotM and the
viscosity and shows a Comptonized power-law with a high-energy cutoff. The
model is used to explain the spectral properties of narrow line Seyfert 1
galaxies (NLS1s). In particular, it can explain the spectrum of extreme NLS1s
like NLS1 RE J1034+396. Our spectral estimate of the black hole mass in this
source is in good agreement with the mass obtained by applying the
reververation mapping correlation. We also examine the Eddington ratios in a
large NLS1 sample and find that most objects show super-Eddington accretion
rates. We argue that soft X-ray humps in NLS1s are natural consequences of
super-Eddington accretion in such objects.Comment: 11 pages, 5 figures. A&A in pres
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