604 research outputs found
The role of voltage-gated potassium channels in the regulation of mouse uterine contractility
<p>Abstract</p> <p>Background</p> <p>Uterine smooth muscle cells exhibit ionic currents that appear to be important in the control of uterine contractility, but how these currents might produce the changes in contractile activity seen in pregnant myometrium has not been established. There are conflicting reports concerning the role of voltage-gated potassium (Kv) channels and large-conductance, calcium-activated potassium (BK) channels in the regulation of uterine contractility. In this study we provide molecular and functional evidence for a role for Kv channels in the regulation of spontaneous contractile activity in mouse myometrium, and also demonstrate a change in Kv channel regulation of contractility in pregnant mouse myometrium.</p> <p>Methods</p> <p>Functional assays which evaluated the effects of channel blockers and various contractile agonists were accomplished by quantifying contractility of isolated uterine smooth muscle obtained from nonpregnant mice as well as mice at various stages of pregnancy. Expression of Kv channel proteins in isolated uterine smooth muscle was evaluated by Western blots.</p> <p>Results</p> <p>The Kv channel blocker 4-aminopyridine (4-AP) caused contractions in nonpregnant mouse myometrium (EC50 = 54 micromolar, maximal effect at 300 micromolar) but this effect disappeared in pregnant mice; similarly, the Kv4.2/Kv4.3 blocker phrixotoxin-2 caused contractions in nonpregnant, but not pregnant, myometrium. Contractile responses to 4-AP were not dependent upon nerves, as neither tetrodotoxin nor storage of tissues at room temperature significantly altered these responses, nor were responses dependent upon the presence of the endometrium. Spontaneous contractions and contractions in response to 4-AP did not appear to be mediated by BK, as the BK channel-selective blockers iberiotoxin, verruculogen, or tetraethylammonium failed to affect either spontaneous contractions or 4-AP-elicited responses. A number of different Kv channel alpha subunit proteins were found in isolated myometrium from both nonpregnant and term-pregnant mice, and one of these proteins – Kv4.3 – was found to disappear in term-pregnant tissues.</p> <p>Conclusion</p> <p>These findings suggest a role for Kv channels in the regulation of uterine contractility, and that changes in the expression and/or function of specific Kv channels may account for the functional changes seen in pregnant myometrium.</p
High Efficiency Coupling of Alpha-i Adrenergic Receptors to lnositol Phospholipid Metabolism Revealed by Denervation of Rat Vas Deferens1 ABSTRACT
Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory
Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling
Evading the cosmological domain wall problem
Discrete symmetries are commonplace in field theoretical models but pose a
severe problem for cosmology since they lead to the formation of domain walls
during spontaneous symmetry breaking in the early universe. However if one of
the vacuua is favoured over the others, either energetically, or because of
initial conditions, it will eventually come to dominate the universe. Using
numerical methods, we study the evolution of the domain wall network for a
variety of field configurations in two and three dimensions and quantify the
rate at which the walls disappear. Good agreement is found with a recent
analytic estimate of the termination of the scaling regime of the wall network.Comment: 17 pages (revtex), including 9 figures (epsf); Revised to include
test of numerical approximation used; No change in results or conclusions;
accepted for publication in Phys Rev D. PostScript available at
ftp://ftp.physics.ox.ac.uk/pub/local/users/sarkar/Domainwalls.ps.g
Cryptosporidium, Enterocytozoon, and Cyclospora Infections in Pediatric and Adult Patients with Diarrhea in Tanzania.
Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children with chronic diarrhea (of whom 23 of 59 were positive [+] for human immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55 were HIV+), and HIV control children without diarrhea. Cryptosporidium was identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were malnourished, compared with 10/48 without cryptosporidiosis (P < .01). Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control children. All four controls were underweight (P < .01). Cyclospora was identified in specimens from one adult and one child with acute diarrhea (HIV-). Thus, Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen identified. Cryptosporidium and Enterocytozoon were associated with malnutrition. Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children has not been described previously
Persistence of Anderson localization in Schr\"odinger operators with decaying random potentials
We show persistence of both Anderson and dynamical localization in
Schr\"odinger operators with non-positive (attractive) random decaying
potential. We consider an Anderson-type Schr\"odinger operator with a
non-positive ergodic random potential, and multiply the random potential by a
decaying envelope function. If the envelope function decays slower than
at infinity, we prove that the operator has infinitely many
eigenvalues below zero. For envelopes decaying as at infinity,
we determine the number of bound states below a given energy ,
asymptotically as . To show that bound states located at
the bottom of the spectrum are related to the phenomenon of Anderson
localization in the corresponding ergodic model, we prove: (a) these states are
exponentially localized with a localization length that is uniform in the decay
exponent ; (b)~ dynamical localization holds uniformly in
GRACKLE: a chemistry and cooling library for astrophysics
We present the Grackle chemistry and cooling library for astrophysical
simulations and models. Grackle provides a treatment of non-equilibrium
primordial chemistry and cooling for H, D, and He species, including H2
formation on dust grains; tabulated primordial and metal cooling; multiple UV
background models; and support for radiation transfer and arbitrary heat
sources. The library has an easily implementable interface for simulation codes
written in C, C++, and Fortran as well as a Python interface with added
convenience functions for semi-analytical models. As an open-source project,
Grackle provides a community resource for accessing and disseminating
astrochemical data and numerical methods. We present the full details of the
core functionality, the simulation and Python interfaces, testing
infrastructure, performance, and range of applicability. Grackle is a fully
open-source project and new contributions are welcome.Comment: 20 pages, 8 figures, accepted for publication in MNRAS. For more
info, visit grackle.readthedocs.i
Observations of Arp 220 using Herschel-SPIRE: An Unprecedented View of the Molecular Gas in an Extreme Star Formation Environment
We present Herschel SPIRE-FTS observations of Arp~220, a nearby ULIRG. The
FTS continuously covers 190 -- 670 microns, providing a good measurement of the
continuum and detection of several molecular and atomic species. We detect
luminous CO (J = 4-3 to 13-12) and water ladders with comparable total
luminosity; very high-J HCN absorption; OH+, H2O+, and HF in absorption; and CI
and NII. Modeling of the continuum yields warm dust, with T = 66 K, and an
unusually large optical depth of ~5 at 100 microns. Non-LTE modeling of the CO
shows two temperature components: cold molecular gas at T ~ 50 K and warm
molecular gas at T ~1350 K. The mass of the warm gas is 10% of the cold gas,
but dominates the luminosity of the CO ladder. The temperature of the warm gas
is in excellent agreement with H2 rotational lines. At 1350 K, H2 dominates the
cooling (~20 L_sun/M_sun) in the ISM compared to CO (~0.4 L_sun/M_sun). We
found that only a non-ionizing source such as the mechanical energy from
supernovae and stellar winds can excite the warm gas and satisfy the energy
budget of ~20 L_sun/M_sun. We detect a massive molecular outflow in Arp 220
from the analysis of strong P-Cygni line profiles observed in OH+, H2O+, and
H2O. The outflow has a mass > 10^{7} M_sun and is bound to the nuclei with
velocity < 250 km/s. The large column densities observed for these molecular
ions strongly favor the existence of an X-ray luminous AGN (10^{44} ergs/s) in
Arp 220.Comment: Accepted in ApJ on September 1, 201
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