2,098 research outputs found
Differential Sialylation Modulates Voltage-gated Na+ Channel Gating throughout the Developing Myocardium
Voltage-gated sodium channel function from neonatal and adult rat cardiomyocytes was measured and compared. Channels from neonatal ventricles required an ā¼10 mV greater depolarization for voltage-dependent gating events than did channels from neonatal atria and adult atria and ventricles. We questioned whether such gating shifts were due to developmental and/or chamber-dependent changes in channel-associated functional sialic acids. Thus, all gating characteristics for channels from neonatal atria and adult atria and ventricles shifted significantly to more depolarized potentials after removal of surface sialic acids. Desialylation of channels from neonatal ventricles did not affect channel gating. After removal of the complete surface N-glycosylation structures, gating of channels from neonatal atria and adult atria and ventricles shifted to depolarized potentials nearly identical to those measured for channels from neonatal ventricles. Gating of channels from neonatal ventricles were unaffected by such deglycosylation. Immunoblot gel shift analyses indicated that voltage-gated sodium channel Ī± subunits from neonatal atria and adult atria and ventricles are more heavily sialylated than Ī± subunits from neonatal ventricles. The data are consistent with approximately 15 more sialic acid residues attached to each Ī± subunit from neonatal atria and adult atria and ventricles. The data indicate that differential sialylation of myocyte voltage-gated sodium channel Ī± subunits is responsible for much of the developmental and chamber-specific remodeling of channel gating observed here. Further, cardiac excitability is likely impacted by these sialic acidādependent gating effects, such as modulation of the rate of recovery from inactivation. A novel mechanism is described by which cardiac voltage-gated sodium channel gating and subsequently cardiac rhythms are modulated by changes in channel-associated sialic acids
EPR of Cu\u3csup\u3e2+\u3c/sup\u3e Prion Protein Constructs at 2 GHz Using the \u3cem\u3eg\u3c/em\u3e\u3csub\u3eā„\u3c/sub\u3e Region to Characterize Nitrogen Ligation
A double octarepeat prion protein construct, which has two histidines, mixed with copper sulfate in a 3:2 molar ratio provides at most three imidazole ligands to each copper ion to form a square-planar Cu2+ complex. This work is concerned with identification of the fourth ligand. A new (to our knowledge) electron paramagnetic resonance method based on analysis of the intense features of the electron paramagnetic resonance spectrum in the gā„ region at 2 GHz is introduced to distinguish between three and four nitrogen ligands. The methodology was established by studies of a model system consisting of histidine imidazole ligation to Cu2+. In this spectral region at 2 GHz (S-band), g-strain and broadening from the possible rhombic character of the Zeeman interaction are small. The most intense line is identified with the MI = +1/2 extra absorption peak. Spectral simulation demonstrated that this peak is insensitive to cupric Ax and Ay hyperfine interaction. The spectral region to the high-field side of this peak is uncluttered and suitable for analysis of nitrogen superhyperfine couplings to determine the number of nitrogens. The spectral region to the low-field side of the intense extra absorption peak in the gā„ part of the spectrum is sensitive to the rhombic distortion parameters Ax and Ay. Application of the method to the prion protein system indicates that two species are present and that the dominant species contains four nitrogen ligands. A new loop-gap microwave resonator is described that contains ā¼1 mL of frozen sample
Site-specific identification and quantitation of endogenous SUMO modifications under native conditions.
Small ubiquitin-like modifier (SUMO) modification regulates numerous cellular processes. Unlike ubiquitin, detection of endogenous SUMOylated proteins is limited by the lack of naturally occurring protease sites in the C-terminal tail of SUMO proteins. Proteome-wide detection of SUMOylation sites on target proteins typically requires ectopic expression of mutant SUMOs with introduced tryptic sites. Here, we report a method for proteome-wide, site-level detection of endogenous SUMOylation that uses Ī±-lytic protease, WaLP. WaLP digestion of SUMOylated proteins generates peptides containing SUMO-remnant diglycyl-lysine (KGG) at the site of SUMO modification. Using previously developed immuno-affinity isolation of KGG-containing peptides followed by mass spectrometry, we identified 1209 unique endogenous SUMO modification sites. We also demonstrate the impact of proteasome inhibition on ubiquitin and SUMO-modified proteomes using parallel quantitation of ubiquitylated and SUMOylated peptides. This methodological advancement enables determination of endogenous SUMOylated proteins under completely native conditions
Quantum Nonlocality without Entanglement
We exhibit an orthogonal set of product states of two three-state particles
that nevertheless cannot be reliably distinguished by a pair of separated
observers ignorant of which of the states has been presented to them, even if
the observers are allowed any sequence of local operations and classical
communication between the separate observers. It is proved that there is a
finite gap between the mutual information obtainable by a joint measurement on
these states and a measurement in which only local actions are permitted. This
result implies the existence of separable superoperators that cannot be
implemented locally. A set of states are found involving three two-state
particles which also appear to be nonmeasurable locally. These and other
multipartite states are classified according to the entropy and entanglement
costs of preparing and measuring them by local operations.Comment: 27 pages, Latex, 6 ps figures. To be submitted to Phys. Rev. A.
Version 2: 30 pages, many small revisions and extensions, author added.
Version 3: Proof in Appendix D corrected, many small changes; final version
for Phys. Rev. A Version 4: Report of Popescu conjecture modifie
Quantum-noise--randomized data-encryption for WDM fiber-optic networks
We demonstrate high-rate randomized data-encryption through optical fibers
using the inherent quantum-measurement noise of coherent states of light.
Specifically, we demonstrate 650Mbps data encryption through a 10Gbps
data-bearing, in-line amplified 200km-long line. In our protocol, legitimate
users (who share a short secret-key) communicate using an M-ry signal set while
an attacker (who does not share the secret key) is forced to contend with the
fundamental and irreducible quantum-measurement noise of coherent states.
Implementations of our protocol using both polarization-encoded signal sets as
well as polarization-insensitive phase-keyed signal sets are experimentally and
theoretically evaluated. Different from the performance criteria for the
cryptographic objective of key generation (quantum key-generation), one
possible set of performance criteria for the cryptographic objective of data
encryption is established and carefully considered.Comment: Version 2: Some errors have been corrected and arguments refined. To
appear in Physical Review A. Version 3: Minor corrections to version
Reconsidering "the love of art" : evaluating the potential of art museum outreach
Art museums have long been identified as bastions of social and cultural exclusion. This conclusion was best evidenced by the large-scale 1967 French study by Bourdieu and Darbel demonstrating the exclusionary nature of āThe Love of Art.ā However, in recent years there have been increasing efforts to reach out to a broader range of visitors beyond conventional
audiences. The present study investigates the impacts of an outreach program at a UK art museum, which sought to engage socially excluded young mothers. This study employs ethnographic research methods on a longitudinal basis to develop qualitative insights about the program seeking to mitigate cultural exclusion. While the studyās findings uphold many longstanding critiques of art museumsā conventional approaches, the study also indicates that carefully designed outreach activities can overcome such limitations and enhance cultural
engagement. Thus, art museumsā limited appeal is tied to problematic public engagement practices that can be changed
Reduction of Healthcare-Associated Infections by Exceeding High Compliance with Hand Hygiene Practices
Improving hand hygiene from high to very high compliance has not been documented to decrease healthcare-associated infections. We conducted longitudinal analyses during 2013ā2015 in an 853-bed hospital and observed a significantly increased hand hygiene compliance rate (p<0.001) and a significantly decreased healthcare-associated infection rate (p = 0.0066)
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