469 research outputs found
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Sarcoplasmic reticular Ca 2+ -ATPase inhibition paradoxically upregulates murine skeletal muscle Na v 1.4 function
Abstract: Skeletal muscle Na+ channels possess Ca2+- and calmodulin-binding sites implicated in Nav1.4 current (INa) downregulation following ryanodine receptor (RyR1) activation produced by exchange protein directly activated by cyclic AMP or caffeine challenge, effects abrogated by the RyR1-antagonist dantrolene which itself increased INa. These findings were attributed to actions of consequently altered cytosolic Ca2+, [Ca2+]i, on Nav1.4. We extend the latter hypothesis employing cyclopiazonic acid (CPA) challenge, which similarly increases [Ca2+]i, but through contrastingly inhibiting sarcoplasmic reticular (SR) Ca2+-ATPase. Loose patch clamping determined Na+ current (INa) families in intact native murine gastrocnemius skeletal myocytes, minimising artefactual [Ca2+]i perturbations. A bespoke flow system permitted continuous INa comparisons through graded depolarizing steps in identical stable membrane patches before and following solution change. In contrast to the previous studies modifying RyR1 activity, and imposing control solution changes, CPA (0.1 and 1 ”M) produced persistent increases in INa within 1â4 min of introduction. CPA pre-treatment additionally abrogated previously reported reductions in INa produced by 0.5 mM caffeine. Plots of peak current against voltage excursion demonstrated that 1 ”M CPA increased maximum INa by ~ 30%. It only slightly decreased half-maximal activating voltages (V0.5) and steepness factors (k), by 2 mV and 0.7, in contrast to the V0.5 and k shifts reported with direct RyR1 modification. These paradoxical findings complement previously reported downregulatory effects on Nav1.4 of RyR1-agonist mediated increases in bulk cytosolic [Ca2+]. They implicate possible local tubule-sarcoplasmic triadic domains containing reduced [Ca2+]TSR in the observed upregulation of Nav1.4 function following CPA-induced SR Ca2+ depletion
Sarcoplasmic reticular Ca 2+ -ATPase inhibition paradoxically upregulates murine skeletal muscle Na v 1.4 function
Abstract: Skeletal muscle Na+ channels possess Ca2+- and calmodulin-binding sites implicated in Nav1.4 current (INa) downregulation following ryanodine receptor (RyR1) activation produced by exchange protein directly activated by cyclic AMP or caffeine challenge, effects abrogated by the RyR1-antagonist dantrolene which itself increased INa. These findings were attributed to actions of consequently altered cytosolic Ca2+, [Ca2+]i, on Nav1.4. We extend the latter hypothesis employing cyclopiazonic acid (CPA) challenge, which similarly increases [Ca2+]i, but through contrastingly inhibiting sarcoplasmic reticular (SR) Ca2+-ATPase. Loose patch clamping determined Na+ current (INa) families in intact native murine gastrocnemius skeletal myocytes, minimising artefactual [Ca2+]i perturbations. A bespoke flow system permitted continuous INa comparisons through graded depolarizing steps in identical stable membrane patches before and following solution change. In contrast to the previous studies modifying RyR1 activity, and imposing control solution changes, CPA (0.1 and 1 ”M) produced persistent increases in INa within 1â4 min of introduction. CPA pre-treatment additionally abrogated previously reported reductions in INa produced by 0.5 mM caffeine. Plots of peak current against voltage excursion demonstrated that 1 ”M CPA increased maximum INa by ~ 30%. It only slightly decreased half-maximal activating voltages (V0.5) and steepness factors (k), by 2 mV and 0.7, in contrast to the V0.5 and k shifts reported with direct RyR1 modification. These paradoxical findings complement previously reported downregulatory effects on Nav1.4 of RyR1-agonist mediated increases in bulk cytosolic [Ca2+]. They implicate possible local tubule-sarcoplasmic triadic domains containing reduced [Ca2+]TSR in the observed upregulation of Nav1.4 function following CPA-induced SR Ca2+ depletion
Oxidation of Fish Oil Oleogels Formed by Natural Waxes in Comparison With Bulk Oil
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143663/1/ejlt201700378.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143663/2/ejlt201700378_am.pd
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Biophysics at the coffee shop: lessons learned working with George Oster
Over the past 50 years, the use of mathematical models, derived from physical reasoning, to describe molecular and cellular systems has evolved from an art of the few to a cornerstone of biological inquiry. George Oster stood out as a pioneer of this paradigm shift from descriptive to quantitative biology not only through his numerous research accomplishments, but also through the many students and postdocs he mentored over his long career. Those of us fortunate enough to have worked with George agree that his sharp intellect, physical intuition, and passion for scientific inquiry not only inspired us as scientists but also greatly influenced the way we conduct research. We would like to share a few important lessons we learned from George in honor of his memory and with the hope that they may inspire future generations of scientists.National Science Foundation [MCB-1616755, DMS-1462049]; Johns Hopkins UniversityThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Stellar spectroscopy: Fermions and holographic Lifshitz criticality
Electron stars are fluids of charged fermions in Anti-de Sitter spacetime.
They are candidate holographic duals for gauge theories at finite charge
density and exhibit emergent Lifshitz scaling at low energies. This paper
computes in detail the field theory Green's function G^R(w,k) of the
gauge-invariant fermionic operators making up the star. The Green's function
contains a large number of closely spaced Fermi surfaces, the volumes of which
add up to the total charge density in accordance with the Luttinger count.
Excitations of the Fermi surfaces are long lived for w <~ k^z. Beyond w ~ k^z
the fermionic quasiparticles dissipate strongly into the critical Lifshitz
sector. Fermions near this critical dispersion relation give interesting
contributions to the optical conductivity.Comment: 38 pages + appendices. 9 figure
A Bimodal Science Measurements for Earth Remote Sensing on a 3U CubeSat Platform
Solar energetic events, which include solar flares and solar mass ejections affect the Earth\u27s atmosphere. While solar energetic events have been observed to influence the chemistry of the mesospheric ozone, a comprehensive collection of quantitative data detailing the frequency, energy, and intensity of these interactions with the mesosphere have, to our knowledge, not before been collected. High-energy charged particles from solar energetic events can ionize molecules found within the mesosphere, accelerating the formation rate of reactive hydrogen atoms and nitrogen oxides. This results in reactions that catalyze the conversion of ozone back into diatomic oxygen. The Variability in Atmosphere â Solar Energetic Event study (VIA-SEEs) mission intends to utilize a 3U-CubeSat in Low Earth Orbit (LEO) to establish a singular data set for the purpose of understanding the correlation between flux in solar energetic events and variability in total reactive nitrogen oxides (NOy) and ozone (O3) concentrations in the mesosphere. This mission intends to produce a unique data set using a bimodal measurement scheme involving two instruments â one Variability in Atmosphere (VIA) commercial-off-the-shelf spectrophotometer for measuring NOy and O3 concentrations, and one in-house designed and fabricated solid-state radiation detector for observing the energy and flux of solar energetic electrons and protons
The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protectionâevaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology
Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury
Phosphorene: Fabrication, Properties and Applications
Phosphorene, the single- or few-layer form of black phosphorus, was recently
rediscovered as a twodimensional layered material holding great promise for
applications in electronics and optoelectronics. Research into its fundamental
properties and device applications has since seen exponential growth. In this
Perspective, we review recent progress in phosphorene research, touching upon
topics on fabrication, properties, and applications; we also discuss challenges
and future research directions. We highlight the intrinsically anisotropic
electronic, transport, optoelectronic, thermoelectric, and mechanical
properties of phosphorene resulting from its puckered structure in contrast to
those of graphene and transition-metal dichalcogenides. The facile fabrication
and novel properties of phosphorene have inspired design and demonstration of
new nanodevices; however, further progress hinges on resolutions to technical
obstructions like surface degradation effects and non-scalable fabrication
techniques. We also briefly describe the latest developments of more
sophisticated design concepts and implementation schemes that address some of
the challenges in phosphorene research. It is expected that this fascinating
material will continue to offer tremendous opportunities for research and
development for the foreseeable future.Comment: invited perspective for JPC
Functional Reconstitution of a Tunable E3-Dependent Sumoylation Pathway in Escherichia coli
SUMO (small ubiquitin-related modifier) is a reversible post-translational protein modifier that alters the localization, activity, or stability of proteins to which it is attached. Many enzymes participate in regulated SUMO-conjugation and SUMO-deconjugation pathways. Hundreds of SUMO targets are currently known, with the majority being nuclear proteins. However, the dynamic and reversible nature of this modification and the large number of natively sumoylated proteins in eukaryotic proteomes makes molecular dissection of sumoylation in eukaryotic cells challenging. Here, we have reconstituted a complete mammalian SUMO-conjugation cascade in Escherichia coli cells that involves a functional SUMO E3 ligase, which effectively biases the sumoylation of both native and engineered substrate proteins. Our sumo-engineered E. coli cells have several advantages including efficient protein conjugation and physiologically relevant sumoylation patterns. Overall, this system provides a rapid and controllable platform for studying the enzymology of the entire sumoylation cascade directly in living cells
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