Direct imaging of magnetohydrodynamic wave mode conversion near a 3D null point on the sun.

Mutual conversion of various kinds of magnetohydrodynamic (MHD) waves can have profound impacts on wave propagation, energy transfer, and heating of the solar chromosphere and corona. Mode conversion occurs when an MHD wave travels through a region where the Alfvén and sound speeds are equal (e.g.

Initial Experience with F(ab')2 Antivenom Compared with Fab Antivenom for Rattlesnake Envenomations Reported to a single poison center during 2019.

Background: There are two Food and Drug Administration (FDA)-approved antivenoms available for rattlesnake envenomations in the United States: the equine-derived F (ab')2 product sold with the brand name Anavip (F (ab')2 AV) and the ovine-derived Fab product sold with the brand name Crofab (FabAV).

Objective: To compare the clinical outcomes of rattlesnake envenomation patients treated either with FabAV or F (ab')AV or a combination of these.

Methods: This is a retrospective chart review of all human rattlesnake envenomations requiring antivenom reported to one regional poison control center in 2019.

EVIDENCE FOR THE MAGNETIC BREAKOUT MODEL IN AN EQUATORIAL CORONAL-HOLE JET.

Small, impulsive jets commonly occur throughout the solar corona, but are especially visible in coronal holes. Evidence is mounting that jets are part of a continuum of eruptions that extends to much larger coronal mass ejections and eruptive flares. Because coronal-hole jets originate in relatively simple magnetic structures, they offer an ideal testbed for theories of energy buildup and release in the full range of solar eruptions.

Reconnection-Driven Magnetohydrodynamic Turbulence in a Simulated Coronal-Hole Jet.

Extreme-ultraviolet and X-ray jets occur frequently in magnetically open coronal holes on the Sun, especially at high solar latitudes. Some of these jets are observed by white-light coronagraphs as they propagate through the outer corona toward the inner heliosphere, and it has been proposed that they give rise to microstreams and torsional Alfvén waves detected in the solar wind. To predict and understand the signatures of coronal-hole jets, we have performed a detailed statistical analysis of such a jet simulated with an adaptively refined magnetohydrodynamics model.

A model for straight and helical solar jets: II. Parametric study of the plasma beta.

Context: Jets are dynamic, impulsive, well-collimated plasma events that develop at many different scales and in different layers of the solar atmosphere.

Aims: Jets are believed to be induced by magnetic reconnection, a process central to many astrophysical phenomena. Within the solar atmosphere, jet-like events develop in many different environments, e.

Three-Dimensional Simulations of Tearing and Intermittency in Coronal Jets.

Observations of coronal jets increasingly suggest that local fragmentation and intermittency play an important role in the dynamics of these events. In this work we investigate this fragmentation in high-resolution simulations of jets in the closed-field corona. We study two realizations of the embedded-bipole model, whereby impulsive helical outflows are driven by reconnection between twisted and untwisted field across the domed fan plane of a magnetic null.

Halogen substituents on the aromatic moiety of the tetracaine scaffold improve potency of cyclic nucleotide-gated channel block.

A series of new tetracaine derivatives with substituents on the aromatic ring was prepared and evaluated for block of retinal rod cyclic nucleotide-gated (CNG) channels. Aromatic substitutions had little effect starting with the basic tetracaine scaffold, but electron-withdrawing substituents significantly improved the blocking potency of an octyl-tail derivative of tetracaine. In particular, halogen substitutions at either the 2- or 3-position on the ring resulted in compounds that were up to eight-fold more potent than the parent octyl-tail derivative and up to 50-fold more potent than tetracaine.

Cyclic nucleotide-gated channel block by hydrolysis-resistant tetracaine derivatives.

To meet a pressing need for better cyclic nucleotide-gated (CNG) channel antagonists, we have increased the biological stability of tetracaine-based blockers by synthesizing amide and thioamide linkage substitutions of tetracaine (1) and a higher affinity octyl tail derivative (5). We report the apparent K(D) values, the mechanism of block, and the in vitro hydrolysis rates for these compounds. The ester linkage substitutions did not adversely affect CNG channel block; unexpectedly, thioamide substitution in 1 (compound 8) improved block significantly.

Block of cyclic nucleotide-gated channels by tetracaine derivatives: role of apolar interactions at two distinct locations.

A series of new tetracaine derivatives was synthesized to explore the effects of hydrophobic character on blockade of cyclic nucleotide-gated (CNG) channels. Increasing the hydrophobicity at either of two positions on the tetracaine scaffold, the tertiary amine or the butyl tail, yields blockers with increased potency. However, shape also plays an important role.

Novel N7- and N1-substituted cGMP derivatives are potent activators of cyclic nucleotide-gated channels.

Cyclic nucleotide-gated (CNG) channels, key players in olfactory and visual signal transduction, generate electrical responses to odorant- and light-induced changes in cyclic nucleotide concentration. Previous work suggests that substitutions are tolerated solely at the C8 position on the purine ring of cGMP. Our studies with C8, 2'-OH, and 2-NH2-modified cGMP derivatives support this assertion.

The pharmacology of cyclic nucleotide-gated channels: emerging from the darkness.

Cyclic nucleotide-gated (CNG) ion channels play a central role in vision and olfaction, generating the electrical responses to light in photoreceptors and to odorants in olfactory receptors. These channels have been detected in many other tissues where their functions are largely unclear. The use of gene knockouts and other methods have yielded some information, but there is a pressing need for potent and specific pharmacological agents directed at CNG channels.

Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels.

Phosphatidylinositol-3,4,5-trisphosphate (PIP3) has been proposed to modulate the odorant sensitivity of olfactory sensory neurons by inhibiting activation of cyclic nucleotide-gated (CNG) channels in the cilia. When applied to the intracellular face of excised patches, PIP3 has been shown to inhibit activation of heteromeric olfactory CNG channels, composed of CNGA2, CNGA4, and CNGB1b subunits, and homomeric CNGA2 channels. In contrast, we discovered that channels formed by CNGA3 subunits from cone photoreceptors were unaffected by PIP3.

Cellular mechanisms underlying prostaglandin-induced transient cAMP signals near the plasma membrane of HEK-293 cells.

We have previously used cyclic nucleotide-gated (CNG) channels as sensors to measure cAMP signals in human embryonic kidney (HEK)-293 cells. We found that prostaglandin E(1) (PGE(1)) triggered transient increases in cAMP concentration near the plasma membrane, whereas total cAMP levels rose to a steady plateau over the same time course. In addition, we presented evidence that the decline in the near-membrane cAMP levels was due primarily to a PGE(1)-induced stimulation of phosphodiesterase (PDE) activity, and that the differences between near-membrane and total cAMP levels were largely due to diffusional barriers and differential PDE activity.

Modifications to the tetracaine scaffold produce cyclic nucleotide-gated channel blockers with widely varying efficacies.

Five new tetracaine analogues were synthesized and evaluated for potency of blockade of cyclic nucleotide-gated channels relative to a multiply charged tetracaine analogue described previously. Increased positive charge at the tertiary amine end of tetracaine results in higher potency and voltage dependence of block. Modifications that reduce the hydrophobic character at the butyl tail are deleterious to block.

High-throughput screening of phosphodiesterase activity in living cells.

Phosphodiesterases (PDEs) hydrolyze the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine 5'-monophosphate (cGMP) and play a crucial role in the termination and spatial segregation of cyclic nucleotide signals. Despite a wealth of molecular information, very little is known about how PDEs regulate cAMP and cGMP signals in living cells because conventional methods lack the necessary spatial and temporal resolution. We present here a sensitive optical method for monitoring cAMP levels and PDE activity near the membrane, using cyclic nucleotide-gated (CNG) ion channels as sensors.

High-resolution measurements of cyclic adenosine monophosphate signals in 3D microdomains.

A large number of hormones, neurotransmitters, and odorants exert their effects on cells by triggering changes in intracellular levels of cyclic adenosine monophosphate (cAMP). Although the effector proteins that bind cAMP have been identified, it is not known how this single messenger can differentially regulate the activities of hundreds of cellular proteins. It has been clear, for some time, that compartmentation of cAMP signals must be taking place, but the physical basis for compartmentation and the nature of local cAMP signals are mostly unknown.

Resolution of cAMP signals in three-dimensional microdomains using novel, real-time sensors.

A large number of hormones, neurotransmitters, and odorants alter cellular behavior by triggering changes in intracellular levels of cAMP. Although the effector proteins that bind cAMP have been identified, it is not known how this one messenger can differentially regulate the activities of hundreds of cellular proteins. The spatial and temporal nature of cAMP signals and, thus, their information content remain largely unknown.

Functional role of lipid raft microdomains in cyclic nucleotide-gated channel activation.

Cyclic nucleotide-gated (CNG) channels are the primary targets of light- and odorant-induced signaling in photoreceptors and olfactory sensory neurons. Compartmentalized cyclic nucleotide signaling is necessary to ensure rapid and efficient activation of these nonselective cation channels. However, relatively little is known about the subcellular localization of CNG channels or the mechanisms of their membrane partitioning.

A multiply charged tetracaine derivative blocks cyclic nucleotide-gated channels at subnanomolar concentrations.

Cyclic nucleotide-gated (CNG) ion channels are central participants in sensory transduction, generating the electrical response to light in retinal photoreceptors and to odorants in olfactory receptors. They are expressed in many other tissues where their specific roles in signaling remain unclear. As is true for many other ion channels, there is a paucity of specific blockers needed to dissect the contributions of these channels to cell signaling.

Review article: cyclic AMP sensors in living cells: what signals can they actually measure?

Cyclic AMP is a ubiquitous intracellular second messenger that transmits information to several proteins including cyclic nucleotide-gated ion channels and protein kinase A (PKA). In turn, these effectors regulate such diverse cellular functions as Ca2+ influx, excitability, and gene expression, as well as cell-specific processes such as glycogenolysis and lipolysis. The enzymes known to regulate cAMP levels, adenylyl cyclase and phosphodiesterase, have been studied in detail.

Ion channels: does each subunit do something on its own?

The advent of the patch-clamp technique 25 years ago revolutionized the study of ion channels. This method also made it possible to measure the kinetic behavior of single protein molecules. The low-noise recordings of ionic currents through single channels, coupled with other cutting-edge technologies, have revealed a rich complexity of functional states that are not readily explained by simple allosteric protein models such as the popular concerted model and the sequential model.

A uniform extracellular stimulus triggers distinct cAMP signals in different compartments of a simple cell.

cAMP, the classical second messenger, regulates many diverse cellular functions. The primary effector of cAMP signals, protein kinase A, differentially phosphorylates hundreds of cellular targets. Little is known, however, about the spatial and temporal nature of cAMP signals and their information content.