Catecholamine-induced Ischemic Necrosis of the Hand.

This case highlights the rare complication of ischemic hand necrosis following peripheral administration of epinephrine and norepinephrine.

Ultrasound use during cardiopulmonary resuscitation is associated with delays in chest compressions.

Aim: High-quality chest compressions are a critical component of the resuscitation of patients in cardiopulmonary arrest. Point-of-care ultrasound (POCUS) is used frequently during emergency department (ED) resuscitations, but there has been limited research assessing its benefits and harms during the delivery of cardiopulmonary resuscitation (CPR). We hypothesized that use of POCUS during cardiac arrest resuscitation adversely affects high-quality CPR by lengthening the duration of pulse checks beyond the current cardiopulmonary resuscitation guidelines recommendation of 10s.

Immune history shapes specificity of pandemic H1N1 influenza antibody responses.

Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are predominantly directed against conserved epitopes in the stalk and receptor-binding domain of the hemagglutinin (HA) protein. This is in stark contrast to pH1N1 antibody responses generated in ferrets, which are focused on the variable Sa antigenic site of HA. Here, we show that most humans born between 1983 and 1996 elicited pH1N1 antibody responses that are directed against an epitope near the HA receptor-binding domain.

Single hemagglutinin mutations that alter both antigenicity and receptor binding avidity influence influenza virus antigenic clustering.

The hemagglutination inhibition (HAI) assay is the primary measurement used for identifying antigenically novel influenza virus strains. HAI assays measure the amount of reference sera required to prevent virus binding to red blood cells. Receptor binding avidities of viral strains are not usually taken into account when interpreting these assays.

Two mutations associated with macrolide resistance in Treponema pallidum: increasing prevalence and correlation with molecular strain type in Seattle, Washington.

Background: Although azithromycin promised to be a safe and effective single-dose oral treatment of early syphilis, azithromycin treatment failure has been documented and is associated with mutations in the 23S rDNA of corresponding Treponema pallidum strains. The prevalence of strains harboring these mutations varies throughout the United States and the world. We examined T.

Structure and age jointly influence rates of protein evolution.

What factors determine a protein's rate of evolution are actively debated. Especially unclear is the relative role of intrinsic factors of present-day proteins versus historical factors such as protein age. Here we study the interplay of structural properties and evolutionary age, as determinants of protein evolutionary rate.

Selective complexation of K+ and Na+ in simple polarizable ion-ligating systems.

An influx of experimental and theoretical studies of ion transport protein structure has inspired efforts to understand underlying determinants of ionic selectivity. Design principles for selective ion binding can be effectively isolated and interrogated using simplified models composed of a single ion surrounded by a set of ion-ligating molecular species. While quantum mechanical treatments of such systems naturally incorporate electronic degrees of freedom, their computational overhead typically prohibits thorough dynamic sampling of configurational space and, thus, requires approximations when determining ion-selective free energy.

An Australian environmental survey reveals moderate Spiroplasma biodiversity: characterization of four new serogroups and a continental variant.

An environmental survey of tabanid host spiroplasma carriage was undertaken at 10 collection sites in Australia during February 1999. A total of 164 tabanid flies, representing 27 species, were collected and sustainable spiroplasma isolations were made from 48 of the flies. The morphology of the cultured spiroplasmas, as observed in M1D medium under dark-field microscopy, was typical of either (i) Apis group spiroplasmas (relatively thick cells (approximately 150 nm) with six or more turns) or (ii) chrysopicola-syrphidicola-TAAS-1 clade spiroplasmas (narrower, often much shorter cells) serologically related to Spiroplasma serogroup VIII.

Statistical determinants of selective ionic complexation: ions in solvent, transport proteins, and other "hosts".

To provide utility in understanding the molecular evolution of ion-selective biomembrane channels/transporters, globular proteins, and ionophoric compounds, as well as in guiding their modification and design, we present a statistical mechanical basis for deconstructing the impact of the coordination structure and chemistry of selective multidentate ionic complexes. The deconstruction augments familiar ideas in liquid structure theory to realize the ionic complex as an open ion-ligated system acting under the influence of an "external field" provided by the host (or surrounding medium). Using considerations derived from this basis, we show that selective complexation arises from exploitation of a particular ion's coordination preferences.

K+/Na+ selectivity in toy cation binding site models is determined by the 'host'.

The macroscopic ion-selective behavior of K(+) channels is mediated by a multitude of physiological factors. However, considering the carbonyl-lined binding site of a conductive K(+) channel as a canonical eightfold coordinated construct can be useful in understanding the principles that correlate the channel's structure with its function. We probe the effects of structure and chemical composition on the K(+)/Na(+) selectivity provided by a variety of simplified droplet-like ion binding site models.

Selectivity in K+ channels is due to topological control of the permeant ion's coordinated state.

The selectivity filter of K+ channels provides specific coordinative interactions between dipolar carbonyl ligands, water, and the permeant cation, which allow for selective flow of K+ over (most importantly) Na+ across the cell membrane. Although a structural viewpoint attributes K+ selectivity to coordination geometry provided by the filter, recent molecular dynamics simulation studies attribute it to dynamic and unique chemical/electrostatic properties of the filter's carbonyl ligands. Here we provide a simple theoretical analysis of K+ and Na+ complexation with water in the context of simplified binding site models and bulk solution.

On the equivalence point for ammonium (de)protonation during its transport through the AmtB channel.

Structural characterization of the bacterial channel, AmtB, provides a glimpse of how members of its family might control the protonated state of permeant ammonium to allow for its selective passage across the membrane. In a recent study, we employed a combination of simulation techniques that suggested ammonium is deprotonated and reprotonated near dehydrative phenylalanine landmarks (F107 and F31, respectively) during its passage from the periplasm to the cytoplasm. At these landmarks, ammonium is forced to maintain a critical number ( approximately 3) of hydrogen bonds, suggesting that the channel controls ammonium (de)protonation by controlling its coordination/hydration.

Deprotonation by dehydration: the origin of ammonium sensing in the AmtB channel.

The AmtB channel passively allows the transport of NH4(+) across the membranes of bacteria via a "gas" NH3 intermediate and is related by homology (sequentially, structurally, and functionally) to many forms of Rh protein (both erythroid and nonerythroid) found in animals and humans. New structural information on this channel has inspired computational studies aimed at clarifying various aspects of NH4(+) recruitment and binding in the periplasm, as well as its deprotonation. However, precise mechanisms for these events are still unknown, and, so far, explanations for subsequent NH3 translocation and reprotonation at the cytoplasmic end of the channel have not been rigorously addressed.

Exterior site occupancy infers chloride-induced proton gating in a prokaryotic homolog of the ClC chloride channel.

The ClC family of anion channels mediates the efficient, selective permeation of Cl(-) across the biological membranes of living cells under the driving force of an electrochemical gradient. In some eukaryotes, these channels are known to exhibit a unique gating mechanism, which appears to be triggered by the permeant Cl(-) anion. We infer details of this gating mechanism by studying the free energetics of Cl(-) occupancy in the pore of a prokaryotic ClC homolog.

A simple topological representation of protein structure: implications for new, fast, and robust structural classification.

A topological representation of proteins is developed that makes use of two metrics: the Euclidean metric for identifying natural nearest neighboring residues via the Delaunay tessellation in Cartesian space and the distance between residues in sequence space. Using this representation, we introduce a quantitative and computationally inexpensive method for the comparison of protein structural topology. The method ultimately results in a numerical score quantifying the distance between proteins in a heuristically defined topological space.

Complexation of phosphatidylcholine lipids with cholesterol.

It is postulated that the specific interactions between cholesterol and lipids in biological membranes are crucial in the formation of complexes leading subsequently to membrane domains (so-called rafts). These interactions are studied in molecular dynamics simulations performed on a dipalmitoylphosphatidylcholine (DPPC)-cholesterol bilayer mixture and a dilauroylphosphatidylcholine (DLPC)-cholesterol bilayer mixture, both having a cholesterol concentration of 40 mol %. Complexation of the simulated phospholipids with cholesterol is observed and visualized, exhibiting 2:1 and 1:1 stoichiometries.

Mixed bilayer containing dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine: lipid complexation, ion binding, and electrostatics.

Two mixed bilayers containing dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine at a ratio of 5:1 are simulated in NaCl electrolyte solutions of different concentration using the molecular dynamics technique. Direct NH.O and CH.

The implementation of slab geometry for membrane-channel molecular dynamics simulations.

Slab geometric boundary conditions are applied in the molecular dynamics simulation of a simple membrane-channel system. The results of the simulation were compared to those of an analogous system using normal three-dimensional periodic boundary conditions. Analysis of the dynamics and electrostatics of the system show that slab geometric periodicity eliminates the artificial bulk water orientational polarization that is present while using normal three-dimensional periodicity.

Molecular dynamics simulation of a dipalmitoylphosphatidylcholine bilayer with NaCl.

Molecular dynamics simulations are performed on two hydrated dipalmitoylphosphatidylcholine bilayer systems: one with pure water and one with added NaCl. Due to the rugged nature of the membrane/electrolyte interface, ion binding to the membrane surface is characterized by the loss of ion hydration. Using this structural characterization, binding of Na(+) and Cl(-) ions to the membrane is observed, although the binding of Cl(-) is seen to be slightly weaker than that of Na(+).

A new topological method to measure protein structure similarity.

A method for the quantitative evaluation of structural similarity between protein pairs is developed that makes use of a Delaunay-based topological mapping. The result of the mapping is a three-dimensional array which is representative of the global structural topology and whose elements can be used to construe an integral scoring scheme. This scoring scheme was tested for its dependence on the protein length difference in a pairwise comparison, its ability to provide a reasonable means for structural similarity comparison within a family of structural neighbors of similar length, and its sensitivity to the differences in protein conformation.