Estimation of circumferential fiber shortening velocity by echocardiography

The M-mode and two-dimensional echocardiograms of 40 young patients were analyzed to compare the mean circumferential fiber shortening velocity (Vcf) of the left ventricle calculated separately by two methods. The mean circumferential fiber shortening velocity was derived from the M-mode echocardiogram as minor axis shortening/ ejection time and derived from the two-dimensional echocardiogram as actual circumference change/ejection time. With computer assistance, circumference was determined from the short-axis two-dimensional echocardiography images during end-diastole and end-systole. Good correlations were obtained between the left ventricular diameter derived by M-mode echocardiography and the vertical axis during end-diastole (r = 0.79) and end-systole (r = 0.88) derived by two-dimensional echocardiography. Likewise, high correlations were noted between diameter and circumference in end-diastole (r = 0.89) and end-systole (r = 0.88). However, comparison of Vcf obtained by M-mode echocardiography with that obtained by two-dimensional echocardiography showed only fair correlation (r = 0.68). Moreover, the diameter/circumference ratio determined in end-diastole and end-systole differed significantly (p < 0.001), possibly owing to the change in geometry of the ventricular sector image during systole. Although Vcf derived by M-mode echocardiography is a useful index of left ventricular performance, it does not truly reflect the circumference change during systole

Cation-selective channel is regulated by anions according to their Hofmeister ranking

Specificity of small ions, the Hofmeister ranking, is long-known and has many applications including medicine. Yet it evades consistent theoretical description. Here we study the effect of Hofmeister anions on gramicidin A channels in lipid membranes. Counterintuitively, we find that conductance of this perfectly cation-selective channel increases about two-fold in the H2PO4−<Cl−≈Br−≈NO3−<ClO4−<SCN− series. Channel dissociation kinetics show even stronger dependence, with the dwell time increasing ~20-fold. While the conductance can be quantitatively explained by the changes in membrane surface potential due to exclusion of kosmotropes from (or accumulation of chaotropes at) the surface, the kinetics proved to be more difficult to treat. We estimate the effects of changes in the energetics at the bilayer surfaces on the channel dwell time, concluding that the change would have to be greater than typically observed for the Hofmeister effect outside the context of the lipid bilayer., Ion specificity and, in particular, the distinctive effects of anions in salt-induced protein precipitation have been known since the 1880’s, when Franz Hofmeister established the ranking of anions in their ability to regulate egg yolk protein water solubility []. Experimental and theoretical studies have given a detailed empirical picture of the phenomenon, the nature of the ionic interactions with the surfaces leading to the Hofmeister effect is still under debate []. The only consensus is that it cannot be explained by standard theories of electrolytes. For example, bromide is unique in that its salts were recognized as a drug to treat epilepsy a couple of dozen years before Hofmeister’s studies [] and they are still in use to treat specific types of refractory seizures in children [], but the mechanism of their action remains elusive., , Hofmeister effect studied with a nanopore in a neutral lipid membrane. Rather unexpectedly, we find that conductance of a purely cation-selective peptide pore is regulated by anions in correlation with their position in the Hofmeister series. Moreover, the pore conformational dynamics are highly sensitive to the anion species. We relate both effects to preferential depletion of kosmotropic anions (accumulation of chaotropic anions) at the membrane-water interface

Characterizing Residue-Bilayer Interactions Using Gramicidin A as a Scaffold and Tryptophan Substitutions as Probes

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.jctc.7b00400.Previous experiments have shown that the lifetime of a gramicidin A dimer channel (which forms from two non-conducting monomers) in a lipid bilayer is modulated by mutations of the tryptophan (Trp) residues at the bilayer-water interface. We explore this further using extensive molecular dynamics simulations of various gA dimer and monomer mutants at the Trp positions in phosphatidylcholine bilayers with different tail lengths. gA interactions with the surrounding bilayer are strongly modulated by mutating these Trp residues. There are three principal effects: eliminating residue hydrogen bonding ability (i.e., reducing the channel-monolayer coupling strength) reduces the extent of the bilayer deformation caused by the assembled dimeric channel; a residue’s size and geometry affects its orientation, leading to different hydrogen bonding partners; and increasing a residue’s hydrophobicity increases the depth of gA monomer insertion relative to the bilayer center, thereby increasing the lipid bending frustration

How the web was won … by some

HILJ readers may have encountered the phrase library 2.0 which has polarised librarians, with some sceptical whether library 2.0 offers anything new. Others are confident that the convergence of service goals and ideas with emerging Web 2.0 technologies will lead to a new generation of library services. Andrew Tattersall’s article, ‘How the Web was Won’, belongs in the latter camp. His thesis is that Web 2.0 and Library 2.0 have opened up a whole new world for exploration by information and library professionals. Although the Web has created problems for the modern day explorer, potentially there is a bright future for information professionals if they are to succeed in deploying the resources

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development

Biomolecular simulations: From dynamics and mechanisms to computational assays of biological activity

Biomolecular simulation is increasingly central to understanding and designing biological molecules and their interactions. Detailed, physics‐based simulation methods are demonstrating rapidly growing impact in areas as diverse as biocatalysis, drug delivery, biomaterials, biotechnology, and drug design. Simulations offer the potential of uniquely detailed, atomic‐level insight into mechanisms, dynamics, and processes, as well as increasingly accurate predictions of molecular properties. Simulations can now be used as computational assays of biological activity, for example, in predictions of drug resistance. Methodological and algorithmic developments, combined with advances in computational hardware, are transforming the scope and range of calculations. Different types of methods are required for different types of problem. Accurate methods and extensive simulations promise quantitative comparison with experiments across biochemistry. Atomistic simulations can now access experimentally relevant timescales for large systems, leading to a fertile interplay of experiment and theory and offering unprecedented opportunities for validating and developing models. Coarse‐grained methods allow studies on larger length‐ and timescales, and theoretical developments are bringing electronic structure calculations into new regimes. Multiscale methods are another key focus for development, combining different levels of theory to increase accuracy, aiming to connect chemical and molecular changes to macroscopic observables. In this review, we outline biomolecular simulation methods and highlight examples of its application to investigate questions in biology. This article is categorized under: Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Free Energy Method