Refractory Period Modulates the Spatiotemporal Evolution of Cortical Spreading Depression: A Computational Study

Cortical spreading depression (CSD) is a pathophysiological phenomenon, which underlies some neurological disorders, such as migraine and stroke, but its mechanisms are still not completely understood. One of the striking facts is that the spatiotemporal evolution of CSD wave is varying. Observations in experiments reveal that a CSD wave may propagate through the entire cortex, or just bypass some areas of the cortex. In this paper, we have applied a 2D reaction-diffusion equation with recovery term to study the spatiotemporal evolution of CSD. By modulating the recovery rate from CSD in the modeled cortex, CSD waves with different spatiotemporal evolutions, either bypassing some areas or propagating slowly in these areas, were present. Moreover, spiral CSD waves could also be induced in case of the transiently altered recovery rate, i.e. block release from the absolute refractory period. These results suggest that the refractory period contributes to the different propagation patterns of CSD, which may help to interpret the mechanisms of CSD propagation.     

Decision Making during the Psychological Refractory Period

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Highlights? The PRP interferes with decision making and routing to the motor response ? Sensory evidence accumulation can occur for multiple decisions at the same time ? A large fraction of the PRP occurs after the commitment to a choice ? Evidence accumulation and sensory-motor mapping are distinct processes     

Structural Heterogeneity Modulates Effective Refractory Period: A Mechanism of Focal Arrhythmia Initiation

Reductions in electrotonic loading around regions of structural and electrophysiological heterogeneity may facilitate capture of focal triggered activity, initiating reentrant arrhythmias. How electrotonic loading, refractoriness and capture of focal ectopics depend upon the intricate nature of physiological structural anatomy, as well as pathological tissue remodelling, however, is not well understood. In this study, we performed computational bidomain simulations with anatomically-detailed models representing the rabbit left ventricle. We used these models to quantify the relationship between local structural anatomy and spatial heterogeneity in action potential (AP) characteristics, electrotonic currents and effective refractory periods (ERPs) under pacing and restitution protocols. Regions surrounding vessel cavities, in addition to tissue surfaces, had significantly lower peak downstream electrotonic currents than well coupled myocardium ( vs A/cm²), with faster maximum AP upstroke velocities ( vs mV/ms), although noticeably very similar APDs ( vs ms) and AP restitution properties. Despite similarities in APDs, ERPs in regions of low electrotonic load in the vicinity of surfaces, intramural vessel cavities and endocardial structures were up to ms shorter compared to neighbouring well-coupled tissue, leading to regions of sharp ERP gradients. Consequently, focal extra-stimuli timed within this window of ERP heterogeneity between neighbouring regions readily induced uni-directional block, inducing reentry. Most effective induction sites were within channels of low ERPs between large vessels and epicardium. Significant differences in ERP driven by reductions in electrotonic loading due to fine-scale physiological structural heterogeneity provides an important mechanism of capture of focal activity and reentry induction. Application to pathological ventricles, particularly myocardial infarction, will have important implications in anti-arrhythmia therapy.     

Evolutionary History of the Vertebrate Period Genes

Circadian clock genes are remarkably conserved between eucoelomates. Although Drosophila has one copy of each major component, vertebrates have two or (in the case of the Period genes) three paralogs (Per1-3). We investigated the possibility that the vertebrate Per genes arose through two genome duplications during the emergence of vertebrates. Phylogenetic trees have placed zebrafish and mammalian Per1 and 2 together in a separate branch from Per3. The positions of four coding region splice sites were conserved between Drosophila per and the human paralogs, the fifth one being unique to Drosophila. The human PER genes shared the positions of all coding region splice sites, except the first two in PER1 and PER2 (which PER3 lacks). The phases of all splice sites were conserved between all four genes with two exceptions. Analysis of all genes within 10 Mb of the human PER1-3 genes, which are located 7.8—8.8 Mb from the telomeres on chromosomes 17, 2, and 1, identified several orthologous neighbors shared by at least two PER genes. Two gene families, HES (hairy and Enhancer of Split) and KIF1 (kinesin-like protein 1), were represented in all three of these paralogons. Although no functional fourth human PER paralog exists, five representatives from the same gene families were found close to the telomer of chromosome 3. We conclude that the ancestral chordate Per gene underwent two duplication events, giving rise to Per1—3 and a lost fourth paralog. [Reviewing Editor: Dr. John Onkeshott]     

The Population of Europe: A History

The Population of Europe:. History. Massimo Livi-Bacci. Cynthia De Nardi Ipsen and Carl Ipsen. trans. Maiden, MA: Blackwell Publishers, 2000. 220 pp.     

Vagility: The Neglected Component in Historical Biogeography

The conceptual gap between ecological and historical biogeography is wide, although both disciplines are concerned with explaining how distributions have been shaped. A central aim of modern historical biogeography is to use a phylogenetic framework to reconstruct the geographic history of a group in terms of dispersals and vicariant events, and a number of analytical methods have been developed to do so. To date the most popular analytical methods in historical biogeography have been parsimony-based. Such methods can be classified into two groups based on the assumptions used. The first group assumes that vicariance between two areas creates common patterns of disjunct distributions across several taxa whereas dispersals and extinctions generate clade specific patterns. The second group of methods assumes that passive vicariance and within-area speciation have a higher probability of occurrence than active dispersal events and extinction. Typically, none of these methods takes into account the ecology of the taxa in question. I discuss why these methods can be potentially misleading if the ecology of the taxon is ignored. In particular, the vagility or dispersal ability of taxa plays a pivotal role in shaping the distributions and modes of speciation. I argue that the vagility of taxa should be explicitly incorporated in biogeographic analyses. Likelihood-based methods with models in which more realistic probabilities of dispersal and modes of speciation can be specified are arguably the way ahead. Although objective quantification will pose a challenge, the complete ignorance of this vital aspect, as has been done in many historical biogeographic analyses, can be dangerous. I use worked examples to show a simple way of utilizing such information, but better methods need to be developed to more effectively use ecological knowledge in historical biogeography.     

The Open Access Malaria Box: A Drug Discovery Catalyst for Neglected Diseases

Historically, one of the key problems in neglected disease drug discovery has been identifying new and interesting chemotypes. Phenotypic screening of the malaria parasite, Plasmodium falciparum has yielded almost 30,000 submicromolar hits in recent years. To make this collection more accessible, a collection of 400 chemotypes has been assembled, termed the Malaria Box. Half of these compounds were selected based on their drug-like properties and the others as molecular probes. These can now be requested as a pharmacological test set by malaria biologists, but importantly by groups working on related parasites, as part of a program to make both data and compounds readily available. In this paper, the analysis and selection methodology and characteristics of the compounds are described.     

Neglected Food Bubbles: The Espresso Coffee Foam

Coffee beverage known as espresso, must be topped by a velvety thick, reddish-brown foam called crema, to be considered properly prepared and to be appreciated by connoisseurs. In spite of the relevant role played by crema as a quality marker, espresso coffee foam has not yet been the subject of detailed investigations. Only recently, some aspects of the Physics and Chemistry behind the espresso coffee foam have attracted the attention of scientists. In addition to sharing several characteristics with other food foams like beer foam, for instance, the espresso coffee foam may contain solid particles (minute coffee cell-wall fragments), it is subjected to a remarkable temperature gradient and its continuous phase is an oil in water emulsion rendering it a very complex system to be studied. Moreover, in the typical regular espresso coffee cup volume (serving) of 25–30 mL, crema represents at least 10% of the total volume, and this is a limitation in obtaining experimental data by conventional instruments. The present work is aimed at reviewing the literature on espresso coffee foam. The traditional espresso brewing method will be briefly described with emphasis on the steps particularly relevant to foam formation and stabilization. In addition to present up-dated experimental data on surface properties at solid/beverage and air/beverage interface, recent advances on the espresso foam formation mechanism, as well as on foam stability, will be critically examined. The key role played by carbon dioxide generated by roasting and the effects of low and high-molecular-weight coffee compounds in promoting/inhibiting the espresso coffee foam will be discussed and emphasized.     

Parameters of Surface Electromyograms in Full-Term and Preterm Infants in the Neonatal Period: The Possible Contribution of Gravity

The purpose of this study was to compare the postnatal evolution of spectral–amplitude and nonlinear parameters of surface electromyogram (sEMG) in the full-term and preterm infants with regard to their biological and calendar age. In full-term infants, all sEMG parameters (dimension, entropy, mean frequency, and amplitude) are increased by 10–30% two weeks after birth. On the contrary, sEMG parameters in preterm infants were constant for six weeks after birth. This finding indicates that both postnatal and antenatal periods are important for the development of the motor system of infants. Therefore, the adaptation of the motor system to extrauterine conditions consists of two stages. The authors suppose that gravity can be a driving factor of these sEMG metamorphoses.     

A Neglected Science: Applying Behavior to Aquatic Conservation

Behavioral theories, insights, and techniques are too frequently ignored by conservation biologists. Yet an animal's survival and reproductive success clearly depend on its behavior. Using examples from marine, freshwater, and terrestrial realms, I assert that behavioral information is invaluable in five conservation areas: (1) managing wild species (e.g., designing marine reserves; reducing animal–human conflicts; understanding and managing species' responses to human-induced environmental stress such as fishing, introduced species, and chemical, visual, and acoustic pollution); (2) actively reversing the decline of imperiled wild species (e.g., reducing bycatch by improving selectivity of fishing gear; re-establishing breeding populations and boosting reproduction); (3) assessing biodiversity (e.g., modeling population viability; censusing and monitoring populations and species); (4) captive breeding and reintroduction programs (e.g., minimizing loss of valuable phenotypes; teaching or maintaining valuable survival skills); and (5) changing human behavior in resource exploitation (e.g., using principles from social psychology). Both realized and potential applications to fishes are stressed. Finally, behavioral diversity, a valuable but neglected element of biodiversity, needs to be explicitly conserved to maintain diverse populations. Arguments are presented that the conservation of species diversity and genetic diversity alone does not necessarily protect important behavioral diversity. The maintenance of both individual and population variability may be essential for the preservation of a species.     

The Yellow Fever Vaccine: A History

After failed attempts at producing bacteria-based vaccines, the discovery of a viral agent causing yellow fever and its isolation in monkeys opened new avenues of research. Subsequent advances were the attenuation of the virus in mice and later in tissue culture; the creation of the seed lot system to avoid spontaneous mutations; the ability to produce the vaccine on a large scale in eggs; and the removal of dangerous contaminants. An important person in the story is Max Theiler, who was Professor of Epidemiology and Public Health at Yale from 1964-67, and whose work on virus attenuation created the modern vaccine and earned him the Nobel Prize.     

The AIDS Crisis: A Documentary History

The AIDS Crisis:. Documentary History. Douglas A. Feldman and Julia Wang Miller. Westport, CT: Greenwood Press, 1998.266 pp.     

The Fate of Place: A Philosophical History

The Fate of Place:. Philosophical History. Edward S. Casey. Berkeley: University of California Press, 1997.488 pp.     

The Early History of Syphilis: A Reappraisal

The historical record and examination of disinterred human bones indicate that venereal syphilis is very old in America but did not appear in the Old World until about 1500. Traditionally it has been believed that the disease was brought to the Old World by Columbus in the 1490s. The most popular alternative hypothesis at present is that venereal syphilis is really only one facet of a disease—treponematosis, appearing as yaws in the tropics, nonvenereal syphilis in the Middle East, pinta in Mexico, etc.—that is present wherever man has settled and has been his unshakable companion for thousands of years in all the continents. Unfortunately, the latter, or Unitarian, theory has no more claim to validity than the Columbian. The diseases mentioned are similar but we cannot be sure that they are all really the same. And the testimony of the sixteenth-century Spaniards, who knew Columbus and his men, that syphilis was an American import cannot be easily brushed aside. The hypothesis of this paper is that treponematosis, originally a single disease, evolved into several related but distinct maladies as man spread through the world and that venereal syphilis is the variant that developed in the remote cul-de-sac of America, from which it probably was indeed introduced to Europe with the return of Columbus.