Turning points in the evolution of peroxidase–catalase superfamily: molecular phylogeny of hybrid heme peroxidases

Heme peroxidases and catalases are key enzymes of hydrogen peroxide metabolism and signaling. Here, the reconstruction of the molecular evolution of the peroxidase–catalase superfamily (annotated in pfam as PF00141) based on experimentally verified as well as numerous newly available genomic sequences is presented. The robust phylogenetic tree of this large enzyme superfamily was obtained from 490 full-length protein sequences. Besides already well-known families of heme b peroxidases arranged in three main structural classes, completely new (hybrid type) peroxidase families are described being located at the border of these classes as well as forming (so far missing) links between them. Hybrid-type A peroxidases represent a minor eukaryotic subfamily from Excavates, Stramenopiles and Rhizaria sharing enzymatic and structural features of ascorbate and cytochrome c peroxidases. Hybrid-type B peroxidases are shown to be spread exclusively among various fungi and evolved in parallel with peroxidases in land plants. In some ascomycetous hybrid-type B peroxidases, the peroxidase domain is fused to a carbohydrate binding (WSC) domain. Both here described hybrid-type peroxidase families represent important turning points in the complex evolution of the whole peroxidase–catalase superfamily. We present and discuss their phylogeny, sequence signatures and putative biological function.     

Role of toxins in evolution and ecology of plant pathogenic fungi

Many fungal pathogens of plants adapt readily to changes in agriculture. Among the most revealing is a fungal group whose species produce host-selective toxins as key determinants of disease. Several lines of evidence support the hypothesis that these fungi evolved from opportunistic, low-grade pathogens by gaining new genetic information leading to toxin production; in some species, toxin production is known to be under single gene control. as a result of this evolution, these fungi became virulent and host-specialized. The best-known model cases belong to the generaCochliobolus andAlternaria; there are suggestions of evolutionary lines among these genera, with species that range from saprophytes to opportunists to specialized pathogens. Host specialization can lead to genetic isolation, a first step in speciation. Ability to produce host-selective toxin has allowed these fungi to exploit the monocultures and genetic uniformity of modern agriculture. Destructive epidemics have been the result.     

Transformation: a tool for studying fungal pathogens of plants

Plant diseases caused by plant pathogenic fungi continuously threaten the sustainability of global crop production. An effective way to study the disease-causing mechanisms of these organisms is to disrupt their genes, in both a targeted and random manner, so as to isolate mutants exhibiting altered virulence. Although a number of techniques have been employed for such an analysis, those based on transformation are by far the most commonly used. In filamentous fungi, the introduction of DNA by transformation typically results in either the heterologous (illegitimate) integration or the homologous integration of the transforming DNA into the target genome. Homologous integration permits a targeted gene disruption by replacing the wild-type allele on the genome with a mutant allele on transforming DNA. This process has been widely used to determine the role of newly isolated fungal genes in pathogenicity. The heterologous integration of transforming DNA causes a random process of gene disruption (insertional mutagenesis) and has led to the isolation of many fungal mutants defective in pathogenicity. A big advantage of insertional mutagenesis over the more traditional chemical or radiation mutagenesis procedures is that the mutated gene is tagged by transforming DNA and can subsequently be cloned using the transforming DNA. The application of various transformation-based techniques for fungal gene manipulation and how they have increased our understanding and appreciation of some of the most serious plant pathogenic fungi are discussed. Received 9 May 2001; received after revision 2 July 2001; accepted 3 July 2001     

Toxin bioportides: exploring toxin biological activity and multifunctionality

Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides—a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrome c (CYCS), calcitonin receptor (camptide), and endothelial nitric oxide synthase (nosangiotide). However, toxins are usually disregarded as potential bioportides. In this review, we discuss the inclusion of some toxins and molecules derived thereof as a new class of bioportides based on structure activity relationship, minimization, and biological activity studies. The comparative analysis of the amino acid residue composition of toxin-derived bioportides and their short molecular variants is an innovative analytical strategy which allows us to understand natural toxin multifunctionality in vivo and plan novel pharmacological and biotechnological products. Furthermore, we discuss how many bioportide toxins have a rigid structure with amphiphilic properties important for both cell penetration and bioactivity.     

Biochemical approaches to the study of plant-fungal interactions in arbuscular mycorrhiza

This communication compares some biochemical methods for quantifying colonization by arbuscular mycorrhizal (AM) fungi. The degree of mycorrhizal colonization can conveniently be measured by determining fungal specific sterols. AM-colonized plants show a specific synthesis of 24-methylene cholesterol and an enhanced level of campesterol (=24-methyl cholesterol). A gene probe for nitrate reductase, the key enzyme for nitrogen assimilation, has been developed, which allows the monitoring of the distribution of this enzyme in fungi. Among the phytohormones tested, only abscisic acid (ABA) is found at a considerably higher level in AM-colonized plants than in controls. The concentration of ABA is about twenty times higher in spores and hyphae of the AM fungusGlomus than in maize roots. Other phytohormones (auxins, cytokinins) do not show such alterations after mycorrhizal colonization. The roots of gramineous plants become yellow as a result of mycorrhizal colonization. The yellow pigment(s) formed is (are) deposited in larger quantities in the vacuole(s) of the root parenchyma and endodermis cells during the development of the gramineous plants. A substance isolated from such roots has now been identified as a C-14 carotenoid with two carboxylic groups, and named mycorradicin.     

Differential influences of various arsenic compounds on glutathione redox status and antioxidative enzymes in porcine endothelial cells

The cellular response and detoxification mechanisms in porcine endothelial cells (PAECs) to arsenic trioxide (As2O3), sodium arsenite (NaAsO2) and sodium arsenate (Na2HAsO4) were investigated. NaAsO2 at 20 microM for 72 h increased Cu/Zn superoxide dismutase activity resulting in elevated intracellular hydrogen peroxide levels, but As2O3 and Na2HAsO4 did not. Trivalent arsenic compounds increased intracellular oxidized glutathione (GSSG) and total glutathione (GSH) and cellular glutathione peroxidase (cGPX) and glutathione S-transferase (GST) activity, but not glutathione reductase activity. The increased cGPX activity resulted in an elevated cellular GSSG content. Na2HAsO4 increased the cellular GSSG level at 72 h compared to controls. These results imply that the increased GSH content responding to the oxidative stress by trivalent arsenic compounds may be mainly related to the regulation of GSH turnover. The increased GST activity implies that the elevated intracellular GSH level responding to the oxidative stress may be used to conjugate arsenic in PAECs and facilitate arsenic efflux.     

Two problems in Aristarchus’s treatise on the sizes and distances of the sun and moon

The book of Aristarchus of Samos, On the distances and sizes of the sun and moon, is one of the few pre-Ptolemaic astronomical works that have come down to us in complete or nearly complete form. The simplicity and cleverness of the basic ideas behind the calculations are often obscured in the reading of the treatise by the complexity of the calculations and reasoning. Part of the complexity could be explained by the lack of trigonometry and part by the fact that Aristarchus appears unwilling to make some simplifications that could be simply taken for granted. But an important part of the complexities is due to some unnecessary inconsistencies, as recently discovered by Berggren and Sidoli (Arch Hist Exact Sci 61:213–254, 2007). In the first part of this paper, I will try to show that some of these inconsistencies are just apparent. But the complexity of the calculations and reasoning is not the only reason that could disturb a reader of the treatise. The great inaccuracy—even for the measurement methods and instruments available at those times—of one of the three input values of the treatise is really astonishing. In the sixth and last hypothesis, Aristarchus states that the moon’s apparent size is equal to 2 $^{\circ }$ , while the correct value is one-fourth of that. Some attempts have been made in order to explain such a big value, but all of them have problems. In the second part of this paper, I will propose a new speculative but plausible explanation of the origin of this value.     

The chemistry and biology of inhibitors and pro-drugs targeted to glutathione S-transferases

The cytosolic glutathione S-transferases are a family of structurally homologous enzymes with multiple functions, including xenobiotic detoxification, clearance of oxidative stress products, and modulation of cell proliferation and apoptosis signaling pathways. This wideranging functional repertoire leads to several possible therapeutic uses for isoform-specific GST inhibitors. These inhibitors may be used, in principle, to modulate tumor cell drug resistance, as sensitizers to therapeutically directed oxidative stress, to enhance cell proliferation and to augment anti-malarial drugs. With increasing knowledge of GST structural and function, rational design strategies and mechanism-based inhibitors have been exploited successfully. However, design of isoform specificity remains a significant challenge in GST inhibitor development. Strategies for further inhibitor design and their possible limitations, along with potential therapeutic uses, are summarized.Received 24 November 2004; received after revision 12 January 2005; accepted 11 February 2005     

Was Newtonian cosmology really inconsistent?

This paper follows up a debate as to the consistency of Newtonian cosmology. Whereas Malament [(1995). Is Newtonian cosmology really inconsistent? Philosophy of Science 62, 489–510] has shown that Newtonian cosmology is not inconsistent, to date there has been no analysis of Norton's claim [(1995). The force of Newtonian cosmology: Acceleration is relative. Philosophy of Science 62, 511–522.] that Newtonian cosmology was inconsistent prior to certain advances in the 1930s, and in particular prior to Seeliger's seminal paper of Seeliger [(1895). Über das Newton'sche Gravitationsgesetz. Astronomische Nachrichten 137 (3273), 129–136.] In this paper I agree that there are assumptions, Newtonian and cosmological in character, and relevant to the real history of science, which are inconsistent. But there are some important corrections to make to Norton's account. Here I display for the first time the inconsistencies—four in total—in all their detail. Although this extra detail shows there to be several different inconsistencies, it also goes some way towards explaining why they went unnoticed for 200 years.     

Proposition II (Book I) of Newton’s <Emphasis Type="Italic">Principia</Emphasis>

After preparing the way with comments on evanescent quantities and then Newton’s interpretation of his second law, this study of Proposition II (Book I)— Proposition II Every body that moves in some curved line described in a plane and, by a radius drawn to a point, either unmoving or moving uniformly forward with a rectilinear motion, describes areas around that point proportional to the times, is urged by a centripetal force tending toward that same point. —asks and answers the following questions: When does a version of Proposition II first appear in Newton’s work? What revisions bring that initial version to the final form in the 1726 Principia? What, exactly, does this proposition assert? In particular, what does Newton mean by the motion of a body “urged by a centripetal force”? Does it assert a true mathematical claim? If not, what revision makes it true? Does the demonstration of Proposition II persuade? Is it as convincing, for example, as the most convincing arguments of the Principia? If not, what revisions would make the demonstration more persuasive? What is the importance of Proposition II, to the physics of Book III and the mathematics of Book I?     

Structures and strategies in ancient Greek and Roman technical writing: An Introduction

Most of our knowledge of Greek and Roman scientific practice and its place in ancient culture is derived from our study of ancient texts. In the last few decades, this written evidence—ancient technical or specialist literature—has begun to be studied using tools of literary analysis to help answer questions about, for instance, how these works were composed, their authors’ intentions and the expectations of their readers.This introduction to Structures and strategies in ancient Greek and Roman technical writing provides an overview of recent scholarship in the area, and the difficulty in pinning down what ‘technical/specialist literature’ might mean in an ancient context, since Greek and Roman authors communicated scientific knowledge using a wide variety of styles and forms of text (e.g. poetry, dialogues, letters).An outline of the three sections is provided: Form as a mirror of method, in which Sabine Föllinger and Alexander Mueller explore ways in which the structures of texts by Aristotle and Plutarch may reflect methodological concerns; Authors and their implied readers, with contributions by Oliver Stoll, David Creese, Boris Dunsch and Paula Olmos, which examines what ancient texts can tell us about the place of technical knowledge in antiquity; Science and the uses of poetry, with articles by Jochen Althoff, Michael Coxhead and Laurence Totelin, and a new English translation of the Aetna poem by Harry Hine, which explores the (to us) unexpected roles of poetry in ancient scientific culture.     

Celestial chaos: The new logics of theory-testing in orbital dynamics

I explore how the nature, scope, and limits of the knowledge obtained in orbital dynamics has changed in recent years. Innovations in the design of spacecraft trajectories, as well as in astronomy, have led to new logics of theory-testing—that is, new research methodologies—in orbital dynamics. These methodologies—which combine resonance overlap theories, numerical experiments, and the implementation of space missions—were developed in response to the discovery of chaotic dynamical systems in our solar system. In the past few decades, they have replaced the methodology that dominated orbital research in the centuries following Newton's Principia. As a result, the kind of knowledge achieved by orbital research has changed: we can know how orbiting bodies in chaotic systems behave, but only over sufficiently short time scales; and we can reliably measure those temporal limitations, using Lyapunov time.     

Mononuclear phagocyte-mediated antifungal immunity: the role of chemotactic receptors and ligands

Over the past two decades, fungal infections have emerged as significant causes of morbidity and mortality in patients with hematological malignancies, hematopoietic stem cell or solid organ transplantation and acquired immunodeficiency syndrome. Besides neutrophils and CD4⁺ T lymphocytes, which have long been known to play an indispensable role in promoting protective antifungal immunity, mononuclear phagocytes are now being increasingly recognized as critical mediators of host defense against fungi. Thus, a recent surge of research studies has focused on understanding the mechanisms by which resident and recruited monocytes, macrophages and dendritic cells accumulate and become activated at the sites of fungal infection. Herein, we critically review how a variety of G-protein coupled chemoattractant receptors and their ligands mediate mononuclear phagocyte recruitment and effector function during infection by the most common human fungal pathogens.     

Tumor suppressor C-RASSF proteins

Human genome has ten genes that are collectedly called Ras association domain family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N-RASSF and C-RASSF encode Ras association domain-containing proteins and are frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF and N-RASSF are quite different. Six C-RASSF proteins (RASSF1–6) are characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo domain, while four N-RASSF proteins (RASSF7–10) lack it. C-RASSF proteins interact with mammalian Ste20-like kinases—the core kinases of the tumor suppressor Hippo pathway—and cross-talk with this pathway. Some of them share the same interacting molecules such as MDM2 and exert the tumor suppressor role in similar manners. Nevertheless, each C-RASSF protein has distinct characters. In this review, we summarize our current knowledge of how C-RASSF proteins play tumor suppressor roles and discuss the similarities and differences among C-RASSF proteins.     

Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.     

Evaluating predictive performance of value‐at‐risk models in emerging markets: a reality check

We investigate the predictive performance of various classes of value‐at‐risk (VaR) models in several dimensions—unfiltered versus filtered VaR models, parametric versus nonparametric distributions, conventional versus extreme value distributions, and quantile regression versus inverting the conditional distribution function. By using the reality check test of White (2000), we compare the predictive power of alternative VaR models in terms of the empirical coverage probability and the predictive quantile loss for the stock markets of five Asian economies that suffered from the 1997–1998 financial crisis. The results based on these two criteria are largely compatible and indicate some empirical regularities of risk forecasts. The Riskmetrics model behaves reasonably well in tranquil periods, while some extreme value theory (EVT)‐based models do better in the crisis period. Filtering often appears to be useful for some models, particularly for the EVT models, though it could be harmful for some other models. The CaViaR quantile regression models of Engle and Manganelli (2004) have shown some success in predicting the VaR risk measure for various periods, generally more stable than those that invert a distribution function. Overall, the forecasting performance of the VaR models considered varies over the three periods before, during and after the crisis. Copyright © 2006 John Wiley & Sons, Ltd.     

Self-induced decoherence: a new approach

According to Zurek, decoherence is a process resulting from the interaction between a quantum system and its environment; this process singles out a preferred set of states, usually called “pointer basis”, that determines which observables will receive definite values. This means that decoherence leads to a sort of selection which precludes all except a small subset of the states in the Hilbert space of the system from behaving in a classical manner: environment-induced-superselection—einselection—is a consequence of the process of decoherence. The aim of this paper is to present a new approach to decoherence, different from the mainstream approach of Zurek and his collaborators. We will argue that this approach offers conceptual advantages over the traditional one when problems of foundations are considered; in particular, from the new perspective, decoherence in closed quantum systems becomes possible and the preferred basis acquires a well founded definition.     

Potentiation of antifungal activity of sesquiterpene dialdehydes againstCandida albicans and two other fungi

The antifungal activity of two drimane sesquiterpene dialdehydes, polygodial (1) and warburganal (2), alone and in combination with several other substances, was examined against three fungi,Candida albicans, Saccharomyces cerevisiae andPityrosporum ovale employing a broth dilution method. Anethole significantly synergized the activity of the two sesquiterpenoids againstC. albicans andS. cerevisiae however, it had only an, additive effect againstP. ovale. By contrast, two antioxidants, ascorbic acid (vitamin C) and BHA (butylated hydroxyanisole), noticeably enhanced the activity of the sesquiterpenoids againstP. ovale, but had no, effect againstC. albicans andS. cerevisiae.     

Pre-Euclidean geometry and Aeginetan coin design: some further remarks

Some ancient Greek coins from the island state of Aegina depict peculiar geometric designs. Hitherto they have been interpreted as anticipations of some Euclidean propositions. But this paper proposes geometrical constructions which establish connections to pre-Euclidean treatments of incommensurability. The earlier Aeginetan coin design from about 500 bc onwards appears as an attempt not only to deal with incommensurability but also to conceal it. It might be related to Plato’s dialogue Timaeus. The newer design from 404 bc onwards reveals incommensurability, namely in the context of ‘doubling the square’. It thereby covers the same topic but a different geometry as passages in Plato’s dialogue Meno (385 bc). This coin design incorporates important elements of ancient Greek geometrical analysis of the fifth century bc like the gnomon, Hippocrates’ squaring of the lunule (ca. 430 bc), and a geometrical version of monetary equivalence. Through this venue, the design’s conceptual lineage might be traced as far back as Heraclitus’ cosmology of about 500 bc.