The Newtonian Myth

I examine Popper’s claims about Newton’s use of induction in Principia with the actual contents of Principia and draw two conclusions. Firstly, in common with most other philosophers of his generation, it appears that Popper had very little acquaintance with the contents and methodological complexities of Principia beyond what was in the famous General Scholium. Secondly Popper’s ideas about induction were less sophisticated than those of Newton, who recognised that it did not provide logical proofs of the results obtained using it, because of the possibilities of later, contrary evidence. I also trace the historical background to commonplace misconceptions about Newton’s method.     

Response to one point in Gingras’s review of Gravity’s shadow

Yves Gingras says of my book Gravity’s shadow that it is too long, the style is poor, and in its 870 pages there is nothing new that is not to be regretted. Gingras’s purity of vision would be a cause for congratulation were it not for the appalling implications of one of his claims. For the sake of the future of social science—indeed for the sake of the future of civilisation—it is impossible to leave unchallenged the idea that respondents, who don’t like to see their use of data questioned, are to be commended when they withhold those data from public scrutiny.     

Antimalarial drugs: recent advances in molecular determinants of resistance and their clinical significance

Molecular determinants of antimalarial drug resistance are useful and informative tools that complement phenotypic assays for drug resistance. They also guide the design of strategies to circumvent such resistance once it has reached levels of clinical significance. Established resistance to arylaminoalcohols such as mefloquine and lumefantrine in SE Asia is mediated primarily by gene amplification of the P. falciparum drug transporter, pfmdr1. Single nucleotide polymorphisms in pfmdr1, whether assessed in field isolates or transfection experiments, are associated with changes in IC₅₀ values (to arylaminoalcohols and chloroquine), but not of such magnitude as to influence clinical treatment outcomes. Recently described emerging in vitro resistance to artemisinins in certain areas correlates with mutations in the SERCA-like sequence PfATP6 and supports PfATP6 as a key target for artemisinins. Received 13 February 2006; revised after revision 7 March 2006; accepted 29 March 2006     

Genomic sources of regulatory variation in cis and in trans

Regulatory variation results from genetic changes with both cis and trans acting effects on gene expression. Here I describe the types of genetic variants that alter cis and trans regulation and discuss differences in the potential for cis and trans changes among different classes of genes. I argue that the molecular function of the protein encoded by each gene and how the gene is wired into the genomic regulatory network may influence its propensity for cis and trans regulatory changes.Received 15 February 2005; received after revision 12 April 2005; accepted 26 April 2005     

Studies on the fungal phytotoxin victorin: Structures of three novel amino acids from the acid hydrolyzate

Summary The host-selective phytotoxin victorin, produced by the fungusCochliobolus victoriae, was found to be at least partially peptidic in nature, and did not contain victoxinine. The exact mass of the M-H ion was measured by FABMS as 795.1877. Derivatives of three major acid hydrolysis products were isolated. The structures of the corresponding amino acids were assigned as 2S,3R-3-hydroxyleucine, 5,5-dichloroleucine, and 3-hydroxylysine. A into victorin by the fungus in vivo.     

Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product Calcipressin 1 (or RCAN1) in disease

The DSCR1 (Adapt78) gene¹ is transiently induced by stresses to temporarily protect cells against further potentially lethal challenges. However, chronic expression of the DSCR1 (Adapt78) gene has now been implicated in several pathological conditions including Alzheimer’s disease, Down syndrome and cardiac hypertrophy. Calcipressin 1 has been shown to function through direct binding and inhibition of the serine threonine protein phosphatase Calcineurin. Pharmacological inhibition of calcineurin, by the immunosuppressive drugs cyclosporin A and FK506, affects a wide variety of diseases. It is, therefore, likely that this endogenous calcineurin inhibitor, calcipressin 1, may also play a role in a variety of human diseases. ¹Please note that the mammalian DSCR1 gene is also called Adapt78 or RCAN1, and its protein products have been named Calcipressin1, MCIP1 and RCAN1. A proposal to adopt a single gene name of RCAN1 and a protein name RCAN1 (for Regulator of Calcineurin) has been endorsed by the HUGO Gene Nomenclature Committee, but final approval must await agreement from a majority of researchers in the field. Received 2 March 2005; received after revision 27 May 2005; accepted 19 July 2005     

Between autobiography and reality: Popper's inductive years

On the basis of his unpublished thesis ‘Gewohnheit und Gesetzerlebnis in der Erziehung’ (1926–7) a historical reconstruction is given of the genesis of Popper's ideas on induction and demarcation which differs radically from his own account in Unended quest. It is shown not only that he wholeheartedly endorses inductive epistemology and psychology but also that his ‘demarcation’ criterion is inductivistic. Moreover it is shown that his later demarcation thesis arises not from his worries about, on the one hand, Marxism and psychoanalysis and, on the other hand, Einstein's physics, but rather from his urgent preoccupation with providing pedagogy with a psychological foundation, which has its sources in Karl Bühler's cognitive psychology as well as, surprisingly, Adler's Characterology. Aside from Adler some lesser known psychologists, such as Karl Groos, will also be seen to have played a formative role on Popper's early thinking.     

Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis

Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining ‘increased angiogenesis’ as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.Received 24 November 2004; received after revision 21 January 2005; accepted 2 March 2005     

Effects of diapause and host species on some morphometric characters inTrichogramma (Hym.: Trichogrammatidae)

Adult morphology ofTrichogramma is modified by environmental conditions during the preimaginal development. For instance, the low temperatures inducing diapause cause a decrease of the ratio length of longest seta on male flagellum/width of flagellum inT. evanescens. The species of the host also influences numerous body ratios. So, in females, the development of tibiae with regard to wings is more important withScotia ipsilon than withGalleria mellonella. These results confirm the necessity of performing comparative morphological studies on individuals reared in the same conditions.     

RNA editing in plant organelles: machinery, physiological function and evolution

In plants, RNA editing is a process for converting a specific nucleotide of RNA from C to U and less frequently from U to C in mitochondria and plastids. To specify the site of editing, the cis-element adjacent to the editing site functions as a binding site for the trans-acting factor. Genetic approaches using Arabidopsis thaliana have clarified that a member of the protein family with pentatricopeptide repeat (PPR) motifs is essential for RNA editing to generate a translational initiation codon of the chloroplast ndhD gene. The PPR motif is a highly degenerate unit of 35 amino acids and appears as tandem repeats in proteins that are involved in RNA maturation steps in mitochondria and plastids. The Arabidopsis genome encodes approximately 450 members of the PPR family, some of which possibly function as trans-acting factors binding the cis-elements of the RNA editing sites to facilitate access of an unidentified RNA editing enzyme. Based on this breakthrough in the research on plant RNA editing, I would like to discuss the possible steps of co-evolution of RNA editing events and PPR proteins. Received 30 September 2005; received after revision 5 November 2005; accepted 28 November 2005     

Thiyl radicals in biosystems: effects on lipid structures and metabolisms

Thiyl radicals are intermediates of enzyme- and radical-driven biochemical processes, and their potential as reactive species in the biological environment has been somehow underestimated. From organic chemistry, however, it is known that thiyl radicals isomerize the double bonds of unsaturated fatty acids to a mixture with very dominating trans isomers. Recently, this reaction has been particularly studied for biosystems, focusing on the effect of thiyl radicals on the natural all-cis double bonds of unsaturated phospholipids, which undergo a conversion to the unnatural trans form. In this paper we report briefly the role of thiyl radicals in biosystems, describe the main features of the radical-induced cis-trans isomerization process under both in vitro and in vivo conditions, and reflect on some consequences for membrane structures, lipid metabolism and enzymatic reactions.Received 29 October 2004; received after revision 3 December 2004; accepted 4 January 2005     

Hidden depths: Halley, hell and other people

During the long eighteenth century, boundaries between theology and natural philosophy, between imaginary and factual travel narratives, between fiction and social commentary, were far more fluid than they are today. To explore these relationships, this paper links Mary Shelley’s Frankenstein—a book often hailed as the first science fiction novel—to two earlier works which are now less well known: Edmond Halley’s article about terrestrial magnetism, in which he suggested that God had created inhabited illuminated cavities inside the earth; and a satirical fantasy voyage written by the Danish author Ludvig Holberg, but published anonymously as Niels Klim’s journey to the underground and immediately translated into many languages. Attention is focussed on how the ambiguous presentation of these and other texts blurs any straightforward classification of genres. The aim of examining these writers together is not to search for direct mappings from one project to another, but instead to introduce Holberg’s unfamiliar yet important book and also to cast new light on Frankenstein, one of England’s most famous works of literature.     

Heterologous expression of G-protein-coupled receptors: comparison of expression systems from the standpoint of large-scale production and purification

G-protein-coupled receptors (GPCRs) are of prime importance for cell signal transduction mechanisms and are the target of many current and potential drugs. However, structural data on these membrane proteins is still scarce because of their low natural abundance and the low efficiency of most of the expression systems currently available. This review presents the most important expression systems currently employed for heterologous expression of GPCRs; Escherichia coli, yeast, insect cells and mammalian cells. After briefly recalling the specificity, advantages and limitations of each system, particular emphasis is put on the quantitative comparison of these expression systems in terms of overall expression yield, and on the influence of various factors (primary sequence, origin, cell type, N- and C-terminal tags) on the results.     

Reconsidering the Fresnel–Maxwell theory shift: how the realist can have her cake and EAT it too

This paper takes another look at a case study which has featured prominently in a variety of arguments for rival realist positions. After critically reviewing the previous commentaries of the theory shift that took place in the transition from Fresnel’s ether to Maxwell’s electromagnetic theory of optics, it will defend a slightly different reading of this historical case study. Central to this task is the notion of explanatory approximate truth, a concept which must be carefully analysed to begin with. With this notion properly understood, it will be finally argued, the popular Fresnel–Maxwell case study points towards a novel formulation of scientific realism.     

Interferons and indoleamine 2,3-dioxygenase: Role in antimicrobial and antitumor effects

Summary Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)-induced protein that initiates the metabolism of tryptophan along the kynurenine pathway. Although IDO can be induced by IFN- in many cell types, only mononuclear phagocytes have been shown to be induced to decyclize tryptophan by all three IFN classes. Since tryptophan is an essential amino acid necessary for a variety of metabolic processes, depletion of available tryptophan may be an important mechanism for control of rapidly-dividing microbial pathogens and tumors. The purpose of this review is to present evidence that documents the effects of IFN-induced IDO on prokaryotic and eukaryotic pathogens, as well as on a variety of tumor cell lines.     

Implications of toxins in the ecology and evolution of plant pathogenic microorganisms: Bacteria

This review attempts to rationalise what is known about bacterial phytotoxins and associate it with the ecology and possible evolution of the producing organisms. Study of non-toxin producing variants gives insight into the ecological role of the toxin. Elucidation of chemical structures of phytotoxins has shown that many exist as families of analogous compounds. Studies on the variation of chemical structures and how they are distributed across species and genera can lead to development of hypotheses on evolutionary relationships. Knowledge on biosynthetic pathways to tosins allows recognition of specific enzymatic steps involved in developing the characteristic features of the structures. Phytotoxins often have a potent biochemical activity, and in some cases the producing organism has associated mechanisms to prevent action of the toxin upon itself; in such cases toxigenesis is clearly not a chance event. The various aspects of bacterial toxigenesis indicate that bacterial phytotoxins are special secondary metabolic products that play beneficial roles to the producing organisms in their various ecological niches.     

<Emphasis Type="Italic">Drosophila melanogaster</Emphasis> innate immunity: an emerging role for peptidoglycan recognition proteins in bacteria detection

Over the past years, parallel studies conducted in mammals and flies have emphasized the existence of common mechanisms regulating the vertebrate and invertebrate innate immune systems. This culminated in the discovery of the central role of the Toll pathway in Drosophila immunity and in the implication of Toll-like receptors (TLRs)/interleukin-1(IL-1) in the mammalian innate immune response. In spite of clear similarities, such as shared intracellular pathway components, important divergences are expected between the two groups, whose last common ancestor lived more than half a billion years ago. The most obvious discrepancies lie in the mode of activation of the signalling receptors by microorganisms. In mammals, TLRs are part of protein complexes which directly recognize microbe-associated patterns, whereas Drosophila Toll functions like a classical cytokine receptor rather than a pattern recognition receptor. Recent studies demonstrate that members of the evolutionarily conserved peptidoglycan recognition protein family play an essential role in microbial sensing during immune response of Drosophila.Received 26 June 2003; received after revision 29 July 2003; accepted 25 August 2003     

Sex-peptides: seminal peptides of the <Emphasis Type="Italic">Drosophila</Emphasis> male

Mating affects the reproductive behaviour of insect females: the egg-laying rate increases and courting males are rejected. These post-mating responses are induced mainly by seminal fluid. In Drosophila melanogaster, males transfer two peptides (sex-peptides, = Sps) that reduce receptivity and elicit increased egg laying in their mating partners. Similarities in the open reading frames of the genes suggest that they have arisen by gene duplication. In females, Sps bind to specific sites in the central and peripheral nervous system, and to the genital tract. The binding proteins of the nervous system and genital tract are membrane proteins, but they differ molecularly. The former protein is proposed to be a receptor located at the top of a signalling cascade leading to the two post-mating responses, whereas the latter is a carrier protein moving Sps from the genital tract into the haemolymph. Sps bind to sperm. Together with sperm they are responsible for the persistence of the two post-mating responses. But Sps are the molecular basis of the sperm effect; sperm is merely the carrier.Received 10 February 2003; received after revision 25 April 2003; accepted 1 May 2003This article is dedicated to the 85th birthday of the discover of the sex-peptide, Prof. Dr. Pei Shen Chen, Zoological Institute, University of Zürich, Switzerland. P. S. Chen has served on the Editorial Board of Experientia (now CMLS) from 1974 to 1988.