La biologie des hématinoprotéides oxygénables

Summary The author reviews a series of biological aspects of the study of oxygenable hematinoproteids, particularly with respect to evolution and adaptation. After a statement of some fundamental concepts of comparative biochemistry and of possible evolutionary relations between oxidation catalysts and oxygen carriers, the natural distribution of hemoglobins is reviewed and their specific characters are enumerated.A review is made of the data relating to the shape of the oxygen-dissociation curves and to the affinity of hæmoglobin for oxygen. It appears, generally speaking, that hyperbolic or almost hyperbolic curves and high affinity for oxygen are characteristic of primitive or embryonic hæmoglobins.A study of the function of hæmoglobin in the respiratory cycle of several animal species shows the vital importance of the oxygen carrier as well as the adaptation of the shape and position of the dissociation curve to the character of the respiratory function in the animal considered.The function of hæmoglobin in invertebrates, as oxygen carrier as well as providing a store of oxygen, is emphasized by a review of experimental data.The function of oxygen in the transport of carbon dioxide is reviewed from the standpoint of comparative biochemistry, and the lack of our knowledge is deplored.The characteristics of chlorocruorin show it to be a chemical mutation of an Annelid hæmoglobin.Our lack of knowledge in the field of the comparative biochemistry of hæmoglobin and chlorocruorin metabolism is pointed out.

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Conférence principale, présentée à la Société suisse de biologie médicale lors de la 127^e Assemblée générale de la Société helvétique des sciences naturelles à Genève, le 31 août 1947.     

The birth of modern science: culture, mentalities and scientific innovation

In a recent paper, Luc Faucher and others have argued for the existence of deep cultural differences between ‘Chinese’ and ‘East Asian’ ways of understanding the world and those of ‘ancient Greeks’ and ‘Americans’. Rejecting Alison Gopnik’s speculation that the development of modern science was driven by the increasing availability of leisure and information in the late Renaissance, they claim instead—following Richard Nisbett—that the birth of mathematical science was aided by ‘Greek’, or ‘Western’, cultural norms that encouraged analytic, abstract and rational theorizing. They argue that ‘Chinese’ and ‘East Asian’ cultural norms favoured, by contrast, holistic, concrete and dialectical modes of thinking. After clarifying some of the things that can be meant by ‘culture’ and ‘mentality’, the present paper shows that Faucher and his colleagues make a number of appeals—to the authority of comparative studies and history of science, to the psychological studies of Nisbett and his colleagues, and to a hidden assumption of strong cultural continuity in the West. It is argued that every one of these appeals is misguided, and, further, that the psychological findings of Nisbett and others have little bearing on questions concerning the origins of modern science. Finally, it is suggested that the ‘Needham question’ about why the birth of modern science occurred in Europe rather than anywhere else is itself multiply confused to the extent that it may express no significant query.     

Kinetik der hepatischen Farbstoffaufnahme von Indocyaningrün. Einfluss von Bilirubin und Natriumglykocholat

Summary Kinetics of hepatic uptake of indocyanine green, a dye which is used for evaluation of liver function, were studied in the rat. The results indicate that the relationship between ICG-dose and initial hepatic dye uptake obeys Michaelis-Menten kinetics suggesting an interaction of the dye with a carrier or fixed site in the liver cell. Thus it was possible to calculate maximum ICG-uptake (v _max ) and the Michaelis constant (K _m ) of this transport system from several submaximal values.v _max was 7.65 (6-06-9.65)²² mg per 100 g liver/min and K _m 0.56 (0.31–0.81)²². Under the influence of substances which inhibit the elimination of dyes by the liver the parametersv _max and K _m showed changes which allowed characterization of the type of inhibition. While sodium glycocholate had no influence on maximum hepatic ICG-uptake and the Michaelis constant bilirubin caused a significant increase of K _m to 1.29 (0.68–1.90)²² without significantly changingv _max . These data suggest that bilirubin interferes with hepatic uptake of indocyanine green by competitive inhibition and that uptake of bile acids is dependent on a different mechanism.     

Sonnenflecken und ihre terrestrischen Wirkungen

Summary After a discussion of the 11-year solar-cycle as regarded from the standpoint of the eruption-hypothesis, which offers a possibility to predict the solar activity for several years and after a review of the magnetic properties of the sun and the sunspots, the paper deals with the new theories of the spots and the solar-cycle as suggested byAlfvén andWalén.The terrestrial effects of the phenomena associated with the solar cycle are classified into 4 groups: effects produced by a) a wave radiationW _k emitted continuously by the sun, b) a wave radiationW _e emitted from the chromospheric eruptions, c) a particle radiationP _k emitted by the so-called M-regions, and d) a particle radiationP _e ejected from the eruptions. The connection between the solar eruptions and the radiationsP _e ,W _e is a well established fact; on the other hand the radiationsW _k ,P _k could be connected by the author with the solar corona and the stationary solar prominences respectively.To account for the intensity of theW _k -radiation a temperature of the solar corona of one million degree is required in agreement with the observed temperature. The heating of the corona occurs in the electric field around an increasing sunspot. As in the corona the mean free path amounts to several kilometers, particles may be accelerated up to 1000 eV, so far the conditionh=0 is fulfilled. Generally speaking acceleration is possible only in such regions whereh andh are not perpendicular to each other.     

Cryo-bioorganic chemistry: freezing effect on stereoselection of l- and dl-leucine cooligomerization in aqueous solution

The chirality of l-/dl-leucine (50–50%) cooligomerization was investigated in liquid and frozen aqueous solutions. Cooligomerization was carried out by carbonyldiimidazole activation without initiator at an ambient (+22°C) and frozen (−18°C) temperature, respectively. The separated samples obtained after different time intervals of treatment were completely hydrolyzed (HCl) and the diastereomeric l- and d-leucine derivates of Marfey's reagent (1-fluoro-2,4-dinitrophenyl-5-l-alanine amide) were then traced and evaluated by RP-HPLC analysis. After 9 days of oligomerization, the l-Leu content was slightly enhanced in the liquid (57%) and somewhat more enhanced in the frozen (64%) samples. After 17 days, however, the l-Leu content had decreased in the liquid (53%) and frozen (56%) conditions. These l-enantiomer amplifications indicate that an l-antipode is preferentially incorporated into the α-helical turn of the oligomer in the earlier stage of cooligomerization, while, later, the d-antipode is also incorporated. The role of ice in the improved stereoselection is discussed. This is the first recorded example of the effect of freezing on stereoselection. Received 27 October 2000; revised 11 December 2000; accepted 4 January 2000     

In pre-sterol carrier protein 2 (SCP2) in solution the leader peptide 1 – 20 is flexibly disordered, and residues 21 – 143 adopt the same globular fold as in mature SCP2

The preform of the rabbit sterol carrier protein 2 (pre-rSCP2) was cloned, the uniformly ¹⁵N-labelled protein expressed in Escherichia coli and studied by three-dimensional ¹⁵N-resolved nuclear magnetic resonance spectroscopy. In spite of its low solubility in aqueous solution of only ∼0.3 mM, sequential ¹⁵N and ¹H backbone resonance assignments were obtained for 105 out of the 143 residues. From comparison of the sequential and medium-range nuclear Overhauser effects (NOEs) in the two proteins, all regular secondary structures previously determined in mature human SCP2 (hSCP2) [Szyperski et al. (1993) FEBS Lett. 335: 18–26] were also identified in pre-rSCP2. Near-identity of the backbone ¹⁵N and ¹H chemical shifts and 1 : 1 correspondence of 24 long-range NOEs to backbone amide groups in the two proteins show that the residues 21 – 143 adopt the same globular fold in pre-rSCP2 and mature hSCP2. The N-terminal 20-residue leader peptide of pre-rSCP2 is flexibly disordered in solution and does not observably affect the conformation of the polypeptide segment 21 – 143. Received 11 May 1998; accepted 15 May 1998     

Announcement of the Editor-in-chief

Announcement.  Once in a year (in July) we have decided to publish the names of the authors and the titles of the two most read (by internet) research papers and reviews published in CMLS the previous year. Thus we have the pleasure to provide you with the results of 2004.Research Articles  

“... in Christophorum Clavium de Contactu Linearum Apologia” Considerazioni attorno alla polemica fra Peletier e Clavio circa l'angolo di contatto (1579–1589)

Summary In this work 1 focus my attention upon the question of the angle of tangency in the XVI^th Century, especially in the polemic between J. Peletier and Chr. Clavius (1579–1589). The interest in the question favored deliberation about the theory of proportions, the principle of Eudoxus-Archimedes and the set of angles of tangency (this is a non-Archimedian set); there were problems about logical proofs and geometrical proofs.

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Memoria presentata da H. Freudenthal     

Heterochromatization in opossum,Didelphys virginiana

Conclusion Somatic heterochromatization of the opossum,D. virginiana, was studied from prophase and tritiated thymidine-labeled metaphase chromosome preparations. In both sexes of this mammal, a number of prophase autosomes and the sex chromosomes were observed displaying deeply stained condensed areas. These chromosomal areas were interpreted as evidence for heterochromatization. The extent of heterochromatization in the opossum was found much greater in certain autosomes than either theX orY chromosome alone. This assertion that some opossum autosomes possess more heterochromatin than the sex chromosomes was supported by data collected on the terminal labeling patterns of the chromosomes. Metaphase autoradiographs prepared from cultured leucocytes of the animals unequivocally suggested that certain opossum autosomes completed replication later than the sex chromosomes. If one assumes that there is heterochromatin in the autosomes, as the evidence suggests, then it merely becomes a question as to what block of heterochromatin replicates last — a phenomenon that is probably size dependent.

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Résumé L'héterochromatisation somatique de l'opossum (Didelphys virginiana) a été étudiée sur des préparations de chromosomes aux stades de la prophase et de la métaphase, la thymidine ayant été utilisée comme marqueur. Dans les 2 sexes de ce mammifère de nombreux autosomes et les chromosomes sexuels montrent, à la prophase, des plages denses fortement colorées. Ces plages chromosomiales ont été interprétées comme un signe évident d'héterochromatisation. L'héterochromatisation est beaucoup plus accentuée dans certains autosomes que dans les chromosomesX ouY. Les autoradiographies de stades métaphasiques dans des préparations effectuées de leucocytes en cultures suggèrent d'une façon non équivoque que certains autosomes de l'opossum achèvent leur réplication plus tardivement que les chromosomes sexuels. Si l'on assume que l'héterochromatine est présente dans les autosomes, comme le démontrent nos observations, il semble évident que l'héterochromatine autosomale a un rôle significatif dans le développement.

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Supported in part by Baylor University College of Medicine General Research Grant (No. P-13) and grants from the James Picker Foundation and the Texas Heart Association. The auther wishes to thank Dr.W. Hill for his help at the vivarium and MissMarion Gay and MissShirley Powell for technical assistance. The editorial assistance of MissMarilyn Morningstar is also appreciated.     

Regulating the large Sec7 ARF guanine nucleotide exchange factors: the when,where and how of activation

Eukaryotic cells require selective sorting and transport of cargo between intracellular compartments. This is accomplished at least in part by vesicles that bud from a donor compartment, sequestering a subset of resident protein “cargos” destined for transport to an acceptor compartment. A key step in vesicle formation and targeting is the recruitment of specific proteins that form a coat on the outside of the vesicle in a process requiring the activation of regulatory GTPases of the ARF family. Like all such GTPases, ARFs cycle between inactive, GDP-bound, and membrane-associated active, GTP-bound, conformations. And like most regulatory GTPases the activating step is slow and thought to be rate limiting in cells, requiring the use of ARF guanine nucleotide exchange factor (GEFs). ARF GEFs are characterized by the presence of a conserved, catalytic Sec7 domain, though they also contain motifs or additional domains that confer specificity to localization and regulation of activity. These domains have been used to define and classify five different sub-families of ARF GEFs. One of these, the BIG/GBF1 family, includes three proteins that are each key regulators of the secretory pathway. GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs and thus these GEFs are the upstream regulators that define the site and timing of vesicle production. Paradoxically, while we have detailed molecular knowledge of how GEFs activate ARFs, we know very little about how GEFs are recruited and/or activated at the right time and place to initiate transport. This review summarizes the current knowledge of GEF regulation and explores the still uncertain mechanisms that position GEFs at “budding ready” membrane sites to generate highly localized activated ARFs.     

Cartesian analysis and synthesis

This paper aims to provide an explication of the meaning of ‘analysis’ and ‘synthesis’ in Descartes’ writings. In the first part I claim that Descartes’ method is entirely captured by the term ‘analysis’, and that it is a method of theory elaboration that fuses the modern methods of discovery and confirmation in one enterprise. I discuss Descartes’ methodological writings, assess their continuity and coherence, and I address the major shortcoming of previous interpretations of Cartesian methodology. I also discuss the Cartesian method in the context of other conceptions of scientific method of that era and argue that Descartes’ method significantly transforms these conceptions. In the second part I argue that mathematical and natural-philosophical writings exhibit this kind of analysis. To that effect I examine in Descartes’ writings on the method as used in mathematics, and Descartes’ account of the discovery of the nature of the rainbow in the Meteors. Finally, I briefly assess Descartes’ claim regarding the universality of his method.     

Complement factor H in host defense and immune evasion

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.     

Age and evolution of bacteria

Summary Age and evolution of bacteria can be estimated, including facts and hypotheses belonging to morphology, biochemistry, paleontology, ecology and pathogenicity. The corresponding dates are summarized in the following.About 3.5×10⁹ years: Origin of heterotrophic eobiontes.—About 3.0×10⁹ years: The increasing lack of prebiogenic substances is due to the evolution of the respiratory pathway, that is due to the evolution of the photoautotrophy and now released O₂ is due to the evolution of strictly aerobic cells. There is, simultaneously, a transition of spheres to long forms, development of an amoebalike motility, the evolution of spirochetes and the substitution of cholesterol for cardiolipin in the more evolved cells (i.e. strictly aerobic cells etc.).—About 2.0×1.0×10⁹ years: Evolution of the eucyte by symbiosis of a great, primitive, anaerobic, cholesterol-containing cell with a little, strictly aerobic, cardiolipin-containing cell, with a spirochete and in some extent also with photoautotrophic cell.—About 1.0×10⁹ years (maximum: 1.8–1.5×10⁹ years, minimum: 7×10⁸ years): Evolution of metazoa and begin of cell differentiation.—About 2.0–1.0×10⁹ years: Evolution of the bacterial murein sacculus and then development of flagella mediated motility.—About 6×10⁸ years (maximum:1.0×10⁹ years, minimum: 4.5×10⁸ years): Evolution of the gram-negative cell wall.—About 4.0×10⁸ years: Evolution of the gram-positive cell wall.—About 5.0×10⁸ years: Gram-negative, strictly anaerobic bacteria become the first enteric bacteria in coelenterates. About 4.0×10⁸ years: gram-negative, microaerophilic bacteria become Enterobacteriaceae in vertebrates in addition to the strictly anaerobic organisms.—About 3.0–2.0×10⁸ years: Consolidation of the Salmonella in reptiles.—About 2.0–1.5×10⁸ years: Consolidation of Escherichia and other coliform species in mammals.—About 10⁶ years: Evolution of typically human pathogenic organisms, transmitted in homogeneous-homonomous infection ways, i.e. N. gonorrhoeae, S. typhi, T. pallidum, etc.Dedicated to Prof. H. Habs, Bonn, to his 75th anniversary on 11 September 1977.Acknowledgment. I thank Prof. F. Müller, Hamburg, and Prof. P. Sitte, Freiburg i. Br., for stimulating discussions.     

Unique evolution of Bivalvia arginine kinases

The clams Pseudocardium, Solen, Corbicula and Ensis possess a unique form of arginine kinase (AK) with a molecular mass of 80 kDa and an unusual two-domain structure, a result of gene duplication and subsequent fusion. These AKs also lack two functionally important amino acid residues, Asp⁶² and Arg¹⁹³, which are strictly conserved in other 40-kDa AKs and are assumed to be key residues for stabilizing the substrate-bound structure. However, these AKs show higher enzyme activity. The cDNA-derived amino acid sequences of 40-kDa AKs from the blood clam Scapharca broughtonii and the oyster Crassostrea gigas were determined. While Asp⁶² and Arg¹⁹³ are conserved in Scapharca AK, these two key residues are replaced by Asn and Lys, respectively, in Crassostrea AK. The native enzyme from Crassostrea and both of the recombinant enzymes show an enzyme activity similar to that of two-domain clam AKs and at least twofold higher than that of other molluskan AKs. Although the replacement of Asp⁶² or Arg¹⁹³ by Gly in normal AK causes a considerable decrease in V_max (6–15% of wild-type enzyme) and a two- to threefold increase in K_m for arginine, the same replacement in Scapharca AK had no pronounced effect on enzyme activity. Together with the observation that bivalve AKs are phylogenetically distinct from other molluskan AKs, these results suggest that bivalve AKs have undergone a unique molecular evolution; the characteristic stabilizing function of residues 62 and 193 has been lost and, consequently, the enzyme shows higher activity than normal.Received 14 October 2003; accepted 1 November 2003     

Ligand recognition by the I domain-containing integrins

Seven of the integrin α subunits described to date, α ₁ , α ₂ , α _L , α _X , α _d , α _M and α _E , contain a highly conserved I (or A) domain of approximately 200 amino acid residues inserted near the amino-terminus of the subunit. As the result of a variety of independent experimental approaches, a large body of data has recently accumulated that indicates that the I domains are independent, autonomously folding domains capable of directly binding ligands that play a necessary and important role in ligand binding by the intact integrins. Recent crystallographic studies have elucidated the structures of recombinant α _M and α _L I domains and also delineated a novel divalent cation-binding motif within the I domains (metal ion-dependent adhesion site, MIDAS) that appears to mediate the divalent cation binding of the I domains and the I domain-containing integrins to their ligands.     

Newton and the classical theory of probability

Summary Probabilistic ideas and methods from Newton's writings are discussed in § 1: Newton's ideas pertaining to the definition of probability, his probabilistic method in chronology, his probabilistic ideas and method in the theory of errors and his probabilistic reasonings on the system of the world. Newton's predecessors and his influence upon subsequent scholars are dealt with in §2: beginning with his predecessors the discussion continues with his contemporaries Arbuthnot and De Moiver, then Bentley. The section ends with Laplace, whose determinism is seen as a development of the Newtonian determinism.An addendum is devoted to Lambert's reasoning on randomness and to the influence of Darwin on statistics. A synopsis is attached at the end of the article.Abbreviations PT abridged Philosophical Transactions of the Royal Society 1665–1800 abridged. London, 1809 - Todhunter I. Todhunter, History of the mathematical theory of probability, Cambridge, 1865 To the memory of my mother, Sophia Sheynin (1900–1970)