The “therapeutic range” of the one-stage prothrombin time in the control of anticoagulant therapy: The effect of different thromboplastin preparations

Commercially available thromboplastin reagents and two human brain preparations have been compared using the one-stage prothrombin time and plasma samples from patients receiving long-term oral anticoagulant therapy. Considerable variation is noted between various thromboplastins using the same plasma sample. The commercially available thromboplastins give shorter prothrombin times than do human brain preparations. With the latter, the “therapeutic range” is represented by a prothrombin time of about 1.8 to 3.0 times the normal control value, whereas with commercial preparations the “therapeutic range” is about 1.25 to 1.75 times normal. The implications of these observations are discussed; the desirability of standardization of the one-stage prothrombin time is emphasized.     

A historical perspective of the biophysics of the thrombin–heparin system: an example of nonspecific binding and the consequent parking problem in action

Difficulties are encountered in the thermodynamic characterization of interactions between a protein ligand and a linear acceptor, such as a polynucleotide or a polysaccharide, because of the involvement of more than one unit of the polymer chain in each attachment of a protein molecule. Complications arise from the fact that random attachment of ligand to the polymer chain, each unit of which is a potential binding site, initially leads to suboptimal location of protein molecules along the polymer chain—a situation that has to be rectified before the attainment of thermodynamic equilibrium can be realized. Kinetic as well as thermodynamic consequences of such nonspecific binding, termed the parking problem, therefore need to be considered in any quantitative characterization of the interaction between a large ligand and a linear polymer acceptor chain. Results for the thrombin–heparin interaction have been used to illustrate a thermodynamic characterization of nonspecific binding that takes into account these consequences of the parking problem.     

The characterization of the whey proteins of guinea-pig milk: The isolation and properties of α-lactalbumin

1. The whey proteins of guinea-pig milk were examined by electrophoresis on paper, cellulose acetate, starch gel and polyacrylamide gel. 2. Two major proteins were detected, one of which was identified as blood serum albumin. 3. The major whey protein was isolated by CM-cellulose chromatography and on columns of Sephadex G-100. 4. The amino acid composition of the protein, taken in conjunction with its other properties, indicated that the major whey protein in guinea-pig milk is homologous with cow α-lactalbumin and that β-lactoglobulin is absent from guinea-pig milk. 5. Guinea-pig α-lactalbumin, which was obtained crystalline, had mol.wt. 15800, N-terminal lysine and C-terminal glutamine.     

The influence of storage on the “chemical age” of red wines

Storage conditions and duration have a considerable influence on wine quality. Optimum temperature and humidity conditions may improve wine quality through ageing, while incorrect or excessively long storage leads to negative results. In order to evaluate the global effects of storage on red wine composition, 20 Sangiovese wines were stored in two different conditions (cellar or house) for a period of 2 years and analysed every 6 months. Untargeted LC–MS analysis showed various putative markers for the type and length of conservation (i.e. pigments, flavanols, pantothenic acid etc.), while targeted LC–MS confirmed and expanded these results within specific metabolic groups. The results of multivariate analysis showed that wines stored in the cellar changed little even after 2 years of storage, while wines stored in typical domestic conditions (house) developed approximately four times faster, reaching a composition similar to wines stored in the cellar for 2 years after just 6 months. The formation of several monosulfonated flavanols during domestic ageing provided the first evidence in wine of a reaction between wine tannins—both catechins and proanthocyanidins—and the exogenous antioxidant bisulfite. Moreover, ageing in domestic conditions appeared to induce an accelerated decrease in wine pigments, while specifically promoting the formation of pinotin A-like pigments and the hydrolysis of flavonol glycosides.     

The relation of protein binding to function: what is the significance of munc18 and synaptotagmin binding to syntaxin 1, and where are the corresponding binding sites?

The Q-SNARE syntaxin 1 is a central component of the synaptic membrane fusion machinery. Syntaxin probably interacts with multiple proteins during synaptic vesicle exocytosis. In vitro, the tightest binding partners for syntaxin 1 are other SNAREs (synaptobrevin/VAMP and SNAP-25) and munc18-1 (also known as rbsec1/nsec1). Recent studies on Drosophila syntaxin led to the surprising finding that a syntaxin mutant which does not bind the munc18-homolog Rop nevertheless functionally substitutes for wild-type syntaxin in membrane fusion (Wu et al., Neuron 23, 593-605, 1999). This observation suggested that syntaxin 1 binding to munc18-1 is not essential for fusion, a puzzling conclusion in view of the tight binding of munc18 and syntaxin homologs in all organisms. To address this issue, we have now reinvestigated the interaction of syntaxin with munc18 and Rop. We find that the syntaxin sequence that was mutated in the Drosophila studies is not essential for munc18/Rop binding, and that the mutant is in fact able to bind to munc18/Rop. Thus the fact that the mutant syntaxin rescues release cannot be used as an argument that munc18 binding is not essential. In addition to munc18 and SNAREs, several other proteins have been suggested to interact with various domains of syntaxin 1, notably the calcium-sensor synaptotagmin and the vesicle protein CSP. Our results confirm that the SNARE motif in syntaxin binds to synaptotagmin, but this interaction does not require the very C-terminus of the motif. Interestingly, binding of synaptotagmin appears to be decreased in the closed conformation of syntaxin. In contrast, no interaction of CSP with syntaxin was detected even under low-stringency conditions. Our data suggest 1., that assays measuring protein/protein interactions that involve syntaxin may be more difficult to evaluate than is often assumed because of the sticky nature of the proteins involved, and 2., that it is currently not possible to draw conclusions about the importance of the various interactions with the available data from Drosophila or vertebrates.     

The physico-chemical “anatomy” of the tautomerization through the DPT of the biologically important pairs of hypoxanthine with DNA bases: QM and QTAIM perspectives

The biologically important tautomerization of the Hyp·Cyt, Hyp*·Thy and Hyp·Hyp base pairs to the Hyp*·Cyt*, Hyp·Thy* and Hyp*·Hyp* base pairs, respectively, by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (ε?=?4) corresponding to hydrophobic interfaces of protein–nucleic acid interactions by combining theoretical investigations at the B3LYP/6-311++G(d,p) level of QM theory with QTAIM topological analysis. Based on the sweeps of the energetic, electron-topological, geometric and polar parameters, which describe the course of the tautomerization along the intrinsic reaction coordinate (IRC), it was proved that the tautomerization through the DPT is concerted and asynchronous process for the Hyp·Cyt and Hyp*·Thy base pairs, while concerted and synchronous for the Hyp·Hyp homodimer. The continuum with ε?=?4 does not affect qualitatively the course of the tautomerization reaction for all studied complexes. The nine key points along the IRC of the Hyp·Cyt?Hyp*·Cyt* and Hyp*·Thy?Hyp·Thy* tautomerizations and the six key points of the Hyp·Hyp?Hyp*·Hyp* tautomerization have been identified and fully characterized. These key points could be considered as electron-topological “fingerprints” of concerted asynchronous (for Hyp·Cyt and Hyp*·Thy) or synchronous (for Hyp·Hyp) tautomerization process via the DPT. It was found, that in the Hyp*·Cyt*, Hyp·Thy*, Hyp·Hyp and Hyp*·Hyp* base pairs all H-bonds are significantly cooperative and mutually reinforce each other, while the C2H…O2 H-bond in the Hyp·Cyt base pair and the O6H…O4 H-bond in the Hyp*·Thy base pair behave anti-cooperatively, i.e., they become weakened, while two others become strengthened.     

The effects of structural variations of thiophene-containing Ru(II) complexes on the acid–base and DNA binding properties

A phenylthiophenyl-bearing Ru(II) complex of [Ru(bpy)₂(Hbptip)](PF₆)₂ {bpy?=?2,2′-bipyridine, Hbptip?=?2-(4-phenylthiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline} was synthesized and characterized by elemental analysis, ¹H NMR spectroscopy, and electrospray ionization mass spectrometry. The ground- and excited-state acid–base properties of the complex were studied by UV–visible absorption and photoluminescence spectrophotometric pH titrations and the negative logarithm values of the ground-state acid ionization constants were derived to be pK _a1?=?1.31?±?0.09 and pK _a2?=?5.71?±?0.11 with the pK _a2 associated deprotonation/protonation process occurring over 3 pK _a units more acidic than thiophenyl-free parent complex of [Ru(bpy)₂(Hpip)]²⁺ {Hpip?=?2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline}. The calf thymus DNA-binding properties of [Ru(bpy)₂(Hbptip)]²⁺ in Tris–HCl buffer (pH 7.1 and 50?mM NaCl) were investigated by DNA viscosities and density functional theoretical calculations as well as UV–visible and emission spectroscopy techniques of UV–visible and luminescence titrations, steady-state emission quenching by [Fe(CN)₆]^4?, DNA competitive binding with ethidium bromide, DNA melting experiments, and reverse salt effects. The complex was evidenced to bind to the DNA intercalatively with binding affinity being greater than those for previously reported analogs of [Ru(bpy)₂(Hip)]²⁺, [Ru(bpy)₂(Htip)]²⁺, and [Ru(bpy)₂(Haptip)]²⁺ {Hip?=?1H-imidazo[4,5-f][1,10]phenanthroline, Htip?=?2-thiophenimidazo[4,5-f][1,10]phenanthroline, Haptip?=?2-(5-phenylthiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline}.     

The properties of “active” Cl transport across the cornea of the toad Bufo marinus

• 1.1. Active Cl transport occurs from the endothelial to epithelial side of the cornea of Bufo marinus. Na transport is much less and is in the opposite direction.
• 2.2. The rate of Cl transport is not saturable and is linearly related to the Cl concentration on the endothelial side.
• 3.3. Active efflux (endo to epi) of Cl is reduced (50%) by CN and abolished by IAA. Ouabain and Na-free solutions on the endothelial side also reduce Cl efflux.
• 4.4. O₂ consumption or lactate production are also decreased by ouabain or Na-free solutions. However, metabolism was not inhibited by Cl-free solutions or a specific Cl blocking drug bumetanide.
• 5.5. Cl transport exhibits some rather unusual characters and a model is proposed to account for them which involves an exchange of Cl for metabolically produced organic anions.

     

The “tale” of poly(A) binding protein: The MLLE domain and PAM2-containing proteins

The cytoplasmic poly(A) binding protein 1 (PABPC1) is an essential eukaryotic translational initiation factor first described over 40 years ago. Most studies of PABPC1 have focused on its N-terminal RRM domains, which bind the mRNA 3′ poly(A) tail and 5′ translation complex eIF4F via eIF4G; however, the protein also contains a C-terminal MLLE domain that binds a peptide motif, termed PAM2, found in many proteins involved in translation regulation and mRNA metabolism. Studies over the past decade have revealed additional functions of PAM2-containing proteins (PACs) in neurodegenerative diseases, circadian rhythms, innate defense, and ubiquitin-mediated protein degradation. Here, we summarize functional and structural studies of the MLLE/PAM2 interaction and discuss the diverse roles of PACs.     

The enantiomers of the 1′,6′-isomer of neplanocin A: Synthesis and antiviral properties

Both enantiomers of 1′,6′-isoneplanocin have been prepared from a common substituted cyclopentane epoxide in 7 steps. Both compounds were subjected to DNA and RNA viral assessments with moderate to high activity found for both towards human cytomegalovirus, measles, Ebola, norovirus, and dengue. The D-like congener also showed vaccinia and HBV effectiveness. In many of the other antiviral assays both compounds showed cytotoxicity making, in some cases, an EC₅₀ determination not possible. The S-adenosylhomocysteine hydrolase inhibitory effects showed the D-like target to be equal that of neplanocin itself and better than 3-deazaneplanocin whereas the L-like analogue was 13 to 30 times less inhibitory than 3-deazaneplanocin and neplanocin, respectively.     

The “polarizing inducer” in hydra: A reexamination of its properties and its origin

Summary In order to prove the gradient hypothesis an attempt was made to isolate and accumulate the polarizing inducer present in homogenates of hydra and assumed to be a neurosecretory product. By means of gel chromatography two fractions were obtained which brought about the development of supernumary apical structures (tentacles and hypostomes) thus exhibiting the symptoms attributed to this polarizing agent: a low molecular fraction with only modest effectiveness and a main fraction with strong animalizing ability. Increasing the concentration affected only the quantity but not the qualitative properties of the structures produced, a result inconsistent with the postulate of the gradient hypothesis. By analysing the chemical and biological nature of the main agent and by applying pure isolated toxins compelling evidence is given that the inducer in question is nothing but a component of the nematocyst toxins. This component, being heat-stable and trypsin-sensitive, elicites its animalizing effect in unspecific means by disturbing the normal pattern of morphallactic events. A side effect with interest in respect of graded tissue properties could be recorded: by the influence of the relevant toxin, growing together of regenerating animals occurs whereby predominantly apical primordia fuse with apical primordia, thus forming stable parabioses. This observation may indicate the significance of surface bound, contact establishing components in polar differentiation.

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Zusammenfassung Zur Prüfung der entwicklungsphysiologischen Gradiententheorie wird der Versuch unternommen, den polarisierenden Induktor zu isolieren und anzureichern, der in Homogenaten von Hydra zugegen ist und als neurosekretorisches Produkt angesehen wird. Die Gelchromatographie wäßriger Extrakte liefert 2 Fraktionen, welche die Entwicklung überzähliger apikaler Strukturen (Tentakel und Mundkegel) hervorrufen: eine niedermolekulare Fraktion mit nur mäßiger Wirksamkeit und eine Hauptfraktion im mittelmolekularen Bereich mit starker animalisierender Kapazität. Entgegen dem Postulat der Gradiententheorie besteht keine Korrelation zwischen der applizierten Konzentration und der Qualität ausgelöster Formbildungen. Nur die Anzahl überzähliger Strukturen ist dosisabhängig. Die Analyse der biologischen und chemischen Eigenschaften der Hauptfraktion bringt den Hinweis, daß das polarisierende Agens eine Hitze-stabile, Trypsin-sensitive Komponenteder Nesselgifte ist, die ihre animalisierende Wirkung in unspezifischer Weise zeitigt. Die Applikation isolierter, reiner Nesselgifte erhärtet diese Vermutung zum klaren Beweis. Ein Nebeneffekt des relevanten Gifts legt graduierte Gewebseigenschaften offen: Unter seinem Einfluß verwachsen die Testpolypen, sowie sie in Kontakt zueinander kommen. Hierbei verbinden sich vorzugsweise apikale Primordien mit apikalen Primordien, um stabile Parabiosen zu bilden. Diese Beobachtung mag die Bedeutung Kontakt-vermittelnder Oberflächenstrukturen für das polare Differenzierungsgeschehen anzeigen.

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Supported by Deutsche Forschungsgemeinschaft.     

The Origin and Dispersal of the “Lower” Hamamelidae

The “lower” Hamamelidae sensu Endress (1989a) comprises seven families: Trochodendraceae, Tetracentraceae, Cercidiphyllaceae, Myrothamnaceae, Eupteleaceae, Platanaceae and Hamamelidaceae. In the present paper, the systematic position, modern distribution pattern and fossil history of each family are analyzed, and the origin and dispersal of them are discussed according to the principle of the unity between the phylogeny and distribution of plants. The paper consists of three parts. The conclusions are as follows: 1. The center of distribution According to Takhtajan's (1986) regionalization of the world flora, there are 13 distribution types in the “lower” Hamamelidae (Table 1 ). Eastern Asiatic Region, with five families, 19 genera and 73 species, ranks the first based on the numbers of species, genera and families. Four families: Trochodendraceae, Tetracentraceae, Cercidiphyllaceae and Eupteleaceae which were considered as more primitive in the “lower” Hamamelidae and three genera: Disanthus, Exbucklandia and Rhodoleia, primitive in the Hamamelidaceae, are all found in Eastern Asiatic Region. In addition, the groups at different evolutionary stages in the “lower” Hamamelidae survive in this region. Indochinese Region, with two families, 15 genera and 32 species, ranks the second. It was shown that southern Eastern Asiatic region and northern Indochinese Region are the distribution center of the “lower”Hamamelidae based on further analysis (see Table 2). 2. The place and time of the origin The fossil records of the “lower” Hamamelidae are abundant in angiosperms. Nordenskioldia, supposed as the extinct ancestral group of Trochodendraceae and Tetracentraceae, was widely distributed during the latest Cretaceous and the early Tertiary in the Northern Hemisphere; Trochodendroides appeared during the Cretaceous in North America, former USSR and Japan; the ancestral group of Cercidiphyllaceae, the Joffrea-Nyssidum complex, also occurred during the Cretaceous in the middle and higher latitude area of the Norhern Hemisphere. In addition, the earliest fossil records of the Eupteleaceae, Platanaceae and Hamamelidaceae appeared in North America, Europe and Asia of the Northern Hemisphere respectively. Therefore, the Laurasian origin of the “lower” Hamamelidae is supported by fossil evidence. On the other hand, the fossil data are still insufficient to determine the place of the origin, especially because the fossil records are rather poor in Asia. For this reason, the analyses of birthplace should combine with the information from the distribution of the primitive groups or outgroup of the “lower” Hamamelidae. Based on the statistics of distribution types, there are four primitive families in the “lower” Hamamelidae and three primitive genera in the Hamamelidaceae in southern Eastern Asiatic Region and northern Indochinese Region. Platanus kerrii Gagnep. of the Platanaceae, distributed in northern Vietnam, is considered as one of the most primitive species which has survived in modern times in this family because of its pistillate inflorescence comprising 10-12 heads. The Magnoliaceae was selected as an outgroup in our other paper “A phylogenetic analysis of families in the Hamamelidae” (Lu et al. 1991 ). All its 13 genera and most species occur from East to Southeast Asia, but in North America only three genera are found. Takhtajan (1969) considered that it was plants of the Magnoliaceae that were dispersed from East Asia to North America. Because the primitive groups of the “lower” Hamamelidae and its outgroup almost occur in the same area, their ancestor also appeared most probably in this area according to the principle of common origin. It was inferred that the area from southern Eastern Asiatic Region to northern Indochinese Region is the birthplace of the “lower"” Hamamelidae. The differentiation of the “lower” Hamamelidae took place rather early in angiosperms. The origin of them may be traced at least back to the Barremian of the early Cretaceous according to pollen fossil records. From more unequivocal fossil evidence, Platanoid plants appeared during the late Albian of the early Cretaceous, and the Trochodendraceae, Tetracentraceae, Cercidiphyllaceae and Hamamelidaceae diverged from their ancestral groups respectively no later than the late Cretaceous (Fig. 6). 3. The causes for the formation of the modern distribution pattern The “lower” Hamamelidae is a. rather old group. It is one of the most abundant and widespread components of fossil floras in the Northern Hemisphere during the late Cretaceous-middle Tertiary, the interval, when the global temperature was warm, although the extant Trochodendraceae, Tetracentraceae, Cercidiphyllaceae and Eupteleaceae which are now confined to East Asia are monotypical or oligotypical families. This distribution pattern indicates that most plants became extinct in Europe, northern Asia and North America because of the climatic changes during the late Tertiary, and especially the Quaternary glaciation, but East Asia, usually called “plant refuge”during the glacial period, became the survival place of many plants. From the viewpoint of evolution, these four families might be “living fossil plants” preserved from the Tertiary. The distribution of Hamamelidaceae is disjunct, but the causes leading to this pattern are not the same in different genera. The disjunction among Europe, North America, Australia and southern Africa is due to the tectonic movements of the earth; , and that between southeastern Europe-northern West Asia and southeastern Asia is developed as a result of the Quaternary glaciation. Fothergilla found from Carolina to Alabama in the United States and Hamamelis disjunct between East Asia and North America were widely distributed during the Tertiary in the Northern Hemisphere (Hu & Chaney 1940). The formation of their distribution patterns is a synthetic process owing to the tectonic movements and the Quaternary glaciation. Parrotia and Parrotiopsis, endemic to Iran and the West Himalayas respectively, are very similar in morphology. They might have a common ancestor, and the latter is more primitive than the former. It seems that several groups in the Hamamelidaceae were dispersed from east to west in Eurasia. Of the five genera in the Southern Hemisphere, Dicoryphe and Trichocladus are Madagascarian and southern African, and Ostrearia, Neostrearia and Noahdendron occur in northeastern Australia. They are usually considered as rather isolated groups, but Hufford and Endress (1989) found that they are closely related. The African genera might be dispersed from Asia via India, Sri Lanka and Lemuria continent; the Australian Hamamelidaceae also from Asia, but via the islands distributed in the Pacific Ocean. The Myrothamnaceae, comprising 2 species distributed in Madagascar and southern Africa, is closely related to the Hamamelidaceae. Based on morphological analyses, an evolutionary series exists among Myrothamnus, Dicoryphe and Trichocladus in which the distribution patterns are the same, and Myrothamnus is more specialized than the two genera of the Hamamelidaceae. 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The “evolutionary argument” and the metaphilosophy of commonsense

Recently in these pages it has been argued that a relatively straightforward version of an old argument based on evolutionary biology and psychology can be employed to support the view that innate ideas are a naturalistic source of metaphysical knowledge. While sympathetic to the view that the “evolutionary argument” is pregnant with philosophical implications, I show in this paper how it needs to be developed and deployed in order to avoid serious philosophical difficulties and unnecessary complications. I sketch a revised version of the evolutionary argument, place it in a new context, and show that this version in this context is not vulnerable to the standard criticisms levelled against arguments of this general type. The philosophical import of this version of the argument lies not in any metaphysical conclusions it sanctions directly, but in the support it lends to the metaphilosophy of commonsense.     

“The tools of the discipline: Biochemists and molecular biologists”: A comment

Conclusion and Issues for Further Investigation This last result leads, rather naturally, to some concluding observations and a series of questions for further investigation. These case studies show that in all of the sites examined, the institutionalization of molecular biology as a discipline was primarily driven by the need to separate groups of practitioners with divergent but overlapping interests within the local context. Thus molecular biology was contingently separated from agricultural or medical biochemistry, virology, work on the physiology of nucleic acids, and so forth for contingent local institutional reasons. This makes it even more pressing to try to understand how molecular biology came to be delimited on a larger scale. How did it come to be a discipline with specific intellectual content (or did it?), including some problems, tools, and practices and excluding others? How did it gain authority as the forefront biological science by the mid-1960s? We need to understand the ways in which the tensions between different practices, projects, aims, understandings of the goals of molecular biology, and so on were resolved, on what scale and in what venues, so that something approximating the political character of a discipline, rather than a federation, was achieved. If these case studies provide a sound starting point, it will nevertheless prove difficult to answer the interconnected questions implicit here satisfactorily.One means of getting at such questions that should prove of considerable interest is to examine carefully the work of those who were widely cited in the papers of the late fifties through the mid-seventies by the people now considered major founders of molecular biology. By studying the contributions of those who are now omitted in the standard histories and recollections, we will gain a clearer sense of the possibilities that were open as molecular biology took shape. It is already widely recognized that the contributions of a number of biochemists have been given short shrift, but (as the example of Ernest Gale in Rheinberger's study illustrates) there are a great many more figures whose line of work were then crucial but who are now overlooked.⁶ To understand both what molecular biology was at the time of its early institutionalization and what is has become, it will be enormously helpful to understand at what point the definition or ideology hardened and the grounds for inclusion and exclusion of individuals and lines of work were reformed. Studies of this sort are appropriate in many other areas as well, of course; in general, they should different histories, political standing, and institutional bases of those disciplines in their national cultures. It is likely (but a matter for investigation!) that such differences influenced the opportunities for introducing new bench practices, if in no other way than by delimiting the niches within which certain practices could be initiated.⁷ And since new practices can fail to achieve their objectives, can transform the direction of work and disciplinary allegiances of their practitioners, can lead to only routine results, or can open up important new vistas, the character of the available niches from which to work can prove to have a strong influence on the direction that new work takes if and when it starts to flourish. A key aspect of this problematic (not yet adequately studied, I believe) is the problem of drawing boundaries between different kinds of work and determining where each should fit among established disciplines and/or within some new construct. To the extent that an international solution is ultimately achieved to such problems, it must surely be achieved in light of initially different ways of dealing with it in different countries.Underlying work of the sort we have been exploring is the thorny problem of how best to contextualize the work being studied. This, I believe, is one of the major historiographic problems that we must face in the history of science. It is by no means a new problem, of course, but a particularization of the age-old problem of the (seeming) overdetermination of historical events. If we deal with local cultures, to understand how they develop and their fate we need to understand their location within larger cultures. But it is utterly unclear how to draw appropriate boundaries on the relevant larger culture(s). As even this brief discussion has shown, institutional cultures, the cultures of sponsoring agencies, the culture of science (or of biological science, physical science, etc., as appropriate), and national cultures all can provide relevant contexts, all can occasionally determine the fate of work undertaken in a particular local context. The potentially intractable problem of delimiting the boundaries of investigation looms large here, but it is one that must be faced explicity if we are to profit fully from the enormously stimulating investigations of local cultures exemplified in the four papers published in this symposium. My own view is that we have no abstract standard available for determining which boundaries are appropriate to a given study, and, indeed, that no single contextualization is adequate to the examination of any given case, but that, nonetheless, we can (at least sometimes) distinguish useful and explanatory delimitations of the larger context from others that prove to be misleading.Against this background, I hope that the four papers published in this special issue will stimulate the readers of the JHB to carry out similar studies—that is, studies that seek to characterize and contextualize local experimental cultures —over a wide range of cases. I also hope that some of those who take up this challenge will deal with the larger questions raised by the need to find a way of balancing different, sometimes competing, contextualizations of such studies. The fact that any given case requires multiple contextualizations, resulting in multifaceted representations no one of which is alone adequate, will surely land us in fascinating, hopefully fruitful and productive, controversies.     

The history of the homology concept and the “Phylogenetisches Symposium”

The homology concept has had a long and varied history, starting out as a geometrical term in ancient Greece. Here we describe briefly how a typological use of homology to designate organs and body parts in the same position anatomically in different organisms was changed by Darwin’s theory of evolution into a phylogenetic concept. We try to indicate the diversity of opinions on how to define and test for homology that has prevailed historically, before the important books by Hennig (1950. Grundzüge einer Theorie der Phylogenetischen Systematik. Deutscher Zentralverlag, Berlin) and Remane (1952. Die Grundlagen des Natürlichen Systems, der Vergleichenden Anatomie und der Phylogenetik. Geest & Portig, Leipzig) brought more rigor into both the debate on homology and into the usage of the term homology among systematists. Homology as a theme has recurred repeatedly throughout the history of the “Phylogenetisches Symposium” and we give a very brief overview of the different aspects of homology that have been discussed at specific symposia over the last 48 years. We also honour the fact that the 2004 symposium was held in Jena by pointing to the roles played by biologists active in Jena, such as Ernst Haeckel and Carl Gegenbaur, in starting the development towards a homology concept concordant with an evolutionary world view. As historians of biology, we emphasize the importance of major treatises on homology and its history that may be little read by systematists active today, and have sometimes also received less attention by historians of biology than they deserve. Prominent among these are the works of Dietrich Starck, who also happened to be both a student, and later a benefactor, of systematics at Jena University.     

A Delicate Adjustment: Wallace and Bates on the Amazon and “The Problem of the Origin of Species”

For over a century it has been believed that Alfred Russel Wallace and Henry Walter Bates set out for the Amazon in 1848 with the aim of “solving the problem of the origin of species”. Yet this enticing story is based on only one sentence. Bates claimed in the preface to his 1863 book that Wallace stated this was the aim of their expedition in an 1847 letter. Bates gave a quotation from the letter. But Wallace himself never endorsed or repeated this story. Many writers have acknowledged that this letter still survives. Yet the wording is different from that quoted by Bates and the letter says nothing of an expedition. It is argued that the sentence given by Bates is not a genuine quotation from this or any other Wallace letter but was modified by Bates to promote his own reputation. More significantly, this leads to the conclusion that there was a very sudden and dramatic shift in the way species were thought of and discussed after Darwin’s Origin of species appeared. Something called “the problem of the origin of species” (and similar variants) never occurred before Darwin’s book but exploded in frequency immediately after it. A profound change in how species origins were discussed happened which no one seemed to notice.     

The rise and fall of handicap principle: a commentary on the “Modelling and the fall and rise of the handicap principle”

The honesty of animal communication is in the spot lights in the last 30 years. During most of this time the field was dominated by one explanation: Zahavi’s handicap principle (Zahavi, J Theor Biol 67:603–605, 1975; Grafen, J Theor Biol 144:517–546, 1990). Grose (Biol Philos 2011) embarks to explain both the success of the theory and the empirical difficulties that exist despite this success. While I wholeheartedly agree with the criticism offered by Grose and with almost all the claims he makes, the treatment of the issue is far from complete and it still leaves much to be explained. Accordingly, my commentary consist of six sections: in the first section I clear up some technical issues left unexposed, most importantly the role of strategic cost in handicap signalling; in the second section I relate this to empirical testing; in the next section I comment on the historical development of the handicap principle; in the fourth section I review the biological models that came up with conclusions that contradict the handicap principle; in the fifth section I discuss the reasons behind the success of the handicap theory; finally, in the last section I discuss the application of the handicap theory to anthropology and human sciences.