‘The happy thought of a single man’: On the legendary beginnings of a style of reasoning

In this paper I direct attention to one feature of Hacking’s recent work on styles of reasoning and argue that this feature is of far greater philosophical significance than Hacking’s limited discussion of this suggests. The feature in question is his use of ‘legendary beginnings’ in setting out a given style, viz. the method of introducing a style of reasoning by recounting a popular and quasi-mythical narrative that ties the crystallisation of that style to a particular person in a particular place and at a particular time. Whilst Hacking both deploys and discusses this method, his comments suggest that this is primarily a stylistic device employed for reasons of expedience. In contrast, it is argued here that recounting the legendary origins of a style of reasoning affords a distinctive way of vindicating that style, a vindication from within the style itself.     

The urokinase receptor: a ligand or a receptor? Story of a sociable molecule

In this last decade, the structure and functions of the receptor for the urokinase-type plasminogen activator have been extensively studied and characterized. This interesting receptor plays a key role in cell adhesion, migration and proliferation. It was identified 20 years ago as the specific cell-surface molecule that could bind and concentrate urokinase on the cell membrane, thus initiating the proteolytic cascade promoted by the activation of plasminogen. The identification of new extracellular ligands, such as vitronectin, and of cell-surface interactors, such as integrins and fMet-Leu-Phe receptors, shed new light on its possible roles, totally independent of the enzymatic properties of its ligand. uPAR ligands and interactors and the functional consequences of the multiple binding capability of this intriguing receptor are reviewed here. Received 19 September 2005; received after revision 4 December 2005; accepted 6 December 2005     

The story of ‘Scientist: The Story of a Word’

This examination of an important paper by Sydney Ross is the first in a projected series of occasional reflections on ‘Annals of Science Classic Papers’ that have had enduring utility within the field of history of science and beyond. First the messages of the paper are examined, some well known but others, particularly Ross's own contemporary concerns about the use of the word ‘scientist’, less so. The varied uses made of the paper by scholars are then traced before Ross's biography is examined in order to try to understand how a figure professionally marginal to the field of history of science came to write such a significant piece. Ross’s interest in the topic appears to have been informed by a romantically tinged scientific progressivism and a deep concern with the importance of linguistic precision in science and in public affairs. The inspirations of the author and the interests of his audience have been only partially aligned, but the paper's insights remain of broad historical interest and have wider ramifications since the denotation ‘scientist’ and its proper application are much debated today in contests over the authority of science.     

Goitrin — a nitrosatable constituent of plant foodstuffs

Summary N-nitrosamides are known as direct-acting carcinogens at the site of their formation; they do not need any metabolic activation in vivo. The conditions leading to their formation in the stomach, and also their genotoxicity, have been thoroughly studied with some model compounds^{1, 2}. Several reports link this type of compound to the induction of gastric cancer in human^{3, 4}. However, only limited data are presently available about possible precursors of N-nitrosamides in foods. In the present study we found that goitrin — a naturally occurring compound in cruciferous vegetables and rape—could be easily nitrosated by treatment with nitrite under stomach conditions, yielding with loss of sulfur the N-nitroso-oxazolidone4 (fig.). This product has a mutagenicity pattern and potency similar to that of N-nitroso-N-methyl-N-nitroguanidine (MNNG) in the Ames Salmonella/mammalian microsome test.     

Occurrence of β-chitin in the cuticle of a Pentastomid Raillietiella gowrii

Summary The purified chitin from the cuticle of a pentastomid was examined by X-ray method. The X-ray photograph discloses that the chitin in question is of -type. Since the arthropod cuticle contains -chitin, it is suggested that Pentastomida may be considered an independent phylum.Thanks are due to Prof. Dr. G. Sundara Rajulu for guidance and encouragement.     

Sirenids: a family of polyploid urodeles?

Riassunto I tre Sirenidi viventi hanno 46, 52 e 64 cromosomi; il corredo diS. lacertina sembra tetraploide (4n=52). Viene fatta l'ipotesi che anche i corredi delle altre due specie derivino per (allo-)poliploidia da corredi a minor numero cromosomico, come si ritrovano nelle famiglie superiori dell'Ordine.

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Research carried out through a contribution from the C.N.R.     

Direct thrombin inhibitors – a survey of recent developments

Thrombin is a plasma serine protease that plays a key role in coagulation and hemostasis but also in thromboembolic diseases. Direct thrombin inhibitors could, therefore, be beneficial for future anticoagulant therapy in the prophylaxis of venous and arterial thrombosis as well as myocardial infarction. However, development of direct thrombin inhibitors has brought researchers more heartache than success. The most recent setback came this year when AstraZeneca withdrew Ximelagatran, the first orally bioavailable direct thrombin inhibitor that had received regulatory approval (France, 2003), after reports of serious hepatoxicity in a fraction of patients. This review describes the status of direct thrombin inhibitors, focusing on drug candidates that are at present in clinical trials. In addition, some more recent research strategies in the design of novel direct thrombin inhibitors are discussed, which may very well contribute to future developments of potent anticoagulants. Received 9 May 2006; received after revision 15 June 2006; accepted 23 August 2006     

Hoplonemertine worms—a new source of pyridine neurotoxins

Summary Two pyridine bases were isolated from the marine hoplonemertineAmphiporus angulatus (Fabricius) and identified by mass and PMR-spectroscopy as 2,3-bipyridyl and 3,2; 3,2; 4,3'-tetrapyridyl (Nemertelline). Nemertelline, the first tetrapyridyl natural product to be reported, shows a structural resemblance to the tobacco constituent nicotelline. The crustacean toxicity of 2,3-bipyridyl is very similar to that of nicotine, but its mammalian toxicity is negligible.We thank DoctorsN. Meinkoth andN. Riser for collecting specimens, Dr.F. Kuffner for providing the nicotelline sample, Dr.C. Westerman for recording initial PMR-spectra, and Dr.R. King for furnishing the computer simulation program and recording the high resolution mass spectra, and Mr.J. Babashak for use of the Kontes densitometer. This research was supported by an NIH-GRS grant and by the Veterans Administration (No. MRIS-9416).     

Synthesis of a pregnancy-associatedα-macroglobulin by human leucocytes

Résumé Le sang des femmes enceintes peut contenir plusierus protéines sériques uniques en leur genre. Celle qui se présente le plus souvent est une -globuline de grand poids moléculaire. Un test in vitro utilisant l'incorporation de¹⁴C-glutamine ou³H-leucine dans la glycoprotéine a montré que celle-ci peut être synthétisée par des leucocytes.

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We thank Dr.J. E. O'Grady and Dr.A. Shephard for obtaining the blood samples. This work was supported by a grant from the Scottish Home and Health Department.     

The “Unknown Heritage”: trace of a forgotten locus of mathematical sophistication

The “unknown heritage” is the name usually given to a problem type in whose archetype a father leaves to his first son 1 monetary unit and \({\frac{1}{n}}\) (n usually being 7 or 10) of what remains, to the second 2 units and \({\frac{1}{n}}\) of what remains, and so on. In the end, all sons get the same, and nothing remains. The earliest known occurrence is in Fibonacci’s Liber abbaci, which also contains a number of much more sophisticated versions, together with a partial algebraic solution for one of these and rules for all which do not follow from his algebraic calculation. The next time the problem turns up is in Planudes’s late thirteenth century Calculus according to the Indians, Called the Great. After that the simple problem type turns up regularly in Provençal, Italian and Byzantine sources. It seems never to appear in Arabic or Indian writings, although two Arabic texts (one from c. 1190) contain more regular problems where the number of shares is given; they are clearly derived from the type known from European and Byzantine works, not its source. The sophisticated versions turn up again in Barthélemy de Romans’ Compendy de la praticque des nombres (c. 1467) and, apparently inspired from there, in the appendix to Nicolas Chuquet’s Triparty (1484). Apart from a single trace in Cardano’s Practica arithmetice et mensurandi singularis, the sophisticated versions never surface again, but the simple version spreads for a while to German practical arithmetic and, more persistently, to French polite recreational mathematics. Close examination of the texts shows that Barthélemy cannot have drawn his familiarity with the sophisticated rules from Fibonacci. It also suggests that the simple version is originally either a classical, strictly Greek or Hellenistic, or a medieval Byzantine invention; and that the sophisticated versions must have been developed before Fibonacci within an environment (located in Byzantium, Provence, or possibly in Sicily?) of which all direct traces has been lost, but whose mathematical level must have been quite advanced.     

Nicotianamine,the ‘normalizing factor’ for the auxotroph tomato mutantChloronerva; a representative of a new class of plant effectors

Summary The article surveys our knowledge of the normalizing factor, gained from its discovery a quarter of a century ago up to the present time, under the following headings: Discovery; Physiological properties; Isolation and characterization; Structure determination (Identity of the normalizing factor with nicotianamine); Chemical properties; Analysis; Synthesis; Occurrence and physiological role; Related compounds; Prospects.     

Variability of β-amylase isoenzymes within a collection of inbred lines of rye (Secale cereale L.)

Summary Within one collection of 18 inbred rye lines, seven distinct isoenzymatic patterns of -amylase were found, and five of them formed a group of similar patterns shifting to distinct positions in the gel. It was proved that the shift of the pattern was due to genetic factors. In crossed immunoelectrophoresis, drastic differences were shown in the quantity of the different -amylase constituents. No antigenic differences could be demonstrated between the analyzed isoenzymes.     

The peroxisomal protein import machinery – a case report of transient ubiquitination with a new flavor

The peroxisomal protein import machinery displays remarkable properties. Be it its capacity to accept already folded proteins as substrates, its complex architecture or its energetics, almost every aspect of this machinery seems unique. The list of unusual properties is still growing as shown by the recent finding that one of its central components, Pex5p, is transiently monoubiquitinated at a cysteine residue. However, the data gathered in recent years also suggest that the peroxisomal import machinery is not that exclusive and similarities with p97/Cdc48-mediated processes and with multisubunit RING-E3 ligases are starting to emerge. Here, we discuss these data trying to distill the principles by which this complex machinery operates. Received 16 July 2008; received after revision 25 August 2008; accepted 29 August 2008     

Proteases of Antarctic krill—a new system for effective enzymatic debridement of necrotic ulcerations

Summary The Antarctic krill (Euphausia superba) possesses an over-dimensioned digestive system, which is of vital importance for the survival of this euphaucean shrimp in the extreme marine environment. The isolated enzymes contain a well-balanced mixture of both endo- and exopeptidases, assuring fast and complete breakdown of proteinaceous material. These unique properties have now been shown to be extremely valuable for the effective removal of necrotic debris, fibrin or blood crusts in vitro. Therefore the krill enzymes should be considered as an important resource in the future management of necrotic wounds.     

Pregnancy specificβ 1 — a product of the syncytiotrophoblast

Summary Pregnancy specific ₁ (PSG) has been identified in vitro in trophoblast cultures and in vivo, using transmission electron microscopy, in the syncytiotrophoblast, PSG may, like other pregnancy proteins, have immunosuppressive properties.This study was supported by a grant from the Medical Research Council. We thank Dr.D. R. Abramovich for making available the first trimester placentae and MissWanda Emslie for help in the tissue culture studies.     

Nestin expression – a property of multi-lineage progenitor cells?

Tissue-specific progenitor cells are characterized by proliferation and differentiation, but, in contrast to embryonic stem (ES) cells, have limited capacities for self-renewal and no tumourigenic potential. These latter traits make progenitor cells an ideal source for regenerative cell therapies. In this review, we describe what is currently known about nestin, an intermediate filament first identified in neuroepithelial stem cells. During embryogenesis, nestin is expressed in migrating and proliferating cells, whereas in adult tissues, nestin is mainly restricted to areas of regeneration. We show that nestin is abundant in ES-derived progenitor cells that have the potential to develop into neuroectodermal, endodermal and mesodermal lineages. Although it remains unclear what factors regulate in vitro and in vivo expression of nestin, we conclude that nestin represents a characteristic marker of multi-lineage progenitor cells and suggest that its presence in cells may indicate multi-potentiality and regenerative potential.     

Some highlights of a 47 year career in research

No Abstract. .M.D., Ph. D. The John S. Dunn Professor and Chair of Integrative Biology and Pharmacology and Director of the Institute of Medicine at the University of Texas-Houston Health Science CenterReceived 1 October 2004; accepted 21 October 2004     

Nucleolar control of p53: a cellular Achilles’ heel and a target for cancer therapy

Nucleoli perform a crucial cell function, ribosome biogenesis, and of critical relevance to the subject of this review, they are also extremely sensitive to cellular stresses, which can cause loss of function and/or associated structural disruption. In recent years, we have learned that cells take advantage of this stress sensitivity of nucleoli, using them as stress sensors. One major protein regulated by this role of nucleoli is the tumor suppressor p53, which is activated in response to diverse cellular injuries in order to exert its onco-protective effects. Here we discuss a model of nucleolar regulation of p53, which proposes that key steps in the promotion of p53 degradation by the ubiquitin ligase MDM2 occur in nucleoli, thus providing an explanation for the observed link between nucleolar disruption and p53 stability. We review current evidence for this compartmentalization in p53 homeostasis and highlight current limitations of the model. Interestingly, a number of current chemotherapeutic agents capable of inducing a p53 response are likely to do so by targeting nucleolar functions and these compounds may serve to inform further improved therapeutic targeting of nucleoli.