The modulus of elasticity of lobster aorta microfibrils

The presence of elastic fibres in the extracellular matrix (ECM) provides physiologically important elastic properties for many tissues. Until recently, microfibrils, one component of the ECM, were thought primarily to serve as a scaffolding on which elastin is deposited during development to form elaunin fibres [1]. The most prominent protein that forms mammalian microfibrils is fibrillin. It is known that mutations in the fibrillin gene cause a heterogenous connective tissue disease called marfan syndrome [2], so information on mechanical properties of microfibrils or their role in tissue function would be useful. Microfibrils are also found in the ECM of some invertebrate tissues, and there is growing evidence that the protein forming the structure is homologous to mammalian fibrillin [3, 4]. It has been shown that the microfibril-based arterial wall of the lobster has viscoelastic properties [5], and we have now utilized this primitive artery to measure the modulus of elasticity of microfibrils. It is similar to that of the rubber-like protein elastin.     

Chitin in the epidermal cuticle of a vertebrate (Paralipophrys trigloides,Blenniidae, Teleostei)

Lectin binding, endo-chitinase binding and enzymatic degradation studies show that the epidermal cuticle of the bony fishParalipophrys trigloides (Blenniidae) is chitinous. This is the first evidence that a vertebrate species possesses a chitinous tissue. Recently aXenopus gene has been identified which has significant sequence similarity to the catalytic domain of yeast chitin synthase III, a chitin producing enzyme^1,2. Taken together these two findings imply that chitin synthesis capability may be a basic vertebrate feature.     

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: a possible new mechanism for hypoxia-induced vasodilatation of the rat heart

In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.     

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: A possible new mechanism for hypoxia-induced vasodilatation of the rat heart

Summary In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.This research was supported by the British Heart Foundation and the excellent technical assistance of Jon Bokor is gratefully acknowledged.     

Physicochemical profiling in drug research: a brief survey of the state-of-the-art of experimental techniques

This review begins with a general presentation of the new paradigm of drug discovery, with its emphasis on the rapid identification and elimination of compounds with unsuitable physicochemical and pharmacokinetic properties. The focus of the paper is on the various experimental methods used to determine such key physicochemical properties as ionization, lipophilicity and distribution in isotropic and anisotropic systems, solubility, and permeability across artificial membranes. Both traditional and high-throughput methods are presented and their limits highlighted. The text concludes with the trade-off between quantity/speed in high-throughput screening techniques versus greater data quality in the more labor-intensive methods. Received 23 April 2002; received after revision 25 June 2002; accepted 11 July 2002 RID="*" ID="*"Corresponding author.     

K252a: A new blocker of the cell-cycle at G1 phase in a human hepatoma cell line

The administration of 200 nM K252a to HuH7 suppressed the proliferation of the cells almost completely. The uptake of [³H]thymidine was inhibited, and flow cytometry revealed only one peak at 2C on day 3 after treatment with 100 nM K252a. The expression of proto-oncogene c-myc was not reduced. Despite the blockage at G1, both the size of the cells and the amount of cell protein had increased by 4 times by day 3 after treatment with K252a, while the cells secreted albumin and -fetoprotein into the medium as usual. These results show that K252a can increase the cell size of HuH7 without losing its function by blocking the cell cycle at G1 phase.     

Short-distance homing in a small mammal: the role of exteroceptive cues and path integration

Summary When hoarding food under IR light, the golden hamster returns to its nest by path integration after an active outward journey, and it is capable of compensating the angular component of a passive outward journey independently of auditory, olfactory, tactile and geomagnetic cues. If, however, peripheral visual cues are available, they predominate over information which is gained during the active or passive outward journey. Further experiments show the limitations of homing by path integration, which is open to cumulative errors and therefore needs to be complemented by other categories of information.Acknowledgments. This research was supported by the Fonds national suisse de la recherche scientique, grants No. 3.349.0.74 and 3.753.0.80. We are very grateful to Dr J. Bovet, Dr W. Heiligenberg, Dr J. G. Mather and to an unknown referee for their critical comments and to Mr R. Schumacher for all his ingenious technical help.     

The cell cycle: a new entry in the field of Ca2+ signaling

Ca²⁺ signaling plays a crucial role in virtually all cellular processes, from the origin of new life at fertilization to the end of life when cells die. Both the influx of external Ca²⁺ through Ca²⁺-permeable channels and its release from intracellular stores are essential to the signaling function. Intracellular Ca²⁺ is influenced by mitogenic factors which control the entry and progression of the cell cycle; this is a strong indication for a role of Ca²⁺ in the control of the cycle, but surprisingly, the possibility of such a role has only been paid scant attention in the literature. Substantial progress has nevertheless been made in recent years in relating Ca²⁺ and the principal decoder of its information, calmodulin, to the modulation of various cycle steps. The aim of this review is to critically discuss the evidence for a role of Ca²⁺ in the cell cycle and to discuss Ca²⁺-dependent pathways regulating cell growth and differentiation. Received 2 March 2005; received after revision 9 May 2005; accepted 24 May 2005     

From successful measurement to the birth of a law: Disentangling coordination in Ohm's scientific practice

In this paper, I argue for a distinction between two scales of coordination in scientific inquiry, through which I reassess Georg Simon Ohm's work on conductivity and resistance. Firstly, I propose to distinguish between measurement coordination, which refers to the specific problem of how to justify the attribution of values to a quantity by using a certain measurement procedure, and general coordination, which refers to the broader issue of justifying the representation of an empirical regularity by means of abstract mathematical tools. Secondly, I argue that the development of Ohm's measurement practice between the first and the second experimental phase of his work involved the change of the measurement coordination on which he relied to express his empirical results. By showing how Ohm relied on different calibration assumptions and practices across the two phases, I demonstrate that the concurrent change of both Ohm's experimental apparatus and the variable that Ohm measured should be viewed based on the different form of measurement coordination. Finally, I argue that Ohm's assumption that tension is equally distributed in the circuit is best understood as part of the general coordination between Ohm's law and the empirical regularity that it expresses, rather than measurement coordination.     

Experiment versus mechanical philosophy in the work of Robert Boyle: a reply to Anstey and Pyle

We can distinguish ‘mechanical’ in the strict sense of the mechanical philosophers from ‘mechanical’ in the common sense. My claim is that Boyle's experimental science owed nothing to, and offered no support for, the mechanical philosophy in the strict sense. The attempts by my critics to undermine my case involve their interpreting ‘mechanical’ in something like the common sense. I certainly accept that Boyle's experimental science was productively informed by mechanical analogies, where ‘mechanical’ is interpreted in a common sense. But this leaves my original claim untouched and, in the main, unchallenged.     

History and scientific practice in the construction of an adequate philosophy of science: revisiting a Whewell/Mill debate

William Whewell raised a series of objections concerning John Stuart Mill’s philosophy of science which suggested that Mill’s views were not properly informed by the history of science or by adequate reflection on scientific practices. The aim of this paper is to revisit and evaluate this incisive Whewellian criticism of Mill’s views by assessing Mill’s account of Michael Faraday’s discovery of electrical induction. The historical evidence demonstrates that Mill’s reconstruction is an inadequate reconstruction of this historical episode and the scientific practices Faraday employed. But a study of Faraday’s research also raises some questions about Whewell’s characterization of this discovery. Thus, this example provides an opportunity to reconsider the debate between Whewell and Mill concerning the role of the sciences in the development of an adequate philosophy of scientific methodology.     

Resuscitation of cadaveric livers from non-heart-beating donors after warm ischemic insult: a novel technique tested in the rat

Clinical liver transplantation has become the therapy of choice in end-stage liver disease, but the limited availability of suitable donor organs still impedes its widespread application. In order to increase the availability of donor organs for liver transplantation, it would be advantageous if ischemically damaged livers could be resuscitated from cadavers in which the heart has stopped beating. A method for doing this has been developed in a rat model. Compared to livers excised from rats in which the heart is still beating, severe deteriorations of tissue integrity and functional performance were evident in predamaged livers after cold preservation without supplementary treatment. A treatment of those livers which included an antioxidant rinse with superoxide dismutase, and venous vascular insufflation of gaseous oxygen during preservation, completely prevented tissue alterations upon reperfusion, and promoted a functional recovery of the livers, making them comparable to organs harvested from heart-beating donors.     

Energy consumption,survey data and the prediction of industrial production in Italy: a comparison and combination of different models

We investigate the prediction of italian industrial production and first specify a model based on electricity consumption showing that the cubic trend in such a model mostly captures the evolution over time of the electricity coefficient, which can be well approximated by a smooth transition model, with no gains in predictive power. We also analyse the performance of models based on data of two different business surveys. According to the standard statistics of forecasting accuracy, the linear energy‐based model is not outperformed by any other model, nor by a combination of forecasts. However, a more comprehensive set of evaluation criteria sheds light on the relative merit of each individual model. A modelling strategy which makes full use of all information available is proposed. Copyright © 2000 John Wiley & Sons, Ltd.     

Extra-nuclear inheritance in a sexually produced aphid: the ability to overcome host plant resistance by biotype hybrids of the greenbug,Schizaphis graminum

Summary Greenbugs of biotype E that grow and reproduce well on a biotype C-resistant sorghum (IS 809) were crossed with biotype C greenbugs. The resulting hybrids were tested on IS 809 to study how the ability to overcome the cultivar's resistance is inherited. Only those hybrids stemming from biotype E mothers were able to overcome the resistance of IS 809 plants, indicating that this trait is inherited by the sexually-produced fundatrices in an extra-nuclear manner from the mother. A plausible explanation for this phenomenon is presented.     

Re-examining the impact of European astronomy in seventeenth-century China: a study of Xue Fengzuo’s system of thought and his integration of Chinese and Western knowledge

ABSTRACT

During the late Ming and early Qing period, Jesuit missionaries introduced European science into China, and thereby profoundly influenced the later development of Chinese astronomy. Not only did European astronomy become the official system of the Qing dynasty, but the traditional way to ‘attain up above’ by connecting the study of astronomy and Yi learning gradually fell into disuse. However, the astronomers in this period expressed different views on these two processes. As one of the most important early Qing astronomers, Xue Fengzuo’s case presents a distinctive and important example. Firstly, under the influences of both Chinese tradition and European science, Xue Fengzuo rebuilt the way to ‘attain up above’ based on his three-fold ‘calendrical learning’, i.e. calendrical astronomy, astrology and related pragmatic applications, through which he could realize the highest Confucian ideal. Secondly, he integrated Chinese and Western knowledge for all three aspects of his ‘calendrical learning’, instead of ceding the dominant position to Western methods. From Xue Fengzuo’s example, many of the complex effects of the encounter between different cultures and the process of knowledge transfer can be revealed.     

Changes in calpastatin localization and expression during calpain activation: a new mechanism for the regulation of intracellular Ca<Superscript>2+</Superscript>-dependent proteolysis

The amount of calpastatin directly available in cytosol is under the control of [Ca²⁺] and [cyclic AMP]. Prolonged calpain activation also promotes degradation of calpastatin. The fluctuation of calpastatin concentration in cell soluble fraction is accompanied by an initial decrease in calpastatin gene expression, followed by a fivefold increase in its expression when the inhibitor protein is degraded. This process can be conceptualized as a mechanism to regulate calpastatin availability in the cell. This conclusion is supported by the fact that calpain, the other component of this proteolytic system, undergoes changes in its levels of expression in a much more limited manner. Furthermore, this process can be observed both in cells exposed to different natural stimuli, or in other cell lines. Modification of calpastatin gene expression might represent a new tool for the in vivo control of the regulatory machinery required for the modulation of Ca²⁺-dependent proteolysis.Received 18 July 2003; received after revision 3 September 2003; accepted 23 September 2003