Expression of a bacterial gene, cloned in the yeast, Saccharomyces cerevisiae]

Vectors allowing cloning of foreign D.N.A. in the yeast Saccharomyces cerevisiae have been recently described. We have introduced in this yeast the lac Z gene of the bacteria Escherichia coli. An active beta-galactosidase, which is absent in the recipient strain, has been detected in transformed yeast. We thus conclude that the bacterial lac Z gene is expressed in yeast. We further showed that the enzyme found in the transformed yeast is identical to the bacterial enzyme with respect to size and immunological criteria.     

Anti-arthritic activity of bredinin,an immunosuppressive agent

Summary Bredinin has been found to have an inhibitory effect upon the secondary lesions occurring from adjuvant injection in rats.Acknowledgment. We thank Mr Clark Briggs for correction of the print.     

String theory and general methodology: A mutual evaluation

String theory has been the dominating research field in theoretical physics during the last decades. Despite the considerable time elapse, no new testable predictions have been derived by string theorists and it is understandable that doubts have been voiced. Some people have argued that it is time to give up since testability is wanting. But the majority has not been convinced and they continue to believe that string theory is the right way to go. This situation is interesting for philosophy of science since it highlights several of our central issues. In this paper we will discuss string theory from a number of different perspectives in general methodology. We will also relate the realism/antirealism debate to the current status of string theory. Our goal is two-fold; both to take a look at string theory from philosophical perspectives and to use string theory as a test case for some philosophical issues.     

Chronic hyperesthesia in rats caused by lesions in the dorsal roots of the branchial plexus]

Traumatic avulsions of the brachial plexus in Man is followed by development of hyperesthesia which is known to be reistant to pharmacological medication. We have been able to reproduce this syndrome in the Rat and have used this disturbed animal as a model. This model will give us the possibility of studying nervous mechanisms responsible for these abnormal pains and to look for effective treatments.     

Anti-endotoxin (anti-lipid-A) antibodies

Summary Anti-lipid-A, anti-endotoxin, antibodies have been measured by a passive haemolysis test using antigen from anE. coli Re mutant. Titres in the normal population are low but do rise in situations in which there has been gram-negative sepsis. Absence of raised titres in other situations has profound implications.We are most grateful to Dr Günter Schmidt of Freiburg for his gift of Lipid-A antigen. We also thank Dr L. Monnens of Nijmegen and Dr T.M. Barratt of London for their sera.     

Chemical components of the rectal gland secretions of maleDacus cucurbitae,the melon fly

Summary The volatile constituents of the rectal gland secretion of maleDacus cucurbitae have been shown to contain 2-methoxy-N-3-methylbutyl acetamide together with 2 other amides, 3 pyrazine derivatives and 2-ethoxybenzoic acid. Excised male rectal glands have been demonstrated to elicit strong responses from female melon flies.Acknowledgment. We thank Dr P. Howse for valuable discussions and advice.     

Such small hands: the roles of centrins/caltractins in the centriole and in genome maintenance

Centrins are small, highly conserved members of the EF-hand superfamily of calcium-binding proteins that are found throughout eukaryotes. They play a major role in ensuring the duplication and appropriate functioning of the ciliary basal bodies in ciliated cells. They have also been localised to the centrosome, which is the major microtubule organising centre in animal somatic cells. We describe the identification, cloning and characterisation of centrins in multiple eukaryotic species. Although centrins have been implicated in centriole biogenesis, recent results have indicated that centrosome duplication can, in fact, occur in the absence of centrins. We discuss these data and the non-centrosomal functions that are emerging for the centrins. In particular, we discuss the involvement of centrins in nucleotide excision repair, a process that repairs the DNA lesions that are induced primarily by ultraviolet irradiation. We discuss how centrin may be involved in these diverse processes and contribute to nuclear and cytoplasmic events.     

Yeast prions and human prion-like proteins: sequence features and prediction methods

Prions are self-propagating infectious protein isoforms. A growing number of prions have been identified in yeast, each resulting from the conversion of soluble proteins into an insoluble amyloid form. These yeast prions have served as a powerful model system for studying the causes and consequences of prion aggregation. Remarkably, a number of human proteins containing prion-like domains, defined as domains with compositional similarity to yeast prion domains, have recently been linked to various human degenerative diseases, including amyotrophic lateral sclerosis. This suggests that the lessons learned from yeast prions may help in understanding these human diseases. In this review, we examine what has been learned about the amino acid sequence basis for prion aggregation in yeast, and how this information has been used to develop methods to predict aggregation propensity. We then discuss how this information is being applied to understand human disease, and the challenges involved in applying yeast prediction methods to higher organisms.     

Natural hybridization inDrosophila

Summary Although at least 159 cases of interspecific hybridization between closely related species ofDrosophila have been obtained under laboratory conditions, only 7 cases of natural interspecific hybridization have been recorded. We report yet another case, concerningD. malerkotliana andD. bipectinata.Thanks are due to the University Grants Commission for supporting the research project of J.P.G. and to the Head of the Department for laboratory facilities.     

Forecasting with money demand functions: the UK case

Money demand functions have long been known to be frequently subject to structural change. Since their use for optimal monetary policy design is basically a forecasting exercise, it is crucial to analyse the effect of time instability on the quality of their forecasts. We discuss in this paper whether instability of demand for money functions precludes their use for policy experiments, analysing a 1963–84 sample for the UK which has been widely used in the literature. © 1998 John Wiley & Sons, Ltd.     

Inbreeding considerations in a REM sleep model for rat swimming activity

Over the past few years, our laboratory group has elaborated a repeated measures rat swimming test. It provides an animal base for showing that the REM sleep mechanism is important to both emotional responsiveness and environmental adaptations. All of that work has been done with Sprague-Dawley rats obtained from a local supplier. Work done with two European rat stocks (by researchers in France and The Netherlands) shows general agreement with our own. In this presentation, we directly compare rats derived from an English vendor's Sprague-Dawley stock with the U.S. based Sprague-Dawley stock which we have been using. We also make strain comparisons via the F344 and the Long Evans strains. Although the literature has numerous examples of swimming test differences between inbred and wild rat stocks, strain difference effects have not been reported. We report that there are significant differences attributable to inbred strain but not to vendor on this measure.     

Signal Diffusion Mapping: Optimal Forecasting with Time‐Varying Lags

We introduce a new methodology for forecasting, which we call signal diffusion mapping. Our approach accommodates features of real‐world financial data which have been ignored historically in existing forecasting methodologies. Our method builds upon well‐established and accepted methods from other areas of statistical analysis. We develop and adapt those models for use in forecasting. We also present tests of our model on data in which we demonstrate the efficacy of our approach. Copyright © 2015 John Wiley & Sons, Ltd.     

Identification and localization of volatile hairpencil components in maleAmauris ochlea butterflies (Danaidae)

Summary By gas-chromatography and mass-spectroscopy 7 volatile substances have been found on the abdominal hairpencils ofAmauris ochlea males. 6 substances have been identified. The spatial distribution of compounds is correlated to the 5 types of hairs comprising the scent organ.Acknowledgments. We thank our colleagues M. Kaib and P. Lounibos for their continous effort to supply us with danaids from Kenya. Support by a research grant from the National Institute of Health (AI 12020) is acknowledged with pleasure.     

Demonstration of retinoic acid isomers in human urine under physiological conditions

Untransformed retinoic acid has never been demonstrated in human excreta under normal physiological conditions. We have developed a two-step liquid chromatographic system for the demonstration of subnanogram amounts of this compound in human urine without administration of any precursor.     

Mechanistic explanation,cognitive systems demarcation,and extended cognition

Approaches to the Internalism–Externalism controversy in the philosophy of mind often involve both (broadly) metaphysical and explanatory considerations. Whereas originally most emphasis seems to have been placed on metaphysical concerns, recently the explanation angle is getting more attention. Explanatory considerations promise to offer more neutral grounds for cognitive systems demarcation than (broadly) metaphysical ones. However, it has been argued that explanation-based approaches are incapable of determining the plausibility of internalist-based conceptions of cognition vis-à-vis externalist ones. On this perspective, improved metaphysics is the route along which to solve the Internalist–Externalist stalemate. In this paper we challenge this claim. Although we agree that explanation-orientated approaches have indeed so far failed to deliver solid means for cognitive system demarcation, we elaborate a more promising explanation-oriented framework to address this issue. We argue that the mutual manipulability account of constitutive relevance in mechanisms, extended with the criterion of ‘fat-handedness’, is capable of plausibly addressing the cognitive systems demarcation problem, and thus able to decide on the explanatory traction of Internalist vs. Externalist conceptions, on a case-by-case basis. Our analysis also highlights why some other recent mechanistic takes on the problem of cognitive systems demarcation have been unsuccessful. We illustrate our claims with a case on gestures and learning.     

Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications

Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discuss the influence of hypoxia on the phenotype and functionality of hASCs in terms of viability, stemness, proliferation, differentiation, soluble factor secretion, and biosafety. We provide a glimpse of the possible cellular mechanism that involved under hypoxia and discuss the potential clinical applications. We then highlight the existing challenges and discuss the future perspective on the use of hypoxic-treated hASCs.     

The EM immunocytochemical demonstration of lysozyme in macrophage giant cells in sarcoidosis

Summary The giant cells (multinucleate macrophages) of human sarcoidosis have been shown by the unlabelled antibody immunoperoxidase technique at electron microscope level to contain lysozyme within cytoplasmic granules.Acknowledgment. We are grateful to M. R. C. Canada for financial support, to Dr S. Erlandsen for instruction in technique, and to Dr L. Black for help in obtaining fresh material.     

Identification of 2 phosphorylated amino acids in chicken bone phosphoproteins]

Phosphoproteins of Chicken bone have been extracted by 0.5 M EDTA pH 7.5. Their amino acid composition was similar to that of phosphoproteins of other calcified tissues. The crude EDTA extract contained 80 to 90% proteins, only 70% of the total organic phosphorus was bound to the proteins. We have studied and identified two phosphorylated components. o-phosphoserine and o-phosphothreonine have been identified by amino acid analysis at pH 1.7 from a partial acid hydrolysate, and confirmed by the liberation of the parent amino acids after total hydrolysis. In addition, phosphorus was found equimolecular to both of them. The presence of these phosphorylated groups is important for an understanding of the role of these proteins in the mechanism of mineralization.     

Modelling gene regulation: (De)compositional and template-based strategies

Although the interdisciplinary nature of contemporary biological sciences has been addressed by philosophers, historians, and sociologists of science, the different ways in which engineering concepts and methods have been applied in biology have been somewhat neglected. We examine – using the mechanistic philosophy of science as an analytic springboard – the transfer of network methods from engineering to biology through the cases of two biology laboratories operating at the California Institute of Technology. The two laboratories study gene regulatory networks, but in remarkably different ways. The research strategy of the Davidson lab fits squarely into the traditional mechanist philosophy in its aim to decompose and reconstruct, in detail, gene regulatory networks of a chosen model organism. In contrast, the Elowitz lab constructs minimal models that do not attempt to represent any particular naturally evolved genetic circuits. Instead, it studies the principles of gene regulation through a template-based approach that is applicable to any kinds of networks, whether biological or not. We call for the mechanists to consider whether the latter approach can be accommodated by the mechanistic approach, and what kinds of modifications it would imply for the mechanistic paradigm of explanation, if it were to address modelling more generally.