Melatonin, hormone of darkness and more – occurrence, control mechanisms, actions and bioactive metabolites

In its role as a pineal hormone, melatonin is a pleiotropic, nocturnally peaking and systemically acting chronobiotic. These effects are largely explained by actions via G protein-coupled membrane receptors found in the suprachiasmatic nucleus, but also in numerous other sites. Nuclear (ROR/RZR), cytoplasmic (quinone reductase-2, calmodulin, calreticulin) and mitochondrial binding sites and radical-scavenging properties contribute to the actions of melatonin. Regulation of pineal melatonin biosynthesis is largely explained by control mechanisms acting on arylalkylamine N-acetyltransferase, at the levels of gene expression and/or enzyme stability influenced by phosphorylation and interaction with 14-3-3 proteins. Melatonin is not only a hormone but is also synthesized in numerous extrapineal sites, in which it sometimes attains much higher quantities than in the pineal and the circulation. It is also present in many taxonomically distant groups of organisms, including bacteria, fungi, and plants. Moreover, melatonin is a source of bioactive metabolites, such as 5-methoxytryptamine, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxykynuramine.     

Comparison of the effects of lithium,β-phenylethylamine and tyrosine onXenopus embryos

Résumé On a étudié les effets du lithium, de la -phényléthylamine et de la tyrosine sur le développement embryonnaire deXenopus laevis. La tyrosine n'a pas d'effet, mais le lithium ou la -phényléthylamine ont végétalisé les embryons s'ils ont été exposés avant le stade blastula.     

Crystal and molecular structure of 3, 3′-dibromobenzophenone

Résumé La structure du cristal de 3, 3-dibromobenzophénone a été définie par l'emploi de données obtenues par rayons X dans trois dimensions. Les distances et les angles de liaison ont été obtenus et l'on a trouvé que deux anneaux de phényle de la molécule ne sont pas dans le même plan, l'angle compris entre eux étant de 39,9°.     

The effects of 9α-halohydrocortisones and of aldosterone on survival,growth and sodium-potassium excretion in adrenalectomized rats

Zusammenfassung Die Wirkungen von Aldosteron und 9-Halogenhydrocortison-azetaten auf das Überleben und Wachstum adrenalektomierter Ratten wurden studiert. Im Na/K-Ausscheidungstest zeigten sich 9-Chlor-hydrocortison-azetat bzw. 9-Fluor-hydrocortison-azetat 35-bzw. 10mal wirksamer als DCA und wiesen 1/3 bzw. 1/10 der Wirksamkeit von Aldosteron auf.     

A fungus pigment of novel type,and the nature of fungus ‘lignin’

Zusammenfassung In den Früchten des höheren PilzesPolyporus hispidus bildet sichin situ ein ligninähnlicher Stoff durch Oxidation-Polymerisation von Phenolen des Phenylpropantyps, hauptsächlich Hispidin (I), dessen Struktur als Enollacton der 3,4-Dihydroxycinnamoylacetessigsäure erkannt wurde.     

A suggested mechanism for the action of choline esters on animal organs,inferred from a study of the effect of choline-,β-methylcholine-, and thiocholine-esters

Résumé Le mécanisme d'action des esters carboxyliques de la choline commence, probablement, par une hydrolyse enzymatique provoquée par une des cholinestérases. Les produits de l'hydrolyse réagissent avec un facteur inconnu, dont la spécificité est cependant définissable par la structure du résidu cholinique.     

Properties of γ-glutamyltranspeptidase,and glutathione levels in rat mammary gland

Summary -Glutamyltranspeptidase activity and glutathione levels were studied in rat mammary gland during the lactogenic cycle; both increased during mid-lactation. The enzyme's specific activity with several amino acids showed that glutamine and methionine were the best substrates. Maleate decreased the transpeptidation reaction and increased the hydrolytic activity. These results suggest that -glutamyltranspeptidase from the mammary gland is similar to the enzyme described in other tissues in relation to these properties and the physiological role proposed in amino acids transport.     

Phylogenetic distribution, functional epitopes and evolution of the CSαβ superfamily

A superfamily of proteins often conserves a common structural scaffold but develops diverse biochemical and biological functions during evolution. The understanding of evolutionary mechanisms responsible for this diversity is of fundamental importance not only in structural genomics but also in nature-guided drug design. A superfamily of peptides with a conserved CSalphabeta structural motif provides a considerably intriguing example to approach such an issue. The peptides from this superfamily have wide origins, ranging from plants to animals, and exhibit diverse biological activities, varying from a sweet-tasting protein to antibacterial defensins and animal toxins targeting ion channels. This review describes the phylogenetic distribution and structural classifi cation of this unique scaffold and provides new insights into its functional diversity from the perspective of sequence, structure and evolution.     

Animal experiments, vital forces and courtrooms: Mateu Orfila, François Magendie and the study of poisons in nineteenth-century France

The paper follows the lives of Mateu Orfila and Fran?ois Magendie in early nineteenth-century Paris, focusing on their common interest in poisons. The first part deals with the striking similarities of their early careers: their medical training, their popular private lectures, and their first publications. The next section explores their experimental work on poisons by analyzing their views on physical and vital forces in living organisms and their ideas about the significance of animal experiments in medicine. The last part describes their contrasting research on the absorption of poisons and the divergences in their approaches, methods, aims, standards of proof, and intended audiences. The analysis highlights the connections between nineteenth-century courtrooms and experimental laboratories, and shows how forensic practice not only prompted animal experimentation but also provided a substantial body of information and new research methods for dealing with major theoretical issues like the absorption of poisons.     

WNT signaling,the development of the sympathoadrenal–paraganglionic system and neuroblastoma

Neuroblastoma (NB) is a tumor of the sympathoadrenal system arising in children under 15 years of age. In Germany, NB accounts for 7% of childhood cancer cases, but 11% of cancer deaths. It originates from highly migratory progenitor cells that leave the dorsal neural tube and contribute neurons and glial cells to sympathetic ganglia, and chromaffin and supportive cells to the adrenal medulla and paraganglia. Clinically, histologically and molecularly, NBs present as extremely heterogeneous, ranging from very good to very poor prognosis. The etiology of NB still remains unclear and needs to be elucidated, however, aberrant auto- and paracrine embryonic cell communications seem to be likely candidates to initiate or facilitate the emergence, progression and regression of NB. The wingless-type MMTV integration site (WNT) family of proteins represents an evolutionary highly conserved signaling system that orchestrates embryogenesis. At least 19 ligands in the human, numerous receptors and co-receptors are known, which control not only proliferation, but also cell polarity, migration and differentiation. Here we seek to interconnect aspects of WNT signaling with sympathoadrenal and paraganglionic development to define new WNT signaling cues in the etiology and progression of NB.     

The Making of Modern Science: Science,Technology, Medicine and Modernity: 1789–1914

We offer a novel historical-philosophical framework for discussing experimental practice which we call ‘Generating Experimental Knowledge’. It combines three different perspectives: experimental systems, concept formation, and the pivotal role of error. We then present an historical account of the invention of the Scanning Tunnelling Microscope (STM), or Raster-Tunnelmikroskop, and interpret it within the proposed framework. We show that at the outset of the STM project, Binnig and Rohrer—the inventors of the machine—filed two patent disclosures; the first is dated 22 December 1978 (Switzerland), and the second, two years later, 12 September 1980 (US). By studying closely these patent disclosures, the attempts to realize them, and the subsequent development of the machine, we present, within the framework of generating experimental knowledge, a new account of the invention of the STM. While the realization of the STM was still a long way off, the patent disclosures served as blueprints, marking the changes that had to be introduced on the way from the initial idea to its realization.     

Good, bad or offal? The evaluation of raw pancreas therapy and the rhetoric of control in the therapeutic trial, 1925

In 1925 a debate erupted in the correspondence columns of the British Medical Journal concerning the effectiveness of eating raw pancreas as a treatment for diabetes. Enthusiasts were predominantly general practitioners (GPs), who claimed success for the therapy on the basis of their clinical impressions. Their detractors were laboratory-oriented 'biochemist-physicians,' who considered that their own experiments demonstrated that raw pancreas therapy was ineffective. The biochemist-physicians consistently dismissed the GPs' observations as inadequately 'controlled'. They did not define the meaning of 'control' in this context, although it clearly did not have the term's present-day meaning of a trial employing an untreated comparison group of patients. Rather, the physician-biochemists' 'properly controlled' experiments involved careful regulation of their patients' diet and other environmental factors, and evaluation of the therapy's success through biochemical, rather than just clinical, criteria. However, my analysis suggests that these factors alone are inadequate to account for the biochemist-physicians' dismissal of the GPs' work as 'uncontrolled'. I suggest that the biochemist-physicians were deliberately exploiting the powerful rhetorical connotations of the term 'control'. Ultimately, they implied that only a trial which they themselves had conducted could be deemed 'adequately controlled'.     

The use of benzylpenicillinacylase fromEscherichia coli in the resolution of some racemicβ-,γ-,δ- andɛ-amino-acids

Summary The enzymatic hydrolysis of N-phenylacetyl derivatives of racemic amino-acids having the chiral centre removed from the usual -position is examined. The reaction is found to have different degrees of stereoselectivity. In the case of -amino-acids and of -aminovaleric acid, both enantiomers can be obtained in good yields and high optical purity. S-directed stereochemical preference was found for all the substrates examined.     

The in vivo expression of the globin genes of theβ cistron in γ-,δ-, andδβ-thalassemia heterozygotes

There is considerable evidence suggesting that the switch from to and chain production after birth is due, in part, to silencing of the genes by stage-specific factors which bind to their promoters and to the competition from the adult ( and ) genes for a common enhancer element located in the locus control region. As a consequence one can expect that the increased Hb F production in adults with hereditary persistence of fetal hemoglobin or -thalassemia is directed mainly by -globin genes in cis to the deletion(s) responsible for these conditions. Here we review data on heterozygotes with -, -, or -thalassemia, who also had an^AT mutation, in cis or in trans, which was used as a marker of gene expression. The results show that a deletion affecting adult genes favors the expression of genes in cis, while the deletion of a single gene does not affect the expression of the gene in cis but leads to a faster switch postnatally.     

Objectivity, abstraction, and the individual: the influence of Søren Kierkegaard on Paul Feyerabend

This paper explores the influence of Søren Kierkegaard upon Paul Feyerabend by examining their common criticisms of totalising accounts of human nature. Both complained that philosophical and scientific theories of human nature which were methodologically committed to objectivity and abstraction failed to capture the richness of human experience. Kierkegaard and Feyerabend argued that philosophy and the science were threatening to become obstacles to human development by imposing abstract theories of human nature and reality which denied the complexities of both. In both cases, this took the form of asserting an ‘existential’ criterion for the assessment of philosophical and scientific theories. Kierkegaard also made remarks upon the inappropriateness of applying natural scientific methods to human beings which Feyerabend later expanded and developed in his criticisms of the inability of the ‘scientific worldview’ to accommodate the values necessary to a flourishing human life. I conclude by noting some differences between Kierkegaard and Feyerabend’s positions and by affirming the value of existential criticisms of scientific knowledge.