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.     

The application of Hudson's lactone rule toγ- andδ-hydroxyamino acids and the question of the configuration ofδ-hydroxy-l-lysine from collagen

Zusammenfassung Die Anwendung von Hudsons Lakton-Regel auf eine Reihe von Laktonen von- und-Oxyaminosäuren bestätigte die unabhängig auf chemischem Wege bewiesenen Konfigurationen an den- und-Kohlenstoffatomen. Im Falle des erstmalig dargestellten Laktons des,-Dibenzoyl--hydroxy-d-lysins führte die Anwendung der Regel zurerythro-Struktur XV, und folglich für natürliches-Oxylysin aus Collagen zur Formel XIa, deren Beweis auf chemischem Wege noch aussteht.     

Characterization of 17β-estradiol 3-(β-D-glucopyranoside) and 17-(α-D-glucopyranoside) as the metabolites of 17β-estradiol in the cultured ovaries of the silkworm,Bombyx mori

Summary The structures of the metabolites formed upon incubation of 17-estradiol with the ovaries of silkworm,Bombyx mori, have been determined as 17-estradiol 3-(-D-glucopyranoside) (1) and 17-(-D-glucopyranoside) (2) by spectroscopic means.     

The binding of polyphenols (rutin and some of itsO-β-hydroxyethyl derivatives) to human serum proteins

Summary A binding of polyphenols (rutin and its o--hydroxyethyl derivatives) to human serum was demonstrated. The results showed an increase of binding proportional to the number of free phenolic groups on the molecule of rutin.Acknowledgments. We should like to thank MissC. Gaillard and MissE. Engels for their valuable assistance in this study.     

Biosynthesis ofα- andβ-ecdysone by the CrayfishOrconectes limosus in vivo and by its Y-Organs in vitro

Summary - and -ecdysone were synthesized from labelled cholesterol by premolt crayfish in vivo and by their Y-organs in vitro.     

The platypus in Edinburgh: Robert Jameson,Robert Knox and the place of the Ornithorhynchus in nature, 1821–24

The duck-billed platypus, or Ornithorhynchus, was the subject of an intense debate among natural historians in the late eighteenth and early nineteenth centuries. Its paradoxical mixture of mammalian, avian and reptilian characteristics made it something of a taxonomic conundrum. In the early 1820s Robert Jameson (1774–1854), the professor of natural history at the University of Edinburgh and the curator of the University's natural history museum, was able to acquire three valuable specimens of this species. He passed one of these on to the anatomist Robert Knox (1791–1862), who dissected the animal and presented his results in a series of papers to the Wernerian Natural History Society, which later published them in its Memoirs. This paper takes Jameson's platypus as a case study on how natural history specimens were used to create and contest knowledge of the natural world in the early nineteenth century, at a time when interpretations of the relationships between animal taxa were in a state of flux. It shows how Jameson used his possession of this interesting specimen to provide a valuable opportunity for his protégé Knox while also helping to consolidate his own position as a key figure in early nineteenth-century natural history.     

Dopamine-β-hydroxylase,adrenaline, noradrenaline and dopamine in the venous blood of adrenal gland of man: A comparison with levels in the periphery of the circulation

Summary In 10 human subjects plasma dopamine--hydroxylase activity was found in the adrenal vein blood to be as high as in the periphery of the circulation. Adrenaline concentration in the adrenal vein blood was in the mean 170 times, noradrenaline concentration 11 times and dopamine concentration little higher than levels in the periphery.This study was supported by the Deutsche Forschungsgemeinschaft.     

Optical rotatory dispersion and spectral data of some steroidal ring D ketol acetates of the 14β-series

Zusammenfassung Die optische Rotationsdispersion sowie die UV- und IR-Spektren der Epimeren von 17-Acetoxy-16-keto-bzw. 16-Acetoxy-17-keto-14-steroiden wurden gemessen. Mögliche Beziehungen zwischen Rotationsdispersion und Stereochemie der untersuchten Verbindungen werden diskutiert.

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Paper LXI ofOptical Rotatory Dispersion Studies. For Paper LX seeC. Djerassi, Science134, 649 (1961).     

Reflecting ‘Popular Culture’: The Introduction,Diffusion, and Construction of the Reflecting Telescope in the Netherlands

The eighteenth century was an era in which science came to play a major role in the cultural ideal of the city elite. The phenomenon of the ‘gentleman-scientist’ arose: a layman without a scientific education who for a variety of often socially desirable reasons devoted himself to scientific endeavours. Scientific instruments were the tools for this interest. This article describes the introduction, diffusion, and construction in the Netherlands of one of the most prominent eighteenth-century instruments: the reflecting telescope. The reception of this instrument casts new light on the usually almost invisible network of gentleman-scientists and instrument-makers in this region. The specific economic and political factors of the Netherlands led to a totally different development of this instrument compared with the ‘motherland’ England. Whereas in Great Britain the reflecting telescope was a great success well into the nineteenth century, in the Netherlands it became a symbol of technical inability and stagnation.     

The language of the “Givens”: its forms and its use as a deductive tool in Greek mathematics

The aim of this article is to present and discuss the language of the «givens», a typical stylistic resource of Greek mathematics and one of the major features of the proof format of analysis and synthesis. I shall analyze its expressive function and its peculiarities, as well as its general role as a deductive tool, explaining at the same time its particular applications in subgenres of a geometrical proposition like the locus theorems and the so-called «porisms». The main interpretative theses of this study are the following: the language of the «givens» (1) is the standard idiom in which “existence and uniqueness” of a mathematical object was proved, (2) was conceived as an unified framework reducing to a strictly deductive format disparate argumentative steps such as deductions, constructions, and calculations.     

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'.     

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.     

Influence of cyproterone acetate on the activity ofβ-glucuronidase in the hypothalamus and cerebral cortex of the male mouse

Summary Daily s.c. injections of cyproterone acetate greatly decrease the protein content and-glucuronidase activity in the mouse hypothalamus. These effects are reversible and the recovery capacity of the animal seems to be inversely related to the duration of antiandrogenic treatment.Financial aid was given by CNR (finalized project Biologia della Riproduzione) and Ministry of Education. Thanks are also due to Prof. G. Chieffi for suggestions and to Mr R. Auriemma for maintenance of experimental animals.     

The influence of N-methyl-N-β-chloroethyl hydrazines on the mitotic index of Ehrlich ascites tumor cells and the leukopoiesis of the mouse

Summary The cytostatic activity of N-methyl-N--chloroethylbenzaldehyd hydrazone, (B1) is at least equal to that of procarbazine when its effect is tested with the Ehrlich ascites tumor cells of the mouse and the Yoshida sarcoma of the rat. B1 causes a slighter decrease of mitotic cells and no shift from prophase to metaphase. These results suggest that the cytostatic effect of B1 is due to interference with cell metabolism or an effect at the cell membrane and not to an effect on cell proliferation. This assumption is supported by a considerable depression, of lymphocytes and a minor effect on granulopoiesis, which is especially sensitive towards proliferation toxins. All these findings suggest a different mechanism of action of B1 and procarbazine.     

The presence of β-phenylethylamine,p-tyramine,m-tyramine and tryptamine in ganglia and foot muscle of the garden snail (Helix aspersa)

Summary The concentrations of -phenylethylamine,p-tyramine,m-tyramine,m-octopamine and tryptamine in the ganglia or foot muscle ofHelix aspersa range from <0.6 to 11 ng/g.p-Octopamine levels are higher in ganglia (327 ng/g) than in foot muscle (4.1 ng/g). Dopamine and 5-hydroxytryptamine range from 840 to 2710 ng/g while their acid metabolites, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid and 5-hydroxyindoleacetic acid range from <20 to 130 ng/g.Acknowledgments. We thank Dr A.A. Boulton for helpful discus sion, Dr D.A. Durden for supervising the mass spectrometric analyses, Dr B.A. Davis for the synthesis of the deuterated standards, G.H. Wheatley, E.P. Zarycki and M. Mizuno for expert technical assistance, and Saskatchewan Health and the MRC of Canada for providing financial support.     

The effect of γ-irradiation on the amount of 5-hydroxytryptamine in the gut and spleen in the early phase after irradiation

Résumé 24 et 48 h après irradiation- (900 r) la quantité de 5-hydroxytryptamine dans l'intestin du rat n'a pas changé de manière significative. La quantité de 5-hydroxytryptamine dans la rate du rat, exprimée par g de tissu frais a augmenté. Le prétraitement avec de la cystéamine abaisse nettement la quantité de 5-hydroxytryptamine dans la rate, après l'irradiation.     

Sesquiterpenoids minor constituents ofPinus parviflora. On the relationship between (−)-δ-cadinol, (+)-δ-cadinol,sesquigoyol, torreyol,and brown alga cadinol

Zusammenfassung 1-Dokosanol, Sesquigoyol,-Sitosterin und 3,5-Dimethoxystilben wurden ausP. formosana isoliert. Es konnte gezeigt werden, dass Sesquigoyol der optische Antipode von (–)--Cadinol ist.

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Sesquiterpenoids II. For the previous paper in this series, seeW. G. Dauben, B. Weinstein, P. Lim, andA. B. Anderson, Tetrahedron15, 217 (1961).

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On leave of absence from the Department of Chemistry, National Taiwan University, Taipei, Taiwan, Republic of China.

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The National Council of Science, Republic of China, is thanked for the award of a fellowship for advanced study to one of us (K.-T.W.).     

The role of estrogen receptor α in the regulation of bone and growth plate cartilage

Estrogens are important endocrine regulators of skeletal growth and maintenance in both females and males. Studies have demonstrated that the estrogen receptor (ER)-α is the main mediator of these estrogenic effects in bone. Therefore, estrogen signaling via ERα is a target both for affecting longitudinal bone growth and bone remodeling. However, treatment with estradiol (E2) leads to an increased risk of side effects such as venous thromboembolism and breast cancer. Thus, an improved understanding of the signaling pathways of ERα will be essential in order to find better bone specific treatments with minimal adverse effects for different estrogen-related bone disorders. This review summarizes the recent data regarding the intracellular signaling mechanisms, in vivo, mediated by the ERα activation functions (AFs), AF-1 and AF-2, and the effect on bone, growth plate and other estrogen responsive tissues. In addition, we review the recent cell-specific ERα-deleted mouse models lacking ERα specifically in neuronal cells or growth plate cartilage. The newly characterized signaling pathways of estrogen, described in this review, provide a better understanding of the ERα signaling pathways, which may facilitate the design of new, bone-specific treatment strategies with minimal adverse effects.