The genomic basis of the Williams – Beuren syndrome

The Williams-Beuren syndrome is a genomic disorder (prevalence: 1/7,500 to 1/20,000), caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Typical symptoms comprise supravalvular aortic stenosis, mental retardation, overfriendliness and visuospatial impairment. The common deletion sizes range of 1.5–1.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotype-phenotype correlation has been established. The best-explored gene within this region is the elastin gene; its haploinsufficiency causes arterial stenosis. The region of the Williams-Beuren syndrome consists of a single copy gene region (~1.2 Mb) flanked by repetitive sequences – Low Copy Repeats (LCR). The deletions arise as a consequence of misalignment of these repetitive sequences during meiosis and a following unequal crossing over due to high similarity of LCRs. This review presents an overview of the Williams-Beuren syndrome region considering the genomic assembly, chromosomal rearrangements and their mechanisms (i.e. deletions, duplications, inversions) and evolutionary and historical aspects. Received 11 July 2008; received after revision 15 October 2008; accepted 16 October 2008     

The physiology of the smooth muscle: an interdisciplinary review—part II

Summary In the guinea pig taenia coli, when glycogen is depleted by repeating Ca-induced contracture in excess K solution containing no glucose, the tension cannot be maintained. The decrease in tension is accompanied by reduction of high energy phosphate compounds and oxygen consumption. When substrate is readmitted to the glycogendepleted preparation in the presence of 2.4 mM Ca and 20 mM K, the first response is hyperpolarization of the membrane and relaxation, and this is followed by depolarization and development of contracture. The latter response is blocked by verapamil, suggesting that energy supply increases the Ca conductance of the plasma membrane. The early response is considered to be due to activation of electrogenic Ca pump, since this is not affected by ouabain as well as removal of Na and K. ATP produced by substrate readmission is probably preferentially utilized for Ca pump activation to reduce the intracellular. Ca. The recovery of tension is likely to be brought about by ATP supply not only to the contractile machinery but also to the plasma membrane to remove inactivation of Ca conductance. It is postulated that as the energy source is depleted, energy consumption is automatically limited by suppressing Ca influx, as a selfdefence mechanism. Since HB is as effective as glucose in the recovery of these processes, and also in the activation of electrogenic Na pump, the matabolic pathway of oxidative phosphorylation alone can support these functions without a contribution of the glycolytic pathway.     

A myth revealed: The case of the ‘Beeldsnyder achromatic objective’

This paper examines the efforts of two young Russian chemists during the late 1850s and early 1860s to establish a professional chemistry journal and a public laboratory for chemistry research in Russia. These two, N. N. Sokolov and A. N. Engel' gardt, were important participants in the early efforts to institutionalize and professionalize chemistry in Russia. However, both the chemistry laboratory and the chemistry journal ended after only a few years. The chemistry journal was curtailed not because of Government interference, as is sometimes asserted, but because of a conflict over editorial policy and independence. The chemistry laboratory was closed and the equipment donated to St Petersburg University when Sokolov was appointed to the position of adjunct there.     

Unraveling the pathogenesis of Parkinson’s disease – the contribution of monogenic forms

The field of Parkinsons disease pathogenesis is rapidly evolving from the one of a monolithic and obscure entity into the one of a complex scenario with several known molecular players. The ongoing systematic exploration of the genome holds great promise for the identification of the genetic factors conferring susceptibility to the common non-Mendelian forms of this disease. However, most of the progress of the last 5 years has come from the successful mapping and cloning of genes responsible for rare Mendelian variants of Parkinsons disease. These discoveries are providing tremendous help in understanding the molecular mechanisms of this devastating disease. Here we review the genetics of the monogenic forms of Parkinsons disease. Moreover, we focus on the mechanisms of disease caused by -synuclein and parkin mutations, and the implications of this growing body of knowledge for understanding the pathogenesis of the common forms of the disease. Received 10 March 2004; received after revision 26 April 2004; accepted 29 April 2004     

Science in the american south through the eyes of four natural historians, 1750–1850

A national scientific community developed in the United States following the American Revolution. The independent scientific societies, journals and other institutions that formed the basis of this community were, however, centred in the North. An analysis of the work of four leading natural historians of the Southern tidewater (two from before the Revolution and two from after it) suggests that their region participated in this development by shifting scientific ties and allegiances from Europe to the North rather than by creating national or regional scientific institutions.     

The semantic conception and the structuralist view of theories: A critique of Suppe’s criticisms

Different conceptions of scientific theories, such as the state spaces approach of Bas van Fraassen, the phase spaces approach of Frederick Suppe, the set-theoretical approach of Patrick Suppes, and the structuralist view of Joseph Sneed et al. are usually put together into one big family. In addition, the definite article is normally used, and thus we speak of the semantic conception (view or approach) of theories and of its different approaches (variants or versions). However, in The Semantic Conception of Theories and Scientific Realism (Urban and Chicago: University of Illinois Press, 1989), starting from certain remarks already made in “Theory Structure” (in P. Asquith and H. Kyburg (Eds.), Current Research in Philosophy of Science, East Lansing: Philosophy of Science Association, 1979, pp. 317–338), Frederick Suppe excludes the structuralist view as well as other “European” versions from the semantic conception of theories. In this paper I will critically examine the reasons put forward by Suppe for this decision and, later, I will provide a general characterization of the semantic family and of the structuralist view of theories in such a way as to justify the inclusion of the structuralist view (as well as other “European” versions) as a member of this family.     

The peritoneal “soil” for a cancerous “seed”: a comprehensive review of the pathogenesis of intraperitoneal cancer metastases

Various types of tumors, particularly those originating from the ovary and gastrointestinal tract, display a strong predilection for the peritoneal cavity as the site of metastasis. The intraperitoneal spread of a malignancy is orchestrated by a reciprocal interplay between invading cancer cells and resident normal peritoneal cells. In this review, we address the current state-of-art regarding colonization of the peritoneal cavity by ovarian, colorectal, pancreatic, and gastric tumors. Particular attention is paid to the pro-tumoral role of various kinds of peritoneal cells, including mesothelial cells, fibroblasts, adipocytes, macrophages, the vascular endothelium, and hospicells. Anatomo-histological considerations on the pro-metastatic environment of the peritoneal cavity are presented in the broader context of organ-specific development of distal metastases in accordance with Paget’s “seed and soil” theory of tumorigenesis. The activity of normal peritoneal cells during pivotal elements of cancer progression, i.e., adhesion, migration, invasion, proliferation, EMT, and angiogenesis, is discussed from the perspective of well-defined general knowledge on a hospitable tumor microenvironment created by the cellular elements of reactive stroma, such as cancer-associated fibroblasts and macrophages. Finally, the paper addresses the unique features of the peritoneal cavity that predispose this body compartment to be a niche for cancer metastases, presents issues that are topics of an ongoing debate, and points to areas that still require further in-depth investigations.     

The early years of the Lycée and the Lycée des Arts. A chapter in the lives of A. L. Lavoisier and A. F. de Fourcroy

The first professors at the newly-established London University (later University College London) were appointed in 1827, but a chair in geology was not created there until 1841. In the intervening years, teaching in geology and palaeontology was included in other natural science courses. Early in 1831, John Phillips, keeper of the Yorkshire Museum at York, was prompted to give a formal course of geological lectures and subsequently he was informally offered the professorship, which he declined.     

The presence of RNA of the A–U type in citrate nuclei isolated from rabbit liver cells

Zusammenfassung Die in 5% iger Zitronensäure isolierten Kaninchenleberkerne enthalten eine minimale Fraktion von RNS, die sich durch ihren Gehalt an Basen der DNS annähert (A+U/G+C>1). Diese RNS wird während der Extraktion mit dem 6% igen Natrium-p-Amino-salicylat und dem Phenol zusammen mit der DNS und RNS vom G+C-Typ gewonnen.     

Everettian quantum mechanics and physical probability: Against the principle of “State Supervenience”

Everettian quantum mechanics faces the challenge of how to make sense of probability and probabilistic reasoning in a setting where there is typically no unique outcome of measurements. Wallace has built on a proof by Deutsch to argue that a notion of probability can be recovered in the many worlds setting. In particular, Wallace argues that a rational agent has to assign probabilities in accordance with the Born rule. This argument relies on a rationality constraint that Wallace calls state supervenience. I argue that state supervenience is not defensible as a rationality constraint for Everettian agents unless we already invoke probabilistic notions.     

The motion of the moon in the Romaka Siddhānta

Summary Formulae are fitted to the different sets of values, given by the translators, for the equation of centre for the motion of the moon according to the Romaka Siddhnta, as found in the Pañcasiddhntik of Varha Mihira.     

Polar transport of the plant hormone auxin – the role of PIN-FORMED (PIN) proteins

The PIN-FORMED (PIN) protein family is a group of plant transmembrane proteins with a predicted function as secondary transporters. PINs have been shown to play a rate-limiting role in the catalysis of efflux of the plant growth regulator auxin from cells, and their asymmetrical cellular localization determines the direction of cell-to-cell auxin flow. There is a functional redundancy of PINs and their biochemical activity is regulated at many levels. PINs constitute a flexible network underlying the directional auxin flux (polar auxin transport) which provides cells in any part of the plant body with particular positional and temporal information. Thus, the PIN network, together with downstream auxin signalling system(s), coordinates plant development. This review summarizes recent progress in the elucidation of the role of PIN proteins in polar auxin transport at the cellular level, with emphasis on their structure and evolution and regulation of their function. Received 28 December 2006; received after revision 16 February 2007; accepted 26 March 2007     

The secret of truffles: A steroidal pheromone?

Summary The steroid 5-androst-16-en-3-ol has a pronounced musk-like scent. It is a major constituent of the pheromone of the boar. It occurs also in axillary sweat of men but is devoid of androgenic activity. The presence of this steroid has been demonstrated in truffles (Tuber melanosporum) both by radioimmunoassay and by gas chromatography-mass spectrometry in quantities of 40–60 ng/g fresh material. This offers an explanation for the ability of pigs to detect truffles growing as deep as 1 m under ground.     

The problem of ‘conditioning’ the action of antiphlogistic corticoids by the thyroid gland

Zusammenfassung Experimentell wurde die Wirkung von Prednison und Hydrocortisonacetat auf die Entwicklung des Fremdk?rpergranuloms an intakten und an thyreoid- und parathyreoidektomierten Tieren untersucht. Nach beidseitiger Thyreoidektomie konnte keine Unterdrückung der entwicklungshemmenden Effekte der Corticoide festgestellt werden.