Mylip makes an Idol turn into regulation of LDL receptor

High blood low-density-lipoprotein (LDL) cholesterol is a serious health problem among an increased number of patients in the Western world. Statins and other cholesterol lowering drugs have proven to be beneficial as therapy but are not optimal and show adverse effects in some patients. The LDL receptor is a crucial determinant of cholesterol metabolism in the body and amenable for drug interventions. Novel insights into the physiology of this receptor come from studies on the ubiquitination and degradation of LDL receptor by the ubiquitin ligase Mylip/Idol that is induced in cells by the nuclear receptor, LXR. This may open up new possibilities in the future to influence LDL receptor levels and cholesterol metabolism pharmacologically in various diseases.     

When and how to use scenario planning: A heuristic approach with illustration

This paper offers a step-by-step analysis of a heuristic approach to scenario planning, taking a managerial perspective. The scenario method is contrasted in general with more traditional planning techniques, which tend to perform less well when faced with high uncertainty and complexity. An actual case involving a manufacturing company is used to illustrate the main steps of the proposed heuristic. Its essence is to identify relevant trends and uncertainties, and blend them into scenarios that are internally consistent. In addition, the scenarios should bound the range of plausible uncertainties and challenge managerial thinking. Links to decision making are examined next, including administrative policies as well as integrative techniques. At the strategic level, a key-success-factor matrix is proposed for integrating scenarios, competitor analysis and strategic vision. At the operational level, Monte Carlo simulation is suggested and illustrated as one useful technique for combining scenario thinking with formal project evaluation (after appropriate translations). The paper concludes with a general discussion of scenario planning, to place it in a broader perspective.     

Putting a spin on circulating reference,or how to rediscover the scientific subject

Bruno Latour claims to have shown that a Kantian model of knowledge, which he describes as seeking to unite a disembodied transcendental subject with an inaccessible thing-in-itself, is dramatically falsified by empirical studies of science in action. Instead, Latour puts central emphasis on scientific practice, and replaces this Kantian model with a model of “circulating reference.” Unfortunately, Latour's alternative schematic leaves out the scientific subject. I repair this oversight through a simple mechanical procedure. By putting a slight spin on Latour's diagrammatic representation of his theory, I discover a new space for a post-Kantian scientific subject, a subject brilliantly described by Ludwik Fleck. The neglected subjectivities and ceaseless practices of science are thus re-united.     

Bimodal processing of olfactory information in an amphibian nose: odor responses segregate into a medial and a lateral stream

In contrast to the single sensory surface present in teleost fishes, several spatially segregated subsystems with distinct molecular and functional characteristics define the mammalian olfactory system. However, the evolutionary steps of that transition remain unknown. Here we analyzed the olfactory system of an early diverging tetrapod, the amphibian Xenopus laevis, and report for the first time the existence of two odor-processing streams, sharply segregated in the main olfactory bulb and partially segregated in the olfactory epithelium of pre-metamorphic larvae. A lateral odor-processing stream is formed by microvillous receptor neurons and is characterized by amino acid responses and Gα_o/Gα_i as probable signal transducers, whereas a medial stream formed by ciliated receptor neurons is characterized by responses to alcohols, aldehydes, and ketones, and Gα_olf/cAMP as probable signal transducers. To reveal candidates for the olfactory receptors underlying these two streams, the spatial distribution of 12 genes from four olfactory receptor gene families was determined. Several class II and some class I odorant receptors (ORs) mimic the spatial distribution observed for the medial stream, whereas a trace amine-associated receptor closely parallels the spatial pattern of the lateral odor-processing stream. Other olfactory receptors (some class I odorant receptors and vomeronasal type 1 receptors) and odor responses (to bile acids, amines) were not lateralized, the latter not even in the olfactory bulb, suggesting an incomplete segregation. Thus, the olfactory system of X. laevis exhibits an intermediate stage of segregation and as such appears well suited to investigate the molecular driving forces behind olfactory regionalization.     

William Thomson's dynamical theory: An insight into a scientist's thinking

William Thomson, later Lord Kelvin, played a major role in the nineteenth century in changing scientific theory from the statical view, associated with imponderables, to the dynamical view which conceived of energy as a separate and convertible entity. Thomson's conversion from the statical to the dynamical view of nature was due to the influence of experimentalists, Michael Faraday and James Prescott Joule. It was Thomson's use of mathematical metaphor that enabled him to interpret on a theoretical level the physical explanation given by Faraday and Joule.     

The flow of a solution into a tube filled with solvent: Mathematical derivations

Résumé On offre un ensemble d'équations qui s'appliquent à l'écoulement laminaire de deux solutions A et B, de même viscosité, lorsqu'on introduit B dans un tube préalablement rempli de solution A.     

Tubes,randomness, and Brownian motions: or,how engineers learned to start worrying about electronic noise

In this paper, we examine the pioneering research on electronic noise—the current fluctuations in electronic circuit devices due to their intrinsic physical characteristics rather than their defects—in Germany and the U.S. during the 1910s–1920s. Such research was not just another demonstration of the general randomness of the physical world Einstein’s work on Brownian motion had revealed. In contrast, we stress the importance of a particular engineering context to electronic noise studies: the motivation to design and improve high-gain thermionic-tube amplifiers for radio and wired communications. Engineering scientists’ endeavors to understand electronic noise started in 1918, when Walter Schottky at Siemens formulated a theory of “shot noise,” current fluctuations owing to the random emissions of discrete electrons in a tube. Schottky’s theory was revised and experimentally tested at Siemens, General Electric, and AT&T during the 1920s, leading to the discoveries of several other types of noise and an increasing interest in the thermal fluctuations in electronic circuits. In 1925–1928, J.B. Johnson and Harry Nyquist at Bell Labs developed a theory of thermal noise for any electrical resistor at a non-zero temperature. Although these studies were initiated to chart the fundamental performance limit of electronic technology, they ended up assisting the empirical determination of individual electronic components’ characteristics.     

Aristotle and Galen on sex difference and reproduction: a new approach to an ancient rivalry

[I]n contrast to Aristotle's male oriented explanation of procreation the Galenic was 'feminist' inasmuch as both sexes were presented as contributing equally in conception and accordingly both had to experience pleasure... Anatomically, the two sexes were presented in Galenic accounts as complementary, the difference being that the man's genitalia were on the outside and the woman's on the inside. The clitoris was likened to the penis and the ovaries considered 'testicles' or 'stones' that produced seed. The male seed was, it is true, depicted by Galenists as superior in having 'spiritual' qualities lacking in the female, but Galen's reproductive schema was far more egalitarian than Aristotle's. (McLaren, 1985, p. 327)     

Dps-like proteins: structural and functional insights into a versatile protein family

Dps-like proteins are key factors involved in the protection of prokaryotic cells from oxidative damage. They act by either oxidizing iron to prevent the formation of oxidative radicals or by forming Dps-DNA complexes to physically protect DNA. All Dps-like proteins are characterized by a common three-dimensional architecture and are found as spherical dodecamers with a hollow central cavity. Despite their structural similarities, recent biochemical and structural data have suggested different functions among members of the family that range from protection inside the cells in response to various stress signals to adhesion and virulence during bacterial infections. Moreover, the Dps-like proteins have lately attracted considerable interest in the field of nanotechnology owing to their ability to act as protein cages for iron and various other metals. A better understanding of their function and mechanism could therefore lead to novel applications in biotechnology and nanotechnology.     

Muscle development, regeneration and laminopathies: how lamins or lamina-associated proteins can contribute to muscle development, regeneration and disease

The aim of this review article is to evaluate the current knowledge on associations between muscle formation and regeneration and components of the nuclear lamina. Lamins and their partners have become particularly intriguing objects of scientific interest since it has been observed that mutations in genes coding for these proteins lead to a wide range of diseases called laminopathies. For over the last 10 years, various laboratories worldwide have tried to explain the pathogenesis of these rare disorders. Analyses of the distinct aspects of laminopathies resulted in formulation of different hypotheses regarding the mechanisms of the development of these diseases. In the light of recent discoveries, A-type lamins—the main building blocks of the nuclear lamina—together with other key elements, such as emerin, LAP2α and nesprins, seem to be of great importance in the modulation of various signaling pathways responsible for cellular differentiation and proliferation.     

Kinetics of transformation of aflatoxin B1 into aflatoxin M1 in lactating mouse: an ELISA analysis

A new enzyme-linked immunosorbent assay (ELISA) was used to study the kinetics of transformation of aflatoxin B1 into aflatoxin M1 in lactating mice. Aflatoxin M1 concentration in the milk samples reached a maximum 30 min after injection of aflatoxin B1 and decreased thereafter. At the maximum time, the levels of aflatoxin M1 in the samples were proportional to the dosages administered. Aflatoxin B1 was also detected in the milk samples but at a lower concentration.     

Enteropathogenic Escherichia coli: a pathogen that inserts its own receptor into host cells

Enteropathogenic Escherichia coli (EPEC) is a major cause of infant diarrhea, killing hundreds of thousands of children per year worldwide. Intimate attachment to the host cell leading to the formation of actin-rich pedestals beneath the adhering bacteria is an essential feature of EPEC pathogenesis. EPEC attaches to host cells via the outer membrane adhesin, intimin. It was recently shown that EPEC inserts its own receptor for intimate adherence, Tir (translocated intimin receptor) into the host cell membrane. The focus of this review is on the discovery and characterization of this novel receptor, and our current understanding of its role in pedestal formation. Gram-negative bacterial secretion systems, including type III secretion systems, are reviewed and discussed in the context of Tir delivery into the host cell membrane. The relationship and relevance of in vitro models compared to the actual in vivo situation is essential to understanding disease. We have critically reviewed the use of animal models in studying EPEC infection. Elucidating the function of Tir will contribute to our understanding of how EPEC mediates disease.     

Antioxidant survey to assess antagonism to redox stress using a prokaryotic and an eukaryotic system

Using a prokaryote (Escherichia coli) and a metazoa-resembling eukaryote (Ochromonas danica), we surveyed antioxidants which might overcome redox stress imposed by menadione sodium bisulphite (MD) and buthionine sulphoximine (BSO). BSO oxidant stress was evident only inO. danica; MD oxidant stress was evident in both organisms. Glutathione, its precursors, e.g. cysteine, homocysteine, and 2-oxo-4-thiazolidine carboxylic acid, and red blood cells, emerged as prime antioxidants for relieving BSO and MD oxidant stress. BSO and MD oxidant activity and antioxidant-annulling effect inO. danica were judged comparable to those found in animal cells whereas the resultsE. coli were not entirely equivalent. TheO. danica system emerged as a practical, rapid, and useful system for pinpointing oxidant stressors and antioxidants, and shows promise for studies with mammalian systems.     

The total synthesis of delphinine: Resolution of the racemic relay compound into optical antipodes by an asymmetric reaction

Zusammenfassung Das totalsynthetische Razematdl 1a gab bei Reaktion mitl-Camphorsulfonylchlorid das Sulfonamid 2 und die optisch-aktive Base 1b. Die Identität dieser totalsynthetischen, optisch aktiven Base 1b mit dem entsprechenden Abbauprodukt von Delfinin wurde bewiesen.