Periodic acid as a new oxidant for the degradation of bile pigments. Isolation of a biliverdine type of reaction intermediate on oxidation of bilirubin with periodic acid

Zusammenfassung Die Oxydation des Gallenfarbstoffs Bilirubin mit Perjodsäure in wässeriger Dimethylsulfoxid-Lösung führte zu einem neuen Biliverdin-Jod-Komplex, dem die Struktur eines «charge-transfer»-Komplexes erteilt wurde.

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The authors are most pleased to acknowledge the partial support of this work by the National Institute for General Medical Sciences (NIH).

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Part VIII of the Series: Periodic Acid, a Novel Oxidant. For some previous parts, see ref.².     

ATP-sensitive potassium channels mediate survival during infection in mammals and insects

Specific homeostatic mechanisms confer stability in innate immune responses, preventing injury or death from infection. Here we identify, from a screen of N-ethyl-N-nitrosourea-mutagenized mice, a mutation causing both profound susceptibility to infection by mouse cytomegalovirus and approximately 20,000-fold sensitization to lipopolysaccharide (LPS), poly(I.C) and immunostimulatory (CpG) DNA. The LPS hypersensitivity phenotype is not suppressed by mutations in Myd88, Trif, Tnf, Tnfrsf1a, Ifnb, Ifng or Stat1, genes contributing to LPS responses, and results from an abnormality extrinsic to hematopoietic cells. The phenotype is due to a null allele of Kcnj8, encoding Kir6.1, a protein that combines with SUR2 to form an ATP-sensitive potassium channel (K(ATP)) expressed in coronary artery smooth muscle and endothelial cells. In Drosophila melanogaster, suppression of dSUR by RNA interference similarly causes hypersensitivity to infection by flock house virus. Thus, K(ATP) evolved to serve a homeostatic function during infection, and in mammals it prevents coronary artery vasoconstriction induced by cytokines dependent on TLR and/or MDA5 immunoreceptors.     

Electrically induced structure formation and pattern transfer

The wavelength of light represents a fundamental technological barrier to the production of increasingly smaller features on integrated circuits. New technologies that allow the replication of patterns on scales less than 100 nm need to be developed if increases in computing power are to continue at the present rate. Here we report a simple electrostatic technique that creates and replicates lateral structures in polymer films on a submicrometre length scale. Our method is based on the fact that dielectric media experience a force in an electric field gradient. Strong field gradients can produce forces that overcome the surface tension in thin liquid films, inducing an instability that features a characteristic hexagonal order. In our experiments, pattern formation takes place in polymer films at elevated temperatures, and is fixed by cooling the sample to room temperature. The application of a laterally varying electric field causes the instability to be focused in the direction of the highest electric field. This results in the replication of a topographically structured electrode. We report patterns with lateral dimensions of 140 nm, but the extension of the technique to pattern replication on scales smaller than 100 nm seems feasible.     

Swedenborg's Lunars

The celebrated Swedish natural philosopher and visionary theologian Emanuel Swedenborg (1688–1772) devoted major efforts to the establishment of a reliable method for the determination of longitude at sea. He first formulated a method, based on the astronomical observation of lunar position, while in London in 1710–12. He issued various versions of the method, both in Latin and in Swedish, throughout his career. In 1766, at the age of 78, he presented his scheme for judgment by the Board of Longitude in London. The rich archive of Swedenborg's career allows an unusually detailed historical analysis of his longitude project, an analysis rather better documented than that available for the host of contemporary projectors who launched longitude schemes, submitted their proposals to the Board of Longitude, and have too often been ignored or dismissed by historians. This analysis uses the longitude work to illuminate key aspects of Swedenborg's wider enterprises, including his scheme to set up an astronomical observatory in southern Sweden to be devoted to lunar and stellar observation, his complex attitude to astronomical and magnetic cosmology, and his attempt to fit the notion of longitude into his visionary world-view. Swedenborg's programme also helps make better sense of the metropolitan and international networks of diplomatic and natural philosophical communication in which the longitude schemes were developed and judged. It emerges that his longitude method owed much to the established principles of earlier Baroque and Jesuit natural philosophy while his mature cosmology sought a rational and enlightened model of the universe.     

FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation

X-linked mental retardation (XLMR) is an inherited condition that causes failure to develop cognitive abilities, owing to mutations in a gene on the X chromosome. The latest XLMR update lists up to 136 conditions leading to 'syndromic', or 'specific', mental retardation (MRXS) and 66 entries leading to 'nonspecific' mental retardation (MRX). For 9 of the 66 MRX entries, the causative gene has been identified. Our recent discovery of the contiguous gene deletion syndrome ATS-MR (previously known as Alport syndrome, mental retardation, midface hypoplasia, elliptocytosis, OMIM #300194), characterized by Alport syndrome (ATS) and mental retardation (MR), indicated Xq22.3 as a region containing one mental retardation gene. Comparing the extent of deletion between individuals with ATS-MR and individuals with ATS alone allowed us to define a critical region for mental retardation of approximately 380 kb, containing four genes. Here we report the identification of two point mutations, one missense and one splice-site change, in the gene FACL4 in two families with nonspecific mental retardation. Analysis of enzymatic activity in lymphoblastoid cell lines from affected individuals of both families revealed low levels compared with normal cells, indicating that both mutations are null mutations. All carrier females with either point mutations or genomic deletions in FACL4 showed a completely skewed X-inactivation, suggesting that the gene influences survival advantage. FACL4 is the first gene shown to be involved in nonspecific mental retardation and fatty-acid metabolism.