Identification of collagen-induced arthritis loci in aged multiparous female mice

Collagen-induced arthritis in mice is one of the most commonly used autoimmune experimental models, with many similarities to rheumatoid arthritis. Since collagen-induced arthritis is a complex polygenic disease there is a need for identification of several major disease-controlling genes. Because rheumatoid arthritis particularly affects aged women, we have in the present study identified new genetic regions critical for collagen-induced arthritis by studying aged female mice of a cross between NFR/N and B10.Q (H-2^q haplotype). The mice in the present study had different reproductive histories, which did not significantly affect the onset, incidence or severity of the disease. A total of 200 female mice were used in a total genome-wide screening with 125 microsatellite markers. We found one new significant quantitative trait locus affecting the arthritis incidence, severity and day of onset on chromosome 11 (denoted Cia40), which colocalizes with a locus controlling pregnancy failure. Furthermore, a quantitative trait locus of suggestive significance associated with the incidence, severity and day of onset was identified on chromosome 1. Finally, a suggestively significant quantitative trait locus associated with collagen type II antibody titers was identified on chromosome 13. This study indicates that several gene loci control arthritis in aged multiparous females, and that at least one of these loci coincides with pregnancy failure.     

Effects after inhalation of (1-->3)-beta-D-glucan and relation to mould exposure in the home

BACKGROUND: Damp conditions indoors favour the growth of microorganisms, and these contain several agents that may cause inflammation when inhaled. Moulds contain a polyglucose in their cell wall, defined as (1-->3)-beta-D-glucan, exhibiting effects on inflammatory cells. AIM: The aim of the present study was to evaluate whether an inhalation challenge to purified (1-->3)-beta-D-glucan (grifolan) in humans could induce effects on inflammatory markers in blood, and to evaluate whether the reactions were related to the home exposure to (1-->3)-beta-D-glucan. METHODS: Seventeen subjects in homes with high levels of airborne (1-->3)-beta-D-glucan (G-high) and 18 subjects in homes with low levels of (1-->3)-beta-D-glucan (G-low) underwent two randomised, double-blind inhalation challenges, one to (1-->3)-beta-D-glucan suspended in saline and one to saline alone. A blood sample was taken before and after the challenges, and differential cell count, granulocyte enzymes in serum and the secretion of cytokines from peripheral blood mononuclear cells (PBMC) were measured. RESULTS: Inhalation challenge with (1-->3)-beta-D-glucan induced a decrease in the secretion of tumour necrosis factor alpha from endotoxin-stimulated PBMC in the G-high group as well as in the G-low group. In the G-high group, the inhalation of (1-->3)-beta-D-glucan induced an increase in blood lymphocytes that was significantly different from the saline-induced effect. CONCLUSIONS: The results suggest that an inhalation challenge to (1-->3)-beta-D-glucan has an effect on inflammatory cells and this effect may be related to a chronic exposure to moulds at home.     

Carbon monoxide stimulates insulin release and propagates Ca2+ signals between pancreatic beta-cells

A key question for understanding the mechanisms of pulsatile insulin release is how the underlying beta-cell oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i) are synchronized within and among the islets in the pancreas. Nitric oxide has been proposed to coordinate the activity of the beta-cells by precipitating transients of [Ca2+]i. Comparing ob/ob mice and lean controls, we have now studied the action of carbon monoxide (CO), another neurotransmitter with stimulatory effects on cGMP production. A strong immunoreactivity for the CO-producing constitutive heme oxygenase (HO-2) was found in ganglionic cells located in the periphery of the islets and in almost all islet endocrine cells. Islets from ob/ob mice had sixfold higher generation of CO (1 nmol.min-1.mg protein-1) than the lean controls. This is 100-fold the rate for their constitutive production of NO. Moreover, islets from ob/ob mice showed a threefold increase in HO-2 expression and expressed inducible HO (HO-1). The presence of an excessive islet production of CO in the ob/ob mouse had its counterpart in a pronounced suppression of the glucose-stimulated insulin release from islets exposed to the HO inhibitor Zn-protoporhyrin (10 microM) and in a 16 times higher frequency of [Ca2+]i transients in their beta-cells. Hemin (0.1 and 1.0 microM), the natural substrate for HO, promoted the appearance of [Ca2+]i transients, and 10 microM of the HO inhibitors Zn-protoporphyrin and Cr-mesoporphyrin had a suppressive action both on the firing of transients and their synchronization. It is concluded that the increased islet production of CO contributes to the hyperinsulinemia in ob/ob mice. In addition to serving as a positive modulator of glucose-stimulated insulin release, CO acts as a messenger propagating Ca2+ signals with coordinating effects on the beta-cell rhythmicity.     

The nature and perception of fluctuations in human musical rhythms

Although human musical performances represent one of the most valuable achievements of mankind, the best musicians perform imperfectly. Musical rhythms are not entirely accurate and thus inevitably deviate from the ideal beat pattern. Nevertheless, computer generated perfect beat patterns are frequently devalued by listeners due to a perceived lack of human touch. Professional audio editing software therefore offers a humanizing feature which artificially generates rhythmic fluctuations. However, the built-in humanizing units are essentially random number generators producing only simple uncorrelated fluctuations. Here, for the first time, we establish long-range fluctuations as an inevitable natural companion of both simple and complex human rhythmic performances. Moreover, we demonstrate that listeners strongly prefer long-range correlated fluctuations in musical rhythms. Thus, the favorable fluctuation type for humanizing interbeat intervals coincides with the one generically inherent in human musical performances.     

The Thymic Microenvironment of the Common Sole,Solea solea

Abstract The thymus of the sole Solea solea contained lymphoblasts and thymocytes within a network of pale and dark epithelial cells. The pale cells were characterized by tonofilaments and desmosomes and some embraced rodlet cells within their cytoplasmic processes. The dark epithelial cells had numerous electron-dense inclusions and electron-lucent vacuoles. Lymphocytes were closely associated with the plasma membrane of both types of epithelial cells and with macrophages. Breakdown of effete lymphocytes appeared to be the main function of the macrophages. Some macrophages were multinucleated. Those containing melanin granules associated with phagosomes were classified as melanomacrophages. Pigment cells including melanophores and guanophores were present along the connective tissue trabeculae and surrounding the blood vessels. A few plasma cells and mucous cells were present.     

Über den Gärungsmechanismus in der lebenden Hefezelle

Ohne Zusammenfassung     

The praeoptico-hypophysial system,Nucleus tuberis lateralis and the subcommissural organ of Gasterosteus aculeatus after changes in osmotic stimuli

Summary The histology and cytology of the praeoptico-hypophysial system, nucleus tuberis lateralis and subcommissural organ in Gasterosteus aculeatus were analyzed after the fishes had been put in waters of different salinity (see Tables 1–4).These three structures are all identical in fishes which are accustomed to fresh water and to 32 salt-water. A transference to hypertonic water causes changes in the neurosecretory system which suggest the existence of an antidiuretic principle in the neurosecretory substance. No such relationship is found when the fishes are put into hypotonic water. Further, no connection is found between either the secretion production in nucleus tuberis lateralis or in the subcommissural organ and variations in osmotic value.Aided by grants from the Swedish Natural Science Research Council.     

The distribution of the serin ( Serinus serinus L., 1766) in the 16th century

All the sources of records of the serin (Serinus serinus) in 16th century Europe are (re-)examined, both those already known and some that have been newly discovered. Interpretation of this more detailed information confirms the results which were published by Ernst Mayr in 1926 in his doctoral thesis: north of 48°N there were no free-living populations of Serinus serinus in the 16th century. All 11 localities identified refer to captive birds or to specimens in the bird trade, the origins of which can be convincingly traced. However, free-living populations are recorded from Carinthia (Austria), Trentino (Italy), Ticino (Switzerland), Provence and Gascony (France). An occurrence in the Swiss Jura (Bötzberg), and indications that it was present throughout the whole Tyrol and the Rhône Valley, suggest that the serin had already begun to expand its range, but was halted by colder periods of the Little Ice Age after 1585, only resuming a rapid expansion at the beginning of the 19th century. The zoogeographic situation suggests that the western and eastern parts of the Central European population have a separate history of immigration. Their possible heterogeneity and subsequent fusion urgently require a genetic investigation.Communicated by F. Bairlein