Über einen erblichen ß2-glykoprotein I-Mangel

Zusammenfassung Es wird über einen erblichen Mangel an ₂-Glykoprotein I berichtet. Dieses Protein, dessen Gehalt im Serum gesunder Blutspender nach quantitativen immunologischen Bestimmungen 20 mg/100 ml beträgt, fehlt bei 2 Mitgliedern der untersuchten Familien vollständig und ist im Serum von 5 weiteren Familienmitgliedern auf die Hälfte (7–11 mg/100 ml) verringert.

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Summary A congenital failure of ₂-glycoprotein is described. Whereas in the blood of normal donors 20 mg of this protein per 100 ml serum are proved by quantitative immunological methods, a total lack of ₂-glycoprotein was found with two members of the family in question and the serum of five others contains only half of the normal amount (7–11 mg per 100 ml).

     

Effects of insulin,glucagon and dexamethasone on pyruvate kinase in cultured hepatocytes

Long-term (24–48 h) and short-term (10–30 min) regulation by hormones of hepatic pyruvate kinase activity was investigated in adult rat hepatocytes cultured under serum-free conditions. In the absence of hormones, pyruvate kinase total activity decreased to 83%, 67% and 39% of the initial level at 24, 48 and 72 h of culture. Insulin (100 nM) maintained total activity significantly above control levels throughout this period. In contrast, glucagon (100 nM) and dexamethasone (100 nM) accelerated the gradual decrease within 24 h (glucagon) or 48 h (dexamethasone) of culture. In these long-term experiments, activity at non-saturating concentrations of phosphoenolpyruvate was decreased by glucagon and dexamethasone but not directly modulated by insulin. However, insulin increased the cellular content of the pyruvate kinase activator fructose-1,6-diphosphate. In short-term experiments on cells cultured under serum- and hormone-free conditions for 48 h, both glucagon and dexamethasone independently caused a rapid, dose-dependent increase of the K_0.5 for phosphoenolpyruvate within 10 min, while V_max was not affected. Insulin inhibited this action of glucagon and dexamethasone and, in their absence, significantly increased substrate affinity for phosphoenolpyruvate within 30 min. Cellular fructose-1,6-diphosphate contents remained unchanged under these conditions. The data identify glucocorticoids and insulin - in addition to glucagon - as short-term regulators of the catalytic properties of pyruvate kinase. All three hormones are effective in the long-term control of total enzyme activity.     

A Gelatin Fixative for Paraffin Sections

Mayer's albumen fixative, of which the active principle is white of egg, is used almost universally for affixing paraffin ribbons to the slide. About eight years ago the writer's attention was called to a gelatin fixative which has proved to be so superior to albumen that he has used it almost exclusively ever since in the making of a great variety of botanical preparations, and has recommended it to a number of other workers whose experience with it subsequently has been just as satisfactory. The gelatin method was first described by Szombathy¹ and later discussed by Artschwager,² but it does not seem to have received the attention in the literature which its importance deserves. It certainly merits a wide spread use among both botanists and zoologists.     

Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort

Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death overall in developed countries and is the second most frequent cause of cancer death in women. Early diagnosis increases 5-year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains attach, ubiquitous to the cell surface and within the extracellular matrix. HSPG side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interactions with cell-signalling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated a single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-O desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case–control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic levels (allele, p = 0.016; genotype, p = 0.032). Our results suggest that the rs2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with an increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.     

Spatial variability and temporal trends in water‐use efficiency of European forests

The increasing carbon dioxide (CO₂) concentration in the atmosphere in combination with climatic changes throughout the last century are likely to have had a profound effect on the physiology of trees: altering the carbon and water fluxes passing through the stomatal pores. However, the magnitude and spatial patterns of such changes in natural forests remain highly uncertain. Here, stable carbon isotope ratios from a network of 35 tree‐ring sites located across Europe are investigated to determine the intrinsic water‐use efficiency (iWUE), the ratio of photosynthesis to stomatal conductance from 1901 to 2000. The results were compared with simulations of a dynamic vegetation model (LPX‐Bern 1.0) that integrates numerous ecosystem and land–atmosphere exchange processes in a theoretical framework. The spatial pattern of tree‐ring derived iWUE of the investigated coniferous and deciduous species and the model results agreed significantly with a clear south‐to‐north gradient, as well as a general increase in iWUE over the 20th century. The magnitude of the iWUE increase was not spatially uniform, with the strongest increase observed and modelled for temperate forests in Central Europe, a region where summer soil‐water availability decreased over the last century. We were able to demonstrate that the combined effects of increasing CO₂ and climate change leading to soil drying have resulted in an accelerated increase in iWUE. These findings will help to reduce uncertainties in the land surface schemes of global climate models, where vegetation–climate feedbacks are currently still poorly constrained by observational data.     

Cryptic properties of a cluster of dominant flavivirus cross-reactive antigenic sites

A number of flaviviruses are important human pathogens, including yellow fever, dengue, West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE) viruses. Infection with or immunization against any of these viruses induces a subset of antibodies that are broadly flavivirus cross-reactive but do not exhibit significant cross-neutralization. Nevertheless, these antibodies can efficiently bind to the major envelope protein (E), which is the main target of neutralizing and protective antibodies because of its receptor-binding and membrane fusion functions. The structural basis for this phenomenon is still unclear. In our studies with TBE virus, we have provided evidence that such cross-reactive antibodies are specific for a cluster of epitopes that are partially occluded in the cage-like assembly of E proteins at the surfaces of infectious virions and involve-but are not restricted to-amino acids of the highly conserved internal fusion peptide loop. Virus disintegration leads to increased accessibility of these epitopes, allowing the cross-reactive antibodies to bind with strongly increased avidity. The cryptic properties of these sites in the context of infectious virions can thus provide an explanation for the observed lack of efficient neutralizing activity of broadly cross-reactive antibodies, despite their specificity for a functionally important structural element in the E protein.