Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations

Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.     

Estimating the young evolutionary age of marbled crayfish from museum samples

ABSTRACT

The obligately parthenogenetic, all-female marbled crayfish, Procambarus virginalis, is a triploid descendant of the similarly looking, sexually reproducing slough crayfish, Procambarus fallax, native to Florida and southern Georgia. We have earlier hypothesised that marbled crayfish may have originated from P. fallax only some 25 years ago, perhaps in captivity. In order to investigate the young evolutionary age hypothesis in more detail, I searched the P. fallax collection of the Smithsonian Institution Museum of Natural History (USNM, Washington, D.C.) for evidence of marbled crayfish before its detection in the German aquarium trade in 1995. In particular, I analysed the sex ratio of P. fallax and the frequency of pure female samples throughout its entire distribution range to detect potentially misidentified marbled crayfish among the P. fallax. If marbled crayfish had originated from P. fallax long ago, spread throughout Florida and Georgia and erroneously been sampled as P. fallax, then the sex ratio of the P. fallax in the collection should be significantly biased towards females and pure female samples should be much more frequent than in related Procambarus species. Comparison of P. fallax (n = 2299) with its closest relatives P. seminolae (n = 801) and P. leonensis (n = 150) revealed female proportions of 55.33%, 53.93% and 54.67%, respectively, which are not significantly different from each other. The average female proportion of the 14 Procambarus species investigated (8641 specimens) was 52.54 ± 7.54% (mean ± standard deviation). Moreover, pure female samples consisting of more than 3 specimens that could represent hidden marbled crayfish were not conspicuously more common in P. fallax (2.33%) than in all Procambarus species investigated (1.24 ± 1.79%). These data suggest that the P. fallax collection of the USNM consists of real, sexually reproducing P. fallax and does most likely not include hidden marbled crayfish, supporting the young evolutionary age hypothesis for marbled crayfish.     

Development of Oxide Ceramics for Application in Solid Oxide Fuel Cells

1 Results Solid oxide fuel cells (SOFC) are ceramic fuel cells that convert chemical into electrical energy in a temperature region between 650 ℃ and 1 000 ℃.Systems are currently under development for a variety of applications e.g. for both small and large scale stationary combined heat and power systems but also for the supply of electrical energy in the automotive area. The current objectives in the development of SOFCs is to lower the operating temperature from 850 ℃ down to below 750 ℃ in order to ...     

Pheromone binding and inactivation by moth antennae

The antennae of male silk moths are extremely sensitive to the female sex pheromone such that a male moth can find a female up to 4.5 km away. This remarkable sensitivity is due to both the morphological and biochemical design of these antennae. Along the branches of the plumose antennae are the sensilla trichodea, each consisting of a hollow cuticular hair containing two unbranched dendrites bathed in a fluid, the receptor lymph ,3. The dendrites and receptor lymph are isolated from the haemolymph by a barrier of epidermal cells which secreted the cuticular hair. Pheromone molecules are thought to diffuse down 100 A-wide pore tubules through the cuticular wall and across the receptor lymph space to receptors located in the dendritic membrane. To prevent the accumulation of residual stimulant and hence sensory adaptation, the pheromone molecules are subsequently inactivated in an apparent two-step process of rapid 'early inactivation' followed by much slower enzymatic degradation. The biochemistry involved in this sequence of events is largely unknown. We report here the identification of three proteins which interact with the pheromone of the wild silk moth Antheraea polyphemus: a pheromone-binding protein and a pheromone-degrading esterase, both uniquely located in the pheromone-sensitive sensilla; and a second esterase common to all cuticular tissues except the sensilla.     

Lymphocytopenic reaction after glucose administration in thymectomized rats

Zusammenfassung Die Lymphocytopenie nach Glukoseinjektion wurde bei thymektomierten Ratten untersucht. Ein Unterschied gegenüber normalen Tieren wurde hierbei nicht gefunden.     

Abtrennung des anaphylatoxinbildenden Prinzips aus Cobragift von anderen Giftkomponenten

Summary Cobra venom contains an anaphylatoxin-forming principle. This component has been purified by gel filtration and ion exchange chromatography. It has been obtained free from proteolytic or hemolytic activity as well as from phospholipase A. It seems to be an enzyme that splits the anaphylatoxin from its inactive precursor.