Functional diversification of closely related ARF-GEFs in protein secretion and recycling

Guanine-nucleotide exchange factors on ADP-ribosylation factor GTPases (ARF-GEFs) regulate vesicle formation in time and space by activating ARF substrates on distinct donor membranes. Mammalian GBF1 (ref. 2) and yeast Gea1/2 (ref. 3) ARF-GEFs act at Golgi membranes, regulating COPI-coated vesicle formation. In contrast, their Arabidopsis thaliana homologue GNOM (GN) is required for endosomal recycling, playing an important part in development. This difference indicates an evolutionary divergence of trafficking pathways between animals and plants, and raised the question of how endoplasmic reticulum-Golgi transport is regulated in plants. Here we demonstrate that the closest homologue of GNOM in Arabidopsis, GNOM-LIKE1 (GNL1; NM_123312; At5g39500), performs this ancestral function. GNL1 localizes to and acts primarily at Golgi stacks, regulating COPI-coated vesicle formation. Surprisingly, GNOM can functionally substitute for GNL1, but not vice versa. Our results suggest that large ARF-GEFs of the GBF1 class perform a conserved role in endoplasmic reticulum-Golgi trafficking and secretion, which is done by GNL1 and GNOM in Arabidopsis, whereas GNOM has evolved to perform an additional plant-specific function of recycling from endosomes to the plasma membrane. Duplication and diversification of ARF-GEFs in plants contrasts with the evolution of entirely new classes of ARF-GEFs for endosomal trafficking in animals, which illustrates the independent evolution of complex endosomal pathways in the two kingdoms.     

Inside the Kunstkammer: the circulation of optical knowledge and instruments at the Dresden Court

The Kunstkammer of the Electors of Saxony, founded in Dresden around 1560, housed one of the richest collections of tools and scientific instruments in its day. A close analysis of the optical objects in the collection in the decades around 1600 is undertaken here—in particular, their arrangement by a mathematically trained curator, Lucas Brunn, and their use in an ‘experiment’ by a distinguished visitor, Johannes Kepler. It is argued that the selection, display and use of optical objects within this collection reflect a specific, playful image of optics promoted at the Saxon court.     

Ein für Massenspektrometrie und Gaschromatographie geeignetes Argininderivat

Summary Arginine has been converted into a suitable pyrimidine derivative to permit its qualitative analysis in the presence of other amino acids by means of mass spectrometric and gas-chromatographic techniques.     

Linkage disequilibrium in the human genome

With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting 'haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1-3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000-53,000 years ago.     

Loss and recovery of wings in stick insects

The evolution of wings was the central adaptation allowing insects to escape predators, exploit scattered resources, and disperse into new niches, resulting in radiations into vast numbers of species. Despite the presumed evolutionary advantages associated with full-sized wings (macroptery), nearly all pterygote (winged) orders have many partially winged (brachypterous) or wingless (apterous) lineages, and some entire orders are secondarily wingless (for example, fleas, lice, grylloblattids and mantophasmatids), with about 5% of extant pterygote species being flightless. Thousands of independent transitions from a winged form to winglessness have occurred during the course of insect evolution; however, an evolutionary reversal from a flightless to a volant form has never been demonstrated clearly for any pterygote lineage. Such a reversal is considered highly unlikely because complex interactions between nerves, muscles, sclerites and wing foils are required to accommodate flight. Here we show that stick insects (order Phasmatodea) diversified as wingless insects and that wings were derived secondarily, perhaps on many occasions. These results suggest that wing developmental pathways are conserved in wingless phasmids, and that 're-evolution' of wings has had an unrecognized role in insect diversification.     

Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin

We have identified nonsense mutations in the gene CDSN (encoding corneodesmosin) in three families suffering from hypotrichosis simplex of the scalp (HSS; OMIM 146520). CDSN, a glycoprotein expressed in the epidermis and inner root sheath (IRS) of hair follicles, is a keratinocyte adhesion molecule. Truncated CDSN aggregates were detected in the superficial dermis and at the periphery of hair follicles. Our findings suggest that CDSN is important in normal scalp hair physiology.     

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.     

Die Sinneswelt der Fledermäuse

Ohne Zusammenfassung