Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome

Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.     

Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence

The number of genes in the human genome is unknown, with estimates ranging from 50,000 to 90,000 (refs 1, 2), and to more than 140,000 according to unpublished sources. We have developed 'Exofish', a procedure based on homology searches, to identify human genes quickly and reliably. This method relies on the sequence of another vertebrate, the pufferfish Tetraodon nigroviridis, to detect conserved sequences with a very low background. Similar to Fugu rubripes, a marine pufferfish proposed by Brenner et al. as a model for genomic studies, T. nigroviridis is a more practical alternative with a genome also eight times more compact than that of human. Many comparisons have been made between F. rubripes and human DNA that demonstrate the potential of comparative genomics using the pufferfish genome. Application of Exofish to the December version of the working draft sequence of the human genome and to Unigene showed that the human genome contains 28,000-34,000 genes, and that Unigene contains less than 40% of the protein-coding fraction of the human genome.     

Clay minerals in surface sediments of the Pearl River drainage basin and their contribution to the South China Sea

Clay minerals have played a significant role in the study of the East Asian monsoon evolution in the South China Sea by being able to track oceanic current variations and to reveal contemporaneous paleoclimaUc changes prevailing in continental source areas. As one of the most important rivers inputting terrigenous matters to the northern South China Sea, the Pearl River was not previously paid attention to from the viewpoint of clay mineralogy. This paper presents a detailed study on clay minerals in surface sediments collected from the Pearl River drainage basin （including all three main channels, various branches, and the Lingdingyang in the estuary） by using the X-ray diffraction （XRD） method. The results indicate that the clay mineral assemblage consists dominantly of kaolinite （35%-65%）, lesser abundance of chlorite （20%-35%） and illite （12%-42%）, and very scare smectite occurrences （generally 〈5%）. Their respective distribution does not present any obvious difference throughout the Pearl River drainage basin. However, downstream the Pearl River to the northern South China Sea, the clay mineral assemblage varies significantly： kaolinite decreases gradually, smecUte and illite increase gradually. Additionally, illite chemistry index steps down and illite crystallinity steps up. These variations indicate the contribution of major kaolinite, lesser illite and chlorite, and very scarce smecUte to the northern South China Sea from the Pearl River drainage basin. The maximum contribution of clay minerals from the Pearl River is 72% to the northern margin and only 15% to the northern slope of the South China Sea. In both glacials and interglacials, kaolinite indicates that the ability of mechanical erosion occurred in the Pearl River drainage basin.     

Multilevel Innovation in Remote Networked Schools

Small remote rural schools in Quebec face an ongoing challenge to provide similar quality educational services than bigger schools. Since 2002, the Remote Network Schools (RNS) initiative afforded schools the opportunity to reinvent their practice by using online tools to experience collaborative learning activities with other remote schools. Teachers and students experienced quality learning and demonstrated agency by implementing the RNS in their context. Measures include: diversity of learning activities, quality of online classroom interactions, changes in teacher beliefs, and shifts in teacher and student roles. Our results show that it is a viable operating method for such schools and that other schools could contemplate implementing such innovative practices.     

200 Jahre Naturforschende Gesellschaft in Zürich

Ohne Zusammenfassung     

L'isolement de l'α-amylase de pancréas

Summary The -amylase of hog pancreas has been purified and the degree of purity controled by electrophoresis. The active substance is a protein which can dissociate in an unstable high molecular component and a thermostable component of low molecular weight.