Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion

Release of neurotransmitter occurs when synaptic vesicles fuse with the plasma membrane. This neuronal exocytosis is triggered by calcium and requires three SNARE (soluble-N-ethylmaleimide-sensitive factor attachment protein receptors) proteins: synaptobrevin (also known as VAMP) on the synaptic vesicle, and syntaxin and SNAP-25 on the plasma membrane. Neuronal SNARE proteins form a parallel four-helix bundle that is thought to drive the fusion of opposing membranes. As formation of this SNARE complex in solution does not require calcium, it is not clear what function calcium has in triggering SNARE-mediated membrane fusion. We now demonstrate that whereas syntaxin and SNAP-25 in target membranes are freely available for SNARE complex formation, availability of synaptobrevin on synaptic vesicles is very limited. Calcium at micromolar concentrations triggers SNARE complex formation and fusion between synaptic vesicles and reconstituted target membranes. Although calcium does promote interaction of SNARE proteins between opposing membranes, it does not act by releasing synaptobrevin from synaptic vesicle restriction. Rather, our data suggest a mechanism in which calcium-triggered membrane apposition enables syntaxin and SNAP-25 to engage synaptobrevin, leading to membrane fusion.     

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.     

Dietary overlap in giant salamanders (Dicamptodon): applying null models to resource partitioning

We examined stomach contents of preserved specimens of larval Pacific giant salamander ( Dicamptodon tenebrosus ) and Cope's giant salamander ( D. copei ) collected from sympatric and allopatric stream populations. The dietary components of these specimens were used to calculate dietary overlap between the 2 species and to determine if changes in overlap existed between sympatric and allopatric populations. To statistically test overlap values, a randomization algorithm was used to construct a simulated data matrix (i.e., null model) in order to compare observed values of dietary overlap to a distribution of overlap values from the null model. Significant levels ( P < 0.05) of dietary overlap occurred in all cases of sympatry as well as allopatry. Average dietary overlap in sympatry was significantly lower than in allopatry, suggesting a dietary shift when in sympatry to reduce competition. Diet composition also differed between sympatric and allopatric populations of each species, further suggesting a partitioning of food resources by one or both species when in the presence of its congener.     

Population structure, differential bias and genomic control in a large-scale, case-control association study

The main problems in drawing causal inferences from epidemiological case-control studies are confounding by unmeasured extraneous factors, selection bias and differential misclassification of exposure. In genetics the first of these, in the form of population structure, has dominated recent debate. Population structure explained part of the significant +11.2% inflation of test statistics we observed in an analysis of 6,322 nonsynonymous SNPs in 816 cases of type 1 diabetes and 877 population-based controls from Great Britain. The remainder of the inflation resulted from differential bias in genotype scoring between case and control DNA samples, which originated from two laboratories, causing false-positive associations. To avoid excluding SNPs and losing valuable information, we extended the genomic control method by applying a variable downweighting to each SNP.     

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.     

加拿大不列颠哥伦比亚东北部伊维湖地区几维特阶斯雷夫波音特组的层孔虫

本文描述采自泥盆系几维特阶斯雷夫波音特组石灰岩的层孔虫9属11种,标本为石油天然气钻孔的礁相岩心。石灰岩多为砾状灰岩及粒泥状灰岩,被沥青质充填,微细构造保存完好。层孔虫以穹状及枝状为主。本动物群中的Trupetostroma warreni,Stachyodes thomasclarki,S.spongiosa以及Actinostroma cf.clathratum均与天鹅山生物确相同,而以出现Actinostroma whiteavesii及Pseudotrupetostroma vitreum为明显特征。后一种以及Taleastroma logansportense种一块保存完好的标本,说明此动物群与波兰及美国俄亥俄山谷地区的几维特期动物群的关系密切。     

Structural and functional conservation of key domains in InsP3 and ryanodine receptors

Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca(2+) channels. In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6??) and without (3.0??) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-β and IBC-α, identifies two discrete interfaces (α and β) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R and of the ABC domains docked into RyR are remarkably similar. The importance of the α-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations. Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the β-interface and pulling the SD towards the IBC. This reorients an exposed SD loop ('hotspot' (HS) loop) that is essential for InsP(3)R activation. The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease. The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-β or B domain), to gate the pore.     

KATP channels as molecular sensors of cellular metabolism

In responding to cytoplasmic nucleotide levels, ATP-sensitive potassium (K(ATP)) channel activity provides a unique link between cellular energetics and electrical excitability. Over the past ten years, a steady drumbeat of crystallographic and electrophysiological studies has led to detailed structural and kinetic models that define the molecular basis of channel activity. In parallel, the uncovering of disease-causing mutations of K(ATP) has led to an explanation of the molecular basis of disease and, in turn, to a better understanding of the structural basis of channel function.