Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene

Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis in which oculocutaneous albinism, bleeding and pulmonary fibrosis result from defects of melanosomes, platelet dense granules and lysosomes. HPS is common in Puerto Rico, where it is caused by mutations in the genes HPS1 and, less often, HPS3 (ref. 8). In contrast, only half of non-Puerto Rican individuals with HPS have mutations in HPS1 (ref. 9), and very few in HPS3 (ref. 10). In the mouse, more than 15 loci manifest mutant phenotypes similar to human HPS, including pale ear (ep), the mouse homolog of HPS1 (refs 13,14). Mouse ep has a phenotype identical to another mutant, light ear (le), which suggests that the human homolog of le is a possible human HPS locus. We have identified and found mutations of the human le homolog, HPS4, in a number of non-Puerto Rican individuals with HPS, establishing HPS4 as an important HPS locus in humans. In addition to their identical phenotypes, le and ep mutant mice have identical abnormalities of melanosomes, and in transfected melanoma cells the HPS4 and HPS1 proteins partially co-localize in vesicles of the cell body. In addition, the HPS1 protein is absent in tissues of le mutant mice. These results suggest that the HPS4 and HPS1 proteins may function in the same pathway of organelle biogenesis.     

Catalase activity among leptospires

Summary Catalase activity was measured by a quantitative method as an additional screening for discriminating between saprophytic and pathogenic leptospires. Results indicate that water-leptospires have little or no catalase activity.     

Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication

Human subtelomeres are polymorphic patchworks of interchromosomal segmental duplications at the ends of chromosomes. Here we provide evidence that these patchworks arose recently through repeated translocations between chromosome ends. We assess the relative contribution of the principal mechanisms of ectopic DNA repair to the formation of subtelomeric duplications and find that non-homologous end-joining predominates. Once subtelomeric duplications arise, they are prone to homology-based sequence transfers as shown by the incongruent phylogenetic relationships of neighbouring sections. Interchromosomal recombination of subtelomeres is a potent force for recent change. Cytogenetic and sequence analyses reveal that pieces of the subtelomeric patchwork have changed location and copy number with unprecedented frequency during primate evolution. Half of the known subtelomeric sequence has formed recently, through human-specific sequence transfers and duplications. Subtelomeric dynamics result in a gene duplication rate significantly higher than the genome average and could have both advantageous and pathological consequences in human biology. More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements.     

Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography

Unconventional myosin V (myoV) is an actin-based molecular motor that has a key function in organelle and mRNA transport, as well as in membrane trafficking. MyoV was the first member of the myosin superfamily shown to be processive, meaning that a single motor protein can 'walk' hand-over-hand along an actin filament for many steps before detaching. Full-length myoV has a low actin-activated MgATPase activity at low [Ca2+], whereas expressed constructs lacking the cargo-binding domain have a high activity regardless of [Ca2+] (refs 5-7). Hydrodynamic data and electron micrographs indicate that the active state is extended, whereas the inactive state is compact. Here we show the first three-dimensional structure of the myoV inactive state. Each myoV molecule consists of two heads that contain an amino-terminal motor domain followed by a lever arm that binds six calmodulins. The heads are followed by a coiled-coil dimerization domain (S2) and a carboxy-terminal globular cargo-binding domain. In the inactive structure, bending of myoV at the head-S2 junction places the cargo-binding domain near the motor domain's ATP-binding pocket, indicating that ATPase inhibition might occur through decreased rates of nucleotide exchange. The actin-binding interfaces are unobstructed, and the lever arm is oriented in a position typical of strong actin-binding states. This structure indicates that motor recycling after cargo delivery might occur through transport on actively treadmilling actin filaments rather than by diffusion.     

Ultrathin compound semiconductor on insulator layers for high-performance nanoscale transistors

Over the past several years, the inherent scaling limitations of silicon (Si) electron devices have fuelled the exploration of alternative semiconductors, with high carrier mobility, to further enhance device performance. In particular, compound semiconductors heterogeneously integrated on Si substrates have been actively studied: such devices combine the high mobility of III-V semiconductors and the well established, low-cost processing of Si technology. This integration, however, presents significant challenges. Conventionally, heteroepitaxial growth of complex multilayers on Si has been explored-but besides complexity, high defect densities and junction leakage currents present limitations in this approach. Motivated by this challenge, here we use an epitaxial transfer method for the integration of ultrathin layers of single-crystal InAs on Si/SiO(2) substrates. As a parallel with silicon-on-insulator (SOI) technology, we use 'XOI' to represent our compound semiconductor-on-insulator platform. Through experiments and simulation, the electrical properties of InAs XOI transistors are explored, elucidating the critical role of quantum confinement in the transport properties of ultrathin XOI layers. Importantly, a high-quality InAs/dielectric interface is obtained by the use of a novel thermally grown interfacial InAsO(x) layer (~1?nm thick). The fabricated field-effect transistors exhibit a peak transconductance of ~1.6?mS?μm(-1) at a drain-source voltage of 0.5?V, with an on/off current ratio of greater than 10,000.     

Crystal structure of a potassium ion transporter, TrkH

The TrkH/TrkG/KtrB proteins mediate K(+) uptake in bacteria and probably evolved from simple K(+) channels by multiple gene duplications or fusions. Here we present the crystal structure of a TrkH from Vibrio parahaemolyticus. TrkH is a homodimer, and each protomer contains an ion permeation pathway. A selectivity filter, similar in architecture to those of K(+) channels but significantly shorter, is lined by backbone and side-chain oxygen atoms. Functional studies showed that TrkH is selective for permeation of K(+) and Rb(+) over smaller ions such as Na(+) or Li(+). Immediately intracellular to the selectivity filter are an intramembrane loop and an arginine residue, both highly conserved, which constrict the permeation pathway. Substituting the arginine with an alanine significantly increases the rate of K(+) flux. These results reveal the molecular basis of K(+) selectivity and suggest a novel gating mechanism for this large and important family of membrane transport proteins.     

Structural diversity in binary nanoparticle superlattices

Assembly of small building blocks such as atoms, molecules and nanoparticles into macroscopic structures--that is, 'bottom up' assembly--is a theme that runs through chemistry, biology and material science. Bacteria, macromolecules and nanoparticles can self-assemble, generating ordered structures with a precision that challenges current lithographic techniques. The assembly of nanoparticles of two different materials into a binary nanoparticle superlattice (BNSL) can provide a general and inexpensive path to a large variety of materials (metamaterials) with precisely controlled chemical composition and tight placement of the components. Maximization of the nanoparticle packing density has been proposed as the driving force for BNSL formation, and only a few BNSL structures have been predicted to be thermodynamically stable. Recently, colloidal crystals with micrometre-scale lattice spacings have been grown from oppositely charged polymethyl methacrylate spheres. Here we demonstrate formation of more than 15 different BNSL structures, using combinations of semiconducting, metallic and magnetic nanoparticle building blocks. At least ten of these colloidal crystalline structures have not been reported previously. We demonstrate that electrical charges on sterically stabilized nanoparticles determine BNSL stoichiometry; additional contributions from entropic, van der Waals, steric and dipolar forces stabilize the variety of BNSL structures.     

长江口滨海湿地有机碳循环过程及影响因素研究进展

滨海湿地是“蓝碳生态系统”的重要组成部分。综述了长江口滨海湿地土壤有机碳时空分布及含量、碳汇速率、有机碳横向输入输出通量及量化方法、有机碳循环定量分析模型以及有机碳储量和组分对不同影响因素所做出的动态响应规律,发现在土壤有机碳水平空间分布上,崇西湿地＞崇明东滩＞九段沙＞南汇潮滩;有机碳通量和浓度变化主要受到植物生物量和结构、水和土壤的理化性质、陆源输入和潮汐动力、间隙水交换以及人类活动和全球气候变化的影响。未来应加强长江口湿地土壤碳库和有机碳输运通量统一观测,准确量化各主要因素对有机碳的贡献,这对研究盐沼湿地的碳循环机理和碳汇评估具有重要意义。