Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis

Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Initially, Cl- conductance in the sweat duct was discovered to be impaired in CF, a finding that has been extended to all CFTR-expressing cells. Subsequent cloning of the gene showed that CFTR functions as a cyclic-AMP-regulated Cl- channel; and some CF-causing mutations inhibit CFTR Cl- channel activity. The identification of additional CF-causing mutants with normal Cl- channel activity indicates, however, that other CFTR-dependent processes contribute to the disease. Indeed, CFTR regulates other transporters, including Cl(-)-coupled HCO3- transport. Alkaline fluids are secreted by normal tissues, whereas acidic fluids are secreted by mutant CFTR-expressing tissues, indicating the importance of this activity. HCO3- and pH affect mucin viscosity and bacterial binding. We have examined Cl(-)-coupled HCO3- transport by CFTR mutants that retain substantial or normal Cl- channel activity. Here we show that mutants reported to be associated with CF with pancreatic insufficiency do not support HCO3- transport, and those associated with pancreatic sufficiency show reduced HCO3- transport. Our findings demonstrate the importance of HCO3- transport in the function of secretory epithelia and in CF.     

A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis

X-linked inhibitor-of-apoptosis protein (XIAP) interacts with caspase-9 and inhibits its activity, whereas Smac (also known as DIABLO) relieves this inhibition through interaction with XIAP. Here we show that XIAP associates with the active caspase-9-Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspase-9, which becomes exposed after proteolytic processing of procaspase-9 at Asp315. Supporting this observation, point mutations that abrogate the proteolytic processing but not the catalytic activity of caspase-9, or deletion of the linker peptide, prevented caspase-9 association with XIAP and its concomitant inhibition. We note that the N-terminal four residues of caspase-9 linker peptide share significant homology with the N-terminal tetra-peptide in mature Smac and in the Drosophila proteins Hid/Grim/Reaper, defining a conserved class of IAP-binding motifs. Consistent with this finding, binding of the caspase-9 linker peptide and Smac to the BIR3 domain of XIAP is mutually exclusive, suggesting that Smac potentiates caspase-9 activity by disrupting the interaction of the linker peptide of caspase-9 with BIR3. Our studies reveal a mechanism in which binding to the BIR3 domain by two conserved peptides, one from Smac and the other one from caspase-9, has opposing effects on caspase activity and apoptosis.     

Plant diversity enhances ecosystem responses to elevated CO2 and nitrogen deposition

Human actions are causing declines in plant biodiversity, increases in atmospheric CO2 concentrations and increases in nitrogen deposition; however, the interactive effects of these factors on ecosystem processes are unknown. Reduced biodiversity has raised numerous concerns, including the possibility that ecosystem functioning may be affected negatively, which might be particularly important in the face of other global changes. Here we present results of a grassland field experiment in Minnesota, USA, that tests the hypothesis that plant diversity and composition influence the enhancement of biomass and carbon acquisition in ecosystems subjected to elevated atmospheric CO2 concentrations and nitrogen deposition. The study experimentally controlled plant diversity (1, 4, 9 or 16 species), soil nitrogen (unamended versus deposition of 4 g of nitrogen per m2 per yr) and atmospheric CO2 concentrations using free-air CO2 enrichment (ambient, 368 micromol mol-1, versus elevated, 560 micromol mol-1). We found that the enhanced biomass accumulation in response to elevated levels of CO2 or nitrogen, or their combination, is less in species-poor than in species-rich assemblages.     

Integration of cytogenetic landmarks into the draft sequence of the human genome

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.     

Nanostructure. Epitaxial diamond polytypes on silicon

Carbon is unique in the variety of configurations it can adopt with itself and other elements. Here we show how ion beams can be used to nanostructure various diamond polytypes, epitaxially aligning them to a silicon substrate. The ready controllability of ion beams, which are already used to manufacture submicrometre-scale devices, means that our findings should enable new carbon and non-carbon materials to be nanostructured for a host of applications.     

Tsix, a gene antisense to Xist at the X-inactivation centre

In mammals, dosage compensation is achieved by X inactivation and is regulated in cis by the X-inactivation centre (Xic) and Xist. The Xic controls X-chromosome counting, choice of X to inactivate and initiation of silencing. Xic action culminates in a change in Xist RNA property from a scarce, unstable RNA to highly expressed Xist RNA that coats the future inactive X. Deleting a 65-kb region downstream of Xist results in constitutive Xist expression and X inactivation, implying the presence of a cis-regulatory element. In this region, we now report the discovery of a gene antisense to Xist. Tsix is a 40-kb RNA originating 15 kb downstream of Xist and transcribed across the Xist locus. Tsix sequence is conserved at the human XIC. Tsix RNA has no conserved ORFs, is seen exclusively in the nucleus and is localized at Xic. Before the onset of X inactivation, Tsix is expressed from both X chromosomes. At the onset of X inactivation, Tsix expression becomes monoallelic, is associated with the future active X and persists until Xist is turned off. Tsix is not found on the inactive X once cells enter the X-inactivation pathway. Tsix has features suggesting a role in regulating the early steps of X inactivation, but not the silencing step.     

The earliest angiosperms: evidence from mitochondrial, plastid and nuclear genomes

Angiosperms have dominated the Earth's vegetation since the mid-Cretaceous (90 million years ago), providing much of our food, fibre, medicine and timber, yet their origin and early evolution have remained enigmatic for over a century. One part of the enigma lies in the difficulty of identifying the earliest angiosperms; the other involves the uncertainty regarding the sister group of angiosperms among extant and fossil gymnosperms. Here we report a phylogenetic analysis of DNA sequences of five mitochondrial, plastid and nuclear genes (total aligned length 8,733 base pairs), from all basal angiosperm and gymnosperm lineages (105 species, 103 genera and 63 families). Our study demonstrates that Amborella, Nymphaeales and Illiciales-Trimeniaceae-Austrobaileya represent the first stage of angiosperm evolution, with Amborella being sister to all other angiosperms. We also show that Gnetales are related to the conifers and are not sister to the angiosperms, thus refuting the Anthophyte Hypothesis. These results have far-reaching implications for our understanding of diversification, adaptation, genome evolution and development of the angiosperms.     

AN/SPS-40雷达的250千瓦固态发射机

固态雷达发射机的性能和成本在过去的十年中进行了激烈的角逐和竞争,到目前为止,固态雷达发射机在新系统的设计和某些旧系统的改型设计(只少在L波段)中已经得到了非常普遍的应用。由于固态雷达发射     

Plants lacking the main light-harvesting complex retain photosystem II macro-organization

Photosystem II (PSII) is a key component of photosynthesis, the process of converting sunlight into the chemical energy of life. In plant cells, it forms a unique oligomeric macrostructure in membranes of the chloroplasts. Several light-harvesting antenna complexes are organized precisely in the PSII macrostructure-the major trimeric complexes (LHCII) that bind 70% of PSII chlorophyll and three minor monomeric complexes-which together form PSII supercomplexes. The antenna complexes are essential for collecting sunlight and regulating photosynthesis, but the relationship between these functions and their molecular architecture is unresolved. Here we report that antisense Arabidopsis plants lacking the proteins that form LHCII trimers have PSII supercomplexes with almost identical abundance and structure to those found in wild-type plants. The place of LHCII is taken by a normally minor and monomeric complex, CP26, which is synthesized in large amounts and organized into trimers. Trimerization is clearly not a specific attribute of LHCII. Our results highlight the importance of the PSII macrostructure: in the absence of one of its main components, another protein is recruited to allow it to assemble and function.