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31.
Western US ponderosa pine forests have recently suffered extensive stand-replacing fires followed by hillslope erosion and sedimentation. These fires are usually attributed to increased stand density as a result of fire suppression, grazing and other land use, and are often considered uncharacteristic or unprecedented. Tree-ring records from the past 500 years indicate that before Euro-American settlement, frequent, low-severity fires maintained open stands. However, the pre-settlement period between about ad 1500 and ad 1900 was also generally colder than present, raising the possibility that rapid twentieth-century warming promoted recent catastrophic fires. Here we date fire-related sediment deposits in alluvial fans in central Idaho to reconstruct Holocene fire history in xeric ponderosa pine forests and examine links to climate. We find that colder periods experienced frequent low-severity fires, probably fuelled by increased understory growth. Warmer periods experienced severe droughts, stand-replacing fires and large debris-flow events that comprise a large component of long-term erosion and coincide with similar events in sub-alpine forests of Yellowstone National Park. Our results suggest that given the powerful influence of climate, restoration of processes typical of pre-settlement times may be difficult in a warmer future that promotes severe fires. 相似文献
32.
Cell surfaces are endowed with biological functionality designed to mediate extracellular communication. The cell-surface repertoire can be expanded to include abiotic functionality through the biosynthetic introduction of unnatural sugars into cellular glycans, a process termed metabolic oligosaccharide engineering. This technique has been exploited in fundamental studies of glycan-dependent cell-cell and virus-cell interactions and also provides an avenue for the chemical remodelling of living cells. Unique chemical functional groups can be delivered to cell-surface glycans by metabolism of the corresponding unnatural precursor sugars. These functional groups can then undergo covalent reaction with exogenous agents bearing complementary functionality. The exquisite chemical selectivity required of this process is supplied by the Staudinger ligation of azides and phosphines, a reaction that has been performed on cultured cells without detriment to their physiology. Here we demonstrate that the Staudinger ligation can be executed in living animals, enabling the chemical modification of cells within their native environment. The ability to tag cell-surface glycans in vivo may enable therapeutic targeting and non-invasive imaging of changes in glycosylation during disease progression. 相似文献
33.
Krantz ID McCallum J DeScipio C Kaur M Gillis LA Yaeger D Jukofsky L Wasserman N Bottani A Morris CA Nowaczyk MJ Toriello H Bamshad MJ Carey JC Rappaport E Kawauchi S Lander AD Calof AL Li HH Devoto M Jackson LG 《Nature genetics》2004,36(6):631-635
Cornelia de Lange syndrome (CdLS; OMIM 122470) is a dominantly inherited multisystem developmental disorder characterized by growth and cognitive retardation; abnormalities of the upper limbs; gastroesophageal dysfunction; cardiac, ophthalmologic and genitourinary anomalies; hirsutism; and characteristic facial features. Genital anomalies, pyloric stenosis, congenital diaphragmatic hernias, cardiac septal defects, hearing loss and autistic and self-injurious tendencies also frequently occur. Prevalence is estimated to be as high as 1 in 10,000 (ref. 4). We carried out genome-wide linkage exclusion analysis in 12 families with CdLS and identified four candidate regions, of which chromosome 5p13.1 gave the highest multipoint lod score of 2.7. This information, together with the previous identification of a child with CdLS with a de novo t(5;13)(p13.1;q12.1) translocation, allowed delineation of a 1.1-Mb critical region on chromosome 5 for the gene mutated in CdLS. We identified mutations in one gene in this region, which we named NIPBL, in four sporadic and two familial cases of CdLS. We characterized the genomic structure of NIPBL and found that it is widely expressed in fetal and adult tissues. The fly homolog of NIPBL, Nipped-B, facilitates enhancer-promoter communication and regulates Notch signaling and other developmental pathways in Drosophila melanogaster. 相似文献
34.
Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation 总被引:64,自引:0,他引:64
Engagement of the NKG2D receptor by tumour-associated ligands may promote tumour rejection by stimulating innate and adaptive lymphocyte responses. In humans, NKG2D is expressed on most natural killer cells, gammadelta T cells and CD8alphabeta T cells. Ligands of NKG2D include the major histocompatibility complex class I homologues MICA and MICB, which function as signals of cellular stress. These molecules are absent from most cells and tissues but can be induced by viral and bacterial infections and are frequently expressed in epithelial tumours. MIC engagement of NKG2D triggers natural killer cells and costimulates antigen-specific effector T cells. Here we show that binding of MIC induces endocytosis and degradation of NKG2D. Expression of NKG2D is reduced markedly on large numbers of tumour-infiltrating and matched peripheral blood T cells from individuals with cancer. This systemic deficiency is associated with circulating tumour-derived soluble MICA, causing the downregulation of NKG2D and in turn severe impairment of the responsiveness of tumour-antigen-specific effector T cells. This mode of T-cell silencing may promote tumour immune evasion and, by inference, compromise host resistance to infections. 相似文献
35.
A radiation hybrid map of mouse genes 总被引:13,自引:0,他引:13
Hudson TJ Church DM Greenaway S Nguyen H Cook A Steen RG Van Etten WJ Castle AB Strivens MA Trickett P Heuston C Davison C Southwell A Hardisty R Varela-Carver A Haynes AR Rodriguez-Tome P Doi H Ko MS Pontius J Schriml L Wagner L Maglott D Brown SD Lander ES Schuler G Denny P 《Nature genetics》2001,29(2):201-205
A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome. 相似文献
36.
Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments. However, this alone does not determine the intracellular destination of organelles. For example, the yeast class V myosin, Myo2p, moves several organelles to distinct locations during the cell cycle. Thus the movement of each type of Myo2p cargo must be regulated uniquely. Here we report a regulatory mechanism that specifically provides directionality to vacuole movement. The vacuole-specific Myo2p receptor, Vac17p, has a key function in this process. Vac17p binds simultaneously to Myo2p and to Vac8p, a vacuolar membrane protein. The transport complex, Myo2p-Vac17p-Vac8p, moves the vacuole to the bud, and is then disrupted through the degradation of Vac17p. The vacuole is ultimately deposited near the centre of the bud. Removal of a PEST sequence (a potential signal for rapid protein degradation) within Vac17p causes its stabilization and the subsequent 'backward' movement of vacuoles, which mis-targets them to the neck between the mother cell and the bud. Thus the regulated disruption of this transport complex places the vacuole in its proper location. This may be a general mechanism whereby organelles are deposited at their terminal destination. 相似文献
37.
Read TD Peterson SN Tourasse N Baillie LW Paulsen IT Nelson KE Tettelin H Fouts DE Eisen JA Gill SR Holtzapple EK Okstad OA Helgason E Rilstone J Wu M Kolonay JF Beanan MJ Dodson RJ Brinkac LM Gwinn M DeBoy RT Madpu R Daugherty SC Durkin AS Haft DH Nelson WC Peterson JD Pop M Khouri HM Radune D Benton JL Mahamoud Y Jiang L Hance IR Weidman JF Berry KJ Plaut RD Wolf AM Watkins KL Nierman WC Hazen A Cline R Redmond C Thwaite JE White O Salzberg SL Thomason B Friedlander AM Koehler TM Hanna PC 《Nature》2003,423(6935):81-86
Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis. 相似文献
38.
Floyd JA Gold DA Concepcion D Poon TH Wang X Keithley E Chen D Ward EJ Chinn SB Friedman RA Yu HT Moriwaki K Shiroishi T Hamilton BA 《Nature genetics》2003,35(3):221-228
Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements. 相似文献
39.
Huang E Ishida S Pittman J Dressman H Bild A Kloos M D'Amico M Pestell RG West M Nevins JR 《Nature genetics》2003,34(2):226-230
40.
Luo Y Frey EA Pfuetzner RA Creagh AL Knoechel DG Haynes CA Finlay BB Strynadka NC 《Nature》2000,405(6790):1073-1077
Intimin and its translocated intimin receptor (Tir) are bacterial proteins that mediate adhesion between mammalian cells and attaching and effacing (A/E) pathogens. Enteropathogenic Escherichia coli (EPEC) causes significant paediatric morbidity and mortality world-wide. A related A/E pathogen, enterohaemorrhagic E. coli (EHEC; O157:H7) is one of the most important food-borne pathogens in North America, Europe and Japan. A unique and essential feature of A/E bacterial pathogens is the formation of actin-rich pedestals beneath the intimately adherent bacteria and localized destruction of the intestinal brush border. The bacterial outer membrane adhesin, intimin, is necessary for the production of the A/E lesion and diarrhoea. The A/E bacteria translocate their own receptor for intimin, Tir, into the membrane of mammalian cells using the type III secretion system. The translocated Tir triggers additional host signalling events and actin nucleation, which are essential for lesion formation. Here we describe the the crystal structures of an EPEC intimin carboxy-terminal fragment alone and in complex with the EPEC Tir intimin-binding domain, giving insight into the molecular mechanisms of adhesion of A/E pathogens. 相似文献