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91.
The T-box genes Tbx4 and Tbx5 have been shown to have key functions in the specification of the identity of the vertebrate forelimb (Tbx5) and hindlimb (Tbx4). Here we show that in zebrafish, Tbx5 has an additional early function that precedes the formation of the limb bud itself. Functional knockdown of zebrafish tbx5 through the use of an antisense oligonucleotide resulted in a failure to initiate fin bud formation, leading to the complete loss of pectoral fins. The function of the tbx5 gene in the development of zebrafish forelimbs seems to involve the directed migration of individual lateral-plate mesodermal cells into the future limb-bud-producing region. The primary defect seen in the tbx5-knockdown phenotype is similar to the primary defects described in known T-box-gene mutants such as the spadetail mutant of zebrafish and the Brachyury mutant of the mouse, which both similarly exhibit an altered migration of mesodermal cells. A common function for many of the T-box genes might therefore be in mediating the proper migration and/or changes in adhesive properties of early embryonic cells. 相似文献
92.
Genome shuffling leads to rapid phenotypic improvement in bacteria 总被引:51,自引:0,他引:51
For millennia, selective breeding, on the basis of biparental mating, has led to the successful improvement of plants and animals to meet societal needs. At a molecular level, DNA shuffling mimics, yet accelerates, evolutionary processes, and allows the breeding and improvement of individual genes and subgenomic DNA fragments. We describe here whole-genome shuffling; a process that combines the advantage of multi-parental crossing allowed by DNA shuffling with the recombination of entire genomes normally associated with conventional breeding. We show that recursive genomic recombination within a population of bacteria can efficiently generate combinatorial libraries of new strains. When applied to a population of phenotypically selected bacteria, many of these new strains show marked improvements in the selected phenotype. We demonstrate the use of this approach through the rapid improvement of tylosin production from Streptomyces fradiae. This approach has the potential to facilitate cell and metabolic engineering and provide a non-recombinant alternative to the rapid production of improved organisms. 相似文献
93.
Lee J Kim H Kahng SJ Kim G Son YW Ihm J Kato H Wang ZW Okazaki T Shinohara H Kuk Y 《Nature》2002,415(6875):1005-1008
Motivated by the technical and economic difficulties in further miniaturizing silicon-based transistors with the present fabrication technologies, there is a strong effort to develop alternative electronic devices, based, for example, on single molecules. Recently, carbon nanotubes have been successfully used for nanometre-sized devices such as diodes, transistors, and random access memory cells. Such nanotube devices are usually very long compared to silicon-based transistors. Here we report a method for dividing a semiconductor nanotube into multiple quantum dots with lengths of about 10nm by inserting Gd@C82 endohedral fullerenes. The spatial modulation of the nanotube electronic bandgap is observed with a low-temperature scanning tunnelling microscope. We find that a bandgap of approximately 0.5eV is narrowed down to approximately 0.1eV at sites where endohedral metallofullerenes are inserted. This change in bandgap can be explained by local elastic strain and charge transfer at metallofullerene sites. This technique for fabricating an array of quantum dots could be used for nano-electronics and nano-optoelectronics. 相似文献
94.
RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta 总被引:18,自引:0,他引:18
Takayanagi H Kim S Matsuo K Suzuki H Suzuki T Sato K Yokochi T Oda H Nakamura K Ida N Wagner EF Taniguchi T 《Nature》2002,416(6882):744-749
95.
96.
Grimm DR Colter MB Braunschweig M Alexander LJ Neame PJ Kim HK 《Cellular and molecular life sciences : CMLS》2001,58(1):148-159
Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance,
the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor
V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine
factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human,
and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of
conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome
4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and
therefore likely important residues.
Received 3 October 2000; revised 23 November 2000; accepted 6 December 2000 相似文献
97.
Montgomery KT Lee E Miller A Lau S Shim C Decker J Chiu D Emerling S Sekhon M Kim R Lenz J Han J Ioshikhes I Renault B Marondel I Yoon SJ Song K Murty VV Scherer S Yonescu R Kirsch IR Ried T McPherson J Gibbs R Kucherlapati R 《Nature》2001,409(6822):945-946
Our sequence-tagged site-content map of chromosome 12 is now integrated with the whole-genome fingerprinting effort. It provides accurate and nearly complete bacterial clone coverage of chromosome 12. We propose that this integrated mapping protocol serves as a model for constructing physical maps for entire genomes. 相似文献
98.
Fernandez-Lopez S Kim HS Choi EC Delgado M Granja JR Khasanov A Kraehenbuehl K Long G Weinberger DA Wilcoxen KM Ghadiri MR 《Nature》2001,412(6845):452-455
The rapid emergence of bacterial infections that are resistant to many drugs underscores the need for new therapeutic agents. Here we report that six- and eight-residue cyclic d,l-alpha-peptides act preferentially on Gram-positive and/or Gram-negative bacterial membranes compared to mammalian cells, increase membrane permeability, collapse transmembrane ion potentials, and cause rapid cell death. The effectiveness of this class of materials as selective antibacterial agents is highlighted by the high efficacy observed against lethal methicillin-resistant Staphylococcus aureus infections in mice. Cyclic d,l-alpha-peptides are proteolytically stable, easy to synthesize, and can be derived from a potentially vast membrane-active sequence space. The unique abiotic structure of the cyclic peptides and their quick bactericidal action may also contribute to limit temporal acquirement of drug resistant bacteria. The low molecular weight d,l-alpha-peptides offer an attractive complement to the current arsenal of naturally derived antibiotics, and hold considerable potential in combating a variety of existing and emerging infectious diseases. 相似文献
99.
100.
ICOS is essential for effective T-helper-cell responses 总被引:60,自引:0,他引:60
Tafuri A Shahinian A Bladt F Yoshinaga SK Jordana M Wakeham A Boucher LM Bouchard D Chan VS Duncan G Odermatt B Ho A Itie A Horan T Whoriskey JS Pawson T Penninger JM Ohashi PS Mak TW 《Nature》2001,409(6816):105-109
The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma. 相似文献