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101.
Ding H Wu X Boström H Kim I Wong N Tsoi B O'Rourke M Koh GY Soriano P Betsholtz C Hart TC Marazita ML Field LL Tam PP Nagy A 《Nature genetics》2004,36(10):1111-1116
PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This phenotype was less severe than that of Pdgfra(-/-) embryos. Pdgfc(-/-) Pdgfa(-/-) embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate the development of craniofacial structures, the neural tube and mesodermal organs. Our results also show that PDGF-C signaling is a new pathway in palatogenesis, different from, and independent of, those previously implicated. 相似文献
102.
Now that some genomes have been completely sequenced, the ability to direct specific mutations into genomes is particularly desirable. Here we present a method to create mutations in the Caenorhabditis elegans genome efficiently through transgene-directed, transposon-mediated gene conversion. Engineered deletions targeted into two genes show that the frequency of obtaining the desired mutation was higher using this approach than using standard transposon insertion-deletion approaches. We also targeted an engineered green fluorescent protein insertion-replacement cassette to one of these genes, thereby confirming that custom alleles of different types can be created in vitro to make the corresponding mutations in vivo. This approach should also be applicable to heterologous transposons in C. elegans and other organisms, including vertebrates. 相似文献
103.
Davila S Furu L Gharavi AG Tian X Onoe T Qian Q Li A Cai Y Kamath PS King BF Azurmendi PJ Tahvanainen P Kääriäinen H Höckerstedt K Devuyst O Pirson Y Martin RS Lifton RP Tahvanainen E Torres VE Somlo S 《Nature genetics》2004,36(6):575-577
Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease. 相似文献
104.
Jaffe W Meisenheimer K Röttgering HJ Leinert Ch Richichi A Chesneau O Fraix-Burnet D Glazenborg-Kluttig A Granato GL Graser U Heijligers B Köhler R Malbet F Miley GK Paresce F Pel JW Perrin G Przygodda F Schoeller M Sol H Waters LB Weigelt G Woillez J De Zeeuw PT 《Nature》2004,429(6987):47-49
Active galactic nuclei (AGNs) display many energetic phenomena--broad emission lines, X-rays, relativistic jets, radio lobes--originating from matter falling onto a supermassive black hole. It is widely accepted that orientation effects play a major role in explaining the observational appearance of AGNs. Seen from certain directions, circum-nuclear dust clouds would block our view of the central powerhouse. Indirect evidence suggests that the dust clouds form a parsec-sized torus-shaped distribution. This explanation, however, remains unproved, as even the largest telescopes have not been able to resolve the dust structures. Here we report interferometric mid-infrared observations that spatially resolve these structures in the galaxy NGC 1068. The observations reveal warm (320 K) dust in a structure 2.1 parsec thick and 3.4 parsec in diameter, surrounding a smaller hot structure. As such a configuration of dust clouds would collapse in a time much shorter than the active phase of the AGN, this observation requires a continual input of kinetic energy to the cloud system from a source coexistent with the AGN. 相似文献
105.
The interface between silicon and a high-k oxide 总被引:1,自引:0,他引:1
The ability of the semiconductor industry to continue scaling microelectronic devices to ever smaller dimensions (a trend known as Moore's Law) is limited by quantum mechanical effects: as the thickness of conventional silicon dioxide (SiO(2)) gate insulators is reduced to just a few atomic layers, electrons can tunnel directly through the films. Continued device scaling will therefore probably require the replacement of the insulator with high-dielectric-constant (high-k) oxides, to increase its thickness, thus preventing tunnelling currents while retaining the electronic properties of an ultrathin SiO(2) film. Ultimately, such insulators will require an atomically defined interface with silicon without an interfacial SiO(2) layer for optimal performance. Following the first reports of epitaxial growth of AO and ABO(3) compounds on silicon, the formation of an atomically abrupt crystalline interface between strontium titanate and silicon was demonstrated. However, the atomic structure proposed for this interface is questionable because it requires silicon atoms that have coordinations rarely found elsewhere in nature. Here we describe first-principles calculations of the formation of the interface between silicon and strontium titanate and its atomic structure. Our study shows that atomic control of the interfacial structure by altering the chemical environment can dramatically improve the electronic properties of the interface to meet technological requirements. The interface structure and its chemistry may provide guidance for the selection process of other high-k gate oxides and for controlling their growth. 相似文献
106.
The Madagascan fat-tailed dwarf lemur, Cheirogaleus medius, hibernates in tree holes for seven months of the year, even though winter temperatures rise to over 30 degrees C. Here we show that this tropical primate relies on a flexible thermal response that depends on the properties of its tree hole: if the hole is poorly insulated, body temperature fluctuates widely, passively following the ambient temperature; if well insulated, body temperature stays fairly constant and the animal undergoes regular spells of arousal. Our findings indicate that arousals are determined by maximum body temperatures and that hypometabolism in hibernating animals is not necessarily coupled to a low body temperature. 相似文献
107.
Summary The involvement of the noradrenergic system in hypothermia induced by intrahypothalamically-injected carbachol (CCh) was studied by depleting hypothalamic noradrenaline (NA) with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) and repeating the CCh injections after 6-OHDA treatment. The results suggest that noradrenergic neurons may be involved in hypothermia produced by CCh in the pigeon. 相似文献
108.
E. J. Zöllner G. Seibert H. Slor R. K. Zahn 《Cellular and molecular life sciences : CMLS》1981,37(6):548-550
Summary The purification procedure for a nuclease from human serum is described. It includes ammonium sulfate precipitation, chromatography on DEAE-Sephadex and on Sephacryl-S 200, and preparative electrophoresis. The enzyme, purified about 2000-fold, is homogeneous in a sodium dodecyl sulfate electrophoretic system, where it has a mol. wt of 78,000. The pH optimum lies around pH 6.5; it is a sugar-nonspecific endonuclease.Acknowledgment. This work has been supported by a research grant from Stiftung Volkswagenwerk through the Akademie der Wissenschaften und der Literatur, Mainz. We thank Mrs R. Nehrbass and Mrs C. Wolpert for technical assistance. 相似文献
109.
Summary A method for cultivating the early chick embryo in an artificial medium has been developed that permits the determination of the stage at the onset of the treatment and the continuous observation of the embryogenesis.Kungliga Fysiografiska Sällskapet, Lund, supported this work. 相似文献
110.