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31.
The tropics have been suggested as the drivers of global ocean and atmosphere circulation and biogeochemical cycling during the extreme warmth of the Cretaceous period; but the links between orbital forcing, freshwater runoff and the biogeochemistry of continental margins in extreme greenhouse conditions are not fully understood. Here we present Cretaceous records of geochemical tracers for freshwater runoff obtained from a sediment core off the Ivory Coast that indicate that alternating periods of arid and humid African climate were driven by orbital precession. Our simulations of the precession-driven patterns of river discharge with a global climate model suggest that ocean anoxia and black shale sedimentation were directly caused by high river discharge, and occurred specifically when the northern equinox coincided with perihelion (the minimum distance between the Sun and the Earth). We conclude that, in a warm climate, the oceans off tropical continental margins respond rapidly and sensitively to even modest changes in river discharge. 相似文献
32.
Involvement of chemokine receptors in breast cancer metastasis 总被引:344,自引:0,他引:344
Müller A Homey B Soto H Ge N Catron D Buchanan ME McClanahan T Murphy E Yuan W Wagner SN Barrera JL Mohar A Verástegui E Zlotnik A 《Nature》2001,410(6824):50-56
Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells. 相似文献
33.
Kawai J Shinagawa A Shibata K Yoshino M Itoh M Ishii Y Arakawa T Hara A Fukunishi Y Konno H Adachi J Fukuda S Aizawa K Izawa M Nishi K Kiyosawa H Kondo S Yamanaka I Saito T Okazaki Y Gojobori T Bono H Kasukawa T Saito R Kadota K Matsuda H Ashburner M Batalov S Casavant T Fleischmann W Gaasterland T Gissi C King B Kochiwa H Kuehl P Lewis S Matsuo Y Nikaido I Pesole G Quackenbush J Schriml LM Staubli F Suzuki R Tomita M Wagner L Washio T Sakai K Okido T Furuno M Aono H Baldarelli R Barsh G 《Nature》2001,409(6821):685-690
The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones. 相似文献
34.
Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells 总被引:102,自引:0,他引:102
R L Williams D J Hilton S Pease T A Willson C L Stewart D P Gearing E F Wagner D Metcalf N A Nicola N M Gough 《Nature》1988,336(6200):684-687
Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice. 相似文献
35.
随着软构件技术的快速发展,聚集软构件设计复杂软件系统的软件开发方法日趋成熟.如何利用系统架构和软构件的可靠性分析软件系统的可靠性成为一个亟待解决的问题.提出了一种基于场景的软构件自动化测试模型,给出基于统一建模语言UML的顺序图构造测试场景具体方法,并对基于UML顺序图构造测试场景方法的有效性进行了分析. 相似文献
36.
Bonardi V Pesaresi P Becker T Schleiff E Wagner R Pfannschmidt T Jahns P Leister D 《Nature》2005,437(7062):1179-1182
Illumination changes elicit modifications of thylakoid proteins and reorganization of the photosynthetic machinery. This involves, in the short term, phosphorylation of photosystem II (PSII) and light-harvesting (LHCII) proteins. PSII phosphorylation is thought to be relevant for PSII turnover, whereas LHCII phosphorylation is associated with the relocation of LHCII and the redistribution of excitation energy (state transitions) between photosystems. In the long term, imbalances in energy distribution between photosystems are counteracted by adjusting photosystem stoichiometry. In the green alga Chlamydomonas and the plant Arabidopsis, state transitions require the orthologous protein kinases STT7 and STN7, respectively. Here we show that in Arabidopsis a second protein kinase, STN8, is required for the quantitative phosphorylation of PSII core proteins. However, PSII activity under high-intensity light is affected only slightly in stn8 mutants, and D1 turnover is indistinguishable from the wild type, implying that reversible protein phosphorylation is not essential for PSII repair. Acclimation to changes in light quality is defective in stn7 but not in stn8 mutants, indicating that short-term and long-term photosynthetic adaptations are coupled. Therefore the phosphorylation of LHCII, or of an unknown substrate of STN7, is also crucial for the control of photosynthetic gene expression. 相似文献
37.
Meiotic crossover (CO) recombination establishes physical linkages between homologous chromosomes that are required for their proper segregation into developing gametes, and promotes genetic diversity by shuffling genetic material between parental chromosomes. COs require the formation of double strand breaks (DSBs) to create the substrate for strand exchange. DSBs occur in small intervals called hotspots and significant variation in hotspot usage exists between and among individuals. This variation is thought to reflect differences in sequence identity and chromatin structure, DNA topology and/ or chromosome domain organization. Chromosomes show different frequencies of nondisjunction (NDJ), reflecting inherent differences in meiotic crossover control, yet the underlying basis of these differences remains elusive. Here we show that a novel chromatin factor, X non-disjunction factor 1 (xnd-1), is responsible for the global distribution of COs in C. elegans. xnd-1 is also required for formation of double-strand breaks (DSBs) on the X, but surprisingly XND-1 protein is autosomally enriched. We show that xnd-1 functions independently of genes required for X chromosome-specific gene silencing, revealing a novel pathway that distinguishes the X from autosomes in the germ line, and further show that xnd-1 exerts its effects on COs, at least in part, by modulating levels of H2A lysine 5 acetylation. 相似文献
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