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981.
Angiogenesis and signal transduction in endothelial cells 总被引:11,自引:0,他引:11
Muñoz-Chápuli R Quesada AR Angel Medina M 《Cellular and molecular life sciences : CMLS》2004,61(17):2224-2243
Endothelial cells receive multiple information from their environment that eventually leads them to progress along all the stages of the process of formation of new vessels. Angiogenic signals promote endothelial cell proliferation, increased resistance to apoptosis, changes in proteolytic balance, cytoskeletal reorganization, migration and, finally, differentiation and formation of a new vascular lumen. We aim to review herein the main signaling cascades that become activated in angiogenic endothelial cells as well as the opportunities of modulating angiogenesis through pharmacological interference with these signaling mechanisms. We will deal mainly with the mitogen-activated protein kinases pathway, which is very important in the transduction of proliferation signals; the phosphatidylinositol-3-kinase/protein kinase B signaling system, particularly essential for the survival of the angiogenic endothelium; the small GTPases involved in cytoskeletal reorganization and migration; and the kinases associated to focal adhesions which contribute to integrate the pathways from the two main sources of angiogenic signals, i.e. growth factors and the extracellular matrix.Received 13 February 2004; received after revision 25 March 2004; accepted 19 April 2004 相似文献
982.
983.
Overview of mammalian zinc transporters 总被引:27,自引:0,他引:27
984.
Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis 总被引:11,自引:0,他引:11
Hellemans J Preobrazhenska O Willaert A Debeer P Verdonk PC Costa T Janssens K Menten B Van Roy N Vermeulen SJ Savarirayan R Van Hul W Vanhoenacker F Huylebroeck D De Paepe A Naeyaert JM Vandesompele J Speleman F Verschueren K Coucke PJ Mortier GR 《Nature genetics》2004,36(11):1213-1218
Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways in human cells. 相似文献
985.
Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome 总被引:11,自引:0,他引:11
Ferland RJ Eyaid W Collura RV Tully LD Hill RS Al-Nouri D Al-Rumayyan A Topcu M Gascon G Bodell A Shugart YY Ruvolo M Walsh CA 《Nature genetics》2004,36(9):1008-1013
Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors. 相似文献
986.
Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus 总被引:22,自引:0,他引:22
Hong YK Foreman K Shin JW Hirakawa S Curry CL Sage DR Libermann T Dezube BJ Fingeroth JD Detmar M 《Nature genetics》2004,36(7):683-685
Kaposi sarcoma is considered a neoplasm of lymphatic endothelium infected with Kaposi sarcoma-associated herpesvirus. It is characterized by the expression of lymphatic lineage-specific genes by Kaposi sarcoma tumor cells. Here we show that infection of differentiated blood vascular endothelial cells with Kaposi sarcoma-associated herpesvirus leads to their lymphatic reprogramming; induction of approximately 70% of the main lymphatic lineage-specific genes, including PROX1, a master regulator of lymphatic development; and downregulation of blood vascular genes. 相似文献
987.
988.
The knockout mouse project 总被引:1,自引:0,他引:1
Austin CP Battey JF Bradley A Bucan M Capecchi M Collins FS Dove WF Duyk G Dymecki S Eppig JT Grieder FB Heintz N Hicks G Insel TR Joyner A Koller BH Lloyd KC Magnuson T Moore MW Nagy A Pollock JD Roses AD Sands AT Seed B Skarnes WC Snoddy J Soriano P Stewart DJ Stewart F Stillman B Varmus H Varticovski L Verma IM Vogt TF von Melchner H Witkowski J Woychik RP Wurst W Yancopoulos GD Young SG Zambrowicz B 《Nature genetics》2004,36(9):921-924
Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. 相似文献
989.
Thibault ST Singer MA Miyazaki WY Milash B Dompe NA Singh CM Buchholz R Demsky M Fawcett R Francis-Lang HL Ryner L Cheung LM Chong A Erickson C Fisher WW Greer K Hartouni SR Howie E Jakkula L Joo D Killpack K Laufer A Mazzotta J Smith RD Stevens LM Stuber C Tan LR Ventura R Woo A Zakrajsek I Zhao L Chen F Swimmer C Kopczynski C Duyk G Winberg ML Margolis J 《Nature genetics》2004,36(3):283-287
With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences. 相似文献
990.
The massive star that underwent a collapse of its core to produce supernova (SN)1993J was subsequently identified as a non-variable red supergiant star in images of the galaxy M81 taken before explosion. It showed an excess in ultraviolet and B-band colours, suggesting either the presence of a hot, massive companion star or that it was embedded in an unresolved young stellar association. The spectra of SN1993J underwent a remarkable transformation from the signature of a hydrogen-rich type II supernova to one of a helium-rich (hydrogen-deficient) type Ib. The spectral and photometric peculiarities were best explained by models in which the 13-20 solar mass supergiant had lost almost its entire hydrogen envelope to a close binary companion, producing a 'type IIb' supernova, but the hypothetical massive companion stars for this class of supernovae have so far eluded discovery. Here we report photometric and spectroscopic observations of SN1993J ten years after the explosion. At the position of the fading supernova we detect the unambiguous signature of a massive star: the binary companion to the progenitor. 相似文献