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排序方式: 共有466条查询结果,搜索用时 31 毫秒
1.
Fibulin-5/DANCE is essential for elastogenesis in vivo. 总被引:19,自引:0,他引:19
Tomoyuki Nakamura Pilar Ruiz Lozano Yasuhiro Ikeda Yoshitaka Iwanaga Aleksander Hinek Susumu Minamisawa Ching-Feng Cheng Kazuhiro Kobuke Nancy Dalton Yoshikazu Takada Kei Tashiro John Ross Jr Tasuku Honjo Kenneth R Chien 《Nature》2002,415(6868):171-175
The elastic fibre system has a principal role in the structure and function of various types of organs that require elasticity, such as large arteries, lung and skin. Although elastic fibres are known to be composed of microfibril proteins (for example, fibrillins and latent transforming growth factor (TGF)-beta-binding proteins) and polymerized elastin, the mechanism of their assembly and development is not well understood. Here we report that fibulin-5 (also known as DANCE), a recently discovered integrin ligand, is an essential determinant of elastic fibre organization. fibulin-5-/- mice generated by gene targeting exhibit a severely disorganized elastic fibre system throughout the body. fibulin-5-/- mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphysema, and loose skin (cutis laxa). These tissues contain fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibres. Fibulin-5 interacts directly with elastic fibres in vitro, and serves as a ligand for cell surface integrins alphavbeta3, alphavbeta5 and alpha9beta1 through its amino-terminal domain. Thus, fibulin-5 may provide anchorage of elastic fibres to cells, thereby acting to stabilize and organize elastic fibres in the skin, lung and vasculature. 相似文献
2.
T Dalton 《Experientia》1976,32(11):1421-1423
5-Hydroxytryptamine creatinine sulphate loses its biological activity when maintained at room temperature. The loss of 5-HT activity (in stimulating sodium transport across frog skin) is greater than the loss of creatinine sulphate activity (inhibition of sodium transport). 相似文献
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Mullighan CG Goorha S Radtke I Miller CB Coustan-Smith E Dalton JD Girtman K Mathew S Ma J Pounds SB Su X Pui CH Relling MV Evans WE Shurtleff SA Downing JR 《Nature》2007,446(7137):758-764
Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer. 相似文献
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Lissauer JJ Fabrycky DC Ford EB Borucki WJ Fressin F Marcy GW Orosz JA Rowe JF Torres G Welsh WF Batalha NM Bryson ST Buchhave LA Caldwell DA Carter JA Charbonneau D Christiansen JL Cochran WD Desert JM Dunham EW Fanelli MN Fortney JJ Gautier TN Geary JC Gilliland RL Haas MR Hall JR Holman MJ Koch DG Latham DW Lopez E McCauliff S Miller N Morehead RC Quintana EV Ragozzine D Sasselov D Short DR Steffen JH 《Nature》2011,470(7332):53-58
When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47?days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation. 相似文献
9.
Ruth Seelige Stephen Searles Jack D. Bui 《Cellular and molecular life sciences : CMLS》2018,75(2):225-240
The purpose of this review is to explore immune-mediated mechanisms of stress surveillance in cancer, with particular emphasis on the idea that all cancers have classical hallmarks (Hanahan and Weinberg in Cell 100:57–70, 67; Cell 144:646–674, 68) that could be interrelated. We postulate that hallmarks of cancer associated with cellular stress pathways (Luo et al. in Cell 136:823–837, 101) including oxidative stress, proteotoxic stress, mitotic stress, DNA damage, and metabolic stress could define and modulate the inflammatory component of cancer. As such, the overarching goal of this review is to define the types of cellular stress that cancer cells undergo, and then to explore mechanisms by which immune cells recognize, respond to, and are affected by each stress response. 相似文献
10.
Bis JC DeCarli C Smith AV van der Lijn F Crivello F Fornage M Debette S Shulman JM Schmidt H Srikanth V Schuur M Yu L Choi SH Sigurdsson S Verhaaren BF DeStefano AL Lambert JC Jack CR Struchalin M Stankovich J Ibrahim-Verbaas CA Fleischman D Zijdenbos A den Heijer T Mazoyer B Coker LH Enzinger C Danoy P Amin N Arfanakis K van Buchem MA de Bruijn RF Beiser A Dufouil C Huang J Cavalieri M Thomson R Niessen WJ Chibnik LB Gislason GK Hofman A Pikula A Amouyel P Freeman KB Phan TG Oostra BA Stein JL 《Nature genetics》2012,44(5):545-551
Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia. 相似文献