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排序方式: 共有119条查询结果,搜索用时 31 毫秒
71.
Cranial design and function in a large theropod dinosaur 总被引:3,自引:0,他引:3
Rayfield EJ Norman DB Horner CC Horner JR Smith PM Thomason JJ Upchurch P 《Nature》2001,409(6823):1033-1037
Finite element analysis (FEA) is used by industrial designers and biomechanicists to estimate the performance of engineered structures or human skeletal and soft tissues subjected to varying regimes of stress and strain. FEA is rarely applied to problems of biomechanical design in animals, despite its potential to inform structure-function analysis. Non-invasive techniques such as computed tomography scans can be used to generate accurate three-dimensional images of structures, such as skulls, which can form the basis of an accurate finite element model. Here we have applied this technique to the long skull of the large carnivorous theropod dinosaur Allosaurus fragilis. We have generated the most geometrically complete and complex FEA model of the skull of any extinct or extant organism and used this to test its mechanical properties and examine, in a quantitative way, long-held hypotheses concerning overall shape and function. The combination of a weak muscle-driven bite force, a very 'light' and 'open' skull architecture and unusually high cranial strength, suggests a very specific feeding behaviour for this animal. These results demonstrate simply the inherent potential of FEA for testing mechanical behaviour in fossils in ways that, until now, have been impossible. 相似文献
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73.
Summary Pre- and simultaneous treatments ofVicia faba root tip meristems with urea and ethyl alcohol, mitomycin C, maleic hydrazide,3H-thymidine and X-rays, respectively, were found to result in mutagen-specific changes of the spectrum and yield of induced chromatid aberrations. 相似文献
74.
Cichon S Buervenich S Kirov G Akula N Dimitrova A Green E Schumacher J Klopp N Becker T Ohlraun S Schulze TG Tullius M Gross MM Jones L Krastev S Nikolov I Hamshere M Jones I Czerski PM Leszczynska-Rodziewicz A Kapelski P Bogaert AV Illig T Hauser J Maier W Berrettini W Byerley W Coryell W Gershon ES Kelsoe JR McInnis MG Murphy DL Nurnberger JI Reich T Scheftner W O'Donovan MC Propping P Owen MJ Rietschel M Nöthen MM McMahon FJ Craddock N 《Nature genetics》2004,36(8):783-4; author reply 784-5
75.
LKB1 modulates lung cancer differentiation and metastasis 总被引:1,自引:0,他引:1
Ji H Ramsey MR Hayes DN Fan C McNamara K Kozlowski P Torrice C Wu MC Shimamura T Perera SA Liang MC Cai D Naumov GN Bao L Contreras CM Li D Chen L Krishnamurthy J Koivunen J Chirieac LR Padera RF Bronson RT Lindeman NI Christiani DC Lin X Shapiro GI Jänne PA Johnson BE Meyerson M Kwiatkowski DJ Castrillon DH Bardeesy N Sharpless NE Wong KK 《Nature》2007,448(7155):807-810
Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis. 相似文献
76.
77.
CD4 and CD8 T lymphocyte interplay in controlling tumor growth 总被引:1,自引:0,他引:1
Dmitrij Ostroumov Nora Fekete-Drimusz Michael Saborowski Florian Kühnel Norman Woller 《Cellular and molecular life sciences : CMLS》2018,75(4):689-713
The outstanding clinical success of immune checkpoint blockade has revived the interest in underlying mechanisms of the immune system that are capable of eliminating tumors even in advanced stages. In this scenario, CD4 and CD8 T cell responses are part of the cancer immune cycle and both populations significantly influence the clinical outcome. In general, the immune system has evolved several mechanisms to protect the host against cancer. Each of them has to be undermined or evaded during cancer development to enable tumor outgrowth. In this review, we give an overview of T lymphocyte-driven control of tumor growth and discuss the involved tumor-suppressive mechanisms of the immune system, such as senescence surveillance, cancer immunosurveillance, and cancer immunoediting with respect to recent clinical developments of immunotherapies. The main focus is on the currently existing knowledge about the CD4 and CD8 T lymphocyte interplay that mediates the control of tumor growth. 相似文献
78.
Davis EE Zhang Q Liu Q Diplas BH Davey LM Hartley J Stoetzel C Szymanska K Ramaswami G Logan CV Muzny DM Young AC Wheeler DA Cruz P Morgan M Lewis LR Cherukuri P Maskeri B Hansen NF Mullikin JC Blakesley RW Bouffard GG;NISC Comparative Sequencing Program Gyapay G Rieger S Tönshoff B Kern I Soliman NA Neuhaus TJ Swoboda KJ Kayserili H Gallagher TE Lewis RA Bergmann C Otto EA Saunier S Scambler PJ Beales PL Gleeson JG Maher ER Attié-Bitach T Dollfus H Johnson CA Green ED Gibbs RA Hildebrandt F 《Nature genetics》2011,43(3):189-196
Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ~5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders. 相似文献
79.
Taal HR St Pourcain B Thiering E Das S Mook-Kanamori DO Warrington NM Kaakinen M Kreiner-Møller E Bradfield JP Freathy RM Geller F Guxens M Cousminer DL Kerkhof M Timpson NJ Ikram MA Beilin LJ Bønnelykke K Buxton JL Charoen P Chawes BL Eriksson J Evans DM Hofman A Kemp JP Kim CE Klopp N Lahti J Lye SJ McMahon G Mentch FD Müller-Nurasyid M O'Reilly PF Prokopenko I Rivadeneira F Steegers EA Sunyer J Tiesler C Yaghootkar H;Cohorts for Heart Aging Research in Genetic Epidemiology Consortium 《Nature genetics》2012,44(5):532-538
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume, Parkinson's disease and other neurodegenerative diseases, indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life. 相似文献
80.
Sotoodehnia N Isaacs A de Bakker PI Dörr M Newton-Cheh C Nolte IM van der Harst P Müller M Eijgelsheim M Alonso A Hicks AA Padmanabhan S Hayward C Smith AV Polasek O Giovannone S Fu J Magnani JW Marciante KD Pfeufer A Gharib SA Teumer A Li M Bis JC Rivadeneira F Aspelund T Köttgen A Johnson T Rice K Sie MP Wang YA Klopp N Fuchsberger C Wild SH Mateo Leach I Estrada K Völker U Wright AF Asselbergs FW Qu J Chakravarti A Sinner MF Kors JA Petersmann A Harris TB Soliman EZ Munroe PB Psaty BM 《Nature genetics》2010,42(12):1068-1076