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991.
Oshima T Sasaki M Kataoka H Miwa H Takeuchi T Joh T 《Cellular and molecular life sciences : CMLS》2007,64(23):3139-3147
Tight junctions (TJs) create a paracellular permeability barrier. Although reactive oxygen species have been implicated as
mediators of inflammation in inflammatory bowel diseases, their influence on the function of colonic epithelial TJs remains
unknown. Oxidative stress-mediated colonic epithelial permeability was significantly attenuated by a p38 mitogen-activated
protein (MAP) kinase inhibitor, SB203580. Although the amount of TJ proteins was not altered, hydrogen peroxide (H2O2) changed the localization of claudin-4 protein from an NP-40 insoluble fraction to a soluble fraction and from an apical
TJ to lateral membrane. The p38 MAP kinase inactivator Wip1 significantly attenuated phosphorylation of p38 MAP kinase, and
oxidative stress mediated permeability. H2O2-induced changes in claudin-4 localization were abolished by SB203580 pretreatment as well as Wip1-expressing adenovirus infection.
This is the first study to demonstrate that exogenous Wip1 functions to protect oxidative stress-mediated colonic mucosal
permeability and that H2O2-induced claudin-4 dislocalization is abolished by Wip1.
Received 14 June 2007; received after revision 8 October 2007; accepted 8 October 2007 相似文献
992.
Reproduction is essential to all organisms if they are to contribute to the next generation. There are various means and ways
of achieving this goal. This review focuses on the role of asexual reproduction for eukaryotic organisms and how its integration
in a life cycle can influence their population genetics and evolution. An important question for evolutionary biologists as
to why some organisms reproduce sexually, as opposed to asexually, is addressed. We also discuss the economic and medical
importance of asexual organisms.
Received 4 December 2006; received after revision 25 January 2007; accepted 20 February 2007 相似文献
993.
Mignot T 《Cellular and molecular life sciences : CMLS》2007,64(21):2733-2745
Bacterial motility is essential for chemotaxis, virulence and complex social interactions leading to biofilm and fruiting
body formation. Although bacterial swimming in liquids with a flagellum is well understood, little is known regarding bacterial
movements across solid surfaces. Gliding motility, one such mode of locomotion, has remained largely mysterious because cells
move smoothly along their long axis in the absence of any visible organelle. In this review, I discuss recent evidence that
focal adhesion systems mediate gliding motility in the social bacterium Myxococcus xanthus and combine this evidence with previous work to suggest a new working hypothesis inspired from knowledge in apicomplexan
parasites. I then propose experimental directions to test the model and compare it to other pre-existing models. Finally,
evidence on gliding mechanisms of selected organisms are presented to ask whether some features of the model have precedents
in other bacteria and whether this complex biological process could be explained by a single mechanism or involves multiple
distinct mechanisms.
Received 12 April 2007; received after revision 8 June 2007; accepted 27 June 2007 相似文献
994.
Pujana MA Han JD Starita LM Stevens KN Tewari M Ahn JS Rennert G Moreno V Kirchhoff T Gold B Assmann V Elshamy WM Rual JF Levine D Rozek LS Gelman RS Gunsalus KC Greenberg RA Sobhian B Bertin N Venkatesan K Ayivi-Guedehoussou N Solé X Hernández P Lázaro C Nathanson KL Weber BL Cusick ME Hill DE Offit K Livingston DM Gruber SB Parvin JD Vidal M 《Nature genetics》2007,39(11):1338-1349
Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic (or 'omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer-associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes. 相似文献
995.
Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes 总被引:1,自引:0,他引:1
Gudmundsson J Sulem P Steinthorsdottir V Bergthorsson JT Thorleifsson G Manolescu A Rafnar T Gudbjartsson D Agnarsson BA Baker A Sigurdsson A Benediktsdottir KR Jakobsdottir M Blondal T Stacey SN Helgason A Gunnarsdottir S Olafsdottir A Kristinsson KT Birgisdottir B Ghosh S Thorlacius S Magnusdottir D Stefansdottir G Kristjansson K Bagger Y Wilensky RL Reilly MP Morris AD Kimber CH Adeyemo A Chen Y Zhou J So WY Tong PC Ng MC Hansen T Andersen G Borch-Johnsen K Jorgensen T Tres A Fuertes F 《Nature genetics》2007,39(8):977-983
We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes. 相似文献
996.
Zanke BW Greenwood CM Rangrej J Kustra R Tenesa A Farrington SM Prendergast J Olschwang S Chiang T Crowdy E Ferretti V Laflamme P Sundararajan S Roumy S Olivier JF Robidoux F Sladek R Montpetit A Campbell P Bezieau S O'Shea AM Zogopoulos G Cotterchio M Newcomb P McLaughlin J Younghusband B Green R Green J Porteous ME Campbell H Blanche H Sahbatou M Tubacher E Bonaiti-Pellié C Buecher B Riboli E Kury S Chanock SJ Potter J Thomas G Gallinger S Hudson TJ Dunlop MG 《Nature genetics》2007,39(8):989-994
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer. 相似文献
997.
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus 总被引:1,自引:0,他引:1
Lee-Kirsch MA Gong M Chowdhury D Senenko L Engel K Lee YA de Silva U Bailey SL Witte T Vyse TJ Kere J Pfeiffer C Harvey S Wong A Koskenmies S Hummel O Rohde K Schmidt RE Dominiczak AF Gahr M Hollis T Perrino FW Lieberman J Hübner N 《Nature genetics》2007,39(9):1065-1067
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. 相似文献
998.
Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes 总被引:3,自引:0,他引:3
Kantarci S Al-Gazali L Hill RS Donnai D Black GC Bieth E Chassaing N Lacombe D Devriendt K Teebi A Loscertales M Robson C Liu T MacLaughlin DT Noonan KM Russell MK Walsh CA Donahoe PK Pober BR 《Nature genetics》2007,39(8):957-959
Donnai-Barrow syndrome is associated with agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. By studying multiplex families, we mapped this disorder to chromosome 2q23.3-31.1 and identified LRP2 mutations in six families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome. LRP2 encodes megalin, a multiligand uptake receptor that regulates levels of diverse circulating compounds. This work implicates a pathway with potential pharmacological therapeutic targets. 相似文献
999.
Studies have shown that DNA (cytosine-5-)-methyltransferase 1 (DNMT1) is the principal enzyme responsible for maintaining CpG methylation and is required for embryonic development and survival of somatic cells in mice. The role of DNMT1 in human cancer cells, however, remains highly controversial. Using homologous recombination, here we have generated a DNMT1 conditional allele in the human colorectal carcinoma cell line HCT116 in which several exons encoding the catalytic domain are flanked by loxP sites. Cre recombinase-mediated disruption of this allele results in hemimethylation of approximately 20% of CpG-CpG dyads in the genome, coupled with activation of the G2/M checkpoint, leading to arrest in the G2 phase of the cell cycle. Although cells gradually escape from this arrest, they show severe mitotic defects and undergo cell death either during mitosis or after arresting in a tetraploid G1 state. Our results thus show that DNMT1 is required for faithfully maintaining DNA methylation patterns in human cancer cells and is essential for their proliferation and survival. 相似文献
1000.
A conserved microRNA module exerts homeotic control over Petunia hybrida and Antirrhinum majus floral organ identity 总被引:3,自引:0,他引:3
Cartolano M Castillo R Efremova N Kuckenberg M Zethof J Gerats T Schwarz-Sommer Z Vandenbussche M 《Nature genetics》2007,39(7):901-905
It is commonly thought that deep phylogenetic conservation of plant microRNAs (miRNAs) and their targets indicates conserved regulatory functions. We show that the blind (bl) mutant of Petunia hybrida and the fistulata (fis) mutant of Antirrhinum majus, which have similar homeotic phenotypes, are recessive alleles of two homologous miRNA-encoding genes. The BL and FIS genes control the spatial restriction of homeotic class C genes to the inner floral whorls, but their ubiquitous early floral expression patterns are in contradiction with a potential role in patterning C gene expression. We provide genetic evidence for the unexpected function of the MIRFIS and MIRBL genes in the center of the flower and propose a dynamic mechanism underlying their regulatory role. Notably, Arabidopsis thaliana, a more distantly related species, also contains this miRNA module but does not seem to use it to confine early C gene expression to the center of the flower. 相似文献