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31.
Ellinghaus E Ellinghaus D Stuart PE Nair RP Debrus S Raelson JV Belouchi M Fournier H Reinhard C Ding J Li Y Tejasvi T Gudjonsson J Stoll SW Voorhees JJ Lambert S Weidinger S Eberlein B Kunz M Rahman P Gladman DD Gieger C Wichmann HE Karlsen TH Mayr G Albrecht M Kabelitz D Mrowietz U Abecasis GR Elder JT Schreiber S Weichenthal M Franke A 《Nature genetics》2010,42(11):991-995
32.
Sophie Chauvet Katja Burk Fanny Mann 《Cellular and molecular life sciences : CMLS》2013,70(10):1685-1703
Many organs, such as lungs, nerves, blood and lymphatic vessels, consist of complex networks that carry flows of information, gases, and nutrients within the body. The morphogenetic patterning that generates these organs involves the coordinated action of developmental signaling cues that guide migration of specialized cells. Precision guidance of endothelial tip cells by vascular endothelial growth factors (VEGFs) is well established, and several families of neural guidance molecules have been identified to exert guidance function in both the nervous and the vascular systems. This review discusses recent advances in VEGF research, focusing on the emerging role of neural guidance molecules as key regulators of VEGF function during vascular development and on the novel role of VEGFs in neural cell migration and nerve wiring. 相似文献
33.
Bourdon A Minai L Serre V Jais JP Sarzi E Aubert S Chrétien D de Lonlay P Paquis-Flucklinger V Arakawa H Nakamura Y Munnich A Rötig A 《Nature genetics》2007,39(6):776-780
Mitochondrial DNA (mtDNA) depletion syndrome (MDS; MIM 251880) is a prevalent cause of oxidative phosphorylation disorders characterized by a reduction in mtDNA copy number. The hitherto recognized disease mechanisms alter either mtDNA replication (POLG (ref. 1)) or the salvage pathway of mitochondrial deoxyribonucleosides 5'-triphosphates (dNTPs) for mtDNA synthesis (DGUOK (ref. 2), TK2 (ref. 3) and SUCLA2 (ref. 4)). A last gene, MPV17 (ref. 5), has no known function. Yet the majority of cases remain unexplained. Studying seven cases of profound mtDNA depletion (1-2% residual mtDNA in muscle) in four unrelated families, we have found nonsense, missense and splice-site mutations and in-frame deletions of the RRM2B gene, encoding the cytosolic p53-inducible ribonucleotide reductase small subunit. Accordingly, severe mtDNA depletion was found in various tissues of the Rrm2b-/- mouse. The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis. 相似文献
34.
A combination of in vitro and in vivo models with validation in human tumors has identified AXL activation as a new mechanism of acquired resistance to EGFR inhibitors in non-small cell lung cancer. The identification of this mechanism, alongside the current development of specific AXL inhibitors, provides the rationale for further studies that may improve treatment for EGFR inhibitor-resistant patients. 相似文献
35.
Stolk L Perry JR Chasman DI He C Mangino M Sulem P Barbalic M Broer L Byrne EM Ernst F Esko T Franceschini N Gudbjartsson DF Hottenga JJ Kraft P McArdle PF Porcu E Shin SY Smith AV van Wingerden S Zhai G Zhuang WV Albrecht E Alizadeh BZ Aspelund T Bandinelli S Lauc LB Beckmann JS Boban M Boerwinkle E Broekmans FJ Burri A Campbell H Chanock SJ Chen C Cornelis MC Corre T Coviello AD d'Adamo P Davies G de Faire U de Geus EJ Deary IJ Dedoussis GV Deloukas P Ebrahim S Eiriksdottir G Emilsson V 《Nature genetics》2012,44(3):260-268
To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause. 相似文献
36.
37.
Meriem El Ghachi Nicole Howe Rodolphe Auger Alexandre Lambion Annick Guiseppi François Delbrassine Guillaume Manat Sophie Roure Sabine Peslier Eric Sauvage Lutz Vogeley Juan-Carlos Rengifo-Gonzalez Paulette Charlier Dominique Mengin-Lecreulx Maryline Foglino Thierry Touzé Martin Caffrey Frédéric Kerff 《Cellular and molecular life sciences : CMLS》2017,74(12):2319-2332
Type 2 phosphatidic acid phosphatases (PAP2s) can be either soluble or integral membrane enzymes. In bacteria, integral membrane PAP2s play major roles in the metabolisms of glycerophospholipids, undecaprenyl-phosphate (C55-P) lipid carrier and lipopolysaccharides. By in vivo functional experiments and biochemical characterization we show that the membrane PAP2 coded by the Bacillus subtilis yodM gene is the principal phosphatidylglycerol phosphate (PGP) phosphatase of B. subtilis. We also confirm that this enzyme, renamed bsPgpB, has a weaker activity on C55-PP. Moreover, we solved the crystal structure of bsPgpB at 2.25 Å resolution, with tungstate (a phosphate analog) in the active site. The structure reveals two lipid chains in the active site vicinity, allowing for PGP substrate modeling and molecular dynamic simulation. Site-directed mutagenesis confirmed the residues important for substrate specificity, providing a basis for predicting the lipids preferentially dephosphorylated by membrane PAP2s. 相似文献
38.
Maisnier-Patin S Roth JR Fredriksson A Nyström T Berg OG Andersson DI 《Nature genetics》2005,37(12):1376-1379
The relationship between the number of randomly accumulated mutations in a genome and fitness is a key parameter in evolutionary biology. Mutations may interact such that their combined effect on fitness is additive (no epistasis), reinforced (synergistic epistasis) or mitigated (antagonistic epistasis). We measured the decrease in fitness caused by increasing mutation number in the bacterium Salmonella typhimurium using a regulated, error-prone DNA polymerase (polymerase IV, DinB). As mutations accumulated, fitness costs increased at a diminishing rate. This suggests that random mutations interact such that their combined effect on fitness is mitigated and that the genome is buffered against the fitness reduction caused by accumulated mutations. Levels of the heat shock chaperones DnaK and GroEL increased in lineages that had accumulated many mutations, and experimental overproduction of GroEL further increased the fitness of lineages containing deleterious mutations. These findings suggest that overexpression of chaperones contributes to antagonistic epistasis. 相似文献
39.
E. Guttes Vimala R. Devi Sophie Guttes 《Cellular and molecular life sciences : CMLS》1969,25(6):615-616
Zusammenfassung Nach Fusion von promitotischen mit postmitotischen Fragmenten des SchleimpilzesPhysarum polycephalum (Zahlenverhältnis von postmitotischen zu promitotischen Kernen: 1/1) teilten sich die Kerne der so hergestellten Plasmodien synchron.
Supported by AEC contract No. COO-1432-8. 相似文献
Supported by AEC contract No. COO-1432-8. 相似文献
40.
Ricardo C. Garcez Nicole M. Le Douarin Sophie E. Creuzet 《Cellular and molecular life sciences : CMLS》2014,71(11):2149-2164
The combinatorial expression of Hox genes is an evolutionarily ancient program underlying body axis patterning in all Bilateria. In the head, the neural crest (NC)––a vertebrate innovation that contributes to evolutionarily novel skeletal and neural features––develops as a structure free of Hox-gene expression. The activation of Hoxa2 in the Hox-free facial NC (FNC) leads to severe craniofacial and brain defects. Here, we show that this condition unveils the requirement of three Six genes, Six1, Six2, and Six4, for brain development and morphogenesis of the maxillo-mandibular and nasofrontal skeleton. Inactivation of each of these Six genes in FNC generates diverse brain defects, ranging from plexus agenesis to mild or severe holoprosencephaly, and entails facial hypoplasia or truncation of the craniofacial skeleton. The triple silencing of these genes reveals their complementary role in face and brain morphogenesis. Furthermore, we show that the perturbation of the intrinsic genetic FNC program, by either Hoxa2 expression or Six gene inactivation, affects Bmp signaling through the downregulation of Bmp antagonists in the FNC cells. When upregulated in the FNC, Bmp antagonists suppress the adverse skeletal and cerebral effects of Hoxa2 expression. These results demonstrate that the combinatorial expression of Six1, Six2, and Six4 is required for the molecular programs governing craniofacial and cerebral development. These genes are crucial for the signaling system of FNC origin, which regulates normal growth and patterning of the cephalic neuroepithelium. Our results strongly suggest that several congenital craniofacial and cerebral malformations could be attributed to Six genes’ misregulation. 相似文献