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111.
Summary Condensed chromatin shows globules of 300 Å formed by 8 to 10 nucleosomes. Each globule might be an uncoiled turn of a supercoil. This supercoil forms major coils along the fibre.This work was supported by grants from Brazilian CNPq, FAPESP and FEDIB.We thank Dr A. Brunner Jr for the permission to use the electron microscope. 相似文献
112.
Maria Rosa Antognazza 《Studies in history and philosophy of science》2003,34(2):309-327
This paper employs the revised conception of Leibniz emerging from recent research to reassess critically the ‘radical spiritual revolution’ which, according to Alexandre Koyré’s landmark book, From the closed world to the infinite universe (1957) was precipitated in the seventeenth century by the revolutions in physics, astronomy, and cosmology. While conceding that the cosmological revolution necessitated a reassessment of the place of value-concepts within cosmology, it argues that this reassessment did not entail a spiritual revolution of the kind assumed by Koyré, in which ‘value-concepts, such as perfection, harmony, meaning and aim’ were shed from the conception of the structure of the universe altogether. On the contrary, thanks to his pioneering intuition of the distinction between physical and metaphysical levels of explanation, Leibniz saw with great clarity that a scientific explanation of the universe which rejected the ‘closed world’ typical of Aristotelian cosmology did not necessarily require the abandonment of key metaphysical doctrines underlying the Aristotelian conception of the universe. Indeed the canon of value-concepts mentioned by Koyré—meaning, aim, perfection and harmony—reads like a list of the most important concepts underlying the Leibnizian conception of the metaphysical structure of the universe. Moreover, Leibniz’s universe, far from being a universe without God—because, as Clarke insinuated, it does not need intervention from God—is a universe which in its deepest ontological fabric is interwoven with the presence of God. 相似文献
113.
Gabriele Eden Marco Archinti Ralitsa Arnaudova Giuseppina Andreotti Andrea Motta Federico Furlan Valentina Citro Maria Vittoria Cubellis Bernard Degryse 《Cellular and molecular life sciences : CMLS》2018,75(10):1889-1907
The urokinase receptor (uPAR) stimulates cell proliferation by forming a macromolecular complex with αvβ3 integrin and the epidermal growth factor receptor (EGFR, ErbB1 or HER1) that we name the uPAR proliferasome. uPAR transactivates EGFR, which in turn mediates uPAR-initiated mitogenic signal to the cell. EGFR activation and EGFR-dependent cell growth are blocked in the absence of uPAR expression or when uPAR activity is inhibited by antibodies against either uPAR or EGFR. The mitogenic sequence of uPAR corresponds to the D2A motif present in domain 2. NMR analysis revealed that D2A synthetic peptide has a particular three-dimensional structure, which is atypical for short peptides. D2A peptide is as effective as EGF in promoting EGFR phosphorylation and cell proliferation that were inhibited by AG1478, a specific inhibitor of the tyrosine kinase activity of EGFR. Both D2A and EGF failed to induce proliferation of NR6-EGFR-K721A cells expressing a kinase-defective mutant of EGFR. Moreover, D2A peptide and EGF phosphorylate ERK demonstrating the involvement of the MAP kinase signalling pathway. Altogether, this study reveals the importance of sequence D2A of uPAR, and the interdependence of uPAR and EGFR. 相似文献
114.
Gian Maria Fimia Mauro Piacentini 《Cellular and molecular life sciences : CMLS》2010,67(10):1581-1588
A growing number of publications show that apoptosis induction is often associated with increased autophagy indicating the
existence of an interplay between these two important cellular events. The simultaneous activation of both phenomena has been
detected not only in experimental settings but also in vivo under physiological and pathological conditions. Despite these
studies, the reciprocal influence of the two pathways in vivo has still not been completely understood. It is clear that autophagy
and apoptosis are strictly interconnected, as highlighted by the finding that the two pathways share key molecular regulators.
Many novel aspects of the crosstalk between
apoptosis and autophagy have recently emerged showing how complex is this
relationship and how critical is for the overall fate of the cell. In this mini-review we will focus on some key experiments
trying to decipher as to whether autophagy contributes to apoptosis modulation in vivo. 相似文献
115.
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy 总被引:14,自引:0,他引:14
Pandit B Sarkozy A Pennacchio LA Carta C Oishi K Martinelli S Pogna EA Schackwitz W Ustaszewska A Landstrom A Bos JM Ommen SR Esposito G Lepri F Faul C Mundel P López Siguero JP Tenconi R Selicorni A Rossi C Mazzanti L Torrente I Marino B Digilio MC Zampino G Ackerman MJ Dallapiccola B Tartaglia M Gelb BD 《Nature genetics》2007,39(8):1007-1012
Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes approximately 60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2. Most mutations altered a motif flanking Ser259, a residue critical for autoinhibition of RAF1 through 14-3-3 binding. Of 19 subjects with a RAF1 mutation in two hotspots, 18 (or 95%) showed hypertrophic cardiomyopathy (HCM), compared with the 18% prevalence of HCM among individuals with Noonan syndrome in general. Ectopically expressed RAF1 mutants from the two HCM hotspots had increased kinase activity and enhanced ERK activation, whereas non-HCM-associated mutants were kinase impaired. Our findings further implicate increased RAS signaling in pathological cardiomyocyte hypertrophy. 相似文献
116.
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
117.
Cotton RG; Human Variome Project Appelbe W Auerbach AD Becker K Bodmer W Boone DJ Boulyjenkov V Brahmachari S Brody L Brookes A Brown AF Byers P Cantu JM Cassiman JJ Claustres M Concannon P Cotton RG den Dunnen JT Flicek P Gibbs R Hall J Hasler J Katz M Kwok PY Laradi S Lindblom A Maglott D Marsh S Masimirembwa CM Minoshima S de Ramirez AM Pagon R Ramesar R Ravine D Richards S Rimoin D Ring HZ Scriver CR Sherry S Shimizu N Stein L Tadmouri GO Taylor G Watson M 《Nature genetics》2007,39(4):433-436
Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization-cosponsored meeting on June 20-23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations. 相似文献
118.
Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis 总被引:17,自引:0,他引:17
Gregory SG Schmidt S Seth P Oksenberg JR Hart J Prokop A Caillier SJ Ban M Goris A Barcellos LF Lincoln R McCauley JL Sawcer SJ Compston DA Dubois B Hauser SL Garcia-Blanco MA Pericak-Vance MA Haines JL;Multiple Sclerosis Genetics Group 《Nature genetics》2007,39(9):1083-1091
Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor alpha chain (IL7R) as a significant risk factor for multiple sclerosis in four independent family-based or case-control data sets (overall P = 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer. 相似文献
119.
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
120.