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Roscioli T Kamsteeg EJ Buysse K Maystadt I van Reeuwijk J van den Elzen C van Beusekom E Riemersma M Pfundt R Vissers LE Schraders M Altunoglu U Buckley MF Brunner HG Grisart B Zhou H Veltman JA Gilissen C Mancini GM Delrée P Willemsen MA Ramadža DP Chitayat D Bennett C Sheridan E Peeters EA Tan-Sindhunata GM de Die-Smulders CE Devriendt K Kayserili H El-Hashash OA Stemple DL Lefeber DJ Lin YY van Bokhoven H 《Nature genetics》2012,44(5):581-585
Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. 相似文献
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Locke DP Hillier LW Warren WC Worley KC Nazareth LV Muzny DM Yang SP Wang Z Chinwalla AT Minx P Mitreva M Cook L Delehaunty KD Fronick C Schmidt H Fulton LA Fulton RS Nelson JO Magrini V Pohl C Graves TA Markovic C Cree A Dinh HH Hume J Kovar CL Fowler GR Lunter G Meader S Heger A Ponting CP Marques-Bonet T Alkan C Chen L Cheng Z Kidd JM Eichler EE White S Searle S Vilella AJ Chen Y Flicek P Ma J Raney B Suh B Burhans R Herrero J Haussler D Faria R Fernando O Darré F Farré D Gazave E Oliva M 《Nature》2011,469(7331):529-533
'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000?years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts. 相似文献
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王朝元 Duan Yourong Boban Markovic James Barbara C.Rolfe Howlett Zhang Xingdong Hala Zreiqat 《高技术通讯(英文版)》2004,10(2):46-50
Hydroxyapatite ceramics (.HA) has been proved to be excellent in biocompatibility and bioactivity.However, limited information is available concerning how HA ceramics affects the maturation of es-tcoblasts in molecular biological level /n v/tro. This study examines the mRNA expression and protein production of hone-related genes in estcoblast-like cell line(Saos-2) cultured on HA disks. Saos-2 cells are seeded onto the substrates and cultured for 18 days. Harvested cells are tested for the cell growth rate, expression of mRNAs for esteocalcin and alkaline phosphatase, and protein production of bone sialo-protein and esteocalcin. MTS assay shows that cell proliferates well on HA ceramic substrate. After 9d,bone sialoprotein and esteocalcin protein production in SAPS-2 increases more on HA surfaces than on control material. As bone sialoprotein and esteocalcin are the genes to be highly expressed at the late stage of estcoblast differentiation, this study reveals that after long time culture in HA, HA can induce Saos-2 maturation. The behavior of Saos-2 on HA surfaces revealed in this study provides valuable infor-mation for the understanding of the biocompatibility and bioactivity of HA ceramics. 相似文献
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羟基磷灰石陶瓷诱导成骨细胞的研究 总被引:4,自引:0,他引:4
通过定量检测在羟基磷灰石(HA)表面生长的成骨细胞骨涎蛋白和骨钙蛋白的表达,研究了羟基磷灰石陶瓷对成骨细胞的影响.研究结果表明,随着成骨细胞培养时间的延长,在羟基磷灰石表面生长的成骨细胞骨钙蛋白和骨涎蛋白的表达量相对于对照组有显著增加.由于骨钙蛋白和骨涎蛋白是成骨细胞分化晚期高度表达的两种标志性蛋白质,因此其表达量的显著提高意味着羟基磷灰石陶瓷可以诱导成骨细胞的成熟。这一结果可进一步为理解HA陶瓷的生物相容性和生物活性提供分子生物学依据。 相似文献
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Isakovic A Harhaji L Stevanovic D Markovic Z Sumarac-Dumanovic M Starcevic V Micic D Trajkovic V 《Cellular and molecular life sciences : CMLS》2007,64(10):1290-1302
The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density
cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G0/G1 phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction
of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and
oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition
(cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis
(sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C,
an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed
in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic
action of metformin.
Received 14 February 2007; received after revision 26 March 2007; accepted 3 April 2007 相似文献
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