Search results for "Spindle Apparatus"
showing 4 items of 24 documents
Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors
2014
SummaryExome sequencing analysis of over 2,000 children with complex malformations of cortical development identified five independent (four homozygous and one compound heterozygous) deleterious mutations in KATNB1, encoding the regulatory subunit of the microtubule-severing enzyme Katanin. Mitotic spindle formation is defective in patient-derived fibroblasts, a consequence of disrupted interactions of mutant KATNB1 with KATNA1, the catalytic subunit of Katanin, and other microtubule-associated proteins. Loss of KATNB1 orthologs in zebrafish (katnb1) and flies (kat80) results in microcephaly, recapitulating the human phenotype. In the developing Drosophila optic lobe, kat80 loss specificall…
Dis-organizing centrosomal clusters: specific cancer therapy for a generic spread?
2015
Cancer is a leading cause of mortality and the annual incidence of new cancer cases is rising worldwide. Due to the frequent development of resistance and the side effects of established anti-cancer drugs, the quest for new drugs with improved therapeutic features goes on. In contrast to cytotoxic chemotherapy of the past, the concept of targeted chemotherapy attempts to increase specificity of therapy by attacking tumor-related mechanisms. A novel emerging treatment concept represents the inhibition of centrosomal clustering. The centrosome regulates mitotic spindle formation assuring uniform separation of chromosomes to daughter cells. Many tumors contain supernumerary centrosomes, which …
Effect of different cryopreservation protocols on the metaphase II spindle in human oocytes.
2008
The aim of this study was to evaluate the impact of different cryopreservation protocols on the repolymerization of metaphase (M)II spindles in human oocytes. Fresh aspirated donor oocytes were cryopreserved 3–4 h after retrieval using four different protocols: slow freezing using 1.5 mol/l 1,2-propanediol (PROH) + 0.2 mol/l sucrose (n = 36); 1.5 mol/l PROH + 0.3 mol/l sucrose (n = 34); 1.5 mol/l PROH + 0.3 mol/l sucrose with Na + depleted–choline replaced media (n = 27), and vitrification by the Cryotip method (n = 23). The control group comprised 34 fresh oocytes. Three hours after thawing, surviving and control oocytes were fixed for meiotic spindle/chromatin assessment. Survival rates w…
Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.
2011
International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…