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排序方式: 共有142条查询结果,搜索用时 15 毫秒
51.
Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome 总被引:7,自引:0,他引:7
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Stoetzel C Muller J Laurier V Davis EE Zaghloul NA Vicaire S Jacquelin C Plewniak F Leitch CC Sarda P Hamel C de Ravel TJ Lewis RA Friederich E Thibault C Danse JM Verloes A Bonneau D Katsanis N Poch O Mandel JL Dollfus H 《American journal of human genetics》2007,80(1):1-11
Bardet-Biedl syndrome (BBS) is primarily an autosomal recessive ciliopathy characterized by progressive retinal degeneration, obesity, cognitive impairment, polydactyly, and kidney anomalies. The disorder is genetically heterogeneous, with 11 BBS genes identified to date, which account for ~70% of affected families. We have combined single-nucleotide-polymorphism array homozygosity mapping with in silico analysis to identify a new BBS gene, BBS12. Patients from two Gypsy families were homozygous and haploidentical in a 6-Mb region of chromosome 4q27. FLJ35630 was selected as a candidate gene, because it was predicted to encode a protein with similarity to members of the type II chaperonin superfamily, which includes BBS6 and BBS10. We found pathogenic mutations in both Gypsy families, as well as in 14 other families of various ethnic backgrounds, indicating that BBS12 accounts for approximately 5% of all BBS cases. BBS12 is vertebrate specific and, together with BBS6 and BBS10, defines a novel branch of the type II chaperonin superfamily. These three genes are characterized by unusually rapid evolution and are likely to perform ciliary functions specific to vertebrates that are important in the pathophysiology of the syndrome, and together they account for about one-third of the total BBS mutational load. Consistent with this notion, suppression of each family member in zebrafish yielded gastrulation-movement defects characteristic of other BBS morphants, whereas simultaneous suppression of all three members resulted in severely affected embryos, possibly hinting at partial functional redundancy within this protein family. 相似文献
52.
rx1 and pax6 are necessary for the establishment of the vertebrate eye field and for the maintenance of the retinal stem cells that give rise to multiple retinal cell types. They also are differentially expressed in cellular layers in the retina when cell fates are being specified, and their expression levels differentially affect the production of amacrine cell subtypes. To determine whether rx1 and pax6 expression after the eye field is established simply maintains stem cell-like qualities or affects cell type differentiation, we used hormone-inducible constructs to increase or decrease levels/activity of each protein at two different neural plate stages. Our results indicate that rx1 regulates the size of the retinal stem cell pool because it broadly affected all cell types, whereas pax6 regulates more restricted retinal progenitor cells because it selectively affected different cell types in a time-dependent manner. Analysis of rx1 and pax6 effects on proliferation, and expression of stem cell or differentiation markers demonstrates that rx1 maintains cells in a stem cell state by promoting proliferation and delaying expression of neural identity and differentiation markers. Although pax6 also promotes proliferation, it differentially regulates neural identity and differentiation genes. Thus, these two genes work in parallel to regulate different, but overlapping aspects of retinal cell fate determination. 相似文献
53.
Marburg virus (MARV) matrix protein VP40 plays a key role in virus assembly, recruiting nucleocapsids and the surface protein GP to filopodia, the sites of viral budding. In addition, VP40 is the only MARV protein able to induce the release of filamentous virus-like particles (VLPs) indicating its function in MARV budding. Here, we demonstrated that VP40 is phosphorylated and that tyrosine residues at positions 7, 10, 13 and 19 represent major phosphorylation acceptor sites. Mutagenesis of these tyrosine residues resulted in expression of a non-phosphorylatable form of VP40 (VP40(mut) ). VP40(mut) was able to bind to cellular membranes, produce filamentous VLPs, and inhibit interferon-induced gene expression similarly to wild-type VP40. However, VP40(mut) was specifically impaired in its ability to recruit nucleocapsid structures into filopodia, and released infectious VLPs (iVLPs) had low infectivity. These results indicated that tyrosine phosphorylation of VP40 is important for triggering the recruitment of nucleocapsids to the viral envelope. 相似文献
54.
Emmanuel Cornillot Kamel Hadj-Kaddour Amina Dassouli Benjamin Noel Vincent Ranwez Beno?t Vacherie Yoann Augagneur Virginie Brès Aurelie Duclos Sylvie Randazzo Bernard Carcy Fran?oise Debierre-Grockiego Stéphane Delbecq Karina Moubri-Ménage Hosam Shams-Eldin Sahar Usmani-Brown Frédéric Bringaud Patrick Wincker Christian P. Vivarès Ralph T. Schwarz Theo P. Schetters Peter J. Krause André Gorenflot Vincent Berry Valérie Barbe Choukri Ben Mamoun 《Nucleic acids research》2012,40(18):9102-9114
We have sequenced the genome of the emerging human pathogen Babesia microti and compared it with that of other protozoa. B. microti has the smallest nuclear genome among all Apicomplexan parasites sequenced to date with three chromosomes encoding ∼3500 polypeptides, several of which are species specific. Genome-wide phylogenetic analyses indicate that B. microti is significantly distant from all species of Babesidae and Theileridae and defines a new clade in the phylum Apicomplexa. Furthermore, unlike all other Apicomplexa, its mitochondrial genome is circular. Genome-scale reconstruction of functional networks revealed that B. microti has the minimal metabolic requirement for intraerythrocytic protozoan parasitism. B. microti multigene families differ from those of other protozoa in both the copy number and organization. Two lateral transfer events with significant metabolic implications occurred during the evolution of this parasite. The genomic sequencing of B. microti identified several targets suitable for the development of diagnostic assays and novel therapies for human babesiosis. 相似文献
55.
Nanotubes impregnated human olfactory bulb neural stem cells promote neuronal differentiation in Trimethyltin‐induced neurodegeneration rat model
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56.
Integrating biogeography,threat and evolutionary data to explore extinction crisis in the taxonomic group of cycads
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Kowiyou Yessoufou Barnabas H. Daru Respinah Tafirei Hosam O. Elansary Isaac Rampedi 《Ecology and evolution》2017,7(8):2735-2746
Will the ongoing extinction crisis cause a severe loss of evolutionary information accumulated over millions of years on the tree of life? This question has been largely explored, particularly for vertebrates and angiosperms. However, no equivalent effort has been devoted to gymnosperms. Here, we address this question focusing on cycads, the gymnosperm group exhibiting the highest proportion of threatened species in the plant kingdom. We assembled the first complete phylogeny of cycads and assessed how species loss under three scenarios would impact the cycad tree of life. These scenarios are as follows: (1) All top 50% of evolutionarily distinct (ED ) species are lost; (2) all threatened species are lost; and (3) only all threatened species in each IUCN category are lost. Finally, we analyzed the biogeographical pattern of cycad diversity hotspots and tested for gaps in the current global conservation network. First, we showed that threatened species are not significantly clustered on the cycad tree of life. Second, we showed that the loss of all vulnerable or endangered species does not depart significantly from random loss. In contrast, the loss of all top 50% ED , all threatened or all critically endangered species, would result in a greater loss of PD (Phylogenetic Diversity) than expected. To inform conservation decisions, we defined five hotpots of diversity, and depending on the diversity metric used, these hotspots are located in Southern Africa, Australia, Indo‐Pacific, and Mexico and all are found within protected areas. We conclude that the phylogenetic diversity accumulated over millions of years in the cycad tree of life would not survive the current extinction crisis. As such, prioritizing efforts based on ED and concentrating efforts on critically endangered species particularly in southern Africa, Australia, Indo‐Pacific, and Mexico are required to safeguarding the evolutionary diversity in the cycad tree of life. 相似文献
57.
Shankargouda Patil Hytham N. Fageeh Hammam Ibrahim Fageeh Wael Ibraheem Abdulrahman Saleh Alshehri Ashraf Al-Brakati Salem Almoammar Mohammad Almagbol Harisha Dewan Samar Saeed Khan Hosam Ali Baeshen Vikrant R Patil A. Thirumal Raj Shilpa Bhandi 《Saudi Journal of Biological Sciences》2022,29(5):3568-3576
Gingival mesenchymal stem cells (GMSCs) have significant regenerative potential. Their potential applications range from the treatment of inflammatory diseases, wound healing, and oral disorders. Preconditioning these stem cells can optimize their biological properties. Hypoxia preconditioning of MSCs improves stem cell properties like proliferation, survival, and differentiation potential. This research explored the possible impact of hypoxia on the pluripotent stem cell properties that GMSCs possess. We evaluated the morphology, stemness, neurotrophic factors, and stemness-related genes. We compared the protein levels of secreted neurotrophic factors between normoxic and hypoxic GMSC-conditioned media (GMSC-CM). Results revealed that hypoxic cultured GMSC’s had augmented expression of neurotrophic factors BDNF, GDNF, VEGF, and IGF1 and stemness-related gene NANOG. Hypoxic GMSCs showed decreased expression of the OCT4 gene. In hypoxic GMSC-CM, the neurotrophic factors secretions were significantly higher than normoxic GMSC-CM. Our data demonstrate that culturing of GMSCs in hypoxia enhances the secretion of neurotrophic factors that can lead to neuronal lineage differentiation. 相似文献
58.
Andaloussi SE Lehto T Mäger I Rosenthal-Aizman K Oprea II Simonson OE Sork H Ezzat K Copolovici DM Kurrikoff K Viola JR Zaghloul EM Sillard R Johansson HJ Said Hassane F Guterstam P Suhorutšenko J Moreno PM Oskolkov N Hälldin J Tedebark U Metspalu A Lebleu B Lehtiö J Smith CI Langel U 《Nucleic acids research》2011,39(9):3972-3987
59.
60.
Sylvain Geny Pedro?M.?D. Moreno Tomasz Krzywkowski Olof Gissberg Nicolai K. Andersen Abdirisaq J. Isse Amro M. El-Madani Chenguang Lou Y. Vladimir Pabon Brooke A. Anderson Eman M. Zaghloul Rula Zain Patrick J. Hrdlicka Per T. J?rgensen Mats Nilsson Karin E. Lundin Erik B. Pedersen Jesper Wengel C.?I.?Edvard Smith 《Nucleic acids research》2016,44(5):2007-2019
Targeting and invading double-stranded DNA with synthetic oligonucleotides under physiological conditions remain a challenge. Bis-locked nucleic acids (bisLNAs) are clamp-forming oligonucleotides able to invade into supercoiled DNA via combined Hoogsteen and Watson–Crick binding. To improve the bisLNA design, we investigated its mechanism of binding. Our results suggest that bisLNAs bind via Hoogsteen-arm first, followed by Watson–Crick arm invasion, initiated at the tail. Based on this proposed hybridization mechanism, we designed next-generation bisLNAs with a novel linker able to stack to adjacent nucleobases, a new strategy previously not applied for any type of clamp-constructs. Although the Hoogsteen-arm limits the invasion, upon incorporation of the stacking linker, bisLNA invasion is significantly more efficient than for non-clamp, or nucleotide-linker containing LNA-constructs. Further improvements were obtained by substituting LNA with 2′-glycylamino-LNA, contributing a positive charge. For regular bisLNAs a 14-nt tail significantly enhances invasion. However, when two stacking linkers were incorporated, tail-less bisLNAs were able to efficiently invade. Finally, successful targeting of plasmids inside bacteria clearly demonstrates that strand invasion can take place in a biologically relevant context. 相似文献