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排序方式: 共有926条查询结果,搜索用时 156 毫秒
921.
Marijana Samardzija Andrea Corna Raquel Gomez-Sintes Mohamed Ali Jarboui Angela Armento Jerome E. Roger Eleni Petridou Wadood Haq Francois Paquet-Durand Eberhart Zrenner Pedro de la Villa Günther Zeck Christian Grimm Patricia Boya Marius Ueffing Dragana Trifunovi 《Cell death and differentiation》2021,28(4):1317
Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and, ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors, while cones remain initially unaffected. Extensive rod loss in advanced stages of the disease triggers cone death by a mechanism that is still largely unknown. Here, we show that secondary cone cell death in animal models for RP is associated with increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at late stages of the disease, when the majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival in two mouse models for RP, affected by mutations in the phosphodiesterase 6b gene. Moreover, the surviving cones remained light-sensitive, leading to an improvement in visual function. RNA-seq analysis of protected cones demonstrated that HDAC inhibition initiated multi-level protection via regulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique opportunity for targeted pharmacological protection of secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients even in advanced disease stages.Subject terms: Neuroscience, Neurological disorders 相似文献
922.
Marius Mihăşan 《Biologia》2010,65(5):760-768
Based on similarity searches, two putative pathways were previously described as being encoded by the pAO1 megaplasmid of
Arthrobacter nicotinovorans: an almost fully established nicotine-degrading pathway and a yet unknown putative sugar-catabolic pathway. The general organization
of the open reading frames (ORFs) of the latter indicated possible gene products as targets for docking experiments, aimed
at identifying possible sugar substrates of this pathway. Homology modelling and docking results with the deduced proteins
of three ORFs of the putative sugar catabolic pathway indicated D-tagatose-1,6-bisphosphate as a common ligand and thus as
substrate of the pathway. 相似文献
923.
Charles D. Schwieters Guillermo A. Bermejo G. Marius Clore 《Protein science : a publication of the Protein Society》2020,29(1):100-110
We introduce a new hydrogen bonding potential of mean force generated from high‐quality crystal structures for use in Xplor‐NIH structure calculations. This term applies to hydrogen bonds involving both backbone and sidechain atoms. When used in structure refinement calculations of 10 example protein systems with experimental distance, dihedral and residual dipolar coupling restraints, we demonstrate that the new term has superior performance to the previously developed hydrogen bonding potential of mean force used in Xplor‐NIH. 相似文献
924.
Wen Jie Zhang Frank T. Christiansen Xiongwen Wu Lawrence J. Abraham Marius Giphart Roger L. Dawkins 《Immunogenetics》1993,37(3):170-176
The evolutionary relationship between two central major histocompatibility complex (MHC) genes, C4 and CYP21, was investigated by employing pulsed field gel electrophoresis (PFGE) and conventional restriction fragment length polymorphism (RFLP) analyses in human and nonhuman primates. Using Taq I in conjunction with C4 and CYP21 probes, it has been found that there are four major types of C4 genes [defined by 7.0, 6.4, 6.0, and 5.4 kilobases (kb) Taq I fragments] and two major types of CYP21 genes (3.7 and 3.2 kb fragments) in human and nonhuman primates including chimpanzee, gorilla, and orangutan. All of the eight possible combinations of C4 and CYP21 genes can be identified on one or more human ancestral haplotypes (AH). It is concluded that each of the major types of C4 and CYP21 (and each of the combinations between these) predated human speciation. PFGE analysis with Mlu I and Pvu I suggested that each C4 + CYP21 segment has a specific length of 30–50 kb and that each AH carries one, two, three, or even more segments. In the case of C4, it is important to note that there is no simple relationship between the RFLP and the protein classifications. Thus, at least some of the expressed polymorphisms could be relatively recent in that they are carried by the same or different gene types. These findings are consistent with the hypothesis that M MHC AHs have been formed from a large pool of specific genomic segments and that further haplospecific polymorphism has developed subsequently. 相似文献
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926.