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141.
Seval Türkmen Gao Guo Masoud Garshasbi Katrin Hoffmann Amjad J. Alshalah Claudia Mischung Andreas Kuss Nicholas Humphrey Stefan Mundlos Peter N. Robinson 《PLoS genetics》2009,5(5)
We describe a consanguineous Iraqi family in which affected siblings had mild mental retardation and congenital ataxia characterized by quadrupedal gait. Genome-wide linkage analysis identified a 5.8 Mb interval on chromosome 8q with shared homozygosity among the affected persons. Sequencing of genes contained in the interval revealed a homozygous mutation, S100P, in carbonic anhydrase related protein 8 (CA8), which is highly expressed in cerebellar Purkinje cells and influences inositol triphosphate (ITP) binding to its receptor ITPR1 on the endoplasmatic reticulum and thereby modulates calcium signaling. We demonstrate that the mutation S100P is associated with proteasome-mediated degradation, and thus presumably represents a null mutation comparable to the Ca8 mutation underlying the previously described waddles mouse, which exhibits ataxia and appendicular dystonia. CA8 thus represents the third locus that has been associated with quadrupedal gait in humans, in addition to the VLDLR locus and a locus at chromosome 17p. Our findings underline the importance of ITP-mediated signaling in cerebellar function and provide suggestive evidence that congenital ataxia paired with cerebral dysfunction may, together with unknown contextual factors during development, predispose to quadrupedal gait in humans. 相似文献
142.
Moghadam M Nasr-Esfahani M Tangestaninejad S Mirkhani V 《Bioorganic & medicinal chemistry letters》2006,16(7):2026-2030
Mild and efficient oxidation of Hantzsch 1,4-dihydropyridines with sodium periodate catalyzed by Mn(TTP)Cl supported on polystyrene-bound imidazole is reported. This heterogeneous catalyst is of great stability and reusability in the oxidation of 1,4-dihydropyridines with sodium periodate without significant loss of its catalytic activity. 相似文献
143.
Tarlan Eslami-Arshaghi Saeid Vakilian Ehsan Seyedjafari Abdolreza Ardeshirylajimi Masoud Soleimani Mohammad Salehi 《In vitro cellular & developmental biology. Animal》2017,53(4):371-380
A combination of nanotopographical cues and surface modification of collagen and fibronectin is a potential platform in primordial germ cells (PGCs) differentiation. In the present study, the synergistic effect of nanotopography and surface modification on differentiation of nuclear transfer embryonic stem cells (nt-ESCs) toward PGC lineage was investigated. In order to achieve this goal, poly-anyline (PANi) was mix within poly-l-lactic acid (PLLA). Afterward, the random composite mats were fabricated using PLLA and PANi mix solution. The nanofiber topography notably upregulated the expressions of prdm14, mvh and c-kit compared with tissue culture polystyrene (TCP). Moreover, the combination of nanofiber topography and surface modification resulted in more enhancement of PGCs differentiation compared with non-modified nanofibrous scaffold. Additionally, gene expression results showed that mvh and c-kit were expressed at higher intensity in cells exposed to collagen and fibronectin rather than collagen or fibronectin solitary. These results demonstrated the importance of combined effect of collagen and fibronectin in order to develop a functional extracellular matrix (ECM) mimic in directing stem cell fate and the potential of such biofunctional scaffolds for treatment of infertility. 相似文献
144.
145.
Hamdan FF Gauthier J Araki Y Lin DT Yoshizawa Y Higashi K Park AR Spiegelman D Dobrzeniecka S Piton A Tomitori H Daoud H Massicotte C Henrion E Diallo O;SD Group Shekarabi M Marineau C Shevell M Maranda B Mitchell G Nadeau A D'Anjou G Vanasse M Srour M Lafrenière RG Drapeau P Lacaille JC Kim E Lee JR Igarashi K Huganir RL Rouleau GA Michaud JL 《American journal of human genetics》2011,(3):1427-316
Little is known about the genetics of nonsyndromic intellectual disability (NSID). We hypothesized that de novo mutations (DNMs) in synaptic genes explain an important fraction of sporadic NSID cases. In order to investigate this possibility, we sequenced 197 genes encoding glutamate receptors and a large subset of their known interacting proteins in 95 sporadic cases of NSID. We found 11 DNMs, including ten potentially deleterious mutations (three nonsense, two splicing, one frameshift, four missense) and one neutral mutation (silent) in eight different genes. Calculation of point-substitution DNM rates per functional and neutral site showed significant excess of functional DNMs compared to neutral ones. De novo truncating and/or splicing mutations in SYNGAP1, STXBP1, and SHANK3 were found in six patients and are likely to be pathogenic. De novo missense mutations were found in KIF1A, GRIN1, CACNG2, and EPB41L1. Functional studies showed that all these missense mutations affect protein function in cell culture systems, suggesting that they may be pathogenic. Sequencing these four genes in 50 additional sporadic cases of NSID identified a second DNM in GRIN1 (c.1679_1681dup/p.Ser560dup). This mutation also affects protein function, consistent with structural predictions. None of these mutations or any other DNMs were identified in these genes in 285 healthy controls. This study highlights the importance of the glutamate receptor complexes in NSID and further supports the role of DNMs in this disorder. 相似文献
146.
Bayat PD Ghanbari A Saeid B Khazaei M Ghorbani R Ayubian M 《Indian journal of experimental biology》2011,49(8):634-638
Total body weight of newborns, the volume of spleen, and the number of megakaryocytes decreased following the exposure to ELF-MF (6 x 10(-3) T and 50 Hz) at 1-5, 6-10, 11-15, and 16-20 days of pregnancy of mice. The complete period of gestation was sensitive to ELF-MF exposure; the initial days were more prone to exposure. The results suggest that the use of ELF-MF producing instruments should be limited during gestation. 相似文献
147.
Although CD8+ cytotoxic T lymphocyte (CTL) epitope-based DNA vaccination is valuable experience on vaccine research but many attempts are still continued to achieve acceptable protective response. To study the role of full length antigen in CTL epitope immunization, we evaluated cellular immunity of diverse patterns of complete Herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) and the immunodominant CTL epitope (498–505) DNA injection in C57BL/6 mice. Optimal immune response was observed in the group immunized with the full length of gB in the first injection and CTL epitope in the second and third vaccination as assessed by lymphocyte proliferation assay (MTT), cytokine assay (ELISA) and CTL assay. B cell and spatially CD4+ T cell epitopes in full length protein might be important for appropriate priming of CTL immune response. These findings may have important implication for the improvement of CTL epitope based DNA vaccine against HSV and other pathogens. 相似文献
148.
Ceccarelli DF Tang X Pelletier B Orlicky S Xie W Plantevin V Neculai D Chou YC Ogunjimi A Al-Hakim A Varelas X Koszela J Wasney GA Vedadi M Dhe-Paganon S Cox S Xu S Lopez-Girona A Mercurio F Wrana J Durocher D Meloche S Webb DR Tyers M Sicheri F 《Cell》2011,145(7):1075-1087
In the ubiquitin-proteasome system (UPS), E2 enzymes mediate the conjugation of ubiquitin to substrates and thereby control protein stability and interactions. The E2 enzyme hCdc34 catalyzes the ubiquitination of hundreds of proteins in conjunction with the cullin-RING (CRL) superfamily of E3 enzymes. We identified a small molecule termed CC0651 that selectively inhibits hCdc34. Structure determination revealed that CC0651 inserts into a cryptic binding pocket on hCdc34 distant from the catalytic site, causing subtle but wholesale displacement of E2 secondary structural elements. CC0651 analogs inhibited proliferation of human cancer cell lines and caused accumulation of the SCF(Skp2) substrate p27(Kip1). CC0651 does not affect hCdc34 interactions with E1 or E3 enzymes or the formation of the ubiquitin thioester but instead interferes with the discharge of ubiquitin to acceptor lysine residues. E2 enzymes are thus susceptible to noncatalytic site inhibition and may represent a viable class of drug target in the UPS. 相似文献
149.
We develop a simple elastic model to study the conformation of DNA in the nucleosome core particle. In this model, the changes in the energy of the covalent bonds that connect the base pairs of each strand of the DNA double helix, as well as the lateral displacements and the rotation of adjacent base pairs are considered. We show that because of the rigidity of the covalent bonds in the sugar-phosphate backbones, the base pair parameters are highly correlated, especially, strong twist-roll-slide correlation in the conformation of the nucleosomal DNA is vividly observed in the calculated results. This simple model succeeds to account for the detailed features of the structure of the nucleosomal DNA, particularly, its more important base pair parameters, roll and slide, in good agreement with the experimental results. 相似文献
150.
Majid Ghorbani Javid Ali Sorooshzadeh Seyed Ali Mohammad Modarres Sanavy Iraj Allahdadi Foad Moradi 《Plant Growth Regulation》2011,65(2):305-313
Phytohormones, such as auxin and cytokinin, are known to be involved in the regulation of plant responses to salinity stress
and counteract the adverse effect of stress conditions. This work investigated the effects of the exogenous spraying of indole-3-acetic
acid (IAA) and kinetin (KIN) during the reproductive phase on grain yield by examining the 1000-grain weight and filled-grain
percentage as well as the changes in starch, total soluble sugars, sucrose, glucose and fructose concentrations in the grains
of two rice cultivars under salt stress. The results indicated that the applied IAA and KIN led to an increased grain yield,
1000-grain weight and filled-grain percentage for both rice cultivars under salt stress. The storage starch content in the
grain of the salt-sensitive cultivar was more than that in the salt-tolerant cultivar under IAA application compared with
KIN, whereas a decrease in the total soluble sugar content was observed with both IAA and KIN treatments, in comparison to
the non-hormone treatment. Interestingly, this study showed that IAA led to a much higher increase in the sucrose content
in grain, as compared to the KIN. Furthermore, this experiment suggests that glucose and fructose may play important roles
during salt stress because there were clearly higher concentrations of these sugars in the grain of the stressed cultivars
under IAA and KIN application: it appears that their accumulation was the earliest response detected during the grain-filling
period in rice. Finally, this work indicated that an increase in the rice grain yield, 1000-grain weight and filled-grain
percentage are associated with an increase in the contents of starch, sucrose, glucose and fructose in grain caused by the
application of IAA and KIN. 相似文献