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951.
Ting-Yi Lin Yun-Chia Chang Yu-Jer Hsiao Yueh Chien Ying-Chun Jheng Jing-Rong Wu Lo-Jei Ching De-Kuang Hwang Chih-Chien Hsu Tai-Chi Lin Yu-Bai Chou Yi-Ming Huang Shih-Jen Chen Yi-Ping Yang Ping-Hsing Tsai 《International journal of molecular sciences》2021,22(11)
Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia. 相似文献
952.
953.
本文提出了模型参数优化的降维计算方法的基本思想。它通过构造参向量空间某个子空间某个子空间族的极小化点集,使一个高维优化问题转化成等价的低维优化问题。降维法的应用常常可以有效地避免高维优化问题中的发散和伪收敛。由于降维法具有很强的收敛性和很宽的收敛初值范围,因此对许多函数性态较差,参数之间相关程度较大的优化问题,一般的通用方法较难给出理想的结果,而降维法的应用却可以使收敛情况大为改观。本文结合相平衡中的一些实例阐明了降维法的基本思想和极小化点集的构造技巧。 相似文献
954.
Chia-Hung Lin Chen-Chung Liao Mei-Yu Chen Teh-Ying Chou 《International journal of molecular sciences》2021,22(7)
Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis. 相似文献
955.
There are large variations between different previously published lightness difference experimental data sets. Two hundred and eight pairs of matt and glossy paint samples exhibiting mainly lightness differences were accumulated. Each pair was assessed about twenty times by a panel of fourteen observers using the grey scale method. The results were used to derive a new lightness difference formula (CII), and to a large extent, a possible new CIE lightness difference formula (CMC99). Both formulae were found to be more accurate than the typical deviation of an individual assessment from the mean of a panel of 20 observers, and outperformed the existing formulae using the present data set. The new CMC99 lightness difference formula is integrated into the new CIE colour difference equation CIEDE2000. The results also showed that special attention should be paid to measuring very dark samples. This is caused by poor instrument repeatability and inter-instrument agreement in this colour region. 相似文献
956.
High‐level extracellular production of penicillin acylase by genetic engineering of Escherichia coli
Wen‐Jer Lin Shin‐Wei Huang C Perry Chou 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2001,76(10):1030-1037
The extracellular production of penicillin acylase (PAC) in genetically engineered Escherichia coli by coexpression of the brp gene encoding bacteriocin release protein (BRP) and the pac gene was demonstrated. Cell physiology was affected while PAC was released into the medium, depending on the strategy for brp expression. The performance for the production and release of PAC was optimized by taking several culture parameters, including host, inducer (mitomycin C) concentration, and induction timing for brp expression, into consideration. The effect of PAC release on inclusion body formation was also investigated. It was observed that the amount of inclusion bodies was significantly affected by brp expression. A reason for the limitation of PAC production and a strategy for resolving this problem are proposed. © 2001 Society of Chemical Industry 相似文献
957.
Due to strong anti-poisoning ability, good emission stability, high emission current density, lanthanum hexaboride (LaB6) and cerium hexaboride (CeB6) have been maturely applied in electron emission emitter. In this paper, a new manufacturing method for LaB6 (or CeB6) powder was proposed by using La2O3 (or CeO2), B4C, and Al as raw materials. After high-temperature reaction in the range of 1673–1773 K and the following alkaline leaching at 90°C, LaB6 or CeB6 powder with particle size of about 10 μm was obtained. Furthermore, by Al metal flux method, the obtained powder was used to manufacture single crystal block with size of several millimeters. 相似文献
958.
Yi-Fan Chou Yu-Hsuan Lan Jun-Han Hsiao Chiao-Yun Chen Pei-Yu Chou Ming-Jyh Sheu 《International journal of molecular sciences》2022,23(7)
Background: Angiogenesis is primarily attributed to the excessive proliferation and migration of endothelial cells. Targeting the vascular endothelial growth factor (VEGF) is therefore significant in anti-angiogenic therapy. Although these treatments have not reached clinical expectations, the upregulation of alternative angiogenic pathways (endoglin/Smad1) may play a critical role in drug (VEGF-neutralizing agents) resistance. Enhanced endoglin expression following a VEGF-neutralizing therapy (semaxanib®) was noted in patients. Treatment with an endoglin-targeting antibody augmented VEGF expression in human umbilical vein endothelial cells (HUVECs). Therefore, approaches that inhibit both the androgen and VEGF pathways enhance the HUVECs cytotoxicity and reverse semaxanib resistance. The purpose of this study was to find natural-occurring compounds that inhibited the endoglin-targeting pathway. Methods: Curcuminoids targeting endoglin were recognized from two thousand compounds in the Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan) using Discovery Studio 4.5. Results: Our results, obtained using cytotoxicity, migration/invasion, and flow cytometry assays, showed that curcumin (Cur) and demethoxycurcumin (DMC) reduced angiogenesis. In addition, Cur and DMC downregulated endoglin/pSmad1 phosphorylation. Conclusions: The study first showed that Cur and DMC demonstrated antiangiogenic activity via the inhibition of endoglin/Smad1 signaling. Synergistic effects of curcuminoids (i.e., curcumin and DMC) and semaxanib on HUVECs were found. This might be attributed to endoglin/pSmad1 downregulation in HUVECs. Combination treatment with curcuminoids and a semaxanib is therefore expected to reverse semaxanib resistance. 相似文献
959.
Conjugation and Evaluation of Triazole‐Linked Single Guide RNA for CRISPR‐Cas9 Gene Editing 下载免费PDF全文
Dr. Kaizhang He Eldon T. Chou Shawn Begay Dr. Emily M. Anderson Dr. Anja van Brabant Smith 《Chembiochem : a European journal of chemical biology》2016,17(19):1809-1812
The CRISPR‐Cas9 gene editing system requires Cas9 endonuclease and guide RNAs (either the natural dual RNA consisting of crRNA and tracrRNA or a chimeric single guide RNA) that direct site‐specific double‐stranded DNA cleavage. This communication describes a click ligation approach that uses alkyne–azide cycloaddition to generate a triazole‐linked single guide RNA (sgRNA). The conjugated sgRNA shows efficient and comparable genome editing activity to natural dual RNA and unmodified sgRNA constructs. 相似文献
960.