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961.
962.
Silke Schreiner Anna Didio Lee-Hsueh Hung Albrecht Bindereif 《Nucleic acids research》2020,48(21):12326
Circular RNAs (circRNAs) are a class of noncoding RNAs, generated from pre-mRNAs by circular splicing of exons and functionally largely uncharacterized. Here we report on the design, expression, and characterization of artificial circRNAs that act as protein sponges, specifically binding and functionally inactivating hnRNP (heterogeneous nuclear ribonucleoprotein) L. HnRNP L regulates alternative splicing, depending on short CA-rich RNA elements. We demonstrate that designer hnRNP L-sponge circRNAs with CA-repeat or CA-rich sequence clusters can efficiently and specifically modulate splicing-regulatory networks in mammalian cells, including alternative splicing patterns and the cellular distribution of a splicing factor. This new strategy can in principle be applied to any RNA-binding protein, opening up new therapeutic strategies in molecular medicine. 相似文献
963.
Finn Hung Liang Deng Paula Ravnikar Russ Condon Benson Li Lien Do Deba Saha Yung-Shyeng Tsao Ankit Merchant Zhong Liu Shuangping Shi Dr. 《Biotechnology journal》2010,5(4):393-401
The productivity of stably transfected cell lines is of critical importance for the manufacturing of therapeutic proteins. Various methods have been successfully implemented to increase the production output of mammalian cell cultures. Increasing evidence suggests that optimization of the gene coding sequences of an expression vector can improve specific cell line yield of the recombinant protein. Here we demonstrate that gene optimization substantially enhances antibody production in Chinese hamster ovary cells. When gene optimization was applied to the heavy and light chain genes of a therapeutic antibody, we observed increased antibody production in transient transfection. Elevated heavy chain mRNA level was associated with the increase of antibody production. Further analysis suggested that the increased antibody expression is attributable to enhanced mRNA stability resulting from gene optimization. Gene optimization also led to increased antibody production in stable clones. 相似文献
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967.
N. C. Yang K. L. Hwang D. Z. Hung H. H. Wuhh W. M. Ho 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2000,742(2):173
Isoflurane is a nonflammable, liquid, volatile inhalation anesthetic administered by vaporizing. Although it is now commonly used, fatal cases resulting from its abuse or misuse have been reported. A combined system of a gas chromatograph–mass spectrometer and a headspace autosampler is therefore proposed for the detection of blood isoflurane. This analytic method showed sharp and well separated peaks, and revealed a good linear relationship (r=0.9994) with a function of y=7.3768x−0.0222 at concentrations between 18.7 and 299.2 μg/ml. The limits of detection and quantitation of this method were 1.2 and 4.7 μg/ml, respectively. The within- and between-run precision for spiked samples, assessed by the coefficient of variations, ranged from 1.7 to 10.0% and from 4.1 to 12.8%, respectively. The within- and between-run accuracy, assessed by errors from theoretical values, were 2.2–7.8% and 2.4–9.6%, respectively. In addition, practical sample analysis showed a good applicability, with a within-run precision rate of 5.6 to 7.7% and a between-run precision rate of 5.2–10.6%. In summary, the present work presents a valid alternative for blood isoflurane analysis. 相似文献
968.
Burton M. Wice Songyan Wang Dan L. Crimmins Kelly A. Diggs-Andrews Matthew C. Althage Eric L. Ford Hung Tran Matthew Ohlendorf Terry A. Griest Qiuling Wang Simon J. Fisher Jack H. Ladenson Kenneth S. Polonsky 《The Journal of biological chemistry》2010,285(26):19842-19853
The intestinal peptides GLP-1 and GIP potentiate glucose-mediated insulin release. Agents that increase GLP-1 action are effective therapies in type 2 diabetes mellitus (T2DM). However, GIP action is blunted in T2DM, and GIP-based therapies have not been developed. Thus, it is important to increase our understanding of the mechanisms of GIP action. We developed mice lacking GIP-producing K cells. Like humans with T2DM, “GIP/DT” animals exhibited a normal insulin secretory response to exogenous GLP-1 but a blunted response to GIP. Pharmacologic doses of xenin-25, another peptide produced by K cells, restored the GIP-mediated insulin secretory response and reduced hyperglycemia in GIP/DT mice. Xenin-25 alone had no effect. Studies with islets, insulin-producing cell lines, and perfused pancreata indicated xenin-25 does not enhance GIP-mediated insulin release by acting directly on the β-cell. The in vivo effects of xenin-25 to potentiate insulin release were inhibited by atropine sulfate and atropine methyl bromide but not by hexamethonium. Consistent with this, carbachol potentiated GIP-mediated insulin release from in situ perfused pancreata of GIP/DT mice. In vivo, xenin-25 did not activate c-fos expression in the hind brain or paraventricular nucleus of the hypothalamus indicating that central nervous system activation is not required. These data suggest that xenin-25 potentiates GIP-mediated insulin release by activating non-ganglionic cholinergic neurons that innervate the islets, presumably part of an enteric-neuronal-pancreatic pathway. Xenin-25, or molecules that increase acetylcholine receptor signaling in β-cells, may represent a novel approach to overcome GIP resistance and therefore treat humans with T2DM. 相似文献
969.
Growth and energy budget were measured for three sizes (2.4, 11.1 and 22.5 g) of juvenile white sturgeon Acipenser transmontanus held at 18.5° C and fed tubificid worms at different levels ranging from starvation to ad libitum . For each size-class, specific growth rate increased linearly with increasing ration, and conversion efficiency was highest at the maximum ration. Growth rate decreased with increasing fish size at the maximum ration, but increased with size at each restricted ration. Conversion efficiency increased with increasing ration for each size-class and was usually highest at the maximum ration. Faecal production accounted for 3.2–5.2% of food energy. The proportion of food energy lost in nitrogenous excretion decreased with increasing ration. With increases in ration, the allocation of metabolizable energy to metabolism decreased, while that to growth increased. Fish size had no significant effect on the allocation of metabolizable energy to metabolism or growth. At the maximum ration, on average 64.9% of metabolizable energy was spent on metabolism, and 35.1% on growth. 相似文献
970.