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1.
Recent studies have emphasized the important role of microRNA (miRNA) clusters and common target genes in disease progression. Despite the known involvement of the miR‐192/215 family in many human diseases, its biological role in Hirschsprung disease (HSCR) remains undefined. In this study, we explored the role of the miR‐192/215 family in the pathogenesis of HSCR. Quantitative real‐time PCR and western blotting measured relative expression levels of miRNAs, mRNAs, and proteins in 80 HSCR patients and 77 normal colon tissues. Targets were evaluated by dual‐luciferase reporter assays, and the functional effects of miR‐192/215 on human 293T and SH‐SY5Y cells were detected by the Transwell assay, CCK8 assay and flow cytometry. MiR‐192/215 was significantly down‐regulated in HSCR tissue samples, and their knockdown inhibited cell migration and proliferation in the human 293T and SH‐SY5Y cell lines. Nidogen 1 (NID1) was confirmed as a common target gene of miR‐192/215 by dual‐luciferase reporter gene assay and its expression was inversely correlated with that of miR‐192/215 in tissue samples and cell lines. Silencing of NID1 could rescue the extent of the suppressing effects by miR‐192/215 inhibitor. The down‐regulation of miR‐192/215 may contribute to HSCR development by targeting NID1.

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2.
Kernel size and kernel weight are important factors possibly involved in the determination of grain yield in maize, so identifying the genetic basis of kernel-related traits provides insights into the breeding of high-yield maize varieties. Kernel length (KL), kernel width (KW) and hundred kernel weight (HKW) were evaluated in three various planting conditions for the 240 field-grown double haploid (DH) lines derived from the single-cross hybrid Xianyu335. Variations in KL, KW and HKW were observed among DH lines, and all three traits showed a broad sense heritability of 76%. A total of 964 single nucleotide polymorphisms (SNPs) from the MaizeSNP3072 chip was utilised to create a high-density genetic map of 1546.4 cM and to identify quantitative trait loci (QTLs). Using composite interval mapping, a total of five, seven and five QTLs have been mapped for KL, KW and HKW, respectively. qkl1-2 and qkl4-1 explained 17.8% and 14.2% of the phenotypic variation in KL, respectively, and the other three QTLs contributed 3.2–4.0%. The phenotypic variation explained (PVE) of seven QTLs responsible for KW ranged from 3.3 to 9.5%. Three QTLs for HKW, qhkw1, qhkw5 and qhkw10 each explained more than 10% of the phenotypic variation, and qhkw4 and qhkw9 accounted for 3.0% and 6.0%, respectively. Due to their detection in multiple planting environments, the loci mapped here appear to be potential targets for the improvement of maize grain yield.  相似文献   
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α1‐adrenoceptors (α1‐ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α1‐ARs stimulation enhances glutamatergic transmission via both pre‐ and post‐synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre‐synaptic mechanisms may contribute to α1‐ARs‐induced enhancement of glutamate release. In this study, we blocked the possible post‐synaptic action mediated by α1‐ARs to investigate how α1‐ARs activation regulates pre‐synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α1‐ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe‐induced potentiation was mediated by enhancing pre‐synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C‐dependent pathway. The mechanisms of Phe‐induced potentiation included interaction with both glutamate release machinery and N‐type Ca2+ channels, probably via a pre‐synaptic Gq/phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α1‐ARs‐mediated influence on PFC cognitive functions.

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Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2f/f) and their corresponding wild-type background mice (MyhCre.Tgfbr2WT/WT) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.  相似文献   
7.
Mesenchymal stem cells (MSCs) are non-hematopoietic cells with multi-lineage potential, which makes them attractive targets for regenerative medicine applications. Efficient gene transfer into MSCs is essential for basic research in developmental biology and for therapeutic applications involving gene-modification in regenerative medicine. Adenovirus vectors (Advs) can efficiently and transiently introduce an exogenous gene into many cell types via their primary receptors, the coxsackievirus and adenovirus receptors (CARs), but not into MSCs, which lack CAR expression. To overcome this problem, an Adv coated with cationic polymer polyethyleneimine (PEI) was developed. In this study, we demonstrated that PEI coating with an optimal ratio can enhance adenoviral transduction of MSCs without cytotoxicity. We also investigated the physicochemical properties and internalization mechanisms of the PEI-coated Adv. These results could help to evaluate the potentiality of the PEI-coated Adv as a prototype vector for efficient and safe transduction into MSCs.  相似文献   
8.
Polyomavirus BK (BKV) infection is an important cause of renal allograft failure. Viral microRNAs are known to play a crucial role in viral replication. This study investigated the expression of BKV-encoded microRNAs (miR-B1) in patients with polyomavirus-associated nephropathy (PVAN) and their role in viral replication. Following BKV infection in renal proximal tubular cells, the 3p and 5p miR-B1 levels were significantly increased. Cells transfected with the vector containing the miR-B1 precursor (the miR-B1 vector) showed a significant increase in expression of 3p and 5p miR-B1 and decrease in luciferase activity of a reporter containing the 3p and 5p miR-B1 binding sites, compared to cells transfected with the miR-B1-mutated vector. Transfection of the miR-B1 expression vector or the 3p and 5p miR-B1 oligonucleotides inhibited expression of TAg. TAg-enhanced promoter activity and BKV replication were inhibited by miR-B1. In contrast, inhibition of miR-B1 expression by addition of miR-B1 antagomirs or silencing of Dicer upregulated the expression of TAg and VP1 proteins in BKV-infected cells. Importantly, patients with PVAN had significantly higher levels of 3p and 5p miR-B1 compared to renal transplant patients without PVAN. In conclusion, we demonstrated that (1) miR-B1 expression was upregulated during BKV infection and (2) miR-B1 suppressed TAg-mediated autoregulation of BKV replication. Use of miR-B1 can be evaluated as a potential treatment strategy against BKV infection.  相似文献   
9.
A novel actinobacterium, designated strain NEAU-ML12T, was isolated from a millipede (Kronopolites svenhedind Verhoeff), which was collected from Fenghuang Mountain in Wuchang, Heilongjiang Province, north China. The strain was characterized using a polyphasic approach. Strain NEAU-ML12T was found to have morphological and chemotaxonomic characteristics typical of the members of the genus Rhodococcus. 16S rRNA gene sequence similarity analysis showed that the strain NEAU-ML12T belongs to the genus Rhodococcus, and was most closely related to Rhodococcus tukisamuensis Mb8T (98.9 %) and Rhodococcus koreensis DNP505T (97.7 %). Phylogenetic analysis based on 16S rRNA gene sequences also demonstrated that strain NEAU-ML12T should be classified in the genus Rhodococcus, forming a distinct clade with R. tukisamuensis Mb8T supported by a 99 % bootstrap value. However, the DNA–DNA relatedness between strain NEAU-ML12T and R. tukisamuensis Mb8T was found to be 41.9 ± 0.7 %. Furthermore, strain NEAU-ML12T could also be differentiated from R. tukisamuensis Mb8T and other closely related strains (R. koreensis DNP505T and Rhodococcus maanshanensis M712T) by morphological and physiological characteristics. Therefore, it is proposed that strain NEAU-ML12T represents a novel species of the genus Rhodococcus, for which the name Rhodococcus kronopolitis sp. nov. is proposed. The type strain is NEAU-ML12T (=CGMCC 4.7145T = DSM 46702T).  相似文献   
10.
The insulin receptor (IR) binds insulin and plays important roles in glucose homeostasis by regulating the tyrosine kinase activity at its C-terminus. Its transmembrane domain (TMD) is shown to be important for transferring conformational changes induced by insulin across the cell membrane to regulate kinase activity. In this study, a construct IR940–988 containing the TMD was expressed and purified for structural studies. Its solution structure in dodecylphosphocholine (DPC) micelles was determined. The sequence containing residues L962 to Y976 of the TMD of the IR in micelles adopts a well-defined helical structure with a kink formed by glycine and proline residues present at its N-terminus, which might be important for its function. Paramagnetic relaxation enhancement (PRE) and relaxation experimental results suggest that residues following the TMD are flexible and expose to aqueous solution. Although purified IR940–988 in micelles existed mainly as a monomeric form verified by gel filtration and relaxation analysis, cross-linking study suggests that it may form a dimer or oligomers under micelle conditions.  相似文献   
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