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61.
62.
C-W Fan T Chen Y-N Shang Y-Z Gu S-L Zhang R Lu S-R OuYang X Zhou Y Li W-T Meng J-K Hu Y Lu X-F Sun H Bu Z-G Zhou X-M Mo 《Cell death & disease》2013,4(10):e828
Accumulating evidence indicates that cancer-initiating cells (CICs) are responsible for cancer initiation, relapse, and metastasis. Colorectal carcinoma (CRC) is typically classified into proximal colon, distal colon, and rectal cancer. The gradual changes in CRC molecular features within the bowel may have considerable implications in colon and rectal CICs. Unfortunately, limited information is available on CICs derived from rectal cancer, although colon CICs have been described. Here we identified rectal CICs (R-CICs) that possess differentiation potential in tumors derived from patients with rectal adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R-CICs and their immediate progenies carried potential epithelial–mesenchymal transition characteristics. These R-CICs generated tumors similar to their tumor of origin when injected into immunodeficient mice, differentiated into rectal epithelial cells in vitro, and were capable of self-renewal both in vitro and in vivo. More importantly, subpopulations of R-CICs resisted both 5-fluorouracil/calcium folinate/oxaliplatin (FolFox) and cetuximab treatment, which are the most common therapeutic regimens used for patients with advanced or metastatic rectal cancer. Thus, the identification, expansion, and properties of R-CICs provide an ideal cellular model to further investigate tumor progression and determine therapeutic resistance in these patients. 相似文献
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64.
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor that plays an essential role in regulating energy homeostasis. Defects in MC4R are the most common monogenic form of obesity, with about 170 distinct mutations identified in human. In addition to the conventional Gs-stimulated adenylyl cyclase pathway, it has been recently demonstrated that MC4R also activates mitogen-activated protein kinases, extracellular signal-regulated kinases 1 and 2 (ERK1/2). Herein, we investigated the potential of four MC4R ligands that are inverse agonists at the Gs-cAMP signaling pathway, including agouti-related peptide (AgRP), MCL0020, Ipsen 5i and ML00253764, to regulate ERK1/2 activation (pERK1/2) in wild type and six naturally occurring constitutively active mutant (CAM) MC4Rs. We showed that these four inverse agonists acted as agonists for the ERK1/2 signaling cascade in wild type and CAM MC4Rs. Three mutants (P230L, L250Q and F280L) had significantly increased pERK1/2 level upon stimulation with all four inverse agonists, with maximal induction ranging from 1.6 to 4.2-fold. D146N had significantly increased pERK1/2 level upon stimulation with AgRP, MCL0020 or ML00253764, but not Ipsen 5i. The pERK1/2 levels of H76R and S127L were significantly increased only upon stimulation with AgRP or MCL0020. In summary, our studies demonstrated for the first time that MC4R inverse agonists at the Gs-cAMP pathway could serve as agonists in the MAPK pathway. These results suggested that there were multiple activation states of MC4R with ligand-specific and/or mutant-specific conformations capable of differentially coupling the MC4R to distinct signaling pathways. 相似文献
65.
Molecular cloning, characterization, and heterologous expression of a new κ-carrageenase gene from marine bacterium Zobellia sp. ZM-2 总被引:1,自引:0,他引:1
Zhemin Liu Guiyang Li Zhaolan Mo Haijin Mou 《Applied microbiology and biotechnology》2013,97(23):10057-10067
κ-Carrageenases exhibit apparent distinctions in gene sequence, molecular weight, enzyme properties, and posttranslational processes. In this study, a new κ-carrageenase gene named cgkZ was cloned from the marine bacterium Zobellia sp. ZM-2. The gene comprised an open reading frame of 1,638 bp and encoded 545 amino acids. The natural signal peptide of κ-carrageenase was used successfully for the secretory production of the recombinant enzyme in Escherichia coli. A posttranslational process that removes an amino acid sequence of about 20 kDa from the C-terminal end of κ-carrageenase was first discovered in E. coli. An increase in enzyme activity by 167.3 % in the presence of 5 mM DTT was discovered, and Na+ at a certain concentration range was positively correlated with enzyme activity. The κ-carrageenase production of E. coli was 9.0 times higher than that of ZM-2. These results indicate the potential use of the enzyme in the biotechnological industry. 相似文献
66.
Zhao Y Yu Y Zhai J Ramachandran V Dinh TT Meyers BC Mo B Chen X 《Current biology : CB》2012,22(8):689-694
MicroRNAs (miRNAs), small interfering RNAs (siRNAs), and piwi-interacting RNAs (piRNAs) impact numerous biological processes in eukaryotes. In addition to biogenesis, turnover contributes to the steady-state levels of small RNAs. One major factor that stabilizes miRNAs and siRNAs in plants as well as siRNAs and piRNAs in animals is 2'-O-methylation on the 3' terminal ribose by the methyltransferase HUA ENHANCER1 (HEN1) [1-6]. Genetic studies with Arabidopsis, Drosophila, and zebrafish hen1 mutants show that 2'-O-methylation protects small RNAs from 3'-to-5' truncation and 3' uridylation, the addition of nontemplated nucleotides, predominantly uridine [2, 7, 8]. Uridylation is a widespread phenomenon that is not restricted to small RNAs in hen1 mutants and is often associated with their reduced accumulation ([7, 9, 10]; reviewed in [11]). The enzymes responsible for 3' uridylation of small RNAs when they lack methylation in plants or animals have remained elusive. Here, we identify the Arabidopsis HEN1 SUPPRESSOR1 (HESO1) gene as responsible for small RNA uridylation in hen1 mutants. HESO1 exhibits terminal nucleotidyl transferase activity, prefers uridine as the substrate nucleotide, and is completely inhibited by 2'-O-methylation. We show that uridylation leads to miRNA degradation, and the degradation is most likely through an enzyme that is distinct from that causing the 3' truncation in hen1 mutants. 相似文献
67.
68.
Yaoyao Zhang Xiaodong Sun Zhiwen Nong Mo Chen Yujiang Hao Jianghua Wang Kexiong Wang Ding Wang Zhigang Mei 《Marine Mammal Science》2024,40(2):e13082
The establishment of marine protected areas (MPAs) for cetaceans is an important strategy to mitigate human disturbance and protect biodiversity. Despite abundant cetacean species, there are only a few MPAs dedicated to cetacean conservation in China, all of which are for inshore dolphins. Bryde's whales, the only nearshore baleen whale population in mainland China, are conflicting with intensive human activities, yet an effective conservation strategy is lacking. This study used species distribution models to analyze distribution patterns and suitable habitats of Bryde's whales in the Beibu Gulf and proposes the first baleen whale MPA in China. Our results showed Bryde's whales have a seasonal distribution pattern in the Beibu Gulf, and that the waters around Weizhou Island and the southeastern coast of Vietnam were their core habitats. The seasonal nighttime light data indicated a negative relationship between the number of ship lights and Bryde's whale sightings and suggest that Bryde's whales might be threatened by fisheries. We proposed an MPA based on the results, suggesting that the waters within 20 km around Weizhou Island should be declared a protected area. Furthermore, we recommend that anthropogenic activities in the waters around Weizhou Island are better managed to reduce negative impacts on marine life. 相似文献
69.
Xiao-Qing Li Ning Ma Xin-Gang Li Bo Wang Shu-Sen Sun Feng Gao Da-Peng Mo Li-Gang Song Xuan Sun Lian Liu Xing-Quan Zhao Yi-Long Wang Yong-Jun Wang Zhi-Gang Zhao Zhong-Rong Miao 《PloS one》2016,11(2)
Background and Purpose
Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes.Methods
Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients.Results
A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03–2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10–3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12–3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events.Conclusions
PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events. 相似文献70.
气候变化对黄淮海平原冬小麦产量和耗水的影响及品种适应性评估 总被引:2,自引:0,他引:2
基于IPCC5 3种代表性温室气体浓度排放路径(RCP)的情景集成数据,采用VIP生态水文模型,模拟分析了黄淮海平原未来冬小麦产量、蒸散量的气候变化响应.模拟结果表明:未考虑CO2肥效时,3种典型排放路径下,冬小麦生育期都将因气温上升而缩短,其产量和蒸散量将呈下降趋势.CO2浓度增加对作物生长的有利影响强于气候变化带来的不利影响,是未来情景下冬小麦产量增加的主要原因.以RCP4.5为例,2050s黄淮海地区冬小麦平均产量将增加14.8%(无CO2肥效时产量下降2.5%),蒸散量降低2.1%.采用积温需求更高的品种将有利于冬小麦利用CO2肥效提高其产量,但耗水量将有所增加.因此,培育适应气候变化的作物品种、发展节水农业和管理技术是应对气候变化的关键. 相似文献