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https://www.readbyqxmd.com/read/28934472/controlled-re-activation-of-epigenetically-silenced-tet-promoter-driven-transgene-expression-by-targeted-demethylation
#1
Natascha Gödecke, Lisha Zha, Shawal Spencer, Sara Behme, Pamela Riemer, Michael Rehli, Hansjörg Hauser, Dagmar Wirth
Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934209/microbial-translocation-is-correlated-with-hiv-evolution-in-hiv-hcv-co-infected-patients
#2
Jean-Jacques Tudesq, Catherine Dunyach-Remy, Christophe Combescure, Régine Doncesco, Didier Laureillard, Jean-Philippe Lavigne, Albert Sotto
Microbial translocation (MT) is characterized by bacterial products passing into the blood through the gut barrier and is a key phenomenon in the pathophysiology of Human Immunodeficiency Virus (HIV) infection. MT is also associated with liver damage in Hepatitis C Virus (HCV) patients. The aim of the study was to assess MT in plasma of HIV-HCV co-infected patients. 16S rDNA (16 S Ribosomal DNA subunit) marker and other markers of MT such as Lipopolysaccharide (LPS)-binding protein (LBP), soluble CD14 (sCD14), intestinal fatty acid binding protein (I-FABP) were used...
2017: PloS One
https://www.readbyqxmd.com/read/28933767/hemin-improves-insulin-sensitivity-and-lipid-metabolism-in-cultured-hepatocytes-and-mice-fed-a-high-fat-diet
#3
Yi Luan, Fang Zhang, Yalan Cheng, Jun Liu, Rui Huang, Menghong Yan, Yuangao Wang, Zhishui He, Hejin Lai, Hui Wang, Hao Ying, Feifan Guo, Qiwei Zhai
Hemin is a breakdown product of hemoglobin. It has been reported that the injection of hemin improves lipid metabolism and insulin sensitivity in various genetic models. However, the effect of hemin supplementation in food on lipid metabolism and insulin sensitivity is still unclear, and whether hemin directly affects cellular insulin sensitivity is yet to be elucidated. Here we show that hemin enhances insulin-induced phosphorylation of insulin receptors, Akt, Gsk3β, FoxO1 and cytoplasmic translocation of FoxO1 in cultured primary hepatocytes under insulin-resistant conditions...
July 26, 2017: Nutrients
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#4
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933603/autophagy-enables-retromer-dependent-plasma-membrane-translocation-of-slc2a1-glut-to-enhance-glucose-uptake
#5
Srirupa Roy, Jayanta Debnath
Macroautophagy/autophagy is traditionally viewed as an intracellular catabolic pathway that recycles core metabolites during starvation or stress. Recently, we found that autophagy also functions in the control of glucose uptake from the extracellular environment by facilitating cell surface expression of the glucose transporter SLC2A1/GLUT1. In response to increased glycolytic demand or acute glucose starvation, autophagosome induction titrates the RabGAP protein TBC1D5 away from its inhibitory interaction with the retromer complex and into MAP1LC3(+) compartments...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28932107/bioinformatics-study-of-m-9053g-a-mutation-at-the-atp6-gene-in-relation-to-type-2-diabetes-mellitus-and-cataract-diseases
#6
Iman Permana Maksum, Sandy Risfi Saputra, Nenden Indrayati, Muhammad Yusuf, Toto Subroto
The mitochondrial disease often associated with various illnesses in relation to the activity of cells metabolites and the synthesis of adenosine triphosphate (ATP), including alteration in the mitochondrial DNA. The mutation of m.9053G>A at the ATP6 gene was found in patients with type 2 diabetes mellitus (DM type 2) and cataract. Therefore, this mutation is predicted to be clinical features of the 2 diseases. ATP6 gene encodes protein subunit of ATPase6, a part of ATP synthase, which is important in the electron transfer and proton translocation in intracellular respiration system...
2017: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/28931916/salidroside-ameliorates-sepsis-induced-acute-lung-injury-and-mortality-via-downregulating-nf-%C3%AE%C2%BAb-and-hmgb1-pathways-through-the-upregulation-of-sirt1
#7
Kuo-Cheng Lan, Sung-Chuan Chao, Hsiao-Yi Wu, Chia-Lien Chiang, Ching-Chia Wang, Shing-Hwa Liu, Te-I Weng
Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931913/cell-free-synthesis-of-functional-antibodies-using-a-coupled-in-vitro-transcription-translation-system-based-on-cho-cell-lysates
#8
M Stech, O Nikolaeva, L Thoring, W F M Stöcklein, D A Wüstenhagen, M Hust, S Dübel, S Kubick
Antibodies are indispensable tools for basic research as well as diagnostic and therapeutic applications. Consequently, the development of alternative manufacturing strategies which circumvent the hurdles connected to conventional antibody production technologies is of enormous interest. To address this issue, we demonstrate the synthesis of complex antibody formats, in particular immunoglobulin G (IgG) and single-chain variable fragment Fc fusion (scFv-Fc), in a microsome-containing cell-free system based on translationally active chinese hamster ovary (CHO) cell lysates...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931557/protective-effect-of-cyanidin-3-o-glucoside-on-neonatal-porcine-islets
#9
Chao Li, Bin Yang, Zhihao Xu, Eric Boivin, Mazzen Black, Wenlong Huang, Baoyou Xu, Ping Wu, Bo Zhang, Xian Li, Kunsong Chen, Yulian Wu, Gina Rayat
Oxidative stress is a major cause of islet injury and dysfunction during isolation and transplantation procedures. Cyanidin-3-O-glucoside (C3G), which is present in various fruits and vegetables especially in Chinese bayberry, shows potent antioxidant property. In this study, we determined whether C3G could protect neonatal porcine islets (NPI) from reactive oxygen species (H2O2)-induced injury in vitro and promote the function of NPI in diabetic mice. We found that C3G had no deleterious effect on NPI and that C3G protected NPI from damage induced by H2O2...
September 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28931214/baicalin-alleviates-radiation-induced-epithelial-mesenchymal-transition-of-primary-type-ii-alveolar-epithelial-cells-via-tgf-%C3%AE-and-erk-gsk3%C3%AE-signaling-pathways
#10
Jinhua Lu, Yazhen Zhong, Zechen Lin, Xianlei Lin, Zhaohui Chen, Xuping Wu, Nan Wang, Haiqiao Zhang, Siyu Huang, Yuan Zhu, Yuanyuan Wang, Shengyou Lin
BACKGROUND: Radiation therapy is commonly used to treat thoracic malignancies. However, it may lead to severe lung pneumonitis and ultimately fibrosis. Irradiation has been reported to increase epithelial-mesenchymal transition (EMT) of type II alveolar epithelial cells (AEC), which play an important role in pulmonary fibrosis. The transforming growth factor-β (TGF-β) and ERK/glycogen synthase kinase 3β (GSK3β) pathways are critically involved in radiation-induced EMT. In the present study, we investigated whether baicalin was a novel therapeutic candidate for radiation-induced EMT in type II AEC...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28931104/-molecular-diagnostics-of-alk-positive-lung-cancer
#11
József Tímár, Gábor Lotz, Erzsébet Rásó, Judit Moldvay
ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH)...
September 20, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28931056/heterogeneity-in-the-expression-and-subcellular-localization-of-polyol-monosaccharide-transporter-genes-in-lotus-japonicus
#12
Lu Tian, Leru Liu, Yehu Yin, Mingchao Huang, Yanbo Chen, Xinlan Xu, Pingzhi Wu, Meiru Li, Guojiang Wu, Huawu Jiang, Yaping Chen
Polyols can serve as a means for the translocation of carbon skeletons and energy between source and sink organs as well as being osmoprotective solutes and antioxidants which may be involved in the resistance of some plants to biotic and abiotic stresses. Polyol/Monosaccharide transporter (PLT) proteins previously identified in plants are involved in the loading of polyols into the phloem and are reported to be located in the plasma membrane. The functions of PLT proteins in leguminous plants are not yet clear...
2017: PloS One
https://www.readbyqxmd.com/read/28931009/ndfip-allows-nedd4-nedd4l-induced-aqp2-ubiquitination-and-degradation
#13
Christiane Trimpert, Daniel Wesche, Theun de Groot, Martha M Pimentel Rodriguez, Victoria Wong, Dennis T M van den Berg, Lydie Cheval, Carolina A Ariza, Alain Doucet, Igor Stagljar, Peter M T Deen
Regulation of our water homeostasis is fine-tuned by dynamic translocation of Aquaporin-2 (AQP2)-bearing vesicles to and from the plasma membrane of renal principal cells. Whereas binding of vasopressin to its type-2 receptor initiates a cAMP-protein kinase A cascade and AQP2 translocation to the apical membrane, this is counteracted by protein kinase C-activating hormones, resulting in ubiquitination-dependent internalization of AQP2. The proteins targeting AQP2 for ubiquitin-mediated degradation are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28930149/anti-inflammatory-effects-of-a-mytilus-coruscus-%C3%AE-d-glucan-mp-a-in-activated-macrophage-cells-via-tlr4-nf-%C3%AE%C2%BAb-mapk-pathway-inhibition
#14
Fuyan Liu, Xiaofeng Zhang, Yuqiu Li, Qixin Chen, Fei Liu, Xiqiang Zhu, Li Mei, Xinlei Song, Xia Liu, Zhigang Song, Jinhua Zhang, Wen Zhang, Peixue Ling, Fengshan Wang
The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus, and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells...
September 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28928854/b-cell-translocation-gene-1-is-downregulated-by-promoter-methylation-in-ovarian-carcinoma
#15
Ji-Ye Kim, Sung-Im Do, Go Eun Bae, Hyun-Soo Kim
A better understanding of tumor biology is important in the identification of molecules that are downregulated in malignancy and in determining their role in tumor suppression. B-cell translocation gene 1 (BTG1) has been shown to act as a tumor suppressor in several types of human malignancy. In this study, we analyzed BTG1 expression in ovarian carcinoma cell lines, and we investigated the mechanism underlying the observed alterations. The methylation status of the BTG1 promoter region was determined by methylation-specific polymerase chain reaction, and the effect of demethylation on BTG1 expression was analyzed...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928762/novel-protein-protein-inhibitor-based-approach-to-control-plant-ethylene-responses-synthetic-peptides-for-ripening-control
#16
Mareike Kessenbrock, Simone M Klein, Lena Müller, Mauricio Hunsche, Georg Noga, Georg Groth
Ethylene signaling is decisive for many plant developmental processes. Among these, control of senescence, abscission and fruit ripening are of fundamental relevance for global agriculture. Consequently, detailed knowledge of the signaling network along with the molecular processes of signal perception and transfer are expected to have high impact on future food production and agriculture. Recent advances in ethylene research have demonstrated that signaling of the plant hormone critically depends on the interaction of the ethylene receptor family with the NRAMP-like membrane protein ETHYLENE INSENSITIVE 2 (EIN2) at the ER membrane, phosphorylation-dependent proteolytic processing of ER-localized EIN2 and subsequent translocation of the cleaved EIN2 C-terminal polypeptide (EIN2-CEND) to the nucleus...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28928392/mucosa-associated-lymphoid-tissue-lymphoma-translocation-1-as-a-novel-therapeutic-target-for-rheumatoid-arthritis
#17
Chang Hoon Lee, Su Jeong Bae, Miok Kim
Emerging evidence suggests that mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) is a key regulator of inflammatory diseases; however, the pathological role of MALT1 in rheumatoid arthritis (RA) is not well understood. Consequently, this protein has not been therapeutically targeted for the treatment of RA. MALT1 plays a role in the paracaspase pathway, has proteolytic activity and is involved in the regulation of inflammatory responses. In this study, we found that the MALT1-targeting inhibitory small molecule, MALT1 selective inhibitor 2-chloro-N-[4-[5-(3,4-dichlorophenyl)-3-(2-methoxyethoxy)-1H-1,2,4-triazol-1-yl]phenylacetamide (MI-2) strongly suppresses the differentiation of monocytes into osteoclasts in the absence or presence of the inflammatory cytokine tumour necrosis factor α...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928268/mild-acidosis-delays-neutrophil-apoptosis-via-multiple-signaling-pathways-and-acts-in-concert-with-inflammatory-mediators
#18
Driss El Kebir, Everton de Oliveira Lima Dos Santos, Soukaina Mansouri, Meriem Sekheri, János G Filep
Accumulating evidence indicates development of local extracellular acidosis in inflamed tissues in response to infection and tissue injury. Activation of infiltrating neutrophils contributes to a transient decrease in pH, which, in turn, triggers innate immunity. In this study, we investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory response and analyzed the underlying signaling pathways. Culture of human isolated neutrophils in mildly acidotic conditions (pH 6...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28928132/seca-mediates-cotranslational-targeting-and-translocation-of-an-inner-membrane-protein
#19
Shuai Wang, Chien-I Yang, Shu-Ou Shan
Protein targeting to the bacterial plasma membrane was generally thought to occur via two major pathways: cotranslational targeting by signal recognition particle (SRP) and posttranslational targeting by SecA and SecB. Recently, SecA was found to also bind ribosomes near the nascent polypeptide exit tunnel, but the function of this SecA-ribosome contact remains unclear. In this study, we show that SecA cotranslationally recognizes the nascent chain of an inner membrane protein, RodZ, with high affinity and specificity...
September 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28927344/structural-elucidation-of-transmembrane-domain-zero-tmd0-of-ecdl-a-multidrug-resistance-associated-protein-mrp-family-of-atp-binding-cassette-transporter-protein-revealed-by-atomistic-simulation
#20
Krishnendu Bera, Priyanka Rani, Gaurav Kishor, Shikha Agarwal, Antresh Kumar, Durg Vijay Singh
ATP-Binding cassette (ABC) transporters play an extensive role in the translocation of diverse sets of biologically important molecules across membrane. EchnocandinB (antifungal) and EcdL protein of Aspergillus rugulosus are encoded by the same cluster of genes. Co-expression of EcdL and echinocandinB reflects tightly linked biological functions. EcdL belongs to Multidrug Resistance associated Protein (MRP) subfamily of ABC transporters with an extra transmembrane domain zero (TMD0). Complete structure of MRP subfamily comprising of TMD0 domain, at atomic resolution is not known...
September 20, 2017: Journal of Biomolecular Structure & Dynamics
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