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https://www.readbyqxmd.com/read/28528274/angiopoietin-like-8-angptl8-controls-adipocyte-lipolysis-and-phospholipid-composition
#1
Raghavendra Mysore, Gerhard Liebisch, You Zhou, Vesa M Olkkonen, P A Nidhina Haridas
Angiopoietin-like 8 (Angptl8) inhibits lipolysis in the circulation together with Angplt3 and controls post-prandial fat storage in white adipose tissue (WAT). It is strongly induced by insulin in vivo in WAT and in vitro in adipocytes. In this study we addressed the function of Angptl8 in adipocytes by its stable lentivirus-mediated knock-down in 3T3-L1 cells, followed by analyses of triglyceride (TG) storage, lipid droplet (LD) morphology, the cellular lipidome, lipolysis, and gene expression. Depletion of Angptl8 did not drastically affect the adipocytic differentiation of 3T3-L1 cells but resulted in a moderate (18-19%) reduction of stored TGs...
May 17, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28527665/therapeutic-editing-of-hepatocyte-genome-in-vivo
#2
REVIEW
Marina Ruiz de Galarreta, Amaia Lujambio
The recent development of gene editing platforms enables making precise changes in the genome of eukaryotic cells. Programmable nucleases, such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-associated nucleases, have revolutionized the way research is conducted as they facilitate the rapid production of mutant or knock-out cellular and animal models. These same genetic tools can potentially be applied to cure or alleviate a variety of diseases, including genetic diseases that lack an efficient therapy...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28527416/ochratoxin-a-induces-nephrotoxicity-and-immunotoxicity-through-different-mapk-signaling-pathways-in-pk15-cells-and-porcine-primary-splenocytes
#3
Fang Gan, Yaojiao Zhou, Lili Hou, Gang Qian, Xingxiang Chen, Kehe Huang
Ochratoxin A (OTA) is reported to be a potent nephrotoxin and immunotoxin in animals and humans. However, the mechanisms underlying OTA toxicity have not been clearly determined until now. Toxicity of OTA and its mechanism was investigated in PK15 cells and in porcine primary splenocytes. The results showed that OTA at 2.0-8.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in PK 15 cells. OTA at 0.5-4.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in porcine primary splenocytes...
May 9, 2017: Chemosphere
https://www.readbyqxmd.com/read/28526842/revealing-genome-scale-transcriptional-regulatory-landscape-of-ompr-highlights-its-expanded-regulatory-roles-under-osmotic-stress-in-escherichia-coli-k-12-mg1655
#4
Sang Woo Seo, Ye Gao, Donghyuk Kim, Richard Szubin, Jina Yang, Byung-Kwan Cho, Bernhard O Palsson
A transcription factor (TF), OmpR, plays a critical role in transcriptional regulation of the osmotic stress response in bacteria. Here, we reveal a genome-scale OmpR regulon in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 37 genes in 24 transcription units (TUs) belong to OmpR regulon. Among them, 26 genes show more than two-fold changes in expression level in an OmpR knock-out strain. Specifically, we find that: 1) OmpR regulates mostly membrane-located gene products involved in diverse fundamental biological processes, such as narU (encoding nitrate/nitrite transporter), ompX (encoding outer membrane protein X), and nuoN (encoding NADH:ubiquinone oxidoreductase); 2) by investigating co-regulation of entire sets of genes regulated by other stress-response TFs, stresses are surprisingly independently regulated among each other; and, 3) a detailed investigation of the physiological roles of the newly discovered OmpR regulon genes reveals that activation of narU represents a novel strategy to significantly improve osmotic stress tolerance of E...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526804/ova12-promotes-tumor-growth-by-regulating-p53-expression-in-human-cancer-cells
#5
Renfeng Zhang, Xicai Wu, Xiangfeng Xia, Asma Khanniche, Feifei Song, Bingchang Zhang, Ying Wang, Hailiang Ge
Ovarian cancer-associated antigen 12 (OVA12) was first identified in an ovarian carcinoma complementary DNA (cDNA) expression library and has been shown to play an important role in tumor growth. Here, we found that overexpression of OVA12 accelerated tumor growth in different tumor cells, whereas OVA12 depletion was associated with the opposite effect. Moreover, knocking down OVA12 led to a significant increase in the protein levels of p53, and the overexpression of OVA12 significantly decreased endogenous p53 levels...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#6
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524857/a-defined-metabolic-state-in-pre-b-cells-governs-b-cell-development-and-is-counterbalanced-by-swiprosin-2-efhd1
#7
Merle Stein, Sebastian Dütting, Dimitrios Mougiakakos, Michael Bösl, Kristin Fritsch, Dorothea Reimer, Sophia Urbanczyk, Tobit Steinmetz, Wolfgang Schuh, Aline Bozec, Thomas H Winkler, Hans-Martin Jäck, Dirk Mielenz
B-cell development in the bone marrow comprises proliferative and resting phases in different niches. We asked whether B-cell metabolism relates to these changes. Compared to pro B and small pre B cells, large pre B cells revealed the highest glucose uptake and ROS but not mitochondrial mass, whereas small pre B cells exhibited the lowest mitochondrial membrane potential. Small pre B cells from Rag1(-/-);33.C9 μ heavy chain knock-in mice revealed decreased glycolysis (ECAR) and mitochondrial spare capacity compared to pro B cells from Rag1(-/-) mice...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28524599/modulation-of-nuclear-rest-by-alternative-splicing-a-potential-therapeutic-target-for-huntington-s-disease
#8
Guo-Lin Chen, Qi Ma, Dharmendra Goswami, Jianyu Shang, Gregory M Miller
Huntington's disease (HD) is caused by a genetically mutated huntingtin (mHtt) protein with expanded polyQ stretch, which impairs cytosolic sequestration of the repressor element-1 silencing transcription factor (REST), resulting in excessive nuclear REST and subsequent repression of neuronal genes. We recently demonstrated that REST undergoes extensive, context-dependent alternative splicing, of which exon-3 skipping (∆E3 )-a common event in human and nonhuman primates-causes loss of a motif critical for REST nuclear targeting...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28524166/homology-mediated-end-joining-based-targeted-integration-using-crispr-cas9
#9
Xuan Yao, Xing Wang, Xinde Hu, Zhen Liu, Junlai Liu, Haibo Zhou, Xiaowen Shen, Yu Wei, Zijian Huang, Wenqin Ying, Yan Wang, Yan-Hong Nie, Chen-Chen Zhang, Sanlan Li, Leping Cheng, Qifang Wang, Yan Wu, Pengyu Huang, Qiang Sun, Linyu Shi, Hui Yang
Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome...
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28523759/role-of-sulfotransferases-in-resveratrol-metabolism-in-human-adipocytes
#10
Nele Gheldof, Sofia Moco, Christian Chabert, Tony Teav, Denis Barron, Jorg Hager
SCOPE: Polyphenols such as resveratrol received interest for their wide-ranging biological benefits, including anti-obesity potential, mimicking effects of caloric restriction with reduced body fat and increased energy expenditure. However, resveratrol is rapidly metabolized, and it is not completely understood which form of resveratrol is responsible for the effects observed within target cells such as adipocytes. Also the role of metabolizing enzymes has not been investigated before...
May 18, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28523736/hyper-activation-of-%C3%AE-catenin-signalling-induced-by-ikk%C3%AE%C2%B5-inhibition-thwarts-colorectal-cancer-cell-proliferation
#11
Jie Chen, Jun Zhao, Xuan Chen, Chengming Ding, Katie Lee, Zeming Jia, Yaoting Zhang, Yuzheng Zhou, Chaoying Wei, Jiantai He, Zanxian Xia, Jian Peng
OBJECTIVE: Aberrant activation of Wnt/β-catenin signalling contributes significantly to the development of human colorectal cancers and β-catenin is the key signalling molecule transducing canonical Wnt/β-catenin signalling. Therefore, β-catenin is a promising therapeutic target for cancer treatment. This study demonstrates that the oncogenic IKKε kinase phosphorylates β-catenin to restrain its hyper activation, therefore promoting colorectal cancer (CRC) cell proliferation. MATERIALS AND METHODS: IKKε and β-catenin expression levels in human colorectal cancer tissues and cell lines were analysed by immunohistochemical staining and Western blotting...
May 19, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28523731/wble2-transcription-factor-in-streptomyces-griseus-s4-7-plays-an-important-role-in-plant-protection
#12
Hyun Ji Cho, Young Sang Kwon, Da-Ran Kim, Gyeongjun Cho, Seong Won Hong, Dong-Won Bae, Youn-Sig Kwak
Streptomyces griseus S4-7 was originally isolated from the strawberry rhizosphere as a microbial agent responsible for Fusarium wilt suppressive soils. S. griseus S4-7 shows specific and pronounced antifungal activity against Fusarium oxysporum f. sp. fragariae. In the Streptomyces genus, the whi transcription factors are regulators of sporulation, cell differentiation, septation, and secondary metabolites production. wblE2 function as a regulator has emerged as a new group in whi transcription factors. In this study, we reveal the involvement of the wblE2 transcription factor in the plant-protection by S...
May 19, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28522854/genetic-tools-to-study-juvenile-hormone-action-in-drosophila
#13
A A Baumann, M J Texada, H M Chen, J N Etheredge, D L Miller, S Picard, R Warner, J W Truman, L M Riddiford
The insect juvenile hormone receptor is a basic helix-loop-helix (bHLH), Per-Arnt-Sim (PAS) domain protein, a novel type of hormone receptor. In higher flies like Drosophila, the ancestral receptor germ cell-expressed (gce) gene has duplicated to yield the paralog Methoprene-tolerant (Met). These paralogous receptors share redundant function during development but play unique roles in adults. Some aspects of JH function apparently require one receptor or the other. To provide a foundation for studying JH receptor function, we have recapitulated endogenous JH receptor expression with single cell resolution...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#14
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Asis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522564/decreased-phosphatase-pten-amplifies-pi3k-signaling-and-enhances-pro-inflammatory-cytokine-release-in-copd
#15
Satoru Yanagisawa, Jonathan R Baker, Chaitanya Vuppusetty, Peter Fenwick, Louise E Donnelly, Kazuhiro Ito, Peter J Barnes
The phosphatidylinositol 3-kinase (PI3K) pathway is activated in chronic obstructive pulmonary disease (COPD), but the regulatory mechanisms for this pathway are yet to be elucidated. Our aim was to determine the expression and role of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the PI3K pathway, in COPD. PTEN expression and activity were measured in the peripheral lung of COPD patients compared to smoking and non-smoking controls. The direct influence of cigarette smoke extract (CSE) on PTEN expression was assessed using primary lung epithelial cells and a cell line (BEAS-2B) in the presence or absence of L-buthionine-sulfoximine (BSO) to deplete intracellular glutathione...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28521463/endoplasmic-reticulum-protein-erp46-in-prostate-adenocarcinoma
#16
Wilhelmina C M Duivenvoorden, Sarah N Hopmans, Richard C Austin, Jehonathan H Pinthus
Endoplasmic reticulum (ER) protein ERp46 is a member of the protein disulfide isomerase family of oxidoreductases, which facilitates the reduction of disulfides in proteins and their folding. Accumulation of misfolded proteins has been implicated in cancer. The objectives of the present study were to investigate the role of ERp46 in prostate cancer, its expression and its effects on prostate cancer growth. A tissue microarray with human prostate cancer and normal prostate tissue samples was stained for ERp46 followed by image analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521398/effect-of-satb1-silencing-on-the-proliferation-invasion-and-apoptosis-of-te-1-esophageal-cancer-cells
#17
Bo Huang, Fei Xiong, Siwang Wang, Xianping Lang, Xiaodong Wang, Hongli Zhou
The aim of the present study was to investigate the effect of special AT-rich sequence-binding protein-1 (SATB1)-targeted small interfering RNA (siRNA) on the proliferation, invasion and apoptosis of TE-1 human esophageal cancer cells. SATB1 has been correlated with the metastasis and poor prognosis of colon and breast cancer, but the role of SATB1 in esophageal cancer remains unknown. Therefore, the present study constructed and transfected SATB1-siRNA into TE-1 cells in order to knockdown the expression of the SATB1 gene...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520978/ldb1-mediated-enhancer-looping-can-be-established-independent-of-mediator-and-cohesin
#18
Ivan Krivega, Ann Dean
Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28520923/decrease-in-expression-of-hoxa10-in-the-decidua-after-embryo-implantation-promotes-trophoblast-invasion
#19
Geeta Godbole, Pankaj Suman, Ankita Malik, Mosami Galvankar, Niraj Joshi, Asgerally Fazleabas, Satish Kumar Gupta, Deepak Modi
A central step towards successful pregnancy involves invasion of the trophoblast cells into the decidua for placentation. Herein, we show that in the human and baboon decidua, HOXA10 expression is downregulated post-implantation and this reduction is most prominent in the decidual cells juxtaposed to the invading placental villi. Intriguingly, the supernatants derived from HOXA10 depleted human decidual cells increase the invasiveness of the trophoblast cell lines ACH-3P and JEG3 in vitro; this increase is due to higher expression and activity of matrix metalloproteases (MMPs) and reduced expression of tissue inhibitors of MMPs (TIMPs) in both the cell lines...
May 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#20
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
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