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https://www.readbyqxmd.com/read/28343361/genetic-dissociation-of-morphine-analgesia-from-hyperalgesia-in-mice
#1
Gina F Marrone, Valerie Le Rouzic, Andras Varadi, Jin Xu, Anjali M Rajadhyaksha, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
RATIONALE: Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM). OBJECTIVES: This study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions...
March 25, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28342933/regulation-of-airway-inflammation-and-remodeling-in-asthmatic-mice-by-tlr3-trif-signal-pathway
#2
Mei Yang, Hao-Ying Wang, Jian-Chang Chen, Jing Zhao
This paper aims to investigate the effect of Toll-like receptors 3 (TLR3)/TIR-domain-containing adapter-inducing interferon-β (TRIF) signal pathway on the airway inflammation and remodeling in asthmatic mice. C57BL/6 and TLR3(-/-) mice were randomly divided into three groups (10 mice per group), including Control group (mice inhaled phosphate buffer saline (PBS)), Asthma group (mice inhaled ovalbumin (OVA)) and polyriboinosinic-ribocytidylic acid (poly (I: C)) group (asthmatic mice were injected intraperitoneally with TLR3 agonist poly (I: C))...
March 23, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28342843/the-stress-response-molecule-nr4a1-resists-ros-induced-pancreatic-%C3%AE-cells-apoptosis-via-wt1
#3
Chen Zong, Dandan Qin, Cong Yu, Peng Gao, Jicui Chen, Sumei Lu, Yuchao Zhang, Yuantao Liu, Yingfeng Yang, Zeqing Pu, Xia Li, Yuchang Fu, Qingbo Guan, Xiangdong Wang
Pancreatic β-cells often face endoplasmic reticulum stress and/or ROS-associated oxidative stress under adverse conditions. Our previous work has verified that NR4A1 protects pancreatic β-cells from ER-stress induced apoptosis. However, It remains unknown whether NR4A1 is able to protect pancreatic β-cells against ROS-associated oxidative stress. In the present study, our data showed that NR4A1 protein expression rapidly increased in MIN6 cells upon H2O2 treatment, and overexpression of NR4A1 in MIN6 cells conferred resistance to cell apoptosis induced by H2O2...
March 22, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28342455/repair-of-oxidatively-induced-dna-damage-by-dna-glycosylases-mechanisms-of-action-substrate-specificities-and-excision-kinetics
#4
REVIEW
Miral Dizdaroglu, Erdem Coskun, Pawel Jaruga
Endogenous and exogenous reactive species cause oxidatively induced DNA damage in living organisms by a variety of mechanisms. As a result, a plethora of mutagenic and/or cytotoxic products are formed in cellular DNA. This type of DNA damage is repaired by base excision repair, although nucleotide excision repair also plays a limited role. DNA glycosylases remove modified DNA bases from DNA by hydrolyzing the glycosidic bond leaving behind an apurinic/apyrimidinic (AP) site. Some of them also possess an accompanying AP-lyase activity that cleaves the sugar-phosphate chain of DNA...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28340332/super-elongation-complex-promotes-early-hiv-transcription-and-its-function-is-modulated-by-p-tefb
#5
Alona Kuzmina, Simona Krasnopolsky, Ran Taube
Early work on the control of transcription of the human immunodeficiency virus (HIV) laid the foundation for our current knowledge of how RNA Polymerase II is released from promoter-proximal pausing sites and transcription elongation is enhanced. The viral Tat activator recruits Positive Transcription Elongation Factor b (P-TEFb) and Super Elongation Complex (SEC) that jointly drive transcription elongation. While substantial progress in understanding the role of SEC in HIV gene transcription elongation has been obtained, defining of the mechanisms that govern SEC functions is still limited, and the role of SEC in controlling HIV transcription in the absence of Tat is less clear...
February 17, 2017: Transcription
https://www.readbyqxmd.com/read/28340115/cellular-senescence-in-mouse-hippocampus-after-irradiation-and-the-role-of-p53-and-p21
#6
Zoey Cheng, Yan Zhen Zheng, Yu-Qing Li, C Shun Wong
Diverse stress signals including irradiation may trigger cellular senescence. We asked whether irradiation induced senescence in mouse hippocampus, and whether p53 or p21 played a role in this response. Following whole-brain irradiation, polymerase chain reaction (PCR) arrays for senescence-associated genes showed increased expression of CDKN1A (p21) and CDKN2A (p19ARF) in mouse hippocampus at 9 weeks. Upregulation of p21 and p19ARF was confirmed using real-time PCR, which also demonstrated increased CDKN2A/p16INKa expression after irradiation...
March 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28340032/osptr7-osnpf8-1-a-putative-peptide-transporter-in-rice-is-involved-in-dimethylarsenate-accumulation-in-rice-grain
#7
Zhong Tang, Yi Chen, Fei Chen, Yuchen Ji, Fang-Jie Zhao
Rice (Oryza sativa) is a major dietary source of arsenic (As) for the population consuming rice as their staple food. Rice grain contains both inorganic As and methylated As species, especially dimethyarsinate (DMA). DMA is highly mobile in long-distance translocation in plants, but the underlying mechanism remains unknown. In the present study, we showed that OsPTR7 (OsNPF8.1), a putative peptide transporter in rice, was permeable to DMA in Xenopus laevis oocytes. Transient expression of the OsPTR7-green fluorescent protein (GFP) in tobacco protoplasts showed that OsPTR7 was localized in the cell plasma membrane...
March 2, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28339907/o-linked-%C3%AE-n-acetylglucosamine-modification-of-proteins-is-essential-for-foot-process-maturation-and-survival-in-podocytes
#8
Shinya Ono, Shinji Kume, Mako Yasuda-Yamahara, Kosuke Yamahara, Naoko Takeda, Masami Chin-Kanasaki, Hisazumi Araki, Osamu Sekine, Hideki Yokoi, Masashi Mukoyama, Takashi Uzu, Shin-Ichi Araki, Hiroshi Maegawa
Background.: O-linked β- N -acetylglucosamine modification O-GlcNAcylation) is a post-translational modification of intracellular proteins, serving as a nutrient sensor. Growing evidence has demonstrated its physiological and pathological importance in various mammalian tissues. This study examined the physiological role of O-GlcNAcylation in podocyte function and development. Methods.: O-GlcNAc transferase (Ogt) is a critical enzyme for O-GlcNAcylation and resides on the X chromosome...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#9
Yong Hwan Kim, Mi-Jung Kim, Se-Woon Choe, Dennis Sprecher, Young Jae Lee, S Paul Oh
BACKGROUND: Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult onset arteriovenous malformations (AVMs). OBJECTIVES: The goal of this study is to evaluate potential therapeutic effects of oral delivery of four anti-angiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult onset AVMs in a murine model of HHT...
March 24, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28339062/p53-microrna-374b-akt1-regulates-colorectal-cancer-cell-apoptosis-in-response-to-dna-damage
#10
Hangjun Gong, Yu Cao, Gang Han, Yun Zhang, Qing You, Yidong Wang, Yamin Pan
Colorectal cancer (CRC) has a rising morbidity worldwide and its resistance to chemotherapy has been observed in clinical treatment. Tumor suppressor p53 is well-studied in CRC, but little is known about its effects during DNA damage of CRC cells. This study was aimed at uncovering potential mechanisms of p53 regarding microRNA-374b and v-akt murine thymoma viral oncogene homolog 1 (AKT1) during DNA damage of CRC cells. CRC cells HCT116 and HT29 were transfected with p53-specific small interfering RNA (siRNA), p53 overexpression vector or miR-374b inhibitor, and then treated with 10 µM bleomycin (BLM) for 24 h to induce DNA damage...
March 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338991/mir-30e-is-negatively-regulated-by-myostatin-in-skeletal-muscle-and-is-functionally-related-to-fiber-type-composition
#11
Haixue Jia, Yixia Zhao, Tingting Li, Yong Zhang, Dahai Zhu
Myostatin (MSTN) negatively regulates skeletal myogenesis in which microRNAs (miRNAs) also play critical roles. Using miRNA microarrays of skeletal muscle from MSTN-knockout (MSTN-/-) mice, we recently showed that miR-431 is regulated by MSTN signaling. To identify additional miRNAs regulated by MSTN, we re-analyzed these miRNA arrays and validated their expression by quantitative RT-PCR. Herein, we demonstrated that miR-30e was significantly upregulated in skeletal muscle of MSTN-/- mice compared with that of the wild-type littermates...
March 17, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28338883/the-effects-of-oleanolic-acid-on-atherosclerosis-in-different-animal-models
#12
Hanqiong Luo, Jine Liu, Qiong Ouyang, Chunxiao Xuan, Lanlan Wang, Tingting Li, Jun Liu
In the present study, three animal models, including C57BL/6J mice, low-density lipoprotein receptor knockout (LDLR-/-) mice, and rabbit that mimicked atherosclerosis, were established to investigate the inhibitory effect of oleanolic acid (OA) on atherosclerosis. In rabbit model, serum total cholesterol (TC), triglyceride, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were measured. Carotid artery lesions were isolated for histological analysis. The red oil O and hematoxylin-eosin staining in liver were examined...
March 4, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28338736/microcompartmentation-of-cytosolic-aldolase-by-interaction-with-the-actin-cytoskeleton-in-arabidopsis
#13
Constantine Garagounis, Kalliopi-Ioanna Kostaki, Tim J Hawkins, Ian Cummins, Mark D Fricker, Patrick J Hussey, Alistair M Hetherington, Lee J Sweetlove
Evidence is accumulating for molecular microcompartments formed when proteins interact in localized domains with the cytoskeleton, organelle surfaces, and intracellular membranes. To understand the potential functional significance of protein microcompartmentation in plants, we studied the interaction of the glycolytic enzyme fructose bisphosphate aldolase with actin in Arabidopsis thaliana. Homology modelling of a major cytosolic isozyme of aldolase, FBA8, suggested that the tetrameric holoenzyme has two actin binding sites and could therefore act as an actin-bundling protein, as was reported for animal aldolases...
February 17, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28338729/revealing-the-roles-of-gork-channels-and-nadph-oxidase-in-acclimation-to-hypoxia-in-arabidopsis
#14
Feifei Wang, Zhong-Hua Chen, Xiaohui Liu, Timothy D Colmer, Lana Shabala, Anya Salih, Meixue Zhou, Sergey Shabala
Regulation of root cell K+ is essential for acclimation to low oxygen stress. The potential roles of GORK (depolarization-activated guard cell outward-rectifying potassium) channels and RBOHD (respiratory burst oxidase homologue D) in plant adaptive responses to hypoxia were investigated in the context of tissue specificity (epidermis versus stele; elongation versus mature zone) in roots of Arabidopsis. The expression of GORK and RBOHD was down-regulated by 2- to 3-fold within 1 h and 24 h of hypoxia treatment in Arabidopsis wild-type (WT) roots...
October 19, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28338101/the-histone-deacetylase-inhibitor-valproic-acid-inhibits-nkg2d-expression-in-natural-killer-cells-through-suppression-of-stat3-and-hdac3
#15
Lulu Ni, Lixin Wang, Chao Yao, Zhongya Ni, Fei Liu, Chenyuan Gong, Xiaowen Zhu, Xuewei Yan, Stephanie S Watowich, Dean A Lee, Shiguo Zhu
NKG2D is a major activating receptor of NK cells and plays a critical role in tumor immunosurveillance. NKG2D expression in NK cells is inhibited by the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and enhanced by the narrow-spectrum HDAC inhibitor entinostat. We previously demonstrated that entinostat enhanced NKG2D transcription by increasing acetylation of Histones H3 and H4. However, the mechanism by which VPA reduces NKG2D expression in NK cells is not known. We have also shown that NKG2D transcription is regulated by STAT3 phosphorylation...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338078/the-transmembrane-serine-protease-hat-like-4-is-important-for-epidermal-barrier-function-to-prevent-body-fluid-loss
#16
Zhiwei Zhang, Yae Hu, Ruhong Yan, Liang Dong, Yizhi Jiang, Zhichao Zhou, Meng Liu, Tiantian Zhou, Ningzheng Dong, Qingyu Wu
Membrane-bound proteases are essential for epidermal integrity. Human airway trypsin-like protease 4 (HAT-L4) is a type II transmembrane serine protease. Currently, its biochemical property, cellular distribution and physiological function remain unknown. Here we examined HAT-L4 expression and function in vitro and in vivo. In Western analysis, HAT-L4 expressed in transfected CHO cells appeared as a 48-kDa protein. Flow cytometry confirmed HAT-L4 expression on the cell surface with the expected membrane topology...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338017/a-role-of-the-sam-domain-in-epha2-receptor-activation
#17
Xiaojun Shi, Vera Hapiak, Ji Zheng, Jeannine Muller-Greven, Deanna Bowman, Ryan Lingerak, Matthias Buck, Bing-Cheng Wang, Adam W Smith
Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338009/resveratrol-attenuates-icam-1-expression-and-monocyte-adhesiveness-to-tnf-%C3%AE-treated-endothelial-cells-evidence-for-an-anti-inflammatory-cascade-mediated-by-the-mir-221-222-ampk-p38-nf-%C3%AE%C2%BAb-pathway
#18
Chen-Wei Liu, Hsin-Ching Sung, Shu-Rung Lin, Chun-Wei Wu, Chiang-Wen Lee, I-Ta Lee, Yi-Fan Yang, I-Shing Yu, Shu-Wha Lin, Ming-Hsien Chiang, Chan-Jung Liang, Yuh-Lien Chen
Resveratrol, an edible polyphenolic phytoalexin, improves endothelial dysfunction and attenuates inflammation. However, the mechanisms have not been thoroughly elucidated. Therefore, we investigated the molecular basis of the effects of resveratrol on TNF-α-induced ICAM-1 expression in HUVECs. The resveratrol treatment significantly attenuated the TNF-α-induced ICAM-1 expression. The inhibition of p38 phosphorylation mediated the reduction in ICAM-1 expression caused by resveratrol. Resveratrol also decreased TNF-α-induced IκB phosphorylation and the phosphorylation, acetylation, and translocation of NF-κB p65...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337968/crispr-cas9-mutagenesis-invalidates-a-putative-cancer-dependency-targeted-in-on-going-clinical-trials
#19
Ann Lin, Christopher J Giuliano, Nicole M Sayles, Jason M Sheltzer
The Maternal Embryonic Leucine Zipper Kinase (MELK) has been reported to be a genetic dependency in several cancer types. MELK RNAi and small-molecule inhibitors of MELK block the proliferation of various cancer cell lines, and MELK knockdown has been described as particularly effective against the highly-aggressive basal/triple-negative subtype of breast cancer. Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials. Here, we report that mutagenizing MELK with CRISPR/Cas9 has no effect on the fitness of basal breast cancer cell lines or cell lines from six other cancer types...
March 24, 2017: ELife
https://www.readbyqxmd.com/read/28337831/interleukin-1-alpha-deficiency-increases-the-expression-of-follicle-stimulating-hormone-receptors-in-granulosa-cells
#20
Shiri Uri-Belapolsky, Irit Miller, Aviv Shaish, Mattan Levi, Dror Harats, Lihi Ninio-Many, Yehuda Kamari, Ruth Shalgi
Follicle-stimulating hormone receptor (FSHR) is a pivotal regulator of ovarian response to hormonal stimulation. Inflammatory conditions have been linked to lower FSHR expression in granulosa cells (GCs) as well as an attenuated response to hormonal stimulation. The current study aimed to reveal if deficiency and/or blockage of the pro-inflammatory cytokine interleukin 1-alpha (IL1A) increased Fshr expression in rodent GCs. We found elevated Fshr transcript abundance, as assessed by quantitative PCR, in primary GCs isolated from Il1a-knockout compared to wild-type mice, and that the expression of FSHR is significantly higher in Il1a-knockout compared to wild-type ovaries...
March 24, 2017: Molecular Reproduction and Development
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