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https://www.readbyqxmd.com/read/29677019/mu-opioid-receptors-in-nociceptive-afferents-produce-a-sustained-suppression-of-hyperalgesia-in-chronic-pain
#1
Amie Severino, Wenling Chen, Joshua K Hakimian, Brigitte L Kieffer, Claire Gaveriaux-Ruff, Wendy Walwyn, Juan Carlos Marvizon
The latent sensitization model of chronic pain reveals that recovery from some types of long-term hyperalgesia is an altered state in which nociceptive sensitization persists but is suppressed by the ongoing activity of analgesic receptors such as µ-opioid receptors (MORs). To determine whether these MORs are the ones present in nociceptive afferents, we bred mice expressing Cre-recombinase under the Nav1.8 channel promoter (Nav1.8cre) with MOR-floxed mice (flMOR). These Nav1.8cre/flMOR mice had reduced MOR expression in primary afferents, as revealed by quantitative PCR, in situ hybridization and immunofluorescence colocalization with the neuropeptide CGRP...
April 17, 2018: Pain
https://www.readbyqxmd.com/read/29665845/deletion-of-hp1%C3%AE-in-cardiac-myocytes-affects-h4k20me3-levels-but-does-not-impact-cardiac-growth
#2
Kyohei Oyama, Danny El-Nachef, Chen Fang, Hidemi Kajimoto, Jeremy P Brown, Prim B Singh, W Robb MacLellan
BACKGROUND: Heterochromatin, which is formed when tri-methyl lysine 9 of histone H3 (H3K9me3) is bound by heterochromatin 1 proteins (HP1s), plays an important role in differentiation and senescence by silencing cell cycle genes. Cardiac myocytes (CMs) accumulate heterochromatin during differentiation and demethylation of H3K9me3 inhibits cell cycle gene silencing and cell cycle exit in CMs; however, it is unclear if this process is mediated by HP1s. In this study, we created a conditional CM-specific HP1 gamma (HP1γ) knockout (KO) mouse model and tested whether HP1γ is required for cell cycle gene silencing and cardiac growth...
April 17, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29651133/refined-protocols-of-tamoxifen-injection-for-inducible-dna-recombination-in-mouse-astroglia
#3
Hannah M Jahn, Carmen V Kasakow, Andreas Helfer, Julian Michely, Alexei Verkhratsky, Hans H Maurer, Anja Scheller, Frank Kirchhoff
Inducible DNA recombination of floxed alleles in vivo by liver metabolites of tamoxifen (TAM) is an important tool to study gene functions. Here, we describe protocols for optimal DNA recombination in astrocytes, based on the GLAST-CreERT2 /loxP system. In addition, we demonstrate that quantification of genomic recombination allows to determine the proportion of cell types in various brain regions. We analyzed the presence and clearance of TAM and its metabolites (N-desmethyl-tamoxifen, 4-hydroxytamoxifen and endoxifen) in brain and serum of mice by liquid chromatographic-high resolution-tandem mass spectrometry (LC-HR-MS/MS) and assessed optimal injection protocols by quantitative RT-PCR of several floxed target genes (p2ry1, gria1, gabbr1 and Rosa26-tdTomato locus)...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29629621/pdgfr-%C3%AE-restores-blood-brain-barrier-functions-in-a-mouse-model-of-focal-cerebral-ischemia
#4
Jie Shen, Guihua Xu, Runxiu Zhu, Jun Yuan, Yoko Ishii, Takeru Hamashima, Takako Matsushima, Seiji Yamamoto, Yusuke Takatsuru, Junichi Nabekura, Masakiyo Sasahara
Although platelet-derived growth factor receptor beta (PDGFR-β) mediates the recruitment of vascular pericytes into ischemic lesion to restore the blood-brain barrier (BBB) dysfunction, its mechanisms still remain elusive . Compared with control PDGFR-βfloxed / floxed mice (Floxed), postnatally induced systemic PDGFR-β knockout mice (Esr-KO) not only showed severe brain edema, neurologic functional deficits, decreased expression of tight junction (TJ) proteins, abundant endothelial transcytosis, and deformed TJs in the BBB, but also showed reduced expression of transforming growth factor-β (TGF-β) protein after photothrombotic middle cerebral artery occlusion (MCAO)...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29626067/endothelial-c-type-natriuretic-peptide-acts-on-pericytes-to-regulate-microcirculatory-flow-and-blood-pressure
#5
Katarina Špiranec, Wen Chen, Franziska Werner, Viacheslav O Nikolaev, Takashi Naruke, Franziska Koch, Andrea Werner, Petra Eder-Negrin, Rodrigo Diéguez-Hurtado, Ralf H Adams, Hideo A Baba, Hannes Schmidt, Kai Schuh, Boris V Skryabin, Kiavash Movahedi, Frank Schweda, Michaela Kuhn
Background -Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular tone but the target cells remain controversial. The cGMP-producing guanylyl cyclase-B (GC-B) receptor for CNP is expressed in vascular smooth muscle cells (VSMC). However, whereas endothelial cell-specific CNP knockout mice are hypertensive, mice with deletion of GC-B in VSMC have unaltered blood pressure. Methods -We analyzed whether the vasodilating response to CNP changes along the vascular tree, i...
April 6, 2018: Circulation
https://www.readbyqxmd.com/read/29616043/lineage-specific-analysis-of-syk-function-in-autoantibody-induced-arthritis
#6
Tamás Németh, Krisztina Futosi, Kata Szilveszter, Olivér Vilinovszki, Levente Kiss-Pápai, Attila Mócsai
Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contribute to inflammation and tissue damage in this model. We have previously shown that the Syk tyrosine kinase is critically involved in the development in K/BxN serum-transfer arthritis and bone marrow chimeric experiments indicated that Syk is likely involved in one or more hematopoietic lineages during the disease course...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29615713/targeted-expression-of-step-function-opsins-in-transgenic-rats-for-optogenetic-studies
#7
Hiroyuki Igarashi, Keiko Ikeda, Hiroshi Onimaru, Ryosuke Kaneko, Kyo Koizumi, Kaoru Beppu, Kayo Nishizawa, Yukari Takahashi, Fusao Kato, Ko Matsui, Kazuto Kobayashi, Yuchio Yanagawa, Shin-Ichi Muramatsu, Toru Ishizuka, Hiromu Yawo
Rats are excellent animal models for experimental neuroscience. However, the application of optogenetics in rats has been hindered because of the limited number of established transgenic rat strains. To accomplish cell-type specific targeting of an optimized optogenetic molecular tool, we generated ROSA26/CAG-floxed STOP-ChRFR(C167A)-Venus BAC rats that conditionally express the step-function mutant channelrhodopsin ChRFR(C167A) under the control of extrinsic Cre recombinase. In primary cultured cortical neurons derived from this reporter rat, only Cre-positive cells expressing ChRFR(C167A) became bi-stable, that is, their excitability was enhanced by blue light and returned to the baseline by yellow~red light...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615095/loss-of-xbp1-accelerates-age-related-decline-in-retinal-function-and-neurodegeneration
#8
Todd McLaughlin, Marek Falkowski, Jae Whan Park, Stephen Keegan, Michael Elliott, Joshua J Wang, Sarah X Zhang
BACKGROUND: Aging is the strongest risk factor for neurodegenerative diseases and extended age results in neuronal degeneration and functional decline in the visual system. Among many contributing factors to age-related deterioration of neurons is an insufficient activation of the Unfolded Protein Response (UPR) in the endoplasmic reticulum (ER) in response to cellular stress. X-box binding protein 1 (XBP1) is a major component of the UPR and is essential for maintaining protein homeostasis and reducing cellular stresses...
April 4, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29611893/comparative-proteome-analysis-of-propionate-degradation-by-syntrophobacter-fumaroxidans-in-pure-culture-and-in-coculture-with-methanogens
#9
Vicente T Sedano-Núñez, Sjef Boeren, Alfons J M Stams, Caroline M Plugge
Syntrophobacter fumaroxidans is a sulfate-reducing bacterium able to grow on propionate axenically or in syntrophic interaction with methanogens or other sulfate-reducing bacteria. We performed a proteome analysis of S. fumaroxidans growing with propionate axenically with sulfate or fumarate, and in syntrophy with Methanospirillum hungatei, Methanobacterium formicicum or Desulfovibrio desulfuricans. Special attention was put on the role of hydrogen and formate in interspecies electron transfer (IET) and energy conservation...
April 3, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29611835/essential-role-for-smooth-muscle-cell-stromal-interaction-molecule-1-in-myocardial-infarction
#10
Vishal Mali, Samuel Haddox, Souad Belmadani, Khalid Matrougui
OBJECTIVES: Stromal interacting molecule-1 (STIM1) plays a role in coordinating calcium signaling in different cell types. The increase or deletion of STIM1 expression in cardiomyocyte causes cardiac complication. Moreover, the deletion of STIM1 in endothelial cell causes vascular endothelial dysfunction. However, the disruption of STIM1 in smooth muscle cells (SMC) has no effect on endothelial function but protects vascular function when mice are infused with angiotensin-II. Nevertheless, the role of SMC-STIM1 in acute and chronic myocardial infarction (MI) induced by acute ischemia-reperfusion injury and permanent coronary artery occlusion is unknown...
February 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29593657/lipoprotein-lipase-expression-in-hypothalamus-is-involved-in-the-central-regulation-of-thermogenesis-and-the-response-to-cold-exposure
#11
Elise Laperrousaz, Raphaël G Denis, Nadim Kassis, Cristina Contreras, Miguel López, Serge Luquet, Céline Cruciani-Guglielmacci, Christophe Magnan
Lipoprotein lipase (LPL) is expressed in different areas of the brain, including the hypothalamus and plays an important role in neural control of the energy balance, including feeding behavior and metabolic fluxes. This study tested the hypothesis that hypothalamic LPL participates in the control of body temperature. We first showed that cold exposure induces decreased activity and expression of LPL in the mouse hypothalamus. We then selectively deleted LPL in the mediobasal hypothalamus (MBH) through an adeno-associated virus approach in LPL-floxed mice and generated MBHΔ Lpl mice with 30-35% decrease in hypothalamic LPL activity...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29593101/thalidomide-reduces-hemorrhage-of-brain-arteriovenous-malformations-in-a-mouse-model
#12
Wan Zhu, Wanqiu Chen, Dingquan Zou, Liang Wang, Chen Bao, Lei Zhan, Daniel Saw, Sen Wang, Ethan Winkler, Zhengxi Li, Meng Zhang, Fanxia Shen, Sonali Shaligram, Michael Lawton, Hua Su
BACKGROUND AND PURPOSE: Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current treatments for bAVM are all associated with considerable risks. There is no safe method to prevent bAVM hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary hemorrhagic telangiectasia, an inherited disorder characterized by vascular malformations. In this study, we tested whether thalidomide and its less toxic analog, lenalidomide, reduce bAVM hemorrhage using a mouse model...
March 28, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29575577/smad7-deficiency-decreases-iron-and-haemoglobin-through-hepcidin-up-regulation-by-multilayer-compensatory-mechanisms
#13
Peng An, Hao Wang, Qian Wu, Jiaming Wang, Zhidan Xia, Xuyan He, Xinhui Wang, Yan Chen, Junxia Min, Fudi Wang
To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly controlled by BMP-Smad signalling pathway, but the physiological role of Smad7 in hepcidin regulation remains elusive. We generated and characterized hepatocyte-specific Smad7 knockout mice (Smad7Alb/Alb ), which showed decreased serum iron, tissue iron, haemoglobin concentration, up-regulated hepcidin and increased phosphor-Smad1/5/8 levels in both isolated primary hepatocytes and liver tissues. Increased levels of hepcidin lead to reduced expression of intestinal ferroportin and mild iron deficiency anaemia...
March 25, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29563120/platelet-hmgb1-is-required-for-efficient-bacterial-clearance-in-intra-abdominal-bacterial-sepsis-in-mice
#14
Hui Zhou, Meihong Deng, Yingjie Liu, Chenxuan Yang, Rosemary Hoffman, Jingjiao Zhou, Patricia A Loughran, Melanie J Scott, Matthew D Neal, Timothy R Billiar
Thrombocytopenia impairs host defense and hemostasis in sepsis. However, the mechanisms of how platelets regulate host defense are not fully understood. High-mobility group box 1 (HMGB1), a danger-associated molecular pattern protein, is released during infection and contributes to the pathogenesis of sepsis. Platelets express HMGB1, which is released on activation and has been shown to play a critical role in thrombosis, monocyte recruitment, and neutrophil extracellular trap (NET) production. However, the contribution of platelet HMGB1 to host defense is unknown...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29560354/cardiac-specific-deletion-of-pyruvate-dehydrogenase-impairs-glucose-oxidation-rates-and-induces-diastolic-dysfunction
#15
Keshav Gopal, Malak Almutairi, Rami Al Batran, Farah Eaton, Manoj Gandhi, John Reyes Ussher
Obesity and type 2 diabetes (T2D) increase the risk for cardiomyopathy, which is the presence of ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. As myocardial energy metabolism is altered during obesity/T2D (increased fatty acid oxidation and decreased glucose oxidation), we hypothesized that restricting myocardial glucose oxidation in lean mice devoid of the perturbed metabolic milieu observed in obesity/T2D would produce a cardiomyopathy phenotype, characterized via diastolic dysfunction...
2018: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29560090/mutation-of-tgf%C3%AE-rii-eliminates-nsaid-cancer-chemoprevention
#16
Juana Martín-López, Pierluigi Gasparini, Kevin Coombes, Carlo M Croce, Gregory P Boivin, Richard Fishel
Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit anti-neoplastic (chemoprevention) activity for sporadic cancers and the hereditary cancer predisposition Lynch syndrome (LS/HNPCC). However, the mechanism of NSAID tumor suppression has remained enigmatic. Defects in the core mismatch repair (MMR) genes MSH2 and MLH1 are the principal drivers of LS/HNPCC. Previous work has demonstrated that the villin - Cre+/- Msh2flox/flox (VpC-Msh2) mouse is a reliable model for LS/HNPCC intestinal tumorigenesis, which is significantly suppressed by treatment with the NSAID aspirin (ASA) similar to human chemoprevention...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29546522/novel-reporter-and-deleter-mouse-strains-generated-using-vcre-vloxp-and-scre-sloxp-systems-and-their-system-specificity-in-mice
#17
Yuki Yoshimura, Miyuki Ida-Tanaka, Tsuyoshi Hiramaki, Motohito Goto, Tsutomu Kamisako, Tomoo Eto, Mika Yagoto, Kenji Kawai, Takeshi Takahashi, Manabu Nakayama, Mamoru Ito
DNA site-specific recombination by Cre/loxP is a powerful tool for gene manipulation in experimental animals. VCre/VloxP and SCre/SloxP are novel site-specific recombination systems, consisting of a recombinase and its specific recognition sequences, which function in a manner similar to Cre/loxP. Previous reports using Escherichia coli and Oryzias latipes demonstrated the existence of stringent specificity between each recombinase and its target sites; VCre/VloxP, SCre/SloxP, and Cre/loxP have no cross-reactivity with each other...
March 15, 2018: Transgenic Research
https://www.readbyqxmd.com/read/29546371/generation-of-mouse-for-conditional-expression-of-forkhead-box-a2-foxa2
#18
Peng Wang, San-Pin Wu, Kelsey E Brooks, Andrew M Kelleher, Jessica Milano-Foster, Francesco J DeMayo, Thomas E Spencer
Forkhead box A2 (FOXA2) is a pioneer transcription factor involved in organ development, function and cancer. In the uterus, FOXA2 is essential for pregnancy and expressed specifically in the glands of the endometrium loss of FOXA2 function occurs during development of endometrial cancer in humans. The present study describes the development of a mouse model for conditional expression of mouse FOXA2. Using a system consisting of a minigene located at the Rosa26 locus, a CAG-S-mFOXA2 allele was generated in embryonic stem cells and subsequently in mice; before activation, the minigene is silent due to a floxed stop cassette inserted between the promoter and the transgene...
March 13, 2018: Endocrinology
https://www.readbyqxmd.com/read/29545603/notch2-controls-hepatocyte-derived-cholangiocarcinoma-formation-in-mice
#19
Jingxiao Wang, Mingjie Dong, Zhong Xu, Xinhua Song, Shanshan Zhang, Yu Qiao, Li Che, John Gordan, Kaiwen Hu, Yan Liu, Diego F Calvisi, Xin Chen
Liver cancer comprises a group of malignant tumors, among which hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common. ICC is especially pernicious and associated with poor clinical outcome. Studies have shown that a subset of human ICCs may originate from mature hepatocytes. However, the mechanisms driving the trans-differentiation of hepatocytes into malignant cholangiocytes remain poorly defined. We adopted lineage tracing techniques and an established murine hepatocyte-derived ICC model by hydrodynamic injection of activated forms of AKT (myr-AKT) and Yap (YapS127A) proto-oncogenes...
March 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29535639/vascular-endothelial-cell-specific-connective-tissue-growth-factor-ctgf-is-necessary-for-development-of-chronic-hypoxia-induced-pulmonary-hypertension
#20
Liya Pi, Chunhua Fu, Yuanquing Lu, Junmei Zhou, Marda Jorgensen, Vinayak Shenoy, Kenneth E Lipson, Edward W Scott, Andrew J Bryant
Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown...
2018: Frontiers in Physiology
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