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https://www.readbyqxmd.com/read/29161772/microarray-analysis-of-gene-expression-in-the-cyclooxygenase-cox-knockout-mice-a-connection-to-autism-spectrum-disorder
#1
Ravneet Rai-Bhogal, Eizaaz Ahmad, Hongyan Li, Dorota A Crawford
The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid signalling molecules such as prostaglandin E2 (PGE2 ) play an important role in healthy brain development. Abnormalities along the COX/PGE2 signalling pathway due to genetic or environmental causes have been linked to Autism Spectrum Disorders (ASDs). This study aims to evaluate the effect of altered COX/PGE2 signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and -2 (COX-1(-/-) and COX-2(-/-) ) as potential model systems of ASD...
November 21, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29161470/resequencing-of-a-mutant-bearing-an-iron-starvation-recovery-phenotype-defines-slr1658-as-a-new-player-in-the-regulatory-network-of-a-model-cyanobacterium
#2
Hagit Zer, Ketty Margulis, Jens Georg, Yoram Shotland, Gergana Kostova, Laure Sultan, Wolfgang R Hess, Nir Keren
Photosynthetic microorganisms encounter an erratic nutrient environment characterized by periods of iron limitation and sufficiency. Surviving in such an environment requires mechanisms for handling these transitions. Our study identified a regulatory system involved in the process of recovery from iron limitation in cyanobacteria. We set out to study the role of bacterioferritin co-migratory proteins during transitions in iron bioavailability in the cyanobacterium Synechocystis sp. PCC 6803 using knockout strains coupled with physiological and biochemical measurements...
November 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29160908/connective-tissue-growth-factor-induces-renal-fibrosis-via-epidermal-growth-factor-receptor-activation
#3
Sandra Rayego-Mateos, José Luis Morgado-Pascual, Raúl R Rodrigues-Diez, Raquel Rodrigues-Diez, Lucas Falke, Sergio Mezzano, Alberto Ortiz, Jesús Egido, Roel Goldschmeding, Marta Ruiz-Ortega
Connective tissue growth factor (CCN2/CTGF) is a matricellular protein overexpressed in progressive human renal diseases, mainly in fibrotic areas. In vitro studies have demonstrated that CCN2 regulates production of extracellular matrix (ECM) proteins and epithelial mesenchymal transition (EMT), and therefore could contribute to renal fibrosis. CCN2 blockade ameliorates experimental renal damage, including diminution of ECM accumulation. We have described that CCN2 and its C-terminal degradation product CCN2(IV), bind to epidermal growth factor receptor (EGFR) to modulate renal inflammation...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29160307/a-non-canonical-notch-complex-regulates-adherens-junctions-and-vascular-barrier-function
#4
William J Polacheck, Matthew L Kutys, Jinling Yang, Jeroen Eyckmans, Yinyu Wu, Hema Vasavada, Karen K Hirschi, Christopher S Chen
The vascular barrier that separates blood from tissues is actively regulated by the endothelium and is essential for transport, inflammation, and haemostasis1. Haemodynamic shear stress plays a critical role in maintaining endothelial barrier function2, but how this occurs remains unknown. Here, using an engineered organotypic model of perfused microvessels and confirming in mouse models, we identify that activation of the Notch1 transmembrane receptor directly regulates vascular barrier function through a non-canonical, transcription independent signalling mechanism that drives adherens junction assembly...
November 13, 2017: Nature
https://www.readbyqxmd.com/read/29160120/oral-administration-of-a-novel-lipophilic-ppar%C3%AE-agonist-is-not-neuroprotective-after-rodent-cerebral-ischemia
#5
Samuel Knauss, Matthias Endres, Florian Blaschke, Claudia Hindinger, Alexander Kunz
Peroxisome proliferator-activated receptors are regulators of inflammatory signaling. This has fostered hope that PPAR agonists might have neuroprotective potential. We hypothesized that PPARδ activation by the novel orally administered lipophilic PPARδ agonist SAR145 may improve short- and long-term outcome after focal brain ischemia. We induced ischemia by transient filamentous middle cerebral artery occlusion (MCAo) in 227 C57BL/6 mice and administered SAR145 in varying doses and time windows post-injury...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29160110/peroxiredoxin6-a-multitask-antioxidant-enzyme-involved-in-the-pathophysiology-of-chronic-non-communicable-diseases
#6
Francesca Pacifici, David Della-Morte, Barbara Capuani, Donatella Pastore, Alfonso Bellia, Paolo Sbraccia, Nicola Di Daniele, Renato Lauro, Davide Lauro
SIGNIFICANCE: Chronic Non-Communicable Diseases (NCDs) are the leading causes of disability and death worldwide. NCDs mainly comprise diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease (COPD), cancer, and neurological degenerative diseases, which kill more than 80% of population, especially elderlies, worldwide. Recent Advances: Several recent theories established NCDs as multifactorial diseases, where a combination of genetic, epigenetic and environmental factors contributes to their pathogenesis...
November 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29160014/loss-of-tenascin-x-gene-function-impairs-injury-induced-stromal-angiogenesis-in-mouse-corneas
#7
Takayoshi Sumioka, Hiroki Iwanishi, Yuka Okada, Yuka Nidegawa, Masayasu Miyajima, Ken-Ichi Matsumoto, Shizuya Saika
To determine the contribution by tenascin X (Tnx) gene expression to corneal stromal angiogenesis, the effects were determined of its loss on this response in TNX knockout (KO) mice. In parallel, the effects of such a loss were evaluated on vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGFβ1) gene and protein expression in fibroblasts and macrophages in cell culture. Histological, immunohistochemical and quantitative RT-PCR changes determined if Tnx gene ablation on angiogenic gene expression, inflammatory cell infiltration and neovascularization induced by central corneal stromal cauterization...
November 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29159954/unraveling-the-mechanistic-complexity-of-the-glomerulocystic-phenotype-in-dicer-conditional-ko-mice-by-2d-gel-electrophoresis-coupled-mass-spectrometry
#8
Claudia Vincenza Fiumara, Domenica Scumaci, Anna Iervolino, Angela Mena Perri, Antonio Concolino, Laura Tammè, Federica Petrillo, Giovambattista Capasso, Giovanni Cuda
PURPOSE: Dicer, an RNase III type endonuclease, is a key enzyme involved in miRNA biogenesis. It has been shown that this enzyme is essential for several aspects of postnatal kidney functions and homeostasis. In this study, we have examined conditional knockout (cKO) mice for Dicer in Pax8 (Paired-box gene 8) expressing cells to investigate the kidney protein profile. This specific model develops a glomerulocystic phenotype coupled with urinary concentration impairment, proteinuria and severe renal failure...
November 21, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29159818/c-ebp%C3%AE-dependent-pre-neoplastic-tumor-foci-are-the-origin-of-hepatocellular-carcinoma-and-aggressive-pediatric-liver-cancer
#9
Ashley Cast, Leila Valanejad, Mary Wright, Phuong Nguyen, Anita Gupta, Liqin Zhu, Soona Shin, Nikolai Timchenko
Recent publications show that classic hepatoblastoma (HBL) is the result of failure of hepatic stem cells to differentiate into hepatocytes; while hepatocellular carcinoma (HCC) is caused by the de-differentiation of hepatocytes into Cancer Stem Cells (CSCs). However, the mechanisms of aggressive HBL and mechanisms that cause de-differentiation of hepatocytes into CSCs are unknown. We found that, similar to HCC but opposite to classic HBL, aggressive HBL is the result of de-differentiation of hepatocytes into CSCs...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29159199/dna-mediated-gene-therapy-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2b
#10
Julia Ma, Christophe Pichavant, Haley du Bois, Mital Bhakta, Michele P Calos
Mutations in the gene for dysferlin cause a degenerative disorder of skeletal muscle known as limb girdle muscular dystrophy 2B. To achieve gene delivery of plasmids encoding dysferlin to hind limb muscles of dysferlin knockout mice, we used a vascular injection method that perfused naked plasmid DNA into all major muscle groups of the hind limb. We monitored delivery by luciferase live imaging and western blot, confirming strong dysferlin expression that persisted over the 3-month time course of the experiment...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29158989/activation-of-rho-kinase-and-focal-adhesion-kinase-regulates-the-organization-of-stress-fibers-and-focal-adhesions-in-the-central-part-of-fibroblasts
#11
Kazuo Katoh
Specific regulation and activation of focal adhesion kinase (FAK) are thought to be important for focal adhesion formation, and activation of Rho-kinase has been suggested to play a role in determining the effects of FAK on the formation of stress fibers and focal adhesions. To clarify the role of FAK in stress fiber formation and focal adhesion organization, the author examined the formation of new stress fibers and focal adhesions by activation of Rho-kinase in FAK knockout (FAK(-/-)) fibroblasts. FAK(-/-) cells were elliptical in shape, and showed reduced numbers of stress fibers and focal adhesions in the central part of the cells along with large focal adhesions in the peripheral regions...
2017: PeerJ
https://www.readbyqxmd.com/read/29158846/subcellular-localization-of-survivin-determines-its-function-in-cardiomyocytes
#12
Tien-Jui Tsang, Ying-Chang Hsueh, Erika I Wei, David J Lundy, Bill Cheng, You-Tzung Chen, Shoei-Shen Wang, Patrick C H Hsieh
Rationale: Reducing cardiomyocyte death and enhancing their proliferation after myocardial infarction is perhaps the single largest challenge for cardiac tissue regeneration. Survivin (SVV) is the smallest member of the inhibitor of apoptosis (IAP) family but plays two important roles; inhibiting caspase-9 activation in the intrinsic apoptosis pathway, and regulating microtubule dynamics and chromosome segregation during cell division. Genetic depletion of cardiac SVV leads to incomplete cardiomyocyte division and abnormal heart development...
2017: Theranostics
https://www.readbyqxmd.com/read/29158819/pro-inflammatory-cxcr3-impairs-mitochondrial-function-in-experimental-non-alcoholic-steatohepatitis
#13
Jinghua Du, Xiang Zhang, Juqiang Han, Kwan Man, Yanquan Zhang, Eagle Sh Chu, Yuemin Nan, Jun Yu
Mitochondrial dysfunction plays a crucial role in the development of non-alcoholic steatohepatitis (NASH). However, the regulator of mitochondrial dysfunction in the pathogenesis of NASH is still largely unclear. CXCR3 is an essential pro-inflammatory factor in chronic liver diseases. We explored the significance of CXCR3 in regulating mitochondrial function during NASH development in animal models and cultured hepatocytes. METHODS: The effects of CXCR3 on mitochondrial function were evaluated by genetic knockout or pharmacological inhibition in mouse models and in vitro...
2017: Theranostics
https://www.readbyqxmd.com/read/29158604/antiviral-cd8-t-cells-induce-zika-virus-associated-paralysis-in-mice
#14
Kellie A Jurado, Laura J Yockey, Patrick W Wong, Sarah Lee, Anita J Huttner, Akiko Iwasaki
Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly (1) and Guillain-Barré syndrome (2,3) as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis (4) , meningoencephalitis (5) and fatal encephalitis (6) . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 (-/-) ) mice, an infection model that exhibits high viral burden within the central nervous system...
November 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29158586/insights-into-gene-expression-profiles-induced-by-socs3-depletion-in-keratinocytes
#15
Archana Bajpai, Takashi Ishii, Kosuke Miyauchi, Vipul Gupta, Yuka Nishio-Masaike, Yuki Shimizu-Yoshida, Masato Kubo, Hiroaki Kitano
Specific deletion of suppressor of cytokine signaling 3 (Socs3) in keratinocytes can cause severe skin inflammation with infiltration of immune cells. The molecular mechanisms and key regulatory pathways involved in these processes remain elusive. To investigate the role of Socs3 in keratinocytes, we generated and analyzed global RNA-Seq profiles from Socs3 conditional knockout (cKO) mice of two different ages (2 and 10 weeks). Over 400 genes were significantly regulated at both time points. Samples from 2-week-old mice exhibited down-regulation of genes involved in keratin-related functions and up-regulation of genes involved in lipid metabolism...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158584/ketamine-enhances-structural-plasticity-in-mouse-mesencephalic-and-human-ipsc-derived-dopaminergic-neurons-via-ampar-driven-bdnf-and-mtor-signaling
#16
L Cavalleri, E Merlo Pich, M J Millan, C Chiamulera, T Kunath, P F Spano, G Collo
Among neurobiological mechanisms underlying antidepressant properties of ketamine, structural remodeling of prefrontal and hippocampal neurons has been proposed as critical. The suggested mechanism involves downstream activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which trigger mammalian target of rapamycin (mTOR)-dependent structural plasticity via brain-derived neurotrophic factor (BDNF) and protein neo-synthesis. We evaluated whether ketamine elicits similar molecular events in dopaminergic (DA) neurons, known to be affected in mood disorders, using a novel, translational strategy that involved mouse mesencephalic and human induced pluripotent stem cells-derived DA neurons...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158580/ck2-regulates-5-ht4-receptor-signaling-and-modulates-depressive-like-behavior
#17
J Castello, B LeFrancois, M Flajolet, P Greengard, E Friedman, H Rebholz
The serotonergic neurotransmitter system has been widely implicated in the pathophysiology of mood-related disorders such as anxiety and major depressive disorder (MDD). The onset of therapeutic efficacy of traditional antidepressants is delayed by several weeks. The 5-HT4 receptor has emerged as a new therapeutic target since agonists of this receptor induce rapid antidepressant-like responses in rodents. Here we show that the 5-HT4 receptor is regulated by CK2, at transcriptional and post-transcriptional levels...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29158532/recombinant-decorin-fusion-protein-attenuates-murine-abdominal-aortic-aneurysm-formation-and-rupture
#18
Yue Shen, Valerio Russo, Matthew R Zeglinski, Stephanie L Sellers, Zhengguo Wu, Cameron Oram, Stephanie Santacruz, Yulia Merkulova, Christopher Turner, Keerit Tauh, Hongyan Zhao, Tatjana Bozin, Lubos Bohunek, Haishan Zeng, Michael A Seidman, R Chris Bleackley, Bruce M McManus, Erkki Ruoslahti, Tero A H Järvinen, David J Granville
Decorin (DCN) is a small-leucine rich proteoglycan that mediates collagen fibrillogenesis, organization, and tensile strength. Adventitial DCN is reduced in abdominal aortic aneurysm (AAA) resulting in vessel wall instability thereby predisposing the vessel to rupture. Recombinant DCN fusion protein CAR-DCN was engineered with an extended C-terminus comprised of CAR homing peptide that recognizes inflamed blood vessels and penetrates deep into the vessel wall. In the present study, the role of systemically-administered CAR-DCN in AAA progression and rupture was assessed in a murine model...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158436/pathogenic-role-of-the-damage-associated-molecular-patterns-s100a8-and-s100a9-in-coxsackievirus-b3-induced-myocarditis
#19
Irene Müller, Thomas Vogl, Kathleen Pappritz, Kapka Miteva, Konstantinos Savvatis, David Rohde, Patrick Most, Dirk Lassner, Burkert Pieske, Uwe Kühl, Sophie Van Linthout, Carsten Tschöpe
BACKGROUND: The alarmins S100A8 and S100A9 are damage-associated molecular patterns, which play a pivotal role in cardiovascular diseases, inflammation, and viral infections. We aimed to investigate their role in Coxsackievirus B3 (CVB3)-induced myocarditis. METHODS AND RESULTS: S100A8 and S100A9 mRNA expression was 13.0-fold (P=0.012) and 5.1-fold (P=0.038) higher in endomyocardial biopsies from patients with CVB3-positive myocarditis compared with controls, respectively...
November 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29158345/stable-oxidative-cytosine-modifications-accumulate-in-cardiac-mesenchymal-cells-from-type2-diabetes-patients-rescue-by-alpha-ketoglutarate-and-tet-tdg-functional-reactivation
#20
Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Künne, Stefan Günther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Duran Sueruen, Frank Schnutgen, Harald von Melchner, Antonella Di Stilo, Manuela Aragno, Maarten Braspenning, Wim Van Criekinge, Miles J De Blasio, Rebecca H Ritchie, Germana Zaccagnini, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically-relevant primary cell population. Diabetes compromises CMSC function as consequence of metabolic alterations and incorporation of stable epigenetic changes. Objective: To investigate the role of α-ketoglutarate (αKG) in the epi-metabolic control of DNA demethylation in CMSCs. Methods and Results: Quantitative global analysis, methylated and hydroxymethylated DNA sequencing and gene specific GC methylation detection revealed an accumulation of 5mC, 5hmC and 5fC in the genomic DNA of human CMSCs isolated from diabetic (D) donors (D-CMSCs)...
November 20, 2017: Circulation Research
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