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https://www.readbyqxmd.com/read/27906111/the-functional-significance-of-the-skeletal-muscle-clock-lessons-from-bmal1-knockout-models
#1
REVIEW
Stefano Schiaffino, Bert Blaauw, Kenneth A Dyar
The circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regulated by the central pacemaker, the suprachiasmatic nucleus of the hypothalamus. A unique feature of circadian rhythms in skeletal muscle is motor neuron-dependent contractile activity, which can affect the oscillation of a number of muscle genes independently of the muscle clock. The role of the intrinsic muscle clock has been investigated using different Bmal1 knockout (KO) models...
October 13, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906090/muscle-specific-deletion-of-socs3-increases-the-early-inflammatory-response-but-does-not-affect-regeneration-after-myotoxic-injury
#2
Kristy Swiderski, Savant S Thakur, Timur Naim, Jennifer Trieu, Annabel Chee, David I Stapleton, René Koopman, Gordon S Lynch
BACKGROUND: Muscles of old animals are injured more easily and regenerate poorly, attributed in part to increased levels of circulating pro-inflammatory cytokines. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade is a key mediator of inflammatory cytokine action, and signaling via this pathway is increased in muscles with aging. As a negative regulator of JAK/STAT signaling, a key mediator of myogenic proliferation and differentiation, altered expression of suppressor of cytokine signaling (SOCS3) is likely to have important consequences for muscle regeneration...
October 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906078/four-week-rapamycin-treatment-improves-muscular-dystrophy-in-a-fukutin-deficient-mouse-model-of-dystroglycanopathy
#3
Steven J Foltz, Junna Luan, Jarrod A Call, Ankit Patel, Kristen B Peissig, Marisa J Fortunato, Aaron M Beedle
BACKGROUND: Secondary dystroglycanopathies are a subset of muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (αDG). Loss of αDG functional glycosylation prevents it from binding to laminin and other extracellular matrix receptors, causing muscular dystrophy. Mutations in a number of genes, including FKTN (fukutin), disrupt αDG glycosylation. METHODS: We analyzed conditional Fktn knockout (Fktn KO) muscle for levels of mTOR signaling pathway proteins by Western blot...
June 2, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#4
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906051/the-lysine-methyltransferase-ehmt2-g9a-is-dispensable-for-skeletal-muscle-development-and-regeneration
#5
Regan-Heng Zhang, Robert N Judson, David Y Liu, Jürgen Kast, Fabio M V Rossi
BACKGROUND: Euchromatic histone-lysine N-methyltransferase 2 (G9a/Ehmt2) is the main enzyme responsible for the apposition of H3K9 di-methylation on histones. Due to its dual role as an epigenetic regulator and in the regulation of non-histone proteins through direct methylation, G9a has been implicated in a number of biological processes relevant to cell fate control. Recent reports employing in vitro cell lines indicate that Ehmt2 methylates MyoD to repress its transcriptional activity and therefore its ability to induce differentiation of activated myogenic cells...
May 27, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906050/the-sh3-and-cysteine-rich-domain-3-stac3-gene-is-important-to-growth-fiber-composition-and-calcium-release-from-the-sarcoplasmic-reticulum-in-postnatal-skeletal-muscle
#6
Xiaofei Cong, Jonathan Doering, Davi A G Mazala, Eva R Chin, Robert W Grange, Honglin Jiang
BACKGROUND: The SH3 and cysteine-rich domain 3 (Stac3) gene is specifically expressed in the skeletal muscle. Stac3 knockout mice die perinatally. In this study, we determined the potential role of Stac3 in postnatal skeletal muscle growth, fiber composition, and contraction by generating conditional Stac3 knockout mice. METHODS: We disrupted the Stac3 gene in 4-week-old male mice using the Flp-FRT and tamoxifen-inducible Cre-loxP systems. RESULTS: RT-qPCR and western blotting analyses of the limb muscles of target mice indicated that nearly all Stac3 mRNA and more than 70 % of STAC3 protein were deleted 4 weeks after tamoxifen injection...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906023/surface-area-dependence-of-gas-particle-interactions-influences-pulmonary-and-neuroinflammatory-outcomes
#7
Christina R Tyler, Katherine E Zychowski, Bethany N Sanchez, Valeria Rivero, Selita Lucas, Guy Herbert, June Liu, Hammad Irshad, Jacob D McDonald, Barry E Bleske, Matthew J Campen
BACKGROUND: Deleterious consequences of exposure to traffic emissions may derive from interactions between carbonaceous particulate matter (PM) and gaseous components in a manner that is dependent on the surface area or complexity of the particles. To determine the validity of this hypothesis, we examined pulmonary and neurological inflammatory outcomes in C57BL/6 and apolipoprotein E knockout (ApoE(-/-)) male mice after acute and chronic exposure to vehicle engine-derived particulate matter, generated as ultrafine (UFP) and fine (FP) sizes, with additional exposures using UFP or FP combined with gaseous copollutants derived from fresh gasoline and diesel emissions, labeled as UFP + G and FP + G...
December 1, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27905406/differential-roles-for-l-type-calcium-channel-subtypes-in-alcohol-dependence
#8
Stefanie Uhrig, David Vandael, Andrea Marcantoni, Nina Dedic, Ainhoa Bilbao, Miriam A Vogt, Natalie Hirth, Laura Broccoli, Rick E Bernardi, Kai Schönig, Peter Gass, Dusan Bartsch, Rainer Spanagel, Jan M Deussing, Wolfgang H Sommer, Emilio Carbone, Anita C Hansson
It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol dependent rats during protracted abstinence and naïve controls using in situ hybridization and Western Blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons...
December 1, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27905296/a-pathogenic-role-for-the-integrin-cd103-in-experimental-allergic-airways-disease
#9
Vanessa S Fear, Siew Ping Lai, Graeme R Zosky, Kara L Perks, Shelley Gorman, Fabian Blank, Christophe von Garnier, Philip A Stumbles, Deborah H Strickland
The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4(+) T-cell activation and DC activation and function in airways and lymph nodes...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27905063/efficient-gene-targeting-in-mouse-zygotes-mediated-by-crispr-cas9-protein
#10
Chris J Jung, Junli Zhang, Elizabeth Trenchard, Kent C Lloyd, David B West, Barry Rosen, Pieter J de Jong
The CRISPR/Cas9 system has rapidly advanced targeted genome editing technologies. However, its efficiency in targeting with constructs in mouse zygotes via homology directed repair (HDR) remains low. Here, we systematically explored optimal parameters for targeting constructs in mouse zygotes via HDR using mouse embryonic stem cells as a model system. We characterized several parameters, including single guide RNA cleavage activity and the length and symmetry of homology arms in the construct, and we compared the targeting efficiency between Cas9, Cas9nickase, and dCas9-FokI...
November 30, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27904881/sfr1-a-tetrahymena-thermophila-sfi1-repeat-protein-modulates-the-production-of-cortical-row-basal-bodies
#11
Westley Heydeck, Alexander J Stemm-Wolf, Janin Knop, Christina C Poh, Mark Winey
Basal bodies are essential microtubule-based structures that template, anchor, and orient cilia at the cell surface. Cilia act primarily in the generation of directional fluid flow and sensory reception, both of which are utilized for a broad spectrum of cellular processes. Although basal bodies contribute to vital cell functions, the molecular contributors of their assembly and maintenance are poorly understood. Previous studies of the ciliate Tetrahymena thermophila revealed important roles for two centrin family members in basal body assembly, separation of new basal bodies, and stability...
November 2016: MSphere
https://www.readbyqxmd.com/read/27904679/tongxinluo-inhibits-neointimal-formation-by-regulating-the-expression-and-post-translational-modification-of-klf5-in-macrophages
#12
Wen Jiang, Bin Zheng, Xin-Hua Zhang, Ling-Yan Yue, Chan Liu, Dong Ma, Zhan Yang, Jin-Kun Wen
Neointimal hyperplasia is a common pathological characteristic in diverse vascular remodeling diseases. The inflammatory response that follows vascular injury plays an important role in intimal hyperplasia. Tongxinluo (TXL), a traditional Chinese medicine, can ameliorate neointimal formation via suppressing vascular inflammatory response induced by vascular injury. However, the mechanisms underlying anti-inflammatory and anti-intimal hyperplasia of TXL are still not fully understood. The aim of present study was to examine whether the expression and post-translational modification of KLF5 were involved in the vasoprotective effects of TXL...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#13
Ying Yin, Xian Xue, Qian Wang, Ning Chen, Dengshun Miao
To explore whether polycomb repressor Bmi1 plays an important role in dentin and mandible development homeostasis by maintaining redox balance, 3-week-old Bmi1 gene knockout (Bmi1(-/-)) mice were treated with the antioxidant N-acetylcysteine (NAC) for 2 weeks in their drinking water and phenotypes of the tooth and mandibles were compared with vehicle-treated Bmi1(-/-) mice and wild-type mice by radiograph, histochemistry and immunohistochemistry. Alterations of oxidative stress, DNA damage, cell proliferation and cell cycle-related parameters were also examined in mandibles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27903970/ion-channels-in-control-of-pancreatic-stellate-cell-migration
#14
Hannah Storck, Benedikt Hild, Sandra Schimmelpfennig, Sarah Sargin, Nikolaj Nielsen, Angela Zaccagnino, Thomas Budde, Ivana Novak, Holger Kalthoff, Albrecht Schwab
Pancreatic stellate cells (PSCs) play a critical role in the progression of pancreatic ductal adenocarcinoma (PDAC). Once activated, PSCs support proliferation and metastasis of carcinoma cells. PSCs even co-metastasise with carcinoma cells. This requires the ability of PSCs to migrate. In recent years, it has been established that almost all "hallmarks of cancer" such as proliferation or migration/invasion also rely on the expression and function of ion channels. So far, there is only very limited information about the function of ion channels in PSCs...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903802/a-protective-role-for-il-1-signaling-during-mouse-adenovirus-type-1-induced-encephalitis
#15
Luiza A Castro-Jorge, Carla Pretto, Asa Smith, Oded Foreman, Kelly E Carnahan, Katherine R Spindler
: IL-1β, an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor, Il1r1(-/-) Il1r1(-/-) mice had lower survival, higher disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokines and chemokines than control C57BL/6 mice. We also examined infections of mice defective in IL-1β production (Pycard(-/-)mice) and mice defective in trafficking of TLRs to the endosome (Unc93b1(-/-) mice)...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903773/nlk-mediated-phosphorylation-of-hdac1-negatively-regulates-wnt-signaling
#16
Katarzyna Chmielarska Masoumi, Renée Daams, Wondossen Sime, Valentina Siino, Hengning Ke, Fredrik Levander, Ramin Massoumi
The Wnt signaling pathway is essential in regulating various cellular processes. Different mechanisms of inhibition for Wnt signaling have been proposed. Besides β-catenin degradation, through the proteasome, nemo-like kinase (NLK) is another molecule that is known to negatively regulate Wnt signaling. However, the mechanism by which NLK mediates the inhibition of Wnt signaling is not yet known. In the present study, we used primary embryonic fibroblast cells isolated from NLK-deficient mice and showed that these cells proliferate faster and have a shorter cell cycle compared with wild-type cells...
November 30, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27903744/metallothionein-is-downstream-of-nrf2-and-partially-mediates-sulforaphane-prevention-of-diabetic-cardiomyopathy
#17
Junlian Gu, Yanli Cheng, Hao Wu, Lili Kong, Shudong Wang, Zheng Xu, Zhiguo Zhang, Yi Tan, Bradley B Keller, Honglan Zhou, Yuehui Wang, Zhonggao Xu, Lu Cai
We have reported that sulforaphane prevented diabetic cardiomyopathy in both T1DM and T2DM animal models via the up-regulation of Nrf2 and metallothionein (MT). Here we tested whether sulforaphane protects the heart from T2DM directly through Nrf2, MT or both. Using Nrf2-knockout (KO), MT-KO, and wild-type mice T2DM was induced by feeding high-fat diet (HFD) for 3 months followed by a small dose of streptozotocin. Age-matched controls were given normal diet (ND). Both T2DM and control mice were then treated with or without sulforaphane for 4 months with continually feeding HFD or ND...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903648/evidence-against-a-role-for-the-parkinsonism-associated-protein-dj-1-in-methylglyoxal-detoxification
#18
Daniel H Pfaff, Thomas Fleming, Peter Nawroth, Aurelio A Teleman
Methylglyoxal (MG) is a reactive metabolite that forms adducts on lysine and arginine residues of proteins, thereby affecting their function. Methylglyoxal is detoxified by the Glyoxalase system, consisting of two enzymes, Glo1 and Glo2, that act sequentially to convert MG into D-lactate. Recently, the Parkinsonism-associated protein DJ-1 was described in vitro to have glyoxalase activity, thereby detoxifying the MG metabolite, or deglycase activity, thereby removing the adduct formed by MG on proteins. Since Drosophila is an established model system to study signaling, neurodegeneration and metabolic regulation in vivo, we asked whether DJ-1 contributes to MG detoxification in vivo...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27903531/dream-plays-an-important-role-in-platelet-activation-and-thrombogenesis
#19
Kyungho Kim, Alan Tseng, Andrew Barazia, Joseph E Italiano, Jaehyung Cho
Downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, is known to modulate pain responses. However, it is unknown whether DREAM is expressed in anucleate platelets and plays a role in thrombogenesis. By using intravital microscopy with DREAM-null mice and their bone marrow chimeras, we demonstrated that both hematopoietic and non-hematopoietic cell DREAM are required for platelet thrombus formation following laser-induced arteriolar injury. In a FeCl3-induced thrombosis model, we found that compared to WT control and non-hematopoietic DREAM knockout (KO) mice, DREAM KO control and hematopoietic DREAM KO mice showed a significant delay in time to occlusion...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27903395/-role-of-cytokine-matrix-metalloproteinase-axis-on-promoting-vascular-neointima-hyperplasia-in-mice
#20
Y Liu, W H Ning, X H Shen, D L Guo, L Guo
Objective: To observe the effects of tumor necrosis factor-α (TNF-α) and platelet derived growth factor (PDGF) on vascular neointimal hyperplasia on matrix metalloproteinase 9/2 gene knockout (MMP9/2(-/-)) mice and explore related mechanisms. Methods: Mice of control group, MMP9(-/-) group, MMP2(-/-) group and MMP9/2(-/-) group were studied. Femoral artery was injured by transluminal wire, the mRNA expression levels of TNF-α and PDGF on femoral artery were detected by RT-PCR; the protein expression of MMP9 and MMP2 were assessed by Western blot on day 0, 1, 3, 7, 14 and 28 post injury...
November 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
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