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https://www.readbyqxmd.com/read/28550180/a-novel-de-novo-mutation-in-prkag2-gene-infantile-onset-phenotype-and-signaling-pathway-involved
#1
Yanchun Xu, Alex Gray, David Grahame Hardie, Alper Uzun, Sunil Shaw, James F Padbury, Chanika Phornphutkul, Yi-Tang Tseng
PRKAG2 encodes the γ2-subunit isoform of the 5' AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in regulation of energy metabolism in response to cellular stress. Mutations in PRKAG2 have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload, ventricular preexcitation and hypertrophy. We identified a novel, de novo PRKAG2 mutation (K475E) in a neonate with prenatal onset of HCM. We aimed to investigate the cellular impact, signaling pathways involved and therapeutic options for K475E mutation using cells stably expressing human wild type (WT) or the K475E mutant...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550165/the-clasp2-protein-interaction-network-in-adipocytes-links-clip2-to-agap3-clasp2-to-g2l1-mark2-and-soga1-and-identifies-soga1-as-a-microtubule-associated-protein
#2
Rikke Kruse, James Krantz, Natalie Barker, Richard Coletta, Ruslan Rafikov, Moulun Luo, Kurt Hoejlund, Lawrence J Mandarino, Paul R Langlais
CLASP2 is a microtubule-associated protein that undergoes insulin-stimulated phosphorylation and co-localization with reorganized actin and GLUT4 at the plasma membrane. To gain insight to the role of CLASP2 in this system, we developed and successfully executed a streamlined interactome approach and built a CLASP2 protein network in 3T3-L1 adipocytes. Using two different commercially available antibodies for CLASP2 and an antibody for epitope-tagged, overexpressed CLASP2, we performed multiple affinity purification coupled with mass spectrometry (AP-MS) experiments in combination with label-free quantitative proteomics and analyzed the data with the bioinformatics tool Significance Analysis of Interactome (SAINT)...
May 26, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28549860/crude-terpene-glycoside-component-from-radix-paeoniae-rubra-protects-against-isoproterenol-induced-myocardial-ischemic-injury-via-activation-of-the-pi3k-akt-mtor-signaling-pathway
#3
Zhongcheng Ke, Gang Wang, Lei Yang, Huihui Qiu, Hao Wu, Mei Du, Juan Chen, Jie Song, Xiaobin Jia, Liang Feng
ETHNOPHARMACOLOGICAL RELEVANCE: Radix paeoniae rubra, also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis. It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown...
May 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28549291/antidiabetogenic-efficiency-of-menthol-improves-glucose-homeostasis-and-attenuates-pancreatic-%C3%AE-cell-apoptosis-in-streptozotocin-nicotinamide-induced-experimental-rats-through-ameliorating-glucose-metabolic-enzymes
#4
Udaiyar Muruganathan, Subramani Srinivasan, Veerasamy Vinothkumar
The phytochemical, menthol, has been reported to play many beneficial roles. However, under diabetic conditions, there is no detail mechanism of its beneficial action in the glucose homeostasis. The present study, we investigated to explore the role of menthol, on the glucose metabolic enzymes and pancreatic islet cell apoptosis of streptozotocin-nicotinamide (STZ-NA) induced diabetes in rats. Diabetes was induced by single intraperitoneal (i.p.) injection of STZ (50mg/kg/b.w.) and NA (110mg/kg/b.w.). Diabetic rats were treated with different dose of menthol (25, 50, and 100mg/kg/b...
May 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28548834/subtly-modulating-glycogen-synthase-kinase-3-%C3%AE-allosteric-inhibitors-development-and-their-potential-for-the-treatment-of-chronic-diseases
#5
Valle Palomo, Daniel I Pérez, Carlos Roca, Cara Anderson, Natalia Rodriguez-Muela, Concepción Pérez, Jose A Morales-Garcia, Julio A Reyes, Nuria E Campillo, Ana M Pérez-Castillo, Lee L Rubin, Lubov T Timchenko, Carmen Gil, Ana Martínez
Glycogen synthase kinase 3 β (GSK-3β) is a central target in several unmet diseases. To increase the specificity of GSK-3β inhibitors in chronic treatments we are developing small molecules allowing subtle modulation of GSK-3β activity. Design synthesis, structure-activity relationships and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3β are here presented. Furthermore, we show how allosteric binders may overcome the β-catenin side effects associated to strong GSK-3β inhibition...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28547002/oncolytic-herpes-simplex-virus-inhibits-pediatric-brain-tumor-migration-and-invasion
#6
Julia V Cockle, Anke Brüning-Richardson, Karen J Scott, Jill Thompson, Timothy Kottke, Ewan Morrison, Azam Ismail, Angel M Carcaboso, Ailsa Rose, Peter Selby, Joe Conner, Susan Picton, Susan Short, Richard Vile, Alan Melcher, Elizabeth Ilett
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via immune-mediated mechanisms. Here we investigate a previously unreported mechanism of action: the inhibition of migration and invasion in pediatric brain tumors. We evaluated the effect of oncolytic herpes simplex virus 1716 (HSV1716) on the migration and invasion of pHGG and DIPG both in vitro using 2D (scratch assay, live cell imaging) and 3D (spheroid invasion in collagen) assays and in vivo using an orthotopic xenograft model of DIPG invasion...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28546799/lectin-array-and-glycogene-expression-analyses-of-ovarian-cancer-cell-line-a2780-and-its-cisplatin-resistant-derivate-cell-line-a2780-cp
#7
Ran Zhao, Wenjun Qin, Ruihuan Qin, Jing Han, Can Li, Yisheng Wang, Congjian Xu
BACKGROUND: Ovarian cancer is one of the most lethal gynecological malignancies, in which platinum resistance is a common cause of its relapse and death. Glycosylation has been reported to be involved in drug resistance, and glycomic analyses of ovarian cancer may improve our understanding of the mechanisms underlying cancer cell drug resistance and provide potential biomarkers and therapeutic targets. METHODS: The serous ovarian cancer cell line A2780 and its platinum-resistant counterpart A2780-cp were used in this study...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28545972/lithium-alleviates-neurotoxic-prion-peptide-induced-synaptic-damage-and-neuronal-death-partially-by-the-upregulation-of-nuclear-target-rest-and-the-restoration-of-wnt-signaling
#8
Zhiqi Song, Wei Yang, Xiangmei Zhou, Lifeng Yang, Deming Zhao
Prion diseases are a group of infectious neurodegenerative diseases characterized by multiple neuropathological hallmarks, including accumulation of PrP(Sc), synaptic damage, and neuronal death. We previously reported that the repressor element 1-silencing transcription factor (REST), a novel neuroprotective marker in neurodegeneration, protects neurons against neurotoxic peptide (PrP106-126)-induced neurotoxicity, but fails to maintain survival following prolonged exposure to PrP106-126. Because Wnt signaling partially induces REST and is activated by lithium, we investigated the effects of lithium on REST in prion diseases...
May 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28543747/oxazolo-4-5-b-pyridine-based-piperazinamides-as-gsk-3%C3%AE-inhibitors-with-potential-for-attenuating-inflammation-and-suppression-of-pro-inflammatory-mediators
#9
Mushtaq A Tantray, Imran Khan, Hinna Hamid, Mohammad Sarwar Alam, Abhijeet Dhulap, Ajaz Ahmad Ganai
Recent studies reveal that glycogen synthase kinase-3β (GSK-3β) acts as a pro-inflammatory enzyme, and by inhibiting this kinase, inflammation can be controlled. In this regard, a series of 17 piperazine-linked oxazolo[4,5-b]pyridine-based derivatives was synthesized and evaluated for in vitro GSK-3β inhibitory and in vivo anti-inflammatory activity. The compounds 7d, 7e, 7g, and 7c displayed the best GSK-3β inhibitory activity among all the synthesized compounds, with corresponding IC50 values of 0.34, 0...
May 22, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28543538/clinical-and-histopathological-features-of-myofibrillar-myopathy-in-warmblood-horses
#10
S J Valberg, A M Nicholson, S S Lewis, R A Reardon, C J Finno
BACKGROUND: To report a novel exertional myopathy, myofibrillar myopathy (MFM), in Warmblood horses. OBJECTIVES: To 1) describe the distinctive clinical and myopathic features of MFM in Warmblood horses, 2) investigate the potential inheritance of MFM in a Warmblood family. STUDY DESIGN: Retrospective selection of MFM cases and prospective evaluation of a Warmblood family. METHODS: Retrospectively, muscle biopsies were selected from Warmblood horses diagnosed with MFM and clinical histories obtained (n = 10)...
May 22, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28542051/critical-airway-stenosis-in-an-adolescent-male-with-pompe-disease-and-thoracic-lordosis-a-case-report
#11
B Randall Brenn, Mary T Theroux, Suken A Shah, William G Mackenzie, Robert Heinle, Mena T Scavina
An adolescent male with late-onset Pompe disease (glycogen storage disease type II) presented with a history of restrictive airway disease and a near-cardiorespiratory arrest during anesthesia for a liver biopsy initially thought to be due to bronchospasm. During a subsequent posterior spinal fusion procedure, he suffered cardiorespiratory arrest resulting in the procedure being aborted. Bronchoscopy performed shortly after resuscitation revealed an undiagnosed narrowing of the distal trachea and bronchi. This is the first description of a patient with lateonset Pompe disease with undiagnosed critical tracheal stenosis due to the progression of thoracic lordosis, which was ultimately relieved by posterior spinal fusion...
May 23, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28541039/label-free-discrimination-of-rhizobial-bacteroids-and-mutants-by-single-cell-raman-microspectroscopy
#12
Jiabao Xu, Isabel Webb, Philip Poole, Wei E Huang
Symbiotic rhizobia in legume account for a large portion of nitrogen fixation in the biosphere. Nitrogen fixation is an energy-demanding process requiring tight control of metabolism and redox state. It is of great interest to understand the bacteroid differentiation process and the roles of energy storage molecules, such as glycogen and polyhydroxybutyrate (PHB), in maintaining the Rhizobium-legume symbioses. Traditional biochemical assays for checking phenotypic changes of mutants require a large volume of starting materials, which is difficult for unculturable, terminally differentiated bacteroids...
May 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28541036/non-invasive-diagnosis-of-high-grade-urothelial-carcinoma-in-urine-by-raman-spectral-imaging
#13
Hesham K Yosef, Sascha D Krauß, Tatjana Lechtonen, Hendrik Jütte, Andrea Tannapfel, Heiko Udo Käfferlein, Thomas Brüning, Florian Roghmann, Joachim Noldus, Axel Mosig, Samir F El-Mashtoly, Klaus Gerwert
The current gold standard for diagnosis of bladder cancer is cystoscopy, which is an invasive and painful for patients. Therefore, the non-invasive urine cytology is usually used in clinics as an adjunct to cystoscopy. However, it suffers from low sensitivity. Here, a novel non-invasive, label-free approach on urine is presented with high sensitivity. CARS imaging of urine sediments was used in the first step for fast preselection of urothelial cells, where, the high-grade urothelial cancer cells are characterized by a large nucleus to cytoplasm ratio...
May 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28539729/anti-fatigue-effect-of-green-tea-polyphenols-epigallocatechin-3-gallate-egcg
#14
Yu-Song Teng, Di Wu
BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant of the green tea polyphenols that exhibit a variety of bioactivities. The objective of this study was to evaluate the anti-fatigue effect of EGCG by forced swimming exercise. MATERIALS AND METHODS: The mice were divided into one control group and three EGCG-treated groups. The control group was administered with distilled water and EGCG-treated groups were administered with different dose of EGCG (50, 100, and 200 mg/kg) by oral gavage for 28 days...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28539358/protein-kinase-c-%C3%AE%C2%B5-stabilizes-%C3%AE-catenin-and-regulates-its-subcellular-localization-in-podocytes
#15
Michelle Duong, Xuejiao Yu, Beina Teng, Patricia Schroder, Hermann Haller, Susanne Eschenburg, Mario Schiffer
Kidney disease has been linked to dysregulated signaling via protein kinase C (PKC) in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of β-catenin, which promotes its degradation. β-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with β-catenin has not been studied systematically. Here we demonstrate that PKCε-deficient mice, which develop proteinuria and glomerulosclerosis, display a lower β-catenin expression compared to PKC wildtype mice, consistent with an altered phenotype of podocytes in culture...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28536304/abnormal-glycogen-chain-length-pattern-not-hyperphosphorylation-is-critical-in-lafora-disease
#16
Felix Nitschke, Mitchell A Sullivan, Peixiang Wang, Xiaochu Zhao, Erin E Chown, Ami M Perri, Lori Israelian, Lucia Juana-López, Paola Bovolenta, Santiago Rodríguez de Córdoba, Martin Steup, Berge A Minassian
Lafora disease (LD) is a fatal progressive epilepsy essentially caused by loss-of-function mutations in the glycogen phosphatase laforin or the ubiquitin E3 ligase malin. Glycogen in LD is hyperphosphorylated and poorly hydrosoluble. It precipitates and accumulates into neurotoxic Lafora bodies (LBs). The leading LD hypothesis that hyperphosphorylation causes the insolubility was recently challenged by the observation that phosphatase-inactive laforin rescues the laforin-deficient LD mouse model, apparently through correction of a general autophagy impairment...
May 23, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28536263/axodendritic-sorting-and-pathological-missorting-of-tau-is-isoform-specific-and-determined-by-axon-initial-segment-architecture
#17
Hans Zempel, Frank Dennissen, Yatender Kumar, Julia Luedtke, Jacek Biernat, Eva-Maria Mandelkow, Eckhard Mandelkow
Subcellular mislocalization of the microtubule-associated protein Tau is a hallmark of Alzheimer disease (AD) and other tauopathies. Six Tau isoforms, differentiated by the presence or absence of a second repeat or of N-terminal inserts, exist in the human CNS but their physiological and pathological differences have long remained remain elusive. Here, we investigated the properties and distributions of human and rodent Tau isoforms in primary forebrain rodent neurons. We found that the Tau-Diffusion-Barrier (TDB), located within the Axon-Initial-Segment (AIS), controls retrograde (axon-to-soma) and anterograde (soma-to-axon) traffic of Tau...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28536182/glucagon-s-effect-on-liver-protein-metabolism-in-vivo
#18
Guillaume Kraft, Katie C Coate, Jason J Winnick, Dominique Dardevet, E Patrick Donahue, Alan D Cherrington, Phillip E Williams, Mary Courtney Moore
The postprandial state is characterized by a storage of nutrients in the liver, muscle and adipose tissue for later utilization. In the case of a protein rich meal, amino acids (AA) stimulate glucagon secretion by the α-cell. The aim of the present study was to determine the impact of the rise in glucagon on AA metabolism, particularly in the liver. We used a conscious catheterized dog model to recreate a postprandial condition using a pancreatic clamp. Portal infusions of glucose, AA and insulin were used to achieve postprandial levels while portal glucagon infusion either maintained the basal level or increased it by 3 fold...
May 23, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28536070/cotinine-improves-visual-recognition-memory-and-decreases-cortical-tau-phosphorylation-in-the-tg6799-mice
#19
J Alex Grizzell, Sagar Patel, George E Barreto, Valentina Echeverria
Alzheimer's disease (AD) is associated with the progressive aggregation of hyperphosphorylated forms of the microtubule associated protein Tau in the central nervous system. Cotinine, the main metabolite of nicotine, reduced working memory deficits, synaptic loss, and amyloid β peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3β (GSK3β) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3β sites Serine (Ser)-396/Ser-404 and phospho-CREB were investigated in the Tg6799 and non-transgenic (NT) littermate mice...
May 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28535778/exosomes-from-mesenchymal-stem-cells-induce-the-conversion-of-hepatocytes-into-progenitor-oval-cells
#20
Hao-Hsiang Wu, Oscar K Lee
BACKGROUND: We previously reported that mesenchymal stem cells (MSCs) possess therapeutic effects in a murine model of carbon tetrachloride-induced acute liver failure. In the study, we observed that the majority of repopulated hepatocytes were of recipient origin and were adjacent to transplanted MSCs; only a low percentage of repopulated hepatocytes were from transplanted MSCs. The findings indicate that MSCs guided the formation of new hepatocytes. Exosomes are important messengers for paracrine signaling delivery...
May 23, 2017: Stem Cell Research & Therapy
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