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Cms regulations

Zhihan Zhao, Huan Lan, Ibrahim El-Battrawy, Xin Li, Fanis Buljubasic, Katherine Sattler, Gökhan Yücel, Siegfried Lang, Malte Tiburcy, Wolfram-Hubertus Zimmermann, Lukas Cyganek, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou, Ibrahim Akin
Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are providing new possibilities for the biological study, cell therapies, and drug discovery. However, the ion channel expression and functions as well as regulations in hiPSC-CMs still need to be fully characterized. Methods: Cardiomyocytes were derived from hiPS cells that were generated from two healthy donors. qPCR and patch clamp techniques were used for the study. Results: In addition to the reported ion channels, INa , ICa-L , ICa-T , If , INCX , IK1 , Ito , IKr , IKs IKATP , IK-pH , ISK1-3 , and ISK4 , we detected both the expression and currents of ACh-activated (KACh) and Na+ -activated (KNa) K+ , volume-regulated and calcium-activated (Cl-Ca) Cl- , and TRPV channels...
2018: Stem Cells International
Wei Lei, Tingting Feng, Xing Fang, You Yu, Junjie Yang, Zhen-Ao Zhao, Junwei Liu, Zhenya Shen, Wenbo Deng, Shijun Hu
BACKGROUND: Circular RNAs (circRNAs) are regarded as a novel class of noncoding RNA regulators. Although a number of circRNAs have been identified by bioinformatics analysis of RNA-seq data, tissue and disease-specific circRNAs are still to be uncovered to promote their application in basic research and clinical practice. The purpose of this study was to explore the circRNA profiles in human induced pluripotent stem cells (hiPSCs) and hiPSC-derived cardiomyocytes (hiPSC-CMs), and to identify cardiac or disease-specific circRNAs...
March 9, 2018: Stem Cell Research & Therapy
John Marshall, Xiao-Zhong Zhou, Gang Chen, Su-Qing Yang, Ya Li, Yin Wang, Zhi-Qing Zhang, Qin Jiang, Lutz Birnbaumer, Cong Cao
Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
S Y Wang, S Cui, Z Q Li, L H Ji, J Ma, H H Liu, G Y Zhang, S H Suo, R L Ge
Objective: To investigate the changes of CD71(+) nucleated erythrocyte apoptosis, cytochrome C (Cyt-C) and mitochondrial membrane potential (MMP) in bone marrow of chronic mountain sickness (CMS). Methods: 14 patients with CMS and 15 patients with simple old fracture were divided into CMS group and control group, respectively.Bone marrow mononuclear cells (BMMNC) were separated, marked with CD71 monoclonal antibody and stained with Annexin V-FITC/PI.Then the apoptotic index of CD71(+) nucleated erythrocytes was determined by flow cytometry...
February 13, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Mikako Ito, Kinji Ohno
Endplate acetylcholinesterase (AChE) deficiency is a form of congenital myasthenic syndrome (CMS) caused by mutations in COLQ, which encodes collagen Q (ColQ). ColQ is an extracellular matrix (ECM) protein that anchors AChE to the synaptic basal lamina. Biglycan, encoded by BGN, is another ECM protein that binds to the dystrophin-associated protein complex (DAPC) on skeletal muscle, which links the actin cytoskeleton and ECM proteins to stabilize the sarcolemma during repeated muscle contractions. Upregulation of biglycan stabilizes the DPAC...
February 20, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Man Liu, Guangbin Shi, Anyu Zhou, Cassady E Rupert, Kareen L K Coulombe, Samuel C Dudley
RATIONALE: Heart failure is characterized by electrical remodeling that contributes to arrhythmic risk. The unfolded protein response (UPR) is active in heart failure and can decrease protein levels by increasing mRNA decay, accelerating protein degradation, and inhibiting protein translation. OBJECTIVE: Therefore, we investigated whether the UPR downregulated cardiac ion channels that may contribute to arrhythmogenic electrical remodeling. METHODS: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to study cardiac ion channels...
February 21, 2018: Journal of Molecular and Cellular Cardiology
Emily O'Connor, Vietxuan Phan, Isabell Cordts, George Cairns, Stefan Hettwer, Daniel Cox, Hanns Lochmüller, Andreas Roos
Congenital myasthenic syndromes (CMS) are a group of rare, inherited disorders characterised by compromised function of the neuromuscular junction, manifesting with fatigable muscle weakness. Mutations in MYO9A were previously identified as causative for CMS but the precise pathomechanism remained to be characterised. Based on the role of MYO9A as an actin-based molecular motor and as a negative regulator of RhoA, we hypothesised that loss of MYO9A may affect the neuronal cytoskeleton, leading to impaired intracellular transport...
February 16, 2018: Human Molecular Genetics
Ekaterina Ovchinnikova, Martijn Hoes, Kirill Ustyantsev, Nils Bomer, Tristan V de Jong, Henny van der Mei, Eugene Berezikov, Peter van der Meer
Cardiac hypertrophy accompanies many forms of cardiovascular diseases. The mechanisms behind the development and regulation of cardiac hypertrophy in the human setting are poorly understood, which can be partially attributed to the lack of a human cardiomyocyte-based preclinical test system recapitulating features of diseased myocardium. The objective of our study is to determine whether human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to mechanical stretch can be used as an adequate in vitro model for studying molecular mechanisms of cardiac hypertrophy...
February 8, 2018: Stem Cell Reports
Wei Huang, Yuliang Feng, Jialiang Liang, Hao Yu, Cheng Wang, Boyu Wang, Mingyang Wang, Lin Jiang, Wei Meng, Wenfeng Cai, Mario Medvedovic, Jenny Chen, Christian Paul, W Sean Davidson, Sakthivel Sadayappan, Peter J Stambrook, Xi-Yong Yu, Yigang Wang
The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2...
February 16, 2018: Nature Communications
Mi Zhou, Zhao Liu, Jia Yu, Shuiming Li, Min Tang, Li Zeng, Haiyang Wang, Hong Xie, Li Peng, Haojun Huang, Chanjuan Zhou, Peng Xie, Jian Zhou
The amygdala plays a key role in the pathophysiology of depression, but the molecular mechanisms underlying amygdalar hyperactivity in depression remain unclear. In this study, we used a chronic mild stress (CMS) protocol to separate susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were analyzed differentially across subgroups based on labeling with isobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of 2562 quantified proteins, 102 were differentially expressed...
February 13, 2018: Neuroscience
Yoshie Kametani, Takashi Shiina, Ryuji Suzuki, Erika Sasaki, Sonoko Habu
The common marmoset (CM; Callithrix jacchus) is a small New World monkey with a high rate of pregnancy and is maintained in closed colonies as an experimental animal species. Although CMs are used for immunological research, such as studies of autoimmune disease and infectious disease, their immunological characteristics are less defined than those of other nonhuman primates. We and others have analyzed antigen recognition-related molecules, the development of hematopoietic stem cells (HSCs), and the molecules involved in the immune response...
February 8, 2018: Experimental Animals
Harshal Nemade, Umesh Chaudhari, Aviseka Acharya, Jürgen Hescheler, Jan Georg Hengstler, Symeon Papadopoulos, Agapios Sachinidis
Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines using physiologically relevant human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). Using xCELLigence real-time cell analyser (RTCA), we found that single high dose of ETP induces irreversible increase in hPSC-CMs beating rate and decrease in beating amplitude...
February 3, 2018: Archives of Toxicology
Lavanya M Iyer, Sankari Nagarajan, Monique Woelfer, Eric Schoger, Sara Khadjeh, Maria Patapia Zafiriou, Vijayalakshmi Kari, Jonas Herting, Sze Ting Pang, Tobias Weber, Franziska S Rathjens, Thomas H Fischer, Karl Toischer, Gerd Hasenfuss, Claudia Noack, Steven A Johnsen, Laura C Zelarayán
Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression...
January 31, 2018: Nucleic Acids Research
Viviana Meraviglia, Leonardo Bocchi, Roberta Sacchetto, Maria Cristina Florio, Benedetta M Motta, Corrado Corti, Christian X Weichenberger, Monia Savi, Yuri D'Elia, Marcelo D Rosato-Siri, Silvia Suffredini, Chiara Piubelli, Giulio Pompilio, Peter P Pramstaller, Francisco S Domingues, Donatella Stilli, Alessandra Rossini
SERCA2a is the Ca2+ ATPase playing the major contribution in cardiomyocyte (CM) calcium removal. Its activity can be regulated by both modulatory proteins and several post-translational modifications. The aim of the present work was to investigate whether the function of SERCA2 can be modulated by treating CMs with the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA). The incubation with SAHA (2.5 µM, 90 min) of CMs isolated from rat adult hearts resulted in an increase of SERCA2 acetylation level and improved ATPase activity...
January 31, 2018: International Journal of Molecular Sciences
Chen Yanovich, Michael L Kirby, Izhak Michaelevski, Gal Yadid, Albert Pinhasov
Studies of personality have suggested that dissimilarities in ability to cope with stressful situations results in differing tendency to develop addictive behaviors. The present study used selectively bred stress-resilient, socially-dominant (Dom) and stress-vulnerable, socially-submissive (Sub) mice to investigate the interaction between environmental stress and inbred predisposition to develop addictive behavior to cocaine. In a Conditioned Place Preference (CPP) paradigm using cocaine, Sub mice displayed an aversion to drug, whereas Dom mice displayed drug attraction...
January 29, 2018: Scientific Reports
Yuvasree Purusothaman, Nagamalleswara Rao Alluri, Arunkumar Chandrasekhar, Venkateswaran Vivekananthan, Sang-Jae Kim
A feasible, morphological influence on photoresponse behavior of ZnO microarchitectures such as microwire (MW), coral-like microstrip (CMS), fibril-like clustered microwire (F-MW) grown by one-step carrier gas/metal catalyst "free" vapor transport technique is reported. Among them, ZnO F-MW exhibits higher photocurrent (IPh ) response, i.e., IPh/ZnO F-MW > IPh/ZnO CMS > IPh/ZnO MW . The unique structural alignment of ZnO F-MW has enhanced the IPh from 14.2 to 186, 221, 290 µA upon various light intensities such as 0 to 6, 11, 17 mW cm-2 at λ405 nm ...
January 29, 2018: Small
Ellen Ngar Yun Poon, Baixia Hao, Daogang Guan, Mulin Jun Li, Jun Lu, Yong Yang, Binbin Wu, Stanley Chun Ming Wu, Sarah E Webb, Yan Liang, Andrew L Miller, Xiaoqiang Yao, Junwen Wang, Bin Yan, Kenneth R Boheler
Aims: MicroRNAs (miRNAs) are crucial for the post-transcriptional control of protein-encoding genes, and together with transcription factors (TFs) regulate gene expression; however, the regulatory activities of miRNAs during cardiac development are only partially understood. In this study, we tested the hypothesis that integrative computational approaches could identify miRNAs that experimentally could be shown to regulate cardiomyogenesis. Methods and results: We integrated expression profiles with bioinformatics analyses of miRNA and TF regulatory programs to identify candidate miRNAs involved with cardiac development...
January 24, 2018: Cardiovascular Research
Xingxia Geng, Jiali Ye, Xuetong Yang, Sha Li, Lingli Zhang, Xiyue Song
Cytoplasmic male sterility (CMS) where no functional pollen is produced has important roles in wheat breeding. The anther is a unique organ for male gametogenesis and its abnormal development can cause male sterility. However, the mechanisms and regulatory networks related to plant male sterility are poorly understood. In this study, we conducted comparative analyses using isobaric tags for relative and absolute quantification (iTRAQ) of the pollen proteins in a CMS line and its wheat maintainer. Differentially abundant proteins (DAPs) were analyzed based on Gene Ontology classifications, metabolic pathways and transcriptional regulation networks using Blast2GO...
January 23, 2018: International Journal of Molecular Sciences
Wei Wu, Hang Yao, Helen W Zhao, Juan Wang, Gabriel G Haddad
Chronic mountain sickness (CMS) or Monge's disease is a disease in highlanders. These patients have a variety of neurologic symptoms such as migraine, mental fatigue, confusion, dizziness, loss of appetite, memory loss and neuronal degeneration. The cellular and molecular mechanisms underlying CMS neuropathology is not understood. In the previous study, we demonstrated that neurons derived from CMS patients' fibroblasts have a decreased expression and altered gating properties of voltage-gated sodium channel...
January 17, 2018: Neuroscience
Joanne Barnes, Rachael Butler
OBJECTIVES: To examine community pharmacists' perspectives on CMs regulation in New Zealand, where proposals for CMs regulations had recently been suspended and where, currently, CMs are only weakly regulated. METHODS: Qualitative, in-depth, semi-structured interviews with New Zealand practising community pharmacists are identified through purposive and convenience sampling. Data were analysed using a general inductive approach. KEY FINDINGS: Participants held mixed views regarding harmonisation of CMs regulations across Australia and NZ; some supported an NZ national regulatory framework for CMs, based on the Australian system...
January 19, 2018: International Journal of Pharmacy Practice
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