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https://www.readbyqxmd.com/read/29223072/alteration-of-autophagy-related-proteins-in-peripheral-blood-mononuclear-cells-of-patients-with-parkinson-s-disease
#1
Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6)...
November 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29218721/functional-characterization-of-a-second-pedal-peptide-orcokinin-type-neuropeptide-signaling-system-in-the-starfish-asterias-rubens
#2
Ming Lin, Michaela Egertová, Cleidiane G Zampronio, Alexandra M Jones, Maurice R Elphick
Molluscan pedal peptides (PP) and arthropod orcokinins (OK) are prototypes of a family of neuropeptides that have been identified in several phyla. Recently, starfish myorelaxant peptide (SMP) was identified as a PP/OK-type neuropeptide in the starfish Patiria pectinifera (phylum Echinodermata). Furthermore, analysis of transcriptome sequence data from the starfish Asterias rubens revealed two PP/OK-type precursors: an SMP-type precursor (A. rubens pedal peptide-like neuropeptide precursor 1; ArPPLNP1) and a second precursor (ArPPLNP2)...
December 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29212850/endothelial-transcriptomics-reveals-activation-of-fibrosis-related-pathways-in-hypertension
#3
Jonathan William Nelson, Mohammed Zubaerul Ferdaus, James A McCormick, Jessica Minnier, Sanjiv Kaul, David H Ellison, Anthony Paul Barnes
Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on endothelial cells that form the inner lining of the vasculature and are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension by rapidly isolating these cells from the spontaneous hypertension mouse model BPH/2J and its normotensive BPN/3J control strain and performing and RNA sequencing on both...
December 6, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29204124/alternative-splicing-of-nox4-in-the-failing-human-heart
#4
Zoltán V Varga, Márton Pipicz, Júlia A Baán, Tamás Baranyai, Gábor Koncsos, Przemyslaw Leszek, Mariusz Kuśmierczyk, Fátima Sánchez-Cabo, Pablo García-Pavía, Gábor J Brenner, Zoltán Giricz, Tamás Csont, Luca Mendler, Enrique Lara-Pezzi, Pál Pacher, Péter Ferdinandy
Increased oxidative stress is a major contributor to the development and progression of heart failure, however, our knowledge on the role of the distinct NADPH oxidase (NOX) isoenzymes, especially on NOX4 is controversial. Therefore, we aimed to characterize NOX4 expression in human samples from healthy and failing hearts. Explanted human heart samples (left and right ventricular, and septal regions) were obtained from patients suffering from heart failure of ischemic or dilated origin. Control samples were obtained from donor hearts that were not used for transplantation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29203887/age-dependent-increase-of-oxidative-stress-regulates-microrna-29-family-preserving-cardiac-health
#5
Johanna Heid, Chiara Cencioni, Roberto Ripa, Mario Baumgart, Sandra Atlante, Giuseppina Milano, Alessandro Scopece, Carsten Kuenne, Stefan Guenther, Valerio Azzimato, Antonella Farsetti, Giacomo Rossi, Thomas Braun, Giulio Pompilio, Fabio Martelli, Andreas M Zeiher, Alessandro Cellerino, Carlo Gaetano, Francesco Spallotta
The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12-21 week (adult) and 28-40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29189723/long-non-coding-rnas-in-metabolic-organs-and-energy-homeostasis
#6
REVIEW
Maude Giroud, Marcel Scheideler
Single cell organisms can surprisingly exceed the number of human protein-coding genes, which are thus not at the origin of the complexity of an organism. In contrast, the relative amount of non-protein-coding sequences increases consistently with organismal complexity. Moreover, the mammalian transcriptome predominantly comprises non-(protein)-coding RNAs (ncRNA), of which the long ncRNAs (lncRNAs) constitute the most abundant part. lncRNAs are highly species- and tissue-specific with very versatile modes of action in accordance with their binding to a large spectrum of molecules and their diverse localization...
November 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29178315/3d-aggregate-culture-improves-metabolic-maturation-of-human-pluripotent-stem-cell-derived-cardiomyocytes
#7
Cláudia Correia, Alexey Koshkin, Patrícia Duarte, Dongjian Hu, Madalena Carido, Maria J Sebastião, Patrícia Gomes-Alves, David A Elliott, Ibrahim Domian, Ana P Teixeira, Paula M Alves, Margarida Serra
Three-dimensional (3D) cultures of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) hold great promise for drug discovery, providing a better approximation to the in vivo physiology over standard two-dimensional (2D) monolayer cultures. However, the transition of CM differentiation protocols from 2D to 3D cultures is not straightforward. In this work, we relied on the aggregation of hPSC-derived cardiac progenitors and their culture under agitated conditions to generate highly pure cardiomyocyte aggregates...
November 27, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29162723/the-transcription-factor-foxc1a-in-zebrafish-directly-regulates-expression-of-nkx2-5-encoding-a-transcriptional-regulator-of-cardiac-progenitor-cells
#8
Yunyun Yue, Mingyang Jiang, Luqingqing He, Zhaojunjie Zhang, Qinxin Zhang, Chun Gu, Meijing Liu, Nan Li, Qingshun Zhao
Cardiogenesis is a tightly controlled biological process required for formation of a functional heart. The transcription factor Foxc1 not only plays a crucial role in outflow tract development in mice, but is also involved in  cardiac structure formation and normal function in human. However, the molecular mechanisms by which Foxc1 controls cardiac development remain poorly understood. Previously, we reported that zebrafish embryos deficient in foxc1a, an ortholog of mammalian Foxc1, display pericardial edemas and die 9-10 days post fertilization...
November 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29158000/functional-genomic-fabrics-are-remodeled-in-a-mouse-model-of-chagasic-cardiomyopathy-and-restored-following-cell-therapy
#9
Dumitru A Iacobas, Sanda Iacobas, Herbert B Tanowitz, Antonio Campos de Carvalho, David C Spray
We previously found that, in a mouse model of Chagas cardiomyopathy (CCC), 18% of the 9390 quantified unigenes were significantly regulated by Trypanosoma cruzi infection. However, treatment with bone marrow-derived mononuclear cells (MNCs) resulted in 84% transcriptomic recovery. We have applied new algorithms to reanalyze these datasets with respect to specific pathways [CCC, cardiac muscle contraction (CMC) and chemokine signaling (CCS)]. In addition to the levels of expression of individual genes we also calculated gene expression variability and coordination of expression of each gene with all others...
November 17, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/29155718/the-murine-choline-deficient-ethionine-supplemented-cde-diet-model-of-chronic-liver-injury
#10
Jully Gogoi-Tiwari, Julia Köhn-Gaone, Corey Giles, Dirk Schmidt-Arras, Francis D Gratte, Caryn L Elsegood, Geoffrey W McCaughan, Grant A Ramm, John K Olynyk, Janina E E Tirnitz-Parker
Chronic liver diseases, such as viral hepatitis, alcoholic liver disease, or non-alcoholic fatty liver disease, are characterized by continual inflammation, progressive destruction and regeneration of the hepatic parenchyma, liver progenitor cell proliferation, and fibrosis. The end-stage of every chronic liver disease is cirrhosis, a major risk factor for the development of hepatocellular carcinoma. To study processes regulating disease initiation, establishment, and progression, several animal models are used in laboratories...
October 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29138229/genomic-structural-variations-lead-to-dysregulation-of-important-coding-and-non-coding-rna-species-in-dilated-cardiomyopathy
#11
Jan Haas, Stefan Mester, Alan Lai, Karen S Frese, Farbod Sedaghat-Hamedani, Elham Kayvanpour, Tobias Rausch, Rouven Nietsch, Jes-Niels Boeckel, Avisha Carstensen, Mirko Völkers, Carsten Dietrich, Dietmar Pils, Ali Amr, Daniel B Holzer, Diana Martins Bordalo, Daniel Oehler, Tanja Weis, Derliz Mereles, Sebastian Buss, Eva Riechert, Emil Wirsz, Maximilian Wuerstle, Jan O Korbel, Andreas Keller, Hugo A Katus, Andreas E Posch, Benjamin Meder
The transcriptome needs to be tightly regulated by mechanisms that include transcription factors, enhancers, and repressors as well as non-coding RNAs. Besides this dynamic regulation, a large part of phenotypic variability of eukaryotes is expressed through changes in gene transcription caused by genetic variation. In this study, we evaluate genome-wide structural genomic variants (SVs) and their association with gene expression in the human heart. We detected 3,898 individual SVs affecting all classes of gene transcripts (e...
November 14, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29133306/quaking-inhibits-doxorubicin-mediated-cardiotoxicity-through-regulation-of-cardiac-circular-rna-expression
#12
Shashi K Gupta, Ankita Garg, Christian Bär, Shambhabi Chatterjee, Ariana Foinquinos, Hendrik Milting, Katrin Streckfuss-Bömeke, Jan Fiedler, Thomas Thum
Rationale: RNA-binding proteins (RBPs) have been described to be expressed and regulated in various organs including the heart. Little is known about the role of RBPs in heart failure induced by the chemotherapy drug doxorubicin and their interaction with circular RNAs. Objective: We aimed to identify key RBPs involved in doxorubicin-mediated heart failure and to elucidate their function. Methods and Results: Global transcriptome profiling from murine myocardium exposed to doxorubicin identified five differentially expressed RBPs...
November 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/29128925/transcriptome-profile-analysis-reveals-cardiotoxicity-of-maduramicin-in-primary-chicken-myocardial-cells
#13
Xiuge Gao, Lin Peng, Xiangchun Ruan, Xin Chen, Hui Ji, Junxiao Ma, Han Ni, Shanxiang Jiang, Dawei Guo
Maduramicin, an excellent ionophore antibiotic, is extensively used to control coccidiosis in poultry. Numerous maduramicin intoxications have been reported in farm animal and human due to its relatively narrow safety range, with necrosis or degeneration of cardiac and skeletal muscles as hallmark. To date, the mechanisms of maduramicin-induced cardiotoxicity remain unclear in chicken and other animals. Maduramicin (5 µg/mL)-treated primary chicken myocardial cells were used for RNA sequencing (RNA-Seq) and bioinformatics analysis in this study...
November 11, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29107324/daytime-variation-of-perioperative-myocardial-injury-in-cardiac-surgery-and-its-prevention-by-rev-erb%C3%AE-antagonism-a-single-centre-propensity-matched-cohort-study-and-a-randomised-study
#14
David Montaigne, Xavier Marechal, Thomas Modine, Augustin Coisne, Stéphanie Mouton, Georges Fayad, Sandro Ninni, Cédric Klein, Staniel Ortmans, Claire Seunes, Charlotte Potelle, Alexandre Berthier, Celine Gheeraert, Catherine Piveteau, Rebecca Deprez, Jérome Eeckhoute, Hélène Duez, Dominique Lacroix, Benoit Deprez, Bruno Jegou, Mohamed Koussa, Jean-Louis Edme, Philippe Lefebvre, Bart Staels
BACKGROUND: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. METHODS: We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon...
October 26, 2017: Lancet
https://www.readbyqxmd.com/read/29072293/single-cell-transcriptomics-reconstructs-fate-conversion-from-fibroblast-to-cardiomyocyte
#15
Ziqing Liu, Li Wang, Joshua D Welch, Hong Ma, Yang Zhou, Haley Ruth Vaseghi, Shuo Yu, Joseph Blake Wall, Sahar Alimohamadi, Michael Zheng, Chaoying Yin, Weining Shen, Jan F Prins, Jiandong Liu, Li Qian
Direct lineage conversion offers a new strategy for tissue regeneration and disease modelling. Despite recent success in directly reprogramming fibroblasts into various cell types, the precise changes that occur as fibroblasts progressively convert to the target cell fates remain unclear. The inherent heterogeneity and asynchronous nature of the reprogramming process renders it difficult to study this process using bulk genomic techniques. Here we used single-cell RNA sequencing to overcome this limitation and analysed global transcriptome changes at early stages during the reprogramming of mouse fibroblasts into induced cardiomyocytes (iCMs)...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/29066438/polo-like-kinase-2-is-dynamically-regulated-to-coordinate-proliferation-and-early-lineage-specification-downstream-of-yes-associated-protein-1-in-cardiac-progenitor-cells
#16
Michika Mochizuki, Vera Lorenz, Robert Ivanek, Giacomo Della Verde, Emanuele Gaudiello, Anna Marsano, Otmar Pfister, Gabriela M Kuster
BACKGROUND: Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined. METHODS AND RESULTS: Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (<2 hours)...
October 24, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29054930/the-transcription-factor-mef2a-fine-tunes-gene-expression-in-the-atrial-and-ventricular-chambers-of-the-adult-heart
#17
Jose L Medrano, Francisco J Naya
The distinct morphological and functional properties of the cardiac chambers arise from an elaborate developmental program involving cell lineage determination, morphogenesis, and dynamic spatiotemporal gene expression patterns. While a number of transcription factors have been identified for proper gene regulation in the chambers, the complete transcriptional network that controls these patterns remains poorly defined. Previous studies have implicated the MEF2C transcription factor in the regulation of chamber-restricted enhancers...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29051215/kinome-and-transcriptome-profiling-reveal-broad-and-distinct-activities-of-erlotinib-sunitinib-and-sorafenib-in-the-mouse-heart-and-suggest-cardiotoxicity-from-combined-signal-transducer-and-activator-of-transcription-and-epidermal-growth-factor-receptor-inhibition
#18
Timothy J Stuhlmiller, Jon S Zawistowski, Xin Chen, Noah Sciaky, Steven P Angus, Sean T Hicks, Traci L Parry, Wei Huang, Ju Youn Beak, Monte S Willis, Gary L Johnson, Brian C Jensen
BACKGROUND: Most novel cancer therapeutics target kinases that are essential to tumor survival. Some of these kinase inhibitors are associated with cardiotoxicity, whereas others appear to be cardiosafe. The basis for this distinction is unclear, as are the molecular effects of kinase inhibitors in the heart. METHODS AND RESULTS: We administered clinically relevant doses of sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2 weeks...
October 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29037607/dynamic-organization-of-lncrna-and-circular-rna-regulators-collectively-controlled-cardiac-differentiation-in-humans
#19
Yongsheng Li, Jinwen Zhang, Caiqin Huo, Na Ding, Junyi Li, Jun Xiao, Xiaoyu Lin, Benzhi Cai, Yunpeng Zhang, Juan Xu
Advances in developmental cardiology have increased our understanding of the early aspects of heart differentiation. However, understanding noncoding RNA (ncRNA) transcription and regulation during this process remains elusive. Here, we constructed transcriptomes for both long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in four important developmental stages ranging from early embryonic to cardiomyocyte based on high-throughput sequencing datasets, which indicate the high stage-specific expression patterns of two ncRNA types...
October 2017: EBioMedicine
https://www.readbyqxmd.com/read/29036603/identification-of-optimal-reference-genes-for-transcriptomic-analyses-in-normal-and-diseased-human-heart
#20
Cristina E Molina, Eric Jacquet, Prishila Ponien, Christian Muñoz-Guijosa, Istvan Baczkó, Lars S Maier, Patrick Donzeau-Gouge, Dobromir Dobrev, Rodolphe Fischmeister, Anne Garnier
Aims: Quantitative real-time RT-PCR (RT-qPCR) has become the method of choice for mRNA quantification, but requires an accurate normalization based on the use of reference genes showing invariant expression across various pathological conditions. Only few data exist on appropriate reference genes for the human heart. The objective of this study was to determine a set of suitable reference genes in human atrial and ventricular tissues, from right and left cavities in control and in cardiac diseases...
September 22, 2017: Cardiovascular Research
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