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Yehuda Ben-Shahar
Manganese (Mn) is an essential trace element that acts as a metal co-factor in diverse biochemical and cellular functions. However, chronic environmental exposure to high levels of Mn is a well-established risk factor for the etiology of severe, atypical parkinsonian syndrome (manganism) via its accumulation in the basal ganglia, pallidum, and striatum brain regions, which is often associated with abnormal dopamine, GABA, and glutamate neural signaling. Recent studies have indicated that chronic Mn exposure at levels that are below the risk for manganism can still cause behavioral, cognitive, and motor dysfunctions via poorly understood mechanisms at the molecular and cellular levels...
2018: Frontiers in Genetics
R Asero, M Piantanida, V Pravettoni
Background. Follow-up data about the onset of novel food allergies in patients allergic to lipid transfer protein (LTP) are missing. We investigated the occurrence of novel allergies over time in LTP hypersensitive patients. Methods. Sixty-seven LTP-allergic patients recommended to avoid foods responsible for systemic reactions and encouraged to eat other sensitizing foods avoiding the association with known co-factors, were re-evaluated after ≥ 1 year to assess the occurrence of allergy to novel foods. IgE to rPru p 3, rBet v 1, and r Phl p 12 were measured...
February 16, 2018: European Annals of Allergy and Clinical Immunology
Michael Lie-A-Ling, Elli Marinopoulou, Andrew J Lilly, Mairi Challinor, Rahima Patel, Christophe Lancrin, Valerie Kouskoff, Georges Lacaud
During ontogeny, hematopoietic stem and progenitor cells arise from hemogenic endothelium through an endothelial-to-hematopoietic transition that is strictly dependent on the transcription factor RUNX1. Although it is well established that RUNX1 is essential for the onset of hematopoiesis, little is known about the role of RUNX1 dosage specifically in hemogenic endothelium and during the endothelial-to-hematopoietic transition. Here, we used the mouse embryonic stem cell differentiation system to determine if and how RUNX1 dosage affects hemogenic endothelium differentiation...
March 12, 2018: Development
Yuanyuan Tang, Joshua Berlind, Nirmala Mavila
BACKGROUND: The WNT-beta-catenin pathway is known to regulate cellular homeostasis during development and tissue regeneration. Activation of WNT signaling increases the stability of cytoplasmic beta-catenin and enhances its nuclear translocation. Nuclear beta-catenin function is regulated by transcriptional co-factors such as CREB binding protein (CBP) and p300. Hyper-activated WNT-beta-catenin signaling is associated with many cancers. However, its role in inducing stemness to liver cancer cells, its autoregulation and how it regulates tumor suppressor pathways are not well understood...
March 12, 2018: Cell Communication and Signaling: CCS
Laure-Estelle Cassagnes, Monivan Chhour, Pierre Perio, Jan Sudor, Régis Gayon, Gilles Ferry, Jean A Boutin, Françoise Nepveu, Karine Reybier
There is increasing evidence that oxidative stress is involved in the etiology and pathogenesis of neurodegenerative disorders. Overproduction of reactive oxygen species (ROS) is due in part to the reactivity of catecholamines, such as dopamine, adrenaline, and noradrenaline. These molecules are rapidly converted, chemically or enzymatically, into catechol-quinone and then into highly deleterious semiquinone radicals after 1-electron reduction in cells. Notably, the overexpression of dihydronicotinamide riboside:quinone oxidoreductase (QR2) in Chinese hamster ovary (CHO) cells increases the production of ROS, mainly superoxide radicals, when it is exposed to exogenous catechol-quinones (e...
March 8, 2018: Free Radical Biology & Medicine
Jiangong Jiang, Dicheng Ma, Nan Zou, Xin Yu, Zhengqun Zhang, Feng Liu, Wei Mu
Neonicotinoid insecticides (NIs) have recently been recognized as co-factors in the decline of honeybee colonies because most neonicotinoids are systemic and can transfer into the pollen and nectar of many pollinated crops. In this study, we collected pollen, nectar and leaves from a cotton crop treated with imidacloprid and thiamethoxam to measure the residue levels of these two NIs at different application doses during the flowering period. Then, the residual data were used to assess the risk posed by the systemic insecticides to honeybees following mandated methods published by the European Food Safety Authority (EFSA), and a highly toxic risk to honeybees was highlighted...
February 27, 2018: Chemosphere
Russell P Goodman, Sarah Calvo, Vamsi K Mootha
Compartmentalization is a fundamental design principle of eukaryotic metabolism.  Here, we review the compartmentalization of NAD+/NADH and NADP+/NADPH with a focus on the liver, an organ that experiences the extremes of biochemical physiology each day.  Historical studies of the liver, using classical biochemical  measurements of redox-coupled metabolites, have given rise to the view that mitochondrial NAD(H) pools tend to be oxidized and important for energy homeostasis, whereas cytosolic NADP(H) pools tend to be highly reduced for reductive biosynthesis...
March 7, 2018: Journal of Biological Chemistry
Weiwei Fan, Nanhai He, Chun Shi Lin, Zong Wei, Nasun Hah, Wanda Waizenegger, Ming-Xiao He, Christopher Liddle, Ruth T Yu, Annette R Atkins, Michael Downes, Ronald M Evans
PGC1α is a pleiotropic co-factor that affects angiogenesis, mitochondrial biogenesis, and oxidative muscle remodeling via its association with multiple transcription factors, including the master oxidative nuclear receptor ERRγ. To decipher their epistatic relationship, we explored ERRγ gain of function in muscle-specific PGC1α/β double-knockout (PKO) mice. ERRγ-driven transcriptional reprogramming largely rescues muscle damage and improves muscle function in PKO mice, inducing mitochondrial biogenesis, antioxidant defense, angiogenesis, and a glycolytic-to-oxidative fiber-type transformation independent of PGC1α/β...
March 6, 2018: Cell Reports
Mauricio Cardenas-Rodriguez, Afroditi Chatzi, Kostas Tokatlidis
Iron-sulfur clusters are ubiquitous inorganic co-factors that contribute to a wide range of cell pathways including the maintenance of DNA integrity, regulation of gene expression and protein translation, energy production, and antiviral response. Specifically, the iron-sulfur cluster biogenesis pathways include several proteins dedicated to the maturation of apoproteins in different cell compartments. Given the complexity of the biogenesis process itself, the iron-sulfur research area constitutes a very challenging and interesting field with still many unaddressed questions...
March 6, 2018: Journal of Biological Inorganic Chemistry: JBIC
Lian-Zi Wei, Yan-Qing Wang, Yun-Li Chang, Na An, Xiao Wang, Pei-Jie Zhou, Helen He Zhu, Yu-Xiang Fang, Wei-Qiang Gao
The microRNA-transcription factor auto-regulatory feedback loop is a pivotal mechanism for homeostatic regulation of gene expression, and dysregulation of the feedback loop is tightly associated with tumorigenesis and progression. However, the mechanism underlying such dysregulation is still not well-understood. Here we reported that Krüppel-like factor 4 (KLF4), a stemness-associated transcription factor, promotes the transcription of miR-7 to repress its own translation so that a KLF4-miR-7 auto-regulatory feedback loop is established for mutual regulation of their expression...
2018: American Journal of Cancer Research
Jiulia Satiaputra, Bart A Eijkelkamp, Christopher A McDevitt, Keith E Shearwin, Grant W Booker, Steven W Polyak
Biotin (Vitamin B7) is a critical enzyme co-factor in metabolic pathways important for bacterial survival. Biotin is obtained either from the environment or by de novo synthesis, with some bacteria capable of both. In certain species, the bifunctional protein BirA plays a key role in biotin homeostasis as it regulates expression of biotin biosynthetic enzymes in response to biotin demand and supply. Here, we compare the effect of biotin on the growth of two bacteria that possess a bifunctional BirA, namely Escherichia coli and Staphylococcus aureus...
March 5, 2018: Applied Microbiology and Biotechnology
Egor P Tchesnokov, Parisa Raeisimakiani, Marianne Ngure, David Marchant, Matthias Götte
Here we report on the expression, purification and characterization of recombinant ebola virus RNA-dependent RNA polymerase (EBOV RdRp). Active protein complexes composed of the large L protein and viral protein VP35 were isolated from insect cells and analyzed using a short primer/template substrate that allowed benchmarking against related enzymes. RNA synthesis by multiprotein complexes of EBOV, influenza B, respiratory syncytial virus (RSV) and monomeric enzymes of hepatitis C and Zika (ZIKV) viruses required a 5'-phosporylated primer...
March 5, 2018: Scientific Reports
Bradford H Casey, Rahul K Kollipara, Karine Pozo, Jane E Johnson
During development, transcription factors select distinct gene programs from a shared genome, providing the necessary regulatory complexity for temporal and tissue-specific gene expression. How related factors retain their specificity of activity, especially when they recognize the same DNA motifs, is not understood. We address this paradox using basic Helix-Loop-Helix (bHLH) transcription factors, ASCL1, ASCL2, and MYOD1, crucial mediators of lineage specification. In vivo, these factors recognize the same DNA motifs, yet bind largely different genomic sites and regulate distinct transcriptional programs...
March 2, 2018: Genome Research
Jaecheol Lee, Ning-Yi Shao, David T Paik, Haodi Wu, Hongchao Guo, Vittavat Termglinchan, Jared M Churko, Youngkyun Kim, Tomoya Kitani, Ming-Tao Zhao, Yue Zhang, Kitchener D Wilson, Ioannis Karakikes, Michael P Snyder, Joseph C Wu
Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation...
March 1, 2018: Cell Stem Cell
Agnieszka Bochyńska, Juliane Lüscher-Firzlaff, Bernhard Lüscher
Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes...
March 2, 2018: Cells
Meltem Weger, Nicolas Diotel, Benjamin D Weger, Tanja Beil, Andreas Zaucker, Helen L Eachus, James A Oakes, Jean Luc do Rego, Karl-Heinz Storbeck, Philipp Gut, Uwe Straehle, Sepand Rastegar, Ferenc Mueller, Nils Krone
The spatial and temporal expression of steroidogenic genes in zebrafish has not been fully characterized. Since zebrafish are increasingly employed in endocrine and stress research, a better characterization of steroidogenic pathways is required to target specific steps in the biosynthetic pathways in the future. Here, we have systematically defined the temporal and spatial expression of steroidogenic enzymes involved in glucocorticoid biosynthesis (cyp21a2, cyp11c1, cyp11a1, cyp11a2, cyp17a1, cyp17a2, hsd3b1, hsd3b2), as well as the mitochondrial electron-providing co-factors ferredoxin (fdx1, fdx1b) during zebrafish development...
February 27, 2018: Journal of Neuroendocrinology
Aimo Kannt, Sridharan Rajagopal, Sanjay Venkatachalapathi Kadnur, Juluri Suresh, Ravi Kanth Bhamidipati, Srinivasan Swaminathan, Mahanandeesha Siddappa Hallur, Rajendra Kristam, Ralf Elvert, Jörg Czech, Anja Pfenninger, Christine Rudolph, Herman Schreuder, Devaraj Venkatapura Chandrasekar, Vishal Subhash Mane, Swarnakumari Birudukota, Shama Shaik, Bharat Ravindra Zope, Raghunadha Reddy Burri, Niranjan Naranapura Anand, Manish Kumar Thakur, Manvi Singh, Reejuana Parveen, Saravanan Kandan, Ramesh Mullangi, Takeshi Yura, Ramachandraiah Gosu, Sven Ruf, Saravanakumar Dhakshinamoorthy
Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease...
February 26, 2018: Scientific Reports
Lucinda Kennard, Iason Thomas, Krzysztof Rutkowski, Vian Azzu, Patrick Fk Yong, Bogusia Kasternow, Hannah Hunter, Naeema Mo Cabdi, Alla Nakonechna, Annette Wagner
BACKGROUND: Omega-5 gliadin allergy (also known as wheat-dependent exercise induced anaphylaxis) is a rare allergy to wheat which often presents with intermittent severe anaphylaxis in the context of a co-factor, such as exercise. OBJECTIVES: To undertake a detailed clinical characterisation of the largest cohort of omega 5-gliadin allergic patients to date. METHODS: We retrospectively analysed the demographics, presentation, investigation and management of 132 patients presenting to 4 UK centres with omega-5 gliadin allergy...
February 22, 2018: Journal of Allergy and Clinical Immunology in Practice
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0191185.].
2018: PloS One
Krister Bamberg, Ulrika Johansson, Karl Edman, Lena William-Olsson, Susanna Myhre, Anders Gunnarsson, Stefan Geschwindner, Anna Aagaard, Anna Björnson Granqvist, Frédéric Jaisser, Yufeng Huang, Kenneth L Granberg, Rasmus Jansson-Löfmark, Judith Hartleib-Geschwindner
Excess mineralocorticoid receptor (MR) activation promotes target organ dysfunction, vascular injury and fibrosis. MR antagonists like eplerenone are used for treating heart failure, but their use is limited due to the compound class-inherent hyperkalemia risk. Here we present evidence that AZD9977, a first-in-class MR modulator shows cardio-renal protection despite a mechanism-based reduced liability to cause hyperkalemia. AZD9977 in vitro potency and binding mode to MR were characterized using reporter gene, binding, cofactor recruitment assays and X-ray crystallopgraphy...
2018: PloS One
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