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https://www.readbyqxmd.com/read/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#1
Yang W Zhang, Zhihong Wang, Wenbing Xie, Yi Cai, Limin Xia, Hariharan Easwaran, Jianjun Luo, Ray-Whay Chiu Yen, Yana Li, Stephen B Baylin
TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28106122/comparative-genomics-and-transcriptome-analysis-of-aspergillus-niger-and-metabolic-engineering-for-citrate-production
#2
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains-namely, A. niger H915-1 (citrate titer: 157 g L(-1)), A1 (117 g L(-1)), and L2 (76 g L(-1))-to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105691/the-alcohol-sensitive-period-during-early-octavolateral-organ-development-in-zebrafish-danio-rerio
#3
Lilliann Y Zamora, Kayla C Miguel, Zhongmin Lu
Fetal alcohol exposure can cause Fetal Alcohol Spectrum Disorders (FASD), completely preventable developmental disabilities characterized by permanent birth defects. However, specific gestational timing when developing organs are most sensitive to alcohol exposure is unclear. In this study, we examined the temporal effects of embryonic alcohol exposure on octavolateral organs in zebrafish (Danio rerio), including inner ears and lateral line neuromasts that function in hearing, balance, and hydrodynamic detection, respectively...
January 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28104751/exercise-training-decreases-nadph-oxidase-activity-and-restores-skeletal-muscle-mass-in-heart-failure-rats
#4
Telma F Cunha, Luiz Roberto Grassman Bechara, Aline V N Bacurau, Paulo R Jannig, Vanessa Azevedo Voltarelli, Paulo M Dourado, Andrea R Vasconcelos, Cristóforo Scavone, Julio C B Ferreira, Patricia C Brum
We have recently demonstrated that NADPH oxidase hyperactivity, NF-κB activation and increased p38 phosphorylation lead to atrophy of glycolytic muscle in heart failure (HF). Aerobic exercise training (AET) is an efficient strategy to counteract skeletal muscle atrophy in this syndrome. Therefore, we tested whether AET would regulate muscle redox balance and protein degradation by decreasing NADPH oxidase hyperactivity, reestablishing NF-κB signaling, p38 phosphorylation and proteasome activity in plantaris muscle of myocardial infarcted-induced HF (MI) rats...
January 19, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28103936/elevated-collagen-i-augments-tumor-progressive-signals-intravasation-and-metastasis-of-prolactin-induced-estrogen-receptor-alpha-positive-mammary-tumor-cells
#5
Craig E Barcus, Kathleen A O'Leary, Jennifer L Brockman, Debra E Rugowski, Yuming Liu, Nancy Garcia, Menggang Yu, Patricia J Keely, Kevin W Eliceiri, Linda A Schuler
BACKGROUND: The development and progression of estrogen receptor alpha positive (ERα+) breast cancer has been linked epidemiologically to prolactin. However, activation of the canonical mediator of prolactin, STAT5, is associated with more differentiated cancers and better prognoses. We have reported that density/stiffness of the extracellular matrix potently modulates the repertoire of prolactin signals in human ERα + breast cancer cells in vitro: stiff matrices shift the balance from the Janus kinase (JAK)2/STAT5 cascade toward pro-tumor progressive extracellular regulated kinase (ERK)1/2 signals, driving invasion...
January 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28102754/enhancement-of-antibody-functions-through-fc-multiplications
#6
Qun Wang, Yan Chen, Mark Pelletier, Romana Cvitkovic, Jessica Bonnell, Chien-Ying Chang, Adem C Koksal, Ellen O'Connor, Xizhe Gao, Xiang-Qing Yu, Herren Wu, C Kendall Stover, William F Dall'Acqua, Xiaodong Xiao
Antibodies carry out a plethora of functions through their crystallizable fragment (Fc) regions, which can be naturally tuned by the adoption of several isotypes and post-translational modifications. Protein engineering enables further Fc function modulations through modifications of the interactions between the Fc and its functional partners, including FcγR, FcRn, complement complex, and additions of auxiliary functional units. Due to the many functions embedded within the confinement of an Fc, a suitable balance must be maintained for a therapeutic antibody to be effective and safe...
January 19, 2017: MAbs
https://www.readbyqxmd.com/read/28101188/mir-125a-3p-targetedly-regulates-git1-expression-to-inhibit-osteoblastic-proliferation-and-differentiation
#7
Xiao-Mei Tu, Yang-Lin Gu, Guo-Qin Ren
Osteoblasts are a prerequisite for osteogenesis and bone formation, and play a key role in metabolic balance, growth, development and wound repair. G protein-coupled receptor kinase interacting protein 1 (GIT1) and a series of miRNAs are known to have important effects in the growth and migration of osteoblasts, but little is known about micro RNAs (miRNAs) targeting GIT1. The present study found that miR-125a-3p has matching sites on GIT1. In the osteoblastic differentiation process of human bone marrow-derived mesenchymal stem cells (HMSCs), the expression of miR-125a-3p was suppressed compared with that in non-differentiating (HMSCs) while the expression of GIT1 showed a gradual and significant increase...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100855/trace-elements-as-an-activator-of-antioxidant-enzymes
#8
Marta Wołonciej, Elżbieta Milewska, Wiesława Roszkowska-Jakimiec
Oxidative stress is a state of impaired balance between the formation of free radicals and antioxidant capacity of the body. It causes many defects of the body, e.g. lipid peroxidation, DNA and protein damage. In order to prevent the effects of oxidative stress, the organism has developed defence mechanisms. These mechanisms capture and inhibit the formation of free radicals and also chelate ion metals that catalyse free radical reactions. Trace elements are components of antioxidant enzymes involved in antioxidant mechanisms...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100637/a-zip3-like-protein-plays-a-role-in-crossover-formation-in-the-sc-less-meiosis-of-the-protist-tetrahymena
#9
Anura Shodhan, Kensuke Kataoka, Kazufumi Mochizuki, Maria Novatchkova, Josef Loidl
When programmed meiotic DNA double-strand breaks (DSBs) undergo recombinational repair, genetic crossovers (COs) may be formed. A certain level of these are required for the faithful segregation of chromosomes, but the majority of DSBs are processed toward a safer alternative, namely non-crossovers (NCOs), via non-reciprocal DNA exchange. At the crossroads between these two DSB fates are the Msh4-Msh5 (MutSγ) complex, which stabilizes CO-destined recombination intermediates, and members of the Zip3/RNF212 family of RING finger proteins, which in turn stabilize MutSγ...
January 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28099114/mitochondrial-respiratory-gene-expression-is-suppressed-in-many-cancers
#10
Ed Reznik, Qingguo Wang, Konnor La, Nikolaus Schultz, Chris Sander
The fundamental metabolic decision of a cell, the balance between respiration and fermentation, rests in part on expression of the mitochondrial genome (mtDNA) and coordination with expression of the nuclear genome (nuDNA). Previously we described mtDNA copy number depletion across many solid tumor types (Reznik et al., 2016). Here, we use orthogonal RNA-sequencing data to quantify mtDNA expression (mtRNA), and report analogously lower expression of mtRNA in tumors (relative to normal tissue) across a majority of cancer types...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28098754/drp1-dependent-mitochondrial-fission-plays-critical-roles-in-physiological-and-pathological-progresses-in-mammals
#11
REVIEW
Chenxia Hu, Yong Huang, Lanjuan Li
Current research has demonstrated that mitochondrial morphology, distribution, and function are maintained by the balanced regulation of mitochondrial fission and fusion, and perturbation of the homeostasis between these processes has been related to cell or organ dysfunction and abnormal mitochondrial redistribution. Abnormal mitochondrial fusion induces the fragmentation of mitochondria from a tubular morphology into pieces; in contrast, perturbed mitochondrial fission results in the fusion of adjacent mitochondria...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098556/genetic-defects-in-%C3%AE-spectrin-and-tau-sensitize-c-elegans-axons-to-movement-induced-damage-via-torque-tension-coupling
#12
Michael Krieg, Jan Stühmer, Juan G Cueva, Richard Fetter, Kerri A Spliker, Daniel Cremers, Kang Shen, Alexander R Dunn, Miriam B Goodman
Our bodies are in constant motion and so are the neurons that invade each tissue. Motion-induced neuron deformation and damage are associated with several neurodegenerative conditions. Here, we investigated the question of how the neuronal cytoskeleton protects axons and dendrites from mechanical stress, exploiting mutations in UNC-70 β-spectrin, PTL-1 tau/MAP2-like and MEC-7 β-tubulin proteins in Caenorhabditis elegans. We found that mechanical stress induces supercoils and plectonemes in the sensory axons of spectrin and tau double mutants...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28097817/revisiting-regulation-of-potassium-homeostasis-in-escherichia-coli-the-connection-to-phosphate-limitation
#13
Hannah Schramke, Vera Laermann, Halina E Tegetmeyer, Andreas Brachmann, Kirsten Jung, Karlheinz Altendorf
Two-component signal transduction constitutes the predominant strategy used by bacteria to adapt to fluctuating environments. The KdpD/KdpE system is one of the most widespread, and is crucial for K(+) homeostasis. In Escherichia coli, the histidine kinase KdpD senses K(+) availability, whereas the response regulator KdpE activates synthesis of the high-affinity K(+) uptake system KdpFABC. Here we show that, in the absence of KdpD, kdpFABC expression can be activated via phosphorylation of KdpE by the histidine kinase PhoR...
January 17, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28096576/role-of-edaravone-in-managemant-of-septic-peritonitis
#14
Ghada Fouad Elbaradey, Nagat Sayed Elshmaa, Hossam Hodeib
BACKGROUND AND AIMS: Sepsis is a complex rapidly progressive infectious disease that remain a major cause of morbidity and mortality in surgical patients and trauma victims. Edaravone a novel free radical scavenger was approved in 2001 in Japan for treatment of acute cerebral and myocardial infarction. Hence, in this work we attempt to evaluate its role in cases of septic peritonitis (SP). MATERIAL AND METHODS: This is a prospective randomized observer-blinded study carried out in surgical Intensive Care Unit (ICU) after approval by Hospital Ethical Committee...
October 2016: Journal of Anaesthesiology, Clinical Pharmacology
https://www.readbyqxmd.com/read/28096339/loss-of-astrocyte-cholesterol-synthesis-disrupts-neuronal-function-and-alters-whole-body-metabolism
#15
Heather A Ferris, Rachel J Perry, Gabriela V Moreira, Gerald I Shulman, Jay D Horton, C Ronald Kahn
Cholesterol is important for normal brain function. The brain synthesizes its own cholesterol, presumably in astrocytes. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in sterol regulatory element-binding protein 2 (SREBP2)-regulated transcription. Here we show that coculture of control astrocytes with neurons enhances neurite outgrowth, and this is reduced with SREBP2 knockdown astrocytes. In vivo, mice with knockout of SREBP2 in astrocytes have impaired brain development and behavioral and motor defects...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094761/homeodomain-protein-otp-affects-developmental-neuropeptide-switching-in-oxytocin-neurons-associated-with-a-long-term-effect-on-social-behavior
#16
Einav Wircer, Janna Blechman, Nataliya Borodovsky, Michael Tsoory, Ana Rita Nunes, Rui F Oliveira, Gil Levkowitz
Proper response to stress and social stimuli depends on orchestrated development of hypothalamic neuronal circuits. Here we address the effects of the developmental transcription factor orthopedia (Otp) on hypothalamic development and function. We show that developmental mutations in the zebrafish paralogous gene otpa but not otpb affect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus, otpa and otpb differentially regulate neuropeptide switching in a newly identified subset of OXT neurons that co-express the corticotropin-releasing hormone (CRH)...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28094754/comparable-therapeutic-potential-of-umbilical-cord-mesenchymal-stem-cells-in-collagen-induced-arthritis-to-tnf-inhibitor-or-anti-cd20-treatment
#17
Yue Sun, Wei Kong, Saisai Huang, Bingyu Shi, Hanyu Zhang, Weiwei Chen, Huayong Zhang, Cheng Zhao, Xiaojun Tang, Genhong Yao, Xuebing Feng, Lingyun Sun
OBJECTIVES: The effects of mesenchymal stem cell (MSC) transplantation on established collagen-induced arthritis (CIA) were evaluated and compared to biologic therapies. METHODS: CIA was induced with the immunisation of type II collagen (CII) in DBA/1 mice. Human umbilical cord MSC, anti-TNF antibody, rhTNFR:Fc fusion protein and anti-CD20 antibody were respectively injected intraperitoneally into CIA mice. Arthritis severity was assessed by clinical and histological scoring...
January 15, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28094030/glucocorticoid-induced-leucine-zipper-protein-regulates-sodium-and-potassium-balance-in-the-distal-nephron
#18
Priyanka Rashmi, GianLuca Colussi, Michael Ng, Xinhao Wu, Atif Kidwai, David Pearce
Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice...
January 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28093215/melanocortin-4-receptor-constitutive-activity-inhibits-l-type-voltage-gated-calcium-channels-in-neurons
#19
F Agosti, S Cordisco Gonzalez, V Martinez Damonte, M J Tolosa, N Di Siervi, H B Schioth, C Davio, M Perello, J Raingo
The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain nuclei playing a crucial role in the regulation of energy balance controlling the homeostasis of the organism. It displays both agonist-evoked and constitutive activity, and moreover, it can couple to different G proteins. Most of the research on MC4R has been focused on agonist-induced activity, while the molecular and cellular basis of MC4R constitutive activity remains scarcely studied. We have previously shown that neuronal N-type voltage-gated calcium channels (CaV2...
January 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28093214/the-upr-reduces-glucose-metabolism-via-ire1-signaling
#20
Judith M van der Harg, Jessica C van Heest, Fabian N Bangel, Sanne Patiwael, Jan R T van Weering, Wiep Scheper
Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis...
January 13, 2017: Biochimica et Biophysica Acta
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