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https://www.readbyqxmd.com/read/29935433/microrna-alterations-in-ipsc-derived-dopaminergic-neurons-from-parkinson-disease-patients
#1
Eduard Tolosa, Teresa Botta-Orfila, Xavier Morató, Carles Calatayud, Raquel Ferrer-Lorente, María-José Martí, Manel Fernández, Carles Gaig, Ángel Raya, Antonella Consiglio, Mario Ezquerra, Rubén Fernández-Santiago
MicroRNA (miRNA) misregulation in peripheral blood has been linked to Parkinson disease (PD) but its role in the disease progression remains elusive. We performed an explorative genome-wide study of miRNA expression levels in dopaminergic neurons (DAn) from PD patients generated by somatic cell reprogramming and induced pluripotent stem cells differentiation. We quantified expression levels of 377 miRNAs in DAn from 3 sporadic PD patients (sPD), 3 leucine-rich repeat kinase 2-associated PD patients (L2PD) (total 6 PD), and 4 healthy controls...
May 31, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29935175/targeting-vascular-inflammation-in-ischemic-stroke-recent-developments-on-novel-immunomodulatory-approaches
#2
Shashank Shekhar, Mark W Cunningham, Mallikarjuna R Pabbidi, Shaoxun Wang, George W Booz, Fan Fan
Ischemic stroke is a devastating and debilitating medical condition with limited therapeutic options. However, accumulating evidence indicates a central role of inflammation in all aspects of stroke including its initiation, the progression of injury, and recovery or wound healing. A central target of inflammation is disruption of the blood brain barrier or neurovascular unit. Here we discuss recent developments in identifying potential molecular targets and immunomodulatory approaches to preserve or protect barrier function and limit infarct damage and functional impairment...
June 20, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29934676/a-topological-transition-from-bimolecular-quadruplex-to-g-triplex-tri-g-quadruplex-exhibited-by-truncated-double-repeats-of-human-telomere
#3
Mohan Kumar, Mahima Kaushik, Shrikant Kukreti
Human telomeric G-rich sequences can fold back into various conformations depending upon the salt (Na+ or K+ ) at physiological pH. On the basis of results obtained by native PAGE electrophoresis, circular dichroism, and UV-melting experiments, we report here that truncated sequences of human telomere (d-GGGTTAGGG; GM9, d-AGGGTTAGGG; GM10, d-TAGGGTTAGGG; GM11) adopt a varied range of quadruplex conformations as a function of the cation present. By correlating CD and gel electrophoresis experiments; it was concluded that the GM9 oligonucleotide can self-associate to form a tetramer quadruplex (antiparallel; AP) in Na+ solution and a mixture of G-triplex (AP) or tri-G-quadruplex (parallel; P) along with a tetramer G-quadruplex structure (AP) in K+ ...
June 22, 2018: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/29934589/tlr9-activation-via-microglial-glucocorticoid-receptors-contributes-to-degeneration-of-midbrain-dopamine-neurons
#4
Layal Maatouk, Anne-Claire Compagnion, Maria-Angeles Carrillo-de Sauvage, Alexis-Pierre Bemelmans, Sabrina Leclere-Turbant, Vincent Cirotteau, Mira Tohme, Allen Beke, Michaël Trichet, Virginie Bazin, Bobby N Trawick, Richard M Ransohoff, François Tronche, Bénédicte Manoury, Sheela Vyas
Inflammation is a characteristic feature of Parkinson's disease (PD). We examined the role of TLR9 and its regulation by glucocorticoid receptors (GRs) in degeneration of substantia nigra dopamine neurons (DNs). TLR9 agonist, CpG-ODN, induced DN degeneration in mice lacking GR in microglia but not in controls. TLR9 deletion reduced DN loss in neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. GR regulates TLR9 activation during MPTP neurotoxicity as TLR9 antagonist suppressed increased DN loss in microglia/macrophage GR mutant mice...
June 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29934340/induction-of-thioredoxin-interacting-protein-by-histone-deacetylase-inhibitor-entinostat-is-associated-with-dna-damage-and-apoptosis-in-esophageal-adenocarcinoma
#5
Paul L Feingold, Deborah R Surman, Kate Brown, Yuan Xu, Lucas A McDuffie, Vivek Shukla, Emily S Reardon, Daniel R Crooks, Jane B Trepel, Sunmin Lee, Min-Jung Lee, Shaojian Gao, Sichuan Xi, Kaitlin C McLoughlin, Laurence P Diggs, David G Beer, Derek J Nancarrow, Leonard M Neckers, Jeremy L Davis, Chuong D Hoang, Jonathan M Hernandez, David S Schrump, R Taylor Ripley
In 2017, an estimated 17,000 individuals were diagnosed with esophageal adenocarcinoma (EAC) and less than 20% will survive 5 years. PET-avidity is indicative of high glucose utilization and is nearly universal in EAC. TXNIP blocks glucose uptake and exhibits pro-apoptotic functions. Higher expression in EAC has been associated with improved disease-specific survival, lack of lymph node involvement, reduced perineural invasion, and increased tumor differentiation. We hypothesized that TXNIP may act as a tumor suppressor that sensitizes EAC cells to standard chemotherapeutics...
June 22, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29933956/progress-in-epigenetics-of-depression
#6
Catherine J Peña, Eric J Nestler
Depression is a prevalent and complex psychiatric syndrome. Epigenetic mechanisms bridge the genetic and environmental factors that contribute to the pathophysiology of depression. A surge of research over the last decade has identified changes in DNA methylation, histone modifications, histone organization, and noncoding RNAs associated with depression and stress-induced depression-like behavior in animal models. We focus here on associations of epigenetic factors concurrent with depression and depression-like behavior, although risk for depression and some of the associated epigenetic changes are known to have developmental origins...
2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29933360/lead-induces-genotoxicity-via-oxidative-stress-and-promoter-methylation-of-dna-repair-genes-in-human-lymphoblastoid-tk6-cells
#7
Xiangquan Liu, Jingying Wu, Wenyan Shi, Wenhua Shi, Hekun Liu, Xiaonan Wu
BACKGROUND Lead (Pb) is a widely used metal in modern industry and is regarded as a health hazard. Although lead-induced genotoxicity has been confirmed, the direct evidence that lead induces genotoxicity in human cells and its related mechanisms has not been fully elucidated. In this study, for the first time, we evaluated the genotoxicity induced by lead in human lymphoblastoid TK6 cells. MATERIAL AND METHODS The TK6 cells were incubated with various concentrations of Pb(Ac)2 for 6 h, 12 h, or 24 h. Cell viability was detected by CCK8 assay...
June 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29933101/annealing-novel-nucleobase-lipids-with-oligonucleotides-or-plasmid-dna-based-on-h-bonding-or-%C3%AF-%C3%AF-interaction-assemblies-and-transfections
#8
Yuan Ma, Yuejie Zhu, Chao Wang, Delin Pan, Shuang Liu, Mengyi Yang, Zhangping Xiao, Xiantao Yang, Wenting Zhao, Xinyang Zhou, Yiding Li, Yufei Pan, Jing Sun, Shuhe Wang, Zhu Guan, Lihe Zhang, Zhenjun Yang
Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo...
June 14, 2018: Biomaterials
https://www.readbyqxmd.com/read/29932964/growth-arrest-and-dna-damage-inducible-45-beta-activates-pro-inflammatory-cytokines-and-phagocytosis-in-the-grass-carp-ctenopharyngodon-idella-after-aeromonas-hydrophila-infection
#9
Yulin Bai, Yubang Shen, Xiao-Yan Xu, Yuqi Bai, Yuan Fang, Meng Zhang, Yiheng Miao, Xueshu Zhang, Jia-le Li
Growth arrest and DNA damage inducible 45-beta (Gadd45B) is essential for mitogen-activated protein kinases (MAPK) activities, and involved in regulating growth, apoptosis, and DNA demethylation. In the present study, the cDNA of gcGadd45Ba and gcGadd45Bb in grass carp was identified. And the expression levels show that they were widely distributed in the tested tissues and showed significant immune responses both in vitro and in vivo after challenge with bacteria and pathogen-associated molecular patterns (PAMPs)...
June 19, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29932904/scc2-is-a-potent-activator-of-cohesin-s-atpase-that-promotes-loading-by-binding-scc1-without-pds5
#10
Naomi J Petela, Thomas G Gligoris, Jean Metson, Byung-Gil Lee, Menelaos Voulgaris, Bin Hu, Sotaro Kikuchi, Christophe Chapard, Wentao Chen, Eeson Rajendra, Madhusudhan Srinivisan, Hongtao Yu, Jan Löwe, Kim A Nasmyth
Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, and Scc2. Unlike Pds5, Scc2 is not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations that compromise its interaction with Scc2 adversely affect cohesin's ATPase activity and loading. Moreover, Scc2 mutations that alter how the ATPase responds to DNA abolish loading despite cohesin's initial association with loading sites...
June 21, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29932859/short-duration-rapid-chilling-of-mastectomy-specimens-does-not-interfere-with-breast-cancer-biomarker-and-molecular-testing
#11
Asangi R Kumarapeli, William Bellamy, Ericka Olgaard, Nicole Massoll, Soheila Korourian
CONTEXT: - A thorough gross examination of specimens for breast cancer requires the tissue to be very thinly sectioned, which is often difficult in large mastectomy samples. We have implemented rapid chilling of mastectomy specimens before formalin fixation. OBJECTIVE: - To evaluate the effects of rapid chilling of breast tissue on subsequent biomarker and molecular testing. DESIGN: - Mastectomy specimens were chilled at -80°C for 20 minutes to facilitate uniform sectioning of tissue at 4-mm intervals and enhance proper fixation and identification of small lesions...
June 22, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29932796/defective-dendritic-cell-cytotoxic-activity-of-high-grade-glioma-patients-results-from-the-low-expression-of-membrane-tnf%C3%AE-and-can-be-corrected-in-vitro-by-treatment-with-recombinant-il-2-or-exogenic-double-stranded-dna
#12
Tamara Tyrinova, Olga Leplina, Sergey Mishinov, Marina Tikhonova, Anton Kalinovskiy, Sergey Chernov, Evgeniya Dolgova, Vyacheslav Stupak, Evgeniya Voronina, Sergey Bogachev, Ekaterina Shevela, Alexander Ostanin, Elena Chernykh
Besides initiation of tumor-specific T cell immunity, dendritic cells (DCs) are endowed with tumoricidal activity. Previously, we showed that monocyte-derived DCs of high-grade glioma patients generated in the presence of interferon alpha (IFNα) (IFN-DCs) have impaired cytotoxic activity against tumor necrosis factor alpha (TNFα)-sensitive HEp-2 tumor cells. Herein, we demonstrate that decreased transmembrane TNFα (tmTNFα) expression, but not soluble TNFα (sTNFα) production by high-grade glioma patient IFN-DCs, determines the defective tumoricidal activity against TNFα-sensitive HEp-2 cells...
June 22, 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29932054/transcriptional-modulation-of-entire-chromosomes-dosage-compensation
#13
John C Lucchesi
Dosage compensation is a regulatory system designed to equalize the transcription output of the genes of the sex chromosomes that are present in different doses in the sexes (X or Z chromosome, depending on the animal species involved). Different mechanisms of dosage compensation have evolved in different animal groups. In Drosophila males, a complex (male-specific lethal) associates with the X chromosome and enhances the activity of most X-linked genes by increasing the rate of RNAPII elongation. In Caenorhabditis, a complex (dosage compensation complex) that contains a number of proteins involved in condensing chromosomes decreases the level of transcription of both X chromosomes in the XX hermaphrodite...
June 2018: Journal of Genetics
https://www.readbyqxmd.com/read/29931584/alteration-of-benzo-a-pyrene-biotransformation-by-resveratrol-in-apc-min-mouse-model-of-colon-carcinogenesis
#14
Ashley C Huderson, P V Rekha Devi, Mohammad S Niaz, Samuel E Adunyah, Aramandla Ramesh
Epidemiological surveys have revealed that environmental and dietary factors contribute to most of the human cancers. Our earlier studies have shown that resveratrol (RVT), a phytochemical reduced the tumor number, size and incidence of dysplasias induced by benzo(a)pyrene (BaP), an environmental toxicant in the Apc Min/+ mouse model of colon cancer. In this study we investigated to ascertain whether the preventive effects of RVT on BaP-induced colon carcinogenesis is a result of altered BaP biotransformation by RVT...
June 22, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29931239/effects-of-histone-h2b-ubiquitylation-on-the-nucleosome-structure-and-dynamics
#15
Wladyslaw A Krajewski, Jiabin Li, Yali Dou
DNA in nucleosomes has restricted nucleosome dynamics and is refractory to DNA-templated processes. Histone post-translational modifications play important roles in regulating DNA accessibility in nucleosomes. Whereas most histone modifications function either by mitigating the electrostatic shielding of histone tails or by recruiting 'reader' proteins, we show that ubiquitylation of H2B K34, which is located in a tight space protected by two coils of DNA superhelix, is able to directly influence the canonical nucleosome conformation via steric hindrances by ubiquitin groups...
June 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29930500/epigenetic-modifications-associated-to-neuroinflammation-and-neuropathic-pain-after-neural-trauma
#16
REVIEW
Clara Penas, Xavier Navarro
Accumulating evidence suggests that epigenetic alterations lie behind the induction and maintenance of neuropathic pain. Neuropathic pain is usually a chronic condition caused by a lesion, or pathological change, within the nervous system. Neuropathic pain appears frequently after nerve and spinal cord injuries or diseases, producing a debilitation of the patient and a decrease of the quality of life. At the cellular level, neuropathic pain is the result of neuronal plasticity shaped by an increase in the sensitivity and excitability of sensory neurons of the central and peripheral nervous system...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29929470/anti-neutrophil-extracellular-trap-antibody-in-a-patient-with-relapse-of-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis-a-case-report
#17
Haruki Shida, Nobuhiro Hashimoto, Yoshihiro Kusunoki, Fumihiko Hattanda, Yayoi Ogawa, Terumasa Hayashi, Daigo Nakazawa, Sakiko Masuda, Utano Tomaru, Akihiro Ishizu
BACKGROUND: Neutrophil extracellular traps (NETs) are web-like DNA decorated with antimicrobial proteins, such as myeloperoxidase (MPO), which are extruded from activated neutrophils. Although NETs are essential in innate immunity, an excessive formation of NETs has adverse effects, e.g., induction of anti-neutrophil cytoplasmic antibody (ANCA), to the hosts. Since ANCA can induce NET formation in the primed neutrophils, a positive feedback loop can be formed between NETs and ANCA, which is called "ANCA-NETs vicious cycle...
June 22, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29929421/transcription-infidelity-and-genome-integrity-the-parallax-view
#18
Alasdair J E Gordon, Priya Sivaramakrishnan, Jennifer A Halliday, Christophe Herman
It was recently shown that removal of GreA, a transcription fidelity factor, enhances DNA break repair. This counterintuitive result, arising from unresolved backtracked RNA polymerase impeding DNA resection and thereby facilitating RecA-loading, leads to an interesting corollary: error-free full-length transcripts and broken chromosomes. Therefore, transcription fidelity may compromise genomic integrity.
June 21, 2018: Transcription
https://www.readbyqxmd.com/read/29929045/regulation-of-dna-repair-in-the-absence-of-classical-non-homologous-end-joining
#19
Youn-Jung Kang, Catherine T Yan
Classical non-homologous end-joining (cNHEJ) is the main pathway for the repair of DNA double strand breaks (DSBs) in mammalian cells. In the absence of c-NHEJ, an alternative end-joining (A-EJ) mechanism resolves DSBs. To date, no A-EJ specific factor has been identified. Instead, this mechanism appears to co-opt proteins involved in more than one DNA repair pathway. These include components of base-excision repair (PARP1/XRCC1/LIG3), interstrand cross-link repair (BRCA1/FANCD2), and DSB response/DNA end-resection (MRE11A/RAD50/RBBP8)...
June 12, 2018: DNA Repair
https://www.readbyqxmd.com/read/29929044/nitric-oxide-induced-s-nitrosation-causes-base-excision-repair-imbalance
#20
Marcus C Parrish, Isaac A Chaim, Zachary D Nagel, Steven R Tannenbaum, Leona D Samson, Bevin P Engelward
It is well established that inflammation leads to the creation of potent DNA damaging chemicals, including reactive oxygen and nitrogen species. Nitric oxide can react with glutathione to create S-nitrosoglutathione (GSNO), which can in turn lead to S-nitrosated proteins. Of particular interest is the impact of GSNO on the function of DNA repair enzymes. The base excision repair (BER) pathway can be initiated by the alkyl-adenine DNA glycosylase (AAG), a monofunctional glycosylase that removes methylated bases...
May 5, 2018: DNA Repair
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