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https://www.readbyqxmd.com/read/28508084/clinicopathologic-and-molecular-spectrum-of-rnaseh1-related-mitochondrial-disease
#1
Enrico Bugiardini, Olivia V Poole, Andreea Manole, Alan M Pittman, Alejandro Horga, Iain Hargreaves, Cathy E Woodward, Mary G Sweeney, Janice L Holton, Jan-Willem Taanman, Gordon T Plant, Joanna Poulton, Massimo Zeviani, Daniele Ghezzi, John Taylor, Conrad Smith, Carl Fratter, Meena A Kanikannan, Arumugam Paramasivam, Kumarasamy Thangaraj, Antonella Spinazzola, Ian J Holt, Henry Houlden, Michael G Hanna, Robert D S Pitceathly
OBJECTIVE: Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients with mitochondrial disease and establish clinically meaningful genotype-phenotype correlations. METHODS: RNASEH1 was analyzed in patients with (1) multiple deletions/depletion of muscle mtDNA and (2) mendelian progressive external ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction, but no detectable multiple deletions/depletion of muscle mtDNA...
June 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28490179/-living-dynamics-of-filamentous-bacteria-on-an-adherent-surface-under-hydrodynamic-exposure
#2
Justin P Jahnke, Austin M Smith, Nicole E Zander, Victoria Wiedorn, Kenneth E Strawhecker, Jessica L Terrell, Dimitra N Stratis-Cullum, Xuanhong Cheng
The potential advantages of cell-based biohybrid devices over conventional nonliving systems drive the interest to control the behavior of the underlying biological cells in microdevices. Here, the authors studied how shear influenced the geometry and elongation of fimbriated filaments on affinity substrates. The cells were engineered to express FimH, which binds to mannose with a high affinity. A microfluidic channel was functionalized with RNAse B, which is rich in mannose residues, and the device was used to control the hydrodynamic force on live Escherichia coli under filamentous growth...
May 10, 2017: Biointerphases
https://www.readbyqxmd.com/read/28484023/coronavirus-nonstructural-protein-15-mediates-evasion-of-dsrna-sensors-and-limits-apoptosis-in-macrophages
#3
Xufang Deng, Matthew Hackbart, Robert C Mettelman, Amornrat O'Brien, Anna M Mielech, Guanghui Yi, C Cheng Kao, Susan C Baker
Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28465635/berberine-displays-antitumor-activity-in-esophageal-cancer-cells-in-vitro
#4
Shu-Xian Jiang, Bo Qi, Wen-Jian Yao, Cheng-Wei Gu, Xiu-Feng Wei, Yi Zhao, Yu-Zhen Liu, Bao-Sheng Zhao
AIM: To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms. METHODS: Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer...
April 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28465261/challenges-in-the-evaluation-of-thiol-reactive-inhibitors-of-human-protein-disulfide-isomerase
#5
Celia K Foster, Colin Thorpe
This paper addresses how to evaluate the efficacy of the growing inventory of thiol-reactive inhibitors of mammalian protein disulfide Isomerase (PDI) enzymes under realistic concentrations of potentially competing thiol-containing peptides and proteins. For this purpose, we introduce a variant of the widely-used reductase assay by using a commercially-available cysteine derivative (BODIPY FL L-Cystine; BD-SS) that yields a 55-fold increase in fluorescence (excitation/emission; 490/513nm) on scission of the disulfide bond...
April 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28451245/protecting-micrornas-from-rnase-degradation-with-steric-dna-nanostructures
#6
H Qian, C Y Tay, M I Setyawati, S L Chia, D S Lee, D T Leong
Tumor suppressive microRNAs are potent molecules that might cure cancer, one day. Despite the many advanced strategies for delivery of these microRNAs to the cell, there are few therapeutic microRNAs in clinical use. Progress in microRNA bioapplications is hindered by a high vulnerability of exogeneous microRNA molecules to RNase degradation that occurs in extra- and intracellular physiological conditions. In this proof-of-concept study, we use a programmable self-assembled DNA nanostructure bearing a "shuriken" shape to not only deliver but more importantly protect a tumor suppressive microRNA-145 for a sufficiently long time to exert its therapeutic effect in human colorectal cancer cells...
February 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28446680/non-structural-protein-l-species-specificity-supports-a-mouse-origin-for-vilyuisk-human-encephalitis-virus
#7
Melissa Drappier, Fred R Opperdoes, Thomas Michiels
Vilyuisk human encephalitis virus (VHEV) is a picornavirus related to Theiler's murine encephalomyelitis virus (TMEV). VHEV was isolated from human material passaged in mice. Whether this VHEV is from human or mouse origin is therefore unclear. We took advantage of the species-specific activity of the non-structural L* protein of theiloviruses to track the origin of TMEV isolates. TMEV L* inhibits RNase L, the effector enzyme of the interferon pathway. Using co-immunoprecipitation and functional RNase L assays, the species-specificity of RNase L antagonism was tested for L* from a mouse (DA) and a rat (RTV-1) TMEV strain as well as for VHEV...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28418037/mitochondrial-c11orf83-is-a-potent-antiviral-protein-independent-of-interferon-production
#8
Yun Yang, Shaoquan Xiong, Bei Cai, Hui Luo, E Dong, Qiqi Li, Gaili Ji, Chengjian Zhao, Yanjun Wen, Yuquan Wei, Hanshuo Yang
Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28410117/racial-disparities-disruptive-genes-in-prostate-carcinogenesis
#9
Savita Singh, Alexis Plaga, Girish C Shukla
Population specific studies in prostate cancer (PCa) reveal a unique heterogeneous etiology. Various factors, such as genetics, environment and dietary regimen seems to determine disease progression, therapeutic resistance and rate of mortality. Enormous disparity documented in disease incidences, aggressiveness and mortality in PCa among AAs (African Americans) and CAs (Caucasian Americans) is attributed to the variations in genetics, epigenetics and their association with metabolism. Scientific and clinical evidences have revealed the influence of variations in Androgen Receptor (AR), RNAse L, macrophage scavenger receptor 1 (MRS1), androgen metabolism by cytochrome P450 3A4, differential regulation of microRNAs, epigenetic alterations and diet in racial disparity in PCa incidences and mortality...
June 1, 2017: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28399925/human-serum-rnase-l-level-is-inversely-associated-with-metabolic-syndrome-and-age
#10
Yi-Ting Wang, Ping-Huei Tseng, Chi-Ling Chen, Der-Sheng Han, Yu-Chiao Chi, Fen-Yu Tseng, Wei-Shiung Yang
BACKGROUND: Ribonuclease-L (RNase-L) was known to be a ubiquitous enzyme involved in several cellular functions, especially innate immunity. It was recently shown to participate in adipogenesis in rodents. Here, we developed a method to measure serum levels of RNase-L and analyzed the relationship between RNase-L and metabolic syndrome (MetS). METHODS: A total of 396 subjects were recruited from a health check-up program. An in-house RNase-L immunoassay was developed...
April 11, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28384222/functional-studies-of-e-faecalis-rnase-j2-and-its-role-in-virulence-and-fitness
#11
Peng Gao, Kenneth L Pinkston, Agathe Bourgogne, Barbara E Murray, Ambro van Hoof, Barrett R Harvey
Post-transcriptional control provides bacterial pathogens a method by which they can rapidly adapt to environmental change. Dual exo- and endonucleolytic activities of RNase J enzymes contribute to Gram-positive RNA processing and decay. First discovered in Bacillus subtilis, RNase J1 plays a key role in mRNA maturation and degradation, while the function of the paralogue RNase J2 is largely unknown. Previously, we discovered that deletion of the Enterococcus faecalis rnjB gene significantly attenuates expression of a major virulence factor involved in enterococcal pathogenesis, the Ebp pili...
2017: PloS One
https://www.readbyqxmd.com/read/28371604/polyols-have-unique-ability-to-refold-protein-as-compared-to-other-osmolyte-types
#12
G S Sharma, L R Singh
Effects of solvent environments on protein refolding have gained significant attention due to their biotechnological and pharmaceutical applications. Recent advances have shown that a number of organic osmolytes have the unique ability to induce proper folding of several misfolded proteins and simultaneously inhibit aggregation during the process. In the present study, we investigated the effects of polyol osmolytes on the refolding of guanidinium chloride-denatured ribonuclease-A (RNase-A) and compared it with that of other osmolyte types...
April 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28369217/evolutionary-adaptation-revealed-by-comparative-genome-analysis-of-woolly-mammoths-and-elephants
#13
Sean D Smith, Joseph K Kawash, Spyros Karaiskos, Ian Biluck, Andrey Grigoriev
Comparative genomics studies typically limit their focus to single nucleotide variants (SNVs) and that was the case for previous comparisons of woolly mammoth genomes. We extended the analysis to systematically identify not only SNVs but also larger structural variants (SVs) and indels and found multiple mammoth-specific deletions and duplications affecting exons or even complete genes. The most prominent SV found was an amplification of RNase L (with different copy numbers in different mammoth genomes, up to 9-fold), involved in antiviral defense and inflammasome function...
March 22, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28362255/ribonuclease-l-mediates-the-cell-lethal-phenotype-of-double-stranded-rna-editing-enzyme-adar1-deficiency-in-a-human-cell-line
#14
Yize Li, Shuvojit Banerjee, Stephen A Goldstein, Beihua Dong, Christina Gaughan, Sneha Rath, Jesse Donovan, Alexei Korennykh, Robert H Silverman, Susan R Weiss
ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of ADAR1 leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations are embryonic lethal but are rescued by mutation of the Mda5 or Mavs genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of ADAR1 mutation are unknown. We show that the cell-lethal phenotype of ADAR1 deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the RNASEL gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein...
March 31, 2017: ELife
https://www.readbyqxmd.com/read/28331099/interferon-inducible-oligoadenylate-synthetase-like-protein-acts-as-an-antiviral-effector-against-classical-swine-fever-virus-via-the-mda5-mediated-type-i-interferon-signaling-pathway
#15
Lian-Feng Li, Jiahui Yu, Yuexiu Zhang, Qian Yang, Yongfeng Li, Lingkai Zhang, Jinghan Wang, Su Li, Yuzi Luo, Yuan Sun, Hua-Ji Qiu
Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), which poses a serious threat to the global pig industry. Interferons (IFNs) and IFN-stimulated genes (ISGs) play a key role in host antiviral defense. We have previously screened the porcine 2' -5' -oligoadenylate synthase-like protein (pOASL) as a potential anti-CSFV ISG using a reporter CSFV. This study aimed to clarify the underlying antiviral mechanism of pOASL against CSFV. We confirmed that CSFV replication was significantly suppressed in lentivirus-delivered, pOASL-overexpressing PK-15 cells, whereas silencing the expression of endogenous pOASL by small interfering RNAs markedly enhanced CSFV growth...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28257035/rnase-l-suppresses-androgen-receptor-signaling-cell-migration-and-matrix-metalloproteinase-activity-in-prostate-cancer-cells
#16
Shubham Dayal, Jun Zhou, Praveen Manivannan, Mohammad Adnan Siddiqui, Omaima Farid Ahmad, Matthew Clark, Sahezeel Awadia, Rafael Garcia-Mata, Lirim Shemshedini, Krishnamurthy Malathi
The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration...
March 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28242357/transcriptional-and-post-transcriptional-regulation-of-pst2-operon-expression-in-vibrio-cholerae-o1
#17
Daniel M da C Leite, Livia C Barbosa, Nathalia Mantuano, Carolina L Goulart, Giovani C Veríssimo da Costa, Paulo M Bisch, Wanda M A von Krüger
One of the most abundant proteins in V. cholerae O1 cells grown under inorganic phosphate (Pi) limitation is PstS, the periplasmic Pi-binding component of the high-affinity Pi transport system Pst2 (PstSCAB), encoded in pst2 operon (pstS-pstC2-pstA2-pstB2). Besides its role in Pi uptake, Pst2 has been also associated with V. cholerae virulence. However, the mechanisms regulating pst2 expression and the non-stoichiometric production of the Pst2 components under Pi-limitation are unknown. A computational-experimental approach was used to elucidate the regulatory mechanisms behind pst2 expression in V...
February 27, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28239425/block-ionomer-complexes-consisting-of-sirna-and-araft-synthesized-hydrophilic-block-cationic-copolymers-ii-the-influence-of-cationic-block-charge-density-on-gene-suppression
#18
Keith H Parsons, Andrew C Holley, Gabrielle A Munn, Alex S Flynt, Charles L McCormick
Block ionomer complex (BIC)-siRNA interactions and effectiveness in cell transfection are reported. Aqueous RAFT polymerization was used to prepare a series of hydrophilic-block-cationic copolymers in which the cationic block statistically incorporates increasing amounts of neutral, hydrophilic monomer such that the number of cationic groups remains unchanged but the cationic charge density is diluted along the polymer backbone. Reduced charge density decreases the electrostatic binding strength between copolymers and siRNA with the goal of improving siRNA release after targeted cellular delivery...
October 21, 2016: Polymer Chemistry
https://www.readbyqxmd.com/read/28236279/oas-gene-family-expression-is-associated-with-hiv-related-neurocognitive-disorders
#19
C Sanfilippo, M R Pinzone, D Cambria, A Longo, M Palumbo, R Di Marco, F Condorelli, G Nunnari, L Malaguarnera, M Di Rosa
HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2'-5'-oligoadenylate synthetase (OAS) genes are produced in response to interferon (IFN), mainly by monocytes, and exert their antiviral functions by activation of RNase L that degrades viral and cellular RNAs. In this study, we aimed at exploring OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE), in HIV-associated neurocognitive disorders (HAND), and in HIV-associate dementia (HAD)...
February 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28203566/increased-spontaneous-recombination-in-rnase-h2-deficient-cells-arises-from-multiple-contiguous-rnmps-and-not-from-single-rnmp-residues-incorporated-by-dna-polymerase-epsilon
#20
Anastasiya Epshtein, Catherine J Potenski, Hannah L Klein
Ribonucleotides can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. RNA:DNA hybrids are removed by RNase H enzymes. Single rNMPs in DNA are removed by RNase H2 and if they remain on the leading strand, can lead to mutagenesis in a Top1-dependent pathway. rNMPs in DNA can also stimulate genome instability, among which are homologous recombination gene conversion events. We previously found that, similar to the rNMP-stimulated mutagenesis, rNMP-stimulated recombination was also Top1-dependent...
June 2016: Microbial Cell
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