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cytosolic DNA

Ruifang Li, Ruiling Zhang, Yanhui Yang, Xueqin Wang, Yanjie Yi, Pei Fan, Zhengwei Liu, Chen Chen, Junpeng Chang
CGA-N12 is an antifungal peptide derived from human chromogranin A. In our previous investigation, CGA-N12 was found to have specific anti-candidal activity, though the mechanism of action remained unclear. Herein, we investigated the effects of CGA-N12 on mitochondria. We found that CGA-N12 induced an over-generation of intracellular reactive oxygen species and dissipation in mitochondrial membrane potential, in which the former plays key roles in the initiation of apoptosis and the latter is a sign of the cell apoptosis...
March 20, 2018: Biochemical Journal
Balaram Mohapatra, Pinaki Sar, Sufia Khannam Kazy, Mrinal Kumar Maiti, Tulasi Satyanarayana
Reductive transformation of toxic arsenic (As) species by As reducing bacteria (AsRB) is a key process in As-biogeochemical-cycling within the subsurface aquifer environment. In this study, we have characterized a Gram-stain-negative, non-spore-forming, rod-shaped As reducing bacterium designated KAs 5-3T, isolated from highly As-contaminated groundwater of India. Strain KAs 5-3T displayed high 16S rRNA gene sequence similarity to the members of the genus Pseudoxanthomonas, with P. mexicana AMX 26BT (99.25% similarity), P...
2018: PloS One
Kerri M Malone, Kévin Rue-Albrecht, David A Magee, Kevin Conlon, Olga T Schubert, Nicolas C Nalpas, John A Browne, Alicia Smyth, Eamonn Gormley, Ruedi Aebersold, David E MacHugh, Stephen V Gordon
Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M...
March 20, 2018: Microbial Genomics
Sreejesh Sreedharan, Alessandro Sinopoli, Paul J Jarman, Darren Robinson, Christopher Clemmet, Paul A Scattergood, Craig R Rice, Carl G W Smythe, James A Thomas, Paul I P Elliott
Two new biscyclometalated complexes [Ir(ptzR)2(dppz)]+ (dppz = dipyridophenazene; ptzRH = 4-phenyl-1-benzyl-1,2,3-triazole (1+) and 4-phenyl-1-propyl-1,2,3-triazole (2+)) have been prepared. The hexafluorophosphate salts of these complexes have been fully characterized and, in one case, the X-ray structure of a nitrate salt was obtained. The DNA binding properties of the chloride salts of the complexes were investigated, as well as their cellular uptake by A2780 and MCF7 cell lines. Both complexes display an increase in the intensity of phosphorescence upon titration with duplex DNA, indicating the intercalation of the dppz ligand and, given that they are monocations, the complexes exhibit appreciable DNA binding affinity...
March 19, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Dinesh Kumar Verma, Sonam Gupta, Joyshree Biswas, Neeraj Joshi, Abhishek Singh, Parul Gupta, Shubhangini Tiwari, K Sivarama Raju, Swati Chaturvedi, M Wahajuddin, Sarika Singh
Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation. LPS administration also caused augmented expression of inflammatory cytokines and astrocytes activation...
March 15, 2018: Biochimica et Biophysica Acta
Baomei Wu, Li Li, Tianhang Qiu, Xi Zhang, Suxia Cui
Rice cytoplasmic APX2 is a pleiotropic protein, densely distributed around chloroplasts. It plays key roles in H2 O2 homeostasis and chloroplast protection, and is related to plant architecture and fertility regulation. Ascorbate peroxidases (APXs) catalyze the conversion of H2 O2 into H2 O. In this report, we systematically investigated the function of cytosolic APX2 using a T-DNA knockout mutant. Loss of OsAPX2 altered rice architecture including shoot height and leaf inclination, resulting in shoot dwarfing, leaf dispersion and fertility decline...
March 16, 2018: Plant Cell Reports
Meiguang Xiong, Suyun Wang, Yan-Yi Wang, Yong Ran
The cGAS-MITA pathway of cytosolic DNA sensing plays essential roles in immune response against pathogens that contain DNA or with DNA production in their life cycles. The cGAS-MITA pathway also detects leaked or aberrant accumulated self DNA in the cytoplasm under certain pathological conditions, such as virus induced cell death, DNA damage, mitochondria damage, gene mutations, which results in autoimmune diseases. Therefore, the cGAS-MITA pathway must be tightly controlled to ensure proper immune response against pathogens and to avoid autoimmune diseases...
March 15, 2018: Virologica Sinica
Michelle Brault, Tayla M Olsen, Jennifer Martinez, Daniel B Stetson, Andrew Oberst
The sensing of viral nucleic acids within the cytosol is essential for the induction of innate immune responses following infection. However, this sensing occurs within cells that have already been infected. The death of infected cells can be beneficial to the host by eliminating the virus's replicative niche and facilitating the release of inflammatory mediators. In this study, we show that sensing of intracellular DNA or RNA by cGAS-STING or RIG-I-MAVS, respectively, leads to activation of RIPK3 and necroptosis in bone marrow-derived macrophages...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Jingjing Zhang, Zhijun Zhang, Benshui Shu, Gaofeng Cui, Guohua Zhong
Harmine, one of the natural β-carboline alkaloids extracted from Peganum harmala L., exhibits broad spectrum but limited insecticidal ability against many pests. So there is an urgent need to synthesize novel derivatives with high efficiency. In the present study, a new synthetic compound, [1-(2-naphthyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carboline] (ZC-14), showed a strong proliferation inhibition effect against the Spodoptera frugiperda Sf9 cell line in a dose-dependent manner. Simultaneously, apoptosis induced by 7...
March 11, 2018: International Journal of Molecular Sciences
Xin Mu, Emily Greenwald, Sadeem Ahmad, Sun Hur
The emergence of RNA-based therapeutics demands robust and economical methods to produce RNA with few byproducts from aberrant activity. While in vitro transcription using the bacteriophage T7 RNA polymerase is one such popular method, its transcripts are known to display an immune-stimulatory activity that is often undesirable and uncontrollable. We here showed that the immune-stimulatory activity of T7 transcript is contributed by its aberrant activity to initiate transcription from a promoter-less DNA end...
March 9, 2018: Nucleic Acids Research
Xuanxuan Wang, Hai Liu, Liming Shi, Xiaoli Yu, Yanjun Gu, Xiaonan Sun
LncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1) is an lncRNA which promotes therapeutic resistance in triple-negative breast cancer (TNBC). However, the expression and function of LINP1 in cervical cancer is not yet well-understood. In this study, we evaluated the expression levels of LINP1 in tumor tissues and cell lines of cervical cancer. We found that LINP1 associates with NHEJ proteins (Ku80 and DNA-PKcs). LINP1 translocates from cytosol to nucleus in response to irradiation. In addition, LINP1 knockdown significantly increases the levels of cleaved caspase3 and PARP, leading to enhanced cell apoptosis after ionizing radiation (IR)...
March 12, 2018: Cell Cycle
Judit Danis, Luca Janovák, Barbara Gubán, Anikó Göblös, Kornélia Szabó, Lajos Kemény, Zsuzsanna Bata-Csörgő, Márta Széll
Keratinocytes are non-professional immune cells contributing actively to innate immune responses partially by reacting to a wide range of molecular patterns by activating pattern recognition receptors. Cytosolic nucleotide fragments as pathogen- or self-derived trigger factors are activating inflammasomes and inducing anti-viral signal transduction pathways as well as inducing expression of inflammatory cytokines. We aimed to compare the induced inflammatory reactions in three keratinocyte cell types-normal human epidermal keratinocytes, the HaCaT cell line and the HPV-KER cell line-upon exposure to the synthetic RNA and DNA analogues poly(I:C) and poly(dA:dT) to reveal the underlying signaling events...
March 8, 2018: International Journal of Molecular Sciences
Jerry D Monroe, Heidi L Hruska, Hannah K Ruggles, Kevin M Williams, Michael E Smith
Unlike cisplatin, which forms bifunctional DNA adducts, monofunctional platinum(II) complexes bind only one strand of DNA and might target cancer without causing auditory side-effects associated with cisplatin treatment. We synthesized the monofunctional triamine-ligated platinum(II) complexes, Pt(diethylenetriamine)Cl, [Pt(dien)Cl]+, and Pt(N,N-diethyldiethylenetriamine)Cl, [Pt(Et2dien)Cl]+, and the monofunctional heterocyclic-ligated platinum(II) complexes, pyriplatin and phenanthriplatin, and compared their 5'-GMP binding rates, cellular compartmental distribution and cellular viability effects...
2018: PloS One
Kathryn Volkening, Brian Keller, Cheryl Leysta-Lantz, Michael J Strong
Tar DNA binding protein of 43kDa (TDP-43) is a dual function RNA/DNA binding protein with varied cellular functions. In degenerating motor neurons in ALS, TDP-43 relocalizes from the nucleus to the cytosol where it is sequestered into inclusions. It is likely that the pathogenic role of TDP-43 in ALS can involve either a gain or a loss of function, depending on the nature of its RNA or protein interactor. However, while TDP-43 binding partners have been identified in a range of model systems and from the human brain, interactors from human spinal cord tissue have not...
March 7, 2018: Journal of Proteome Research
Duojiao Wu, Xiangdong Wang, Hongzhi Sun
Mitochondrial malfunction is related to aging and to the onset of many diseases, such as obesity/diabetes, cancer, and cardiovascular and neurodegenerative diseases. The molecular principles of biological and toxicological processes the mitochondria can regulate should be disease-specific, cell type-specific, and drug targetable. Mitochondrial biology and toxicology is evolving and undergoing a revolution through fast-developing biotechnologies garnering increasing attention due to the importance of targeted therapies...
March 6, 2018: Cell Biology and Toxicology
J Papinska, H Bagavant, G B Gmyrek, M Sroka, S Tummala, K A Fitzgerald, U S Deshmukh
Sjögren syndrome (SS), a chronic autoimmune disorder causing dry mouth, adversely affects the overall oral health in patients. Activation of innate immune responses and excessive production of type I interferons (IFNs) play a critical role in the pathogenesis of this disorder. Recognition of nucleic acids by cytosolic nucleic acid sensors is a major trigger for the induction of type I IFNs. Upon activation, cytosolic DNA sensors can interact with the stimulator of interferon genes (STING) protein, and activation of STING causes increased expression of type I IFNs...
March 1, 2018: Journal of Dental Research
Chang Li, Shouwen Du, Mingyao Tian, Yuhang Wang, Jieying Bai, Peng Tan, Wei Liu, Ronglan Yin, Maopeng Wang, Ying Jiang, Yi Li, Na Zhu, Yilong Zhu, Tiyuan Li, Shipin Wu, Ningyi Jin, Fuchu He
Interferons (IFNs) establish dynamic host defense mechanisms by inducing various IFN-stimulated genes that encodes many antiviral innate immune effectors. IFN-inducible transmembrane (IFITM) proteins have been identified as intrinsic antiviral effectors, which block the entry of a broad spectrum of enveloped RNA viruses by interrupting virus-endosomal fusion. However, antiviral activity of IFITM proteins against mammalian DNA virus has not been demonstrated till date. Here, we sought to investigate the antiviral activities and mechanisms of interferon-inducible transmembrane protein 3 (IFITM3) protein against poxvirus infection...
2018: Frontiers in Immunology
Zvonimir Marelja, Silke Leimkühler, Fanis Missirlis
Iron sulfur (Fe-S) clusters and the molybdenum cofactor (Moco) are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism...
2018: Frontiers in Physiology
Fumiaki Ito, Hanjing Yang, Xiao Xiao, Shu-Xing Li, Aaron Wolfe, Brett Zirkle, Vagan Arutiunian, Xiaojiang S Chen
APOBEC3H (A3H) is a member of the APOBEC3 subfamily of DNA cytosine deaminases that are important for innate immune defense and have been implicated in cancer biogenesis. To understand the structural basis for A3H biochemical function, we determined a high-resolution structure of human A3H and performed extensive biochemical analysis. The 2.49 Å crystal structure reveals a uniquely long C-terminal helix 6 (h6), a disrupted β5 strand of the canonical five-stranded β-sheet core, and a long loop 1 around the Zn-active center...
February 28, 2018: Scientific Reports
Iliana Georgana, Rebecca P Sumner, Greg J Towers, Carlos Maluquer de Motes
Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerises and translocates from the ER to a perinuclear region to mediate IRF-3 activation. Poxviruses are dsDNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here we investigated the activation of innate immune signalling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing...
February 28, 2018: Journal of Virology
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