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https://www.readbyqxmd.com/read/27933565/kshv-strategies-for-host-dsdna-sensing-machinery
#1
REVIEW
Hang Gao, Yanyan Song, Chengrong Liu, Qiming Liang
The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling...
December 5, 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27930316/structural-basis-for-glutathione-mediated-activation-of-the-virulence-regulatory-protein-prfa-in-listeria
#2
Michael Hall, Christin Grundström, Afshan Begum, Mikael J Lindberg, Uwe H Sauer, Fredrik Almqvist, Jörgen Johansson, A Elisabeth Sauer-Eriksson
Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could fulfill this function. Here we report the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, the hly operator PrfA box motif. These structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27926991/human-mitochondrial-nucleases
#3
REVIEW
Francesco Bruni, Robert N Lightowlers, Zofia M Chrzanowska-Lightowlers
Mitochondria are cytosolic organelles that have many essential roles including ATP production via oxidative phosphorylation, apoptosis, iron-sulphur cluster biogenesis, heme and steroid synthesis, calcium homeostasis and regulation of cellular redox state. One of the unique features of these organelles is the presence of an extra-chromosomal mitochondrial genome (mtDNA), together with all the machinery required to replicate and transcribe mtDNA. The accurate maintenance of mitochondrial gene expression is essential for correct organellar metabolism, and is in part dependent on the levels of mtDNA and mt-RNA, which are regulated by balancing synthesis against degradation...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27920531/in-vitro-evaluation-of-folic-acid-conjugated-redox-responsive-mesoporous-silica-nanoparticles-for-the-delivery-of-cisplatin
#4
Merlis P Alvarez-Berríos, Juan L Vivero-Escoto
The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27917172/immunization-strategies-against-piscirickettsia-salmonis-infections-review-of-vaccination-approaches-and-modalities-and-their-associated-immune-response-profiles
#5
REVIEW
Øystein Evensen
Salmonid rickettsial septicemia (SRS) is a serious, infectious disease in Chilean salmon farming caused by Piscirickettsia salmonis, causing heavy losses to the salmonid industry. P. salmonis belongs to the Gammaproteobacteria, order Thiotrichales. SRS was first described in Chile in 1989, and infection with P. salmonis has since been described from a high number of fish species and in several geographic regions globally. P. salmonis infection of salmonids causes multifocal, necrotic areas of internal organs such as liver, kidney, and spleen...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27915233/molecular-basis-for-the-autonomous-promotion-of-cell-proliferation-by-angiogenin
#6
Trish T Hoang, Ronald T Raines
Canonical growth factors act indirectly via receptor-mediated signal transduction pathways. Here, we report on an autonomous pathway in which a growth factor is internalized, has its localization regulated by phosphorylation, and ultimately uses intrinsic catalytic activity to effect epigenetic change. Angiogenin (ANG), a secreted vertebrate ribonuclease, is known to promote cell proliferation, leading to neovascularization as well as neuroprotection in mammals. Upon entering cells, ANG encounters the cytosolic ribonuclease inhibitor protein, which binds with femtomolar affinity...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911820/map4-regulated-dynein-dependent-trafficking-of-btn3a1-controls-the-tbk1-irf3-signaling-axis
#7
Minji Seo, Seong-Ok Lee, Ji-Hoon Kim, Yujin Hong, Seongchan Kim, Yeumin Kim, Dal-Hee Min, Young-Yun Kong, Jinwook Shin, Kwangseog Ahn
The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27902332/inhibition-of-hepatitis-b-virus-replication-by-activation-of-the-cgas-sting-pathway
#8
Jing He, Ruidong Hao, Dan Liu, Xing Liu, Shaoshuai Wu, Shuting Guo, Yuan Wang, Deyin Guo
Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyzes synthesis of the second messenger cGAMP, which activates the downstream signaling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, we showed that the replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP...
October 31, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27895620/excessive-cytosolic-dna-fragments-as-a-potential-trigger-of-graves-disease-an-encrypted-message-sent-by-animal-models
#9
REVIEW
Yuqian Luo, Aya Yoshihara, Kenzaburo Oda, Yuko Ishido, Koichi Suzuki
Graves' hyperthyroidism is caused by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves' hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance breakdown that lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs). "Shimojo's model" was the first successful Graves' animal model, wherein immunization with fibroblasts cells expressing TSHR and a major histocompatibility complex (MHC) class II molecule, but not either alone, induced TSAb production in AKR/N (H-2(k)) mice...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27895165/rats-with-a-missense-mutation-in-atm-display-neuroinflammation-and-neurodegeneration-subsequent-to-accumulation-of-cytosolic-dna-following-unrepaired-dna-damage
#10
Hazel Quek, John Luff, KaGeen Cheung, Sergei Kozlov, Magtouf Gatei, C Soon Lee, Mark C Bellingham, Peter G Noakes, Yi Chieh Lim, Nigel L Barnett, Steven Dingwall, Ernst Wolvetang, Tomoji Mashimo, Tara L Roberts, Martin F Lavin
Mutations in the ataxia-telangiectasia (A-T)-mutated (ATM) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes...
November 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27894252/transcriptome-analysis-reveals-the-genetic-basis-underlying-the-seasonal-development-of-keratinized-nuptial-spines-in-leptobrachium-boringii
#11
Wei Zhang, Yue Guo, Jun Li, Li Huang, Eric Gilbert Kazitsa, Hua Wu
BACKGROUND: The expression of sexually selected traits often varies with populations' breeding cycles in many animals. The elucidation of mechanisms underlying the expression of such traits is a research topic in evolutionary biology; however, the genetic basis of the seasonal development of their expression remains unknown. Male Leptobrachium boringii develop keratinized nuptial spines on their upper jaw during the breeding season that fall off when the breeding season ends. To illuminate the genetic basis for the expression of this trait and its seasonal development, we assessed the de novo transcriptome for L...
November 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27889618/cell-death-mechanistic-study-of-photodynamic-therapy-against-breast-cancer-cells-utilizing-liposomal-delivery-of-5-10-15-20-tetrakis-benzo-b-thiophene-porphyrin
#12
Geewoo Nam, Sabarinathan Rangasamy, Hee Ju, Annie Agnes Suganya Samson, Joon Myong Song
5,10,15,20-Tetrakis(benzo[b]thiophene) porphyrin (BTP) is a newly synthesized hydrophobic photosensitizer with fluorescence quantum yield in toluene: ΦF=0.062. Previously, its limitations in solubility had hindered scientific experimentation regarding its photodynamic effects on cancer cells. By utilizing various compositions of liposomes in order to alter the solubility of BTP, the photocytotoxicity, reactive oxygen species generation, and subcellular localization of the liposomal BTP were identified in this work...
November 12, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27889408/an-rna-based-fluorescent-biosensor-for-high-throughput-analysis-of-the-cgas-cgamp-sting-pathway
#13
Debojit Bose, Yichi Su, Assaf Marcus, David H Raulet, Ming C Hammond
In mammalian cells, the second messenger (2'-5',3'-5') cyclic guanosine monophosphate-adenosine monophosphate (2',3'-cGAMP), is produced by the cytosolic DNA sensor cGAMP synthase (cGAS), and subsequently bound by the stimulator of interferon genes (STING) to trigger interferon response. Thus, the cGAS-cGAMP-STING pathway plays a critical role in pathogen detection, as well as pathophysiological conditions including cancer and autoimmune disorders. However, studying and targeting this immune signaling pathway has been challenging due to the absence of tools for high-throughput analysis...
November 18, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27888074/toxoplasma-gondii-immune-mapped-protein-1-is-anchored-to-the-inner-leaflet-of-the-plasma-membrane-and-adopts-a-novel-protein-fold
#14
Yonggen Jia, Stefi Benjamin, Qun Liu, Yingqi Xu, Sunil Kumar Dogga, Jing Liu, Stephen Matthews, Dominique Soldati-Favre
The immune mapped protein 1 (IMP1) was first identified as a protective antigen in Eimeria maxima and described as vaccine candidate and invasion factor in Toxoplasma gondii. We show here that TgIMP1 localizes to the inner leaflet of plasma membrane (PM) via dual acylation. Mutations either in the N-terminal myristoylation or palmitoylation sites (G2 and C5) cause relocalization of TgIMP1 to the cytosol. The first 11 amino acids are sufficient for PM targeting and the presence of lysine (K7) is critical. Disruption of TgIMP1 gene by double homologous recombination revealed no invasion defect or any measurable alteration in the lytic cycle of tachyzoites...
November 22, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27857057/in-vitro-exploration-of-a-myeloid-derived-suppressor-cell-line-as-vehicle-for-cancer-gene-therapy
#15
S Denies, F Combes, C Ghekiere, S Mc Cafferty, L Cicchelero, N N Sanders
Recent research indicates that cell-mediated gene therapy can be an interesting method to obtain intratumoral expression of therapeutic proteins. This paper explores the possibility of using transfected myeloid-derived suppressor cells (MDSCs), derived from a murine cell line, as cellular vehicles for transporting plasmid DNA (pDNA) encoding interleukin-12 (IL-12) to tumors. Transfecting these cells via electroporation caused massive cell death. This was not due to electroporation-induced cell damage, but was mainly the result of the intracellular presence of plasmids...
November 18, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27836664/a-newly-identified-rab-gdi-paralogue-has-a-role-in-neural-development-in-amphibia
#16
Liliya Nazlamova, Anna Noble, Frank R Schubert, John McGeehan, Fiona Myers, Matt Guille, Garry Scarlett
Vesicle shuttling is critical for many cellular and organismal processes, including embryonic development. GDI proteins contribute to vesicle shuttling by regulating the activity of Rab GTPases, controlling their cycling between the inactive cytosol and active membrane bound states. While identifying genes controlled by A-form DNA sequences we discovered a previously unknown member of the GDI family, GDI3. The GDI3 gene is found only in amphibians and fish and is developmentally expressed in Xenopus from neurula stages onwards in the neural plate, and subsequently in both dorsal and anterior structures...
November 9, 2016: Gene
https://www.readbyqxmd.com/read/27832807/sex-specific-variation-in-signaling-pathways-and-gene-expression-patterns-in-human-leukocytes-in-response-to-endotoxin-and-exercise
#17
Asghar Abbasi, Rodolfo de Paula Vieira, Felix Bischof, Michael Walter, Masoud Movassaghi, Nicole C Berchtold, Andreas M Niess, Carl W Cotman, Hinnak Northoff
BACKGROUND: While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. METHODS: We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study...
November 10, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27830677/-the-application-of-yeast-hybrid-systems-in-protein-interaction-analysis
#18
Z-X Zhu, Z-M Yu, J L Taylor, Y-H Wu, J Ni
Yeast hybrid systems have been widely used due to their convenience and low cost. Based on these systems, many methods have been developed to analyze protein-protein, protein-DNA and protein-RNA interactions. In this paper, we are reviewing these different yeast hybrid systems. According to the number of hybrid proteins, yeast hybrid systems can be divided into three categories, yeast one-hybrid, yeast two-hybrid and yeast three-hybrid systems. Alternatively, yeast hybrid systems can be categorized according to the subcellular localization of the protein interaction process in the cell into nuclear protein-protein interactions, cytosol protein-protein interactions and membrane protein-protein interactions...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27829973/common-functions-of-the-chloroplast-and-mitochondrial-co-chaperones-cpdnajl-cdf1-and-mtdnaj-pam16-in-protein-import-and-ros-scavenging-in-arabidopsis-thaliana
#19
REVIEW
John Gray, Sachin Rustgi, Diter von Wettstein, Christiane Reinbothe, Steffen Reinbothe
As semi-autonomous cell organelles that contain only limited coding information in their own DNA, chloroplasts and mitochondria must import the vast majority of their protein constituents from the cytosol. Respective protein import machineries have been identified that mediate the uptake of chloroplast and mitochondrial proteins and interact with molecular chaperones of the HEAT-SHOCK PROTEIN (HSP) 70 family operating as import motors. Recent work identified unexpected new functions of 2 DnaJ co-chaperones in mitochondrial and chloroplast protein translocation and suggest a common mechanism of reactive oxygen species (ROS) scavenging that shall be discussed here...
2016: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/27829146/absence-of-non-histone-protein-complexes-at-natural-chromosomal-pause-sites-results-in-reduced-replication-pausing-in-aging-yeast-cells
#20
Marleny Cabral, Xin Cheng, Sukhwinder Singh, Andreas S Ivessa
There is substantial evidence that genomic instability increases during aging. Replication pausing (and stalling) at difficult-to-replicate chromosomal sites may induce genomic instability. Interestingly, in aging yeast cells, we observed reduced replication pausing at various natural replication pause sites (RPSs) in ribosomal DNA (rDNA) and non-rDNA locations (e.g., silent replication origins and tRNA genes). The reduced pausing occurs independent of the DNA helicase Rrm3p, which facilitates replication past these non-histone protein-complex-bound RPSs, and is independent of the deacetylase Sir2p...
November 8, 2016: Cell Reports
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