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https://www.readbyqxmd.com/read/28222432/extracellular-hmgb1-modulates-glutamate-metabolism-associated-with-kainic-acid-induced-epilepsy-like-hyperactivity-in-primary-rat-neural-cells
#1
Yuji Kaneko, Colleen Pappas, Teresita Malapira, Fernando Ĺ Vale, Naoki Tajiri, Cesar V Borlongan
BACKGROUND/AIMS: Neuroinflammatory processes have been implicated in the pathophysiology of seizure/epilepsy. High mobility group box 1 (HMGB1), a non-histone DNA binding protein, behaves like an inflammatory cytokine in response to epileptogenic insults. Kainic acid (KA) is an excitotoxic reagent commonly used to induce epilepsy in rodents. However, the molecular mechanism by which KA-induced HMGB1 affords the initiation of epilepsy, especially the role of extracellular HMGB1 in neurotransmitter expression, remains to be elucidated...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28221135/impaired-respiration-elicits-srrab-dependent-programmed-cell-lysis-and-biofilm-formation-in-staphylococcus-aureus
#2
Ameya A Mashruwala, Adriana Van De Guchte, Jeffrey M Boyd
Biofilms are communities of microorganisms attached to a surface or each other. Biofilm associated cells are the etiologic agents of recurrent Staphylococcus aureus infections. Infected human tissues are hypoxic or anoxic. S. aureus increases biofilm formation in response to hypoxia, but how this occurs is unknown. In the current study we report that oxygen influences biofilm formation in its capacity as a terminal electron acceptor for cellular respiration. Genetic, physiological, or chemical inhibition of respiratory processes elicited increased biofilm formation...
February 21, 2017: ELife
https://www.readbyqxmd.com/read/28219398/interaction-between-hcmv-pul83-and-human-aim2-disrupts-the-activation-of-the-aim2-inflammasome
#3
Yuan Huang, Di Ma, Heyu Huang, Yuanyuan Lu, Yi Liao, Lingling Liu, Xinglou Liu, Feng Fang
BACKGROUND: AIM2, a cytosolic DNA sensor, plays an important role during infection caused by pathogens with double-stranded DNA; however, its role in human cytomegalovirus (HCMV) infection remains unclear. Previously, we showed an increase in AIM2 protein levels during the early stage of HCMV infection and a decrease 24 h post infection. Because HCMV has developed a variety of strategies to evade host immunity, we speculated that this decline might be attributed to a viral immune escape mechanism...
February 20, 2017: Virology Journal
https://www.readbyqxmd.com/read/28219022/rationale-for-stimulator-of-interferon-genes-targeted-cancer-immunotherapy
#4
REVIEW
Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28215579/mitochondrial-dna-maintenance-defects
#5
REVIEW
Ayman W El-Hattab, William J Craigen, Fernando Scaglia
The maintenance of mitochondrial DNA (mtDNA) depends on a number of nuclear gene-encoded proteins including a battery of enzymes forming the replisome needed to synthesize mtDNA. These enzymes need to be in balanced quantities to function properly that is in part achieved by exchanging intramitochondrial contents through mitochondrial fusion. In addition, mtDNA synthesis requires a balanced supply of nucleotides that is achieved by nucleotide recycling inside the mitochondria and import from the cytosol. Mitochondrial DNA maintenance defects (MDMDs) are a group of diseases caused by pathogenic variants in the nuclear genes involved in mtDNA maintenance resulting in impaired mtDNA synthesis leading to quantitative (mtDNA depletion) and qualitative (multiple mtDNA deletions) defects in mtDNA...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213053/nerol-triggers-mitochondrial-dysfunction-and-disruption-via-elevation-of-ca-2-and-ros-in-candida-albicans
#6
Jun Tian, Zhaoqun Lu, Yanzhen Wang, Man Zhang, Xueyan Wang, Xudong Tang, Xue Peng, Hong Zeng
The antifungal activity of Nerol (NEL) against Candida albicans, a pathogenic fungus, has a minimum inhibitory concentration (MIC) of 4.4mM that causes noteworthy candidacidal activity through an apoptosis-like mechanism. Calcium (Ca(2+)) levels and reactive oxygen species (ROS) production, which are the major causes of apoptosis, were determined in C. albicans cells treated with NEL and were found to increase, which related to mitochondrial dysfunction and disruption. A series of characteristic changes of apoptosis caused by NEL, including mitochondrial membrane depolarization, cytochrome c (cyt c) release, and metacaspase activation were examined using a flow cytometer and Western blot...
February 14, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28204840/inhibition-of-the-innate-immune-receptors-for-foreign-dna-sensing-improves-transfection-efficiency-of-gene-electrotransfer-in-melanoma-b16f10-cells
#7
Masa Bosnjak, Urska Kamensek, Gregor Sersa, Danijela Stolfa, Jaka Lavrencak, Maja Cemazar
Gene electrotransfer upregulate DNA pattern recognition receptors or DNA sensors, which are part of the innate immune system. In this study, we tested if addition of the cocktail of innate immune system inhibitors to the cells during gene electrotransfer (GET) can increase transfection efficiency and cell survival. The results indicate that this cocktail can decrease cytosolic DNA sensors expression after GET, and consequently increase cell survival and transfection efficiency in B16 cells, but only in highly metastatic B16F10 subtype...
February 15, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28194029/ifi16-and-cgas-cooperate-in-the-activation-of-sting-during-dna-sensing-in-human-keratinocytes
#8
Jessica F Almine, Craig A J O'Hare, Gillian Dunphy, Ismar R Haga, Rangeetha J Naik, Abdelmadjid Atrih, Dympna J Connolly, Jordan Taylor, Ian R Kelsall, Andrew G Bowie, Philippa M Beard, Leonie Unterholzner
Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28194022/multifaceted-roles-of-trim38-in-innate-immune-and-inflammatory-responses
#9
REVIEW
Ming-Ming Hu, Hong-Bing Shu
The tripartite motif-containing (TRIM) proteins represent the largest E3 ubiquitin ligase family. The multifaceted roles of TRIM38 in innate immunity and inflammation have been intensively investigated in recent years. TRIM38 is essential for cytosolic RNA or DNA sensor-mediated innate immune responses to both RNA and DNA viruses, while negatively regulating TLR3/4- and TNF/IL-1β-triggered inflammatory responses. In these processes, TRIM38 acts as an E3 ubiquitin or SUMO ligase, which targets key cellular signaling components, or as an enzymatic activity-independent regulator...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193315/survivin-protects-fused-cancer-cells-from-massive-cell-death
#10
Mihyang Do, In-Hae Kwak, Ju-Hyun Ahn, In Jeong Lee, Jae-Ho Lee
Tetraploidy, a potential precursor of cancer-associated aneuploidy, is produced either by cell fusion or cytokinesis failure. Here, we used low p53-expressing HeLa cells to address the fate of cancer cells after fusion. We found that massive cell death or growth arrest occurred a few days after fusion. Interestingly, cells with larger nuclei preferentially died after fusion, suggesting that a larger deviation of DNA content is a strong inducer of apoptosis. Notably, a fraction of cells escaped cell death. It turned out that the stability of survivin was increased, and its localization changed preferentially to the cytosol in fused cells...
February 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28191486/rigulation-of-sting-expression-at-the-crossroads-of-viral-rna-and-dna-sensing-pathways
#11
Yiliu Liu, Rongtuan Lin, David Olagnier
The innate immune sensing of pathogens is important for host to mount defensive responses. STING has emerged in recent years as a critical signaling adaptor in the immune response to cytosolic DNA and RNA derived from pathogens. Liu et al. (2016) demonstrate that the RIG-I-dependent RNA sensing signaling induces STING expression via a TNF-α and IFN-α synergy. The up-regulation of STING is vital for 5'pppRNA restriction of HSV, a DNA virus that infects humans and causes herpes, in vitro and in vivo. This study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING...
January 1, 2017: Inflammation and Cell Signaling
https://www.readbyqxmd.com/read/28190385/evidence-of-pkc-binding-and-translocation-to-explain-the-anticancer-mechanism-of-chlorogenic-acid-in-breast-cancer-cells
#12
S J Deka, S Gorai, D Manna, V Trivedi
Chlorogenic acid (CGA) exhibits potentials towards liver, breast and skin cancer. Cancer cells stimulated with CGA exhibits differential expression of transcriptional factors and regulatory molecules but the molecular target of the molecule is not known. Superposition of biophoric elements of CGA with Curcumin gives maximum common substructure score of 0.90. Molecular modeling studies further suggest that CGA fits into the C1b domain of PKC with extensive interaction with residues lining binding site. It binds PKC in a concentration dependent manner with dissociation constant KD, 28...
February 9, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28188292/cytosolic-dna-promotes-signal-transducer-and-activator-of-transcription-3-stat3-phosphorylation-by-tank-binding-kinase-1-tbk1-to-restrain-stat3-activity
#13
Hung-Ching Hsia, Jessica E Hutti, Albert S Baldwin
Cytosolic DNA can elicit beneficial as well as undesirable immune responses. For example, viral or microbial DNA triggers cell-intrinsic immune responses to defend against infections, whereas aberrant cytosolic accumulation of self-DNA results in pathological conditions, such as autoimmunity. Given the importance of these DNA-provoked responses, a better understanding of their molecular mechanisms is needed. Cytosolic DNA engages stimulator of interferon genes (STING) to activate TANK-binding kinase 1 (TBK1), which subsequently phosphorylates the transcription factor interferon regulatory factor 3 (IRF3) to promote interferon expression...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28186168/ifi16-is-required-for-dna-sensing-in-human-macrophages-by-promoting-production-and-function-of-cgamp
#14
K L Jønsson, A Laustsen, C Krapp, K A Skipper, K Thavachelvam, D Hotter, J H Egedal, M Kjolby, P Mohammadi, T Prabakaran, L K Sørensen, C Sun, S B Jensen, C K Holm, R J Lebbink, M Johannsen, M Nyegaard, J G Mikkelsen, F Kirchhoff, S R Paludan, M R Jakobsen
Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition of microbial DNA in macrophages leads to induction of interferons and cytokines through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway is not clear. Here, we show that IFI16 functions in the cGAS-STING pathway on two distinct levels...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28176788/decreased-expression-of-sting-predicts-poor-prognosis-in-patients-with-gastric-cancer
#15
Shushu Song, Peike Peng, Zhaoqing Tang, Junjie Zhao, Weicheng Wu, Haojie Li, Miaomiao Shao, Lili Li, Caiting Yang, Fangfang Duan, Mingming Zhang, Jie Zhang, Hao Wu, Can Li, Xuefei Wang, Hongshan Wang, Yuanyuan Ruan, Jianxin Gu
STING (stimulator of interferon genes) has recently been found to play an important role in host defenses against virus and intracellular bacteria via the regulation of type-I IFN signaling and innate immunity. Chronic infection with Helicobacter pylori is identified as the strongest risk factor for gastric cancer. Thus, we aim to explore the function of STING signaling in the development of gastric cancer. Immunohistochemistry was used to detect STING expression in 217 gastric cancer patients who underwent surgical resection...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28168148/protein-functionalized-dna-nanostructures-as-tools-to-control-transcription-in-zebrafish-embryos
#16
Alessandro Angelin, Olivier Kassel, Sepand Rastegar, Uwe Strähle, Christof M Niemeyer
The unique structure-directing properties of DNA origami nanostructures (DONs) show great potential to specifically manipulate intracellular processes. We report an innovative concept to selectively activate the transcription of a single gene in the developing zebrafish embryo. We reason that engineering a designer transcription factor in which a rigid DON imposes a fixed distance between the DNA-binding domain (DBD) and the transactivation domain (TAD) would allow the selective activation of a gene harboring the same distance between the corresponding transcription factor binding site and the core promoter...
February 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28159519/intracellular-responsive-dual-delivery-by-endosomolytic-polyplexes-carrying-dna-anchored-porous-silicon-nanoparticles
#17
Mohammad-Ali Shahbazi, Patrick Vingadas Almeida, Alexandra Correia, Barbara Herranz-Blanco, Neha Shrestha, Ermei Mäkilä, Jarno Salonen, Jouni Hirvonen, Hélder A Santos
Bioresponsive cytosolic nanobased multidelivery has been emerging as an enormously challenging novel concept due to the intrinsic protective barriers of the cells and hardly controllable performances of nanomaterials. Here, we present a new paradigm to advance nano-in-nano integration technology amenable to create multifunctional nanovehicles showing considerable promise to overcome restrictions of intracellular delivery, solve impediments of endosomal localization and aid effectual tracking of nanoparticles...
February 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28158302/host-cell-interactions-of-outer-membrane-vesicle-associated-virulence-factors-of-enterohemorrhagic-escherichia-coli-o157-intracellular-delivery-trafficking-and-mechanisms-of-cell-injury
#18
Martina Bielaszewska, Christian Rüter, Andreas Bauwens, Lilo Greune, Kevin-André Jarosch, Daniel Steil, Wenlan Zhang, Xiaohua He, Roland Lloubes, Angelika Fruth, Kwang Sik Kim, M Alexander Schmidt, Ulrich Dobrindt, Alexander Mellmann, Helge Karch
Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28157690/variant-peptide-detection-utilizing-mass-spectrometry-laying-the-foundations-for-proteogenomic-identification-and-validation
#19
Lampros Dimitrakopoulos, Ioannis Prassas, Els M J J Berns, John A Foekens, Eleftherios P Diamandis, George S Charames
BACKGROUND: Proteogenomics is an emerging field at the intersection of genomics and proteomics. Many variant peptides corresponding to single nucleotide variations (SNVs) are associated with specific diseases. The aim of this study was to demonstrate the feasibility of proteogenomic-based variant peptide detection in disease models and clinical specimens. METHODS: We sought to detect p53 single amino acid variant (SAAV) peptides in breast cancer tumor samples that have been previously subjected to sequencing analysis...
February 3, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28155600/green-tea-camellia-sinensis-protects-against-arsenic-neurotoxicity-via-antioxidative-mechanism-and-activation-of-superoxide-dismutase-activity
#20
Smarajit Maiti, Nirmallya Acharyya, Tamal K Ghosh, Sk Sajed Ali, Emili Manna, Aarifa Nazmeen, Nirmalya K Sinha
BACKGROUND: Chronic arsenic-exposure even at a low-dose results in the neural impairment and motor/cognitive dysfunction. However, several preventive approaches are made mainly against hepatic/gastrointestinal damages. Only a few investigations postulate therapeutic strategies for neural anomalies. Here, the protective role of Green tea (Camellia sinensis or CS; 10mg/ml aqueous) has been evaluated against arsenic-induced (0.6ppm/100g bw/28 days) cerebral/cerebellar tissue degeneration, oxidative-threats and neurotransmitter deregulation in female rats...
February 1, 2017: Central Nervous System Agents in Medicinal Chemistry
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