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https://www.readbyqxmd.com/read/28490590/the-c-terminus-of-the-herpes-simplex-virus-pul25-protein-is-required-for-release-of-viral-genomes-from-capsids-bound-to-nuclear-pores
#1
Jamie B Huffman, Gina R Daniel, Erik Falck-Pedersen, Alexis Huet, Greg A Smith, James F Conway, Fred L Homa
The herpes simplex virus (HSV) capsid is released into the cytoplasm after fusion of viral and host membranes, whereupon dynein-dependent trafficking along microtubules targets it to the nuclear envelope. Binding of the capsid to the nuclear pore complex (NPC) is mediated by the capsid protein pUL25 and the capsid-tethered tegument protein pUL36. Temperature-sensitive mutants in both pUL25 and pUL36 dock at the NPC but fail to release DNA. The uncoating reaction has been difficult to study due to the rapid release of the genome once the capsid interacts with the nuclear pore...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28464228/rumination-event-centrality-and-perceived-control-as-predictors-of-post-traumatic-growth-and-distress-the-cognitive-growth-and-stress-model
#2
Matthew Brooks, Nicola Graham-Kevan, Michelle Lowe, Sarita Robinson
OBJECTIVES: The Cognitive Growth and Stress (CGAS) model draws together cognitive processing factors previously untested into a single model. Intrusive rumination, deliberate rumination, present and future perceptions of control, and event centrality were assessed as predictors of post-traumatic growth (PTG) and post-traumatic stress (PTS). METHOD: The CGAS model is tested on a sample of survivors (N = 250) of a diverse range of adverse events using structural equation modelling techniques...
May 2, 2017: British Journal of Clinical Psychology
https://www.readbyqxmd.com/read/28460908/gc-ms-method-to-quantify-bioavailable-phenolic-compounds-and-antioxidant-capacity-determination-of-plasma-after-acute-coffee-consumption-in-human-volunteers
#3
Oscar Javier Lara-Guzmán, Rafael Álvarez-Quintero, Edison Osorio, Mauricio Naranjo-Cano, Katalina Muñoz-Durango
Coffee, a source of chlorogenic acids (CGAs), is recognized for preventing chronic diseases associated with oxidative stress. Therefore, sensitive, selective and easy access methods for the determination of the bioavailability and antioxidant function in vivo are required in clinical studies. The aim of this work was to validate a GC/MS method to quantify caffeic acid (CA) and ferulic acid (FA) and to apply different methodologies to determine the antioxidant capacity of plasma after the acute consumption of 420mg of CGAs provided by 400mL of coffee...
November 2016: Food Research International
https://www.readbyqxmd.com/read/28446670/collateral-damage-during-dengue-virus-infection-making-sense-of-dna-by-cgas
#4
Sebastian Aguirre, Ana Fernandez-Sesma
Early sensing of viral components or infection-induced tissue damage, is a prerequisite for the successful control of pathogenic viruses by the host innate immune system. Recent results from our laboratory show how immune cells use the DNA sensing machinery to detect intracellular damage generated early during infection with an RNA virus, namely dengue virus (DENV). Conversely, we found that DENV can efficiently dismantle this sensing mechanism by targeting the cyclic GMP-AMP synthase (cGAS) and the stimulator of interferon gene (STING); two crucial host factors involved in DNA detection and type I interferon (IFN) production...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28443016/genetics-of-aggression-in-alzheimer-s-disease-ad
#5
Walter J Lukiw, Evgeny I Rogaev
Alzheimer's disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28430817/kaposi-sarcoma-herpesvirus-kshv-latency-associated-nuclear-antigen-lana-recruits-components-of-the-mrn-mre11-rad50-nbs1-repair-complex-to-modulate-an-innate-immune-signaling-pathway-and-viral-latency
#6
Giuseppe Mariggiò, Sandra Koch, Guigen Zhang, Magdalena Weidner-Glunde, Jessica Rückert, Semra Kati, Susann Santag, Thomas F Schulz
Kaposi Sarcoma Herpesvirus (KSHV), a γ2-herpesvirus and class 1 carcinogen, is responsible for at least three human malignancies: Kaposi Sarcoma (KS), Primary Effusion Lymphoma (PEL) and Multicentric Castleman's Disease (MCD). Its major nuclear latency protein, LANA, is indispensable for the maintenance and replication of latent viral DNA in infected cells. Although LANA is mainly a nuclear protein, cytoplasmic isoforms of LANA exist and can act as antagonists of the cytoplasmic DNA sensor, cGAS. Here, we show that cytosolic LANA also recruits members of the MRN (Mre11-Rad50-NBS1) repair complex in the cytosol and thereby inhibits their recently reported role in the sensing of cytoplasmic DNA and activation of the NF-κB pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28422568/cgas-sting-tbk1-irf3-7-induced-interferon-%C3%AE-contributes-to-the-clearing-of-non-tuberculous-mycobacterial-infection-in-mice
#7
Nanthapon Ruangkiattikul, Andreas Nerlich, Ketema Abdissa, Stefan Lienenklaus, Abdulhadi Suwandi, Nina Janze, Kristin Laarmann, Julia Spanier, Ulrich Kalinke, Siegfried Weiss, Ralph Goethe
Type I interferons (IFN-I), such as IFN-α and IFN-β are important messengers in the host response against bacterial infections. Knowledge about the role of IFN-I in infections by nontuberculous mycobacteria (NTM) is limited. Here we show that macrophages infected with pathogens of the Mycobacterium avium complex produced significantly lower amounts of IFN-β than macrophages infected with the opportunistic pathogen M. smegmatis. To dissect the molecular mechanisms of this phenomenon, we focused on the obligate pathogen Mycobacterium avium ssp paratuberculosis (MAP) and the opportunistic M...
April 19, 2017: Virulence
https://www.readbyqxmd.com/read/28416447/evolutionary-origins-of-cgas-sting-signaling
#8
REVIEW
Shally R Margolis, Stephen C Wilson, Russell E Vance
Detection of foreign nucleic acids is an important strategy for innate immune recognition of pathogens. In vertebrates, pathogen-derived DNA is sensed in the cytosol by cGAS, which produces the cyclic dinucleotide (CDN) second messenger cGAMP to activate the signaling adaptor STING. While induction of antiviral type I interferons (IFNs) is the major outcome of STING activation in vertebrates, it has recently become clear that core components of the cGAS-STING pathway evolved more than 600 million years ago, predating the evolution of type I IFNs...
April 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28412547/intracellular-dna-sensing-pathway-of-cgas-cgamp-is-decreased-in-human-newborns-and-young-children
#9
Zhan-Sheng Wang, Yu-Lu Liu, Nan Mi, Dao-Yun Duan
Newborns are highly susceptible to DNA virus infections, which may result from the characteristics of neonatal innate immune systems. Here we analyzed for the first time the development of innate immune sensing and signaling of intracellular DNA virus infection in human newborns and young children. Both mRNA and protein expression of cGAS, an intracellular DNA sensor, were shown to be significantly reduced in neonatal peripheral blood mononuclear cells (PBMCs). In addition, cGAS expression in neonatal PBMCs could be induced upon herpes simplex virus type 1 (HSV-1) or interferon-α (IFNα) stimulation...
April 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28399655/cyclic-gmp-amp-as-an-endogenous-second-messenger-in-innate-immune-signaling-by-cytosolic-dna
#10
Kazuki Kato, Hiroki Omura, Ryuichiro Ishitani, Osamu Nureki
The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/ STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclicGMP-AMP(2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3)...
April 7, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28391515/the-potential-effects-of-chlorogenic-acid-the-main-phenolic-components-in-coffee-on-health-a-comprehensive-review-of-the-literature
#11
REVIEW
Narges Tajik, Mahboubeh Tajik, Isabelle Mack, Paul Enck
Chlorogenic acid (CGA), an important biologically active dietary polyphenol, is produced by certain plant species and is a major component of coffee. Reduction in the risk of a variety of diseases following CGA consumption has been mentioned in recent basic and clinical research studies. This systematic review discusses in vivo animal and human studies of the physiological and biochemical effects of chlorogenic acids (CGAs) on biomarkers of chronic disease. We searched PubMed, Embase, Amed and Scopus using the following search terms: ("chlorogenic acid" OR "green coffee bean extract") AND (human OR animal) (last performed on April 1st, 2015) for relevant literature on the in vivo effects of CGAs in animal and human models, including clinical trials on cardiovascular, metabolic, cancerogenic, neurological and other functions...
April 8, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28377530/topoisomerase-ii-inhibitors-induce-dna-damage-dependent-interferon-responses-circumventing-ebola-virus-immune-evasion
#12
Priya Luthra, Sebastian Aguirre, Benjamin C Yen, Colette A Pietzsch, Maria T Sanchez-Aparicio, Bersabeh Tigabu, Lorraine K Morlock, Adolfo García-Sastre, Daisy W Leung, Noelle S Williams, Ana Fernandez-Sesma, Alexander Bukreyev, Christopher F Basler
Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28363908/nonspecific-dna-binding-of-cgas-n-terminus-promotes-cgas-activation
#13
Jianli Tao, Xiao-Wei Zhang, Jianshi Jin, Xiao-Xia Du, Tengfei Lian, Jing Yang, Xiang Zhou, Zhengfan Jiang, Xiao-Dong Su
The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) mediates innate immune responses against invading pathogens, or against self-dsDNA, which causes autoimmune disorders. Upon nonspecific binding of cytosolic B-form DNA, cGAS synthesizes the second messenger 2'3'-cGAMP and triggers STING-dependent signaling to produce type I IFNs. The cGAS comprises less-conserved N-terminal residues and highly conserved nucleotidyltransferase/Mab21 domains. The function and structure of the well-conserved domains have been extensively studied, whereas the physiological function of the N-terminal domain of cGAS is largely uncharacterized...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28351933/cytosolic-dna-sensor-initiated-innate-immune-responses-in-mouse-ovarian-granulosa-cells
#14
Keqin Yan, Dingqing Feng, Jing Liang, Qing Wang, Lin Deng, Xiao Zhang, Bin Ling, Daishu Han
Viral infections of the ovary may perturb ovarian functions. However, the mechanisms underlying innate immune responses in the ovary are poorly understood. The present study demonstrates that cytosolic viral DNA sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. The cytosolic DNA sensors p204 and cGAS and their common signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in granulosa cells. Transfection with VACV70, a synthetic vaccinia virus (VACV) DNA analogue, induced the expression of type I interferons (IFNA/B) and major inflammatory cytokines (TNFA and IL6) through IRF3 and NF-κB activation, respectively...
March 28, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28346454/viral-pathogenesis-dengue-virus-takes-on-cgas
#15
Michiel van Gent, Michaela U Gack
No abstract text is available yet for this article.
March 27, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28346446/dengue-virus-ns2b-protein-targets-cgas-for-degradation-and-prevents-mitochondrial-dna-sensing-during-infection
#16
Sebastian Aguirre, Priya Luthra, Maria T Sanchez-Aparicio, Ana M Maestre, Jenish Patel, Francise Lamothe, Anthony C Fredericks, Shashank Tripathi, Tongtong Zhu, Jessica Pintado-Silva, Laurence G Webb, Dabeiba Bernal-Rubio, Alexander Solovyov, Benjamin Greenbaum, Viviana Simon, Christopher F Basler, Lubbertus C F Mulder, Adolfo García-Sastre, Ana Fernandez-Sesma
During the last few decades, the global incidence of dengue virus (DENV) has increased dramatically, and it is now endemic in more than 100 countries. To establish a productive infection in humans, DENV uses different strategies to inhibit or avoid the host innate immune system. Several DENV proteins have been shown to strategically target crucial components of the type I interferon system. Here, we report that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection...
March 27, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28340600/an-evaluation-of-the-comparative-effectiveness-of-geriatrician-led-comprehensive-geriatric-assessment-for-improving-patient-and-healthcare-system-outcomes-for-older-adults-a-protocol-for-a-systematic-review-and-network-meta-analysis
#17
Charlene Soobiah, Caitlin Daly, Erik Blondal, Joycelyne Ewusie, Joanne Ho, Meghan J Elliott, Rossini Yue, Jayna Holroyd-Leduc, Barbara Liu, Sharon Marr, Jenny Basran, Andrea C Tricco, Jemila Hamid, Sharon E Straus
BACKGROUND: Comprehensive geriatric assessment (CGA) is an integrated model of care involving a geriatrician and an interdisciplinary team and can prioritize and manage complex health needs of older adults with multimorbidity. CGAs differ across healthcare settings, ranging from shared care conducted in primary care settings to specialized inpatient units in acute care. Models of care involving geriatricians vary across healthcare settings, and it is unclear which CGA model is most effective...
March 24, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28329695/cutting-edge-in-ifn-regulation-inflammatory-caspases-cleave-cgas
#18
Simon Heidegger, Tobias Haas, Hendrik Poeck
Caspases have important functions beyond their established role in driving inflammation and apoptosis. In this issue of Immunity, Wang et al. (2017) demonstrate that inflammasome-triggered caspases cleave and inactivate the DNA sensor cGAS, thus restricting the type I interferon response to cytosolic DNA.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28314590/inflammasome-activation-triggers-caspase-1-mediated-cleavage-of-cgas-to-regulate-responses-to-dna-virus-infection
#19
Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc(-/-) and Casp1(-/-) macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28297677/recombinant-bcg-expressing-esx-1-of-mycobacterium-marinum-combines-low-virulence-with-cytosolic-immune-signaling-and-improved-tb-protection
#20
Matthias I Gröschel, Fadel Sayes, Sung Jae Shin, Wafa Frigui, Alexandre Pawlik, Mickael Orgeur, Robin Canetti, Nadine Honoré, Roxane Simeone, Tjip S van der Werf, Wilbert Bitter, Sang-Nae Cho, Laleh Majlessi, Roland Brosch
Recent insights into the mechanisms by which Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is recognized by cytosolic nucleotide sensors have opened new avenues for rational vaccine design. The only licensed anti-tuberculosis vaccine, Mycobacterium bovis BCG, provides limited protection. A feature of BCG is the partial deletion of the ESX-1 type VII secretion system, which governs phagosomal rupture and cytosolic pattern recognition, key intracellular phenotypes linked to increased immune signaling...
March 14, 2017: Cell Reports
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