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https://www.readbyqxmd.com/read/29791904/the-cgas-sting-pathway-is-important-for-dendritic-cell-activation-but-is-not-essential-to-induce-protective-immunity-against-mycobacterium-tuberculosis-infection
#1
Fabio V Marinho, Sulayman Benmerzoug, Stephanie Rose, Priscila C Campos, João T Marques, André Báfica, Glen Barber, Bernhard Ryffel, Sergio C Oliveira, Valerie F J Quesniaux
Mycobacterium tuberculosis (Mtb) infection remains a major public health concern. The STING (stimulator of interferon genes) pathway contributes to the cytosolic surveillance of host cells. Most studies on the role of STING activation in Mtb infection have focused on macrophages. Moreover, a detailed investigation of the role of STING during Mtb infection in vivo is required. Here, we deciphered the involvement of STING in the activation of dendritic cells (DCs) and the host response to Mtb infection in vivo...
May 23, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29786074/constitutive-interferon-signaling-maintains-critical-threshold-of-mlkl-expression-to-license-necroptosis
#2
Joseph Sarhan, Beiyun C Liu, Hayley I Muendlein, Chi G Weindel, Irina Smirnova, Amy Y Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A Fitzgerald, Alexander Poltorak
Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785755/energy-resolved-mass-spectrometry-of-chlorogenic-acids-and-its-application-to-isomer-quantification-by-direct-infusion-tandem-mass-spectrometry
#3
Javier Hernandez, Anja Müller, Rakesh Jaiswal, Juan Z Davalos, Nikolai Kuhnert
INTRODUCTION: With the advent of high-perfomance liquid chromatography (HPLC)-tandem mass spectrometry (MS) using ion trap mass analysers it is possible to acquire unambigious structural information in particular with respect to aspects of regiochemistry and stereochemistry of organic compounds present in complex mixtures such as coffee extracts. However, HPLC-MS methods are resource extensive, laborious and lacking user friendliness. OBJECTIVE: To introduce a simple parameter - the energy threshhold for fragmentation - determined using energy resolved MS and demonstrate its value for the complete structural characterisation and even relative quantification of individual isomeric chlrogenic acids in direct infusion experiments...
May 21, 2018: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/29781188/a-novel-anti-malarial-drug-derivative-inhibits-cyclic-gmp-amp-synthase-in-trex1-deficient-mice
#4
Jie An, Joshua J Woodward, Weinan Lai, Mark Minie, Xizhang Sun, Lena Tanaka, Jessica M Snyder, Tomikazu Sasaki, Keith B Elkon
OBJECTIVE: Type I interferon (IFN-I) is strongly implicated in the pathogenesis of Systemic Lupus Erythematosus (SLE) as well as rare monogenic 'interferonopathies' such as Aicardi-Goutieres Syndrome (AGS) caused by mutations in the DNA exonuclease, TREX1. The DNA-activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS), is linked to subsets of AGS and lupus. We identified inhibitors of DNA-cGAS interaction and tested lead candidate, X6, in a mouse model of AGS. METHODS: Trex1-/- mice were treated orally from birth with either X6 or HCQ for 8 weeks...
May 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29777215/mn-potentiates-cgas
#5
Ioana Visan
No abstract text is available yet for this article.
June 2018: Nature Immunology
https://www.readbyqxmd.com/read/29770905/congenital-grouped-albinotic-spots-of-the-retinal-pigment-epithelium-in-a-patient-with-hemihypertrophy-and-caf%C3%A3-au-lait-spots
#6
Eugenia C White, Jesse D Sengillo, Galaxy Y Cho, Mathieu F Bakhoum, Stephen H Tsang
PURPOSE: To describe the finding of circularly grouped hypomelanotic spots in the central macula of a patient with syndromic characteristics. METHODS: Case report of a patient with albinotic spots grouped within the macula, café au lait spots, and left-sided hemihypertrophy. RESULTS: A 15-year-old boy presented with hypomelanotic spots which were hyperautofluorescent on fundus autofluorescence imaging with no disruption of the retinal laminae or photoreceptor inner and outer segment (IS/OS) junction on spectral domain optical coherence tomography...
May 16, 2018: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/29769349/hiv-1-activation-of-innate-immunity-depends-strongly-on-the-intracellular-level-of-trex1-and-sensing-of-incomplete-reverse-transcription-products
#7
Swati Kumar, James H Morrison, David Dingli, Eric Poeschla
TREX1 has been reported to degrade cytosolic immune-stimulatory DNA, including viral DNA generated during HIV-1 infection, but the dynamic range of its capacity to suppress innate immune stimulation is unknown and its full role in the viral life cycle remains unclear. A main purpose of our study was to determine how the intracellular level of TREX1 affects HIV-1 activation and avoidance of innate immunity. Using stable over-expression and CRISPR-mediated gene disruption, we engineered a range of TREX1 levels in human THP-1 monocytes...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29765781/bactericidal-and-cytotoxic-activities-of-polyphenol-extracts-from-solanum-tuberosum-spp-tuberosum-and-spp-andigena-cultivars-on-escherichia-coli-and-human-neuroblastoma-sh-sy5y-cells-in-vitro
#8
María Ximena Silveyra, María Luciana Lanteri, Rocío Belén Damiano, Adriana Balbina Andreu
Potatoes ( Solanum tuberosum L.) are a good source of dietary antioxidant polyphenols. This study investigated the potential antioxidant, bactericidal, and cytotoxic activities in vitro of the phenolic compounds present in tubers of one S. tuberosum spp. tuberosum (Summerside), and three S. tuberosum spp. andigena (landraces Moradita, Waicha, and Santa María) cultivars. Both the content of phenolic acids, chlorogenic acids (CGAs) being the most abundant, and the antioxidant activity were higher in extracts from skin than from flesh...
2018: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/29760876/rinck-mediated-monoubiquitination-of-cgas-promotes-antiviral-innate-immune-responses
#9
Zhao-Shan Liu, Zi-Yu Zhang, Hong Cai, Ming Zhao, Jie Mao, Jiang Dai, Tian Xia, Xue-Min Zhang, Tao Li
Background: As an important danger signal, the presence of DNA in cytoplasm triggers potent immune responses. Cyclic GMP-AMP synthase (cGAS) is a recently characterized key sensor for cytoplasmic DNA. The engagement of cGAS with DNA leads to the synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which binds and activates the downstream adaptor protein STING to promote type I interferon production. Although cGAS has been shown to play a pivotal role in innate immunity, the exact regulation of cGAS activation is not fully understood...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29743941/cost-effectiveness-of-dialectical-behaviour-therapy-vs-enhanced-usual-care-in-the-treatment-of-adolescents-with-self-harm
#10
Egil Haga, Eline Aas, Berit Grøholt, Anita J Tørmoen, Lars Mehlum
Background: Studies have shown that dialectical behaviour therapy (DBT) is effective in reducing self-harm in adults and adolescents. Aims: To evaluate the cost-effectiveness of DBT for adolescents (DBT-A) compared to enhanced usual care (EUC). Methods: In a randomised study, 77 adolescents with repeated self-harm were allocated to 19 weeks of outpatient treatment, either DBT-A ( n  = 39) or EUC ( n  = 38). Cost-effective analyses, including estimation of incremental cost-effectiveness ratios, were conducted with self-harm and global functioning (CGAS) as health outcomes...
2018: Child and Adolescent Psychiatry and Mental Health
https://www.readbyqxmd.com/read/29731412/comparison-of-effectiveness-and-cost-effectiveness-of-an-intensive-community-supported-discharge-service-versus-treatment-as-usual-for-adolescents-with-psychiatric-emergencies-a-randomised-controlled-trial
#11
Dennis Ougrin, Richard Corrigall, Jason Poole, Toby Zundel, Mandy Sarhane, Victoria Slater, Daniel Stahl, Paula Reavey, Sarah Byford, Margaret Heslin, John Ivens, Maarten Crommelin, Zahra Abdulla, Daniel Hayes, Kerry Middleton, Benita Nnadi, Eric Taylor
BACKGROUND: Intensive community treatment to reduce dependency on adolescent psychiatric inpatient care is recommended in guidelines but has not been assessed in a randomised controlled trial in the UK. We designed a supported discharge service (SDS) provided by an intensive community treatment team and compared outcomes with usual care. METHODS: Eligible patients for this randomised controlled trial were younger than 18 years and had been admitted for psychiatric inpatient care in the South London and Maudsley NHS Foundation Trust...
May 3, 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29707036/effect-of-chlorogenic-acid-intake-on-cognitive-function-in-the-elderly-a-pilot-study
#12
Morimasa Kato, Ryuji Ochiai, Kazuya Kozuma, Hirotaka Sato, Yoshihisa Katsuragi
Objective: To evaluate the effect of chlorogenic acids (CGAs) intake on cognitive function. Methods: In this pilot study, the Cogstate and CNS Vital Signs test batteries were used to evaluate cognitive function in 8 healthy elderly men and women complaining of subjective memory loss after a 6-month intake of a test beverage containing 330 mg of CGAs just before bedtime. Results: After a 6-month CGA intake period, significant improvement was observed in the One Back Test of the Cogstate, the Shifting Attention Test, and Finger Tapping Test as well as in the composite memory, verbal memory, complex attention, cognitive flexibility, executive function, and motor speed domains of the CNS Vital Signs test battery...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29698400/the-complex-association-between-the-antioxidant-defense-system-and-clinical-status-in-early-psychosis
#13
Saínza García, Susana Alberich, Mónica Martínez-Cengotitabengoa, Celso Arango, Josefina Castro-Fornieles, Mara Parellada, Inmaculada Baeza, Carmen Moreno, Juan Antonio Micó, Esther Berrocoso, Montserrat Graell, Soraya Otero, Tatiana Simal, Ana González-Pinto
Oxidative stress is a pathophysiological mechanism potentially involved in psychiatric disorders. The objective of this study was to assess the relationship between total antioxidant status (TAS) and the functional status of patients with a first episode of psychosis at the onset of the disease. For this purpose, a sample of 70 patients aged between 9 and 17 years with a first episode of psychosis were followed up for a period of two years. Blood samples were drawn to measure TAS levels at three time points: at baseline, at one year, and at two years...
2018: PloS One
https://www.readbyqxmd.com/read/29694889/pro-inflammation-associated-with-a-gain-of-function-mutation-r284s-in-the-innate-immune-sensor-sting
#14
Hiroyasu Konno, Ivan K Chinn, Diana Hong, Jordan S Orange, James R Lupski, Alejandra Mendoza, Luis A Pedroza, Glen N Barber
The cellular sensor stimulator of interferon genes (STING) initiates type I interferon (IFN) and cytokine production following association with cyclic dinucleotides (CDNs) generated from intracellular bacteria or via a cellular synthase, cGAS, after binding microbial or self-DNA. Although essential for protecting the host against infection, unscheduled STING signaling is now known to be responsible for a variety of autoinflammatory disorders. Here, we report a gain-of-function mutation in STING (R284S), isolated from a patient who did not require CDNs to augment activity and who manifested a constitutively active phenotype...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29690626/effects-of-chlorogenic-acid-enriched-and-hydroxyhydroquinone-reduced-coffee-on-postprandial-fat-oxidation-and-antioxidative-capacity-in-healthy-men-a-randomized-double-blind-placebo-controlled-crossover-trial
#15
Shun Katada, Takuya Watanabe, Tomohito Mizuno, Shinichi Kobayashi, Masao Takeshita, Noriko Osaki, Shigeru Kobayashi, Yoshihisa Katsuragi
Chlorogenic acids (CGAs) reduce blood pressure and body fat, and enhance fat metabolism. In roasted coffee, CGAs exist together with the oxidant component hydroxyhydroquinone (HHQ). HHQ counteracts the antihypertensive effects of CGA, but its effects on CGA-induced fat oxidation (FOX) are unknown. Here we assessed the effects of CGA-enriched and HHQ-reduced coffee on FOX. Fifteen healthy male volunteers (age: 38 ± 8 years (mean ± SD); BMI: 22.4 ± 1.5 kg/m²) participated in this crossover study...
April 23, 2018: Nutrients
https://www.readbyqxmd.com/read/29686682/targeting-cytosolic-nucleic-acid-sensing-pathways-for-cancer-immunotherapies
#16
REVIEW
Sandra Iurescia, Daniela Fioretti, Monica Rinaldi
The innate immune system provides the first line of defense against pathogen infection though also influences pathways involved in cancer immunosurveillance. The innate immune system relies on a limited set of germ line-encoded sensors termed pattern recognition receptors (PRRs), signaling proteins and immune response factors. Cytosolic receptors mediate recognition of danger damage-associated molecular patterns (DAMPs) signals. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29679386/hepatitis-b-virus-evasion-from-cgas-sensing-in-human-hepatocytes
#17
Eloi R Verrier, Seung-Ae Yim, Laura Heydmann, Houssein El Saghire, Charlotte Bach, Vincent Turon-Lagot, Laurent Mailly, Sarah C Durand, Julie Lucifora, David Durantel, Patrick Pessaux, Nicolas Manel, Ivan Hirsch, Mirjam B Zeisel, Nathalie Pochet, Catherine Schuster, Thomas F Baumert
Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV infection are still poorly understood. Recently, the cyclic GMP-AMP synthase (cGAS) was identified as a DNA sensor. In this study, we aimed to investigate the functional role of cGAS in sensing of HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss- and gain-of-function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes and HBV-infected human liver chimeric mice...
April 20, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29678065/making-the-care-comprehensive-geriatric-assessment-as-the-core-of-a-total-mobile-long-term-care-support-system-in-china
#18
Yanyan Cui, Dongwei Gong, Bo Yang, Hua Chen, Ming-Hsiang Tu, Chaonan Zhang, Huan Li, Naiwen Liang, Liping Jiang, Polun Chang
Comprehensive Geriatric Assessments (CGAs) have been recommended to be used for better monitoring the health status of elder residents and providing quality care. This study reported how our nurses perceived the usability of CGA component of a mobile integrated-care long term care support system developed in China. We used the Continuity Assessment Record and Evaluation (CARE), developed in the US, as the core CGA component of our Android-based support system, in which apps were designed for all key stakeholders for delivering quality long term care...
2018: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/29670289/samhd1-acts-at-stalled-replication-forks-to-prevent-interferon-induction
#19
Flavie Coquel, Maria-Joao Silva, Hervé Técher, Karina Zadorozhny, Sushma Sharma, Jadwiga Nieminuszczy, Clément Mettling, Elodie Dardillac, Antoine Barthe, Anne-Lyne Schmitz, Alexy Promonet, Alexandra Cribier, Amélie Sarrazin, Wojciech Niedzwiedz, Bernard Lopez, Vincenzo Costanzo, Lumir Krejci, Andrei Chabes, Monsef Benkirane, Yea-Lih Lin, Philippe Pasero
SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29662124/stag2-deficiency-induces-interferon-responses-via-cgas-sting-pathway-and-restricts-virus-infection
#20
Siyuan Ding, Jonathan Diep, Ningguo Feng, Lili Ren, Bin Li, Yaw Shin Ooi, Xin Wang, Kevin F Brulois, Linda L Yasukawa, Xingnan Li, Calvin J Kuo, David A Solomon, Jan E Carette, Harry B Greenberg
Cohesin is a multi-subunit nuclear protein complex that coordinates sister chromatid separation during cell division. Highly frequent somatic mutations in genes encoding core cohesin subunits have been reported in multiple cancer types. Here, using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, we demonstrate that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids...
April 16, 2018: Nature Communications
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