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https://www.readbyqxmd.com/read/29146021/symptom-dimensions-and-subgroups-in-childhood-onset-schizophrenia
#1
Kirsten E S Craddock, Xueping Zhou, Siyuan Liu, Peter Gochman, Dwight Dickinson, Judith L Rapoport
OBJECTIVE: This study investigated symptom dimensions and subgroups in the National Institute of Mental Health (NIMH) childhood-onset schizophrenia (COS) cohort and their similarities to adult-onset schizophrenia (AOS) literature. METHOD: Scores from the Scales for the Assessment of Positive and Negative Symptoms (SAPS & SANS) from 125 COS patients were assessed for fit with previously established symptom dimensions from AOS literature using confirmatory factor analysis (CFA)...
November 13, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/29142107/is-inflammatory-micronucleation-the-key-to-a-successful-anti-mitotic-cancer-drug
#2
REVIEW
T J Mitchison, J Pineda, J Shi, S Florian
Paclitaxel is a successful anti-cancer drug that kills cancer cells in two-dimensional culture through perturbation of mitosis, but whether it causes tumour regression by anti-mitotic actions is controversial. Drug candidates that specifically target mitosis, including inhibitors of kinesin-5, AurkA, AurkB and Plk1, disappointed in the clinic. Current explanations for this discrepancy include pharmacokinetic differences and hypothetical interphase actions of paclitaxel. Here, we discuss post-mitotic micronucleation as a special activity of taxanes that might explain their higher activity in solid tumours...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29128691/type-i-interferon-mediated-autoinflammation-and-autoimmunity
#3
REVIEW
Stefanie Kretschmer, Min Ae Lee-Kirsch
The monogenic type I interferonopathies comprise a heterogenous group of disorders of the innate immune system associated with constitutive activation of antiviral type I interferon (IFN). Despite a remarkable phenotypic diversity, type I interferonopathies are commonly characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. The elucidation of the underlying genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism against inappropriate immune recognition of self nucleic acids by cytosolic sensors such as cGAS or MDA5 through metabolizing or processing of intracellular DNA or RNA...
November 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29125861/identification-of-hospitalized-elderly-patients-at-risk-for-adverse-in-hospital-outcomes-in-a-university-orthopedics-and-trauma-surgery-environment
#4
Janine Gronewold, Christian Dahlmann, Marcus Jäger, Dirk M Hermann
BACKGROUND: As a consequence of demographic changes, hospitals are confronted with increasing numbers of elderly patients, who are at high risk of adverse events during hospitalization. Geriatric risk screening followed by comprehensive geriatric assessment (CGA) and treatment has been requested by geriatric societies and task forces to identify patients at risk. Since empirical evidence on factors predisposing to adverse hospital events is scarce, we now prospectively evaluated implications of geriatric risk screening followed by CGA in a university hospital department of orthopedics and trauma surgery...
2017: PloS One
https://www.readbyqxmd.com/read/29106411/extrachromosomal-telomere-repeat-dna-is-linked-to-alt-development-via-cgas-sting-dna-sensing-pathway
#5
Yi-An Chen, Yi-Ling Shen, Hsuan-Yu Hsia, Yee-Peng Tiang, Tzu-Ling Sung, Liuh-Yow Chen
Extrachromosomal telomere repeat (ECTR) DNA is unique to cancer cells that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, but the role of ECTRs in ALT development remains elusive. We found that induction of ECTRs in normal human fibroblasts activated the cGAS-STING-TBK1-IRF3 signaling axis to trigger IFNβ production and a type I interferon response, resulting in cell-proliferation defects. In contrast, ALT cancer cells are commonly defective in sensing cytosolic DNA. We found that STING expression was inhibited in ALT cancer cell lines and transformed ALT cells...
November 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29106401/irf3-and-type-i-interferons-fuel-a-fatal-response-to-myocardial-infarction
#6
Kevin R King, Aaron D Aguirre, Yu-Xiang Ye, Yuan Sun, Jason D Roh, Richard P Ng, Rainer H Kohler, Sean P Arlauckas, Yoshiko Iwamoto, Andrej Savol, Ruslan I Sadreyev, Mark Kelly, Timothy P Fitzgibbons, Katherine A Fitzgerald, Timothy Mitchison, Peter Libby, Matthias Nahrendorf, Ralph Weissleder
Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections and cancer, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi-Goutières syndrome and STING-associated vasculopathy of infancy (SAVI). Myocardial infarction (MI) elicits inflammation, but the dominant molecular drivers of MI-associated inflammation remain unclear. Here we show that ischemic cell death and uptake of cell debris by macrophages in the heart fuel a fatal response to MI by activating IRF3 and type I IFN production...
November 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29097162/innate-sensing-and-cell-autonomous-resistance-pathways-in-legionella-pneumophila-infection
#7
REVIEW
Jan Naujoks, Juliane Lippmann, Norbert Suttorp, Bastian Opitz
Legionella pneumophila is a facultative intracellular bacterium which can cause a severe pneumonia called Legionnaires' disease after inhalation of contaminated water droplets and replication in alveolar macrophages. The innate immune system is generally able to sense and -in most cases- control L. pneumophila infection. Comorbidities and genetic risk factors, however, can compromise the immune system and high infection doses might overwhelm its capacity, thereby enabling L. pneumophila to grow and disseminate inside the lung...
October 27, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29074428/identification-and-function-analysis-of-canine-stimulator-of-interferon-gene-sting
#8
Yuxiang Zhang, Mengyan Zhu, Gairu Li, Jie Liu, Xiaofeng Zhai, Ruyi Wang, Junyan Zhang, Gang Xing, Jinyan Gu, Liping Yan, Jing Lei, Haifeng Sun, Zhiyu Shi, Fei Liu, Boli Hu, Shuo Su, Jiyong Zhou
Stimulator of interferon gene (STING) plays an important role in the cyclic GMP-AMP synthase (cGAS)-mediated activation of type I IFN responses. In this study, we identified and cloned canine STING gene. Full-length STING encodes a 375 amino acid product that shares the highest similarity with feline STING. Highest levels of mRNA of canine STING were detected in the spleen and lungs while the lowest levels in the heart and muscle. Analysis of its cellular localization showed that STING is localizes to the endoplasmic reticulum...
October 24, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29056047/daily-intake-of-chlorogenic-acids-from-consumption-of-mat%C3%A3-ilex-paraguariensis-a-st-hil-traditional-beverages
#9
Karimi Sater Gebara, Arquimedes Gasparotto-Junior, Patricia Gonçalves Santiago, Claudia Andrea Lima Cardoso, Lauro Mera de Souza, Christine Morand, Telma Aparecida Costa, Euclides Lara Cardozo-Junior
The main objective of this study was to investigate the daily intake of chlorogenic acids (CGAs) and methylxanthines by consumers of maté traditional beverages (MTBs), terere and chimarrão (Ilex paraguariensis A.St.-Hill). In the studied population (450 citizens from Toledo, PR, Brazil), 63% consume the chimarrão and 37% terere, with weighted mean daily intakes estimated at 648-2160 and 244-746 mL, respectively. For every 100 mL of beverage consumed, the average amount of total phenol compounds extracted was 673...
November 7, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29054471/innate-immunity-and-tolerance-toward-mitochondria
#10
REVIEW
Anthony Rongvaux
Mitochondria are intracellular organelles that originate from a bacterial symbiont, and they retain multiple features of this bacterial ancestry. The immune system evolved to detect the presence of invading pathogens, including bacteria, to eliminate them by a diversity of antimicrobial mechanisms and to mount long-term protective immunity. Due to their bacterial ancestry, mitochondria are sensed by the innate immune system, and trigger inflammatory responses comparable to those induced by pathogenic bacteria...
October 17, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29045895/cgas-micro-manages-genotoxic-stress
#11
Mona Motwani, Katherine A Fitzgerald
Maintenance of genome integrity is essential to prevent cancer. Genotoxic stress drives damaged DNA out of the nucleus by forming micronuclei. Two studies in Nature reveal how the cytosolic DNA sensor cGAS gains access to the cargo within micronuclei to drive type I IFN responses.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29042906/low-mood-in-a-sample-of-5-12-year-old-child-psychiatric-patients-a-cross-sectional-study
#12
Katri Maasalo, Jaana Wessman, Eeva T Aronen
BACKGROUND: Not much is known about low mood and its associates in child psychiatric patients. In this study, we examined the prevalence of low mood, how it associates with disruptive behaviour, and affects clinician-rated global functioning in child psychiatric outpatients. METHODS: The study population consisted of 862 5-12 year-old child psychiatric patients. The study sample was a subsample of all 1251 patients attending a child psychiatric outpatient clinic at Helsinki University Hospital in 2013-2015 formed by excluding 4 year-old and 13 year-old patients and those with missing or incomplete data...
2017: Child and Adolescent Psychiatry and Mental Health
https://www.readbyqxmd.com/read/29033128/the-dna-inflammasome-in-human-myeloid-cells-is-initiated-by-a-sting-cell-death-program-upstream-of-nlrp3
#13
Moritz M Gaidt, Thomas S Ebert, Dhruv Chauhan, Katharina Ramshorn, Francesca Pinci, Sarah Zuber, Fionan O'Duill, Jonathan L Schmid-Burgk, Florian Hoss, Raymund Buhmann, Georg Wittmann, Eicke Latz, Marion Subklewe, Veit Hornung
Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29030458/a-noncanonical-function-of-cgamp-in-inflammasome-priming-and-activation
#14
Karen V Swanson, Robert D Junkins, Cathryn J Kurkjian, Elizabeth Holley-Guthrie, Avani A Pendse, Rachid El Morabiti, Alex Petrucelli, Glen N Barber, Chris A Benedict, Jenny P-Y Ting
Recognition of pathogen-associated molecular patterns and danger-associated molecular patterns by host cells is an important step in innate immune activation. The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon genes (STING) to activate IFN-I. Here we show that cGAMP has a noncanonical function in inflammasome activation in human and mouse cells. Inflammasome activation requires two signals, both of which are activated by cGAMP...
October 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29027233/dysregulated-cellular-functions-and-cell-stress-pathways-provide-critical-cues-for-activating-and-targeting-natural-killer-cells-to-transformed-and-infected-cells
#15
REVIEW
David H Raulet, Assaf Marcus, Laurent Coscoy
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29016854/absence-of-rnase-h2-triggers-generation-of-immunogenic-micronuclei-removed-by-autophagy
#16
Kareen Bartsch, Katharina Knittler, Christopher Borowski, Sönke Rudnik, Markus Damme, Konrad Aden, Martina E Spehlmann, Norbert Frey, Paul Saftig, Athena Chalaris, Björn Rabe
Hypomorphic mutations in the DNA repair enzyme RNase H2 cause the neuroinflammatory autoimmune disorder Aicardi-Goutières syndrome (AGS). Endogenous nucleic acids are believed to accumulate in patient cells and instigate pathogenic type I interferon expression. However, the underlying nucleic acid species amassing in the absence of RNase H2 has not been established yet. Here, we report that murine RNase H2 knockout cells accumulated cytosolic DNA aggregates virtually indistinguishable from micronuclei. RNase H2-dependent micronuclei were surrounded by nuclear lamina and most of them contained damaged DNA...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28987891/surface-modified-microbubbles-colloidal-gas-aphrons-for-nanoparticle-removal-in-a-continuous-bubble-generation-flotation-separation-system
#17
Ming Zhang, Pascal Guiraud
The treatment of nanoparticle (NP) polluted aqueous suspensions by flotation can be problematic due to the low probability of collision between particles and bubbles. To overcome this limitation, the present work focuses on developing an enhanced flotation technique using the surface-functionalized microbubbles - colloidal gas aphrons (CGAs). The CGA generator was adapted to be air flow rate controlled based on the classical Sebba system; thus it could be well adopted in a continuous flotation process. Cetyl trimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS) were employed for CGA creation...
December 1, 2017: Water Research
https://www.readbyqxmd.com/read/28982551/a-cell-based-high-throughput-screening-assay-for-the-discovery-of-cgas-sting-pathway-agonists
#18
Bowei Liu, Liudi Tang, Xiaohui Zhang, Julia Ma, Mohit Sehgal, Junjun Cheng, Xuexiang Zhang, Yan Zhou, Yanming Du, John Kulp, Ju-Tao Guo, Jinhong Chang
Stimulator of interferon genes (STING) is an endoplasmic reticulum transmembrane protein that serves as a molecular hub for activation of interferon and inflammatory cytokine response by multiple cellular DNA sensors. Not surprisingly, STING has been demonstrated to play an important role in host defense against microorganisms and pharmacologic activation of STING is considered as an attractive strategy to treat viral diseases and boost antitumor immunity. In light of this we established a HepAD38-derived reporter cell line that expresses firefly luciferase in response to the activation of cyclic GMP-AMP synthase (cGAS)-STING pathway for high throughput screening (HTS) of small molecular human STING agonists...
November 2017: Antiviral Research
https://www.readbyqxmd.com/read/28976970/cytoplasmic-chromatin-triggers-inflammation-in-senescence-and-cancer
#19
Zhixun Dou, Kanad Ghosh, Maria Grazia Vizioli, Jiajun Zhu, Payel Sen, Kirk J Wangensteen, Johayra Simithy, Yemin Lan, Yanping Lin, Zhuo Zhou, Brian C Capell, Caiyue Xu, Mingang Xu, Julia E Kieckhaefer, Tianying Jiang, Michal Shoshkes-Carmel, K M Ahasan Al Tanim, Glen N Barber, John T Seykora, Sarah E Millar, Klaus H Kaestner, Benjamin A Garcia, Peter D Adams, Shelley L Berger
Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer...
October 4, 2017: Nature
https://www.readbyqxmd.com/read/28974621/topoisomerase-1-inhibition-promotes-cyclic-gmp-amp-synthase-dependent-antiviral-responses
#20
Geneviève Pépin, Charlotte Nejad, Jonathan Ferrand, Belinda J Thomas, H James Stunden, Elaine Sanij, Chwan-Hong Foo, Cameron R Stewart, Jason E Cain, Philip G Bardin, Bryan R G Williams, Michael P Gantier
Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS) detection of cytoplasmic DNA...
October 3, 2017: MBio
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