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https://www.readbyqxmd.com/read/29342134/chromosomal-instability-drives-metastasis-through-a-cytosolic-dna-response
#1
Samuel F Bakhoum, Bryan Ngo, Ashley M Laughney, Julie-Ann Cavallo, Charles J Murphy, Peter Ly, Pragya Shah, Roshan K Sriram, Thomas B K Watkins, Neil K Taunk, Mercedes Duran, Chantal Pauli, Christine Shaw, Kalyani Chadalavada, Vinagolu K Rajasekhar, Giulio Genovese, Subramanian Venkatesan, Nicolai J Birkbak, Nicholas McGranahan, Mark Lundquist, Quincey LaPlant, John H Healey, Olivier Elemento, Christine H Chung, Nancy Y Lee, Marcin Imielenski, Gouri Nanjangud, Dana Pe'er, Don W Cleveland, Simon N Powell, Jan Lammerding, Charles Swanton, Lewis C Cantley
Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342053/gradual-symmetric-progression-of-dfna34-hearing-loss-caused-by-an-nlrp3-mutation-and-cochlear-autoinflammation
#2
Hiroshi Nakanishi, Yoshiyuki Kawashima, Kiyoto Kurima, Julie A Muskett, H Jeffrey Kim, Carmen C Brewer, Andrew J Griffith
OBJECTIVE: To characterize the audiometric phenotype of autosomal-dominant DFNA34 hearing loss (HL) caused by a missense substitution in the NLRP3 gene. NLRP3 encodes a critical component of the NLRP3 inflammasome that is activated in innate immune responses. STUDY DESIGN: This study was conducted under protocol 01-DC-0229 approved by the NIH Combined Neurosciences IRB. We performed medical and developmental history interviews and physical and audiological examinations of affected individuals with DFNA34 HL caused by the p...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29341877/characterizing-the-effects-of-insertion-of-a-5-2%C3%A2-kb-region-of-a-vacv-genome-which-contains-known-immune-evasion-genes-on-mva-immunogenicity
#3
Melissa R Ryerson, Joanna L Shisler
Modified Vaccinia virus Ankara (MVA) is an attenuated Vaccinia virus (VACV) that is a popular vaccine vector candidate against many different pathogens. Its replication-restricted nature makes it a safe vaccine. However, higher doses or multiple boosts of MVA are necessary to elicit an immune response similar to wild-type VACV. Multiple strategies have been used to create modified MVA viruses that remain safe, but have increased immunogenicity. For example, one common strategy is to delete MVA immunomodulatory proteins in hopes of increasing the host immune response...
January 13, 2018: Virus Research
https://www.readbyqxmd.com/read/29341872/a-cqferritin-protein-inhibits-white-spot-syndrome-virus-infection-via-regulating-iron-ions-in-red-claw-crayfish-cherax-quadricarinatus
#4
Xiao-Xiao Chen, Yan-Yao Li, Xue-Jiao Chang, Xiao-Lu Xie, Yu-Ting Liang, Ke-Jian Wang, Wen-Yun Zheng, Hai-Peng Liu
It is well known that iron is an essential element for all living organism. The intracellular iron availability is also important for the host's innate immune response to various pathogens, in which the iron homeostasis can be regulated by ferritin due to its iron storage property. In this study, a full-length cDNA sequence of ferritin (named as CqFerritin) was identified with 1410 bp from red claw crayfish Cherax quadricarinatus, which contained an open reading frame of 513 bp, encoding 170 amino acids with a conserved ferritin domain...
January 13, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29341450/characterization-of-a-novel-papain-inducible-murine-model-of-eosinophilic-rhinosinusitis
#5
Anuj Tharakan, Alex Dobzanski, Nyall R London, Syed M Khalil, Nitya Surya, Andrew P Lane, Murugappan Ramanathan
BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu. Current animal models fail to recapitulate many of the innate and adaptive immunologic hallmarks of the disease, thus hindering the development of effective therapeutics. In the present study, mice were exposed intranasally to the cysteine protease papain, which shares functional similarities with parasitic proteases and aeroallergens, to generate a rapidly inducible murine model of eosinophilic rhinosinusitis...
January 17, 2018: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29341118/inhibition-of-the-fgl2-fc%C3%AE-riib-riii-immunosuppressive-pathway-enhances-antiviral-t-cell-and-b-cell-responses-leading-to-clearance-of-lcmv-cl-13
#6
Olga Klingberg, Ramzi Khattar, Kaveh Farrokhi, Dario Ferri, Nataliya Yavorska, Jianhua Zhang, Hassan Sadozai, Oyedele Adeyi, Andrzej Chruscinski, Gary A Levy, Nazia Selzner
Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-Like Protein-2 (FGL2) is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by Lymphocytic Choriomeningitis Virus Clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2+/+ mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells (DC) and impaired production of neutralizing antibody...
January 17, 2018: Immunology
https://www.readbyqxmd.com/read/29340042/identification-of-potential-genetic-causal-variants-for-rheumatoid-arthritis-by-whole-exome-sequencing
#7
Ying Li, Elaine Lai-Han Leung, Hudan Pan, Xiaojun Yao, Qingchun Huang, Min Wu, Ting Xu, Yuwei Wang, Jun Cai, Runze Li, Wei Liu, Liang Liu
Rheumatoid arthritis (RA) is a highly prevalent chronic autoimmune disease. However, genetic and environmental factors involved in RA pathogenesis are still remained largely unknown. To identify the genetic causal variants underlying pathogenesis and disease progression of RA patients, we undertook the first comprehensive whole-exome sequencing (WES) study in a total of 124 subjects including 58 RA cases and 66 healthy controls in Han Chinese population. We identified 378 novel genes that were enriched with deleterious variants in RA patients using a gene burden test...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339724/granulocyte-colony-stimulating-factor-controls-neural-and-behavioral-plasticity-in-response-to-cocaine
#8
Erin S Calipari, Arthur Godino, Emily G Peck, Marine Salery, Nicholas L Mervosh, Joseph A Landry, Scott J Russo, Yasmin L Hurd, Eric J Nestler, Drew D Kiraly
Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339462/direct-manipulation-of-t-lymphocytes-by-proteins-of-gastrointestinal-bacterial-pathogens
#9
Robin L Cassady-Cain, Jayne C Hope, Mark P Stevens
Gastrointestinal bacterial infection represents a significant threat to human health, as well as a burden on food animal production and welfare. Although there is advanced knowledge about the molecular mechanisms underlying pathogenesis, including the development of immune responses to these pathogens, gaps in knowledge persist. It is well established that gastrointestinal bacterial pathogens produce a myriad of proteins that affect the development and effectiveness of innate immune responses. However, relatively few proteins that directly affect lymphocytes responsible for humoral or cell-mediated immunity and memory have been identified...
January 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29339461/cooperative-immune-suppression-by-escherichia-coli-and-shigella-effector-proteins
#10
Maarten F de Jong, Neal M Alto
The enteric attaching and effacing (A/E) pathogens EHEC and EPEC and invasive pathogens EIEC and Shigella encode Type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/Shigella that are involved in suppression of NF-κB and uncovered their cellular and molecular functions. A novel mechanism among these effectors from both groups of pathogens is to coordinate effector function during infection...
January 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29339449/targeting-irf3-as-a-yap-agonist-therapy-against-gastric-cancer
#11
Shi Jiao, Jingmin Guan, Min Chen, Wenjia Wang, Chuanchuan Li, Yugong Wang, Yunfeng Cheng, Zhaocai Zhou
The Hippo pathway plays a vital role in tissue homeostasis and tumorigenesis. The transcription factor IRF3 is essential for innate antiviral immunity. In this study, we discovered IRF3 as an agonist of Yes-associated protein (YAP). The expression of IRF3 is positively correlated with that of YAP and its target genes in gastric cancer; the expression of both IRF3 and YAP is up-regulated and prognosticates patient survival. IRF3 interacts with both YAP and TEAD4 in the nucleus to enhance their interaction, promoting nuclear translocation and activation of YAP...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29339423/immune-protection-against-lethal-fungal-bacterial-intra-abdominal-infections
#12
Elizabeth A Lilly, Melanie Ikeh, Evelyn E Nash, Paul L Fidel, Mairi C Noverr
Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29339104/region-specific-innate-antiviral-responses-of-the-human-epididymis
#13
James A Browne, Shih Hsing Leir, Scott Eggener, Ann Harris
Viral infections of the epididymis are associated with epididymitis, which damages the epithelium and impairs fertility. We showed previously that innate immune response genes were differentially expressed in the corpus and cauda region of the human epididymis in comparison to the caput. Here we investigate the antiviral defense response mechanisms of human epididymis epithelial (HEE) cells. Toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are enriched in HEE cells from the corpus and cauda region...
January 12, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29338837/stromule-extension-along-microtubules-coordinated-with-actin-mediated-anchoring-guides-perinuclear-chloroplast-movement-during-innate-immunity
#14
Amutha Sampath Kumar, Eunsook Park, Alexander Nedo, Ali Alqarni, Li Ren, Kyle Hoban, Shannon Modla, John H McDonald, Chandra Kambhamettu, Savithramma P Dinesh-Kumar, Jeffrey Lewis Caplan
Dynamic tubular extensions from chloroplasts called stromules have recently been shown to connect with nuclei and function during innate immunity. We demonstrate that stromules extend along microtubules (MTs) and MT organization directly affects stromule dynamics since stabilization of MTs chemically or genetically increases stromule numbers and length. Although actin filaments (AFs) are not required for stromule extension, they provide anchor points for stromules. Interestingly, there is a strong correlation between the direction of stromules from chloroplasts and the direction of chloroplast movement...
January 17, 2018: ELife
https://www.readbyqxmd.com/read/29338160/higher-activities-of-hepatic-versus-splenic-cd8-t-cells-in-responses-to-adoptive-t-cell-therapy-and-vaccination-of-b6-mice-with-mhc-class-1-binding-antigen
#15
Mohamed Labib Salem, Randa E El Naggar, Sabry A El Naggar, Maysa A Mobasher, Mohamed H Mahmoud, Gamal Badr
The liver has unique microenvironment which is known to induce tolerance of cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in persistence of infection of the liver by the hepatitis B and C viruses. However, under some conditions, functional immune responses can be elicited in the liver in particular to show preferential retention of activated CD8+ T cells. It is not clear whether this retention depends on the type of the exogenous immunostimulatory or the endogenous innate immune cells...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29338093/longitudinal-profiles-of-metabolism-and-bioenergetics-associated-with-innate-immune-hormonal-inflammatory-responses-and-amino-acid-kinetics-in-severe-sepsis-and-systemic-inflammatory-response-syndrome-in-children
#16
Anna Maria Spanaki, Theonymfi Tavladaki, Helen Dimitriou, Andrey V Kozlov, J Catharina Duvigneau, Eftychia Meleti, Adelheid Weidinger, Evangelos Papakonstantinou, George Briassoulis
BACKGROUND: Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. METHODS: Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX...
January 16, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29338042/a-pharmacological-screen-for-compounds-that-rescue-the-developmental-lethality-of-a-drosophila-atm-mutant
#17
Stacey A Rimkus, David A Wassarman
Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response...
2018: PloS One
https://www.readbyqxmd.com/read/29337856/interaction-between-hepatitis-b-virus-and-toll-like-receptors-current-status-and-potential-therapeutic-use-for-chronic-hepatitis-b
#18
REVIEW
Zhiyong Ma, Qian Cao, Yong Xiong, Ejuan Zhang, Mengji Lu
Immune defense against infection with the hepatitis B virus (HBV) is complex and involves both host innate and adaptive immune systems. It is well accepted that the development of sufficient HBV-specific T cell and B cell responses are required for controlling an HBV infection. However, the contribution of innate immunity to removing HBV has been explored in recent years. Toll-like receptors (TLRs) are recognized as the first line of antiviral immunity because they initiate intracellular signaling pathways to induce antiviral mediators such as interferons (IFNs) and other cytokines...
January 16, 2018: Vaccines
https://www.readbyqxmd.com/read/29337611/interactions-between-parasites-and-the-bacterial-microbiota-of-chickens
#19
Rüdiger Hauck
Except for the important role coccidia have as predisposing factors of necrotic enteritis, the role parasites play in the dynamics of a healthy microbiota of chickens is not well explored. This review describes the interactions of relevant intestinal parasites of chickens with bacteria. Infection with Eimeria spp. favor the growth of Clostridium perfringens and suppress the growth of many other bacteria by increasing viscosity and passage time of the ingesta, and by causing lesions to the intestinal mucosa that improve the availability of nutrients for C...
December 2017: Avian Diseases
https://www.readbyqxmd.com/read/29337420/a-proinflammatory-response-of-bovine-endometrial-epithelial-cells-to-active-sperm-in-vitro
#20
Ahmed Essam Elweza, Mohamed Aboul Ezz, Tomas J Acosta, Anup K Talukder, Takashi Shimizu, Hiroyuki Hayakawa, Masayuki Shimada, Kazuhiko Imakawa, Ahmed Hamed Zaghloul, Akio Miyamoto
In the cow, cryopreserved semen is inseminated into the uterus, and most of sperm are removed by backflow and phagocytes. Nevertheless, the mechanism responsible for sperm phagocytosis is unclear. Here, we used cultured bovine uterine epithelial cells (BUECs) to investigate the uterine response to sperm and the mechanism that activates polymorphonuclear neutrophils (PMNs). BUEC monolayers were co-cultured with different numbers of washed sperm obtained from cryopreserved semen (104 , 105 and 106 sperm/ml) for 3 h...
January 16, 2018: Molecular Reproduction and Development
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