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https://www.readbyqxmd.com/read/28817646/genetic-dissection-of-endothelial-transcriptional-activity-of-zebrafish-aryl-hydrocarbon-receptors-ahrs
#1
Wade W Sugden, Roberto C Leonardo-Mendonça, Darío Acuña-Castroviejo, Arndt F Siekmann
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor conserved across phyla from flies to humans. Activated by a number of endogenous ligands and environmental toxins, studies on AHR function and gene regulation have largely focused on a toxicological perspective relating to aromatic hydrocarbons generated by human activities and the often-deleterious effects of exposure on vertebrates mediated by AHR activation. A growing body of work has highlighted the importance of AHR in physiologic processes, including immune cell differentiation and vascular patterning...
2017: PloS One
https://www.readbyqxmd.com/read/28817385/novel-molecular-defects-associated-with-very-early-onset-inflammatory-bowel
#2
Sara Ciullini Mannurita, Eleonora Gambineri
PURPOSE OF REVIEW: Immune dysregulation disorders present with common clinical features of multiorgan autoimmunity. Gastrointestinal involvement is the hallmark of an impaired immune homeostasis. This review will give an overview on the novel phenotypes, highlighting the major points that will help to enable early diagnosis and treatment. RECENT FINDINGS: The rapid progress on DNA sequencing technologies have led to the identification of monogenic defects that adversely impact the control of immune homeostasis...
August 16, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#3
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28815458/backbone-and-side-chain-resonance-assignments-of-ca-2-4-calmodulin-bound-to-beta-calcineurin-a-cambd-peptide
#4
C Andrew Fowler, Maria F Núñez Hernandez, Susan E O'Donnell, Liping Yu, Madeline A Shea
Calcineurin (CaN) is a heterodimeric and highly conserved serine/threonine phosphatase (PP2B) that plays a critical role in coupling calcium signals to physiological processes including embryonic cardiac development, NF-AT-regulated gene expression in immune responses, and apoptosis. The catalytic subunit (CaNA) has three isoforms (α, β, and γ,) in humans and seven isoforms in Paramecium. In all eukaryotes, the EF-hand protein calmodulin (CaM) regulates CaN activity in a calcium-dependent manner. The N- and C-domains of CaM (CaMN and CaMC) recognize a CaM-binding domain (CaMBD) within an intrinsically disordered region of CaNA that precedes the auto-inhibitory domain (AID) of CaNA...
August 16, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28814613/osteoimmunology-the-conceptual-framework-unifying-the-immune-and-skeletal-systems
#5
REVIEW
Kazuo Okamoto, Tomoki Nakashima, Masahiro Shinohara, Takako Negishi-Koga, Noriko Komatsu, Asuka Terashima, Shinichiro Sawa, Takeshi Nitta, Hiroshi Takayanagi
The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28813466/comprehensive-comparison-of-neonate-and-adult-human-platelet-transcriptomes
#6
Eva Caparrós-Pérez, Raúl Teruel-Montoya, Mª José López-Andreo, Mª Carmen Llanos, José Rivera, Verónica Palma-Barqueros, Jose E Blanco, Vicente Vicente, Constantino Martínez, Francisca Ferrer-Marín
Understanding the underlying mechanisms of the well-substantiated platelet hyporeactivity in neonates is of interest given their implications for the clinical management of newborns, a population at higher bleeding risk than adults (especially sick and preterm infants), as well as for gaining insight into the regulatory mechanisms of platelet biology. Transcriptome analysis is useful in identifying mRNA signatures affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never before been reported...
2017: PloS One
https://www.readbyqxmd.com/read/28812211/the-immune-system-in-obesity-developing-paradigms-amidst-inconvenient-truths
#7
REVIEW
Madhur Agrawal, Philip A Kern, Barbara S Nikolajczyk
PURPOSE OF REVIEW: Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations. RECENT FINDINGS: Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically...
August 15, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28811959/t-helper-and-t-regulatory-cells-modulation-in-head-and-neck-squamous-cell-carcinoma
#8
REVIEW
Daniele Maggioni, Lorenzo Pignataro, Werner Garavello
Head and neck squamous cell carcinoma (HNSCC) is one of the most diffused cancer types, characterized by a high reoccurrence rate, mainly due to the inability of current therapeutic approaches to completely eradicate cancer cells. HNSCC patients often have defective immune functions, thus allowing cancer immune escape and cancer spreading. Particularly important in driving immune escape during HNSCC progression are T-helper and T-regulatory cells. New insights into their mechanisms of action might support the development of effective and long-lasting immunotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811898/lentinula-edodes-mycelia-extract-plus-adjuvant-chemotherapy-for-breast-cancer-patients-results-of-a-randomized-study-on-host-quality-of-life-and-immune-function-improvement
#9
Yukiko Nagashima, Shigehumi Yoshino, Shigeru Yamamoto, Noriko Maeda, Tatsuya Azumi, Yoshifumi Komoike, Kiyotaka Okuno, Tsutomu Iwasa, Junji Tsurutani, Kazuhiko Nakagawa, Oka Masaaki, Nagano Hiroaki
Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double-blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, i...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28811654/characterization-of-the-mollusc-rig-i-mavs-pathway-reveals-an-archaic-antiviral-signalling-framework-in-invertebrates
#10
Baoyu Huang, Linlin Zhang, Yishuai Du, Fei Xu, Li Li, Guofan Zhang
Despite the mitochondrial antiviral signalling protein (MAVS)-dependent RIG-I-like receptor (RLR) signalling pathway in the cytosol plays an indispensable role in the antiviral immunity of the host, surprising little is known in invertebrates. Here we characterized the major members of RLR pathway and investigated their signal transduction a Molluscs. We show that genes involved in RLR pathway were significantly induced during virus challenge, including CgRIG-I-1, CgMAVS, CgTRAF6 (TNF receptor-associated factor 6), and CgIRFs (interferon regulatory factors...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811575/biological-and-functional-characterization-of-bone-marrow-derived-mesenchymal-stromal-cells-from-patients-affected-by-primary-immunodeficiency
#11
Nadia Starc, Daniela Ingo, Antonella Conforti, Valeria Rossella, Luigi Tomao, Angela Pitisci, Fabiola De Mattia, Immacolata Brigida, Mattia Algeri, Mauro Montanari, Giuseppe Palumbo, Pietro Merli, Paolo Rossi, Alessandro Aiuti, Franco Locatelli, Maria Ester Bernardo
Mesenchymal stromal cells (MSCs) represent a key component of bone marrow (BM) microenvironment and display immune-regulatory properties. We performed a detailed analysis of biological/functional properties of BM-MSCs derived from 33 pediatric patients affected by primary immune-deficiencies (PID-MSCs): 7 Chronic Granulomatous Disease (CGD), 15 Wiskott-Aldrich Syndrome (WAS), 11 Severe Combined Immunodeficiency (SCID). Results were compared with MSCs from 15 age-matched pediatric healthy-donors (HD-MSCs). Clonogenic and proliferative capacity, differentiation ability, immunophenotype, immunomodulatory properties were analyzed...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811476/lyn-and-fyn-function-as-molecular-switches-that-control-immunoreceptors-to-direct-homeostasis-or-inflammation
#12
Sanae Ben Mkaddem, Amaya Murua, Héloise Flament, Dimitri Titeca-Beauport, Carine Bounaix, Luca Danelli, Pierre Launay, Marc Benhamou, Ulrich Blank, Eric Daugas, Nicolas Charles, Renato C Monteiro
Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28809000/post-translational-modification-profiling-functional-proteomics-for-the-analysis-of-immune-regulation
#13
Avital Eisenberg-Lerner, Ifat Regev, Yifat Merbl
Posttranslational modifications (PTMs) of proteins are an integral part of major cellular regulatory mechanisms dictating protein function, localization, and stability. The capacity to screen PTMs using protein microarrays has advanced our ability to identify their targets and regulatory role. This chapter discusses a unique procedure that combines functional extract-based activity assay with large-scale screening utilities of protein microarrays. This "PTM-profiling" system offers advantages in quantitatively identifying modifications in an unbiased manner in the context of specific cellular conditions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808862/a-pilot-study-comparing-t-regulatory-cell-function-among-healthy-children-in-different-areas-of-gansu-china
#14
Panhong Gou, Xiaoru Chang, Zhonghui Ye, Yueli Yao, Patton Khuu Nguyen, Sally Katharine Hammond, Junling Wang, Sa Liu
Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions...
August 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#15
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28808155/roca-is-an-accessory-protein-to-the-virulence-regulating-covr-s-two-component-system-in-the-group-a-streptococcus
#16
Ira Jain, Eric W Miller, Jessica L Danger, Kathryn J Pflughoeft, Paul Sumby
Regulating gene expression during infection is critical to the ability of pathogens to circumvent the immune response and cause disease. This is true for the group A Streptococcus (GAS), a pathogen that causes both invasive (e.g. necrotizing fasciitis) and non-invasive (e.g. pharyngitis) diseases. The control of virulence (CovR/S) two-component system has a major role in regulating GAS virulence factor expression. The regulator of cov (RocA) protein, which is a predicted kinase, functions in an undetermined manner through CovR/S to alter gene expression and reduce invasive disease virulence...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28808112/regulation-of-perforin-activation-and-pre-synaptic-toxicity-through-c-terminal-glycosylation
#17
Imran G House, Colin M House, Amelia J Brennan, Omer Gilan, Mark A Dawson, James C Whisstock, Ruby Hp Law, Joseph A Trapani, Ilia Voskoboinik
Perforin is a highly cytotoxic pore-forming protein essential for immune surveillance by cytotoxic lymphocytes. Prior to delivery to target cells by exocytosis, perforin is stored in acidic secretory granules where it remains functionally inert. However, how cytotoxic lymphocytes remain protected from their own perforin prior to its export to secretory granules, particularly in the Ca(2+)-rich endoplasmic reticulum, remains unknown. Here, we show that N-linked glycosylation of the perforin C-terminus at Asn549 within the endoplasmic reticulum inhibits oligomerisation of perforin monomers and thus protects the host cell from premature pore formation...
August 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28805801/small-molecule-studies-identify-cdk8-as-a-regulator-of-il-10-in-myeloid-cells
#18
Liv Johannessen, Thomas B Sundberg, Daniel J O'Connell, Raivo Kolde, James Berstler, Katelyn J Billings, Bernard Khor, Brinton Seashore-Ludlow, Anne Fassl, Caitlin N Russell, Isabel J Latorre, Baishan Jiang, Daniel B Graham, Jose R Perez, Piotr Sicinski, Andrew J Phillips, Stuart L Schreiber, Nathanael S Gray, Alykhan F Shamji, Ramnik J Xavier
Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion from activated dendritic cells. Mechanism-of-action studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation...
August 14, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28805308/lymphocyte-profile-and-cytokine-mrna-expression-in-peripheral-blood-mononuclear-cells-of-patients-with-recurrent-respiratory-papillomatosis-suggest-dysregulated-cytokine-mrna-response-and-impaired-cytotoxic-capacity
#19
Anna Holm, Olga Nagaeva, Ivan Nagaev, Christos Loizou, Göran Laurell, Lucia Mincheva-Nilsson, Karin Nylander, Katarina Olofsson
OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is a relatively rare, chronic disease caused by Human Papilloma Virus (HPV) 6 and 11, and characterized by wart-like lesions in the airway affecting voice and respiratory function. The majority of HPV infections are asymptomatic and resolve spontaneously, however, some individuals are afflicted with persistent HPV infections. Failure to eliminate HPV 6 and 11 due to a defect immune responsiveness to these specific genotypes is proposed to play a major role in the development of RRP...
August 14, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28805251/wiskott-aldrich-syndrome-protein-emerging-mechanisms-in-immunity
#20
REVIEW
Elizabeth Rivers, Adrian J Thrasher
The Wiskott Aldrich syndrome protein (WASP) participates in innate and adaptive immunity through regulation of actin cytoskeleton-dependent cellular processes, including immune synapse formation, cell signaling, migration and cytokine release. There is also emerging evidence for a direct role in nuclear transcription programmes uncoupled from actin polymerization. A deeper understanding of some of the more complex features of Wiskott Aldrich syndrome (WAS) itself, such as the associated autoimmunity and inflammation, has come from identification of defects in the number and function of anti-inflammatory myeloid cells and regulatory T and B cells, as well as defects in positive and negative B-cell selection...
August 14, 2017: European Journal of Immunology
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