273,908 results match your criteria activation associated


Thorny ground, rocky soil: tissue-specific mechanisms of tumor dormancy and relapse.

Semin Cancer Biol 2021 May 9. Epub 2021 May 9.

Public Health Sciences Division/Translational Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address:

Disseminated tumor cells (DTCs) spread systemically yet distinct patterns of metastasis indicate a range of tissue susceptibility to metastatic colonization. Distinctions between permissive and suppressive tissues are still being elucidated at cellular and molecular levels. Although there is a growing appreciation for the role of the microenvironment in regulating metastatic success, we have a limited understanding of how diverse tissues regulate DTC dormancy, the state of reversible quiescence and subsequent awakening thought to contribute to delayed relapse. Read More

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Persistent NF-κB activation in muscle stem cells induces proliferation-independent telomere shortening.

Cell Rep 2021 May;35(6):109098

Department of Orthopaedic Surgery, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA; Institute of Regenerative Medicine, Musculoskeletal Regeneration Program, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

During the repeated cycles of damage and repair in many muscle disorders, including Duchenne muscular dystrophy (DMD), the muscle stem cell (MuSC) pool becomes less efficient at responding to and repairing damage. The underlying mechanism of such stem cell dysfunction is not fully known. Here, we demonstrate that the distinct early telomere shortening of diseased MuSCs in both mice and young DMD patients is associated with aberrant NF-κB activation. Read More

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Role of nuclear localization in the regulation and function of T-bet and Eomes in exhausted CD8 T cells.

Cell Rep 2021 May;35(6):109120

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The transcription factors T-bet and Eomesodermin (Eomes) regulate CD8 T cell exhaustion through undefined mechanisms. Here, we show that the subcellular localization of T-bet and Eomes dictate their regulatory activity in exhausted T cells (Ts). Ts had a higher ratio of nuclear Eomes:T-bet than memory T cells (Ts) during chronic lymphocytic choriomeningitis virus (LCMV) infection in preclinical cancer models and in human tumors. Read More

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α-Synuclein mutation impairs processing of endomembrane compartments and promotes exocytosis and seeding of α-synuclein pathology.

Cell Rep 2021 May;35(6):109099

Department of Molecular and Cellular Biology, The University of Guelph, Guelph, ON N1G 2W1, Canada; Neurodegenerative Disease Center, Scintillon Institute, 6868 Nancy Ridge Drive, San Diego, CA 92121, USA. Electronic address:

Neuronal loss in Parkinson's disease (PD) is associated with impaired proteostasis and accumulation of α-syn microaggregates in dopaminergic neurons. These microaggregates promote seeding of α-synuclein (α-syn) pathology between synaptically linked neurons. However, the mechanism by which seeding is initiated is not clear. Read More

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MDSC: Markers, development, states, and unaddressed complexity.

Immunity 2021 May;54(5):875-884

The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Myeloid-derived suppressor cells (MDSCs) are one of the most discussed biological entities in immunology. While the context and classification of this group of cells has evolved, MDSCs most commonly describe cells arising during chronic inflammation, especially late-stage cancers, and are defined by their T cell immunosuppressive functions. This MDSC concept has helped explain myeloid phenomena associated with disease outcome, but currently lacks clear definitions and a unifying framework across pathologies. Read More

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Network-based identification of key master regulators associated with an immune-silent cancer phenotype.

Brief Bioinform 2021 May 13. Epub 2021 May 13.

Cancer Research Department, Research Branch, Sidra Medicince, Doha, Qatar.

A cancer immune phenotype characterized by an active T-helper 1 (Th1)/cytotoxic response is associated with responsiveness to immunotherapy and favorable prognosis across different tumors. However, in some cancers, such an intratumoral immune activation does not confer protection from progression or relapse. Defining mechanisms associated with immune evasion is imperative to refine stratification algorithms, to guide treatment decisions and to identify candidates for immune-targeted therapy. Read More

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High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages.

Authors:

Sci Transl Med 2021 May 11. Epub 2021 May 11.

Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. Read More

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Unilateral vagotomy alters astrocyte and microglial morphology in the nucleus tractus solitarii of the rat.

Am J Physiol Regul Integr Comp Physiol 2021 May 12. Epub 2021 May 12.

Area Pathobiology, University of Missouri, Columbia, MO, United Statesgrid.134936.a.

The nucleus tractus solitarii (nTS) is the initial site of integration of sensory information from the cardiorespiratory system and contributes to reflex responses to hypoxia. Afferent fibers of the bilateral vagus nerves carry input from the heart, lungs, and other organs to the nTS where it is processed and modulated. Vagal afferents and nTS neurons are integrally associated with astrocytes and microglia which contribute to neuronal activity and influence cardiorespiratory control. Read More

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Surgical management of endometriosis-associated pain.

Minerva Obstet Gynecol 2021 May 12. Epub 2021 May 12.

Latifa Hospital, Dubai, Unated Arab Emirates.

Endometriosis and pelvic pain are associated. However, only half of the subtle and typical, and not all cystic and deep lesions are painful. The mechanism of the pain is explained by cyclical trauma and repair, an inflammatory reaction, activation of nociceptors up to 2. Read More

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Aquaporin 4 differentially modulates osmotic effects on vasopressin neurons in rat supraoptic nucleus.

Acta Physiol (Oxf) 2021 May 12:e13672. Epub 2021 May 12.

Department of Physiology, Harbin Medical University, Harbin, 150086, China.

Aim: Glial fibrillary acidic protein (GFAP) has molecular association with aquaporin 4 (AQP4) in astrocytic plasticity. Here, we further examined how AQP4 modulates osmotic effects on vasopressin (VP) neurons in rat supraoptic nucleus (SON) through interactions with GFAP.

Methods: Brain slices from adult male rats were under osmotic stimulation. Read More

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Mapping Reward Mechanisms by Intracerebral Self Stimulation in the Rhesus Monkey (Macaca mulatta).

J Comp Neurol 2021 May 12. Epub 2021 May 12.

Department of Psychiatry and Behavioral Sciences and National Primate Research Center, University of Washington, Seattle, WA, USA.

The objective of the study was to identify brain structures that mediate reward as evidenced by positive reinforcing effects of stimuli on behavior. Testing by intracerebral self-stimulation enabled monkeys to inform whether activation of ~2900 sites in 74 structures of four sensorimotor pathways and four modulatory loop pathways was positive, negative or neutral. Stimulation was rewarding at 30% of sites, negative at 17%, neutral at 52%. Read More

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The role of mitochondrial oxidative stress and the tumor microenvironment in radiation-related cancer.

Authors:
Tsutomu Shimura

J Radiat Res 2021 May;62(Supplement_1):i36-i43

Department of Environmental Health, National Institute of Public Health, Saitama, 351-0197, Japan.

The health risks associated with low-dose radiation, which are a major concern after the Fukushima Daiichi nuclear power plant accident (the Fukushima accident), have been extensively investigated, and the cancer risks from low-dose radiation exposure (below ~ 100 mSv) are thought to be negligible. According to World Health Organization and the United Nations Scientific Committee on the Effects of Atomic Radiation reports, the level of radiation exposure from the Fukushima accident is limited, estimating no significant increased risk from the accident. Radiation-induced cell injury is mainly caused by oxidative damage to biomolecules, including DNA, lipids and proteins. Read More

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Beneficial effects of natural compounds on experimental liver ischemia-reperfusion injury.

Food Funct 2021 May;12(9):3787-3798

Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development of an excessive inflammatory response. Liver resident cells and those recruited in response to injury generate pro-inflammatory signals such as reactive oxygen species, cytokines, chemokines, proteases and lipid mediators that contribute to hepatocellular necrosis and apoptosis. Besides, dying hepatocytes release damage-associated molecular patterns that actívate inflammasomes to further stimulate inflammatory responses leading to massive cell death. Read More

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Costunolide ameliorates intestinal dysfunction and depressive behaviour in mice with stress-induced irritable bowel syndrome colonic mast cell activation and central 5-hydroxytryptamine metabolism.

Food Funct 2021 May;12(9):4142-4151

Precision Pharmacy & Drug Development Center, Department of Pharmacy, the Second Affiliated Hospital of Air Force Medical University, Xi'an 710038, China.

Irritable bowel syndrome (IBS) is a common chronic functional bowel disease, associated with a high risk of depression and anxiety. The brain-gut axis plays an important role in the pathophysiological changes involved in IBS; however, an effective treatment for the same is lacking. The natural compound costunolide (COS) has been shown to exert gastroprotective, enteroprotective, and neuroprotective effects, but its therapeutic effects in IBS are unclear. Read More

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The association between frailty and clinical outcomes in hospitalised patients requiring Code Blue activation.

Intern Med J 2021 May 12. Epub 2021 May 12.

Peninsula Health. Adjunct Senior Lecturer, Monash University, Melbourne, Australia.

Background: Code Blues allow a rapid, hospital wide response to acutely deteriorating patients. The concept of frailty is being increasingly recognised as an important element in determining outcomes of critically ill patients. We hypothesised that increasing frailty would be associated with worse outcomes following a Code Blue. Read More

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Transcriptome analysis of islets from diabetes-resistant and diabetes-prone obese mice reveals novel gene regulatory networks involved in beta-cell compensation and failure.

FASEB J 2021 Jun;35(6):e21608

Garvan Institute of Medical Research, Sydney, NSW, Australia.

The mechanisms underpinning beta-cell compensation for obesity-associated insulin resistance and beta-cell failure in type 2 diabetes remain poorly understood. We used a large-scale strategy to determine the time-dependent transcriptomic changes in islets of diabetes-prone db/db and diabetes-resistant ob/ob mice at 6 and 16 weeks of age. Differentially expressed genes were subjected to cluster, gene ontology, pathway and gene set enrichment analyses. Read More

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Dissecting Oncogenic RAS Signaling in Melanoma Development in Genetically Engineered Zebrafish Models.

Methods Mol Biol 2021 ;2262:411-422

Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, UK.

Hyper-activation of RAS signaling pathways causes cancer, including melanoma, and RAS signaling pathways have been successfully targeted using drugs for patient benefit. The available drugs alone cannot cure cancer, however, and so investigation continues into RAS signaling pathways, with the goal of identifying further actionable targets. The zebrafish can be used to model human malignancies, and genetic modification of zebrafish to incorporate selective disease-associated genetic alterations is practicable. Read More

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January 2021

Active GTPase Pulldown Protocol.

Methods Mol Biol 2021 ;2262:117-135

Institute of Molecular Cell Biology, Center for Molecular Biomedicine, University Hospital Jena, Jena, Germany.

Ras and its related small GTPases are important signalling nodes that regulate a wide variety of cellular functions. The active form of these proteins exists in a transient GTP bound state that mediates downstream signalling events. The dysregulation of these GTPases has been associated with the progression of multiple diseases, most prominently cancer and developmental syndromes known as Rasopathies. Read More

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January 2021

Vincristine attenuates cardiac fibrosis through inhibiting activation of NLRP3 inflammasome.

Clin Sci (Lond) 2021 May 12. Epub 2021 May 12.

The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Vincristine (VCR) is widely used in cancer therapies, while its benefits on cardiac fibrosis remain unknown. Here, we investigated VCR's efficacy on cardiac fibrosis and elucidated the underlying mechanism of action. Network pharmacology was employed to predict the mechanism of VCR action on cardiac fibrosis. Read More

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Inhibitory control in children with tic disorder: aberrant fronto-parietal network activity and connectivity.

Brain Commun 2021 9;3(2):fcab067. Epub 2021 Apr 9.

Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Chronic tic disorders, including Tourette syndrome, are typically thought to have deficits in cognitive inhibition and top down cognitive control due to the frequent and repetitive occurrence of tics, yet studies reporting task performance results have been equivocal. Despite similar behavioural performance, individuals with chronic tic disorder have exhibited aberrant patterns of neural activation in multiple frontal and parietal regions relative to healthy controls during inhibitory control paradigms. In addition to these top down attentional control regions, widespread alterations in brain activity across multiple neural networks have been reported. Read More

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Cyclophilin A induces macrophage apoptosis and enhances atherosclerotic lesions in high-fat diet-fed hyperglycemic rabbits.

FASEB Bioadv 2021 May 1;3(5):305-322. Epub 2021 Mar 1.

Cardiovascular Diseases and Diabetes Biology Rajiv Gandhi Centre for Biotechnology Trivandrum India.

Macrophage apoptosis is a key contributor to the progression of atherosclerosis. Cyclophilin A, a monocyte secretory protein associated with the initiation of atherosclerosis has an inherent nuclease activity. This study reports the mechanism by which cyclophilin A causes apoptosis of macrophages and accelerates the progression of atherosclerosis. Read More

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Benzo[a]pyrene Cytotoxicity Tolerance in Testicular Sertoli Cells Involves Aryl-hydrocarbon Receptor and Cytochrome P450 1A1 Expression Deficiencies.

Dev Reprod 2021 Mar 31;25(1):15-24. Epub 2021 Mar 31.

Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 49201, Korea.

Benzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as an endocrine-disrupting chemical. In mammalian testes, Sertoli cells support spermatogenesis. Therefore, if these cells are negatively affected by exposure to xenotoxic chemicals, spermatogenesis can be seriously disrupted. Read More

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LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations.

Neurol Genet 2021 Apr 2;7(2):e559. Epub 2021 Feb 2.

Department of Child Neurology, Emma Childrens Hospital, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, The Netherlands (M.D.S., T.E.M.A.); Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Italy (S.F., C.D., P.G.); Area di Ricerca Genetica e Malattie Rare (E.B.), Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy; Laboratory of Oncology and Molecular Genetics (K.A.), Clínica las Condes, Santiago, Chile; Department of Pediatric Neurology (C.C.), Clínica Las Condes, Santiago, Chile; Division of Child Neurology (P.T.), Department of Neurology, Istanbul Faculty of Medicine, Turkey; Department of Paediatrics (C.A.S.), Royal Childrens Hospital, Murdoch Childrens Research Institute and University of Melbourne, Victoria, Australia; Pediatric Neurology (C.E.E.), Radboud University Medical Center, Amalia Childrens Hospital, Nijmegen, The Netherlands; Department of Pediatrics (A.S.-V.), University of South Florida, Tampa; Unit of Pediatric Neurology and Neurorehabilitation (S.L.), Department WomanMother-Child, Lausanne University Hospital, Switzerland; Community Pediatrics, Royal Berkshire Hospital, Reading (S.H.), United Kingdom; Neuropediatric Department (T.S.-M.), Childrens Hospital, Luzern, Switzerland; Unit of Neurorehabilitation (G.V.), Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy; Paediatric Neurology (G.C.), Nottingham Childrens Hospital, United Kingdom; PEDEGO Research Unit (E.R.), Medical Research Center and Department of Clinical Genetics, University of Oulu and Oulu University Hospital, Finland; Radiology (C.O.), Clínica las Condes, Santiago, Chile; Unit of Neuromuscular and Neurodegenerative Disorders (E.S.B), Area di Ricerca Genetica e Malattie Rare and Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy; and Department of Child Neurology (M.S.v.d.K.), Emma Childrens Hospital and Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands.

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in , encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. Read More

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MiRNA-202-5p promotes Colorectal Carcinogenesis through suppression of PTEN.

J Cancer 2021 31;12(11):3154-3163. Epub 2021 Mar 31.

Department of Immunology, the school of Basic Medical Sciences, Anhui Medical University, Hefei, China, 230032.

Colorectal cancer (CRC) is still one of the leading causes of cancer-associated death in the modern society. The biological function of miR-202-5p for CRC development remains controversial, largely due to the fact that miR-202-5p can be tumor-suppressive or oncogenic in different contexts. Obtained results indicated that aberrant expression of miR-202-5p was observed in majority of human CRC samples and miR-202-5p was transcriptionally up-regulated by c-Myc. Read More

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Quinolinic acid is associated with cognitive deficits in schizophrenia but not major depressive disorder.

Sci Rep 2021 May 11;11(1):9992. Epub 2021 May 11.

Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Chemin du Petit-Bel-Air, 1225, Chêne-Bourg, Switzerland.

Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). The relationship to different psychopathological dimensions within these disorders however remains to be elucidated. We thus investigated potential group differences of tryptophan, kynurenine, kynurenic acid, 3-hydroxy kynurenine and quinolinic acid in the plasma of 19 healthy controls (HC), 45 patients with SZ and 43 patients with MDD and correlated plasma proteins with the "motivation and pleasure" dimension and cognition. Read More

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Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia in mice.

Nat Commun 2021 May 11;12(1):2648. Epub 2021 May 11.

National Institute of Biological Sciences (NIBS), Beijing, China.

The neural mechanisms of fear-associated thermoregulation remain unclear. Innate fear odor 2-methyl-2-thiazoline (2MT) elicits rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1-the chemosensor for 2MT. Here we report that Trpa1 mice show diminished 2MT-evoked c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel) and nucleus of the solitary tract (NTS). Read More

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A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages.

Nat Commun 2021 May 11;12(1):2620. Epub 2021 May 11.

Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, USA.

Tumor associated macrophage responses are regulated by distinct metabolic states that affect their function. However, the ability of specific signals in the local tumor microenvironment to program macrophage metabolism remains under investigation. Here, we identify NAMPT, the rate limiting enzyme in NAD salvage synthesis, as a target of STAT1 during cellular activation by interferon gamma, an important driver of macrophage polarization and antitumor responses. Read More

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Engineered red blood cells as an off-the-shelf allogeneic anti-tumor therapeutic.

Nat Commun 2021 May 11;12(1):2637. Epub 2021 May 11.

Rubius Therapeutics, Inc., Cambridge, MA, USA.

Checkpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12. Read More

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Targeting Treg cells with GITR activation alleviates resistance to immunotherapy in murine glioblastomas.

Nat Commun 2021 May 11;12(1):2582. Epub 2021 May 11.

Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA, USA.

Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma (GBM) trials. Here, we show that regulatory T (Treg) cells play a key role in GBM resistance to ICBs in experimental gliomas. Targeting glucocorticoid-induced TNFR-related receptor (GITR) in Treg cells using an agonistic antibody (αGITR) promotes CD4 Treg cell differentiation into CD4 effector T cells, alleviates Treg cell-mediated suppression of anti-tumor immune response, and induces potent anti-tumor effector cells in GBM. Read More

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Bradyrhizobium diazoefficiens USDA110 Nodulation of Aeschynomene afraspera Is Associated with Atypical Terminal Bacteroid Differentiation and Suboptimal Symbiotic Efficiency.

mSystems 2021 May 11;6(3). Epub 2021 May 11.

Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France

Legume plants can form root organs called nodules where they house intracellular symbiotic rhizobium bacteria. Within nodule cells, rhizobia differentiate into bacteroids, which fix nitrogen for the benefit of the plant. Depending on the combination of host plants and rhizobial strains, the output of rhizobium-legume interactions varies from nonfixing associations to symbioses that are highly beneficial for the plant. Read More

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