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https://www.readbyqxmd.com/read/29674970/hypothesis-the-psychedelic-ayahuasca-heals-traumatic-memories-via-a-sigma-1-receptor-mediated-epigenetic-mnemonic-process
#1
Antonio Inserra
Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N -Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29669249/the-transcription-factor-runx3-establishes-chromatin-accessibility-of-cis-regulatory-landscapes-that-drive-memory-cytotoxic-t-lymphocyte-formation
#2
Dapeng Wang, Huitian Diao, Adam J Getzler, Walter Rogal, Megan A Frederick, Justin Milner, Bingfei Yu, Shane Crotty, Ananda W Goldrath, Matthew E Pipkin
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29664561/the-function-and-dysfunction-of-memory-cd8-t-cells-in-tumor-immunity
#3
REVIEW
James L Reading, Felipe Gálvez-Cancino, Charles Swanton, Alvaro Lladser, Karl S Peggs, Sergio A Quezada
The generation and maintenance of CD8+ T cell memory is crucial to long-term host survival, yet the basic tenets of CD8+ T cell immunity are still being established. Recent work has led to the discovery of tissue-resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8+ T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de-repress the anti-tumor response...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29625150/nimodipine-represses-ampk-phosphorylation-and-excessive-autophagy-after-chronic-cerebral-hypoperfusion-in-rats
#4
Yan Chen, Zihu Tan
Chronic cerebral hypofusion (CCH) after bilateral carotid artery occlusion (2VO) causes cognitive damage and neuronal degeneration in the cortex and hippocampal CA1 area, and influences the oxygen and glucose supply in the brain which often results in metabolic alterations and oxidative stress. AMP-activated protein kinase (AMPK) phosphorylation, a sensor of cellular energy status that directs metabolic adaptation to support cellular growth and survival after CCH. Autophagy is also likely to be involved in metabolic adaptation and play an important role in neuronal deterioration and cognitive decline after CCH...
April 3, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29614311/mir-138-sirt1-axis-is-implicated-in-impaired-learning-and-memory-abilities-of-cerebral-ischemia-reperfusion-injured-rats
#5
Feng Tian, Chao Yuan, Hongmei Yue
The present study aimed to explore whether deregulated miR-138 is implicated in cerebral I/R injury-impaired learning and memory abilities. Rats were subjected to bilateral common carotid occlusion followed by reperfusion to induce cerebral I/R injury. A model of oxygen-glucose deprivation and reperfusion (OGD/R) was conducted to mimic cerebral I/R conditions in vitro. MiR-138 expression levels were reduced in the hippocampus of cerebral I/R injured rats. Inhibition of miR-138 ameliorated the impaired learning and memory abilities of rats, and promoted autophagy and thus attenuated apoptosis in the OGD/R-treated hippocampal neurons...
March 31, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29597004/neuroprotective-effect-of-docosahexaenoic-acid-in-rat-traumatic-brain-injury-model-via-regulation-of-tlr4-nf-kappa-b-signaling-pathway
#6
Ri Tang, Yi-Mei Lin, Hong-Xing Liu, Er-Song Wang
OBJECTIVE: The experiments were conducted to prove that docosahexaenoic acid (DHA) alleviates traumatic brain injury (TBI) through regulating TLR4/NF-Kappa B signaling pathway. METHODS: Bioinformatic analysis was performed using published data from Gene Expression Omnibus (GEO) database to investigate differentially expressed genes and signaling pathways. Controlled cortical impact (CCI) injury rat model was built, and DHA (16 mg/kg in DMSO, once each day) was used to treat TBI rats...
March 26, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29535264/tslp-signaling-in-cd4-t-cells-programs-a-pathogenic-t-helper-2-cell-state
#7
Yrina Rochman, Krista Dienger-Stambaugh, Phoebe K Richgels, Ian P Lewkowich, Andrey V Kartashov, Artem Barski, Gurjit K Khurana Hershey, Warren J Leonard, Harinder Singh
Pathogenic T helper 2 (TH 2) cells, which produce increased amounts of the cytokines interleukin-5 (IL-5) and IL-13, promote allergic disorders, including asthma. Thymic stromal lymphopoietin (TSLP), a cytokine secreted by epithelial and innate immune cells, stimulates such pathogenic TH 2 cell responses. We found that TSLP signaling in mouse CD4+ T cells initiated transcriptional changes associated with TH 2 cell programming. IL-4 signaling amplified and stabilized the genomic response of T cells to TSLP, which increased the frequency of T cells producing IL-4, IL-5, and IL-13...
March 13, 2018: Science Signaling
https://www.readbyqxmd.com/read/29519323/icariside-ii-ameliorates-ibotenic-acid-induced-cognitive-impairment-and-apoptotic-response-via-modulation-of-mapk-pathway-in-rats
#8
Lianzi He, Yuanyuan Deng, Jianmei Gao, Lingrong Zeng, Qihai Gong
BACKGROUND: Excitotoxicity is extensively recognized as a major pathological process of neuronal death and has been proved to play a key role in Alzheimer's disease (AD). ICS II, a flavonoid compound from Herba Epimedii Maxim, is attracting great interests due to its neuroprotective properties. PURPOSE: The present study was aimed to explore the effects of ICS II on cognitive dysfunction and apoptotic response induced by excitatory neurotoxin ibotenic acid (IBO) injection in rats...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29499102/lupus-regulator-peptide-p140-represses-b-cell-differentiation-by-reducing-hla-class-ii-molecule-overexpression
#9
Maud Wilhelm, Fengjuan Wang, Nicolas Schall, Jean-François Kleinmann, Michael Faludi, Emil Pablo Nashi, Jean Sibilia, Thierry Martin, Evelyne Schaeffer, Sylviane Muller
OBJECTIVES: To investigate ex vivo the effect on human T and B cells of P140/LupuzorTM , an inhibitor of autophagy, currently evaluated in phase III-clinical trials for treating lupus. METHODS: B cells, T cells and dendritic cells were analyzed by flow cytometry and cellular assays. The autophagy marker expression was evaluated by immunoblotting and flow cytometry; the levels of B cell receptor signaling markers and HLA molecules expression by flow cytometry. TLR ligand screening was made using transfected HEK cells...
March 2, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29474581/thermopriming-triggers-splicing-memory-in-arabidopsis
#10
Yu Ling, Natalia Serrano, Ge Gao, Mohamed Atia, Morad Mokhtar, Yong H Woo, Jeremie Bazin, Alaguraj Veluchamy, Moussa Benhamed, Martin Crespi, Christoph Gehring, A S N Reddy, Magdy M Mahfouz
Abiotic and biotic stresses limit crop productivity. Exposure to a non-lethal stress, referred to as priming, can allow plants to survive subsequent and otherwise lethal conditions; the priming effect persists even after a prolonged stress-free period. However, the molecular mechanisms underlying priming are not fully understood. Here, we investigated the molecular basis of heat shock memory and the role of priming in Arabidopsisthaliana. Comprehensive analysis of transcriptome-wide changes in gene expression and alternative splicing in primed and non-primed plants revealed that alternative splicing functions as a novel component of heat shock memory...
February 21, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29470492/memory-functions-reveal-structural-properties-of-gene-regulatory-networks
#11
Edgar Herrera-Delgado, Ruben Perez-Carrasco, James Briscoe, Peter Sollich
Gene regulatory networks (GRNs) control cellular function and decision making during tissue development and homeostasis. Mathematical tools based on dynamical systems theory are often used to model these networks, but the size and complexity of these models mean that their behaviour is not always intuitive and the underlying mechanisms can be difficult to decipher. For this reason, methods that simplify and aid exploration of complex networks are necessary. To this end we develop a broadly applicable form of the Zwanzig-Mori projection...
February 22, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29459824/-egr3-immediate-early-gene-and-the-brain-derived-neurotrophic-factor-in-bipolar-disorder
#12
Bianca Pfaffenseller, Flavio Kapczinski, Amelia L Gallitano, Fábio Klamt
Bipolar disorder (BD) is a severe psychiatric illness with a consistent genetic influence, involving complex interactions between numerous genes and environmental factors. Immediate early genes (IEGs) are activated in the brain in response to environmental stimuli, such as stress. The potential to translate environmental stimuli into long-term changes in brain has led to increased interest in a potential role for these genes influencing risk for psychiatric disorders. Our recent finding using network-based approach has shown that the regulatory unit of early growth response gene 3 ( EGR3 ) of IEGs family was robustly repressed in postmortem prefrontal cortex of BD patients...
2018: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29301062/regulatory-roles-of-histone-deacetylases-1-and-2-in-pb-induced-neurotoxicity
#13
Yulan Wu, Yi Xu, Xiyao Huang, Danlei Ye, Miaomiao Han, Hui-Li Wang
Lead (Pb) prevails among the environmental hazards against human health. Although increasing evidence highlights the epigenetic roles underlying the Pb-induced neurotoxicity, the exact mechanisms concerning histone acetylation and its causative agents are still at its infancy. In the present study, the roles of histone deacetylases 1 and 2 (HDAC1/2), as well as acetylation of Lys9 on histone H3 (Ac-H3K9), in Pb-induced neurotoxicity were investigated. Pb was administered to PC12 cells at 10 μM for 24 h...
April 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29249600/exhaustion-and-inflation-at-antipodes-of-t-cell-responses-to-chronic-virus-infection
#14
REVIEW
Luka Cicin-Sain, Ramon Arens
Viruses that have coevolved with their host establish chronic infections that are well tolerated by the host. Other viruses, that are partly adapted to their host, may induce chronic infections where persistent replication and viral antigen expression occur. The former induce highly functional and resilient CD8T cell responses called memory inflation. The latter induce dysfunctional and exhausted responses. The reasons compelling T cell responses towards inflationary or exhausted responses are only partly understood...
December 14, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29246443/transcription-factor-irf4-promotes-cd8-t-cell-exhaustion-and-limits-the-development-of-memory-like-t-cells-during-chronic-infection
#15
Kevin Man, Sarah S Gabriel, Yang Liao, Renee Gloury, Simon Preston, Darren C Henstridge, Marc Pellegrini, Dietmar Zehn, Friederike Berberich-Siebelt, Mark A Febbraio, Wei Shi, Axel Kallies
During chronic stimulation, CD8+ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected with lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1...
December 19, 2017: Immunity
https://www.readbyqxmd.com/read/29236683/effector-cd8-t-cells-dedifferentiate-into-long-lived-memory-cells
#16
Ben Youngblood, J Scott Hale, Haydn T Kissick, Eunseon Ahn, Xiaojin Xu, Andreas Wieland, Koichi Araki, Erin E West, Hazem E Ghoneim, Yiping Fan, Pranay Dogra, Carl W Davis, Bogumila T Konieczny, Rustom Antia, Xiaodong Cheng, Rafi Ahmed
Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29212661/disruption-of-an-rna-binding-hinge-region-abolishes-lhp1-mediated-epigenetic-repression
#17
Scott Berry, Stefanie Rosa, Martin Howard, Marc Bühler, Caroline Dean
Epigenetic maintenance of gene repression is essential for development. Polycomb complexes are central to this memory, but many aspects of the underlying mechanism remain unclear. LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binds Polycomb-deposited H3K27me3 and is required for repression of many Polycomb target genes in Arabidopsis Here we show that LHP1 binds RNA in vitro through the intrinsically disordered hinge region. By independently perturbing the RNA-binding hinge region and H3K27me3 (trimethylation of histone H3 at Lys27) recognition, we found that both facilitate LHP1 localization and H3K27me3 maintenance...
November 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29190361/shaping-epigenetic-memory-via-genomic-bookmarking
#18
Davide Michieletto, Michael Chiang, Davide Colì, Argyris Papantonis, Enzo Orlandini, Peter R Cook, Davide Marenduzzo
Reconciling the stability of epigenetic patterns with the rapid turnover of histone modifications and their adaptability to external stimuli is an outstanding challenge. Here, we propose a new biophysical mechanism that can establish and maintain robust yet plastic epigenetic domains via genomic bookmarking (GBM). We model chromatin as a recolourable polymer whose segments bear non-permanent histone marks (or colours) which can be modified by 'writer' proteins. The three-dimensional chromatin organisation is mediated by protein bridges, or 'readers', such as Polycomb Repressive Complexes and Transcription Factors...
January 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29178433/triptolide-inhibits-donor-specific-antibody-production-and-attenuates-mixed-antibody-mediated-renal-allograft-injury
#19
Daqiang Zhao, Siwen Li, Tao Liao, Yuan Wei, Mingyu Liu, Fei Han, Zihuan Luo, Xiaonan Liu, Qiquan Sun
Donor-specific antibodies (DSAs) are major mediators of renal allograft injury, and strategies to inhibit DSAs are important in promoting long-term graft survival. Triptolide exhibits a wide spectrum of antiinflammatory and immunosuppressive activities, and in autoimmune diseases it inhibits autoantibody levels. In this study, we investigated the suppressive role of triptolide in the generation of DSAs in transplant recipients. We found that triptolide treatment of skin allograft recipients in mice significantly suppressed the development of circulating anti-donor-specific IgG and effectively alleviated DSA-mediated renal allograft injury, which led to prolonged allograft survival...
May 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#20
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
December 1, 2017: Brain: a Journal of Neurology
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