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https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#1
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28523006/virtual-plant-tissue-building-blocks-for-next-generation-plant-growth-simulation
#2
Dirk De Vos, Abdiravuf Dzhurakhalov, Sean Stijven, Przemyslaw Klosiewicz, Gerrit T S Beemster, Jan Broeckhove
Motivation: Computational modeling of plant developmental processes is becoming increasingly important. Cellular resolution plant tissue simulators have been developed, yet they are typically describing physiological processes in an isolated way, strongly delimited in space and time. Results: With plant systems biology moving toward an integrative perspective on development we have built the Virtual Plant Tissue (VPTissue) package to couple functional modules or models in the same framework and across different frameworks...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28522735/d3-receptors-regulate-excitability-in-a-unique-class-of-prefrontal-pyramidal-cell
#3
Rebecca L Clarkson, Alayna T Liptak, Steven M Gee, Vikaas S Sohal, Kevin J Bender
The D3 dopamine receptor, a member of the Gi-coupled D2-family of dopamine receptors, is expressed throughout limbic circuits affected in neuropsychiatric disorders, including prefrontal cortex. These receptors are important for prefrontal executive function, as pharmacological and genetic manipulations that affect prefrontal D3 receptors alter anxiety, social interaction, and reversal learning. And yet, the mechanisms by which D3 receptors regulate prefrontal circuits, and whether D3 receptors regulate specific prefrontal subnetworks, remain unknown...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28522599/engineering-macrophages-to-eat-cancer-from-marker-of-self-cd47-and-phagocytosis-to-differentiation
#4
REVIEW
Cory Alvey, Dennis E Discher
The ability of a macrophage to engulf and break down invading cells and other targets provides a first line of immune defense in nearly all tissues. This defining ability to "phagos" or devour can subsequently activate the entire immune system against foreign and diseased cells, and progress is now being made on a decades-old idea of directing macrophages to phagocytose specific targets, such as cancer cells. Engineered T cells provide precedence with recent clinical successes against liquid tumors, but solid tumors remain a challenge, and a handful of clinical trials seek to exploit the abundance of tumor-associated macrophages instead...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28514665/systems-analysis-reveals-high-genetic-and-antigen-driven-predetermination-of-antibody-repertoires-throughout-b-cell-development
#5
Victor Greiff, Ulrike Menzel, Enkelejda Miho, Cédric Weber, René Riedel, Skylar Cook, Atijeh Valai, Telma Lopes, Andreas Radbruch, Thomas H Winkler, Sai T Reddy
Antibody repertoire diversity and plasticity is crucial for broad protective immunity. Repertoires change in size and diversity across multiple B cell developmental stages and in response to antigen exposure. However, we still lack fundamental quantitative understanding of the extent to which repertoire diversity is predetermined. Therefore, we implemented a systems immunology framework for quantifying repertoire predetermination on three distinct levels: (1) B cell development (pre-B cell, naive B cell, plasma cell), (2) antigen exposure (three structurally different proteins), and (3) four antibody repertoire components (V-gene usage, clonal expansion, clonal diversity, repertoire size) extracted from antibody repertoire sequencing data (400 million reads)...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514446/identification-of-preoptic-sleep-neurons-using-retrograde-labelling-and-gene-profiling
#6
Shinjae Chung, Franz Weber, Peng Zhong, Chan Lek Tan, Thuc Nghi Nguyen, Kevin T Beier, Nikolai Hörmann, Wei-Cheng Chang, Zhe Zhang, Johnny Phong Do, Shenqin Yao, Michael J Krashes, Bosiljka Tasic, Ali Cetin, Hongkui Zeng, Zachary A Knight, Liqun Luo, Yang Dan
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28503202/stabilization-of-foxp3-expression-by-crispr-dcas9-based-epigenome-editing-in-mouse-primary-t-cells
#7
Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa, Akihiko Yoshimura
BACKGROUND: Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. RESULTS: In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs)...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28501368/contribution-of-immunology-to-implantation-failure-of-euploid-embryos
#8
REVIEW
Jason M Franasiak, Richard T Scott
Outcomes in assisted reproduction have seen marked improvement. With increased ability in the embryology laboratory to use extended embryo culture which in turn enables other selective techniques, such as trophectoderm biopsy and comprehensive chromosome screening, the chance of success per embryo transfer is increased. However, even the selection of a euploid blastocyst, which selects out many embryonic factors, does not yield successful implantation and ultimately delivery in all cases. Among the factors that affect implantation failure of apparently reproductively competent embryos, the immune system has been perhaps both the most plausible and the most debated...
May 10, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28497800/reciprocal-regulation-of-the-il9-locus-by-counteracting-activities-of-transcription-factors-irf1-and-irf4
#9
Lucia Campos Carrascosa, Matthias Klein, Yohko Kitagawa, Christina Lückel, Federico Marini, Anika König, Anna Guralnik, Hartmann Raifer, Stefanie Hagner-Benes, Diana Rädler, Andreas Böck, Cholho Kang, Michael Lohoff, Holger Garn, Bianca Schaub, Friederike Berberich-Siebelt, Shimon Sakaguchi, Tobias Bopp, Magdalena Huber
The T helper 9 (Th9) cell transcriptional network is formed by an equilibrium of signals induced by cytokines and antigen presentation. Here we show that, within this network, two interferon regulatory factors (IRF), IRF1 and IRF4, display opposing effects on Th9 differentiation. IRF4 dose-dependently promotes, whereas IRF1 inhibits, IL-9 production. Likewise, IRF1 inhibits IL-9 production by human Th9 cells. IRF1 counteracts IRF4-driven Il9 promoter activity, and IRF1 and IRF4 have opposing function on activating histone modifications, thus modulating RNA polymerase II recruitment...
May 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28497488/the-common-parasite-toxoplasma-gondii-induces-prostatic-inflammation-and-microglandular-hyperplasia-in-a-mouse-model
#10
Darrelle L Colinot, Tamila Garbuz, Maarten C Bosland, Liang Wang, Susan E Rice, William J Sullivan, Gustavo Arrizabalaga, Travis J Jerde
BACKGROUND: Inflammation is the most prevalent and widespread histological finding in the human prostate, and associates with the development and progression of benign prostatic hyperplasia and prostate cancer. Several factors have been hypothesized to cause inflammation, yet the role each may play in the etiology of prostatic inflammation remains unclear. This study examined the possibility that the common protozoan parasite Toxoplasma gondii induces prostatic inflammation and reactive hyperplasia in a mouse model...
May 12, 2017: Prostate
https://www.readbyqxmd.com/read/28492073/polyvalent-and-thermosensitive-dna-nanoensembles-for-cancer-cell-detection-and-manipulation
#11
Jinlu Tang, Yanru Yu, Hui Shi, Xiaoxiao He, Yanli Lei, Jingfang Shangguan, Xue Yang, Zhenzhen Qiao, Kemin Wang
Development of smart DNA nanostructures is of great value in cancer studies. Here, by integrating rolling circle amplification (RCA) into split aptamer design, a novel strategy of polyvalent and thermosensitive DNA nanoensembles was first proposed for cancer cell detection and manipulation. In this strategy, a long nanosolo ssDNA with repeated Split-b and Poly T regions was generated through RCA. Split-b supplied polyvalent binding sites while Poly T supported signal output by hybridizing with fluorophore-labeled poly A...
May 11, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28490586/deletion-of-the-k1l-gene-results-in-a-vaccinia-virus-that-is-less-pathogenic-due-to-muted-innate-immune-responses-yet-still-elicits-protective-immunity
#12
Ariana G Bravo Cruz, Aiguo Han, Edward J Roy, Arielle B Guzmán, Rita J Miller, Elizabeth A Driskell, William D O'Brien, Joanna L Shisler
All viruses strategically alter the anti-viral immune response to their benefit. The vaccinia virus (VACV) K1 protein has multiple immunomodulatory effects in tissue culture models of infection, including NF-κB antagonism. However, the effect of K1 during animal infection is poorly understood. We determined that a K1L-less vaccinia virus (vΔK1L) was less pathogenic than wild-type VACV in intranasal and intradermal models of infection. Decreased pathogenicity correlated with diminished virus replication in intranasally-infected mice...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28484465/mitochondrial-control-and-guidance-of-cellular-activities-of-t-cells
#13
REVIEW
Tung Chao, Haiping Wang, Ping-Chih Ho
Immune cells protect us against infection and cancer cells, as well as functioning during healing processes to support tissue repairing and regeneration. These behaviors require that upon stimulation from immune activation the appropriate subsets of immune cells are generated. In addition to activation-induced signaling cascades, metabolic reprogramming (profound changes in metabolic pathways) also provides a novel form of regulation to control the formation of desirable immune responses. Immune cells encounter various nutrient compositions by circulating in bloodstream and infiltrating into peripheral tissues; therefore, proper engagement of metabolic pathways is critical to fulfill the metabolic demands of immune cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28484375/mechanistic-resolution-required-to-mediate-operant-learned-behaviors-insights-from-neuronal-ensemble-specific-inactivation
#14
Brandon L Warren, Nobuyoshi Suto, Bruce T Hope
Many learned behaviors are directed by complex sets of highly specific stimuli or cues. The neural mechanisms mediating learned associations in these behaviors must be capable of storing complex cue information and distinguishing among different learned associations-we call this general concept "mechanistic resolution". For many years, our understanding of the circuitry of these learned behaviors has been based primarily on inactivation of specific cell types or whole brain areas regardless of which neurons were activated during the cue-specific behaviors...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28484005/altered-interactions-between-unicellular-and-multicellular-genes-drive-hallmarks-of-transformation-in-a-diverse-range-of-solid-tumors
#15
Anna S Trigos, Richard B Pearson, Anthony T Papenfuss, David L Goode
Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28480301/vectofusin-1-promotes-rd114-tr-pseudotyped-lentiviral-vector-transduction-of-human-hspcs-and-t-lymphocytes
#16
Claudia Piovan, Virna Marin, Cinzia Scavullo, Stefano Corna, Erica Giuliani, Sergio Bossi, Anne Galy, David Fenard, Claudio Bordignon, Gian Paolo Rizzardi, Chiara Bovolenta
Ex vivo transduction of human CD34(+) hematopoietic stem/progenitor cells (hCD34(+) HSPCs) and T lymphocytes is a key process that requires high efficiency and low toxicity to achieve effective clinical results. So far, several enhancers have been used to improve this process. Among them, Retronectin highly meliorates VSV-G and RD114-TR pseudotyped lentiviral vector delivery in hCD34(+) HSPCs and T lymphocytes. However, Retronectin is expensive and requires pre-coating of culture dishes or bags before cell seeding, resulting in a cumbersome procedure...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28477136/monitoring-the-atm-mediated-dna-damage-response-in-the-cerebellum-using-organotypic-cultures
#17
Efrat Tal, Yosef Shiloh
The ATM gene and its protein product, the ATM protein kinase, were identified as a result of attempts to understand the molecular basis of the genetic disorder, ataxia-telangiectasia (A-T). The cardinal symptom of A-T is neurodegeneration expressed primarily as progressive cerebellar atrophy. A major tool in the investigation of ATM functions in the cerebellum is cerebellar organotypic cultures, which allow cerebellar slices to live in culture for several weeks without losing their viability and organization...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28473706/molecular-mechanisms-underlying-the-evolution-of-the-slp76-signalosome
#18
Xuemei Qu, Xin Lan, Chong Deng, Jiatao Zhou, Jingjing Du, Shengfeng Huang, Yingqiu Li
The well-defined mammalian slp76-signalosome is crucial for T-cell immune response, yet whether slp76-signalosome exists in invertebrates and how it evolved remain unknown. Here we investigated slp76-signalosome from an evolutionary perspective in amphioxus Branchiostoma belcheri (bb). We proved slp76-signalosome components bbslp76, bbGADS and bbItk are present in amphioxus and bbslp76 interacts with bbGADS and bbItk, but differences exist between the interaction manners within slp76-signalosome components of amphioxus and human (h)...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28473535/androgen-receptor-variant-ar-v9-is-co-expressed-with-ar-v7-in-prostate-cancer-metastases-and-predicts-abiraterone-resistance
#19
Manish Kohli, Yeung Ho, David W Hillman, Jamie L Van Etten, Christine Henzler, Rendong Yang, Jame M Sperger, Yingming Li, Elizabeth Tseng, Ting Hon, Tyson Clark, Winston Tan, Rachel E Carlson, Liguo Wang, Hugues Sicotte, Ho Thai, Rafael Jimenez, Haojie Huang, Peter T Vedell, Bruce W Eckloff, J Fernando Quevedo, Henry C Pitot, Brian Costello, Jin Jen, Eric D Wieben, Kevin A T Silverstein, Joshua M Lang, Liewei Wang, Scott M Dehm
Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies.  Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC).  The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies.<br /><br /> Experimental Design:  We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models...
May 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28472904/leveraging-natural-killer-cells-for-cancer-immunotherapy
#20
Steven K Grossenbacher, Ethan G Aguilar, William J Murphy
Natural killer (NK) cells are potent antitumor effector cells of the innate immune system. Based on their ability to eradicate tumors in vitro and in animal models, significant enthusiasm surrounds the prospect of leveraging human NK cells as vehicles for cancer immunotherapy. While interest in manipulating the effector functions of NK cells has existed for over 30 years, there is renewed optimism for this approach today. Although T cells receive much of the clinical and preclinical attention when it comes to cancer immunotherapy, new strategies are utilizing adoptive NK-cell immunotherapy and monoclonal antibodies and engineered molecules which have been developed to specifically activate NK cells against tumors...
May 2017: Immunotherapy
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