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https://www.readbyqxmd.com/read/27914701/il-2-anti-il-2-complexes-ameliorate-lupus-nephritis-by-expansion-of-cd4-cd25-foxp3-regulatory-t%C3%A2-cells
#1
Ji-Jing Yan, Jae-Ghi Lee, Joon Young Jang, Tai Yeon Koo, Curie Ahn, Jaeseok Yang
Adoptive transfer of regulatory T cells (Tregs) can delay disease progression and reduce mortality in lupus-prone mice. Here, we tested whether complex (IL-2C) consisting of IL-2 and anti-IL-2 monoclonal antibody (JES6-1) ameliorates lupus nephritis by expanding Tregs as an alternative to problematic Treg infusion therapy. IL-2C treatment of NZB/W F1 mice induced an effective and sustained expansion of CD4(+)CD25(+)Foxp3(+) Tregs in both the kidneys and spleen along with decreased renal infiltration of T cells, B cells, and innate immune cells...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27913589/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#2
Rashad Hussain, Wendy B Macklin
: During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin linked kinase (ILK) is an important protein expressed at the inner margins of the plasma membrane, which can mediate some of these signals...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27912146/inosine-acedoben-dimepranol-promotes-an-early-and-sustained-increase-in-the-natural-killer-cell-component-of-circulating-lymphocytes-a-clinical-trial-supporting-anti-viral-indications
#3
S Rumel Ahmed, Amy S Newman, James O'Daly, Sean Duffy, Gillian Grafton, Catherine A Brady, S John Curnow, Nicholas M Barnes, John Gordon
Inosine Acedoben Dimepranol (IAD), licensed for the treatment of cell-mediated immune deficiencies associated with viral infections, has been reported to impact a variety of immune parameters both in vitro and in vivo. Here we report the results from a clinical trial where multiple lymphocyte subsets - CD19+ B cells, CD3+ T cells, CD4+ T-helper cells, FoxP3(hi)/CD25(hi)/CD127(lo) regulatory T cells (Tregs), CD3-/CD56+ NK cells, and CD3+/CD56+ NKT cells - were, together with serum immunoglobulins and IgG subclasses, followed during 14days of IAD administration to ten healthy volunteers; these selected from 27 individuals pre-screened in vitro for their capacity to respond to IAD as gauged by increases in the percentage of Treg and/or NKT cells arising in PHA-stimulated cultures...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27912138/human-specific-genomic-signatures-of-neocortical-expansion
#4
REVIEW
Marta Florio, Víctor Borrell, Wieland B Huttner
Neocortex evolutionary expansion is primarily due to increased proliferative capacity of neural progenitor cells during cortical development. Exploiting insights into the cell biology of cortical progenitors gained during the past two decades, recent studies uncovered a variety of gene expression differences that underlie differential cortical progenitor behavior. These comprise both, differences between cortical areas that likely provide a molecular basis for cortical folding, and differences across species thought to be responsible for increases in neocortex size...
November 29, 2016: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#5
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911438/evolutionary-convergence-in-experimental-pseudomonas-populations
#6
Peter A Lind, Andrew D Farr, Paul B Rainey
Model microbial systems provide opportunity to understand the genetic bases of ecological traits, their evolution, regulation and fitness contributions. Experimental populations of Pseudomonas fluorescens rapidly diverge in spatially structured microcosms producing a range of surface-colonising forms. Despite divergent molecular routes, wrinkly spreader (WS) niche specialist types overproduce a cellulosic polymer allowing mat formation at the air-liquid interface and access to oxygen. Given the range of ways by which cells can form mats, such phenotypic parallelism is unexpected...
December 2, 2016: ISME Journal
https://www.readbyqxmd.com/read/27909060/cd6-regulates-intestinal-ischemia-reperfusion-induced-injury-by-modulating-natural-igm-producing-b1a-cell-self-renewal
#7
Gospel Enyindah-Asonye, Yan Li, Wei Xin, Nora Singer, Neetu Gupta, John Fung, Feng Lin
Intestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and later found to be present on some subsets of B cells in humans, however, whether CD6 plays any role in intestinal I/R induced injury and if so, what are the underlying mechanisms, remain unknown...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27909059/the-role-of-the-histone-methyltransferase-enhancer-of-zeste-homolog-2-ezh2-in-the-pathobiological-mechanisms-underlying-inflammatory-bowel-disease-ibd
#8
Olga F Sarmento, Phyllis A Svingen, Yuning Xiong, Zhifu Sun, Adebowale O Bamidele, Angela J Mathison, Thomas C Smyrk, Asha A Nair, Michelle M Gonzalez, Mary R Sagstetter, Saurabh Baheti, Dermot P B McGovern, Jessica J Friton, Konstantinos A Papadakis, Goel Gautam, Ramnik J Xavier, Raul A Urrutia, William A Faubion
Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have previously shown that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2ΔFOXP3+). We find that EZH2 deficiency in FOXP3+ T cells results in lethal multi-organ autoimmunity. We further demonstrate that EZH2ΔFOXP3+ T cells lack a regulatory phenotype in vitro and secrete pro-inflammatory cytokines...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27907249/grainyhead-like-3-grhl3-deficiency-in-brain-leads-to-altered-locomotor-activity-and-decreased-anxiety-like-behaviours-in-aged-mice
#9
Sebastian Dworkin, Alana Auden, Darren D Partridge, Maria Daglas, Robert L Medcalf, Theo Mantamadiotis, Smitha R Georgy, Charbel Darido, Stephen M Jane, Stephen B Ting
The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here we show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviours...
December 1, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/27907175/p53-specifically-binds-triplex-dna-in-vitro-and-in-cells
#10
Marie Brázdová, Vlastimil Tichý, Robert Helma, Pavla Bažantová, Alena Polášková, Aneta Krejčí, Marek Petr, Lucie Navrátilová, Olga Tichá, Karel Nejedlý, Martin L Bennink, Vinod Subramaniam, Zuzana Bábková, Tomáš Martínek, Matej Lexa, Matej Adámik
Triplex DNA is implicated in a wide range of biological activities, including regulation of gene expression and genomic instability leading to cancer. The tumor suppressor p53 is a central regulator of cell fate in response to different type of insults. Sequence and structure specific modes of DNA recognition are core attributes of the p53 protein. The focus of this work is the structure-specific binding of p53 to DNA containing triplex-forming sequences in vitro and in cells and the effect on p53-driven transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27903835/identification-of-microrna-signature-and-potential-pathway-targets-in-prostate-cancer
#11
Ahmed A Moustafa, Mohammed Ziada, Abubaker Elshaikh, Amrita Datta, Hogyoung Kim, Krzysztof Moroz, Sudesh Srivastav, Raju Thomas, Jonathan L Silberstein, Krishnarao Moparty, Fatma Elzahraa H Salem, Ola H El-Habit, Asim B Abdel-Mageed
Prostate cancer (PC) is the most common and the second leading cause of cancer-related death among American men. Early diagnosis is a prerequisite to improving therapeutic benefits. However, the current clinical biomarkers for PC do not reliably decipher indolent PC from other urogenital disorders. Thus, effective clinical intervention necessitates development of new biomarkers for early detection of PC. The present study aimed to identify the miRNA signature in organ-confined (Gleason Score 6) prostate tumors...
November 29, 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27903772/diverse-activities-of-viral-cis-acting-rna-regulatory-elements-revealed-using-multi-color-long-term-single-cell-imaging
#12
Ginger M Pocock, Laraine L Zimdars, Ming Yuan, Kevin W Eliceiri, Paul Ahlquist, Nathan M Sherer
Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other post-transcriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multi-color, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus) and an intron-retaining transcript encoded by the cellular NXF1 gene...
November 30, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#13
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27902946/social-regulation-of-the-lymph-node-transcriptome-in-rhesus-macaques-macaca-mulatta
#14
K Chun, J P Capitanio, D M Lamkin, E K Sloan, J M G Arevalo, S W Cole
Previous research has shown that adverse social conditions may promote a conserved transcriptional response to adversity (CTRA) involving up-regulation of proinflammatory gene expression and down-regulation of Type I interferon anti-viral genes in circulating blood cells. However, the impact of social conditions on lymphoid tissue gene regulation remains largely unexplored. This project assessed how social instability in adult male rhesus macaques (N=10, 5 in unstable, and 5 in stable social conditions) might regulate gene expression within secondary lymphoid tissue (lymph nodes; LN)...
November 14, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27902485/impacts-of-cigarette-smoking-on-immune-responsiveness-up-and-down-or-upside-down
#15
REVIEW
Feifei Qiu, Chun-Ling Liang, Huazhen Liu, Yu-Qun Zeng, Shaozhen Hou, Song Huang, Xiaoping Lai, Zhenhua Dai
Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900675/sirp-alpha-protein-downregulates-in-human-astrocytoma-presumptive-involvement-of-hsa-mir-520d-5p-and-hsa-mir-520d-3p
#16
Ravindra Pramod Deshpande, Y B V K Chandra Sekhar, Manas Panigrahi, Phanithi Prakash Babu
Astrocytomas are the most common brain tumors with poor survival in malignant forms. Signal regulatory protein alpha (SIRP alpha) is a transmembrane protein expressed on immune cells and macrophages and is reported to modulate tumor cell phagocytosis. In the present study, we investigated the involvement of miR-520d-5p and miR-520d-3p in regulation of SIRP alpha expression. Here, we report mRNA and protein expression profile of SIRP alpha in 39 surgically resected human astrocytoma tissue samples and 14 control brain tissue samples...
November 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27900346/preclinical-development-and-qualification-of-zfn-mediated-ccr5-disruption-in-human-hematopoietic-stem-progenitor-cells
#17
David L DiGiusto, Paula M Cannon, Michael C Holmes, Lijing Li, Anitha Rao, Jianbin Wang, Gary Lee, Philip D Gregory, Kenneth A Kim, Samuel B Hayward, Kathleen Meyer, Colin Exline, Evan Lopez, Jill Henley, Nancy Gonzalez, Victoria Bedell, Rodica Stan, John A Zaia
Gene therapy for HIV-1 infection is a promising alternative to lifelong combination antiviral drug treatment. Chemokine receptor 5 (CCR5) is the coreceptor required for R5-tropic HIV-1 infection of human cells. Deletion of CCR5 renders cells resistant to R5-tropic HIV-1 infection, and the potential for cure has been shown through allogeneic stem cell transplantation with naturally occurring homozygous deletion of CCR5 in donor hematopoietic stem/progenitor cells (HSPC). The requirement for HLA-matched HSPC bearing homozygous CCR5 deletions prohibits widespread application of this approach...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27899639/histone-demethylase-phf8-promotes-epithelial-to-mesenchymal-transition-and-breast-tumorigenesis
#18
Peng Shao, Qi Liu, Peterson Kariuki Maina, Jiayue Cui, Thomas B Bair, Tiandao Li, Shaikamjad Umesalma, Weizhou Zhang, Hank Heng Qi
Histone demethylase PHF8 is upregulated and plays oncogenic roles in various cancers; however, the mechanisms underlying its dysregulation and functions in carcinogenesis remain obscure. Here, we report the novel functions of PHF8 in EMT (epithelial to mesenchymal transition) and breast cancer development. Genome-wide gene expression analysis revealed that PHF8 overexpression induces an EMT-like process, including the upregulation of SNAI1 and ZEB1. PHF8 demethylates H3K9me1, H3K9me2 and sustains H3K4me3 to prime the transcriptional activation of SNAI1 by TGF-β signaling...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899441/interferon-regulatory-factor-2-protects-mice-from-lethal-viral-neuroinvasion
#19
Melody M H Li, Leonia Bozzacco, Hans-Heinrich Hoffmann, Gaëlle Breton, Jakob Loschko, Jing W Xiao, Sébastien Monette, Charles M Rice, Margaret R MacDonald
The host responds to virus infection by activating type I interferon (IFN) signaling leading to expression of IFN-stimulated genes (ISGs). Dysregulation of the IFN response results in inflammatory diseases and chronic infections. In this study, we demonstrate that IFN regulatory factor 2 (IRF2), an ISG and a negative regulator of IFN signaling, influences alphavirus neuroinvasion and pathogenesis. A Sindbis virus strain that in wild-type (WT) mice only causes disease when injected into the brain leads to lethal encephalitis in Irf2(-/-) mice after peripheral inoculation...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#20
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
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