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https://www.readbyqxmd.com/read/27902980/gene-expression-profiling-and-functional-characterization-of-macrophages-in-response-to-circulatory-microparticles-produced-during-trypanosoma-cruzi-infection-and-chagas-disease
#1
Imran H Chowdhury, Sue-Jie Koo, Shivali Gupta, Lisa Yi Liang, Bojlul Bahar, Laura Silla, Julio Nuñez-Burgos, Natalia Barrientos, Maria Paola Zago, Nisha Jain Garg
BACKGROUND: Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHODS: MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs...
December 1, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27899560/not5-dependent-co-translational-assembly-of-ada2-and-spt20-is-essential-for-functional-integrity-of-saga
#2
Sari Kassem, Zoltan Villanyi, Martine A Collart
Acetylation of histones regulates gene expression in eukaryotes. In the yeast Saccharomyces cerevisiae it depends mainly upon the ADA and SAGA histone acetyltransferase complexes for which Gcn5 is the catalytic subunit. Previous screens have determined that global acetylation is reduced in cells lacking subunits of the Ccr4-Not complex, a global regulator of eukaryotic gene expression. In this study we have characterized the functional connection between the Ccr4-Not complex and SAGA. We show that SAGA mRNAs encoding a core set of SAGA subunits are tethered together for co-translational assembly of the encoded proteins...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27887569/immune-modulation-of-cd4-cd25-regulatory-t-cells-by-zoledronic-acid
#3
Hsien Liu, Shih-Han Wang, Shin-Cheh Chen, Ching-Ying Chen, Jo-Lin Lo, Tsun-Mei Lin
BACKGROUND: CD4(+)CD25(+) regulatory T (Treg) cells suppress tumor immunity by inhibiting immune cells. Manipulation of Treg cells represents a new strategy for cancer treatment. Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, inhibits the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts to inhibit osteoclastogenesis. In a mouse model of bisphosphonate-related osteonecrosis of the jaw, administration of ZA suppressed Treg-cell activity and activated inflammatory Th17 cells...
November 25, 2016: BMC Immunology
https://www.readbyqxmd.com/read/27868052/friend-or-foe-mogamulizumab-in-allogeneic-hematopoietic-stem-cell-transplantation-for-adult-t-cell-leukemia-lymphoma
#4
REVIEW
Shigeo Fuji, Takero Shindo
Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP) results in a dismal clinical outcome, with a median overall survival of only around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to long-term remission in a proportion of patients with aggressive ATL, the clinical outcome in patients with refractory or relapsed ATL is unsatisfactory...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27863545/porcine-treg-depletion-with-a-novel-diphtheria-toxin-based-anti-human-ccr4-immunotoxin
#5
Zhaohui Wang, Nalu Navarro-Alvarez, Jigesh A Shah, Huiping Zhang, Qi Huang, Qian Zheng, Joren C Madsen, David H Sachs, Christene A Huang, Zhirui Wang
Regulatory T cells (Tregs) are known to play an important role in immunoregulation and have been shown to facilitate induction of transplantation tolerance. Chemokine (C-C motif) receptor 4 (CCR4) is expressed on the surface of effector Tregs involved in controlling alloimmune and autoimmune responses. Recently we have developed a novel diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we have demonstrated that the anti-human CCR4 immunotoxin bound to porcine lymphocytes including CD4(+)FoxP3(+) Tregs...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27851962/reconstitution-of-targeted-deadenylation-by-the-ccr4-not-complex-and-the-yth-domain-protein-mmi1
#6
James A W Stowell, Michael W Webster, Alexander Kögel, Jana Wolf, Kathryn L Shelley, Lori A Passmore
Ccr4-Not is a conserved protein complex that shortens the 3' poly(A) tails of eukaryotic mRNAs to regulate transcript stability and translation into proteins. RNA-binding proteins are thought to facilitate recruitment of Ccr4-Not to certain mRNAs, but lack of an in-vitro-reconstituted system has slowed progress in understanding the mechanistic details of this specificity. Here, we generate a fully recombinant Ccr4-Not complex that removes poly(A) tails from RNA substrates. The intact complex is more active than the exonucleases alone and has an intrinsic preference for certain RNAs...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27820933/secretoglobin-superfamily-protein-scgb3a2-alleviates-house-dust-mite-induced-allergic-airway-inflammation-in-mice
#7
Mitsuhiro Yoneda, Lei Xu, Hiroaki Kajiyama, Shuko Kawabe, Jorge Paiz, Jerrold M Ward, Shioko Kimura
BACKGROUND: Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growth-factor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27819062/reconstitution-of-peripheral-t-cells-by-tissue-derived-ccr4-central-memory-cells-following-hiv-1-antiretroviral-therapy
#8
Yolanda D Mahnke, Kipper Fletez-Brant, Irini Sereti, Mario Roederer
BACKGROUND: Highly active antiretroviral therapy induces clinical benefits to HIV-1 infected individuals, which can be striking in those with progressive disease. Improved survival and decreased incidence of opportunistic infections go hand in hand with a suppression of the plasma viral load, an increase in peripheral CD4(+) T-cell counts, as well as a reduction in the activation status of both CD4(+) and CD8(+) T cells. METHODS: We investigated T-cell dynamics during ART by polychromatic flow cytometry in total as well as in HIV-1-specific CD4(+) and CD8(+) T cells in patients with advanced disease...
2016: Pathogens & Immunity
https://www.readbyqxmd.com/read/27807034/interaction-of-ccr4-not-with-ebf1-regulates-gene-specific-transcription-and-mrna-stability-in-b-lymphopoiesis
#9
Cheng-Yuan Yang, Senthilkumar Ramamoorthy, Sören Boller, Marc Rosenbaum, Alfonso Rodriguez Gil, Gerhard Mittler, Yumiko Imai, Keiji Kuba, Rudolf Grosschedl
Transcription factor EBF1 (early B-cell factor 1) regulates early B-cell differentiation by poising or activating lineage-specific genes and repressing genes associated with alternative cell fates. To identify proteins that regulate the diverse functions of EBF1, we used SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry of proteins associated with endogenous EBF1 in pro-B cells. This analysis identified most components of the multifunctional CCR4-NOT complex, which regulates transcription and mRNA degradation...
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27795537/htlv-1-targeted-immunotherapy
#10
Youko Suehiro
Adult T-cell leukemia/lymphoma (ATL) is a HTLV-1 induced T-cell malignancy with an extremely poor prognosis. There is a long latency period between HTLV-1 infection and the onset of ATL, which indicates the existence of multistep mechanisms of leukemogenesis in the infected cells. Tax, which is encoded by the HTLV-1 pX region, plays a crucial role in HTLV-1 leukemogenesis and is a major target of CTL. We developed an anti-ATL therapeutic vaccine consisting of autologous dendritic cells that is pulsed with Tax peptides (Tax-DC)...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27786349/cd8-t-cell-mediated-interface-dermatitis-after-ccr4-t-cell-depletion-by-mogamulizumab-treatment-of-adult-t-cell-leukaemia-lymphoma
#11
Ayako Ito, Kazunari Sugita, Koji Adachi, Yuzuru Hosoda, Toru Motokura, Osamu Yamamoto
is missing (Short communication).
October 27, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27771561/proteomic-analysis-of-the-gamma-human-papillomavirus-type-197-e6-and-e7-associated-cellular-proteins
#12
Miranda Grace, Karl Munger
Gamma HPV197 was the most frequently identified HPV when human skin cancer specimens were analyzed by deep sequencing (Arroyo Muhr et al., Int. J. Cancer 136: 2546-55, 2015). To gain insight into the biological activities of HPV197, we investigated the cellular interactomes of HPV197 E6 and E7. HPV197 E6 protein interacts with a broad spectrum of cellular LXXLL domain proteins, including UBE3A and MAML1. HPV197 E6 also binds and inhibits the TP53 tumor suppressor and interacts with the CCR4-NOT ubiquitin ligase and deadenylation complex...
January 2017: Virology
https://www.readbyqxmd.com/read/27751964/altered-expression-of-glial-markers-chemokines-and-opioid-receptors-in-the-spinal-cord-of-type-2-diabetic-monkeys
#13
Norikazu Kiguchi, Huiping Ding, Christopher M Peters, Nancy D Kock, Shiroh Kishioka, J Mark Cline, Janice D Wagner, Mei-Chuan Ko
Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6)...
October 14, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27746116/cnot3-dependent-mrna-deadenylation-safeguards-the-pluripotent-state
#14
Xiaofeng Zheng, Pengyi Yang, Brad Lackford, Brian D Bennett, Li Wang, Hui Li, Yu Wang, Yiliang Miao, Julie F Foley, David C Fargo, Ying Jin, Carmen J Williams, Raja Jothi, Guang Hu
Poly(A) tail length and mRNA deadenylation play important roles in gene regulation. However, how they regulate embryonic development and pluripotent cell fate is not fully understood. Here we present evidence that CNOT3-dependent mRNA deadenylation governs the pluripotent state. We show that CNOT3, a component of the Ccr4-Not deadenylase complex, is required for mouse epiblast maintenance. It is highly expressed in blastocysts and its deletion leads to peri-implantation lethality. The epiblast cells in Cnot3 deletion embryos are quickly lost during diapause and fail to outgrow in culture...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27718189/in-silico-adjuvant-design-and-validation
#15
Matthew N Davies, Helene Pere, Iris Bosschem, Freddy Haesebrouck, Bram Flahou, Eric Tartour, Darren R Flower, David F Tough, Jagadeesh Bayry
Adjuvants are substances that boost the protective immune response to vaccine antigens. The majority of known adjuvants have been identified through the use of empirical approaches. Our aim was to identify novel adjuvants with well-defined cellular and molecular mechanisms by combining a knowledge of immunoregulatory mechanisms with an in silico approach. CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) inhibit the protective immune responses to vaccines by suppressing the activation of antigen presenting cells such as dendritic cells (DCs)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27714489/novel-interaction-between-ccr4-and-caf1-in-rice-ccr4-not-deadenylase-complex
#16
Wei-Lun Chou, Yue-Lin Chung, Jhen-Cheng Fang, Chung-An Lu
Rice is an important crop in the world. However, little is known about rice mRNA deadenylation, which is an important regulation step of gene expression at the post-transcriptional level. The CCR4-NOT1 complex contains two key components, CCR4 and CAF1, which are the main cytoplasmic deadenylases in eukaryotic cells. In yeast and humans, CCR4 can interact with CAF1 via its N-terminal LRR domain. However, no CCR4 protein containing N-terminal LRR motifs have been found in plants. In this manuscript, we demonstrate a novel pattern of interaction between OsCCR4 and OsCAF1 in the rice CCR4-NOT complex, and that OsCAF1 acts as a bridge between OsCCR4 and OsNOT1 in this complex...
October 6, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27708140/the-camp-pathway-regulates-mrna-decay-through-phosphorylation-of-the-rna-binding-protein-tis11b-brf1
#17
Felicitas Rataj, Séverine Planel, Agnès Desroches-Castan, Juliette Le Douce, Khadija Lamribet, Josiane Denis, Jean-Jacques Feige, Nadia Cherradi
TPA-inducible sequence 11b/butyrate response factor 1 (TIS11b/BRF1) belongs to the tristetraprolin (TTP) family of zinc-finger proteins, which bind to mRNAs containing AU-rich elements in their 3'-untranslated region and target them for degradation. Regulation of TTP family function through phosphorylation by p38 MAP kinase and Akt/protein kinase B signaling pathways has been extensively studied. In contrast, the role of cAMP-dependent protein kinase (PKA) in the control of TTP family activity in mRNA decay remains largely unknown...
December 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27704052/different-regulations-of-rom2-and-lrg1-expression-by-ccr4-pop2-and-dhh1-in-the-saccharomyces-cerevisiae-cell-wall-integrity-pathway
#18
Xia Li, Tetsuro Ohmori, Kaoru Irie, Yuichi Kimura, Yasuyuki Suda, Tomoaki Mizuno, Kenji Irie
Ccr4, a component of the Ccr4-Not cytoplasmic deadenylase complex, is known to be required for the cell wall integrity (CWI) pathway in the budding yeast Saccharomyces cerevisiae. However, it is not fully understood how Ccr4 and other components of the Ccr4-Not complex regulate the CWI pathway. Previously, we showed that Ccr4 functions in the CWI pathway together with Khd1 RNA binding protein. Ccr4 and Khd1 modulate a signal from Rho1 small GTPase in the CWI pathway by regulating the expression of ROM2 mRNA and LRG1 mRNA, encoding a guanine nucleotide exchange factor (GEF) and a GTPase-activating protein (GAP) for Rho1, respectively...
September 2016: MSphere
https://www.readbyqxmd.com/read/27701073/a-continuum-of-mrnp-complexes-in-embryonic-microrna-mediated-silencing
#19
Edlyn Wu, Ajay A Vashisht, Clément Chapat, Mathieu N Flamand, Emiliano Cohen, Mihail Sarov, Yuval Tabach, Nahum Sonenberg, James Wohlschlegel, Thomas F Duchaine
MicroRNAs (miRNAs) impinge on the translation and stability of their target mRNAs, and play key roles in development, homeostasis and disease. The gene regulation mechanisms they instigate are largely mediated through the CCR4-NOT deadenylase complex, but the molecular events that occur on target mRNAs are poorly resolved. We observed a broad convergence of interactions of germ granule and P body mRNP components on AIN-1/GW182 and NTL-1/CNOT1 in Caenorhabditis elegans embryos. We show that the miRISC progressively matures on the target mRNA from a scanning form into an effector mRNP particle by sequentially recruiting the CCR4-NOT complex, decapping and decay, or germ granule proteins...
October 3, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27695445/ccr4-not-complex-subunit-not2-plays-critical-roles-in-vegetative-growth-conidiation-and-virulence-in-watermelon-fusarium-wilt-pathogen-fusarium-oxysporum-f-sp-niveum
#20
Yi Dai, Zhongye Cao, Lihong Huang, Shixia Liu, Zhihui Shen, Yuyan Wang, Hui Wang, Huijuan Zhang, Dayong Li, Fengming Song
CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon...
2016: Frontiers in Microbiology
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