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https://www.readbyqxmd.com/read/28641094/emerging-concepts-in-cytomegalovirus-infection-following-hematopoietic-stem-cell-transplantation
#1
REVIEW
Jose F Camargo, Krishna V Komanduri
Despite the refinements in molecular methods for the detection of cytomegalovirus (CMV) and the advent of highly effective preemptive strategies, CMV remains a leading cause of morbidity and mortality in hematopoietic cell transplant (HCT) recipients. CMV can cause tissue-invasive disease including pneumonia, hepatitis, colitis, retinitis, and encephalitis. Mortality in HCT recipients with CMV disease can be as high as 60%. CMV infection has been associated with increased risk of secondary bacterial and fungal infections, increased risk of graft-versus-host disease, and high rates of nonrelapse mortality following HCT...
June 14, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#2
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28640810/lassim-a-network-inference-toolbox-for-genome-wide-mechanistic-modeling
#3
Rasmus Magnusson, Guido Pio Mariotti, Mattias Köpsén, William Lövfors, Danuta R Gawel, Rebecka Jörnsten, Jörg Linde, Torbjörn Nordling, Elin Nyman, Sylvie Schulze, Colm E Nestor, Huan Zhang, Gunnar Cedersund, Mikael Benson, Andreas Tjärnberg, Mika Gustafsson
Recent technological advancements have made time-resolved, quantitative, multi-omics data available for many model systems, which could be integrated for systems pharmacokinetic use. Here, we present large-scale simulation modeling (LASSIM), which is a novel mathematical tool for performing large-scale inference using mechanistically defined ordinary differential equations (ODE) for gene regulatory networks (GRNs). LASSIM integrates structural knowledge about regulatory interactions and non-linear equations with multiple steady state and dynamic response expression datasets...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28640587/silica-nanoparticle-as-a-lymph-node-targeting-platform-for-vaccine-delivery
#4
Myunggi An, Meng Li, Jingchao Xi, Haipeng Liu
Nanoparticles have emerged as the platform of choice to improve the efficacy and safety of subunit vaccines. A major challenge underlying the use of nanomaterials in vaccines lies in the particle designs that can efficiently target and activate the antigen-presenting cells, especially dendritic cells. Here we show a toll-like receptor 9 (TLR-9) agonist and antigen co-loaded, silica nanoparticles (SiNPs) are able to accumulate in antigen presenting cells in the draining lymph nodes after injection. Vaccine loaded SiNPs led to dramatically enhanced induction of antigen-specific B and T cell responses as compared to soluble vaccines, which in turn drove a protective antitumoral immunity in a murine tumor model...
June 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28637278/functional-and-structural-analysis-of-at-specific-minor-groove-binders-that-disrupt-dna-protein-interactions-and-cause-disintegration-of-the-trypanosoma-brucei-kinetoplast
#5
Cinthia R Millan, Francisco J Acosta-Reyes, Laura Lagartera, Godwin U Ebiloma, Leandro Lemgruber, J Jonathan Nué Martínez, Núria Saperas, Christophe Dardonville, Harry P de Koning, J Lourdes Campos
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of >70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2-yl)amino)benzamide] as potential drugs for HAT...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637181/crosstalk-between-histone-modifications-indicates-that-inhibition-of-arginine-methyltransferase-carm1-activity-reverses-hiv-latency
#6
Zheng Zhang, Bryan C Nikolai, Leah A Gates, Sung Yun Jung, Edward B Siwak, Bin He, Andrew P Rice, Bert W O'Malley, Qin Feng
In eukaryotic cells, the gene expression status is strictly controlled by epigenetic modifications on chromatin. The repressive status of chromatin largely contributes to HIV latency. Studies have shown that modification of histone H3K27 acts as a key molecular switch for activation or suppression of many cellular genes. In this study, we found that K27-acetylated histone H3 specifically recruited Super Elongation Complex (SEC), the transcriptional elongation complex essential for HIV-1 long terminal repeat (LTR)-mediated and general cellular transcription...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28637123/inhibition-of-swarming-motility-of-pseudomonas-aeruginosa-by-methanol-extracts-of-alpinia-officinarum-hance-and-cinnamomum-tamala-t-nees-and-eberm
#7
Divya Lakshmanan, Jishudas Nanda, K Jeevaratnam
Bacterial drug resistance is a challenge in clinical settings, especially in countries like India. Hence, discovery of novel alternative therapeutics has become a necessity in the fight against drug resistance. Compounds that inhibit bacterial virulence properties form new therapeutic alternatives. Pseudomonas aeruginosa is an opportunistic, nosocomial pathogen that infects immune-compromised patients. Swarming motility is an important virulence property of Pseudomonas which aids it in reaching host cells under nutrient limiting conditions...
June 15, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28637095/selective-cd28-blockade-results-in-superior-inhibition-of-donor-specific-t-follicular-helper-cell-and-antibody-responses-relative-to-ctla-4-ig
#8
I R Badell, G M La Muraglia, D Liu, M E Wagener, G Ding, M L Ford
Donor-specific antibodies (DSA) are a barrier to improved long-term outcomes following kidney transplantation. Costimulation blockade with CTLA-4-Ig has shown promise as a potential therapeutic strategy to control DSA. T follicular helper (Tfh) cells, a subset of CD4(+) T cells required for optimum antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8(+) T cells relative to CTLA-4-Ig, but the impact of CD28-specific blockade on CD4(+) Tfh cells is unknown...
June 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28637010/local-application-of-bacteria-improves-safety-of-salmonella-mediated-tumor-therapy-and-retains-advantages-of-systemic-infection
#9
Dino Kocijancic, Sebastian Felgner, Tim Schauer, Michael Frahm, Ulrike Heise, Kurt Zimmermann, Marc Erhardt, Siegfried Weiss
Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636788/role-of-positively-charged-residues-on-the-polar-and-non-polar-faces-of-amphipathic-%C3%AE-helical-antimicrobial-peptides-amps-on-specificity-and-selectivity-for-gram-negative-pathogens
#10
Ziqing Jiang, Colin T Mant, Michael Vasil, Robert S Hodges
We have designed de novo and synthesized eight 26-residue all D-conformation amphipathic α-helical cationic antimicrobial peptides (AMPs), four with "specificity determinants" which provide specificity for prokaryotic cells over eukaryotic cells and four AMPs without specificity determinants. The eight AMPs contain six positively charged Lys residues on the polar face in four different arrangements to understand the role of these residues have on antimicrobial activity against 14 Acinetobacter baumannii strains, 7 of which were resistant to polymyxin B and colistin; 6 diverse Pseudomonas aeruginosa strains and 17 Staphylococcus aureus strains, 9 of which were Methicillin-sensitive (MSSA) and 8 of which were Methicillin-resistant (MRSA)...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28636654/characterization-of-human-fcrl4-positive-b-cells
#11
Michel Jourdan, Nicolas Robert, Maïlys Cren, Coraline Thibaut, Christophe Duperray, Alboukadel Kassambara, Michel Cogné, Karin Tarte, Bernard Klein, Jérôme Moreaux
FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, FCRL4 is specifically expressed by memory B cells (MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of FCRL4+ B cells has been observed in blood and other tissues in various infectious and autoimmune disorders. Currently, the mechanisms involved in pathological FCRL4+ B cell generation are actively studied, but they remain elusive. As in vivo FCRL4+ cells are difficult to access and to isolate, here we developed a culture system to generate in vitro FCRL4+ B cells from purified MBCs upon stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent and/or T-cell independent activation, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28636593/t-cells-from-patients-with-parkinson-s-disease-recognize-%C3%AE-synuclein-peptides
#12
David Sulzer, Roy N Alcalay, Francesca Garretti, Lucien Cote, Ellen Kanter, Julian Agin-Liebes, Christopher Liong, Curtis McMurtrey, William H Hildebrand, Xiaobo Mao, Valina L Dawson, Ted M Dawson, Carla Oseroff, John Pham, John Sidney, Myles B Dillon, Chelsea Carpenter, Daniela Weiskopf, Elizabeth Phillips, Simon Mallal, Bjoern Peters, April Frazier, Cecilia S Lindestam Arlehamn, Alessandro Sette
Genetic studies have shown the association of Parkinson's disease with alleles of the major histocompatibility complex. Here we show that a defined set of peptides that are derived from α-synuclein, a protein aggregated in Parkinson's disease, act as antigenic epitopes displayed by these alleles and drive helper and cytotoxic T cell responses in patients with Parkinson's disease. These responses may explain the association of Parkinson's disease with specific major histocompatibility complex alleles.
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636592/quantifiable-predictive-features-define-epitope-specific-t-cell-receptor-repertoires
#13
Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi H O Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas
T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10(15) (ref. 1) to as high as 10(61) (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#14
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636433/immunogenicity-of-ags-004-dendritic-cell-therapy-in-patients-treated-during-acute-hiv-infection
#15
Cynthia L Gay, Mark A DeBenedette, Irina Y Tcherepanova, Alicia Gamble, Whitney E Lewis, Anna B Cope, JoAnn D Kuruc, Kara S McGee, Mary F Kearney, John M Coffin, Nancie M Archin, Charles B Hicks, Joseph J Eron, Charles A Nicolette, David M Margolis
AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4(+) T-cell infection (RCI) was measured by quantitative viral outgrowth assay...
June 21, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28634643/acute-high-caffeine-exposure-increases-autophagic-flux-and-reduces-protein-synthesis-in-c2c12-skeletal-myotubes
#16
M A Hughes, R M Downs, G W Webb, C L Crocker, S T Kinsey, Bradley L Baumgarner
Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux...
June 20, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28634614/detection-of-the-circulating-tumor-dnas-in-angioimmunoblastic-t-cell-lymphoma
#17
Mamiko Sakata-Yanagimoto, Rie Nakamoto-Matsubara, Daisuke Komori, Tran B Nguyen, Keiichiro Hattori, Toru Nanmoku, Takayasu Kato, Naoki Kurita, Yasuhisa Yokoyama, Naoshi Obara, Yuichi Hasegawa, Atsushi Shinagawa, Shigeru Chiba
Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis...
June 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28634590/the-immune-epitope-database-how-data-are-entered-and-retrieved
#18
REVIEW
Ward Fleri, Kerrie Vaughan, Nima Salimi, Randi Vita, Bjoern Peters, Alessandro Sette
Easy access to a vast collection of experimental data on immune epitopes can greatly facilitate the development of therapeutics and vaccines. The Immune Epitope Database and Analysis Resource (IEDB) was developed to provide such a resource as a free service to the biomedical research community. The IEDB contains epitope and assay information related to infectious diseases, autoimmune diseases, allergic diseases, and transplant/alloantigens for humans, nonhuman primates, mice, and any other species studied. It contains T cell, B cell, MHC binding, and MHC ligand elution experiments...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#19
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28634419/elevated-plasma-levels-of-sil-2r-in-complex-regional-pain-syndrome-a-pathogenic-role-for-t-lymphocytes
#20
Krishna D Bharwani, Maaike Dirckx, Dirk L Stronks, Willem A Dik, Marco W J Schreurs, Frank J P M Huygen
The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 - Q1 = 5731 pg/ml - 3546 pg/ml) versus 1907 pg/ml (Q3 - Q1: 2206 pg/ml - 1374 pg/ml), p < 0...
2017: Mediators of Inflammation
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