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https://www.readbyqxmd.com/read/29348821/glycan-microarray-reveal-induced-iggs-repertoire-shift-against-a-dietary-carbohydrate-in-response-to-rabbit-anti-human-thymocyte-therapy
#1
Ron Amon, Shani Leviatan Ben-Arye, Limor Engler, Hai Yu, Noha Lim, Ludmilla Le Berre, Kristina M Harris, Mario R Ehlers, Stephen E Gitelman, Xi Chen, Jean-Paul Soulillou, Vered Padler-Karavani
Humans have circulating antibodies against diverse glycans containing N-glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene. This xenogenic non-human carbohydrate is abundant in red meat, xenografts and biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal human endothelial cells, and together with anti-Neu5Gc antibodies could potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins commonly used as an immunosuppressant in human transplantation and autoimmune diseases...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29343892/first-two-bilateral-hand-transplantations-in-india-part-4-immediate-post-operative-care-immunosuppression-protocol-and-monitoring
#2
Subramania Iyer, Mohit Sharma, P Kishore, Jimmy Mathew, R Janarthanan, Raghuveer Reddy, Abhijeet Wakure, Sundeep Vijayaraghavan, S M Chetan Mali, Visakh Varma, Ashish Chaudhari, Swapnil Dhake, Akshay Omkumar, George Kurian, Rajesh Nair, Anil Mathew, Zachariah Paul, Malini Eapen, Lalitha Biswas
Introduction: Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self ' from the 'non-self '. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'. Materials and Methods: Pre-operative evaluation of the recipient evaluation included immunological assessment in the form of panel reactive antibodies (PRA), human leucocyte antigen (HLA) typing, donor-specific antibody detection assays (DSA) and complement-dependent cytotoxicity assays (CDC)...
May 2017: Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India
https://www.readbyqxmd.com/read/29343574/novel-human-polyomavirus-non-coding-control-regions-differ-in-bi-directional-gene-expression-according-to-host-cell-large-t-antigen-expression-and-clinically-occurring-rearrangements
#3
Elvis T Ajuh, Zongsong Wu, Emma Kraus, Fabian H Weissbach, Tobias Bethge, Rainer Gosert, Nicole Fischer, Hans H Hirsch
Human polyomavirus (HPyV) DNA genomes contain three regions denoted early viral gene region (EVGR) encoding the regulatory T-antigens and one microRNA, late viral gene region (LVGR) encoding the structural Vp capsid proteins, and non-coding control region (NCCR). The NCCR harbours the origin of viral genome replication and bi-directional promoter/enhancer functions governing EVGR- and LVGR-expression on opposite DNA strands. Despite principle similarities, HPyV-NCCRs differ in length, sequence, and architecture...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343473/smoking-affects-the-interferon-beta-treatment-response-in-multiple-sclerosis
#4
Eva R Petersen, Annette B Oturai, Nils Koch-Henriksen, Melinda Magyari, Per S Sørensen, Finn Sellebjerg, Helle B Søndergaard
OBJECTIVE: To investigate whether smoking in patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFN-β) is associated with the relapse rate and whether there is an interaction between smoking and human leukocyte antigen (HLA)-DRB1*15:01, HLA-A*02:01, and the N-acetyltransferase-1 (NAT1) variant rs7388368A. METHODS: DNA from 834 IFN-β-treated patients with RRMS from the Danish Multiple Sclerosis Biobank was extracted for genotyping...
January 17, 2018: Neurology
https://www.readbyqxmd.com/read/29343437/memory-b-cells-that-cross-react-with-group-1-and-group-2-influenza-a-viruses-are-abundant-in-adult-human-repertoires
#5
Kevin R McCarthy, Akiko Watanabe, Masayuki Kuraoka, Khoi T Do, Charles E McGee, Gregory D Sempowski, Thomas B Kepler, Aaron G Schmidt, Garnett Kelsoe, Stephen C Harrison
Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to evolving influenza viruses; new exposures update the previously generated B cell memory (Bmem) population. Despite structural similarity of hemagglutinins (HAs) from the two groups of influenza A viruses, cross-reacting antibodies (Abs) are uncommon. We analyzed Bmem compartments in three unrelated, adult donors and found frequent cross-group BCRs, both HA-head directed and non-head directed. Members of a clonal lineage from one donor had a BCR structure similar to that of a previously described Ab, encoded by different gene segments...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29339738/dna-methyltransferase-inhibition-upregulates-mhc-i-to-potentiate-cytotoxic-t-lymphocyte-responses-in-breast-cancer
#6
Na Luo, Mellissa J Nixon, Paula I Gonzalez-Ericsson, Violeta Sanchez, Susan R Opalenik, Huili Li, Cynthia A Zahnow, Michael L Nickels, Fei Liu, Mohammed N Tantawy, Melinda E Sanders, H Charles Manning, Justin M Balko
Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339495/streamlined-circular-proximity-ligation-assay-provides-high-stringency-and-compatibility-with-low-affinity-antibodies
#7
Roxana Jalili, Joe Horecka, James R Swartz, Ronald W Davis, Henrik H J Persson
Proximity ligation assay (PLA) is a powerful tool for quantitative detection of protein biomarkers in biological fluids and tissues. Here, we present the circular proximity ligation assay (c-PLA), a highly specific protein detection method that outperforms traditional PLA in stringency, ease of use, and compatibility with low-affinity reagents. In c-PLA, two proximity probes bind to an analyte, providing a scaffolding that positions two free oligonucleotides such that they can be ligated into a circular DNA molecule...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29333938/structure-based-engineering-to-restore-high-affinity-binding-of-an-isoform-selective-anti-tgf%C3%AE-1-antibody
#8
Dana M Lord, Julie J Bird, Denise M Honey, Annie Best, Anna Park, Ronnie R Wei, Huawei Qiu
Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFβ1-specific antagonist. It was tested in clinical trials for the treatment of scleroderma but later terminated due to lack of efficacy. Subsequent characterization of CAT192 indicated that its TGFβ1 binding affinity was reduced by ∼50-fold upon conversion from the parental single-chain variable fragment (scFv) to IgG4. We hypothesized this result was due to decreased conformational flexibility of the IgG that could be altered via engineering...
January 15, 2018: MAbs
https://www.readbyqxmd.com/read/29330423/t-cell-immunity-to-zika-virus-targets-immunodominant-epitopes-that-show-cross-reactivity-with-other-flaviviruses
#9
C J Reynolds, O M Suleyman, A M Ortega-Prieto, J K Skelton, P Bonnesoeur, A Blohm, V Carregaro, J S Silva, E A James, B Maillère, M Dorner, R J Boyton, D M Altmann
Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327946/posttranscriptional-regulation-of-human-antigen-r-by-mir-133b-enhances-docetaxel-cytotoxicity-through-the-inhibition-of-atp-binding-cassette-subfamily-g-member-2-in-prostate-cancer-cells
#10
Hui Liu, Xiaolong Song, Junqing Hou, Zhenhua Zhao, Junkai Chang
Docetaxel (DTX)-based chemotherapy is a first-line therapy in patients with castration-resistant prostate cancer. However, development of DTX resistance remains a challenge in cancer treatment. miRNAs have been shown to be involved in drug resistance in tumors. Nevertheless, little is known about the function and detailed molecular mechanism of miR-133b in DTX resistance of prostate cancer cells. The current study showed that miR-133b was downregulated, while human antigen R (HuR) was upregulated in prostate cancer cells...
January 12, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29326066/novel-everolimus-loaded-nanocarriers-for-topical-treatment-of-murine-experimental-autoimmune-uveoretinitis-eau
#11
Maren Kasper, Doris Gabriel, Michael Möller, Dirk Bauer, Lena Wildschütz, Herve Courthion, Michael R R Böhm, Martin Busch, Karin Loser, Solon Thanos, Robert Gurny, Arnd Heiligenhaus
In the present study, therapeutic effect of topically applied everolimus (EV)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly (lactic acid) (mPEGhexPLA) nanocarriers on experimental autoimmune uveitis (EAU) were investigated. EAU was induced in B10.RIII mice via immunization with human interphotoreceptor retinoid-binding protein peptide 161-180 (hIRBPp161-180) in complete Freund's adjuvant. Everolimus-loaded mPEGhexPLA (EV/mPEGhexPLA) nanocarriers were prepared by using a solvent evaporation method...
January 8, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29324859/magnetic-resonance-spectroscopy-detects-differential-lipid-composition-in-mammary-glands-on-low-fat-high-animal-fat-versus-high-fructose-diets
#12
Dianning He, Devkumar Mustafi, Xiaobing Fan, Sully Fernandez, Erica Markiewicz, Marta Zamora, Jeffrey Mueller, Joseph R Sachleben, Matthew J Brady, Suzanne D Conzen, Gregory S Karczmar
The effects of consumption of different diets on the fatty acid composition in the mammary glands of SV40 T-antigen (Tag) transgenic mice, a well-established model of human triple-negative breast cancer, were investigated with magnetic resonance spectroscopy and spectroscopic imaging. Female C3(1) SV40 Tag transgenic mice (n = 12) were divided into three groups at 4 weeks of age: low fat diet (LFD), high animal fat diet (HAFD), and high fructose diet (HFruD). MRI scans of mammary glands were acquired with a 9...
2018: PloS One
https://www.readbyqxmd.com/read/29323879/malaria-derived-gpi-anchor-enhances-anti-pfs25-functional-antibodies-that-block-malaria-transmission
#13
Neeraj Kapoor, Ivana Vanjak, James Rozzelle, Aym Berges, Wei Chan, Gang Yin, Cuong Tran, Aaron K Sato, Alexander R Steiner, Thao P Pham, Ashley J Birkett, Carole Long, Jeff Fairman, Kazutoyo Miura
Malaria, one of the most common vector borne human diseas-es, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429,000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts towards development of vaccines to prevent transmission are still needed. Pfs25, a post-fertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidyl-inositol (GPI) linker, which itself possesses proinflammatory properties...
January 11, 2018: Biochemistry
https://www.readbyqxmd.com/read/29322674/exposure-to-west-nile-virus-and-tick-borne-encephalitis-virus-in-dogs-in-spain
#14
I García-Bocanegra, E Jurado-Tarifa, D Cano-Terriza, R Martínez, J E Pérez-Marín, S Lecollinet
In the past decade, the spread of emerging zoonotic flaviviruses (genus Flavivirus, family Flaviviridae) has been reported in many regions worldwide, representing a threat to both human and animal health. A serosurvey was carried out to assess exposure and risk factors associated with antigenically related flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and tick-borne encephalitis virus (TBEV), in dogs in Spain. Flavivirus antibodies were detected in 39 of 815 dogs (4.8%; 95% CI: 3.3-6...
January 11, 2018: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29321020/meta-analysis-of-human-gene-expression-in-response-to-mycobacterium-tuberculosis-infection-reveals-potential-therapeutic-targets
#15
Zhang Wang, Seda Arat, Michal Magid-Slav, James R Brown
BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection...
January 10, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29317357/novel-identified-aluminum-hydroxide-induced-pathways-proof-monocyte-activation-and-pro-inflammatory-preparedness
#16
Sietske Kooijman, Jolanda Brummelman, Cécile A C M van Els, Fabio Marino, Albert J R Heck, Geert P M Mommen, Bernard Metz, Gideon F A Kersten, Jeroen L A Pennings, Hugo D Meiring
Aluminum-based adjuvants are the most widely used adjuvants in human vaccines. A comprehensive understanding of the mechanism of action of aluminum adjuvants at the molecular level, however, is still elusive. Here, we unravel the effects of aluminum hydroxide Al(OH)3 by a systems-wide analysis of the Al(OH)3-induced monocyte response. Cell response analysis by cytokine release was combined with (targeted) transcriptome and full proteome analysis. Results from this comprehensive study revealed two novel pathways to become activated upon monocyte stimulation with Al(OH)3: the first pathway was IFNβ signaling possibly induced by DAMP sensing pathways like TLR or NOD1 activation, and second the HLA class I antigen processing and presentation pathway...
January 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29317356/comparative-proteomics-of-the-larval-and-adult-stages-of-the-model-cestode-parasite-mesocestoides-corti
#17
Jeferson Camargo de Lima, Karina Mariante Monteiro, Tatiana Noel Basika Cabrera, Gabriela Prado Paludo, Hercules Moura, John R Barr, Arnaldo Zaha, Henrique Bunselmeyer Ferreira
Mesocestoides corti is a widely used model for the study of cestode biology, and its transition from the larval tetrathyridium (TT) stage to the strobilated, adult worm (ST) stage can be induced and followed in vitro. Here, a proteomic approach was used to describe and compare M. corti TT and ST protein repertories. Overall, 571 proteins were identified, 238 proteins in TT samples and 333 proteins in ST samples. Among the identified proteins, 207 proteins were shared by TTs and STs, while 157 were stage-specific, being 31 exclusive from TTs, and 126 from STs...
January 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29317305/investigation-of-putative-invasion-determinants-of-actinobacillus-species-using-comparative-genomics
#18
Adina R Bujold, Andrew E Shure, Rui Liu, Andrew M Kropinski, Janet I MacInnes
Actinobacillus spp. are Gram-negative bacteria associated with mucosal membranes. While some are commensals, others can cause important human and animal diseases. A. pleuropneumoniae causes severe fibrinous hemorrhagic pneumonia in swine but not systemic disease whereas other species invade resulting in septicemia and death. To understand the invasive phenotype of Actinobacillus spp., complete genomes of eight isolates were obtained and pseudogenomes of five isolates were assembled and annotated. Phylogenetically, A...
January 6, 2018: Genomics
https://www.readbyqxmd.com/read/29316037/development-of-a-recombinant-murine-tumor-model-using-hepatoma-cells-expressing-hepatitis-c-virus-hcv-non-structural-antigens
#19
K Young, K Haq, S MacLean, R Dudani, S M Elahi, R Gilbert, R Weeratna, L Krishnan
Hepatitis C virus (HCV) chronically infects 2-3% of the world's population, causing liver disease and cancer with prolonged infection. The narrow host range of the virus, being restricted largely to human hepatocytes, has made the development of a relevant infection and reliable model to evaluate the efficacy of vaccines a challenge. We have developed a novel approach to accomplish this by generating a murine hepatoma cell line stably expressing non-structural HCV antigens which can be used in vitro or in vivo to test HCV vaccine efficacies...
January 6, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29313684/interfering-with-hur-rna-interaction-design-synthesis-and-biological-characterization-of-tanshinone-mimics-as-novel-effective-hur-inhibitors
#20
Leonardo Manzoni, Chiara Zucal, Danilo Di Maio, Vito G D'Agostino, Natthakan Thongon, Isabelle Bonomo, Preet Lal, Marco Miceli, Vanessa Baj, Marta Brambilla, Linda Cerofolini, Saioa Elezgarai, Emiliano Biasini, Claudio Luchinat, Ettore Novellino, Marco Fragai, Luciana Marinelli, Alessandro Provenzani, Pierfausto Seneci
The human antigen R (HuR) is an RNA-binding protein known to modulate the expression of target mRNA coding for proteins involved in inflammation, tumorigenesis and stress responses and is a valuable drug target. We previously found that Dihydrotanshinone-I (DHTS, 1) prevents the association of HuR with its RNA substrate, thus imparing its function. Herein, inspired by DHTS structure, we designed and synthesized an array of ortho-quinones (tanshinone mimics) using a function-oriented synthetic approach. Among others, compound 6a and 6n turned out to be more effective than 1, showing a nanomolar Ki and disrupting HuR binding to RNA in cells...
January 9, 2018: Journal of Medicinal Chemistry
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