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Translational immunology

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https://www.readbyqxmd.com/read/28226229/a-perspective-on-the-role-of-computational-models-in-immunology
#1
Arup K Chakraborty
This is an exciting time for immunology because the future promises to be replete with exciting new discoveries that can be translated to improve health and treat disease in novel ways. Immunologists are attempting to answer increasingly complex questions concerning phenomena that range from the genetic, molecular, and cellular scales to that of organs, whole animals or humans, and populations of humans and pathogens. An important goal is to understand how the many different components involved interact with each other within and across these scales for immune responses to emerge, and how aberrant regulation of these processes causes disease...
February 6, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28209609/pancreatic-cancer-progress-and-challenges-in-a-rapidly-moving-field
#2
Eric A Collisson, Kenneth P Olive
"Pancreatic Cancer: Advances in Science and Clinical Care," a Special Conference of the American Association for Cancer Research, was held in Orlando, FL, on May 12 to 15, bringing together more than 450 basic, translational, clinical, and epidemiologic pancreatic cancer researchers as well as pancreatic cancer patients, survivors, and advocates. Pancreatic cancer remains one of the great challenges in medicine, but the accelerating pace of research and early hints of clinical successes to come were palpable throughout the meeting...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28205652/bridging-the-gap-microfluidic-devices-for-short-and-long-distance-cell-cell-communication
#3
REVIEW
Timothy Quang Vu, Ricardo Miguel Bessa de Castro, Lidong Qin
Cell-cell communication is a crucial component of many biological functions. For example, understanding how immune cells and cancer cells interact, both at the immunological synapse and through cytokine secretion, can help us understand and improve cancer immunotherapy. The study of how cells communicate and form synaptic connections is important in neuroscience, ophthalmology, and cancer research. But in order to increase our understanding of these cellular phenomena, better tools need to be developed that allow us to study cell-cell communication in a highly controlled manner...
February 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28197381/immunological-mechanisms-of-intravesical-chitosan-interleukin-12-immunotherapy-against-murine-bladder-cancer
#4
Sean G Smith, John L Baltz, Bhanu Prasanth Koppolu, Sruthi Ravindranathan, Khue Nguyen, David A Zaharoff
There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with a simple co-formulation of interleukin-12 and the biopolymer chitosan not only destroy orthotopic bladder tumors, but also promote a potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, and abscopal antitumor responses at distant non-treated tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194024/regnase-1-a-rapid-response-ribonuclease-regulating-inflammation-and-stress-responses
#5
REVIEW
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28191766/concise-review-mesenchymal-stem-cell-therapy-for-pediatric-disease-perspectives-on-success-and-potential-improvements
#6
Christopher R Nitkin, Tracey L Bonfield
Mesenchymal stem cells (MSCs) represent a potentially revolutionary therapy for a wide variety of pediatric diseases, but the optimal cell-based therapeutics for such diversity have not yet been specified. The published clinical trials for pediatric pulmonary, cardiac, orthopedic, endocrine, neurologic, and hematologic diseases provide evidence that MSCs are indeed efficacious, but the significant heterogeneity in therapeutic approaches between studies raises new questions. The purpose of this review is to stimulate new preclinical and clinical trials to investigate these factors...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191734/integrative-proteomics-genomics-and-translational-immunology-approaches-reveal-mutated-forms-of-proteolipid-protein-1-plp1-and-mutant-specific-immune-response-in-multiple-sclerosis
#7
Veneta Qendro, Grace A Bugos, Debbie H Lundgren, John Glynn, May H Han, David K Han
In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA...
February 12, 2017: Proteomics
https://www.readbyqxmd.com/read/28186688/mechanisms-of-tolerance-induction-by-hematopoietic-chimerism-the-immune-perspective
#8
EDITORIAL
Esma S Yolcu, Haval Shirwan, Nadir Askenasy
Hematopoietic chimerism is one of the effective approaches to induce tolerance to donor-derived tissue and organ grafts without administration of life-long immunosuppressive therapy. Although experimental efforts to develop such regimens have been ongoing for decades, substantial cumulative toxicity of combined hematopoietic and tissue transplants precludes wide clinical implementation. Tolerance is an active immunological process that includes both peripheral and central mechanisms of mutual education of coresident donor and host immune systems...
January 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186681/skin-derived-precursors-as-a-source-of-progenitors-for-corneal-endothelial-regeneration
#9
Emi Inagaki, Shin Hatou, Kazunari Higa, Satoru Yoshida, Shinsuke Shibata, Hideyuki Okano, Kazuo Tsubota, Shigeto Shimmura
Corneal blindness is the fourth leading cause of blindness in the world. Current treatment is allogenic corneal transplantation, which is limited by shortage of donors and immunological rejection. Skin-derived precursors (SKPs) are postnatal stem cells, which are self-renewing, multipotent precursors that can be isolated and expanded from the dermis. Facial skin may therefore be an accessible autologous source of neural crest derived cells. SKPs were isolated from facial skin of Wnt1-Cre/Floxed EGFP mouse. After inducing differentiation with medium containing retinoic acid and GSK 3-β inhibitor, SKPs formed polygonal corneal endothelial-like cells (sTECE)...
February 6, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28176789/the-intraspecies-diversity-of-c-albicans-triggers-qualitatively-and-temporally-distinct-host-responses-that-determine-the-balance-between-commensalism-and-pathogenicity
#10
F A Schönherr, F Sparber, F R Kirchner, E Guiducci, K Trautwein-Weidner, A Gladiator, N Sertour, U Hetzel, G T T Le, N Pavelka, C d'Enfert, M-E Bougnoux, C F Corti, S LeibundGut-Landmann
The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28165712/celiac-disease-lessons-for-and-from-chemical-biology
#11
Chaitan Khosla
Celiac disease is a lifelong immune disorder of the small intestine where inflammation is triggered by dietary gluten. There is an urgent need for the development of non-dietary therapies for this widespread but overlooked disease. More fundamentally, a molecular understanding of gluten-induced pathogenesis in celiac disease has the potential to provide new insights into mucosal immunology. Over the past two decades, three pathogenically critical molecules - gluten, TG2, and HLA-DQ2 - have served as focal points for collaborative efforts between biologists, chemists, engineers, and clinicians with an interest in celiac disease...
February 6, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28162244/pharmacogenetics-of-hypersensitivity-drug-reactions
#12
Simone Negrini, Laurent Becquemont
Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity...
January 3, 2017: Thérapie
https://www.readbyqxmd.com/read/28159936/nitration-of-tyrosines-in-complement-factor-h-domains-alters-its-immunological-activity-and-mediates-a-pathogenic-role-in-age-related-macular-degeneration
#13
Matthew Krilis, Miao Qi, Michele C Madigan, Jason W H Wong, Mahmoud Abdelatti, Robyn H Guymer, John Whitelock, Peter McCluskey, Peng Zhang, Jian Qi, Alex P Hunyor, Steven A Krilis, Bill Giannakopoulos
Nitrosative stress has been implicated in the pathogenesis of age related macular degeneration (AMD). Tyrosine nitration is a unique type of post translational modification that occurs in the setting of inflammation and nitrosative stress. To date, the significance and functional implications of tyrosine nitration of complement factor H (CFH), a key complement regulator in the eye has not been explored, and is examined in this study in the context of AMD pathogenesis.Sections of eyes from deceased individuals with AMD (n = 5) demonstrated the presence of immunoreactive nitrotyrosine CFH...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28153778/accelerating-the-clinical-development-of-protein-based-vaccines-for-malaria-by-efficient-purification-using-a-four-amino-acid-c-terminal-c-tag
#14
Jing Jin, Kathryn A Hjerrild, Sarah E Silk, Rebecca E Brown, Geneviève M Labbé, Jennifer M Marshall, Katherine E Wright, Sandra Bezemer, Stine B Clemmensen, Sumi Biswas, Yuanyuan Li, Aadil El-Turabi, Alexander D Douglas, Pim Hermans, Frank J Detmers, Willem A de Jongh, Matthew K Higgins, Rebecca Ashfield, Simon J Draper
Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example...
January 30, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28150302/immunological-consequences-of-strain-variation-within-the-mycobacterium-tuberculosis-complex
#15
Leopold D Tientcheu, Anastasia Koch, Mthawelenga Ndengane, Genevieve Andoseh, Beate Kampmann, Robert J Wilkinson
In 2015 there were an estimated 10.4 million new cases of Tuberculosis (TB) globally, making it one of the leading causes of death due to an infectious disease. TB is caused by members of the Mycobacterium tuberculosis complex (MTBC), with human disease resulting from infection by M. tuberculosis sensu strico and M. africanum. Recent progress in genotyping techniques, in particular the increasing availability of whole genome sequence data, has revealed previously under appreciated levels of genetic diversity within the MTBC...
February 2, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28150236/bioinformatics-analysis-of-protein-phosphorylation-in-plant-systems-biology-using-p3db
#16
Qiuming Yao, Dong Xu
Protein phosphorylation is one of the most pervasive protein post-translational modification events in plant cells. It is involved in many plant biological processes, such as plant growth, organ development, and plant immunology, by regulating or switching signaling and metabolic pathways. High-throughput experimental methods like mass spectrometry can easily characterize hundreds to thousands of phosphorylation events in a single experiment. With the increasing volume of the data sets, Plant Protein Phosphorylation DataBase (P3DB, http://p3db...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28137295/a-phase-ii-trial-of-stereotactic-body-radiotherapy-with-concurrent-anti-pd1-treatment-in-metastatic-melanoma-evaluation-of-clinical-and-immunologic-response
#17
Katrien De Wolf, Vibeke Kruse, Nora Sundahl, Mireille van Gele, Ines Chevolet, Reinhart Speeckaert, Lieve Brochez, Piet Ost
BACKGROUND: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients...
January 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28134057/hiv-viral-kinetics-and-t-cell-dynamics-in-antiretroviral-na%C3%A3-ve-persons-starting-an-integrase-strand-transfer-inhibitor-and-protease-inhibitor-regimen
#18
Maile Y Karris, Sonia Jain, Tyler R C Day, Josué Pérez-Santiago, Miguel Goicoechea, Michael P Dubé, Xiaoying Sun, Celsa Spina, Eric S Daar, Richard H Haubrich, Sheldon Morris
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed. OBJECTIVE: To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics...
January 30, 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28127571/desensitization-overcoming-the-immunologic-barriers-to-transplantation
#19
REVIEW
Supreet Sethi, Jua Choi, Mieko Toyoda, Ashley Vo, Alice Peng, Stanley C Jordan
HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28126499/bacillus-calmette-guerin-improves-local-and-systemic-response-to-radiotherapy-in-invasive-bladder-cancer
#20
Barbara Prack Mc Cormick, Denise Belgorosky, Yanina Langle, Natalia Balarino, Eduardo Sandes, Ana María Eiján
BACKGROUND: A key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis. PURPOSE: To study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a local tumor vaccine for invasive BCa treatment...
January 23, 2017: Nitric Oxide: Biology and Chemistry
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