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Immune engineering

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https://www.readbyqxmd.com/read/27936513/probing-the-structural-dynamics-of-the-crispr-cas9-rna-guided-dna-cleavage-system-by-coarse-grained-modeling
#1
Wenjun Zheng
In the adaptive immune systems of many bacteria and archaea, the Cas9 endonuclease forms a complex with specific guide/scaffold RNA to identify and cleave complementary target sequences in foreign DNA. This DNA targeting machinery has been exploited in numerous applications of genome editing and transcription control. However, the molecular mechanism of the Cas9 system is still obscure. Recently, high-resolution structures have been solved for Cas9 in different structural forms (e.g., unbound forms, RNA-bound binary complexes, and RNA-DNA-bound tertiary complexes, corresponding to an inactive state, a pre-target-bound state, and a cleavage-competent or product state), which offered key structural insights to the Cas9 mechanism...
December 9, 2016: Proteins
https://www.readbyqxmd.com/read/27936346/antibodies-to-staphylococcus-aureus-capsular-polysaccharides-5-and-8-perform-similarly-in-vitro-but-are-functionally-distinct-in-vivo
#2
Bo Liu, Saeyoung Park, Christopher D Thompson, Xue Li, Jean C Lee
The capsular polysaccharide (CP) produced by Staphylococcus aureus is a virulence factor that allows the organism to evade uptake and killing by host neutrophils. Polyclonal antibodies to the serotype 5 (CP5) and type 8 (CP8) capsular polysaccharides are opsonic and protect mice against experimental bacteremia provoked by encapsulated staphylococci. Thus, passive immunotherapy using CP antibodies has been considered for the prevention or treatment of invasive antibiotic-resistant S. aureus infections. In this report, we generated monoclonal antibodies (mAbs) against S...
December 9, 2016: Virulence
https://www.readbyqxmd.com/read/27935698/tailoring-nanostructure-morphology-for-enhanced-targeting-of-dendritic-cells-in-atherosclerosis
#3
Sijia Yi, Sean David Allen, Yu-Gang Liu, Brian Zhou Ouyang, Xiaomo Li, Punn Augsornworawat, Edward Benjamin Thorp, Evan Alexander Scott
Atherosclerosis, a leading cause of heart disease, results from chronic vascular inflammation that is driven by diverse immune cell populations. Nanomaterials may function as powerful platforms for diagnostic imaging and controlled delivery of therapeutics to inflammatory cells in atherosclerosis, but efficacy is limited by nonspecific uptake by cells of the mononuclear phagocytes system (MPS). MPS cells located in the liver, spleen, blood, lymph nodes, and kidney remove from circulation the vast majority of intravenously administered nanomaterials regardless of surface functionalization or conjugation of targeting ligands...
December 9, 2016: ACS Nano
https://www.readbyqxmd.com/read/27933313/genetic-engineering-of-chimeric-antigen-receptors-using-lamprey-derived-variable-lymphocyte-receptors
#4
Robert Moot, Sunil S Raikar, Lauren Fleischer, Melissa Querrey, Daniel E Tylawsky, Hirotomo Nakahara, Christopher B Doering, H Trent Spencer
Chimeric antigen receptors (CARs) are used to redirect effector cell specificity to selected cell surface antigens. Using CARs, antitumor activity can be initiated in patients with no prior tumor specific immunity. Although CARs have shown promising clinical results, the technology remains limited by the availability of specific cognate cell target antigens. To increase the repertoire of targetable tumor cell antigens we utilized the immune system of the sea lamprey to generate directed variable lymphocyte receptors (VLRs)...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27931684/inhibition-of-apoptosis-by-rv2456c-through-nuclear-factor-%C3%AE%C2%BAb-extends-the-survival-of-mycobacterium-tuberculosis
#5
Kristen L Jurcic Smith, Sunhee Lee
Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8(+) T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID)...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27930092/inflammatory-bowel-disease-meets-systems-biology-a-multi-omics-challenge-and-frontier
#6
Orazio Palmieri, Tommaso Mazza, Stefano Castellana, Anna Panza, Tiziana Latiano, Giuseppe Corritore, Angelo Andriulli, Anna Latiano
The inflammatory bowel disease (IBD) is a systemic disease that is characterized by the inflammation of the gastrointestinal tract. It includes ulcerative colitis and the Crohn's disease. Presently, IBD is one of the most investigated common complex human disorders, although its causes remain unclear. Multi-omics mechanisms involving genomic, transcriptomic, proteomic, and epigenomic variations, not to forget the miRNome, together with environmental contributions, result in an impairment of the immune system in persons with IBD...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27929078/gut-microbiota-from-metabolic-disease-resistant-macrophage-specific-rip140-knockdown-mice-improves-metabolic-phenotype-and-gastrointestinal-integrity
#7
Yi-Wei Lin, Emmanuel Montassier, Dan Knights, Li-Na Wei
While fecal microbiota transplantation (FMT) presents an attractive therapeutic strategy, it remains unclear how to choose the microbiota repertoire that most effectively transfers benefit to recipients. We identified a beneficial taxonomic repertoire in a transgenic mouse model (RIP140mϕKD) which resists the development of high fat diet (HFD)-induced metabolic diseases due to enhanced anti-inflammation engineered by lowering receptor interacting protein (RIP140) expression in macrophage. We confirmed using FMT from HFD-fed RIP140mϕKD to wild type (WT) mice that recipient mice acquired the microbiota repertoire of donor mice...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928884/building-proteomic-tool-boxes-to-monitor-mhc-class-i-and-class-ii-peptides
#8
REVIEW
Frances-Rose Schumacher, Lélia Delamarre, Suchit Jhunjhunwala, Zora Modrusan, Qui T Phung, Joshua E Elias, Jennie R Lill
Major histocompatibility complex Class I (MHCI) and Class II (MHCII) presented peptides powerfully modulate T cell immunity and play a vital role in generating effective anti-tumor and anti-viral immune responses in mammals. Characterizing these MHCI or MHCII presented peptides can help generate therapeutic treatments, afford information on T cell mediated biomarkers, provide insight into disease progression, and reduce adverse anti-drug side effects from engineered biotherapeutics. Here, we explore the tools and techniques commonly employed to discover both MHCI and MHCII presented peptides...
December 8, 2016: Proteomics
https://www.readbyqxmd.com/read/27926545/immune-responses-to-bioengineered-organs
#9
Jordi Ochando, Dominique Charron, Pedro M Baptista, Basak E Uygun
PURPOSE OF REVIEW: Organ donation in the United States registered 9079 deceased organ donors in 2015. This high percentage of donations allowed organ transplantation in 29 851 recipients. Despite increasing numbers of transplants performed in comparison with previous years, the numbers of patients that are in need for a transplant increase every year at a higher rate. This reveals that the discrepancy between the demand and availability of organs remains fundamental problem in organ transplantation...
December 6, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27919783/the-potential-of-induced-pluripotent-stem-cells-as-a-tool-to-study-skeletal-dysplasias-and-cartilage-related-pathologic-conditions
#10
REVIEW
Huan Liu, Lei Yang, Fang Fang Yu, Sen Wang, Cuiyan Wu, Chengjuan Qu, Xiong Guo, Mikko J Lammi
The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too...
December 2, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27917363/future-therapy-for-hepatitis-b-virus-role-of-immunomodulators
#11
REVIEW
Edward A Pham, Ryan B Perumpail, Benjamin J Fram, Jeffrey S Glenn, Aijaz Ahmed, Robert G Gish
Although currently available therapies for chronic hepatitis B virus infection can suppress viremia and provide long-term benefits for patients, they do not lead to a functional cure for most patients. Advances in our understanding of the virus-host interaction and the recent remarkable success of immunotherapy in cancer offer new and promising strategies for developing immune modulators that may become important components of a total therapeutic approach to hepatitis B, some of which are now in clinical development...
2016: Current Hepatology Reports
https://www.readbyqxmd.com/read/27916599/deciphering-communicating-and-engineering-the-crispr-pam
#12
REVIEW
Ryan T Leenay, Chase L Beisel
Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their flanking CRISPR-associated (cas) genes make up RNA-guided, adaptive immune systems in prokaryotes whose effector proteins have become powerful tools for basic research and biotechnology. While the Cas effector proteins are remarkably diverse, they commonly rely on protospacer-adjacent motifs (PAMs) as the first step in target recognition. PAM sequences are known to vary considerably between systems and have proven to be difficult to predict, spurring the need for new tools to rapidly identify and communicate these sequences...
December 1, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27914464/immunogenicity-of-human-interferon-beta-containing-pharmaceuticals
#13
V D Nazarov, S V Lapin, A V Mazing, E P Evdoshenko, A A Totolian
Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-β)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient's immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-β activity also quantifying NAb level are applied because direct measurement of IFN-β antiviral activity is complicated...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27914063/episweep-computationally-driven-reengineering-of-therapeutic-proteins-to-reduce-immunogenicity-while-maintaining-function
#14
Yoonjoo Choi, Deeptak Verma, Karl E Griswold, Chris Bailey-Kellogg
Therapeutic proteins are yielding ever more advanced and efficacious new drugs, but the biological origins of these highly effective therapeutics render them subject to immune surveillance within the patient's body. When recognized by the immune system as a foreign agent, protein drugs elicit a coordinated response that can manifest a range of clinical complications including rapid drug clearance, loss of functionality and efficacy, delayed infusion-like allergic reactions, more serious anaphylactic shock, and even induced auto-immunity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914061/probing-oligomerized-conformations-of-defensin-in-the-membrane
#15
Wenxun Gan, Dina Schneidman, Ning Zhang, Buyong Ma, Ruth Nussinov
Computational prediction and design of membrane protein-protein interactions facilitate biomedical engineering and biotechnological applications. Due to their antimicrobial activity, human defensins play an important role in the innate immune system. Human defensins are attractive pharmaceutical targets due to their small size, broad activity spectrum, reduced immunogenicity, and resistance to proteolysis. Protein engineering based modification of defensins can improve their pharmaceutical properties. Here we present an approach to computationally probe defensins' oligomerization states in the membrane...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#16
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910822/prolonged-in-vitro-precultivation-alleviates-post-implantation-inflammation-and-promotes-stable-subcutaneous-cartilage-formation-in-a-goat-model
#17
Yi Liu, Dan Li, Zongqi Yin, Xusong Luo, Wei Liu, Wenjie Zhang, Zhiyong Zhang, Yilin Cao, Yu Liu, Guangdong Zhou
Synthetic biodegradable scaffolds such as polylactic acid coated polyglycolic acid (PLA-PGA) are especially suitable for engineering shaped cartilage such as auricle, but they induce a serious inflammatory reaction particularly in the immunologically aggressive subcutaneous site, leading to resorption of the engineered autologous cartilage. Our previous study in a rabbit model has demonstrated 2 weeks of in vitro precultivation could significantly alleviate the post-implantation inflammation induced by PLA-PGA engineered cartilaginous grafts, but reproduction of this result failed in a preclinical goat model...
December 2, 2016: Biomedical Materials
https://www.readbyqxmd.com/read/27907157/human-bone-derived-collagen-for-the-development-of-an-artificial-corneal-endothelial-graft-in-vivo-results-in-a-rabbit-model
#18
Natalia Vázquez, Manuel Chacón, Carlos A Rodríguez-Barrientos, Jesús Merayo-Lloves, Miguel Naveiras, Begoña Baamonde, Jose F Alfonso, Iriana Zambrano-Andazol, Ana C Riestra, Álvaro Meana
Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane...
2016: PloS One
https://www.readbyqxmd.com/read/27907088/silver-nanoparticle-directed-mast-cell-degranulation-is-mediated-through-calcium-and-pi3k-signaling-independent-of-the-high-affinity-ige-receptor
#19
Nasser B Alsaleh, Indushekhar Persaud, Jared M Brown
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation...
2016: PloS One
https://www.readbyqxmd.com/read/27905838/engineering-hiv-specific-immunity-with-chimeric-antigen-receptors
#20
Scott G Kitchen, Jerome A Zack
HIV remains a highly important public health and clinical issue despite many recent advances in attempting to develop a cure, which has remained elusive for most people infected with HIV. HIV disease can be controlled with pharmacologic therapies; however, these treatments are expensive, may have severe side effects, and are not curative. Consequently, an improved means to control or eliminate HIV replication is needed. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling viral replication and are an important part in the ability of the immune response to eradicate most viral infections...
December 2016: AIDS Patient Care and STDs
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