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Immune function

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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/27936497/pro-inflammatory-cytokine-ifn%C3%AE-and-microbiome-derived-metabolites-dictate-epigenetic-switch-between-foxp3-isoforms-in-celiac-disease-regulation-of-foxp3-isoforms-in-celiac-disease
#2
Gloria Serena, Shu Yan, Stephanie Camhi, Shilpi Patel, Rosiane S Lima, Anna Sapone, Maureen M Leonard, Rupa Mukherjee, Barbara J Nath, Karen M Lammers, Alessio Fasano
Celiac disease (CD) is an autoimmune enteropathy triggered by gluten and characterized by a strong Th1/Th17 immune response in the small intestine. Treg cells are CD4(+) CD25(++) FOXP3(+) cells that regulate the immune response. Conversely to its counterpart, FOXP3 full length (FL), the alternatively spliced isoform FOXP3 Δ2 cannot properly down-regulate Th17 driven immune response. Since the active state of CD has been associated with impairments in Treg cell function, we aimed at determining whether imbalances between FOXP3 isoforms may be associated with the disease...
December 9, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27936492/lncrna-a-versatile-regulator-of-the-nf-%C3%AE%C2%BAb-signaling-circuit
#3
REVIEW
Xiaohua Mao, Zhenyi Su, Adnan K Mookhtiar
The Nuclear Factor-κB (NF-κB) family of transcription factors play an essential role for the regulation of inflammatory responses, immune function and malignant transformation. Aberrant activity of this signaling pathway may lead to inflammation, autoimmune diseases and oncogenesis. Over the last two decades great progress has been made in the understanding of NF-κB activation and how the response is counteracted for maintaining tissue homeostasis. Therapeutic targeting of this pathway has largely remained ineffective due to the widespread role of this vital pathway and the lack of specificity of the therapies currently available...
December 9, 2016: Immunology
https://www.readbyqxmd.com/read/27936463/virus-like-particles-displaying-h5-h7-h9-hemagglutinins-and-n1-neuraminidase-elicit-protective-immunity-to-heterologous-avian-influenza-viruses-in-chickens
#4
Peter Pushko, Irina Tretyakova, Rachmat Hidajat, Aniko Zsak, Klaudia Chrzastek, Terrence M Tumpey, Darrell R Kapczynski
Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities...
December 6, 2016: Virology
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
#5
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/27936239/a-broad-spectrum-chemokine-binding-protein-of-bovine-papular-stomatitis-virus-inhibits-neutrophil-and-monocyte-infiltration-in-inflammatory-and-wound-models-of-mouse-skin
#6
Saeed Sharif, Yoshio Nakatani, Lyn Wise, Michael Corbett, Nicola C Real, Gabriella S Stuart, Zabeen Lateef, Kurt Krause, Andrew A Mercer, Stephen B Fleming
Bovine papular stomatitis virus (BPSV) is a Parapoxvirus that induces acute pustular skin lesions in cattle and is transmissible to humans. Previous studies have shown that BPSV encodes a distinctive chemokine-binding protein (CBP). Chemokines are critically involved in the trafficking of immune cells to sites of inflammation and infected tissue, suggesting that the CBP plays a role in immune evasion by preventing immune cells reaching sites of infection. We hypothesised that the BPSV-CBP binds a wide range of inflammatory chemokines particularly those involved in BPSV skin infection, and inhibits the recruitment of immune cells from the blood into inflamed skin...
2016: PloS One
https://www.readbyqxmd.com/read/27936218/a-key-role-for-inhibins-in-dendritic-cell-maturation-and-function
#7
Roxana Olguín-Alor, Marisol de la Fuente-Granada, Laura C Bonifaz, Laura Antonio-Herrera, Eduardo A García-Zepeda, Gloria Soldevila
Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function...
2016: PloS One
https://www.readbyqxmd.com/read/27936169/effects-of-supplementation-of-the-synbiotic-ecologic%C3%A2-825-fos-p6-on-intestinal-barrier-function-in-healthy-humans-a-randomized-controlled-trial
#8
E Wilms, J Gerritsen, H Smidt, I Besseling-van der Vaart, G T Rijkers, A R Garcia Fuentes, A A M Masclee, F J Troost
BACKGROUND AND AIMS: Probiotics, prebiotics and synbiotics have been suggested as dietary strategies to improve intestinal barrier function. This study aimed to assess the effect of two weeks synbiotic supplementation on intestinal permeability under basal and stressed conditions. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and gastrointestinal symptoms including defecation pattern. DESIGN: Twenty healthy adults completed a double-blind, controlled, randomized, parallel design study...
2016: PloS One
https://www.readbyqxmd.com/read/27936095/dual-specificity-phosphatase-5-is-essential-for-t-cell-survival
#9
Raman G Kutty, Gang Xin, David M Schauder, Stephanie M Cossette, Michelle Bordas, Weiguo Cui, Ramani Ramchandran
The mitogen-activated protein kinase (MAPK) pathway regulates many key cellular processes such as differentiation, apoptosis, and survival. The final proteins in this pathway, ERK1/2, are regulated by dual specificity phosphatase 5 (DUSP5). DUSP5 is a nuclear, inducible phosphatase with high affinity and fidelity for ERK1/2. By regulating the final step in the MAPK signaling cascade, DUSP5 exerts strong regulatory control over a central cellular pathway. Like other DUSPs, DUSP5 plays an important role in immune function...
2016: PloS One
https://www.readbyqxmd.com/read/27935986/quantifying-adaptive-and-innate-immune-responses-in-hiv-infected-participants-using-a-novel-high-throughput-assay
#10
Michelle K Yong, Paul U Cameron, Tim Spelman, Julian H Elliott, Christopher K Fairley, Jeffrey Boyle, Misato Miyamasu, Sharon R Lewin
OBJECTIVES: HIV infection is characterised by persistent immune dysfunction of both the adaptive and innate immune responses. The aim of this study was to evaluate these responses using a novel high throughput assay in healthy controls and HIV-infected individuals prior to and following anti-retroviral treatment (ART). DESIGN: Cross-sectional study. METHODS: Whole blood was assessed using the QuantiFERON Monitor® (QFM) assay containing adaptive and innate immunostimulants...
2016: PloS One
https://www.readbyqxmd.com/read/27935972/distinct-epigenetic-effects-of-tobacco-smoking-in-whole-blood-and-among-leukocyte-subtypes
#11
Dan Su, Xuting Wang, Michelle R Campbell, Devin K Porter, Gary S Pittman, Brian D Bennett, Ma Wan, Neal A Englert, Christopher L Crowl, Ryan N Gimple, Kelly N Adamski, Zhiqing Huang, Susan K Murphy, Douglas A Bell
Tobacco smoke exposure dramatically alters DNA methylation in blood cells and may mediate smoking-associated complex diseases through effects on immune cell function. However, knowledge of smoking effects in specific leukocyte subtypes is limited. To better characterize smoking-associated methylation changes in whole blood and leukocyte subtypes, we used Illumina 450K arrays and Reduced Representation Bisulfite Sequencing (RRBS) to assess genome-wide DNA methylation. Differential methylation analysis in whole blood DNA from 172 smokers and 81 nonsmokers revealed 738 CpGs, including 616 previously unreported CpGs, genome-wide significantly associated with current smoking (p <1...
2016: PloS One
https://www.readbyqxmd.com/read/27935834/viral-dna-sensors-ifi16-and-cyclic-gmp-amp-synthase-possess-distinct-functions-in-regulating-viral-gene-expression-immune-defenses-and-apoptotic-responses-during-herpesvirus-infection
#12
Benjamin A Diner, Krystal K Lum, Jared E Toettcher, Ileana M Cristea
: The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections...
November 15, 2016: MBio
https://www.readbyqxmd.com/read/27935698/tailoring-nanostructure-morphology-for-enhanced-targeting-of-dendritic-cells-in-atherosclerosis
#13
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/27935687/chemical-synthesis-versatile-structures-and-functions-of-tailorable-adjuvants-for-optimizing-oral-vaccination
#14
Lei Zhang, Chaohua Hu, Wendi Yang, Xiaolin Liu, Yunkun Wu
Oral vaccines have become a recent focus because of their potential significance in disease prevention and therapy. In the development of oral vaccine-based therapeutics, synthetic materials with tailorable structures and versatile functions can act as antigen conveyers with adjuvant effects, reduce the time cost for vaccine optimization, and provide high security and enhanced immunity. This review presents an overview of the current status of tailoring synthetic adjuvants for oral vaccination, modification strategies for producing effectors with specific structures and functions, enhancement of immune-associated efficiencies, including the barrier-crossing capability to protect antigens in the gastrointestinal tract, coordination of the antigens penetrating mucosa and cell barriers, targeting of concentrated antigens to immune-associated cells, and direct stimulation of immune cells...
December 9, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27935637/functional-and-phenotypic-heterogeneity-of-group-3-innate-lymphoid-cells
#15
REVIEW
Felipe Melo-Gonzalez, Matthew R Hepworth
Group 3 ILCs (ILC3), defined by expression of the transcription factor RORγt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR(+) ILC3 and LTi-like ILC3, yet also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets...
December 9, 2016: Immunology
https://www.readbyqxmd.com/read/27935538/the-correlation-of-tas2r38-gene-variants-with-higher-risk-for-chronic-rhinosinusitis-in-polish-patients
#16
Karolina Dżaman, Mariola Zagor, Elżbieta Sarnowska, Antoni Krzeski, Ireneusz Kantor
BACKGROUND: Bitter taste receptors (T2Rs), especially T2R38s appear as innovative regulators of innate immunity in the respiratory system. The single nucleotide polymorphisms (SNPs) in TAS2R38 gene may contribute to individual differences in susceptibility to respiratory infections especially chronic rhinosinusitis (CRS). TAS2R38 genotypes distribution varies by geographic region, race and ethnicity. The aim of the preliminary study was the identification of SNPs in TAS2R38 encoding genes in Polish patients with CRS and finding potential correlation with CRS phenotypes...
October 31, 2016: Otolaryngologia Polska. the Polish Otolaryngology
https://www.readbyqxmd.com/read/27935476/assessing-the-mechanism-and-therapeutic-potential-of-modulators-of-the-human-mediator-complex-associated-protein-kinases
#17
Paul Andrew Clarke, Maria-Jesus Ortiz-Ruiz, Robert TePoele, Olajumoke Adeniji-Popoola, Gary Box, Will Court, Stefanie Czasch, Samer El Bawab, Christina Esdar, Ken Ewan, Sharon Gowan, Alexis De Haven Brandon, Phllip Hewitt, Stephen M Hobbs, Wolfgang Kaufmann, Aurélie Mallinger, Florence Raynaud, Toby Roe, Felix Rohdich, Kai Schiemann, Stephanie Simon, Richard Schneider, Melanie Valenti, Stefan Weigt, Julian Blagg, Andree Blaukat, Trevor C Dale, Suzanne A Eccles, Stefan Hecht, Klaus Urbahns, Paul Workman, Dirk Wienke
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27935137/regulation-mechanism-of-pdk1-on-macrophage-metabolism-and-function
#18
REVIEW
Yueqin Yang, Weiwei Kong, Zhi Xia, Lin Xiao, Song Wang
PDK1 is a member of the atypical glandular cell kinases family that regulates the activities of most atypical glandular cell kinases during different development stages and treatment of cancers. PDK1 is also a critical glucose metabolism enzyme regulating glucolysis or glucose oxidase in cells, and more research is needed to further understand the underlying mechanism. The research of PDK1 presented by recent studies focuses much on cancer treatment and has helped researchers gain much insight in this regard...
December 2016: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27935057/crosstalk-among-uv-induced-inflammatory-mediators-dna-damage-and-epigenetic-regulators-facilitates-suppression-of-the-immune-system
#19
Ram Prasad, Santosh K Katiyar
The suppression of the immune system by overexposure to ultraviolet (UV) radiation has been implicated in the initiation and progression of photocarcinogenesis. Numerous changes occur in the skin on UVB exposure, including the generation of inflammatory mediators, DNA damage, epigenetic modifications, and migration and functional alterations in the antigen-presenting dendritic cells. Although each of these alterations can elicit a cascade of events that have the potential to modulate immune sensitivity alone, there is emerging evidence that there is considerable crosstalk between these cascades...
December 9, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27934954/strap-acts-as-a-scaffolding-protein-in-controlling-the-tlr2-4-signaling-pathway
#20
Hyunbin D Huh, Eun A Ra, Taeyun A Lee, Sujin Kang, Areum Park, Eunhye Lee, Junhee L Choi, Eunji Jang, Ji Eun Lee, Sungwook Lee, Boyoun Park
The WD40-repeat protein serine/threonine kinase receptor-associated protein (STRAP) is involved in the regulation of several biological processes, including cell proliferation and apoptosis, in response to various stresses. Here, we show that STRAP is a new scaffold protein that functions in Toll-like receptor (TLR)-mediated immune responses. STRAP specifically binds transforming growth factor β-activated kinase 1 (TAK1) and IκB kinase alpha (IKKα) along with nuclear factor-κB (NF-κB) subunit p65, leading to enhanced association between TAK1, IKKα, and p65, and subsequent facilitation of p65 phosphorylation and nuclear translocation...
December 9, 2016: Scientific Reports
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