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Yeast display of MHC-II enables rapid identification of peptide ligands from protein antigens(RIPPA)

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Cellular & Molecular Immunology 2021年第8期18卷 1847-1860页

作者： Rongzeng Liu Wei Jiang elizabeth DMellin Department of Pediatrics-Human Gene Therapy Stanford University School of MedicineStanfordCAUSA Stanford Immunology Stanford University School of MedicineStanfordCAUSA Department of Immunology Henan University of Science and Technology School of MedicineLuoyangChina

CD4^(+)T cells orchestrate adaptive immune responses via binding of antigens to their receptors through specific peptide/MHC-II *** study these responses,it is essential to identify protein-derived MHC-II peptide ligands that constitute epitopes for T cell ***,generating cells expressing single MHC-II alleles and isolating these proteins for use in peptide elution or binding studies is time ***,we express human MHC alleles(HLA-DR4 and HLA-DQ6)as native,noncovalentαβdimers on yeast cells for direct flow cytometry-based screening of peptide ligands from selected *** demonstrate rapid,accurate identification of DQ6 ligands from pre-pro-hypocretin,a narcolepsy-related immunogenic *** also identify 20 DR4-binding SARS-CoV-2 spike peptides homologous to SARS-CoV-1 epitopes,and one spike peptide overlapping with the reported SARS-CoV-2 epitope recognized by CD4^(+)T cells from unexposed individuals carrying DR4 *** method is optimized for immediate application upon the emergence of novel pathogens.

关键词： yeast display MHC ligands T cell epitopes RIPPA SARS-CoV-2 S

CHO cell cytotoxicity and genotoxicity analyses of disinfection by-products： An updated review

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Journal of Environmental Sciences 2017年第8期29卷 64-76页

作者： elizabeth D.Wagner Michael J.Plewa Safe Global Water Institute University of Illinois at Urbana-Champaign 1101 W Peabody Dr. Urbana IL 61801 United States Department of Crop Sciences University of Illinois at Urbana-Champaign 1101 W Peabody Dr. Urbana IL 61801 United States

The disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. The disinfection of drinking water to reduce waterborne disease was an outstanding public health achievement of the 20 th *** unintended consequence is the reaction of disinfectants with natural organic matter,anthropogenic contaminants and bromide/iodide to form disinfection by-products（DBPs）.A large number of DBPs are cytotoxic, neurotoxic, mutagenic, genotoxic, carcinogenic and teratogenic. Epidemiological studies demonstrated low but significant associations between disinfected drinking water and adverse health effects. The distribution of DBPs in disinfected waters has been well defined by advances in high precision analytical chemistry. Progress in the analytical biology and toxicology of DBPs has been *** objective of this review was to provide a detailed presentation of the methodology for the quantitative, comparative analyses on the induction of cytotoxicity and genotoxicity of103 DBPs using an identical analytical biological platform and endpoints. A single Chinese hamster ovary cell line was employed in the assays. The data presented are derived from papers published in the literature as well as additional new data and represent the largest direct quantitative comparison on the toxic potency of both regulated and emerging *** data may form the foundation of novel research to define the major forcing agents of DBP-mediated toxicity in disinfected water and may play an important role in achieving the goal of making safe drinking water better.

关键词： DBPs Mammalian cell cytotoxicity Mammalian cell genotoxicity

Analyses of publicly available genomics resources define FGF-2-expressing bladder carcinomas as EMT-prone, proliferative tumors with low mutation rates and high expression of CTLA-4, PD-1 and PD-L1

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Signal Transduction and Targeted Therapy 2017年第1期2卷 258-265页

作者： elizabeth A McNiel Philip N Tsichlis Molecular Oncology Research Institute Tufts Medical CenterBostonMAUSA Cummings School of Veterinary Medicine Tufts UniversityNorth GraftonMAUSA.

Fibroblast growth factor 2(FGF-2)is overexpressed in a subset of invasive bladder carcinomas and its overexpression correlates with poor *** of publicly available databases addressing the molecular mechanisms that may be responsible for the poor prognosis of these tumors,revealed that FGF-2 expression correlates positively with the expression of epithelial to mesenchymal transition(EMT)-promoting transcription factors and with changes in gene expression that are characteristic of *** same analyses also revealed that FGF-2 correlates negatively with the expression,mutation and copy number variations of FGFR-3,all of which are associated with noninvasive bladder ***,they showed that FGF-2 expression correlates with the expression of FGFR-1,the expression of the IIIc variant of FGFR-2 and with the expression of *** latter observation is significant because our earlier studies had shown that Akt3 regulates FGFR-2 alternative splicing,shifting the balance toward the IIIc relative to the IIIb FGFR-2 splice *** the IIIc variant is recognized by FGF-2,while the IIIb variant is not,we conclude that Akt3 may facilitate the FGF-2 ***-2 is known to promote the expression of KDM2B,which functions in concert with EZH2 to repress the EZH2-targeting microRNA miR-101,activating a switch,which stably upregulates *** cancer genome atlas(TCGA)data showing a correlation between KDM2B and EZH2 expression and Oncomine data,showing a correlation between KDM2B and tumor progression,strongly support the role of the FGF-2/KDM2B/miR-101/EZH2 pathway in bladder *** observations combined,suggest a model according to which FGF-2 induces EMT,cell proliferation and cancer stem cell self-renewal by coupling the Akt3 and KDM2B-controlled pathways outlined above,in bladder *** analyses of publicly available databases,revealed that FGF-2-expressing bladder carcinomas carry fewer genetic alterations and they tend to expr

关键词： bladder carcinomas alterations

Modelling mitochondrial dysfunction in Alzheimer’s disease using human induced pluripotent stem cells

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World Journal of Stem Cells 2019年第5期11卷 236-253页

作者： Kate elizabeth Hawkins Michael Duchen Cell and Developmental Biology Division of Biosciences University College London

Alzheimer’s disease (AD) is the most common form of dementia. To date, only five pharmacological agents have been approved by the Food and Drug Administration for clinical use in AD, all of which target the symptoms of the disease rather than the cause. Increasing our understanding of the underlying pathophysiology of AD will facilitate the development of new therapeutic strategies. Over the years, the major hypotheses of AD etiology have focused on deposition of amyloid beta and mitochondrial dysfunction. In this review we highlight the potential of experimental model systems based on human induced pluripotent stem cells (iPSCs) to provide novel insights into the cellular pathophysiology underlying neurodegeneration in AD. Whilst Down syndrome and familial AD iPSC models faithfully reproduce features of AD such as accumulation of Aβ and tau, oxidative stress and mitochondrial dysfunction, sporadic AD is much more difficult to model in this way due to its complex etiology. Nevertheless, iPSC-based modelling of AD has provided invaluable insights into the underlying pathophysiology of the disease, and has a huge potential for use as a platform for drug discovery.

关键词： Induced pluripotent stem cells Alzheimer's disease Mitochondria

Intestinal antigen-presenting cells in mucosal immune homeostasis:Crosstalk between dendritic cells,macrophages and B-cells

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World Journal of Gastroenterology 2014年第29期20卷 9653-9664页

作者： elizabeth R Mann Xuhang Li Division of Gastroenterology Department of MedicineThe Johns Hopkins University School of Medicine

The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease (IBD) involves a breakdown in tolerance towards the microbiota. Dendritic cells (DC), macrophages (MΦ) and B-cells are known as professional antigen-presenting cells (APC) due to their specialization in presenting processed antigen to T-cells, and in turn shaping types of T-cell responses generated. Intestinal DC are migratory cells, unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches, whilst MΦ and B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria. The antigen-sampling function of gut DC and MΦ enables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated. The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A, which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota. Here, we review the role of all three types of APC in intestinal immunity, both in the steady state and in inflammation, and how these cells interact with one another, as well as with the intestinal microenvironment, to shape mucosal immune responses. We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.

关键词： Antigen presenting cells Dendritic cells Macrophages B cells Inflammatory bowel disease

Hepatitis C in non-hepatic solid organ transplant candidatesand recipients:A new horizon

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World Journal of Gastroenterology 2016年第4期22卷 1650-1663页

作者： Sara Belga Karen elizabeth Doucette Division of Infectious Diseases Department of MedicineUniversity of AlbertaEdmontonAlberta T6G 2G3Canada

Hepatitis C virus(HCV) infection is estimated to affect 130-150 million people globally which corresponds to2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to nonhepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon(IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals(DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant(LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post-transplant HCV therapy and future directions.

关键词： Hepatitis C chronic kidney transplantation heart transplantation lung transplantation liver transplantation kidney failure chronic antiviral agents

Role of liver biopsy in nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第27期20卷 9026-9037页

作者： ILKe Nalbantoglu elizabeth M Brunt Department of Pathology and Immunology Washington University School of MedicineSaint Louis MO 63110 United States

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Liver biopsy Histopathology Grading and staging

Consequences of fractal grade distribution for bulk sorting of a copper porphyry deposit

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Geoscience Frontiers 2015年第4期6卷 477-480页

作者： Peter Coghill David Miljak elizabeth Williams CSIRO Mineral Resources Flagship

We show the presence of fractal ordering of copper grade in bore core data at short range in the Cadia Ridgeway porphyry deposit and measure its persistence after mining by monitoring the output of the mine every 20 s for a month using a large scale, zero field magnetic resonance sensor. A simple model is used to investigate this connection and its consequences for sorting of the ore. Fractal distributions, and their associated power laws, have two features highly favourable for segregating ore： a large proportion of low-grade pods and the large scale spatial clustering of grade.

关键词： FractalMagnetic resonanceCopperPorphyry

Distribution of bleeding gastrointestinal angioectasias in a Western population

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World Journal of Gastroenterology 2012年第43期18卷 6235-6239页

作者： elizabeth Bollinger Daniel Raines Patrick Saitta Department of Medicine Section of Gastroenterology Louisiana State University Health Sciences Center New Orleans LA 70112 United States Division of Gastroenterology Lenox Hill Hospital New York NY 10075 United States

AIM:To define which segments of the gastrointestinal tract are most likely to yield angioectasias for ablative therapy. METHODS:A retrospective chart review was performed for patients treated in the Louisiana State University Health Sciences Center Gastroenterology clinics between the dates of July 1, 2007 and October 1, 2010. The selection of cases for review was initiated by use of our electronic medical record to identify all patients with a diagnosis of angioectasia, angiodysplasia, or arteriovenous malformation. Of these cases, chart reviews identified patients who had a complete evaluation of their gastrointestinal tract as defined by at least one upper endoscopy, colonoscopy and small bowel capsule endoscopy within the past three years. Patients without evidence of overt gastrointestinal bleeding or iron deficiency anemia associated with intestinal angioectasias were classified as asymptomatic and excluded from this analysis. Thirty-five patients with confirmed, bleeding intestinal angioectasias who had undergone complete endoscopic evaluation of the gastrointestinal tract were included in the final analysis. RESULTS:A total of 127 cases were reviewed. Sixtysix were excluded during subsequent screening due to lack of complete small bowel evaluation and/or lack of documentation of overt bleeding or iron deficiency anemia. The 61 remaining cases were carefully examined with independent review of endoscopic images as well as complete capsule endoscopy videos. This anal- ysis excluded 26 additional cases due to insufficient records/images for review, incomplete capsule examination, poor capsule visualization or lack of confirmation of typical angioectasias by the principal investigator on independent review. Thirty-five cases met criteria for final analysis. All study patients were age 50 years or older and 13 patients (37.1%) had chronic kidney disease stage 3 or higher. Twenty of 35 patients were taking aspirin (81 mg or 325 mg), clopidogrel, and/or warfarin, w

关键词： Intestinal angioectasias Intestinal angiodysplasias Intestinal arteriovenous malformations Obscure gastrointestinal bleeding