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Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling

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Cellular & Molecular Immunology 2023年第1期20卷 26-37页

作者： Kelly A.Dingess Max Hoek Danique M.Hvan rijswijk Sem Tamara Maurits Aden Boer Tim Veth Mirjam j.A.Damen Arjan Barendregt Michelle romijn Hannah G.juncker Britt jvan Keulen Gestur Vidarsson johannes Bvan Goudoever albert Bondt albert j.r.heck Biomolecular Mass Spectrometry and Proteomics Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical SciencesUniversity of UtrechtPadualaan 8Utrecht 3584 CHThe Netherlands Netherlands Proteomics Center Padualaan 8Utrecht 3584 CHThe Netherlands Amsterdam UMC Vrije UniversiteitUniversity of AmsterdamEmma Children’s HospitalAmsterdam Reproduction&Development Research InstituteDepartment of PediatricsAmsterdamthe Netherlands Department of Experimental Immunohematology Sanquin Research and Landsteiner LaboratoryAmsterdam UMCUniversity of AmsterdamAmsterdamNetherlands

The most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (j-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a j-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and j-chain coupled dimeric IgA1. The serum dimeric j-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins;one of these produces dimeric j-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.

关键词： Antigen binding fragment Immunoglobulin A1 Clonal repertoires human milk Serum

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Object-Based Method Outperforms Per-Pixel Method for Land Cover Classification in a Protected Area of the Brazilian Atlantic rainforest region

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Pedosphere 2013年第3期23卷 290-297页

作者： T.rITTL M.COOPEr r.j.heck M.V.r.BALLESTEr Department of Soil Quality University of Wageningen Department of Soil Science University of So Paulo School of Environmental Sciences University of Guelph Center for Nuclear Energy in Agriculture (CENA) University of So Paulo

Conventional image classification based on pixels hinders the possibilities to obtain information contained in images, while modern object-based classification methods increase the acquisition of information about the object and the context in which it is inserted in the image. The objective of this study was to investigate the performance of different classification methods for land cover mapping in the vicinity of the Alto ribeira Tourist State Park, a Brazilian Atlantic rainforest area. Two classification methods were tested, including i） a hybrid per-pixel classification using the image processing software ErDAS Imagine version 9.1 and ii） an object-based classification using the software eCognition version 5. In the first method, six different classes were established, while in the second method, another two classes were established in addition to the six classes in the first method. Accuracy assessment of the classification results presented showed that the object-based classification with a Kappa index value of 0.8687 outperformed the per-pixel classification with a Kappa index value of 0.2224. Application of the user＇s knowledge during the object-based classification process achieved the desired quality; therefore, the use of inter-relationships between objects, superelasses, subclasses, and neighboring classes were critical to improving the efficiency of land cover classification.

关键词： accuracy assessment image classification Kappa index user's knowledge

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Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions

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World journal of Gastroenterology 2019年第45期25卷 6579-6606页

作者： albert j Czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine and Science

BACKGrOUND Multiple pathogenic mechanisms have been implicated in autoimmune hepatitis,but they have not fully explained susceptibility,triggering events,and maintenance or escalation of the ***,they have not identified a critical defect that can be *** goals of this review are to examine the diverse pathogenic mechanisms that have been considered in autoimmune hepatitis,indicate investigational opportunities to validate their contribution,and suggest interventions that might evolve to modify their *** abstracts were identified in PubMed by multiple search *** length articles were selected for review,and secondary and tertiary bibliographies were *** and epigenetic factors can affect susceptibility by influencing the expression of immune regulatory *** dysfunction,possibly related to deficient production of programmed cell death protein-1,can allow autoreactive T cells to escape deletion,and alterations in the intestinal microbiome may help overcome immune tolerance and affect gender *** factors may trigger the disease or induce epigenetic changes in gene *** mimicry,epitope spread,bystander activation,neo-antigen production,lymphocytic polyspecificity,and disturbances in immune inhibitory mechanisms may maintain or escalate the *** that modify epigenetic effects on gene expression,alter intestinal dysbiosis,eliminate deleterious environmental factors,and target critical pathogenic mechanisms are therapeutic possibilities that might reduce risk,individualize management,and improve *** conclusion,diverse pathogenic mechanisms have been implicated in autoimmune hepatitis,and they may identify a critical factor or sequence that can be validated and used to direct future management and preventive strategies.

关键词： Autoimmune hepatitis Pathogenesis Epigenetics Molecular mimicry Epitope spread Intestinal microbiome

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Hepatic inflammation and progressive liver fibrosis in chronic liver disease

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World journal of Gastroenterology 2014年第10期20卷 2515-2532页

作者： albert j Czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine Rochester MN 55905 United States

Chronic liver inflammation drives hepatic fibrosis,and current immunosuppressive,anti-inflammatory,and anti-viral therapies can weaken this *** fibrosis is reversed,stabilized,or prevented in 57%-79%of patients by conventional treatment regimens,mainly by their anti-inflammatory ***,however,are commonly incomplete and inconsistently *** fibrotic mechanisms associated with liver inflammation have been clarified,and anti-fibrotic agents promise to improve outcomes as adjunctive *** C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within *** can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen ***-oxidants(Nacetylcysteine,S-adenosyl-L-methionine,and vitamin E)and angiotensin inhibitors(losartin)have had antifibrotic actions in preliminary human studies,and they may emerge as supplemental ***-fibrotic agents presage a new era of supplemental treatment for chronic liver disease.

关键词： Inflammation Fibrosis Cirrhosis Treatment Anti-oxidants Angiotensin receptors Investigational drugs

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Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease

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World journal of Gastroenterology 2021年第25期27卷 3705-3733页

作者： albert j Czaja Department of Medicine Mayo Clinic College of Medicine and ScienceRochesterMN 55905United States

Mucosal-associated invariant T(MAIT)cells have been described in liver and nonliver diseases,and they have been ascribed antimicrobial,immune regulatory,protective,and pathogenic *** goals of this review are to describe their biological properties,indicate their involvement in chronic liver disease,and encourage investigations that clarify their actions and therapeutic *** abstracts were identified in PubMed by multiple search terms,and bibliographies were *** cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory *** pro-inflammatory,anti-inflammatory,and immune regulatory cytokines are released;infected cells are eliminated;and memory cells *** MAIT cells are hyper-activated,immune exhausted,dysfunctional,and depleted in chronic liver *** phenotype lacks disease-specificity,and it does not predict the biological *** cells have presumed protective actions in chronic viral hepatitis,alcoholic hepatitis,non-alcoholic fatty liver disease,primary sclerosing cholangitis,and decompensated *** have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary *** factors in the hepatic microenvironment(cytokines,bile acids,gut-derived bacterial antigens,and metabolic by-products)may modulate their response in individual *** manipulations of function are warranted to establish an association with disease severity and *** conclusion,MAIT cells constitute a disease-nonspecific,immune response to chronic liver inflammation and *** pathological role has been deduced from their deficiencies during active liver disease,and future investigations must clarify this role,link it to outcome,and explore therapeutic interventions.

关键词： Innate-like lymphocytes Antimicrobial Immune regulatory Pathogenic Mucosal-associated invariant T cell

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Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis

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World journal of Gastroenterology 2016年第42期22卷 9257-9278页

作者： albert j Czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine

The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora(dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria. Toll-like receptors within the intestine can recognize microbe-associated molecular patterns and shape subsets of T helper lymphocytes that may cross-react with host antigens(molecular mimicry). Activated gutderived lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes and hepatic stellate cells, and they can drive the pro-inflammatory, immune-mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements, re-colonization methods, antibiotics, drugs that decrease intestinal permeability, and molecular interventions that block signaling pathways may emerge as adjunctive regimens that complement conventional immunosuppressive management. In conclusion, investigations of the intestinal microbiome are warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms and suggest alternative management strategies.

关键词： Intestinal microbiome Inflammasomes Autoimmune hepatitis Dysbiosis Toll-like receptors

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recent Trends in Satellite-Derived Chlorophyll and Aerosol Optical Depth Together with Simulated Dimethylsulfide in the Eastern China Marginal Seas

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journal of Ocean University of China 2022年第2期21卷 486-498页

作者： QU Bo GABrIC albert j. School of Science Nantong UniversityNantong 266000China School of Environment and Science Griffith UniversityBrisbaneQLDAustralia

The biogenic compound dimethylsulfide(DMS)produced by a range of marine biota is the major natural source of re-duced sulfur to the atmosphere and plays a major role in the formation and evolution of aerosols,potentially affecting *** spatio-temporal distribution of satellite-derived chlorophyll_a(CHL)and aerosol optical depth(AOD)for the recent years(2011-2019)in the Eastern China Marginal Seas(ECMS)(25°-40°N,120°-130°E)are *** seasonal CHL peaks occurred during late April and the CHL distribution displays a clear zonal *** CHL was also observed along the northern and western coastlines during summer and winter *** analysis shows that mean CHL decreases by about 10%over the 9-year study period,while AOD was higher in south and lower in north during summertime.A genetic algorithm technique is used to calibrate the key model parameters and simulations are carried out for 2015,a year when field data was *** simulation results show that DMS seawater concentration ranges from 1.56 to 5.88 nmol L^(−1) with a mean value of 2.76 nmol L^(−1).DMS sea-air flux ranges from 2.66 to 5.00mmol m^(−2) d^(−1) with mean of 3.80mmol m^(−2) d^(−1).Positive correlations of about 0.5 between CHL and AOD were found in the study region,with higher correlations along the coasts of jiangsu and Zhejiang *** elevated CHL concentration along the west coast is correlated with increased sea-water concentrations of DMS in the *** results suggest a possible influ-ence of DMS-derived aerosol in the local ECMS atmosphere,especially along the western coastline of ECMS.

关键词： dimethylsulfide sea-to-air flux chlorophyll-a aerosol optical depth biogeochemical model Eastern China Marginal Seas

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Using genetic algorithms to calibrate a dimethylsulfide production model in the Arctic Ocean

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Chinese journal of Oceanology and Limnology 2010年第3期28卷 573-582页

作者：瞿波 GABrIC j.albert Nantong University Griffith University

The global climate is intimately connected to changes in the polar oceans. The variability of sea ice coverage affects deep-water formations and large-scale thermohaline circulation patterns. The polar radiative budget is sensitive to sea-ice loss and consequent surface albedo changes. Aerosols and polar cloud microphysics are crucial players in the radioactive energy balance of the Arctic Ocean. The main biogenic source of sulfate aerosols to the atmosphere above remote seas is dimethylsulfide (DMS). recent research suggests the flux of DMS to the Arctic atmosphere may change markedly under global warming. This paper describes climate data and DMS production (based on the five years from 1998 to 2002) in the region of the Barents Sea (30–35°E and 70–80°N). A DMS model is introduced together with an updated calibration method. A genetic algorithm is used to calibrate the chlorophyll-a (CHL) measurements (based on satellite SeaWiFS data) and DMS content (determined from cruise data collected in the Arctic). Significant interannual variation of the CHL amount leads to significant interannual variability in the observed and modeled production of DMS in the study region. Strong DMS production in 1998 could have been caused by a large amount of ice algae being released in the southern region. Forcings from a general circulation model (CSIrO Mk3) were applied to the calibrated DMS model to predict the zonal mean sea-to-air flux of DMS for contemporary and enhanced greenhouse conditions at 70–80°N. It was found that significantly decreasing ice coverage, increasing sea surface temperature and decreasing mixed-layer depth could lead to annual DMS flux increases of more than 100% by the time of equivalent CO2 tripling (the year 2080). This significant perturbation in the aerosol climate could have a large impact on the regional Arctic heat budget and consequences for global warming.

关键词： Arctic Ocean dimethyl sulfide mixed-layer depth chlorophyll-a dimethyl sulfoniopropionate

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Ameliorate Security by Introducing Security Server in Software Defined Network

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Computers, Materials & Continua 2020年第3期62卷 1077-1096页

作者： j.Vijila A.albert raj University College of Engineering Nagercoil629004India Sree Krishna College of Engineering and Technology Coimbatore641008India

Software Defined Network(SDN)deals with huge data processing units which possess network ***,due to centralization behavior ensuring security in SDN is the major *** this work to ensure security,a security server has been at its aid to check the vulnerability of the networks and to keep an eye on the packet according to the screening policies.A Secure Shell Connection(SSH)is established by the security server which does a frequent inspection of the network’s *** detection and the Intrusion Detection System policies are also incorporated in the server for the effective scanning of the *** response to a suspicious log or the packets in the SDN network there is a change in the security *** the proposed work updates the security policies in accordance with the attacker mentality.

关键词： SDN security server malware deduction

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Spike in phytoplankton biomass in Greenland Sea during 2009 and the correlations among chlorophyll-a,aerosol optical depth and ice cover

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Chinese journal of Oceanology and Limnology 2014年第2期32卷 241-254页

作者：瞿波 albert j. GABrIC 路海浪林道荣 School of Science Nantong University School of Environment Griffith University

The distributions and correlations of chlorophyll-a(Chl-a),aerosol optical depth(AOD)and ice cover in the southeast Arctic Ocean-Greenland Sea(10°W–10°E,70°–80°N)between 2003 and 2009 were studied using satellite data and statistical *** analysis showed correlations between Chl-a and AOD,Chl-a and ice cover,and AOD and ice cover with different time *** time lag of Chl-a and AOD indicated their long-term equilibrium *** in AOD and Chl-a and generally occurred in May and july,*** the time lag,the correlation between Chl-a and AOD in the study region was as high as *** peak gap between Chl-a and AOD shifted for about 6 weeks during 2003–*** the summer and autumn of 2009,Chl-a and AOD levels were much higher than during the other years,especially in the northern band of the study region(75°–80°N).The driving forces for this localized increase in phytoplankton biomass could be mainly attributed to the very high rate of ice melting in spring and early summer and the high wind speed in autumn,together with the increased deposition of aerosol throughout the *** unusually high AOD in the spring of 2003 was mainly due to a massive fi re in russia,which occurred in the fi rst half of the *** the 7 years of the study,the sea surface temperature generally *** may have been due to the release of dimethylsulfi de into the air,excreted in large amounts from abundant phytoplankton biomass,and its subsequent reaction,form large amounts of aerosol,and resulting in regional cooling.

关键词： phytoplankton biomass aerosol optical depth (AOD) ice cover wind speed Arctic Ocean

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