Cloning and expression of an envelope gene of West Nile virus and evaluation of the protein for use in an IgM ELISA.

PubMed

Saxena, Divyasha; Parida, Manmohan; Rao, Putcha Venkata L; Kumar, Jyoti S

2013-04-01

West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis. The early confirmatory diagnosis of WNV infections is important for timely clinical management and epidemiologic control in areas where multiple flaviviruses are endemic. The coexistence of WNV along with other members of flaviviruses like dengue and Japanese encephalitis in India has complicated the serodiagnosis due to cross-reactive antigens. In the present study, the development and evaluation of a highly sensitive and specific IgM enzyme-linked immunosorbent assay (ELISA) using the recombinant envelope protein (rWNV-Env) for rapid, early, and accurate diagnosis of WNV are reported. The gene coding for the envelope protein of WNV was cloned and expressed in pET 28a vector followed by purification of recombinant protein by affinity chromatography. An indirect IgM microplate ELISA using purified rWNV-Env protein was optimized having no cross reactivity with healthy human serum. Furthermore, the specificity of this assay was confirmed by cross checking with serum samples obtained from patients with dengue and Japanese encephalitis viruses. The comparative evaluation of this rWNV-Env protein-specific IgM ELISA with plaque reduction neutralization test assay using 105 acute phase of clinical samples revealed 95% concordance with sensitivity and specificity of 92% and 97%, respectively. The positive and negative predictive values of recombinant-based Env ELISA were 94% and 96%, respectively. The recombinant envelope protein-based WNV-specific ELISA reported in this study will be useful for rapid screening of large numbers of clinical samples in endemic areas during outbreaks. Copyright © 2013 Elsevier Inc. All rights reserved.

IGMS Overview

EPA Pesticide Factsheets

The Integrated Grants Management System (IGMS) is a web-based system that contains information on the recipient of the grant, fellowship, cooperative agreement and interagency agreement, including the name of the entity accepting the award.

IGMS Model

EPA Pesticide Factsheets

The Integrated Grants Management System (IGMS) is a web-based system that contains information on the recipient of the grant, fellowship, cooperative agreement and interagency agreement, including the name of the entity accepting the award.

A High-Resolution Study of the IGM at 5 < z < 6.4

NASA Astrophysics Data System (ADS)

Becker, G. D.; Sargent, W. L. W.; Rauch, M.; Simcoe, R. A.

2005-12-01

The complete Lyman-alpha absorption seen in the spectra of z > 6 quasars suggest that the reionization of the IGM may have completed as late as z = 6.2. However, this late reionization scenario remains controversial due in part to studies of galaxy luminosity functions, which favor a highly-ionized IGM out to z > 6.5. In order to improve our understanding of the IGM at these redshifts, we have acquired Keck/HIRES spectra of nine quasars at 4.8 < z < 6.4. These are the first high-resolution spectra ever taken at z > 4.6, and are providing the first detailed look at the very high-redshift IGM. We will present the first results from this data set, highlighting the evolution of the Lyman-alpha forest and the quasar proximity regions. The high-resolution data also reveal an overabundance of O I systems at z > 6 towards SDSS J1148+5251. These O I absorbers may represent the last pockets of neutral gas to be reionized at z ˜ 6. Alternatively, they may be caused by enriched galaxy halos physically similar to those observed at lower redshift. For these systems we are able to measure accurate column densities of O I, C II, and Si II. The relative abundances are consistent with the yields of ordinary Type II supernovae, with at most ˜ 30% of the silicon contributed by very massive stars. GDB and WLWS have been supported by the NSF through grants AST 99-00733 and AST 02-06067. MR has been supported by the NSF under grant AST 00-98492. RAS has been supported by the MIT Pappalardo Fellowship program.

IgM rheumatoid factor removal and performance of the FTA-ABS (IgM) test in congenital syphilis.

PubMed

Meyer, M P; Roditi, D; Louw, S

1992-08-01

To determine the performance of the FTA-ABS (IgM) test in congenital syphilis after eliminating interference by IgM rheumatoid factor (RF) and preventing competitive inhibition by IgG. The FTA-ABS (IgM) test was carried out before and after RF removal (achieved by immunoprecipitation of the IgG) in infants with congenital syphilis and controls. Newborns delivered in the Peninsula Maternal and Neonatal Services in Cape Town and infants presenting at Red Cross War Memorial Children's Hospital. Infants with congenital syphilis aged 0-4 months were divided into those with clinical signs at presentation and those who were asymptomatic at delivery. In addition, patients without congenital syphilis but with similar clinical signs at presentation were investigated as were control infants. The diagnosis of congenital syphilis was based on the criteria suggested by Kaufman et al (1977). Amongst symptomatic infants with congenital syphilis the FTA-ABS (IgM) test was positive in 34 (92%) of 37 cases prior to abolishing the RF effect and in 29 (78.4%) of 37 cases afterwards (p = 0.19). In 12 cases of congenital syphilis who were asymptomatic at birth, 10 had positive FTA-ABS (IgM) tests before RF removal and only three had positive tests afterwards (p = 0.006). False positive tests were not found amongst 15 symptomatic infants whose clinical features mimicked those of the infants with congenital syphilis. Among 51 healthy infants the test had a false-positive rate of 2% in newborns and 13% in older infants. The false positive reactions were eradicated by IgG precipitation. Following IgG and RF removal there was an improvement in the specificity of the FTA-ABS (IgM) test but this was at the expense of a loss of sensitivity, particularly in asymptomatic newborns. For newborns, if the FTA-ABS (IgM) test was positive, the patient was likely to require treatment for congenital syphilis, regardless of whether the result was due to the presence of RF or specific IgM.

A peptide extension dictates IgM assembly.

PubMed

Pasalic, Dzana; Weber, Benedikt; Giannone, Chiara; Anelli, Tiziana; Müller, Roger; Fagioli, Claudio; Felkl, Manuel; John, Christine; Mossuto, Maria Francesca; Becker, Christian F W; Sitia, Roberto; Buchner, Johannes

2017-10-10

Professional secretory cells can produce large amounts of high-quality complex molecules, including IgM antibodies. Owing to their multivalency, polymeric IgM antibodies provide an efficient first-line of defense against pathogens. To decipher the mechanisms of IgM assembly, we investigated its biosynthesis in living cells and faithfully reconstituted the underlying processes in vitro. We find that a conserved peptide extension at the C-terminal end of the IgM heavy (Ig-μ) chains, termed the tailpiece, is necessary and sufficient to establish the correct geometry. Alanine scanning revealed that hydrophobic amino acids in the first half of the tailpiece contain essential information for generating the correct topology. Assembly is triggered by the formation of a disulfide bond linking two tailpieces. This induces conformational changes in the tailpiece and the adjacent domain, which drive further polymerization. Thus, the biogenesis of large and topologically challenging IgM complexes is dictated by a local conformational switch in a peptide extension.

A peptide extension dictates IgM assembly

PubMed Central

Pasalic, Dzana; Weber, Benedikt; Giannone, Chiara; Anelli, Tiziana; Müller, Roger; Fagioli, Claudio; Felkl, Manuel; John, Christine; Mossuto, Maria Francesca; Sitia, Roberto; Buchner, Johannes

2017-01-01

Professional secretory cells can produce large amounts of high-quality complex molecules, including IgM antibodies. Owing to their multivalency, polymeric IgM antibodies provide an efficient first-line of defense against pathogens. To decipher the mechanisms of IgM assembly, we investigated its biosynthesis in living cells and faithfully reconstituted the underlying processes in vitro. We find that a conserved peptide extension at the C-terminal end of the IgM heavy (Ig-μ) chains, termed the tailpiece, is necessary and sufficient to establish the correct geometry. Alanine scanning revealed that hydrophobic amino acids in the first half of the tailpiece contain essential information for generating the correct topology. Assembly is triggered by the formation of a disulfide bond linking two tailpieces. This induces conformational changes in the tailpiece and the adjacent domain, which drive further polymerization. Thus, the biogenesis of large and topologically challenging IgM complexes is dictated by a local conformational switch in a peptide extension. PMID:28973899

A Neutral Network based Early Eathquake Warning model in California region

NASA Astrophysics Data System (ADS)

Xiao, H.; MacAyeal, D. R.

2016-12-01

Early Earthquake Warning systems could reduce loss of lives and other economic impact resulted from natural disaster or man-made calamity. Current systems could be further enhanced by neutral network method. A 3 layer neural network model combined with onsite method was deployed in this paper to improve the recognition time and detection time for large scale earthquakes.The 3 layer neutral network early earthquake warning model adopted the vector feature design for sample events happened within 150 km radius of the epicenters. Dataset used in this paper contained both destructive events and small scale events. All the data was extracted from IRIS database to properly train the model. In the training process, backpropagation algorithm was used to adjust the weight matrices and bias matrices during each iteration. The information in all three channels of the seismometers served as the source in this model. Through designed tests, it was indicated that this model could identify approximately 90 percent of the events' scale correctly. And the early detection could provide informative evidence for public authorities to make further decisions. This indicated that neutral network model could have the potential to strengthen current early warning system, since the onsite method may greatly reduce the responding time and save more lives in such disasters.

Comparison of three commercial IgG and IgM ELISA kits for the detection of tick-borne encephalitis virus antibodies.

PubMed

Ackermann-Gäumann, Rahel; Tritten, Marie-Lise; Hassan, Mona; Lienhard, Reto

2018-05-01

Tick-borne encephalitis (TBE) is endemic in many parts of Europe and Asia. The diagnosis of this disease is essentially based on the demonstration of specific antibodies. For reasons of simplicity, automatization and quick availability of test results, enzyme-linked immunosorbent assays (ELISAs) are the method of choice for serological diagnosis of TBE. Here, we evaluated three commercially available anti-TBEV IgG and IgM ELISAs using 251 serum samples: the SERION ELISA classic FSME Virus/TBE Virus IgG and IgM kit (Virion\\Serion), the RIDASCREEN ® FSME/TBE IgG and IgM kit (R-Biopharm), and the anti-FSME/TBE virus ELISA "Vienna" IgG/anti-FSME/TBE virus ELISA IgM kit (Euroimmun). In total, discrepant test results for IgG and/or IgM were observed for 37/251 (14.7 %) of tested samples; differences were statistically significant. Reference values defined by serum neutralization test (SNT, n = 25) or results provided by EQA organizers (n = 2) were established for a subset of samples. In relation to these values, false-positive results were observed mainly for Euroimmun Vienna IgG and RIDASCREEN IgG, whereas false-negative results were primarily observed for Virion\\Serion IgG and RIDASCREEN IgM kits. In routine diagnostics, specificity problems are of major relevance and may be addressed by analyzing the respective samples using SNT. Copyright © 2018 Elsevier GmbH. All rights reserved.

Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

PubMed Central

Throsby, Mark; van den Brink, Edward; Jongeneelen, Mandy; Poon, Leo L. M.; Alard, Philippe; Cornelissen, Lisette; Bakker, Arjen; Cox, Freek; van Deventer, Els; Guan, Yi; Cinatl, Jindrich; ter Meulen, Jan; Lasters, Ignace; Carsetti, Rita; Peiris, Malik; de Kruif, John; Goudsmit, Jaap

2008-01-01

Background The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. PMID:19079604

The etiology of Rubella IgM positivity in patients with rubella-like illness in Iran from 2011 to 2013.

PubMed

Khorrami, Seyed Mahmood Seyed; Mokhtari-Azad, Talat; Yavarian, Jila; Nasab, Gazal Sadat Fatemi; Naseri, Maryam; Jandaghi, Nazanin Zahra Shafiei

2015-11-01

Rubella is a mild self-limiting contagious viral disease caused by the rubella virus (RV). Although symptoms are often mild, the concern is centralized around the possible effect on a fetus growth and development in case of primary infection during early months of pregnancy. Recently acquired rubella is commonly confirmed by RV-specific IgM antibody detection in the serum. However, rubella primary infection is not always the only cause of IgM positivity. Other possible causes of rubella IgM positivity may include IgM persistence following vaccination or naturally acquired infection or even re-infection. Moreover, nonspecific IgM reactivity can cause false-positive results. There are few articles to differentiate the aetiology of rash in rubella-like illnesses. However, limited studies have been conducted on clarifying the source of IgM positivity in these cases. This article reports the study of 10,896 clinical cases demonstrating rubella-like illness between 2011 and 2013 in Iran. The rate of IgM positivity among these cases was 0.52% (57 cases). As predicted based on the high coverage of vaccination in Iran fewer than 16% of cases with ELISA IgM positive result, were due to current rubella primary infections. The greater part of the positive IgM reactions occurred in cross reactivity with other viruses (31.6%) or in prolonged IgM response post vaccination (24.6%). This research confirmed that the positive result of rubella IgM assay in vaccinated individuals is mainly caused by prolonged IgM production, rubella re-infection, and false positivity due to infection with other viruses, rather than the rubella primary infection itself. © 2015 Wiley Periodicals, Inc.

Serologic Cross-Reactivity of Human IgM and IgG Antibodies to Five Species of Ebola Virus

PubMed Central

MacNeil, Adam; Reed, Zachary; Rollin, Pierre E.

2011-01-01

Five species of Ebola virus (EBOV) have been identified, with nucleotide differences of 30–45% between species. Four of these species have been shown to cause Ebola hemorrhagic fever (EHF) in humans and a fifth species (Reston ebolavirus) is capable of causing a similar disease in non-human primates. While examining potential serologic cross-reactivity between EBOV species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following EBOV infection has not been thoroughly characterized. In order to examine cross-reactivity of human serologic responses to EBOV, we developed antigen preparations for all five EBOV species, and compared serologic responses by IgM capture and IgG enzyme-linked immunosorbent assay (ELISA) in groups of convalescent diagnostic sera from outbreaks in Kikwit, Democratic Republic of Congo (n = 24), Gulu, Uganda (n = 20), Bundibugyo, Uganda (n = 33), and the Philippines (n = 18), which represent outbreaks due to four different EBOV species. For groups of samples from Kikwit, Gulu, and Bundibugyo, some limited IgM cross-reactivity was noted between heterologous sera-antigen pairs, however, IgM responses were largely stronger against autologous antigen. In some instances IgG responses were higher to autologous antigen than heterologous antigen, however, in contrast to IgM responses, we observed strong cross-reactive IgG antibody responses to heterologous antigens among all sets of samples. Finally, we examined autologous IgM and IgG antibody levels, relative to time following EHF onset, and observed early peaking and declining IgM antibody levels (by 80 days) and early development and persistence of IgG antibodies among all samples, implying a consistent pattern of antibody kinetics, regardless of EBOV species. Our findings demonstrate limited cross-reactivity of IgM antibodies to EBOV, however, the stronger tendency for cross-reactive IgG antibody responses can largely

Genetics Home Reference: X-linked hyper IgM syndrome

MedlinePlus

... Home Health Conditions X-linked hyper IgM syndrome X-linked hyper IgM syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked hyper IgM syndrome is a condition that ...

Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea.

PubMed

Jang, J-H; Jung, Y M; Kim, J S; Lee, S H; Kim, J-W; Hwang, S G; Rim, K S; Park, S J; Park, Y M; Kang, S-K; Lee, H S; Yun, H; Kim, J-H; Jeong, S-H

2011-10-01

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution. © 2011 Blackwell Publishing Ltd.

Murine Visceral Leishmaniasis: IgM and Polyclonal B-Cell Activation Lead to Disease Exacerbation

PubMed Central

Deak, Eszter; Jayakumar, Asha; Wing Cho, Ka; Goldsmith-Pestana, Karen; Dondji, Blaise; Lambris, John D.; McMahon-Pratt, Diane

2010-01-01

In visceral leishmaniasis, the draining lymph node (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with L. infantum. Although not unexpected, at early times post-infection there is a marked B cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post-infection, polyclonal antibodies (TNP, OVA, chromatin) were observed and the levels appeared comparable to the specific anti-leishmania response. Although B-cell-deficient JHD BALB/c mice are relatively resistant to infection, neither B-cell-derived IL-10 nor B-cell antigen presentation appear to be primarily responsible for the elevated parasitemia. However, passive transfer and reconstitution of JHD BALB/c with secretory immunoglobulins, (IgM or IgG; specific or non-specific immune complexes) results in increased susceptibility to L. infantum infection. Further, JHD BALB/c mice transgenetically reconstituted to secrete IgM demonstrated exacerbated disease in comparison to wild type BALB/c mice as early as 2 days post-infection. Evidence suggests that complement activation (generation of C5a) and signaling via the C5aR (CD88) is related to the disease exacerbation caused by IgM rather than cytokine levels (IL-10 or IFN-γ). Overall these studies indicate that polyclonal B cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention. PMID:20213734

Evaluation of Two Enzyme-Linked Immunosorbent Assay Kits for Chikungunya Virus IgM Using Samples from Deceased Organ and Tissue Donors.

PubMed

Prince, Harry E; Altrich, Michelle L; Nowicki, Marek J

2016-10-01

The identification of nearly 3,500 cases of chikungunya virus (CHIKV) infection in U.S. residents returning in 2014 and 2015 from areas in which it is endemic has raised concerns within the transplant community that, should recently infected individuals become organ and/or tissue donors, CHIKV would be transmitted to transplant recipients. Thus, tests designed to detect recent CHIKV infection among U.S. organ and tissue donors may become necessary in the future. Accordingly, we evaluated 2 enzyme-linked immunosorbent assays (ELISAs) for CHIKV IgM readily available in the United States using 1,000 deidentified serum or plasma specimens collected from donors between November 2014 and March 2015. The Euroimmun indirect ELISA identified 38 reactive specimens; however, all 38 were negative for CHIKV IgG and IgM in immunofluorescence assays (IFAs) conducted at a reference laboratory and, thus, were falsely reactive in the Euroimmun CHIKV IgM assay. The InBios IgM-capture ELISA identified 26 reactive samples, and one was still reactive (index ≥ 1.00) when retested using the InBios kit with a background subtraction modification to identify false reactivity. This reactive specimen was CHIKV IgM negative but IgG positive by IFAs at two reference laboratories; plaque reduction neutralization testing (PRNT) demonstrated CHIKV-specific reactivity. The IgG and PRNT findings strongly suggest that the InBios CHIKV IgM-reactive result represents true reactivity, even though the IgM IFA result was negative. If testing organ/tissue donors for CHIKV IgM becomes necessary, the limitations of the currently available CHIKV IgM ELISAs and options for their optimization must be understood to avoid organ/tissue wastage due to falsely reactive results. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Evaluation of Two Enzyme-Linked Immunosorbent Assay Kits for Chikungunya Virus IgM Using Samples from Deceased Organ and Tissue Donors

PubMed Central

Altrich, Michelle L.; Nowicki, Marek J.

2016-01-01

The identification of nearly 3,500 cases of chikungunya virus (CHIKV) infection in U.S. residents returning in 2014 and 2015 from areas in which it is endemic has raised concerns within the transplant community that, should recently infected individuals become organ and/or tissue donors, CHIKV would be transmitted to transplant recipients. Thus, tests designed to detect recent CHIKV infection among U.S. organ and tissue donors may become necessary in the future. Accordingly, we evaluated 2 enzyme-linked immunosorbent assays (ELISAs) for CHIKV IgM readily available in the United States using 1,000 deidentified serum or plasma specimens collected from donors between November 2014 and March 2015. The Euroimmun indirect ELISA identified 38 reactive specimens; however, all 38 were negative for CHIKV IgG and IgM in immunofluorescence assays (IFAs) conducted at a reference laboratory and, thus, were falsely reactive in the Euroimmun CHIKV IgM assay. The InBios IgM-capture ELISA identified 26 reactive samples, and one was still reactive (index ≥ 1.00) when retested using the InBios kit with a background subtraction modification to identify false reactivity. This reactive specimen was CHIKV IgM negative but IgG positive by IFAs at two reference laboratories; plaque reduction neutralization testing (PRNT) demonstrated CHIKV-specific reactivity. The IgG and PRNT findings strongly suggest that the InBios CHIKV IgM-reactive result represents true reactivity, even though the IgM IFA result was negative. If testing organ/tissue donors for CHIKV IgM becomes necessary, the limitations of the currently available CHIKV IgM ELISAs and options for their optimization must be understood to avoid organ/tissue wastage due to falsely reactive results. PMID:27535838

IGMS Construction Grants Overview

EPA Pesticide Factsheets

The Integrated Grants Management System (IGMS) is a web-based system that contains information on the recipient of the grant, fellowship, cooperative agreement and interagency agreement, including the name of the entity accepting the award.

IGMS Search User Guide

EPA Pesticide Factsheets

The Integrated Grants Management System (IGMS) is a web-based system that contains information on the recipient of the grant, fellowship, cooperative agreement and interagency agreement, including the name of the entity accepting the award.

Evaluation of the IMMULITE® 2000 CMV IgM assay

PubMed Central

2012-01-01

Background Diagnosis of cytomegalovirus (CMV) infection is challenging because of the high rate of asymptomatic infection and the low specificity of associated symptoms and signs. As a result, laboratory testing is an essential aid in making an accurate diagnosis. The presence of CMV IgM is indicative of primary CMV infection. In pregnancy, diagnosis of primary infection is important because primary maternal infection increases fetal infection risk substantially. Fetal infection can result in serious sequelae ranging from neurological deficits to death. Diagnosis among the immunocompromised is also critical for the timely initiation of therapy that can reduce morbidity and mortality risk. Methods The IMMULITE® 2000 CMV IgM assay qualitatively detects CMV IgM antibodies in human serum or plasma to aid in the diagnosis of current or recent CMV infection. To determine expected values in apparently healthy subjects, 136 samples were tested. Reproducibility, normal range, and method comparison studies were also performed to evaluate the assay's performance. The assay's reproducibility was evaluated across three sites. Seven hundred and eighteen (n = 718) individual patient serum samples, which included samples from CMV IgM-positive (n = 109, determined by the Abbott IMx CMV or the Diamedix CMV IgM assays), pregnant (n = 210), HIV-positive (n = 30), immunosuppressed (n = 102), and transplant patients (n = 17) and from patients with potentially cross-reacting conditions (n = 136) were evaluated in the method comparison study. The positive, negative, and overall agreement between the IMMULITE 2000 CMV IgM assay and the VIDAS CMV IgM assay (predicate assay) were determined. Results The assay demonstrated excellent reproducibility with a total CV of less than 10%. The positive, negative, and overall agreement between the IMMULITE 2000 assay and the VIDAS assay were > 95% for the method comparison samples. Among potentially cross-reactive samples, the overall agreement

Evaluation of the IMMULITE® 2000 CMV IgM assay.

PubMed

Bal, Tricia A; Armstrong, Glenn; Han, Xiang Y

2012-02-29

Diagnosis of cytomegalovirus (CMV) infection is challenging because of the high rate of asymptomatic infection and the low specificity of associated symptoms and signs. As a result, laboratory testing is an essential aid in making an accurate diagnosis. The presence of CMV IgM is indicative of primary CMV infection. In pregnancy, diagnosis of primary infection is important because primary maternal infection increases fetal infection risk substantially. Fetal infection can result in serious sequelae ranging from neurological deficits to death. Diagnosis among the immunocompromised is also critical for the timely initiation of therapy that can reduce morbidity and mortality risk. The IMMULITE® 2000 CMV IgM assay qualitatively detects CMV IgM antibodies in human serum or plasma to aid in the diagnosis of current or recent CMV infection. To determine expected values in apparently healthy subjects, 136 samples were tested. Reproducibility, normal range, and method comparison studies were also performed to evaluate the assay's performance. The assay's reproducibility was evaluated across three sites. Seven hundred and eighteen (n = 718) individual patient serum samples, which included samples from CMV IgM-positive (n = 109, determined by the Abbott IMx CMV or the Diamedix CMV IgM assays), pregnant (n = 210), HIV-positive (n = 30), immunosuppressed (n = 102), and transplant patients (n = 17) and from patients with potentially cross-reacting conditions (n = 136) were evaluated in the method comparison study. The positive, negative, and overall agreement between the IMMULITE 2000 CMV IgM assay and the VIDAS CMV IgM assay (predicate assay) were determined. The assay demonstrated excellent reproducibility with a total CV of less than 10%. The positive, negative, and overall agreement between the IMMULITE 2000 assay and the VIDAS assay were > 95% for the method comparison samples. Among potentially cross-reactive samples, the overall agreement between the two assays was 96

Association between haptoglobin and IgM levels and the clinical progression of caseous lymphadenitis in sheep

PubMed Central

2013-01-01

Background Sheep caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis (Cp), is associated with direct economic losses and presents significant zoonotic potential. Despite the importance of the disease, a satisfactory vaccine model has not been developed. Thus, this study aimed to investigate the association between haptoglobin (Hp) and IgM levels and the clinical progression of CLA in primarily infected sheep and in sheep immunized with Cp- secreted antigens adjuvanted with Quillaja saponaria saponins. These animals were kept with CLA-positive sheep to simulate natural exposure that occurs in field conditions. During the experiment, the Hp and IgM levels were monitored for 21 days, and the development of internal CLA lesions was investigated through necropsies on day182 post-immunization. Results Primarily infected sheep in Group 2 (inoculated with 2x105 Cp virulent strain) had higher Hp values between the first and ninth days post inoculation (PI) than sheep in Group 1 (control; P < 0.05). Immunized animals in Group 3 had significantly higher Hp values between the third and seventh days PI, compared with the control group (P < 0.01). Binary logistic regression (BLR) analysis of primarily infected sheep indicated an association between Hp concentration and CLA clinical progression: animals with high Hp values had 99.9% less risk of having CLA abscesses than animals with low Hp levels (Odds ratio = 0.001, P < 0.05). Both experimental groups had significantly higher IgM titers than the control group around the ninth and eleventh days PI (P < 0.05). The BLR analysis for immunized sheep indicated an association between IgM levels and clinical progression: sheep with high IgM titers had 100.0% less risk of having CLA abscesses than animals with low IgM levels (Odds ratio = 0.000, P < 0.05). Conclusions Resistance to C. pseudotuberculosis infection is supported by the early acute phase response, in which up-regulation of

Diagnostic value of detecting specific IgA and IgM with recombinant Trypanosoma cruzi antigens in congenital Chagas' disease.

PubMed

Lorca, M; Veloso, C; Munoz, P; Bahamonde, M I; Garcia, A

1995-06-01

The present study compares the early diagnosis of congenital Chagas' disease with a DOT assay using recombinant antigens with immunofluorescence antibody testing (IFAT) and an enzyme-linked immunosorbent assay (ELISA). The studies were performed using cord blood and sera of 12 infected newborns (group I) and 12 uninfected ones born to Trypanosoma cruzi-infected mothers (group II). Conventional IFAT and ELISA showed positive results for IgG at high titers, in infants and mothers of both groups; IgA antibodies were detected by ELISA in four of the infected infants and IgM was detected in two of them. All sera of the uninfected infants were negative for IgA and IgM in the ELISA. Application of a DOT assay using eight recombinant T. cruzi antigens allowed detection of specific IgA in the cord blood of six of the infected cases and IgM in eight of them. Repetition of these serologic tests in samples obtained during a monthly follow-up gave positive results for IgA in two of the initially negative infants of group I and for IgM in four of them. This means that diagnosis of congenital T. cruzi infection was confirmed, through demonstration of specific IgM, in all infected infants, and of IgA in eight of them. The importance of late detection of IgM in siblings born of infected mothers is discussed. The detection of IgM and IgA in sera obtained after birth is believed to be due to a congenital transmission of the parasite that occurred late in pregnancy. No IgA or IgM antibodies could be detected by the DOT assay in the sera of the negative controls.(ABSTRACT TRUNCATED AT 250 WORDS)

A sulfhydryl-rich IgM protein with multiple serological specificities.

PubMed Central

Merlini, G; Zettervall, O; Forsgren, A; Galliano, M; Lindberg, A A; Svenson, S B; Pavesi, F; Turesson, I

1987-01-01

A monoclonal IgM lambda protein from a patient (E.T.) suffering from a lymphocytic lymphoma agglutinated Salmonella typhi bacteria and uncoated acryl particles. The antigenic determinant on Salmonella typhi bacteria was found to be 0-12 (alpha-D-Galp-(1-2)-alpha-D-Manp) while the structure on acryl particles recognized by IgM ET has not been defined. Both binding sites for bacteria and acryl particle determinants are localized on the same IgM molecule. The uncommon affinity of this IgM protein for some divalent heavy metal ions led to the finding of an unusually high content of sulfhydryl groups in the Fab portion of the molecule. PMID:2443287

Physiological IgM Class Catalytic Antibodies Selective for Transthyretin Amyloid*

PubMed Central

Planque, Stephanie A.; Nishiyama, Yasuhiro; Hara, Mariko; Sonoda, Sari; Murphy, Sarah K.; Watanabe, Kenji; Mitsuda, Yukie; Brown, Eric L.; Massey, Richard J.; Primmer, Stanley R.; O'Nuallain, Brian; Paul, Sudhir

2014-01-01

Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid β peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function. PMID:24648510

The significance of serum IgM IgA and IgG antibodies specific for Epstein-Barr virus as determined by immunoperoxidase assay in the rapid diagnosis of infectious mononucleosis.

PubMed

Hadar, T; Margalith, M; Sagiv, E; Sarov, B; Sarov, I

1995-05-01

The feasibility of using serum IgM, IgA and IgG antibodies specific to Epstein-Barr virus (EBV) viral capsid antigen (VCA), as determined by immunoperoxidase assay (IPA), for the early diagnosis of mononucleosis was evaluated in 65 patients with infectious mononucleosis (IMN). Control groups consisted of 104 healthy students and 15 cytomegalovirus-infected patients. In the first serum sample obtained upon admission, IgM antibodies (titer > or = 64) to EBV VCA were found in 64 of the 65 IMN patients (98%), while EBV-VCA IgA antibodies (titer > or = 32) were found in 32 patients (49%). In those particular titers, no EBV-VCA IgM or IgA antibodies were found in any of the control sera. EBV-VCA-specific IgM antibodies were also not detected in any of the 15 patients with cytomegalovirus infection. In sera obtained from IMN patients within 10 days of the onset of symptoms, 18 of 19 (95%) were IgM seropositive. This study demonstrates that serum EBV-VCA IgM antibodies (titer > or = 64) as determined by IPA are highly specific (100%) and highly sensitive (98%) and can be of value for the early and rapid diagnosis of EBV-IMN infection.

Successful treatment of IgM paraproteinaemic neuropathy with fludarabine

PubMed Central

Wilson, H.; Lunn, M.; Schey, S.; Hughes, R

1999-01-01

OBJECTIVES—To evaluate the response of four patients with IgM paraproteinaemic neuropathy to a novel therapy—pulsed intravenous fludarabine.
BACKGROUND—The peripheral neuropathy associated with IgM paraproteinaemia usually runs a chronic, slowly progressive course which may eventually cause severe disability. Treatment with conventional immunosuppressive regimens has been unsatisfactory. Fludarabine is a novel purine analogue which has recently been shown to be effective in low grade lymphoid malignancies.
METHODS—Four patients were treated with IgM paraproteinaemic neuropathy with intravenous pulses of fludarabine. Two of the four patients had antibodies to MAG and characteristic widely spaced myelin on nerve biopsy and a third had characteristic widely spaced myelin only. The fourth had an endoneurial lymphocytic infiltrate on nerve biopsy and a diagnosis of Waldenström's macroglobulinaemia.
RESULTS—In all cases subjective and objective clinical improvement occurred associated with a significant fall in the IgM paraprotein concentration in three cases. Neurophysiological parameters improved in the three patients examined. The treatment was well tolerated. All patients developed mild, reversible lymphopenia and 50% mild generalised myelosuppression, but there were no febrile episodes.
CONCLUSION—Fludarabine should be considered as a possible treatment for patients with IgM MGUS paraproteinaemic neuropathy.

 PMID:10209166

Multiplex Microsphere Immunoassays for the Detection of IgM and IgG to Arboviral Diseases

PubMed Central

Basile, Alison J.; Horiuchi, Kalanthe; Panella, Amanda J.; Laven, Janeen; Kosoy, Olga; Lanciotti, Robert S.; Venkateswaran, Neeraja; Biggerstaff, Brad J.

2013-01-01

Serodiagnosis of arthropod-borne viruses (arboviruses) at the Division of Vector-Borne Diseases, CDC, employs a combination of individual enzyme-linked immunosorbent assays and microsphere immunoassays (MIAs) to test for IgM and IgG, followed by confirmatory plaque-reduction neutralization tests. Based upon the geographic origin of a sample, it may be tested concurrently for multiple arboviruses, which can be a cumbersome task. The advent of multiplexing represents an opportunity to streamline these types of assays; however, because serologic cross-reactivity of the arboviral antigens often confounds results, it is of interest to employ data analysis methods that address this issue. Here, we constructed 13-virus multiplexed IgM and IgG MIAs that included internal and external controls, based upon the Luminex platform. Results from samples tested using these methods were analyzed using 8 different statistical schemes to identify the best way to classify the data. Geographic batteries were also devised to serve as a more practical diagnostic format, and further samples were tested using the abbreviated multiplexes. Comparative error rates for the classification schemes identified a specific boosting method based on logistic regression “Logitboost” as the classification method of choice. When the data from all samples tested were combined into one set, error rates from the multiplex IgM and IgG MIAs were <5% for all geographic batteries. This work represents both the most comprehensive, validated multiplexing method for arboviruses to date, and also the most systematic attempt to determine the most useful classification method for use with these types of serologic tests. PMID:24086608

The evolution of multiple isotypic IgM heavy chain genes in the shark.

PubMed

Lee, Victor; Huang, Jing Li; Lui, Ming Fai; Malecek, Karolina; Ohta, Yuko; Mooers, Arne; Hsu, Ellen

2008-06-01

The IgM H chain gene organization of cartilaginous fishes consists of 15-200 miniloci, each with a few gene segments (V(H)-D1-D2-J(H)) and one C gene. This is a gene arrangement ancestral to the complex IgH locus that exists in all other vertebrate classes. To understand the molecular evolution of this system, we studied the nurse shark, which has relatively fewer loci, and characterized the IgH isotypes for organization, functionality, and the somatic diversification mechanisms that act upon them. Gene numbers differ slightly between individuals ( approximately 15), but five active IgM subclasses are always present. Each gene undergoes rearrangement that is strictly confined within the minilocus; in B cells there is no interaction between adjacent loci located > or =120 kb apart. Without combinatorial events, the shark IgM H chain repertoire is based on junctional diversity and, subsequently, somatic hypermutation. We suggest that the significant contribution by junctional diversification reflects the selected novelty introduced by RAG in the early vertebrate ancestor, whereas combinatorial diversity coevolved with the complex translocon organization. Moreover, unlike other cartilaginous fishes, there are no germline-joined VDJ at any nurse shark mu locus, and we suggest that such genes, when functional, are species-specific and may have specialized roles. With an entire complement of IgM genes available for the first time, phylogenetic analyses were performed to examine how the multiple Ig loci evolved. We found that all domains changed at comparable rates, but V(H) appears to be under strong positive selection for increased amino acid sequence diversity, and surprisingly, so does Cmicro2.

Cytomegalovirus IgM Seroprevalence among Women of Reproductive Age in the United States.

PubMed

Wang, Chengbin; Dollard, Sheila C; Amin, Minal M; Bialek, Stephanie R

2016-01-01

Cytomegalovirus (CMV) IgM indicates recent active CMV infection. CMV IgM seroprevalence is a useful marker for prevalence of transmission. Using data from the National Health and Nutrition Examination Survey (NHANES) III 1988-1994, we present estimates of CMV IgM prevalence by race/ethnicity, provide a comparison of IgM seroprevalence among all women and among CMV IgG positive women, and explore factors possibly associated with IgM seroprevalence, including socioeconomic status and exposure to young children. There was no difference in IgM seroprevalence by race/ethnicity among all women (3.1%, 2.2%, and 1.6% for non-Hispanic white, non-Hispanic black and Mexican American, respectively; P = 0.11). CMV IgM seroprevalence decreased significantly with increasing age in non-Hispanic black women (P<0.001 for trend) and marginally among Mexican American women (P = 0.07), while no apparent trend with age was seen in non-Hispanic white women (P = 0.99). Among 4001 IgG+ women, 118 were IgM+, resulting in 4.9% IgM seroprevalence. In IgG+ women, IgM seroprevalence varied significantly by age (5.3%, 7.3%, and 3.7% for women of 12-19, 20-29, and 30-49 years; P = 0.04) and race/ethnicity (6.1%, 2.7%, and 2.0% for non-Hispanic white, non-Hispanic black, and Mexican American; P<0.001). The factors reported associated with IgG seroprevalence were not associated with IgM seroprevalence. The patterns of CMV IgM seroprevalence by age, race/ethnicity, and IgG serostatus may help understanding the epidemiology of congenital CMV infection as a consequence of vertical transmission and are useful for identifying target populations for intervention to reduce CMV transmission.

Search | IGMS | Envirofacts | US EPA

EPA Pesticide Factsheets

2016-02-23

The Integrated Grants Management System (IGMS) is a web-based system that contains information on the recipient of the grant, fellowship, cooperative agreement and interagency agreement, including the name of the entity accepting the award.

The recomBead Borrelia antibody index, CXCL13 and total IgM index for laboratory diagnosis of Lyme neuroborreliosis in children.

PubMed

Skogman, B H; Lager, M; Henningsson, A J; Tjernberg, I

2017-11-01

For laboratory diagnostics of Lyme neuroborreliosis (LNB), the recomBead Borrelia antibody index (AI) assay has shown promising results in a mixed age population, but has not previously been evaluated with specific focus on paediatric patients. The aim of the study was to evaluate the recomBead Borrelia AI assay in cerebrospinal fluid (CSF) for the laboratory diagnosis of LNB in children. We also wanted to explore whether early markers, such as CXCL13 in CSF and/or total IgM index could be useful as complementary diagnostic tools. Children being evaluated for LNB in a Swedish Lyme endemic area were included in the study (n = 146). Serum and CSF were collected on admission. Patients with other specific diagnoses were controls (n = 15). The recomBead Borrelia AI assay and the recomBead CXCL13 assay (Mikrogen) were applied together with total IgM index. The overall sensitivity for recomBead Borrelia AI (IgM and IgG together) was 74% and the specificity was 97%. However, the highest sensitivity (91%) at an acceptable level of specificity (90%) was obtained by recomBead Borrelia AI together with CXCL13 and total IgM index, showing a positive predictive value of 84% and a negative predictive value of 95%. Thus, the recomBead Borrelia AI assay performs with moderate sensitivity and high specificity in paediatric LNB patients. The major advantage seems to be increased sensitivity in the possible LNB group compared to the IDEIA assay. The diagnostic sensitivity may be further increased by using a combination of early markers, such as CXCL13 in CSF and total IgM index.

Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS.

PubMed

Pestronk, Alan; Schmidt, Robert E; Choksi, Rati M; Sommerville, R Brian; Al-Lozi, Muhammad T

2012-06-01

In this investigation we studied clinical and laboratory features of polyneuropathies in patients with serum IgM binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS). We retrospectively compared 58 patients with selective IgM binding to TS-HDS to 41 consecutive patients with polyneuropathies without TS-HDS binding. Patients with IgM vs. TS-HDS commonly had distal, sensory, axonal neuropathies. Weakness was associated with IgM M-proteins. Hand pain and serum IgM M-proteins were more common than in control neuropathy patients. TS-HDS antibody binding was often selectively κ class. Biopsies showed capillary pathology with thickened basal lamina and C5b9 complement deposition. IgM in sera with TS-HDS antibodies often bound to capillaries. Serum IgM binding to TS-HDS is associated with painful, sensory > motor, polyneuropathies with an increased frequency of persistent hand discomfort, serum IgM M-proteins, and capillary pathology. Serum IgM binding to TS-HDS suggests a possible immune etiology underlying some otherwise idiopathic sensory polyneuropathies. Copyright © 2011 Wiley Periodicals, Inc.

Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay.

PubMed

Taylor, Carmel T; Mackay, Ian M; McMahon, Jamie L; Wheatley, Sarah L; Moore, Peter R; Finger, Mitchell J; Hewitson, Glen R; Moore, Frederick A

2018-05-12

Zika virus (ZIKV) has spread widely in the Pacific and recently throughout the Americas. Unless detected by RT-PCR, confirming an acute ZIKV infection can be challenging. We developed and validated a multiplexed flavivirus immunoglobulin M (IgM) microsphere immunoassay (flaviMIA) which can differentiate ZIKV-specific IgM from that due to other flavivirus infections in humans. The flaviMIA bound 12 inactivated flavivirus antigens, including those from ZIKV and yellow fever virus (YFV), to distinct anti-flavivirus antibody coupled beads. These beads were used to interrogate sera from patients with suspected ZIKV infection following travel to relevant countries. FlaviMIA results were validated by comparison to the ZIKV plaque reduction neutralization test (PRNT). The results highlight the complexity of serological ZIKV diagnosis, particularly in patients previously exposed to or vaccinated against other flaviviruses. We confirmed 99 patients with ZIKV infection by a combination of RT-PCR and serology. Importantly, ZIKV antibodies could be discriminated from those ascribed to other flavivirus infections. Serological results were sometimes confounded by the presence of pre-existing antibodies attributed to previous flavivirus infection or vaccination. Where RT-PCR results were negative, testing of appropriately timed paired sera was necessary to demonstrate seroconversion or differentiation of recent from past infection with or exposure to ZIKV.

A reassessment of IgM memory subsets in humans

PubMed Central

Bagnara, Davide; Squillario, Margherita; Kipling, David; Mora, Thierry; Walczak, Aleksandra M.; Da Silva, Lucie; Weller, Sandra; Dunn-Walters, Deborah K.; Weill, Jean-Claude; Reynaud, Claude-Agnès

2015-01-01

From paired blood and spleen samples from three adult donors we performed high-throughput V-h sequencing of human B-cell subsets defined by IgD and CD27 expression: IgD+CD27+ (“MZ”), IgD−CD27+(“memory”, including IgM (“IgM-only”), IgG and IgA) and IgD−CD27− cells (“double-negative”, including IgM, IgG and IgA). 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for Vh-gene mutation, H-CDR3-length, and Vh/Jh usage, comparing these different characteristics with all sequences from their subset of origin, for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency, and lower Vh4 and higher Jh6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (between MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The “IgM-only” subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor-product relationships with CD27+ switched memory B cells, indicating that they represent germinal center-derived IgM memory B cells, and that IgM memory and MZ B cells constitute two distinct entities. PMID:26355154

Reactivity of human monoclonal IgM with nerve glycosphingolipids.

PubMed Central

Hauttecoeur, B; Schmitt, C; Dubois, C; Danon, F; Brouet, J C

1990-01-01

We examined the reactivity of monoclonal IgM of sera from patients with neuropathy and monoclonal IgM, with or without antibody activity to myelin-associated glycoprotein (MAG), as well as sera from non-neurologic patients with Waldenström's macroglobulinaemia, with various nerve glycolipids extracts or with purified gangliosides. As expected from previous studies, all (five cases) anti-MAG IgM stained two glycolipids, the chemical characteristics of which corresponded to sulphated glucuronyl-paragloboside (SGPG) and sulphated glucuronyl-lactosaminyl-paragloboside (SGLPG). Five of 12 sera from patients with neuropathy whose IgM was devoid of anti-MAG reactivity stained nerve extracts greatly enriched (98%) with SGPG and SGLPG. Three of these five sera reacted with additional glycolipids and/or gangliosides. Two of 16 sera from patients with macroglobulinaemia without neuropathy reacted strongly with both SGPG and SGLPG. The latter finding as well as the detection of low titre of anti-sphingolipid antibodies in normal sera may cast a doubt on the pathogenetic significance of this antibody activity. Images Fig. 1 Fig. 2 Fig. 3 PMID:1694117

Factors predicting transformation of asymptomatic IgM monoclonal gammopathy.

PubMed

Greco, Antonino; Tedeschi, Alessandra; Varettoni, Marzia; Nichelatti, Michele; Paris, Laura; Ricci, Francesca; Vismara, Eleonora; Morra, Enrica

2011-02-01

We evaluated the risk of transformation of asymptomatic immunoglobulin (Ig) M monoclonal gammopathy (aIgM MG) into symptomatic lymphoproliferative disease in 287 patients all analyzed for bone marrow histopathology and immunophenotyping. This series included 201 patients with IgM MG of undetermined significance (IgM MGUS) and 86 with smoldering Waldenström's macroglobulinemia (sWM). After a median of 50 months (range, 12-322 months), 32 cases of aIgM-MG (11.1%) evolved into symptomatic malignant lymphoproliferative disease, as follows: symptomatic WM (n=26), non-Hodgkin lymphoma (n=6). The cumulative transformation percentage at 5 and 10 years was 8% and 19.5%, respectively. The parameters significantly correlated with evolution were, at univariate analysis, BM lymphoplasmacytic infiltration, high erythrocyte sedimentation rate, serum MC, serum IgM size, and serum IgA size. Among patients with aIgM-MG, those at high risk of evolution were patients with sWM, a distinct entity with serum IgM monoclonal protein≥3 g/dL and/or ≥10% bone marrow lymphoplasmacytic infiltration.

Multiplex Immunoassay for Lyme Disease Using VlsE1-IgG and pepC10-IgM Antibodies: Improving Test Performance through Bioinformatics ▿

PubMed Central

Porwancher, Richard B.; Hagerty, C. Greg; Fan, Jianqing; Landsberg, Lisa; Johnson, Barbara J. B.; Kopnitsky, Mark; Steere, Allen C.; Kulas, Karen; Wong, Susan J.

2011-01-01

The Centers for Disease Control and Prevention currently recommends a 2-tier serologic approach to Lyme disease laboratory diagnosis, comprised of an initial serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi followed by supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples. Western blot accuracy is limited by subjective interpretation of weakly positive bands, false-positive IgM immunoblots, and low sensitivity for detection of early disease. We developed an objective alternative second-tier immunoassay using a multiplex microsphere system that measures VlsE1-IgG and pepC10-IgM antibodies simultaneously in the same sample. Our study population comprised 79 patients with early acute Lyme disease, 82 patients with early-convalescent-phase disease, 47 patients with stage II and III disease, 34 patients post-antibiotic treatment, and 794 controls. A bioinformatic technique called partial receiver-operator characteristic (ROC) regression was used to combine individual antibody levels into a single diagnostic score with a single cutoff; this technique enhances test performance when a high specificity is required (e.g., ≥95%). Compared to Western blotting, the multiplex assay was equally specific (95.6%) but 20.7% more sensitive for early-convalescent-phase disease (89.0% versus 68.3%, respectively; 95% confidence interval [95% CI] for difference, 12.1% to 30.9%) and 12.5% more sensitive overall (75.0% versus 62.5%, respectively; 95% CI for difference, 8.1% to 17.1%). As a second-tier test, a multiplex assay for VlsE1-IgG and pepC10-IgM antibodies performed as well as or better than Western blotting for Lyme disease diagnosis. Prospective validation studies appear to be warranted. PMID:21367982

Genomic Region Containing Toll-Like Receptor Genes Has a Major Impact on Total IgM Antibodies Including KLH-Binding IgM Natural Antibodies in Chickens

PubMed Central

Berghof, Tom V. L.; Visker, Marleen H. P. W.; Arts, Joop A. J.; Parmentier, Henk K.; van der Poel, Jan J.; Vereijken, Addie L. J.; Bovenhuis, Henk

2018-01-01

Natural antibodies (NAb) are antigen binding antibodies present in individuals without a previous exposure to this antigen. Keyhole limpet hemocyanin (KLH)-binding NAb levels were previously associated with survival in chickens. This suggests that selective breeding for KLH-binding NAb may increase survival by means of improved general disease resistance. Genome-wide association studies (GWAS) were performed to identify genes underlying genetic variation in NAb levels. The studied population consisted of 1,628 adolescent layer chickens with observations for titers of KLH-binding NAb of the isotypes IgM, IgA, IgG, the total KLH-binding (IgT) NAb titers, total antibody concentrations of the isotypes IgM, IgA, IgG, and the total antibodies concentration in plasma. GWAS were performed using 57,636 single-nucleotide polymorphisms (SNP). One chromosomal region on chromosome 4 was associated with KLH-binding IgT NAb, and total IgM concentration, and especially with KLH-binding IgM NAb. The region of interest was fine mapped by imputing the region of the study population to whole genome sequence, and subsequently performing an association study using the imputed sequence variants. 16 candidate genes were identified, of which FAM114A1, Toll-like receptor 1 family member B (TLR1B), TLR1A, Krüppel-like factor 3 (KLF3) showed the strongest associations. SNP located in coding regions of the candidate genes were checked for predicted changes in protein functioning. One SNP (at 69,965,939 base pairs) received the maximum impact score from two independent prediction tools, which makes this SNP the most likely causal variant. This SNP is located in TLR1A, which suggests a fundamental role of TLR1A on regulation of IgM levels (i.e., KLH-binding IgM NAb, and total IgM concentration), or B cells biology, or both. This study contributes to increased understanding of (genetic) regulation of KLH-binding NAb levels, and total antibody concentrations. PMID:29375555

A Reassessment of IgM Memory Subsets in Humans.

PubMed

Bagnara, Davide; Squillario, Margherita; Kipling, David; Mora, Thierry; Walczak, Aleksandra M; Da Silva, Lucie; Weller, Sandra; Dunn-Walters, Deborah K; Weill, Jean-Claude; Reynaud, Claude-Agnès

2015-10-15

From paired blood and spleen samples from three adult donors, we performed high-throughput VH sequencing of human B cell subsets defined by IgD and CD27 expression: IgD(+)CD27(+) ("marginal zone [MZ]"), IgD(-)CD27(+) ("memory," including IgM ["IgM-only"], IgG and IgA) and IgD(-)CD27(-) cells ("double-negative," including IgM, IgG, and IgA). A total of 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for VH gene mutation, H-CDR3-length, and VH/JH usage, comparing these different characteristics with all sequences from their subset of origin for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency and lower VH4 and higher JH6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (among MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The "IgM-only" subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor-product relationships with CD27(+) switched memory B cells, indicating that they represent germinal center-derived IgM memory B cells and that IgM memory and MZ B cells constitute two distinct entities. Copyright © 2015 by The American Association of Immunologists, Inc.

Breaching peripheral tolerance promotes the production of HIV-1–neutralizing antibodies

PubMed Central

Schroeder, Kristin M.S.; Harper, Michael S.; Santiago, Mario L.

2017-01-01

A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env. Importantly, experimentally breaching immunological tolerance in wild-type mice also leads to the production of tier 2 HIV-1–neutralizing antibodies, which increase in breadth and potency following Env immunization. In both genetically prone and experimentally induced mouse models of autoimmunity, increased serum levels of IgM anti-histone H2A autoantibodies significantly correlated with tier 2 HIV-1 neutralization, and anti-H2A antibody clones were found to neutralize HIV-1. These data demonstrate that breaching peripheral tolerance permits a cross-reactive HIV-1 autoantibody response able to neutralize HIV-1. PMID:28698284

IgM myeloma: A multicenter retrospective study of 134 patients.

PubMed

Castillo, Jorge J; Jurczyszyn, Artur; Brozova, Lucie; Crusoe, Edvan; Czepiel, Jacek; Davila, Julio; Dispenzieri, Angela; Eveillard, Marion; Fiala, Mark A; Ghobrial, Irene M; Gozzetti, Alessandro; Gustine, Joshua N; Hajek, Roman; Hungria, Vania; Jarkovsky, Jiri; Jayabalan, David; Laubach, Jacob P; Lewicka, Barbara; Maisnar, Vladimir; Manasanch, Elisabet E; Moreau, Philippe; Morgan, Elizabeth A; Nahi, Hareth; Niesvizky, Ruben; Paba-Prada, Claudia; Pika, Tomas; Pour, Ludek; Reagan, John L; Richardson, Paul G; Shah, Jatin; Spicka, Ivan; Vij, Ravi; Waszczuk-Gajda, Anna; Gertz, Morie A

2017-08-01

IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL -1 with 19% of patients presenting with levels >6,000 mg dL -1 . International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes. © 2017 Wiley Periodicals, Inc.

IgM antiavian antibodies in sera from patients with pigeon breeder's disease.

PubMed

Martínez-Cordero, E; Aguilar León, D E; Retana, V N

2000-01-01

The authors' objective was to study the presence of IgM antiavian antibodies in sera from patients with pigeon breeder's disease. We studied 93 patients with interstitial lung disease admitted for the assessment of pigeon breeder's disease. Eighty sera from healthy donors with no history of bird contact and 47 asymptomatic pigeon breeders were included as controls. The presence of IgM, IgG, and IgA antiavian antibodies was detected by ELISA and Western blot using avian-pooled serum antigen. Fifty-three patients were classified as having definite pigeon breeder's disease, whereas 40 did not fulfill these diagnostic criteria. The levels of IgM antiavian-antibodies in pigeon breeder's disease by ELISA exceeded both the values of healthy subjects with no history of avian contact (P = 2.5 x 10(-8)) and the results of asymptomatic breeders (P = 0. 03). Positive IgA antiavian antibodies were the most frequent abnormalities in pigeon breeder's disease showing values over the reference levels of control groups that reach significant statistical differences. Both precipitin-positive and -negative samples demonstrated IgM reactivity. IgM antiavian antibodies were confirmed by Western blot. A relationship of IgM positive tests with a recent history of avian antigen exposure and acute disease was found. Additionally, the positive IgM group included patients having subacute and chronic lung disease. Antiavian antibodies have previously been considered of minor significance in hypersensitivity pneumonitis; nevertheless, recent studies support their use in clinical diagnosis. Although no specific laboratory tests can confirm the diagnosis in pigeon breeder's disease, IgM antiavian antibodies may be useful for detecting recent antigen exposure and the acute stage of the disease. Copyright 2000 Wiley-Liss, Inc.

Germ Line IgM Is Sufficient, but Not Required, for Antibody-Mediated Alphavirus Clearance from the Central Nervous System.

PubMed

Nilaratanakul, Voraphoj; Chen, Jie; Tran, Oanh; Baxter, Victoria K; Troisi, Elizabeth M; Yeh, Jane X; Griffin, Diane E

2018-04-01

-secreting cells enter the nervous system after infection and produce antiviral IgM before IgG. Clinical studies of human viral encephalomyelitis suggest that prompt production of IgM is associated with recovery, but it was not known whether IgM is effective for clearance. Our studies used mice deficient in production of IgM, IgG, or both to characterize the antibody necessary for alphavirus clearance. All mice developed similar signs of neurologic disease and recovered from infection. Antibody was necessary for virus clearance from the brain, and either early germ line IgM or IgG was sufficient. These studies support the clinical observation that prompt production of antiviral antibody is a determinant of outcome. Copyright © 2018 American Society for Microbiology.

IGMS: An Integrated ISO-to-Appliance Scale Grid Modeling System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmintier, Bryan; Hale, Elaine; Hansen, Timothy M.

This paper describes the Integrated Grid Modeling System (IGMS), a novel electric power system modeling platform for integrated transmission-distribution analysis that co-simulates off-the-shelf tools on high performance computing (HPC) platforms to offer unprecedented resolution from ISO markets down to appliances and other end uses. Specifically, the system simultaneously models hundreds or thousands of distribution systems in co-simulation with detailed Independent System Operator (ISO) markets and AGC-level reserve deployment. IGMS uses a new MPI-based hierarchical co-simulation framework to connect existing sub-domain models. Our initial efforts integrate opensource tools for wholesale markets (FESTIV), bulk AC power flow (MATPOWER), and full-featured distribution systemsmore » including physics-based end-use and distributed generation models (many instances of GridLAB-D[TM]). The modular IGMS framework enables tool substitution and additions for multi-domain analyses. This paper describes the IGMS tool, characterizes its performance, and demonstrates the impacts of the coupled simulations for analyzing high-penetration solar PV and price responsive load scenarios.« less

Site-Specific N-Glycosylation of Recombinant Pentameric and Hexameric Human IgM

NASA Astrophysics Data System (ADS)

Moh, Edward S. X.; Lin, Chi-Hung; Thaysen-Andersen, Morten; Packer, Nicolle H.

2016-07-01

Glycosylation is known to play an important role in IgG antibody structure and function. Polymeric IgM, the largest known antibody in humans, displays five potential N-glycosylation sites on each heavy chain monomer. IgM can exist as a pentamer with a connecting singly N-glycosylated J-chain (with a total of 51 glycosylation sites) or as a hexamer (60 glycosylation sites). In this study, the N-glycosylation of recombinant pentameric and hexameric IgM produced by the same human cell type and culture conditions was site-specifically profiled by RP-LC-CID/ETD-MS/MS using HILIC-enriched tryptic and GluC glycopeptides. The occupancy of all putative N-glycosylation sites on the pentameric and hexameric IgM were able to be determined. Distinct glycosylation differences were observed between each of the five N-linked sites on the IgM heavy chains. While Asn171, Asn332, and Asn395 all had predominantly complex type glycans, differences in glycan branching and sialylation were observed between the sites. Asn563, a high mannose-rich glycosylation site that locates in the center of the IgM polymer, was only approximately 60% occupied in both the pentameric and hexameric IgM forms, with a difference in relative abundance of the glycan structures between the pentamer and hexamer. This study highlights the information obtained by characterization of the site-heterogeneity of a highly glycosylated protein of high molecular mass with quaternary structure, revealing differences that would not be seen by global glycan or deglycosylated peptide profiling.

Optimal Cutoff and Accuracy of an IgM Enzyme-Linked Immunosorbent Assay for Diagnosis of Acute Scrub Typhus in Northern Thailand: an Alternative Reference Method to the IgM Immunofluorescence Assay

PubMed Central

Blacksell, Stuart D.; Tanganuchitcharnchai, Ampai; Jintaworn, Suthatip; Kantipong, Pacharee; Richards, Allen L.; Day, Nicholas P. J.

2016-01-01

The enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative serologic diagnostic test to the indirect immunofluorescence assay (IFA) for scrub typhus. Here, we systematically determine the optimal sample dilution and cutoff optical density (OD) and estimate the accuracy of IgM ELISA using Bayesian latent class models (LCMs). Data from 135 patients with undifferentiated fever were reevaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar and tested with a blood culture for Orientia tsutsugamushi, three different PCR assays, and an IgM IFA. The IgM ELISA was performed for every sample at sample dilutions from 1:100 to 1:102,400 using crude whole-cell antigens of the Karp, Kato, and Gilliam strains of O. tsutsugamushi developed by the Naval Medical Research Center. We used Bayesian LCMs to generate unbiased receiver operating characteristic curves and found that the sample dilution of 1:400 was optimal for the IgM ELISA. With the optimal cutoff OD of 1.474 at a sample dilution of 1:400, the IgM ELISA had a sensitivity of 85.7% (95% credible interval [CrI], 77.4% to 86.7%) and a specificity of 98.1% (95% CrI, 97.2% to 100%) using paired samples. For the ELISA, the OD could be determined objectively and quickly, in contrast to the reading of IFA slides, which was both subjective and labor-intensive. The IgM ELISA for scrub typhus has high diagnostic accuracy and is less subjective than the IgM IFA. We suggest that the IgM ELISA may be used as an alternative reference test to the IgM IFA for the serological diagnosis of scrub typhus. PMID:27008880

Zika Virus and the World Health Organization Criteria for Determining Recent Infection Using Plaque Reduction Neutralization Testing.

PubMed

Ward, Matthew J; Alger, Jackeline; Berrueta, Mabel; Bock, Harry; Buekens, Pierre; Cafferata, Maria Luisa; Ciganda, Alvaro; García, Jorge; García, Kimberly; Lorenzana, Ivette; Lopez, Wendy; Parham, Leda; Wesson, Dawn M

2018-06-25

The recent Zika virus (ZIKV) epidemic swept across Latin America and the Caribbean, where dengue virus (DENV) is endemic. The antigenic similarities of these closely related flaviviruses left researchers and clinicians with challenges to interpret serological tests. Thirty-six women attending a prenatal clinic in Honduras and with positive DENV IgM enzyme-linked immunoabsorbent assays (ELISAs) were screened with a ZIKV IgM ELISA, RT-PCR for ZIKV and DENV 1-4, and plaque reduction neutralization tests (PRNTs) for ZIKV and DENV-2. Plaque reduction neutralization test results were interpreted using the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Using the WHO criteria of a PRNT90 titer ≥ 20 and a 4-fold difference between ZIKV and DENV titers, we determined that 69.4% of samples had a recent ZIKV infection, compared with 5.6% using CDC criteria. The interpretation of ZIKV PRNTs in a DENV-endemic region is highly dependent on the choice of interpretation criteria.

Microangiopathic antiphospholipid antibody syndrome due to anti-phosphatidylserine/prothrombin complex IgM antibody.

PubMed

Senda, Yumi; Ohta, Kazuhide; Yokoyama, Tadafumi; Shimizu, Masaki; Furuichi, Kengo; Wada, Takashi; Yachie, Akihiro

2017-03-01

Herein we describe a case of microangiopathic antiphospholipid syndrome (MAPS) due to anti-phosphatidylserine/prothrombin complex (aPS/PT) IgM antibody successfully treated with rituximab. A significant correlation was observed between the clinical course and the aPS/PT IgM antibody titer, which can rise earlier before the appearance of clinical symptoms. Rituximab can be safely and effectively used for MAPS. Although detection of only aPS/PT IgM antibody is rare, aPS/PT IgM antibody might be associated with the pathogenesis of MAPS and might be a useful marker of disease activity. © 2017 Japan Pediatric Society.

IgM nephropathy; can we still ignore it.

PubMed

Vanikar, Aruna

2013-04-01

IgM nephropathy (IgMN) is a relatively less recognized clinico-immunopathological entity in the domain of glomerulonephritis , often thought to be a bridge between minimal change disease and focal segmental glomerulosclerosis. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. IgM nephropathy can present as nephritic syndrome or less commonly with subnephrotic proteinuria or rarely hematuria. About 30% patients respond to steroids whereas others are steroid dependent / resistant. They should be given a trial of Rituximab or stem cell therapy. IgM nephropathy (IgMN) is an important and rather neglected pathology responsible for renal morbidity in children and adults in developing countries as compared to developed nations with incidence of 2-18.5% of native biopsies. Abnormal T-cell function with hyperfunctioning suppressor T-cells are believed to be responsible for this disease entity. Approximately one third of the patients are steroid responders where as the remaining two thirds are steroid resistant or dependent. Therapeutic trials including cell therapies targeting suppressor T-cells are required.

Relation of carotid plaque with natural IgM antibodies in patients with systemic lupus erythematosus.

PubMed

Grönwall, Caroline; Reynolds, Harmony; Kim, June K; Buyon, Jill; Goldberg, Judith D; Clancy, Robert M; Silverman, Gregg J

2014-07-01

Noninvasive carotid measurements have proven value in the estimation of future cardiovascular (CV) outcomes in systemic lupus erythematosus (SLE). Natural IgM-antibodies to phosphorylcholine (PC) epitopes can enhance apoptotic-cell clearance and induce anti-inflammatory pathways. Herein, we show that subclinical CV disease, as detected by carotid ultrasound, in a cross-sectional SLE cohort was associated with lower levels of IgM anti-PC, as well as lower levels of the ratio of IgM anti-PC/total IgM, compared to patients without plaque (p=0.004 and p=0.02, respectively). The IgM anti-PC/total IgM association remained significant after adjusting for age, cholesterol and hypertension. Adiponectin and sE-selectin were significantly elevated in patients with plaque, and statistical models showed that combining adiponectin, sE-selectin and IgM anti-PC/total IgM was better for predicting plaque than either test alone. These results support the hypothesis that IgM-natural autoantibodies may inhibit atherogenesis, and confirm the utility of IgM anti-PC levels as a biomarker for subclinical CV disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of protection by two endotoxin-neutralizing IgM monoclonal antibodies in different peritonitis models.

PubMed

Hustinx, W N; Benaissa-Trouw, B J; Harmsen, T; Klein, S; Verhoef, J; Hoepelman, A I; Kraaijeveld, K

1997-10-01

Two anti-core glycolipid (CGL) IgM monoclonal antibodies (mAbs 8-2 and 26-20), previously shown to display cross-reactivity with heterologous lipopolysaccharide (LPS) in vitro and to provide cross-protectivity against endotoxin challenge in vivo, were evaluated for their potential to protect mice against death from peritonitis caused by heterologous bacterial challenge. Without concurrent antibiotic treatment neither antibody was protective. Compared with a control mAb, prophylactic treatment with mAb 8-2 significantly increased the survival of gentamicin-treated mice challenged with the rough strain Salmonella minnesota Re595. Both mAb 8-2 and a control mAb, in combination with a suboptimal dose of ceftazidime, increased survival following challenge with the clinical isolate Escherichia coli O7:K1. In a model of mucin-enhanced peritonitis, neither mAb was protective against challenge with inocula of E. coli O7:K1, ranging from 10(2) to 10(4) bacteria. We conclude that protection of mice by anti-CGL mAb 8-2 against heterologous challenge is vitally dependent on concurrent treatment with antibiotics and that protection may not be attributable to the anti-CGL specificity of these antibodies.

Salivary anti-PGL-1 IgM may indicate active transmission of Mycobacterium leprae among young people under 16 years of age.

PubMed

Macedo, Alexandre Casimiro de; Cunha, José Evandro; Yaochite, Juliana Navarro Ueda; Tavares, Clodis Maria; Nagao-Dias, Aparecida Tiemi

Considering that the main route of Mycobacterium leprae transmission is the upper respiratory tract, detection of salivary antibodies can be a useful tool for diagnosing early infection. The study aimed to analyze salivary anti-PGL-1 IgA and IgM antibodies in 169 children aged 4-16 years old, who lived nearby or inside the house of multibacillary or paucibacillary leprosy patients in two endemic cities in Alagoas State - Brazil. Salivary anti-PGL-1 antibodies were quantified by modified ELISA method. The frequency of contact and clinical form of the index case were significantly associated with salivary antibody levels. High frequency of IgM positivity strongly suggests active transmission of M. leprae in these communities. We suggest in the present work that salivary anti-PGL IgA and IgM are important biomarkers to be used for identifying communities with probable active transmission of M. leprae. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

A novel phenoxazine derivative suppresses surface IgM expression in DT40 B cell line

PubMed Central

Gao, Sanyang; Takano, Tomoko; Sada, Kiyonao; He, Jinsong; Noda, Chiseko; Hori-Tamura, Naoko; Tomoda, Akio; Yamamura, Hirohei

2002-01-01

2-amino-4, 4α-dihydro-4α, 7-dimethyl-3H-phenoxazine-3-one (Phx) has been demonstrated to be an actinomycin D-like phenoxazine, and to display anti-tumour activity. In this study, we report on the effect of Phx on B cell antigen receptor (BCR) and receptor-mediated signalling in DT40 B cells. Treatment of B cells with Phx for 12 h inhibited BCR-stimulated tyrosine phosphorylation of cellular proteins. B cells exposed to Phx exhibited down-regulation of surface IgM which is part of BCR. In contracts with actinomycin D, Phx rapidly reduced the expression of IgM without decreasing the expression of other signalling molecules. Analysis with confocal microscopy demonstrated that Phx treatment reduced IgM expression both at the cell surface and inside the cell. Treatment of B cells with Phx resulted in the reduction of IgM secretion. Since MG-132, a proteasomal inhibitor, restored IgM contents to the control levels, Phx has the specific effect of accelerating IgM degradation. These results suggest that Phx down-regulates the expression of IgM and inhibits BCR-mediated signalling and IgM secretion. Phx may be useful as an immunosuppressive agent for therapeutic purposes. PMID:12411404

Evaluation of the Abbott ARCHITECT Toxo IgM assay.

PubMed

Sickinger, Eva; Braun, Hans-Bertram; Praast, Gerald; Stieler, Myriam; Gundlach, Cordelia; Birkenbach, Claudia; Prostko, John; Palafox, Mary Ann; Frias, Edwin; Hsu, Stephen; Matias, Matthew; Pucci, Dominick; Hausmann, Michael; Sagel, Ulrich; Smith, Darwin

2009-07-01

Development of the ARCHITECT Toxo IgM assay has been done to assist the clinician in acute Toxoplasma gondii infection detection, especially in pregnant women. Its use, in conjunction with ARCHITECT Toxo IgG and Toxo Avidity assays, will provide an array of assays particularly useful in the monitoring of pregnant females to determine the risk of maternal transmission of the parasite. Specificity results from 2 testing sites, using populations of pregnant females, hospital patients, and blood donors, demonstrated that the assay has an overall resolved relative specificity of 99.89% (confidence interval, 99.68-99.98%). Relative specificity for pregnant female specimens was 99.95% (n = 2031). Excellent seroconversion sensitivity was observed for the ARCHITECT Toxo IgM assay, which was similar to the Abbott AxSYM Toxo IgM assay (Abbott Laboratories, Abbott Park, IL). In more than 90% of the panels tested, the 1st bleed detected in the serial bleeds was the same for both assays.

Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)

PubMed Central

2014-01-01

Background Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied. PMID:24944545

Detection of LipL32-specific IgM by ELISA in sera of patients with a clinical diagnosis of leptospirosis

PubMed Central

Vedhagiri, Kumaresan; Velineni, Sridhar; Timoney, John F; Shanmughapriya, Santhanam; Vijayachari, Paluru; Narayanan, Ramasamy; Natarajaseenivasan, Kalimuthusamy

2013-01-01

Successful treatment of leptospirosis is heavily dependent on early diagnosis and prompt initiation of antibiotic therapy. An ELISA test to detect specific IgM antibodies against LipL32 for early diagnosis of leptospirosis is described and evaluated here. One thousand one hundred and eighty sera from clinically suspected leptospirosis cases were enrolled together with 109 healthy volunteers selected from an endemic area between October 2007 and January 2010. Patients were categorized based on their clinical signs and symptoms. Sera were screened for leptospiral antibodies by the microscopic agglutination test (MAT) using a panel of locally circulating serovars followed by enzyme-linked immunosorbent assay (ELISA) based on recombinant LipL32 from Leptospira interrogans serovar Autumnalis strain N2. The sensitivity and specificity of the ELISA test were determined to establish its diagnostic efficiency. The cut-off value was determined to be 0.205. Overall sensitivity and specificity compared to the MAT were found to be 96.4 and 90.4%, respectively. The LipL32-specific IgM ELISA had good sensitivity and acceptable specificity and may be a candidate for the early serodiagnosis of human leptospirosis. PMID:23683367

Anti-HBc IgM and anti-delta screening by EIA method.

PubMed Central

Kim, J. S.; Kim, J. M.

1986-01-01

The clinical value of an enzyme-linked immunosorbent assay (ELISA) for the detection of anti-HBc IgM was evaluated by testing 202 sera from acute viral hepatitis B (AVHB), hepatitis B (HB), chronic hepatitis (CAH), chronic liver disease (CLD), cirrhosis, primary hepatoma, HBsAg carrier, acute viral hepatitis A (AVHA), hepatitis A (HA), non-A, non-B (NANB) hepatitis and miscellaneous conditions other than hepatic disease, and 19 additional various hepatic disease cases were examined for anti-delta. In clinical situations the accurate diagnosis of HB is not always possible and the differential diagnosis seems to be very important especially in making decisions of treatment and estimation of prognosis. In overall cases the highest positive rate of anti-HBc IgM was found in AVHB as shown as 74.3% (26/35) comparing to other conditions in which the positive rate was extremely low (2.1%). The anti-HBc IgM appeared to be highly specific to AVHB (83.9%) as compared to the other. The positive rate of HBsAg was high in AVHB, CAH and HBsAg carrier (100.0%) followed by CLD, cirrhosis and HB (up to 70.8%). The ALT activities and ALPalb fractions were significantly high in AVHB (p less than 0.005). The correlation between the positivity of anti-HBc IgM and highly abnormal ALT appeared be high. AVHB was confined mostly to 10-20 age group and the male to female ratio was about 6 to 1. Subgroup of AVHB II with positive anti-HBc IgM appeared to have a greater chance being positive for HBsAg and ALPalb. The S/N ratio of anti-HBc IgM was as high as 20 which was unique to AVHB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3077604

Amylolytic activity of IgM and IgG antibodies from patients with multiple sclerosis.

PubMed

Saveliev, Andrew N; Ivanen, Dina R; Kulminskaya, Anna A; Ershova, Nadezhda A; Kanyshkova, Tat'yana G; Buneva, Valentina N; Mogelnitskii, Alexander S; Doronin, Boris M; Favorova, Olga O; Nevinsky, Georgy A; Neustroev, Kirill N

2003-05-01

IgG and IgM antibodies from the sera of patients with multiple sclerosis (MS) were found to possess amylolytic activity hydrolyzing alpha-(1-->4)-glucosyl linkages of maltooligosaccharides, glycogen, and several artificial substrates. Individual IgM fractions isolated from 54 analyzed patients with the clinically definite diagnoses of MS had approximately three orders of magnitude higher specific amylolytic activity than that for healthy donors, whereas IgG from only a few patients had high amylolytic activity. Strict criteria were used to prove that the amylolytic activity of IgMs and IgGs is their intrinsic property and is not due to any enzyme contamination. Fab fragments produced from IgM and IgG fractions of the MS patients displayed the same amylolytic activity. IgMs from various patients demonstrated different modes of action in hydrolyzing maltooligosaccharides.

Baryonic Content in the Warm-Hot IGM at Low Redshift

NASA Technical Reports Server (NTRS)

Sonneborn, George; Shull, M.; Danforth, C.; Moos, W.

2007-01-01

Baryons are 4.5% of the universe's mass/energy density; only 10% of these are in stars, galaxies, and clusters. At low-redshift 90% of baryons are in the IGM, 30% in Ly-alpha forest, but most are in hot gas (10(exp 5-7) K) produced by shocks during structure formation. O VI 1032-38 A are the best tracers of this gas. The distribution of O VI absorbers observed by FUSE rises as N(sup -2+/-0.2, down to 10(exp 13)/sq cm. Integrated to logN=13, 7% of baryons reside in the O VI-bearing IGM at 10% solar metallicity, T approx. 10(exp 5.5) K. At redshift z<0.1 metals have been transported less than 800/h kpc from L* galaxies and 200/h kpc from 0.1 L* galaxies. The steepness of dN/dz means that low-N absorbers contribute an equal mass of hot IGM as higher N gas. The total mass of O VI-bearing gas in the IGM depends on determining the turnover in dN/dz at low N(O VI). Future observations by FUSE are needed to reach lower N and to reduce the uncertainty in the dN/dz power law.

Antibody class capture assay (ACCA) for rubella-specific IgM antibody.

PubMed

Isaac, M; Payne, R A

1982-01-01

Enzyme-linked immunosorbent assays for IgM antirubella were carried out on 1,546 sera, using an IgM capture method with a F (ab')2 conjugate (ACCA). Under the conditions described, sera containing IgM antirubella bound up to 15 times as much enzyme activity as negative specimens. Paired serum specimens from 27 patients, serial serum specimens from 6 patients, and single serum specimens from 15 patients who had had recent rubella were examined by the haemagglutination inhibition test (HAI) in the presence and absence of 2-mercaptoethanol following sucrose density gradient centrifugation (SDGC). ACCA confirmed all the results found with HAI following SDGC. Specimens were examined from ten patients with congenital rubella; ACCA confirmed the results found with both immunofluorescence following SDGC and radioimmunoassay. Pre- and post-vaccination specimens from 123 patients who had been vaccinated against rubella were examined. An IgM response could only be demonstrated in the 57 cases when IgG was absent in the first specimen. The specificity of the assay was confirmed by testing 31 serum specimens from rubella immune patients that also contained rheumatoid factor, 163 serum specimens from patients with acute infections other than rubella, and 12 serum specimens from infants with miscellaneous neonatal abnormalities other than congenital rubella. The ACCA proved a simple, sensitive, and specific test for IgM antirubella and the results compared favourably with those obtained by the SDGC technique.

Evaluation of a rapid IgM detection test for diagnosis of acute leptospirosis in dogs.

PubMed

Lizer, J; Grahlmann, M; Hapke, H; Velineni, S; Lin, D; Kohn, B

2017-05-27

Recently, a lateral flow assay (LFA) for detection of Leptospira -specific IgM in canine sera became commercially available in Europe. The present study aims to evaluate the diagnostic performance of this assay using canine sera from a collection of diagnostic accessions. Diagnostic sensitivity was assessed by testing 37 acute-phase and 9 corresponding convalescent-phase sera from dogs with a confirmed diagnosis of leptospirosis. Specificity was determined by testing sera from sick dogs with non-leptospiral infections (n=15) and healthy dogs with incomplete history of vaccination (n=45). During acute phase of illness, LFA scored positive for 28/37 sera with a sensitivity of 75.7 per cent while only 9/37 (24.3 per cent) samples were positive on microscopic agglutination test. The specificity of the LFA was 98.3 per cent (59/60). This test showed 89.7 and 100 per cent overall agreements with clinical diagnosis for acute-phase and convalescent-phase sera, respectively. The impact of vaccination on the LFA was also determined and vaccine-stimulated IgM responses were negative in 19/25 (76 per cent) dogs at 12 weeks post vaccination. In conclusion, the LFA is a rapid and reliable test for early detection of Leptospira -specific IgM during acute phase of canine leptospirosis. However, interpretation of a positive result must be made in the context of clinical signs and vaccination history. British Veterinary Association.

Is nevtral NEUTRAL? Visual similarity effects in the early phases of written-word recognition.

PubMed

Marcet, Ana; Perea, Manuel

2017-08-01

For simplicity, contemporary models of written-word recognition and reading have unspecified feature/letter levels-they predict that the visually similar substituted-letter nonword PEQPLE is as effective at activating the word PEOPLE as the visually dissimilar substituted-letter nonword PEYPLE. Previous empirical evidence on the effects of visual similarly across letters during written-word recognition is scarce and nonconclusive. To examine whether visual similarity across letters plays a role early in word processing, we conducted two masked priming lexical decision experiments (stimulus-onset asynchrony = 50 ms). The substituted-letter primes were visually very similar to the target letters (u/v in Experiment 1 and i/j in Experiment 2; e.g., nevtral-NEUTRAL). For comparison purposes, we included an identity prime condition (neutral-NEUTRAL) and a dissimilar-letter prime condition (neztral-NEUTRAL). Results showed that the similar-letter prime condition produced faster word identification times than the dissimilar-letter prime condition. We discuss how models of written-word recognition should be amended to capture visual similarity effects across letters.

Indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) and IgM capture ELISA for detection of antibodies to lipopolysaccharide in adult typhoid fever patients in Pakistan.

PubMed

Sippel, J; Bukhtiari, N; Awan, M B; Krieg, R; Duncan, J F; Karamat, K A; Malik, I A; Igbal, L M; Legters, L

1989-06-01

Sera from 339 adult febrile patients in Pakistan were tested for antibodies to Salmonella typhi lipopolysaccharide by indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assay (ELISA) and IgM capture ELISA. A total of 55 patients had S. typhi cultured from their blood, 20 had S. typhi cultured from their stool, 24 were blood or stool culture positive for S. paratyphi A, 41 were culture negative but clinically diagnosed as having enteric fever, 41 had gastrointestinal or urinary tract infections, 41 were clinically diagnosed as having malaria, 20 were smear-positive patients with malaria, 58 had respiratory infections, and the remaining 39 individuals were placed in a miscellaneous group who did not have Salmonella infection. The sensitivities of the indirect IgG ELISA, indirect IgM ELISA, and IgM capture ELISA determined with specimens obtained from the blood culture-positive patients with typhoid fever (positive controls) were 80, 64, and 62%, respectively. The specificities of the assays determined with sera from the patients with respiratory infections (negative controls) were 95, 95, and 97%, respectively. The percentage of smear-positive patients with malaria who were positive by these assays was lower than that in the negative control group. The percentages of individuals in the other patient categories who were positive by these tests were between those obtained with the positive and negative controls. Of the positive controls, 26 were positive by both IgM assays, 9 were IgM positive only by indirect ELISA, and 8 were IgM positive only by IgM capture ELISA. A total of 70% of the positive control patients who were tested for O agglutinins by the Widal tube agglutination assay were positive; however, 29% of the negative control patients were also positive. The indirect IgG ELISA was the single most effective test for the serodiagnosis of typhoid fever in this population.

Indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) and IgM capture ELISA for detection of antibodies to lipopolysaccharide in adult typhoid fever patients in Pakistan.

PubMed Central

Sippel, J; Bukhtiari, N; Awan, M B; Krieg, R; Duncan, J F; Karamat, K A; Malik, I A; Igbal, L M; Legters, L

1989-01-01

Sera from 339 adult febrile patients in Pakistan were tested for antibodies to Salmonella typhi lipopolysaccharide by indirect immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assay (ELISA) and IgM capture ELISA. A total of 55 patients had S. typhi cultured from their blood, 20 had S. typhi cultured from their stool, 24 were blood or stool culture positive for S. paratyphi A, 41 were culture negative but clinically diagnosed as having enteric fever, 41 had gastrointestinal or urinary tract infections, 41 were clinically diagnosed as having malaria, 20 were smear-positive patients with malaria, 58 had respiratory infections, and the remaining 39 individuals were placed in a miscellaneous group who did not have Salmonella infection. The sensitivities of the indirect IgG ELISA, indirect IgM ELISA, and IgM capture ELISA determined with specimens obtained from the blood culture-positive patients with typhoid fever (positive controls) were 80, 64, and 62%, respectively. The specificities of the assays determined with sera from the patients with respiratory infections (negative controls) were 95, 95, and 97%, respectively. The percentage of smear-positive patients with malaria who were positive by these assays was lower than that in the negative control group. The percentages of individuals in the other patient categories who were positive by these tests were between those obtained with the positive and negative controls. Of the positive controls, 26 were positive by both IgM assays, 9 were IgM positive only by indirect ELISA, and 8 were IgM positive only by IgM capture ELISA. A total of 70% of the positive control patients who were tested for O agglutinins by the Widal tube agglutination assay were positive; however, 29% of the negative control patients were also positive. The indirect IgG ELISA was the single most effective test for the serodiagnosis of typhoid fever in this population. PMID:2754002

Low-Energy Mutual Neutralization Studies for Early Universe Hydrogen Chemistry

NASA Astrophysics Data System (ADS)

Urbain, Xavier

2010-03-01

Low-energy interactions between light ions, as they occur in low density plasmas, are ideally studied under merged-beam conditions. This was the motivation for building the dual-source setup in operation at UCL, Louvain-la-Neuve, since the early eighties. Although initially developed for the study of charge exchange [1], mutual neutralization and transfer ionization, this machine has produced a host of total cross section measurements for a wide variety of associative ionization and other reactive processes involving charged reactants, from H^+ to CO^+, in collision with H^-, D^-, C^- and O^- [2]. A recent paper by Glover et al. [3] has revived the interest for mutual neutralization studies, by stressing the need of the astrophysical community for a precise determination of the low-energy cross section of the H^+/H^- reaction. The mutual neutralization acts as a sink for negative ions which otherwise dominate the primordial formation of H2 by associative detachment with ground state H. Absolute measurements in the range 5 meV to 5 eV are needed to rule out earlier experimental work [4] contradicting the most recent theoretical predictions [5]. Our setup is currently modified to incorporate coincident imaging techniques, giving access to differential cross sections besides the branching among accessible neutral channels. Mutual neutralization reactions of H^- with H2^+ and H3^+ will also be investigated, for the role they play in laboratory plasmas [6].[4pt] [1] S. Sz"ucs, M. Karemera, M. Terao, and F. Brouillard, J. Phys. B 17, 1613 (1983).[0pt] [2] E. A. Naji et al., J. Phys. B 31, 4887 (1998), A. Le Padellec et al., J. Chem. Phys., 124, 154304 (2006) and references therein.[0pt] [3] S. C. Glover, D. W. Savin, and A.-K. Jappsen , Astrophys. J. 640, 553 (2006). [0pt] [4] J. Moseley, W. Aberth, and J. R. Peterson, Phys. Rev. Lett. 24, 435 (1970).[0pt] [5] M. Stenrup, å. Larson, and N. Elander, Phys. Rev. A 79, 012713 (2009).[0pt] [6] M. J. J. Eerden et al., Phys

Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark.

PubMed

Rumfelt, Lynn L; Lohr, Rebecca L; Dooley, Helen; Flajnik, Martin F

2004-05-06

Adult cartilaginous fish express three immunoglobulin (Ig) isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric) IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric) IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3) with non-templated nucleotide (N-region) addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT) expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1) and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge) within a species. As in ratfish, sandbar and horn sharks, most nurse shark IgM VH

Vitreal IgM autoantibodies target neurofilament medium in a spontaneous model of autoimmune uveitis.

PubMed

Swadzba, Margarete E; Hirmer, Sieglinde; Amann, Barbara; Hauck, Stefanie M; Deeg, Cornelia A

2012-01-25

Although the presence of IgG autoantibodies in the vitreous of spontaneous cases of equine recurrent uveitis (ERU) has been demonstrated, the potential role of IgM reactivities during ERU pathogenesis remains unexplored. The purpose of this study was to examine the presence of IgM autoantibodies in vitreous specimens of ERU-affected horses and to test their binding specificity to intraocularly expressed proteins. To test IgM autoantibody responses to retinal tissue, vitreous samples of eye-healthy controls and ERU patients were analyzed via two-dimensional Western blot analysis with equine retinal tissue as an antigen source. A candidate protein, the peptide neurofilament medium (NF-M), was identified via mass spectrometry and validated via enzyme-linked immunosorbent assay. Immunohistochemistry for NF-M expression was performed on healthy and ERU-affected retinal sections. Whereas autoreactivity was never detected in the healthy vitreous samples, NF-M was specifically targeted by vitreal IgM autoantibodies in 44% of the ERU cases. Vitreal anti-NF-M IgG was detected in only 8% of the ERU samples, pointing to a persistent IgM response. In healthy horse retina, NF-M was located in the retinal ganglion cells and their processes, with additional staining in the outer plexiform layer. NF-M expression in ERU-affected retinas decreased considerably, and the remaining expression was limited to the nerve fiber layer. Intraocular anti NF-M IgM autoantibodies occur with high prevalence in vitreous of spontaneous autoimmune uveitis cases. The IgM dominated response may indicate a thymus-independent response to NF-M and merits further investigation in ERU, as well as in its human counterpart, autoimmune uveitis.

Truly selective primary IgM deficiency is probably very rare.

PubMed

Janssen, L M A; Macken, T; Creemers, M C W; Pruijt, J F M; Eijk, J J J; de Vries, E

2018-02-01

Isolated decreased serum-immunoglobulin (Ig)M has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM-deficient patients may reflect the skewed tertiary centre population studied so far. Also, many papers on IgM deficiency have included patients with more abnormalities than simply IgM-deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies (ESID) (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum-IgM in 46 papers) and analysing retrospectively all patients with decreased serum-IgM in a large teaching hospital in 's-Hertogenbosch, the Netherlands [1 July 2005-23 March 2016; n = 8049 IgM < 0·4 g/l; n = 2064 solitary (IgG+IgA normal/IgM < age-matched reference)]. A total of 359 of 2064 (17%) cases from our cohort had primary isolated decreased serum-IgM, proven persistent in 45 of 359 (13%) cases; their medical charts were reviewed. Our main finding is that true sIgMdef is probably very rare. Only six of 261 (2%) literature cases and three of 45 (7%) cases from our cohort fulfilled the ESID criteria completely; 63 of 261 (24%) literature cases also had other immunological abnormalities and fulfilled the criteria for unclassified antibody deficiencies (unPAD) instead. The diagnosis was often uncertain (possible sIgMdef): data on IgG subclasses and/or vaccination responses were lacking in 192 of 261 (74%) literature cases and 42 of 45 (93%) cases from our cohort. Our results also illustrate the clinical challenge of determining the relevance of a serum sample with decreased IgM; a larger cohort of true sIgMdef patients is needed to explore fully its clinical consequences. The ESID online Registry would be a useful tool for this. © 2017 British Society for Immunology.

IgM MGUS associated with anti-MAG neuropathy: a single institution experience.

PubMed

Talamo, Giampaolo; Mir, Muhammad A; Pandey, Manoj K; Sivik, Jeffrey K; Raheja, Divisha

2015-06-01

Anti-MAG neuropathy is a very rare form of acquired polyneuropathy associated with IgM monoclonal gammopathy of undetermined significance (MGUS). We conducted a retrospective review of 194 consecutive MGUS patients seen at the Penn State Hershey Cancer Institute. We identified six patients among 37 (16 %) with IgM MGUS with anti-MAG neuropathy. Interestingly, an additional patient had anti-MAG neuropathy without MGUS. Common clinical manifestations were numbness and paresthesias of the extremities and gait imbalance. All four patients treated with rituximab and none of the three untreated ones had a subjective improvement of their symptoms. We conclude that all patients with IgM MGUS and neuropathy should be screened for anti-MAG antibodies and, if positive, they should be offered treatment with rituximab.

Miscellaneous vitreous-derived IgM antibodies target numerous retinal proteins in equine recurrent uveitis.

PubMed

Zipplies, Johanna K; Hauck, Stefanie M; Eberhardt, Christina; Hirmer, Sieglinde; Amann, Barbara; Stangassinger, Manfred; Ueffing, Marius; Deeg, Cornelia A

2012-09-01

In equine recurrent uveitis (ERU), immune reactions are directed toward known antigens like S-antigen, interphotoreceptor retinoid-binding protein, and cellular retinalaldehyde-binding protein, and anti-retinal antibodies were detected in vitreous samples. The aim of this study was the investigation of intraocular immunoglobulin M (IgM) reactivities to retinal proteome. Retina was separated by one- and two-dimensional gel electrophoresis and blotted semidry on PVDF membranes. To identify intraocular IgM antibody responses to retinal tissue, blots were incubated with vitreous samples of ERU-diseased horses (n = 50) and healthy controls (n = 30), followed by an HRP-labeled secondary antibody specific for equine IgM. Noticeable 2D western blot signals were aligned on a 2D gel of retinal proteome, excised, and subsequently identified by tandem mass spectrometry. Interestingly, frequent and very miscellaneous IgM response patterns to the retinal proteome in 68% of ERU vitreous samples were detected. Binding of IgM antibodies was localized at 17 different molecular weights. The most frequently detected signal, in 21 of the 50 samples, was located at 49 kDa. Comparing the samples interindividually between one and up to nine different signals in one sample could be observed. All healthy vitreous samples were devoid of IgM antibodies. Analysis of targeted spots with mass spectrometry led to the clear identification of 11 different proteins (corresponding to 16 different spots). One candidate could not be discovered so far. The considerable IgM response to retinal proteins demonstrates an ongoing immune response, which might contribute to the remitting relapsing character of ERU. Novel identified target proteins point to a diverse response pattern of individual ERU cases. © 2012 American College of Veterinary Ophthalmologists.

Catalytic properties of IgMs with amylolytic activity isolated from patients with multiple sclerosis.

PubMed

Ivanen, Dina R; Kulminskaya, Anna A; Shabalin, Konstantin A; Isaeva-Ivanova, Luydmila V; Ershova, Nadezhda A; Saveliev, Andrew N; Nevinsky, Gregory A; Neustroev, Kirill N

2004-08-01

Recently, amylolytic activity was detected in IgMs isolated from the sera of the patients with multiple sclerosis. All purified samples of IgM were electrophoretically homogenous and did not contain any co-purified a-amylase and a-glucosidase activities, in accordance with a set of criteria developed for abzymes. The amylolytic activity of abzymes was studied in the hydrolysis of p-nitrophenyl a-D-maltooligosaccharides with different degrees of polymerization from 1 to 8 by TLC and reverse-phase HPLC techniques. All IgM samples isolated from 54 patients with clinically definite multiple sclerosis demonstrated hydrolytic activity towards the above artificial substrates. The Michaelis constant values (Km) in the hydrolysis of p-nitrophenyl a-D-maltoheptaoside were in the range of 10 p-nitrophenyl or p-nitrophenyl a-D-glucosides, thus indicating the presence of an a-D-glucosidase activity. For a number of the investigated samples, specific amylolytic activity increased depending on the length of substrates (from p-nitrophenyl maltopentaoside to p-nitrophenyl maltohexaoside); for other IgMs, the opposite dependence was observed. All IgMs studied did not exhibit any other glycoside hydrolase activities toward p-nitrophenyl glycoside substrates. Abzyme fractions from different donors demonstrated catalytic heterogeneity in Michaelis-Menten parameters and different modes of action in the hydrolysis of p-nitrophenyl maltooligosaccharides. Enzymatic properties of the IgMs tested varied from human a-amylases. All investigated abzyme samples did not show transglycosylating ability.

Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark

PubMed Central

Rumfelt, Lynn L; Lohr, Rebecca L; Dooley, Helen; Flajnik, Martin F

2004-01-01

Background Adult cartilaginous fish express three immunoglobulin (Ig) isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric) IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric) IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3) with non-templated nucleotide (N-region) addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT) expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. Results IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1) and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge) within a species. Conclusion As in ratfish, sandbar and horn

Serum concentrations of IgG, IgA, and IgM in retired racing Greyhound dogs.

PubMed

Clemente, Mónica; Marín, Liliana; Iazbik, M Cristina; Couto, C Guillermo

2010-12-01

Greyhound dogs have significant physiologic, hematologic, and biochemical differences when compared with other breeds, including significantly lower serum globulin concentration owing to decreases in the α- and β-globulin fractions. The specific proteins that account for differences in globulin concentrations are not known, but IgA and IgM, both β-globulins, are potential candidates. The aims of this study were to measure serum IgG, IgA, and IgM in clinically healthy retired racing Greyhounds and compare the results with those of age- and sex-matched non-Greyhound dogs. Study animals included 25 Greyhound and 20 non-Greyhound dogs. Total protein, albumin, and total globulin concentrations were determined. IgG, IgA, and IgM concentrations were measured using a commercially available radial immunodiffusion kit. The Student t-test assuming equal variances was used to compare concentrations of immunoglobulins between groups. Serum concentrations of IgA and IgM in Greyhounds (IgA=49±20 mg/dL; IgM=132±47 mg/dL) were significantly lower than concentrations in non-Greyound dogs (IgA=70±39 mg/dL; Ig M=212±78 mg/dL). Concentrations of IgG did not differ between groups. Mean serum IgA and IgM concentrations in Greyhounds were lower than those in non-Greyhound dogs. This may contribute to low serum concentrations of β-globulins in Greyhounds. Specific reference intervals are recommended for Greyhounds to avoid possible misdiagnosis of IgA or IgM deficiency. ©2010 American Society for Veterinary Clinical Pathology.

Generation, characterization and in vivo biological activity of two distinct monoclonal anti-PEG IgMs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu

PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showedmore » efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two

Synthesis of IgM, IgG and IgA in rheumatoid arthritis.

PubMed Central

Poikonen, K; Oka, M; Möttönen, T; Jokinen, I; Arvilommi, H

1982-01-01

We studied the production of immunoglobulins by lymphocytes separated from the blood of 15 rheumatoid arthritis (RA) patients, of 12 patients suffering from other connective tissue diseases (CTD), and of 18 healthy controls. The production of IgM, IgG and IgA in pokeweed-mitogen-stimulated cultures was measured by counting the number of plaque-forming cells (PFC) and by determining the concentration of secreted immunoglobulins by means of an enzyme immunoassay. Synthesis of immunoglobulins, particularly IgM and IgG, was lower than in other CTD patients or controls. The IgM response of RA patients was 20% and 29% (PFC and Ig concentrations) that of the controls. The respective figures for IgG were 33% and 53% and for IgA 61% and 72%. PMID:6756322

High affinity IgM(+) memory B cells are generated through a germinal center-dependent pathway.

PubMed

Hara, Yasushi; Tashiro, Yasuyuki; Murakami, Akikazu; Nishimura, Miyuki; Shimizu, Takeyuki; Kubo, Masato; Burrows, Peter D; Azuma, Takachika

2015-12-01

During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM(+) memory cells and that this process continues even after CSR is accomplished. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recognition of Porphyromonas gingivalis Gingipain Epitopes by Natural IgM Binding to Malondialdehyde Modified Low-Density Lipoprotein

PubMed Central

Turunen, S. Pauliina; Kummu, Outi; Harila, Kirsi; Veneskoski, Marja; Soliymani, Rabah; Baumann, Marc; Pussinen, Pirkko J.; Hörkkö, Sohvi

2012-01-01

Objective Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL) and apoptotic cells. We aimed to identify epitopes on periodontal pathogen Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA) modified LDL. Methods and Results Mouse monoclonal IgM (MDmAb) specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR−/− mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp) by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans. Conclusion Gingipain of P. gingivalis is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis. PMID:22496875

Capture-ELISA for serum IgM antibody to respiratory syncytial virus.

PubMed Central

Cevenini, R.; Donati, M.; Bertini, S.; Moroni, A.; Sambri, V.

1986-01-01

A four-component solid-phase capture enzyme immunoassay was set up to test for serum IgM antibody to respiratory syncytial (RS) virus and was compared with immunofluorescence assay (IFA). A total of 128 young children with acute respiratory infections were studied. Thirty-six were shown to be RS virus-positive by the detection of RS virus in nasopharyngeal secretions and 92 were RS virus-negative. A serum specimen was collected after admission to the hospital (days 0-4) and a further specimen was obtained during days 10-14. Out of 36 RS virus-positive patients, 28 (77.7%) were found to be positive for IgM by both capture-ELISA and IFA. Out of 92 RS virus-negative patients 5 (5.4%) were IgM-positive. Four false-positive results were obtained by IFA due to the presence of rheumatoid factor. The capture-ELISA was shown to be a reliable technique in detecting specific IgM antibody to RS virus. PMID:3540115

Role of Natural Autoantibodies and Natural IgM Anti-Leucocyte Autoantibodies in Health and Disease

PubMed Central

Lobo, Peter Isaac

2016-01-01

We review how polyreactive natural IgM autoantibodies (IgM-NAA) protect the host from invading micro-organisms and host neo-antigens that are constantly being produced by oxidation mechanisms and cell apoptosis. Second, we discuss how IgM-NAA and IgM anti-leukocyte antibodies (IgM-ALA) inhibits autoimmune inflammation by anti-idiotypic mechanisms, enhancing removal of apoptotic cells, masking neo-antigens, and regulating the function of dendritic cells (DC) and effector cells. Third, we review how natural IgM prevents autoimmune disorders arising from pathogenic IgG autoantibodies, triggered by genetic mechanisms (e.g., SLE) or micro-organisms, as well as by autoreactive B and T cells that have escaped tolerance mechanisms. Studies in IgM knockout mice have clearly demonstrated that regulatory B and T cells require IgM to effectively regulate inflammation mediated by innate, adaptive, and autoimmune mechanisms. It is, therefore, not surprising why the host positively selects such autoreactive B1 cells that generate IgM-NAA, which are also evolutionarily conserved. Fourth, we show that IgM-ALA levels and their repertoire can vary in normal humans and disease states and this variation may partly explain the observed differences in the inflammatory response after infection, ischemic injury, or after a transplant. We also show how protective IgM-NAA can be rendered pathogenic under non-physiological conditions. We also review IgG-NAA that are more abundant than IgM-NAA in plasma. However, we need to understand if the (Fab)2 region of IgG-NAA has physiological relevance in non-disease states, as in plasma, their functional activity is blocked by IgM-NAA having anti-idiotypic activity. Some IgG-NAA are produced by B2 cells that have escaped tolerance mechanisms and we show how such pathogenic IgG-NAA are regulated to prevent autoimmune disease. The Fc region of IgG-NAA can influence inflammation and B cell function in vivo by binding to activating and inhibitory Fc

Multicenter evaluation of the Elecsys Toxo IgG and IgM tests for the diagnosis of infection with Toxoplasma gondii

PubMed Central

Meylan, Pascal; Paris, Luc; Liesenfeld, Oliver

2015-01-01

Detection of IgG and IgM antibodies is commonly performed for the diagnosis of infection with Toxoplasma gondii. We determined the accuracy of the Elecsys Toxo IgG and IgM test at four European laboratories compared to local reference methods. Coefficients of variation for reproducibility ranged from 1.0 to 6.5% for IgG and from 0.8 to 3.2% for IgM. Seroconversion panels revealed high overall concordance with the reference tests. The Elecsys test detected IgG antibodies earlier than the Cobas Core IgG test in 19 of 47 panels; persisting IgM antibodies were observed in the VIDAS but not the Elecsys test in five of 47 panels. In 31.4% of latent stage sera with persistent IgM antibodies (positive LIASON IgM), the Elecsys IgM test gave negative results indicating increased “clinical” specificity. Sensitivity and specificity of the Elecsys IgG assay ranged from 99.45 to 100% and 87.50–99.80%, respectively, and 91.11–95.74 and 98.45–99.79% for the Elecsys IgM assay, respectively. In conclusion, excellent reproducibility and accuracy make the Elecsys Toxo G and M tests highly suitable for the detection of anti-T. gondii IgG and IgM antibodies. The lower detection rates for persistent IgM in the Elecsys IgM test increase “clinical” specificity and decrease the need for follow-up testing. PMID:26185683

Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses.

PubMed

Stonier, Spencer W; Herbert, Andrew S; Kuehne, Ana I; Sobarzo, Ariel; Habibulin, Polina; Dahan, Chen V Abramovitch; James, Rebekah M; Egesa, Moses; Cose, Stephen; Lutwama, Julius Julian; Lobel, Leslie; Dye, John M

2017-09-04

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4 + T cell responses but limited CD8 + T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity. © 2017 Stonier et al.

Incorporation of IgG Depletion in a Neutralization Assay Facilitates Differential Diagnosis of Zika and Dengue in Secondary Flavivirus Infection Cases.

PubMed

Calvert, Amanda E; Boroughs, Karen L; Laven, Janeen; Stovall, Janae L; Luy, Betty E; Kosoy, Olga I; Huang, Claire Y-H

2018-06-01

Zika virus (ZIKV) has emerged as a major global public health concern due to its link as a causative agent of human birth defects. Laboratory diagnosis of suspected ZIKV infections by serological testing of specimens collected a week or more after symptom onset primarily relies on detection of anti-ZIKV-specific IgM antibodies by enzyme-linked immunosorbent assay coupled with detection of ZIKV-specific neutralizing antibody by neutralization tests. A definitive diagnosis based on serological assays is possible during primary ZIKV infections; however, due to the cross-reactivity of antibodies elicited during flaviviral infections, a definitive diagnosis is not always possible, especially among individuals who have previously been exposed to closely related flaviviruses, such as dengue virus (DENV). Here, we investigated the neutralizing IgM antibody profiles of 33 diagnostic specimens collected from individuals with suspected primary and secondary flaviviral infections acquired when visiting areas experiencing active ZIKV transmission in 2015 and 2016. Specimens collected between 1 day and 3 months postexposure were tested for ZIKV and dengue virus type 1 (DENV1) and type 2 (DENV2) by the plaque reduction neutralization test (PRNT) before and after IgG depletion. We found that IgG depletion prior to neutralization testing had little effect in differentiating samples from individuals with secondary infections taken less than 3 weeks postexposure; however, IgG depletion significantly reduced the cross-reactive neutralizing antibody titers and increased the percentage of cases discernible by PRNT from 15.4% (95% confidence interval [CI], 4.3 to 42.2%) to 76.9% (95% CI, 49.7 to 91.8%) for samples collected between roughly 3 and 12 weeks postexposure. These results highlight the potential of IgG depletion to improve the specificity of PRNT for better confirmation and differential diagnosis of flavivirus infections. Copyright © 2018 American Society for Microbiology.

Serum IgG, IgM and slow alpha-globulin levels in carrageenan-treated rats.

PubMed Central

Fowler, E. F.; Thomson, A. W.

1979-01-01

Serum levels of IgM, IgG, slow alpha 1- and slow alpha 2-globulins were measured either by quantitative radial immunodiffusion (IgG) or immunoelectrophoresis (IgM and slow alpha-globulins) during the 3-week period after i.p. injection of 50 mg potassium carrageenan. There was a significant elevation in levels of IgM and slow alpha 1-globulin, maximal on Day 4 and returning to normal by Day 14. Slow alpha 2-globulin was detectable within 24 h, reached a peak at Day 2, and was no longer measurable in most rats by Day 14. Levels of IgG however, were unaffected by carrageenan injection. PMID:92333

Longitudinal Analysis of Early HIV-1-Specific Neutralizing Activity in an Elite Neutralizer and in Five Patients Who Developed Cross-Reactive Neutralizing Activity

PubMed Central

Euler, Zelda; van den Kerkhof, Tom L. G. M.; van Gils, Marit J.; Burger, Judith A.; Edo-Matas, Diana; Phung, Pham; Wrin, Terri

2012-01-01

We previously established that at 3 years postseroconversion, ∼30% of HIV-infected individuals have cross-reactive neutralizing activity (CrNA) in their sera. Here we studied the kinetics with which CrNA develops and how these relate to the development of autologous neutralizing activity as well as viral escape and diversification. For this purpose, sera from five individuals with CrNA and one elite neutralizer that were obtained at three monthly intervals in the first year after seroconversion and at multiple intervals over the disease course were tested for neutralizing activity against an established multiclade panel of six viruses. The same serum samples, as well as sera from three individuals who lacked CrNA, were tested for their neutralizing activities against autologous clonal HIV-1 variants from multiple time points covering the disease course from seroconversion onward. The elite neutralizer already had CrNA at 9.8 months postseroconversion, in contrast with the findings for the other five patients, in whom CrNA was first detected at 20 to 35 months postseroconversion and peaked around 35 months postseroconversion. In all patients, CrNA coincided with neutralizing activity against autologous viruses that were isolated <12 months postseroconversion, while viruses from later time points had already escaped autologous neutralizing activity. Also, the peak in gp160 sequence diversity coincided with the peak of CrNA titers. Individuals who lacked CrNA had lower peak autologous neutralizing titers, viral escape, and sequence diversity than individuals with CrNA. A better understanding of the underlying factors that determine the presence of CrNA or even an elite neutralizer phenotype may aid in the design of an HIV-1 vaccine. PMID:22156522

New 21 cm Power Spectrum Upper Limits From PAPER II: Constraints on IGM Properties at z = 7.7

NASA Astrophysics Data System (ADS)

Pober, Jonathan; Ali, Zaki; Parsons, Aaron; Paper Team

2015-01-01

Using a simulation-based framework, we interpret the power spectrum measurements from PAPER of Ali et al. in the context of IGM physics at z = 7.7. A cold IGM will result in strong 21 cm absorption relative to the CMB and leads to a 21 cm fluctuation power spectrum that can exceed 3000 mK^2. The new PAPER measurements allow us to rule out extreme cold IGM models, placing a lower limit on the physical temperature of the IGM. We also compare this limit with a calculation for the predicted heating from the currently observed galaxy population at z = 8.

Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies

PubMed Central

Meulenbroek, Elisabeth M.; de Haas, Masja; Brouwer, Conny; Folman, Claudia; Zeerleder, Sacha S.; Wouters, Diana

2015-01-01

In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient’s erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients’ sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti-erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients’ sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients’ erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy. PMID:26354757

Biotin IgM Antibodies in Human Blood: A Previously Unknown Factor Eliciting False Results in Biotinylation-Based Immunoassays

PubMed Central

Chen, Tingting; Hedman, Lea; Mattila, Petri S.; Jartti, Laura; Jartti, Tuomas; Ruuskanen, Olli; Söderlund-Venermo, Maria; Hedman, Klaus

2012-01-01

Biotin is an essential vitamin that binds streptavidin or avidin with high affinity and specificity. As biotin is a small molecule that can be linked to proteins without affecting their biological activity, biotinylation is applied widely in biochemical assays. In our laboratory, IgM enzyme immuno assays (EIAs) of µ-capture format have been set up against many viruses, using as antigen biotinylated virus like particles (VLPs) detected by horseradish peroxidase-conjugated streptavidin. We recently encountered one serum sample reacting with the biotinylated VLP but not with the unbiotinylated one, suggesting in human sera the occurrence of biotin-reactive antibodies. In the present study, we search the general population (612 serum samples from adults and 678 from children) for IgM antibodies reactive with biotin and develop an indirect EIA for quantification of their levels and assessment of their seroprevalence. These IgM antibodies were present in 3% adults regardless of age, but were rarely found in children. The adverse effects of the biotin IgM on biotinylation-based immunoassays were assessed, including four inhouse and one commercial virus IgM EIAs, showing that biotin IgM do cause false positivities. The biotin can not bind IgM and streptavidin or avidin simultaneously, suggesting that these biotin-interactive compounds compete for the common binding site. In competitive inhibition assays, the affinities of biotin IgM antibodies ranged from 2.1×10−3 to 1.7×10−4 mol/L. This is the first report on biotin antibodies found in humans, providing new information on biotinylation-based immunoassays as well as new insights into the biomedical effects of vitamins. PMID:22879954

A phase II trial on alpha-interferon (alpha IFN) effect in patients with monoclonal IgM gammopathy.

PubMed

Rotoli, B; De Renzo, A; Frigeri, F; Buffardi, S; Marcenò, R; Cavallaro, A M; Ruggeri, P; Liso, V; Musto, P; Andriani, A

1994-05-01

Waldenström's macroglobulinemia (WM) is an incurable disorder of B cells. Following occasional reports of response to alpha interferon (IFN) and in view of its effectiveness in hairy cell leukemia, we tested this agent in a relatively large group (n = 88) of patients who had an IgM monoclonal component (MC) greater than 10 g/l. Thirty eight patients had a MC > 30 g/l and were classified as Waldenström's macroglobulinemia (WM), while fifty had either WM in an early stage or an IgM monoclonal gammopathy of undeterminated significance (all of them operationally classified as IgM-MGUS). All patients received IFN 3 MU/day for one month and then 3 times/week. Response to treatment was mainly based on MC reduction in two consecutive determinations (> 50%: major response; 25-50%: minor response). Of 36 evaluable WM patients, 12 had a major and 6 a minor response; of 41 evaluable IgM-MGUS patients, 2 had a major and 6 a minor response. In WM patients with a major response, MC reduction was associated with disappearance of hyperviscosity symptoms, raised Hb level and reduced bone marrow lymphoplasmacytosis. At the dose used, tolerance was excellent in the majority of patients; only 15% withdrew from the study due to side effects. Although single cases and very small series have already been reported, no large study collecting quantitative data on the effects of alpha IFN in WM has been published so far. Our results suggest that IFN treatment is not indicated for patients with a low monoclonal component, while it is of clinical benefit in about 50% of patients with IgM > 30 g/l.

Effects of early morning nap sleep on associative memory for neutral and emotional stimuli.

PubMed

Sopp, Marie Roxanne; Michael, Tanja; Mecklinger, Axel

2018-06-18

Emotional events are preferentially retained in episodic memory. This effect is commonly attributed to enhanced consolidation and has been linked specifically to rapid eye movement (REM) sleep physiology. While several studies have demonstrated an enhancing effect of REM sleep on emotional item memory, it has not been thoroughly explored whether this effect extends to the retention of associative memory. Moreover, it is unclear how non-rapid eye movement (NREM) sleep contributes to these effects. The present study thus examined associative recognition of emotional and non-emotional material across an early morning nap (N= 23) and sustained wakefulness (N= 23). Nap group subjects demonstrated enhanced post-sleep associative memory performance, which was evident across both valence categories. Subsequent analyses revealed significant correlations between NREM spindle density and pre-sleep memory performance. Moreover, NREM spindle density was positively correlated with post-sleep neutral associative memory performance but not with post-sleep emotional associative memory. Accordingly, only neutral associative memory, but not emotional associative memory, was significantly correlated with spindle density after an additional night of sleep (+24 h). These results illustrate a temporally persistent relationship between spindle density and memory for neutral associations, whereas post-sleep emotional associative memory appears to be disengaged from NREM-sleep-dependent processes. Copyright © 2018. Published by Elsevier B.V.

Teleost Fish Mount Complex Clonal IgM and IgT Responses in Spleen upon Systemic Viral Infection

PubMed Central

Castro, Rosario; Jouneau, Luc; Pham, Hang-Phuong; Bouchez, Olivier; Giudicelli, Véronique; Lefranc, Marie-Paule; Quillet, Edwige; Benmansour, Abdenour; Cazals, Frédéric; Six, Adrien; Fillatreau, Simon; Sunyer, Oriol; Boudinot, Pierre

2013-01-01

Upon infection, B-lymphocytes expressing antibodies specific for the intruding pathogen develop clonal responses triggered by pathogen recognition via the B-cell receptor. The constant region of antibodies produced by such responding clones dictates their functional properties. In teleost fish, the clonal structure of B-cell responses and the respective contribution of the three isotypes IgM, IgD and IgT remain unknown. The expression of IgM and IgT are mutually exclusive, leading to the existence of two B-cell subsets expressing either both IgM and IgD or only IgT. Here, we undertook a comprehensive analysis of the variable heavy chain (VH) domain repertoires of the IgM, IgD and IgT in spleen of homozygous isogenic rainbow trout (Onchorhynchus mykiss) before, and after challenge with a rhabdovirus, the Viral Hemorrhagic Septicemia Virus (VHSV), using CDR3-length spectratyping and pyrosequencing of immunoglobulin (Ig) transcripts. In healthy fish, we observed distinct repertoires for IgM, IgD and IgT, respectively, with a few amplified μ and τ junctions, suggesting the presence of IgM- and IgT-secreting cells in the spleen. In infected animals, we detected complex and highly diverse IgM responses involving all VH subgroups, and dominated by a few large public and private clones. A lower number of robust clonal responses involving only a few VH were detected for the mucosal IgT, indicating that both IgM+ and IgT+ spleen B cells responded to systemic infection but at different degrees. In contrast, the IgD response to the infection was faint. Although fish IgD and IgT present different structural features and evolutionary origin compared to mammalian IgD and IgA, respectively, their implication in the B-cell response evokes these mouse and human counterparts. Thus, it appears that the general properties of antibody responses were already in place in common ancestors of fish and mammals, and were globally conserved during evolution with possible functional

A patterned recombinant human IgM guides neurite outgrowth of CNS neurons

PubMed Central

Xu, Xiaohua; Wittenberg, Nathan J.; Jordan, Luke R.; Kumar, Shailabh; Watzlawik, Jens O.; Warrington, Arthur E.; Oh, Sang-Hyun; Rodriguez, Moses

2013-01-01

Matrix molecules convey biochemical and physical guiding signals to neurons in the central nervous system (CNS) and shape the trajectory of neuronal fibers that constitute neural networks. We have developed recombinant human IgMs that bind to epitopes on neural cells, with the aim of treating neurological diseases. Here we test the hypothesis that recombinant human IgMs (rHIgM) can guide neurite outgrowth of CNS neurons. Microcontact printing was employed to pattern rHIgM12 and rHIgM22, antibodies that were bioengineered to have variable regions capable of binding to neurons or oligodendrocytes, respectively. rHIgM12 promoted neuronal attachment and guided outgrowth of neurites from hippocampal neurons. Processes from spinal neurons followed grid patterns of rHIgM12 and formed a physical network. Comparison between rHIgM12 and rHIgM22 suggested the biochemistry that facilitates anchoring the neuronal surfaces is a prerequisite for the function of IgM, and spatial properties cooperate in guiding the assembly of neuronal networks. PMID:23881231

IgG avidity test for the diagnosis of acute Toxoplasma gondii infection in early pregnancy.

PubMed

Pour Abolghasem, Shabnam; Bonyadi, Mohammad Reza; Babaloo, Zohre; Porhasan, Abolfazl; Nagili, Behroz; Gardashkhani, Omid Ali; Salehi, Parviz; Hashemi, Mohammad; Varshoghi, Mojtaba; Gaffari, Gafar Olade

2011-12-01

Toxoplasmosis is well known as an important infection in pregnant women. Although many serologic methods are available, diagnosis of early Toxoplasmosis may be extremely difficult. To detect the Toxoplasma IgG antibodies developed at the early stage of infection in pregnant women. 225 pregnant women, who were in the 2nd to 4th month of their pregnancy, enrolled in this study. Anti-toxoplasma IgG, IgM and IgG avidity were evaluated by ELISA method. The patients were categorized into three groups as follows: Group A, 124 cases; IgG+, IgM+, 55.1%; group B, 99 cases; IgG+, IgM-, 44%; and group C, 2 cases; IgG -, IgM +, 0.9%. Fifty five percent of the pregnant women had positive IgG and IgM among which 7.1% had low avidity which revealed an active infection in the pregnant women. In the current study, 44% of pregnant women had positive IgG and negative IgM, all of which had high avidity, which is an indication that in our population the level of toxoplasmosis infection is high and most women have had contacts with this parasite before pregnancy. In this study, the low avidity test was 7.1% showing that the occurrence of toxoplasmosis infection is still a serious issue. Observation of 45.8% high avidity among group A suggests that either IgM has a high half-life or there is a false positive IgM as a result of rheumatologic disorders. Therefore, avidity test is important in predicting maternal toxoplasmosis which is of value in disease treatment.

Detection of koi herpesvirus (KHV) using a monoclonal antibody against Cyprinus carpio IgM.

PubMed

Li, Yingying; Zheng, Shucheng; Wang, Qing; Bergmann, Sven M; Zeng, Weiwei; Wang, Yingying; Liu, Chun; Shi, Cunbin

2017-08-01

Koi herpesvirus disease (KHVD) is associated with high mortality in both common carp and koi carp (Cyprinus carpio L.) worldwide. The indirect detection of fish viruses based on the identification of antibodies has emerged as a practical and reliable means of diagnosis. Thus, it is important to create monoclonal antibodies (MAbs) against carp IgM. By using hybridoma-monoclonal antibody technology, one hybridoma cell line secreting MAbs against IgM from carp was established. In western blot analysis, the secreted MAb from cell line A5-E10 recognized the heavy chain of IgM from common carp or koi but did not react with immunoglobulins from three different fish species: grass carp (Ctenopharyngodon idella), tilapia (Oreochromis mossambicus) and Mandarin fish (Siniperca chuatsi). These results demonstrated that this MAb is highly specific for the IgM of carp and suggested that it can be used for monitoring the immunity level of carp, for example for indirect KHV diagnosis by antibody ELISA. We therefore established an indirect ELISA, which was tested using 200 serum samples from koi from three farms. The final results showed that 147 (73.5%) samples were confirmed to be KHV antibody negative and 53 (26.5%) were definitely positive, containing antibodies against KHV.

Generation of a novel high-affinity monoclonal antibody with conformational recognition epitope on human IgM.

PubMed

Sarikhani, Sina; Mirshahi, Manouchehr; Gharaati, Mohammad Reza; Mirshahi, Tooran

2010-11-01

As IgM is the first isotype of antibody which appears in blood after initial exposure to a foreign antigen in the pattern of primary response, detection, and quantification of this molecule in blood seems invaluable. To approach these goals, generation, and characterization of a highly specific mAb (monoclonal antibody) against human IgM were investigated. Human IgM immunoglobulins were used to immunize Balb/c mice. Spleen cells taken from the immunized animals were fused with SP2/O myeloma cells using PEG (polyethylene glycol, MW 1450) as fusogen. The hybridomas were cultured in HAT containing medium and supernatants from the growing hybrids were screened by enzyme-linked immunosorbent assay (ELISA) using plates coated with pure human IgM and the positive wells were then cloned at limiting dilutions. The best clone designated as MAN-1, was injected intraperitoneally to some Pristane-injected mice. Anti-IgM mAb was purified from the animals' ascitic fluid by protein-G sepharose followed by DEAE-cellulose ion exchange chromatography. MAN-1 interacted with human IgM with a very high specificity and affinity. The purity of the sample was tested by SDS-PAGE and the affinity constant was measured (K(a) = 3.5 x 10(9)M(-1). Immunoblotting and competitive ELISA were done and the results showed that the harvested antibody recognizes a conformational epitope on the mu chain of human IgM and there was no cross-reactivity with other subclasses of immunoglobulins. Furthermore, isotyping test was done and the results showed the subclass of the obtained mAb which was IgG(1)kappa.

Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

PubMed

Tang, Chih-Hang Anthony; Chang, Shiun; Hashimoto, Ayumi; Chen, Yi-Ju; Kang, Chang Won; Mato, Anthony R; Del Valle, Juan R; Gabrilovich, Dmitry I; Hu, Chih-Chi Andrew

2018-06-01

Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS -/- mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS -/- /Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS -/- mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696-710. ©2018 AACR . ©2018 American Association for Cancer Research.

Frequency of anti- Toxoplasma gondii IgA, IgM, and IgG antibodies in high-risk pregnancies, in Brazil.

PubMed

Murata, Fernando Henrique Antunes; Ferreira, Marina Neves; Camargo, Natália Sahyoun; Santos, Gabriela Soria; Spegiorin, Lígia Cosentino Junqueira Franco; Silveira-Carvalho, Aparecida Perpétuo; Pereira-Chioccola, Vera Lucia; Mattos, Luiz Carlos de; Mattos, Cinara Cássia Brandão de

2016-01-01

Toxoplasmosis during pregnancy can be severe; thus, it is essential to diagnose the disease via serological tests. An enzyme-linked immunosorbent assay (ELISA) was used to investigate anti-Toxoplasma gondii immunoglobulin A (IgA), M (IgM) and G (IgG) antibodies in 62 high-risk pregnant women. Forty-three (69.4%) women were positive for IgA, 31 (50%) for IgG, and 57 (91.9%) for IgM; 4 (6,5%) were positive for IgA but negative for IgM; 10 (16.1%) were negative for IgA and IgM but positive for IgG. Testing for these antibodies can help diagnose infection in pregnant women, thereby contributing to clinical management.

The significance of specific IgM antibody in the diagnosis of rubella employing the immunofluorescence technique

PubMed Central

Iwakata, S.; Rhodes, A. J.; Labzoffsky, N. A.

1972-01-01

The applicability of the immunofluorescence (IF) test to the diagnosis of primary rubella infection was investigated. The test is based on the detection of rubella-specific antibodies in the IgM fraction of immunoglobulins. The results indicate the usefulness of the IF test for the diagnosis of primary rubella infection on a single serum specimen collected at a proper time. The test is also of value in the differentiation of primary infection from reinfection, since in reinfection no rubella-specific antibodies are found in the IgM fraction. The test is also valuable for the detection of fetal infection in utero since the persistence of IgM antibodies in pregnant women is indicative of fetal infection. PMID:4551395

GhNAC12, a neutral candidate gene, leads to early aging in cotton (Gossypium hirsutum L).

PubMed

Zhao, Fengli; Ma, Jianhui; Li, Libei; Fan, Shuli; Guo, Yaning; Song, Meizhen; Wei, Hengling; Pang, Chaoyou; Yu, Shuxun

2016-01-15

NAC (NAM, ATAF, and CUC) is one of the largest transcription factor families in plants, and its members play various roles in plant growth, development, and the response to biotic and abiotic stresses. Currently, 77 NAC genes have been reported in cotton (Gossypium hirsutum L.). And GhNAC12 showed up-regulation during leaf senescence, but its role in this process is poorly understood. In the present study, a preliminary function analysis of GhNAC12 was performed during leaf senescence. qRT-PCR analysis indicated that GhNAC12 expression increased during the early-aging process and the aging of cotyledons. Additionally, we observed that overexpression of GhNAC12 in Arabidopsis led to early senescence (early aging). Our findings suggest that GhNAC12 is a candidate gene for early aging in upland cotton cultivars. Neutrality tests suggested that there was no selection pressure imposed on GhNAC12 during the domestication of upland cotton. Copyright © 2015 Elsevier B.V. All rights reserved.

Functional capacities of human IgM memory B cells in early inflammatory responses and secondary germinal center reactions.

PubMed

Seifert, Marc; Przekopowitz, Martina; Taudien, Sarah; Lollies, Anna; Ronge, Viola; Drees, Britta; Lindemann, Monika; Hillen, Uwe; Engler, Harald; Singer, Bernhard B; Küppers, Ralf

2015-02-10

The generation and functions of human peripheral blood (PB) IgM(+)IgD(+)CD27(+) B lymphocytes with somatically mutated IgV genes are controversially discussed. We determined their differential gene expression to naive B cells and to IgM-only and IgG(+) memory B cells. This analysis revealed a high similarity of IgM(+)(IgD(+))CD27(+) and IgG(+) memory B cells but also pointed at distinct functional capacities of both subsets. In vitro analyses revealed a tendency of activated IgM(+)IgD(+)CD27(+) B cells to migrate to B-cell follicles and undergo germinal center (GC) B-cell differentiation, whereas activated IgG(+) memory B cells preferentially showed a plasma cell (PC) fate. This observation was supported by reverse regulation of B-cell lymphoma 6 and PR domain containing 1 and differential BTB and CNC homology 1, basic leucine zipper transcription factor 2 expression. Moreover, IgM(+)IgD(+)CD27(+) B lymphocytes preferentially responded to neutrophil-derived cytokines. Costimulation with catecholamines, carcinoembryonic antigen cell adhesion molecule 8 (CEACAM8), and IFN-γ caused differentiation of IgM(+)IgD(+)CD27(+) B cells into PCs, induced class switching to IgG2, and was reproducible in cocultures with neutrophils. In conclusion, this study substantiates memory B-cell characteristics of human IgM(+)IgD(+)CD27(+) B cells in that they share typical memory B-cell transcription patterns with IgG(+) post-GC B cells and show a faster and more vigorous restimulation potential, a hallmark of immune memory. Moreover, this work reveals a functional plasticity of human IgM memory B cells by showing their propensity to undergo secondary GC reactions upon reactivation, but also by their special role in early inflammation via interaction with immunomodulatory neutrophils.

Chlamydia trachomatis IgM seropositivity during pregnancy and assessment of its risk factors.

PubMed

Rahman, M; Chowdhury, S B; Akhtar, N; Jahan, M; Jahan, M K; Jebunnahar, S

2014-01-01

The study was undertaken to determine socio-demographic and reproductive risk factors associated with Chlamydia trachomaties IgM seropositivity during pregnancy. This cross sectional comparative study was carried out in the obstetrics outdoor of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh in collaboration with the department of Virology between the periods from July 2007 to December 2008. Pregnant women at their first visit to the hospital were approached consecutively and asked to complete a questionnaire and 2cc blood was collected from each subject for Chlamydia trachomatis IgM antibody testing using ELISA method. The study population was divided into two groups according to the presence and absence of serum Chlamydia trachomatis IgM antibody. Finally socio-demographic and reproductive risk factors were compared between the groups. Among 172 women the sero-prevalence of Chlamydia IgM was 41%. The multiple logistic regression model (step wise) finally extracted for characteristics correlated with seropositivity. Ten years or less (≤SSC) education (OR 2.6 95% CI 1.1to 5.9), history of adverse pregnancy outcome (OR 2.8 95% CI 1.2 to 6.5) and multiple sex partner of husband (OR 4.1 95% CI 1.2 to 14.8) were associated with chlamydia infection. The use of condom (OR 0.28 95% CI 0.12 to 0.63) was associated with decreased risk of infection. Chlamydia trachomatis infection during pregnancy is associated with risk factors on the basis of which selective screening can be done.

Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution.

PubMed

Abdel-Azim, Hisham; Elshoury, Amro; Mahadeo, Kris M; Parkman, Robertson; Kapoor, Neena

2017-09-01

Although T cell immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71 pediatric allo-HSCT recipients. Although tetanus toxoid antibody levels were normal at 1 year after allo-HSCT, antipolysaccharide carbohydrate antibodies remained persistently low for up to 5 years. While naive B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for up to 2 years (P = .01); switched memory B cell deficiency normalized by 1 year after allo-HSCT. CD4 + T cell immune reconstitution correlated with that of switched memory B cells as early as 6 months after allo-HSCT (r = .55, P = .002) but did not correlate with IgM memory B cells at any time point after allo-HSCT. Taken together, this suggests that allo-HSCT recipients have impaired antibody immune reconstitution, mainly due to IgM memory B cell maturation block, compared with more prompt T cell-dependent switched memory cell immune reconstitution. We further explored other factors that might affect humoral immune reconstitution. The use of total body irradiation was associated with lower naive B cells counts at 6 months after HSCT (P = .04) and lower IgM (P = .008) and switched (P = .003) memory B cells up to 2 years. Allo-HSCT recipients with extensive chronic graft-versus-host disease had lower IgM memory B cell counts (P = .03) up to 2 years after allo-HSCT. The use of cord blood was associated with better naive (P = .01), IgM (P = .0005), and switched memory (P = .006) B cells immune reconstitution. These findings may inform future prophylaxis and treatment strategies regarding risk of overwhelming infection, graft-versus-host disease, and post-allogeneic HSCT revaccination. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights

Raman spectroscopy-based screening of IgM positive and negative sera for dengue virus infection

NASA Astrophysics Data System (ADS)

Bilal, M.; Saleem, M.; Bilal, Maria; Ijaz, T.; Khan, Saranjam; Ullah, Rahat; Raza, A.; Khurram, M.; Akram, W.; Ahmed, M.

2016-11-01

A statistical method based on Raman spectroscopy for the screening of immunoglobulin M (IgM) in dengue virus (DENV) infected human sera is presented. In total, 108 sera samples were collected and their antibody indexes (AI) for IgM were determined through enzyme-linked immunosorbent assay (ELISA). Raman spectra of these samples were acquired using a 785 nm wavelength excitation laser. Seventy-eight Raman spectra were selected randomly and unbiasedly for the development of a statistical model using partial least square (PLS) regression, while the remaining 30 were used for testing the developed model. An R-square (r 2) value of 0.929 was determined using the leave-one-sample-out (LOO) cross validation method, showing the validity of this model. It considers all molecular changes related to IgM concentration, and describes their role in infection. A graphical user interface (GUI) platform has been developed to run a developed multivariate model for the prediction of AI of IgM for blindly tested samples, and an excellent agreement has been found between model predicted and clinically determined values. Parameters like sensitivity, specificity, accuracy, and area under receiver operator characteristic (ROC) curve for these tested samples are also reported to visualize model performance.

Evaluation of an immunochromatographic assay for the detection of anti-hepatitis A virus IgM

PubMed Central

2010-01-01

Background Hepatitis A virus (HAV) is a causative agent of acute hepatitis, which is transmitted by person-to-person contact and via the faecal-oral route. Acute HAV infection is usually confirmed by anti-HAV IgM detection. In order to detect anti-HAV IgM in the serum of patients infected with HAV, we developed a rapid assay based on immunochromatography (ICA) and evaluated the sensitivity of this assay by comparing it with a commercial microparticle enzyme immunoassay (MEIA) that is widely used for serological diagnosis. Results The newly developed ICA showed 100% sensitivity and specificity when used to test 150 anti-HAV IgM-positive sera collected from infected patients and 75 negative sera from healthy subjects. Also, the sensitivity of ICA is about 10 times higher than MEIA used in this study by determining end point to detect independent on infected genotype of HAV. In addition, the ICA was able to detect 1 positive sample from among 50 sera from acute hepatitis patients that had tested negative for anti-HAV IgM using the MEIA. Conclusion Conclusively, ICA for the detection of anti-HAV IgM will be very effective for rapid assay to apply clinical diagnosis and epidemiological investigation on epidemics due to the simplicity, rapidity and specificity. PMID:20637129

Evaluation of a New Immunochromatography Technology Test (LDBio Diagnostics) To Detect Toxoplasma IgG and IgM: Comparison with the Routine Architect Technique

PubMed Central

Flori, Pierre; Delaunay, Edouard; Guillerme, Cécile; Charaoui, Sana; Raberin, Hélène; Hafid, Jamal; L'Ollivier, Coralie

2017-01-01

ABSTRACT A study comparing the ICT (immunochromatography technology) Toxoplasma IgG and IgM rapid diagnostic test (LDBio Diagnostics, France) with a fully automated system, Architect, was performed on samples from university hospitals of Marseille and Saint-Etienne. A total of 767 prospective sera and 235 selected sera were collected. The panels were selected to test various IgG and IgM parameters. The reference technique, Toxoplasma IgGII Western blot analysis (LDBio Diagnostics), was used to confirm the IgG results, and commercial kits Platelia Toxo IgM (Bio-Rad) and Toxo-ISAgA (bioMérieux) were used in Saint-Etienne and Marseille, respectively, as the IgM reference techniques. Sensitivity and specificity of the ICT and the Architect IgG assays were compared using a prospective panel. Sensitivity was 100% for the ICT test and 92.1% for Architect (cutoff at 1.6 IU/ml). The low-IgG-titer serum results confirmed that ICT sensitivity was superior to that of Architect. Specificity was 98.7% (ICT) and 99.8% (Architect IgG). The ICT test is also useful for detecting IgM without IgG and is both sensitive (100%) and specific (100%), as it can distinguish nonspecific IgM from specific Toxoplasma IgM. In comparison, IgM sensitivity and specificity on Architect are 96.1% and 99.6%, respectively (cutoff at 0.5 arbitrary units [AU]/ml). To conclude, this new test overcomes the limitations of automated screening techniques, which are not sensitive enough for IgG and lack specificity for IgM (rare IgM false-positive cases). PMID:28954897

ABO (histo) blood group phenotype development and human reproduction as they relate to ancestral IgM formation: A hypothesis.

PubMed

Arend, Peter

2016-01-01

The formation of a histo (blood) group) ABO phenotype and the exclusion of an autoreactive IgM or isoagglutinin activity arise apparently in identical glycosylation of complementary domains on cell surfaces and plasma proteins. The fundamental O-glycan emptiness of the circulating IgM, which during the neonatal amino acid sequencing of the variable regions is exerting germline-specific O-GalNAc glycan-reactive serine/threonine residues that in the plasma of the adult human blood group O individuals apparently remain associated with the open glycosidic sites on the ABOH convertible red cell surface, must raise suggestions on a transient expression of developmental glycans, which have been "lost" over the course of maturation. In fact, while the mammalian non-somatic, embryogenic stem cell (ESC)- germ cell (GC) transformation is characterized by a transient and genetically as-yet-undefined trans-species-functional O-GalNAc glycan expression, in the C57BL/10 mouse such expression was potentially identified in growth-dependent, blood group A-like GalNAc glycan-bearing, ovarian glycolipids complementary with the syngeneic anti-A reactive IgM, which does not appear in early ovariectomized animals. This non-somatically encoded, polyreactive, ancestral IgM molecule has not undergone clonal selection and does primarily not differentiate between self and non-self and might, due to amino acid hydroxyl groups, highly suggest substrate competition with subsequent O-glycosylations in ongoing ESC-GC transformations and affecting GC maturation. However, the membrane-bound somatic N/O-glycotransferases, which initiate, after formation of the zygote, the complex construction of the human ABO phenotypes in the trans cisternae of the Golgi apparatus, are associated and/or completed with soluble enzyme versions exerting identical specificities in plasma and likely competing vice versa by glycosylation of neonatal IgM amino acids, where they suggest to accomplish the clearance of anti

Toxoplasmosis serology: an efficient hemagglutination procedure to detect IgG and IgM antibodies.

PubMed

Camargo, M E; Moura, M E; Leser, P G

1989-01-01

In search of an efficient but simple, low cost procedure for the serodiagnosis of Toxoplasmosis, especially suited for routine laboratories facing technical and budget limitations as in less developed countries, the diagnostic capability of Hematoxo, an hemagglutination test for toxoplasmosis, was evaluated in relation to a battery of tests including IgG- and IgM-immunofluorescence tests, hemagglutination and an IgM-capture enzymatic assay. Detecting a little as 5 I.U. of IgG antitoxoplasma antibodies, Hematoxo showed a straight agreement as to reactivity and non-reactivity for the 443 non-reactive and the 387 reactive serum samples, included in this study. In 23 cases presenting a serological pattern of acute toxoplasmosis and showing IgM antibodies, Hematoxo could detect IgM antibodies in 18, indicated by negativation or a significant decrease in titers as a result of treating samples with 2-mercapto-ethanol. However, a neat increase in sensitivity for IgM specific antibodies could be achieved by previously removing IgG from the sample, as demonstrated in a series of acute toxoplasmosis sera. A simple procedure was developed for this purpose, by reconstituting a lyophilized suspension of Protein A--rich Staphylococcus with the lowest serum dilution to be tested. Of low cost and easy to perform, Hematoxo affords not only a practical qualitative procedure for screening reactors and non-reactors, as in prenatal services, but also quantitative assays that permit to titrate antibodies as well as to identify IgM antibodies.

Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without neuromuscular damage.

PubMed

Santafé, Manel M; Sabaté, M Mar; Garcia, Neus; Ortiz, Nico; Lanuza, M Angel; Tomàs, Josep

2008-11-15

We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal IgM, which binds specifically to gangliosides with the common epitope [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement. Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and chronically (10 days). Transmission electron microscopy shows important nerve terminal growth and retraction remodelling though axonal injury can be ruled out. Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled when human complement was added. Therefore, the IgM-induced synaptic changes occur without complement-mediated membrane attack.

West Nile encephalitis outbreak in Kerala, India, 2011.

PubMed

Anukumar, B; Sapkal, Gajanan N; Tandale, Babasheb V; Balasubramanian, R; Gangale, Daya

2014-09-01

An outbreak of acute encephalitis syndrome (AES) was reported in Kerala in India in May 2011. The outbreak features were unusual in terms of seasonality, geographical distribution, age group, and clinical manifestations in comparison to the epidemiological features of Japanese Encephalitis. To detect the etiology of the acute encephalitis syndrome outbreak. Investigation of outbreak was undertaken by collection of brief clinical history and epidemiological details along with the specimens for viral diagnosis. The serum/CSF samples (patients=208) received from the sentinel hospitals were subjected to IgM capture ELISA and RT-PCR specific for Japanese encephalitis (JE) virus and West Nile virus (WNV). The JE/WN IgM positive samples were further tested by serum neutralization assay for the presence of JE and WNV specific neutralizing antibody. Most of the affected patients were aged above 15 years. No spatial clustering of the disease was noticed. Cases were observed in premonsoon and early monsoon season and in JE non-endemic area of Kerala. A total of 47 patient samples were positive for in-house JE IgM capture ELISA and WNV IgM capture ELISA. Serum neutralization assay result revealed that 32 of 42 (76.19%) sera were positive for WNV neutralization antibodies. WNV was isolated from a clinical specimen. Phylogenetic analysis of WNV envelope gene revealed 99% homology with Russian Lineage 1 WNV. West Nile virus (WNV) etiology was confirmed by virus isolation and detection of virus specific antibody from clinical specimen. Phylogenetic analysis grouped the current strain in lineage I West Nile virus. Copyright © 2014 Elsevier B.V. All rights reserved.

Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease.

PubMed

Shindi, Reham; Almehairi, Amna; Negm, Ola H; Kalsheker, Noor; Gale, Nichola S; Shale, Dennis J; Harrison, Timothy W; Bolton, Charlotte E; John, Michelle; Todd, Ian; Tighe, Patrick J; Fairclough, Lucy C

2017-10-01

Autoimmunity occurs in chronic obstructive pulmonary disease (COPD). We describe an antigen microarray for detecting serum autoantibodies (AAbs) to determine how IgM, as well as IgG, AAbs distinguish patients with COPD from controls with a history of smoking without COPD. All COPD patients' sera contained elevated levels of AAbs to some of 30 autoantigens. There were significant differences in the autoantigenic specificities of IgM AAbs compared to IgG AAbs in the COPD sera: for example, AAbs to histone and scl-70 were mainly IgG, whereas AAbs to CENP-B and La/ssB were mainly IgM; by contrast, IgM and IgG AAbs to collagen-V were equally prevalent. Thus, a combination of IgM and IgG AAbs specific for multiple autoantigens are detected in all cases of COPD at a level at which all non-COPD controls are negative for AAbs. This highlights the importance of different classes of AAbs to a range of autoantigens in COPD. Copyright © 2017 Elsevier Inc. All rights reserved.

Peer reactions to early childhood aggression in a preschool setting: Defenders, encouragers, or neutral bystander.

PubMed

Rose, Chad A; Richman, David M; Fettig, Katharine; Hayner, Annamarie; Slavin, Carly; Preast, June L

2016-08-01

The purpose of the current study was to determine if peer reactions to aggression among preschool youth were consistent with those conceptualized in the adolescent bullying literature as defenders, encouragers, and neutral bystanders. Direct observations were used to document patterns for types of peer-directed aggression in early childhood settings to ascertain interaction differences between individuals involved within the bullying dynamic. Observations of 50 students in preschool were conducted over 5.5 months. Event recording procedures were used to document aggressive behaviors and reactions from peers and teachers. Results indicated that the majority of aggression was physical. Additionally, peer reactions, as described in the bullying literature for school-aged youth, occurred very infrequently. Peer aggression tended to be more physical, suggesting that early childhood educators should attend to these physical interactions, and cultivate a classroom community that emphasizes social supports and appropriate interactions.

Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice.

PubMed

Yamashita, Naoya; Jitsuki-Takahashi, Aoi; Ogawara, Miyuki; Ohkubo, Wataru; Araki, Tomomi; Hotta, Chie; Tamura, Tomohiko; Hashimoto, Shu-ichi; Yabuki, Takashi; Tsuji, Toru; Sasakura, Yukie; Okumura, Hiromi; Takaiwa, Aki; Koyama, Chika; Murakami, Koji; Goshima, Yoshio

2015-09-01

Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A both in vitro and in vivo. The anti-Sema3A neutralization chick IgM antibodies were screened by combining an autonomously diversifying library selection system and an in vitro growth cone collapse assay. We further developed function-blocking chick-mouse chimeric and humanized anti-Sema3A antibodies. We found that our anti-Sema3A antibodies were effective for improving the survival rate in lipopolysaccharide-induced sepsis in mice. Our antibody is a potential therapeutic agent that may prevent the onset of or alleviate symptoms of human diseases associated with Sema3A. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Circadian type, chronic fatigue, and serum IgM in the shift workers of an industrial organization

PubMed Central

Khaleghipour, Shahnaz; Masjedi, Mohsen; Kelishadi, Roya

2015-01-01

Background: Night shift workers are more vulnerable to immune-related diseases. Immunoglobulin M (IgM) is a potent activator of complement, and complement has a crucial role in defense against bacterial infections. Circadian type is known as an effective agent on vulnerability and adaptation with shift work due to non-compliance with shift stress. The objective of this study was to investigate the correlation of circadian type and chronic fatigue with the serum concentration of IgM in a group of shift workers. Materials and Methods: This cross-sectional study was performed in an industrial organization in Isfahan, Iran. The study population consisted of 221 male employees working at night shifts who were selected by random cluster sampling. The following questionnaires were used: composite morningness (Torsvall and Akerstedt), circadian type (Folkard), and chronic fatigue (Barton and colleagues). The serum concentration of IgM was measured by the nephelometric method. The data were analyzed with the Pearson coefficient correlation and the path analysis for finding the pattern of the structural equations to evaluate the direct and indirect relationships between variables, using the SPSS 15 and LISREL 8.5 statistical software. Results: Significant correlation was documented between morningness, flexibility, languidness, and chronic fatigue with the serum concentration of IgM (P < 0.01). Conclusion: The results showed that the shift workers with morningness and languidness experienced more problems during the working hours due to more tiredness, and had decreased serum concentration of IgM. Correct management of shift work may attenuate fatigue in workers and also improve many health issues experienced by the shift workers. PMID:25802830

Anti-Streptococcus IgM Antibodies Induce Repetitive Stereotyped Movements: Cell Activation and Co-Localization with Fcα/μ Receptors in the Striatum and Motor Cortex

PubMed Central

Zhang, Danhui; Patel, Ankur; Zhu, Youhua; Siegel, Allan; Zalcman, Steven S.

2012-01-01

Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to Streptococcus Group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fcα/μ receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fcα/μ receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies.

PubMed

Richardson, Simone I; Chung, Amy W; Natarajan, Harini; Mabvakure, Batsirai; Mkhize, Nonhlanhla N; Garrett, Nigel; Abdool Karim, Salim; Moore, Penny L; Ackerman, Margaret E; Alter, Galit; Morris, Lynn

2018-04-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies.

Human Plasma-derived Polymeric IgA and IgM Antibodies Associate with Secretory Component to Yield Biologically Active Secretory-like Antibodies*

PubMed Central

Longet, Stéphanie; Miled, Sarah; Lötscher, Marius; Miescher, Sylvia M.; Zuercher, Adrian W.; Corthésy, Blaise

2013-01-01

Immunotherapy with monoclonal and polyclonal immunoglobulin is successfully applied to improve many clinical conditions, including infection, autoimmune diseases, or immunodeficiency. Most immunoglobulin products, recombinant or plasma-derived, are based on IgG antibodies, whereas to date, the use of IgA for therapeutic application has remained anecdotal. In particular, purification or production of large quantities of secretory IgA (SIgA) for potential mucosal application has not been achieved. In this work, we sought to investigate whether polymeric IgA (pIgA) recovered from human plasma is able to associate with secretory component (SC) to generate SIgA-like molecules. We found that ∼15% of plasma pIgA carried J chain and displayed selective SC binding capacity either in a mixture with monomeric IgA (mIgA) or after purification. The recombinant SC associated covalently in a 1:1 stoichiometry with pIgA and with similar efficacy as colostrum-derived SC. In comparison with pIgA, the association with SC delayed degradation of SIgA by intestinal proteases. Similar results were obtained with plasma-derived IgM. In vitro, plasma-derived IgA and SIgA neutralized Shigella flexneri used as a model pathogen, resulting in a delay of bacteria-induced damage targeted to polarized Caco-2 cell monolayers. The sum of these novel data demonstrates that association of plasma-derived IgA or IgM with recombinant/colostrum-derived SC is feasible and yields SIgA- and SIgM-like molecules with similar biochemical and functional characteristics as mucosa-derived immunoglobulins. PMID:23250751

A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia.

PubMed

Chen, Xu; Gustafsson, Stefan; Whitington, Thomas; Borné, Yan; Lorentzen, Erik; Sun, Jitong; Almgren, Peter; Su, Jun; Karlsson, Robert; Song, Jie; Lu, Yi; Zhan, Yiqiang; Hägg, Sara; Svensson, Per; Smedby, Karin E; Slager, Susan L; Ingelsson, Erik; Lindgren, Cecilia M; Morris, Andrew P; Melander, Olle; Karlsson, Thomas; de Faire, Ulf; Caidahl, Kenneth; Engström, Gunnar; Lind, Lars; Karlsson, Mikael C I; Pedersen, Nancy L; Frostegård, Johan; Magnusson, Patrik K E

2018-05-15

Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined β = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 × 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 × 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.

Endotoxin Neutralization as a Biomonitor for Inflammatory Bowel Disease

PubMed Central

Champion, Keith; Chiu, Laura; Ferbas, John; Pepe, Michael

2013-01-01

Gram-negative bacterial endotoxin is a potent immunostimulant implicated in the development and/or progression of a variety of diseases. The mammalian immune system has both innate and adaptive immune responses to neutralize endotoxin. In this study, a system was developed to monitor bacterial exposure by measuring the extent and nature of endotoxin neutralization in plasma. In control patients, females had higher levels of endotoxin neutralization than males, mirroring clinical outcomes from bacterial infection and sepsis. In addition to the total amount of neutralization, we used inactivation techniques to elucidate the nature of this activity and develop a system to compare early and late immune responses. Using this method to monitor patients with inflammatory bowel disease, we found a more robust total response that relies more on long-term, adaptive components of the immune system and less on early, innate components. Our results indicate that endotoxin neutralization is a valuable method to discern inflammatory bowel disease patients from a control population. Additionally, the nature of neutralization may be valuable in monitoring disease severity and/or the role of medication. PMID:23826338

Serum anti-phenolic glycolipid-1 IgA correlates to IgM isotype in leprosy patients: a possible candidate for seroepidemiological surveys?

PubMed

de Macedo, Alexandre C; Guimarães, Juliana A; Rodrigues, Raphael O; Araújo, Thiago D V; Tavares, Clodis M; Cabral, Paula B; de Moraes-Pinto, Maria Isabel; Nagao-Dias, Aparecida T

2018-03-01

The aim of this study was to compare serum anti-phenolic glycolipid-1 IgA, IgG, and IgM levels in leprosy patients and controls. Analysis of anti-PGL-1 IgA, IgG, or IgM in serum samples from multibacillary (MB, n=32) and paucibacillary (PB, n=22) leprosy patients, and in non-endemic controls (n=17), using an indirect enzyme-linked immunosorbent assay. A strong correlation between serum IgM and IgA isotypes was found (r=.745, P<.0001) in MB patients. A moderate correlation was found in all analyses in PB patients. A moderate agreement was found between anti-PGL1 IgA and IgM tests. Based on the ROC curves, the cut-off values were selected and the parameters of validation were calculated. Considering the clinical forms altogether, the diagnostic sensitivities were 50.0% for IgA, 22.2% for IgG, and 74.1% for IgM. The positive (VPP) and negative (VPN) predictive values were estimated for each isotype. For IgA, the VPP and VPN were, respectively, 100.0% (87.0%-100.0%; 95% confidence interval) and 38.7% (24.4%-54.5%); for IgG, 100% (87.0%-100.0%) and 28.8% (17.8%-42.1%), respectively; and for IgM, 95.2% (83.8%-99.4%) and 51.7% (32.5%-70.6%), respectively. Despite the limiting factors, anti-PGL1 IgA correlates to IgM levels and it could be considered as a possible laboratorial tool to be also used, for instance, in serological follow-up studies. © 2017 Wiley Periodicals, Inc.

VIMOS Ultra-Deep Survey (VUDS): IGM transmission towards galaxies with 2.5 < z < 5.5 and the colour selection of high-redshift galaxies

NASA Astrophysics Data System (ADS)

Thomas, R.; Le Fèvre, O.; Le Brun, V.; Cassata, P.; Garilli, B.; Lemaux, B. C.; Maccagni, D.; Pentericci, L.; Tasca, L. A. M.; Zamorani, G.; Zucca, E.; Amorin, R.; Bardelli, S.; Cassarà, L.; Castellano, M.; Cimatti, A.; Cucciati, O.; Durkalec, A.; Fontana, A.; Giavalisco, M.; Grazian, A.; Hathi, N. P.; Ilbert, O.; Paltani, S.; Pforr, J.; Ribeiro, B.; Schaerer, D.; Scodeggio, M.; Sommariva, V.; Talia, M.; Tresse, L.; Vanzella, E.; Vergani, D.; Capak, P.; Charlot, S.; Contini, T.; Cuby, J. G.; de la Torre, S.; Dunlop, J.; Fotopoulou, S.; Koekemoer, A.; López-Sanjuan, C.; Mellier, Y.; Salvato, M.; Scoville, N.; Taniguchi, Y.; Wang, P. W.

2017-01-01

The observed UV rest-frame spectra of distant galaxies are the result of their intrinsic emission combined with absorption along the line of sight produced by the inter-galactic medium (IGM). Here we analyse the evolution of the mean IGM transmission Tr(Lyα) and its dispersion along the line of sight for 2127 galaxies with 2.5 < z < 5.5 in the VIMOS Ultra Deep Survey (VUDS). We fitted model spectra combined with a range of IGM transmission to the galaxy spectra using the spectral fitting algorithm GOSSIP+. We used these fits to derive the mean IGM transmission towards each galaxy for several redshift slices from z = 2.5 to z = 5.5. We found that the mean IGM transmission defined as Tr(Lyα) = e- τ (with τ as the HI optical depth) is 79%, 69%, 59%, 55%, and 46% at redshifts 2.75, 3.22, 3.70, 4.23, and 4.77, respectively. We compared these results to measurements obtained from quasar lines of sight and found that the IGM transmission towards galaxies is in excellent agreement with quasar values up to redshift z 4. We found tentative evidence for a higher IGM transmission at z ≥ 4 compared to results from QSOs, but a degeneracy between dust extinction and IGM prevents us from firmly concluding whether the internal dust extinction for star-forming galaxies at z > 4 takes a mean value significantly in excess of E(B-V) > 0.15. Most importantly, we found a large dispersion of IGM transmission along the lines of sight towards distant galaxies with 68% of the distribution within 10 to 17% of the median value in δz = 0.5 bins, similar to what is found on the lines of sight towards QSOs. We demonstrate that taking this broad range of IGM transmission into account is important when selecting high-redshift galaxies based on their colour properties (e.g. LBG or photometric redshiftselection) because failing to do so causes a significant incompleteness in selecting high-redshift galaxy populations. We finally discuss the observed IGM properties and speculate that the broad

[Rheumatoid factor activity as a disturbing factor in the serological diagnosis of specific IgM antibodies].

PubMed

Lindenschmidt, E G

1984-04-01

Rheumatoid factors (RF) are autoantibodies mainly directed against autologous IgG. They belong at most to the IgM class antibodies. It is demonstrated at groups with unsolved hepatitis B, rubella, syphilis and toxoplasmose infection that RF do occur not rarely at these patients even without rheumatoid arthritis. This is probably due to stimulation by antigen-IgG-complexes. During serologic detection of specific IgM antibodies they present an antigen independent mu-specificity. So the test for specific IgM might even loose its diagnostic and possibly therapy indicating value. It is shown how the disturbance by RF can be calculated after adsorption with aggregated IgG. Also RF can be titrated by an enzyme immunoassay (ELISA). With IgG coated latex particles RF can be eliminated prior to the IgM-test. Solid phase techniques which are applied with enzyme-coupled antigen instead of marked anti-IgM cannot be disturbed by RF significantly.

Establishing tools for early diagnosis of congenital toxoplasmosis: Flow cytometric IgG avidity assay as a confirmatory test for neonatal screening.

PubMed

de Castro Zacche-Tonini, Aline; Fonseca, Giuliana Schmidt França; de Jesus, Laura Néspoli Nassar Pansini; Barros, Geisa Baptista; Coelho-Dos-Reis, Jordana Grazziela Alves; Béla, Samantha Ribeiro; Machado, Anderson Silva; Carneiro, Ana Carolina Aguiar Vasconcelos; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Ferro, Eloísa Amália Vieira; Mineo, José Roberto; Martins-Filho, Olindo Assis; Lemos, Elenice Moreira

2017-12-01

The aim of this study was to evaluate the performance of conventional serology (Q-Preven™ and ELFAVIDAS™) and flow cytometry-based serologic tools for early serologic diagnosis of congenital toxoplasmosis. The study groups included prospectively confirmed cases of congenital toxoplasmosis (TOXO=88) and age-matching non-infected controls (NI=15).The results demonstrated that all samples tested positive/indeterminate for anti-T. gondii IgM screening at birth using air-dried whole blood samples. Serum samples collected at 30-45days after birth tested positive for ELFAVIDAS™ IgG in both groups. While all NI tested negative for ELFAVIDAS™ IgM and IgA, only 78% and 36% of TOXO tested positive for IgM and IgA, respectively. Flow cytometry-based anti-T. gondii IgM, IgA and IgG reactivity displayed moderate performance with low sensitivity (47.6%, 72.6% and 75.0%, respectively). Regardless the remarkable specificity of IgG1, IgG2 and IgG3 subclasses for early diagnosis, weak or moderate specificity was observed (Se=73.9%, 60.2% and 83.0%, respectively). The analysis of IgG avidity indices (AI) demonstrated the highest performance among the flow cytometry-based methods (Se=96.6%; Sp=93.3%), underscoring the low avidity index (AI<60%) within TOXO (97.0%) in contrast with the high avidity index (AI>60%) in NI (93%). Analysis of anti-T. gondii IgG and IgG3 reactivity for mother:infant paired samples may represent a relevant complementary tests for early diagnosis. In conclusion, a feasible high-standard algorithm (Accuracy=97.1%) was proposed consisting of Q-Preven™ IgM screening at birth, followed by ELFAVIDAS™ IgM and flow cytometric IgG avidity analysis at 30-45days after birth as a high performance tool for early serological diagnosis of congenital toxoplasmosis. Copyright © 2017. Published by Elsevier B.V.

Hypogammaglobulinemia associated with accelerated catabolism of IgG secondary to its interaction with an IgG-reactive monoclonal IgM

PubMed Central

Waldmann, Thomas A.; Johnson, John S.; Talal, Norman

1971-01-01

Hypogammaglobulinemia due to a new pathophysiological mechanism was studied in a patient with Sjögren's syndrome, a monoclonal IgM and a mixed (IgM-IgG) cryoglobulinemia. The IgM (IgMdk) component of the cryogel possessed light chains of λ-type with highly restricted electrophoretic mobility analagous to those of a Waldenström's macroglobulin. IgMdk reacted specifically with native IgG, with IgG subclasses 1, 2, and 4, and with the Fc piece of IgG to form a cryogel. Serum concentrations of IgG 1, 2, and 4 were 10% of normal, whereas the IgG3 level was slightly increased and the IgM level was markedly increased. Viscosity and analytical ultracentrifugation studies with the purified mixed cryogel (IgM-LgG) indicated soluble complex formation over a temperature range (36-38°C) attainable in vivo. Immunoglobulin turnover studies revealed a markedly elevated rate of IgM synthesis with a normal survival of IgM, IgA, and IgE. IgG3, which failed to form complexes with IgMdk at body temperature, had a normal synthetic rate and survival. In contrast, the other IgG subclasses showed reduced synthesis and shortened survival. These studies are the first indicating a short survival of some IgG subclasses with a normal survival of another. The hypogammaglobulinemia appears to be due in part to a new mechanism of accelerated protein catabolism: The rapid elimination of IgG due to its interaction with an IgG-reactive monoclonal IgM. PMID:4993860

Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in newborn macaques

PubMed Central

Hessell, Ann J.; Jaworski, J. Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F.; Hammond, Katherine B.; Cheever, Tracy A.; Barnette, Philip T.; Legasse, Alfred W.; Planer, Shannon; Stanton, Jeffrey J.; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S.; Axthelm, Michael K.; Lewis, Anne; Hirsch, Vanessa M.; Graham, Barney S.; Mascola, John R.; Sacha, Jonah B.; Haigwood, Nancy L.

2016-01-01

Prevention of mother to child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested anti-HIV-1 human neutralizing monoclonal antibodies (NmAb) as post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with SHIVSF162P3. On days 1, 4, 7, and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h following administration. Replicating virus was found in multiple tissues by day 1 in animals without treatment. All NmAb-treated macaques were free of virus in blood and tissues at 6 months post-exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged following CD8+ T cell depletion. These results suggest early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

Serologic Tests of IgG and IgM Antibodies and IgG Avidity for Diagnosis of Ocular Toxoplasmosis.

PubMed

Rahimi-Esboei, Bahman; Zarei, Mohammad; Mohebali, Mehdi; Valian, Hossein Keshavarz; Shojaee, Saeedeh; Mahmoudzadeh, Raziyeh; Salabati, Mirataollah

2018-04-01

This prospective study was aimed to detect acute and chronic ocular toxoplasmosis by comparison of anti- Toxoplasma gondii IgM and IgG antibody levels and IgG avidity test. One hundred and seventeen patients with ocular toxoplasmosis (OT) who referred to the Farabi Eye Hospital, Tehran, Iran were included in this study. Of the patients, 77 cases were positive for anti- T. gondii IgG, and 8 cases were positive for anti- T. gondii IgM. IgG avidity test revealed 11, 4, and 102 cases were low, intermediate, and high, respectively, and 6.8% and 9.4% of cases were positive for IgM and IgG avidity tests, respectively ( P =0.632). Agreement (Kappa value) between paired tests IgG-IgM, IgG-IgG avidity, and IgM-IgG avidity was 0.080, 0.099, and 0.721, respectively ( P <0.05). This study showed that conventional serologic tests (IgM and IgG levels) and IgG avidity correlate well each other and can be used to differentiate recent infections from old OT. It seems that reactivated old infections rather than recently acquired infections are majority of Iranian OT patients.

HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies

PubMed Central

Richardson, Simone I.; Mabvakure, Batsirai; Mkhize, Nonhlanhla N.; Moore, Penny L.; Alter, Galit

2018-01-01

While the induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccination strategies, there is mounting evidence to suggest that antibodies with Fc effector function also contribute to protection against HIV infection. Here we investigated Fc effector functionality of HIV-specific IgG plasma antibodies over 3 years of infection in 23 individuals, 13 of whom developed bNAbs. Antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD), cellular cytotoxicity (ADCC) and cellular trogocytosis (ADCT) were detected in almost all individuals with levels of activity increasing over time. At 6 months post-infection, individuals with bNAbs had significantly higher levels of ADCD and ADCT that correlated with antibody binding to C1q and FcγRIIa respectively. In addition, antibodies from individuals with bNAbs showed more IgG subclass diversity to multiple HIV antigens which also correlated with Fc polyfunctionality. Germinal center activity represented by CXCL13 levels and expression of activation-induced cytidine deaminase (AID) was found to be associated with neutralization breadth, Fc polyfunctionality and IgG subclass diversity. Overall, multivariate analysis by random forest classification was able to group bNAb individuals with 85% sensitivity and 80% specificity based on the properties of their antibody Fc early in HIV infection. Thus, the Fc effector function profile predicted the development of neutralization breadth in this cohort, suggesting that intrinsic immune factors within the germinal center provide a mechanistic link between the Fc and Fab of HIV-specific antibodies. PMID:29630668

A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG.

PubMed

Rumfelt, L L; Avila, D; Diaz, M; Bartl, S; McKinney, E C; Flajnik, M F

2001-02-13

In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM(1gj), from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells ("germline-joined"). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H(1gj) in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H(1gj) chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM(1gj). Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system.

A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG

PubMed Central

Rumfelt, Lynn L.; Avila, David; Diaz, Marilyn; Bartl, Simona; McKinney, E. Churchill; Flajnik, Martin F.

2001-01-01

In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM1gj, from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells (“germline-joined”). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H1gj in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H1gj chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM1gj. Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system. PMID:11172027

Neutralizing Antibodies Induced by Gene-Based Hydrodynamic Injection Have a Therapeutic Effect in Lethal Influenza Infection

PubMed Central

Yamazaki, Tatsuya; Nagashima, Maria; Ninomiya, Daisuke; Ainai, Akira; Fujimoto, Akira; Ichimonji, Isao; Takagi, Hidekazu; Morita, Naoko; Murotani, Kenta; Hasegawa, Hideki; Chiba, Joe; Akashi-Takamura, Sachiko

2018-01-01

The influenza virus causes annual epidemics and occasional pandemics and is thus a major public health problem. Development of vaccines and antiviral drugs is essential for controlling influenza virus infection. We previously demonstrated the use of vectored immune-prophylaxis against influenza virus infection. We generated a plasmid encoding neutralizing IgG monoclonal antibodies (mAbs) against A/PR/8/34 influenza virus (IAV) hemagglutinin (HA). We then performed electroporation of the plasmid encoding neutralizing mAbs (EP) in mice muscles and succeeded in inducing the expression of neutralizing antibodies in mouse serum. This therapy has a prophylactic effect against lethal IAV infection in mice. In this study, we established a new method of passive immunotherapy after IAV infection. We performed hydrodynamic injection of the plasmid encoding neutralizing mAbs (HD) involving rapid injection of a large volume of plasmid-DNA solution into mice via the tail vein. HD could induce neutralizing antibodies in the serum and in several mucosal tissues more rapidly than in EP. We also showed that a single HD completely protected the mice even after infection with a lethal dose of IAV. We also established other isotypes of anti-HA antibody (IgA, IgM, IgD, and IgE) and showed that like anti-HA IgG, anti-HA IgA was also effective at combating upper respiratory tract IAV infection. Passive immunotherapy with HD could thus provide a new therapeutic strategy targeting influenza virus infection. PMID:29416543

Beacons into the Cosmic Dark Ages: Boosted Transmission of Lyα from UV Bright Galaxies at z ≳ 7

NASA Astrophysics Data System (ADS)

Mason, Charlotte A.; Treu, Tommaso; de Barros, Stephane; Dijkstra, Mark; Fontana, Adriano; Mesinger, Andrei; Pentericci, Laura; Trenti, Michele; Vanzella, Eros

2018-04-01

Recent detections of Lyman alpha (Lyα) emission from z > 7.5 galaxies were somewhat unexpected given a dearth of previous non-detections in this era when the intergalactic medium (IGM) is still highly neutral. But these detections were from UV bright galaxies, which preferentially live in overdensities that reionize early, and have significantly Doppler-shifted Lyα line profiles emerging from their interstellar media (ISM), making them less affected by the global IGM state. Using a combination of reionization simulations and empirical ISM models we show, as a result of these two effects, that UV bright galaxies in overdensities have >2× higher transmission through the z ∼ 7 IGM than typical field galaxies, and that this boosted transmission is enhanced as the neutral fraction increases. The boosted transmission is not sufficient to explain the observed high Lyα fraction of M UV ≲ ‑22 galaxies, suggesting that Lyα emitted by these galaxies must be stronger than expected due to enhanced production and/or selection effects. Despite the bias of UV bright galaxies to reside in overdensities we show Lyα observations of such galaxies can accurately measure the global neutral hydrogen fraction, particularly when Lyα from UV faint galaxies is extinguished, making them ideal candidates for spectroscopic follow-up into the cosmic Dark Ages.

Cross-reactions in IgM ELISA tests to Legionella pneumophila sg1 and Bordetella pertussis among children suspected of legionellosis; potential impact of vaccination against pertussis?

PubMed

Pancer, Katarzyna Wanda

2015-01-01

The objective of this study was preliminary evaluation of IgM cross-reaction in sera collected from children hospitalized because of suspected legionellosis. Sera with positive IgM results to L. pneumophila sgs1-7, B. pertussis or with simultaneous detection of IgM antibodies to L. pneumophila sgs1-7 and B. pertussis, or IgM to L. pneumophila sgs1-7 and M. pneumoniae in routine tests, were selected. In total, an adapted pre-absorption test was used for the serological confirmation of legionellosis in the sera of 19 children suspected of legionellosis, and also in 3 adult persons with confirmed Legionnaires' disease. Sera were pre-absorbed with antigens of L. pneumophila sg1, B. pertussis or both, and tested by ELISA tests. The reduction of IgM antibody level by pre-absorption with antigen/antigens was determined. Reduction of anti-Lpsgs1-7 IgM by pre-absorption with L.pneumophila sg1 antigen ranged from 1.5 to 80, and reduction of anti-Bp IgM by pre-absorption with B. pertussis ranged from 2.0 to 23.8. Reduction by both antigens varied depending on the age of the patients: among children <4 yrs.old, the reduction of anti-B. pertussis IgM by both antigens was higher than for B. pertussis antigen alone. Based on the high difference (≥ 2 times) between reduction by L.pneumophila sg1 and by B. pertussis antigen, legionellosis was confirmed in 8/19 children. The majority of them also indicated IgM positive/borderline results for B. pertussis or M.pneumoniae in routine ELISA tests. As a preliminary, we posed a hypothesis of a potential impact of an anti-pertussis vaccination on the results obtained in anti-L. pneumophila ELISA IgM tests among young children.

High seroprevalence of Mycoplasma pneumoniae IgM in acute Q fever by enzyme-linked immunosorbent assay (ELISA).

PubMed

Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Kuo, Li-Li; Lin, Hsi-Hsun; Chen, Yen-Hsu

2013-01-01

Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia.

High Seroprevalence of Mycoplasma pneumoniae IgM in Acute Q Fever by Enzyme-Linked Immunosorbent Assay (ELISA)

PubMed Central

Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Kuo, Li-Li; Lin, Hsi-Hsun; Chen, Yen-Hsu

2013-01-01

Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia. PMID:24147043

Protection Against Lipopolysaccharide-Induced Immunosuppression by IgG and IgM.

PubMed

Kyvelidou, Christiana; Sotiriou, Dimitris; Zerva, Ioanna; Athanassakis, Irene

2018-04-01

Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the potential role of IgG and IgM in reversing LPS endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2 μg/g LPS, which was tolerable by half of the manipulated animals. Such a protocol allowed longer survival, necessary in the prospect of therapeutic treatment application. This treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs; CD11b+Gr1+), CD25+ and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-α, IL-18, and C-reactive protein (CRP) in the serum. The applied LPS protocol did not alter serum procalcitonin levels. MDSCs isolated from the spleen of LPS-treated animals (LPS-MDSCs) decreased proliferation of naive T cells in coculture experiments. The application of IgG and IgM to the naive T cell/LPS-MDSCs cocultures significantly decreased CD25+, Foxp3+, and CD3z+ cells, indicating an anti-suppressive effect of immunoglobulins. The in vivo application of IgG and IgM significantly decreased the percent of CD11b+Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6, TNF-α, and CRP levels in the serum, allowing survival to all animals tested. In conclusion, these results reveal a novel mode of action of IgG/IgM in LPS endotoxemia, strengthening thus the use of immunoglobulin treatment is septic patients.

Human anti-HIV IgM detection by the OraQuick ADVANCE® Rapid HIV 1/2 Antibody Test.

PubMed

Guillon, Geraldine; Yearwood, Graham; Snipes, Casey; Boschi, Daniel; Reed, Michael R

2018-01-01

The Centers for Disease Control and Prevention (CDC) and many public health jurisdictions continue to advocate for the most sensitive rapid HIV test that is available. Currently, the recommendation is to utilize tests that can detect HIV infection biomarkers within 30 days of infection, when initial immune responses are mounted. The infected patient's IgM response is often used to detect acute infection within a 20-25 days window after infection. This requirement applies to lab-based testing with automated analyzers and rapid, point of care (POC) testing used for screening in a non-clinical setting. A recent study has demonstrated that POC tests using a Protein A-based detection system can detect samples with predominantly HIV-1 IgM reactivity (Moshgabadi et al., 2015). The OraQuick ADVANCE ® Rapid HIV-1/2 Antibody Test (OraQuick ADVANCE ®) also uses Protein A as the detection protein in the antibody-binding colloidal gold conjugate, so it is expected that the OraQuick ADVANCE ® Test will also detect samples with predominantly IgM reactivity. This report definitively demonstrates that the OraQuick ADVANCE ® Test can detect IgM antibodies during an acute infection window period of approximately 20-25 days after infection, and is therefore suitable for use in testing environments requiring adherence to current CDC recommendations.

Evaluation of a commercial rubella IgM assay for use on oral fluid samples for diagnosis and surveillance of congenital rubella syndrome and postnatal rubella.

PubMed

Vijaylakshmi, P; Muthukkaruppan, V R; Rajasundari, A; Korukluoglu, G; Nigatu, W; L A Warrener; Samuel, D; Brown, D W G

2006-12-01

Clinical diagnosis (surveillance) of rubella is unreliable and laboratory confirmation is essential. Detection of virus specific IgM in serum is the most commonly used method. However, the use of serum necessitates the drawing of blood, either through venipuncture or finger/heel prick, which can be difficult in young babies. Oral fluid samples have proved useful as an alternative, less invasive sample for virus specific IgM detection however until recently no commercial rubella IgM tests were available, restricting the usefulness of this approach. To evaluate the performance of the Microimmune Rubella IgM capture EIA using oral fluid samples from outbreaks as well as in cases of suspected congenital rubella syndrome (CRS). Paired serum and oral fluids were collected from cases during a rubella outbreak in three provinces in Turkey. Matched serum and oral fluid samples were collected from children with suspected CRS in an active surveillance programme at the Aravind Eye Hospital in South India. Serum samples were collected as part of the measles surveillance programme in Ethiopia. On serum samples the sensitivity and specificity of the Microimmune Rubella IgM capture EIA compared to Behring Enzygnost rubella IgM test was 96.9% (62/64; 95% CI 94.2-100%) and 100% (53/53; 95% CI 93.2-100%). On oral fluids compared to matched Behring results on serum the sensitivity was 95.5% (42/44; 95% CI 84.5-99.4%). The sensitivity and specificity of Microimmune Rubella IgM capture EIA on oral fluids from suspected CRS cases compared to serum results using Behring Enzygnost IgM assay was 100% (95% CI 84.5-100%) and 100% (95% CI 95.8-100.0%) respectively. Microimmune Rubella IgM capture EIA has adequate performance for diagnosis and surveillance of rubella in outbreak using either serum or oral fluid specimens.

False-positive IgM for CMV in pregnant women with autoimmune disease: a novel prognostic factor for poor pregnancy outcome.

PubMed

De Carolis, S; Santucci, S; Botta, A; Garofalo, S; Martino, C; Perrelli, A; Salvi, S; Degennaro, Va; de Belvis, Ag; Ferrazzani, S; Scambia, G

2010-06-01

Our aims were to assess the frequency of false-positive IgM antibodies for cytomegalovirus in pregnant women with autoimmune diseases and in healthy women (controls) and to determine their relationship with pregnancy outcome. Data from 133 pregnancies in 118 patients with autoimmune diseases and from 222 pregnancies in 198 controls were assessed. When positive IgM for cytomegalovirus was detected, IgG avidity, cytomegalovirus isolation and polymerase chain reaction for CMV-DNA in maternal urine and amniotic fluid samples were performed in order to identify primary infection or false positivity. A statistically significantly higher rate of false-positive IgM was found in pregnancies with autoimmune diseases (16.5%) in comparison with controls (0.9%). A worse pregnancy outcome was observed among patients with autoimmune disease and false cytomegalovirus IgM in comparison with those without false positivity: earlier week of delivery (p = 0.017), lower neonatal birth weight (p = 0.0004) and neonatal birth weight percentile (p = 0.002), higher rate of intrauterine growth restriction (p = 0.02) and babies weighing less than 2000 g (p = 0.025) were encountered. The presence of false cytomegalovirus IgM in patients with autoimmune diseases could be used as a novel prognostic index of poor pregnancy outcome: it may reflect a non-specific activation of the immune system that could negatively affect pregnancy outcome. Lupus (2010) 19, 844-849.

Heavy neutral leptons at FASER

NASA Astrophysics Data System (ADS)

Kling, Felix; Trojanowski, Sebastian

2018-05-01

We study the prospects for discovering heavy neutral leptons at Forward Search Experiment (FASER), the newly proposed detector at the LHC. Previous studies showed that a relatively small detector with ˜10 m length and ≲1 m2 cross sectional area can probe large unconstrained parts of parameter space for dark photons and dark Higgs bosons. In this work, we show that FASER will also be sensitive to heavy neutral leptons that have mixing angles with the active neutrinos that are up to an order of magnitude lower than current bounds. In particular, this is true for heavy neutral leptons produced dominantly in B -meson decays, in which case FASER's discovery potential is comparable to the proposed SHiP detector. We also illustrate how the search for heavy neutral leptons at FASER will be complementary to ongoing searches in high-pT experiments at the LHC and can shed light on the nature of dark matter and the process of baryogenesis in the early Universe.

Human monoclonal IgM with autoantibody activity against two gangliosides (GM1 and GD1b) in a patient with motor neuron syndrome.

PubMed

Jauberteau, M O; Gualde, N; Preud'Homme, J L; Rigaud, M; Gil, R; Vallat, J M; Baumann, N

1990-05-01

Small amounts of oligoclonal immunoglobulins were detected by Western blotting in the serum from a patient with motor neuron syndrome. The prominent one, a monoclonal IgM lambda, reacted strongly with the gangliosides GM1 and GD1b and more weakly with asialo GM1, as shown by immunoenzymatic staining of thin-layer chromatograms of gangliosides, ELISA on purified glycolipid coats and immunoadsorption with purified GM1. Affinity-chromatography with purified GM1 resulted in the purification of monoclonal IgM lambda. This purified IgM and its Fab fragments showed the same pattern of reactivity with gangliosides as that observed with whole serum. Such monoclonal IgM could be responsible for motor neuron diseases in some patients with overt or barely detectable monoclonal gammopathies.

Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide

PubMed Central

1993-01-01

The use of monoclonal antibodies (mAbs) directed to lipid A for the therapy of gram-negative sepsis is controversial. In an attempt to understand their biologic basis of action, we used a fluid-phase radioimmunoassay to measure binding between bacterial lipopolysaccharide (LPS) and two IgM mAbs directed to lipid A that are being evaluated for the treatment of gram-negative bacterial sepsis. Both antibodies bound 3H-LPS prepared from multiple strains of gram- negative bacteria when large excesses of antibody were used, although binding was modest and only slightly greater than control preparations. We also studied the ability of each anti-lipid A antibody to neutralize some of the biological effects of LPS in vitro. Despite large molar excesses, neither antibody neutralized LPS as assessed by the limulus lysate test, by a mitogenic assay for murine splenocytes, or by the production of cytokines interleukin (IL)-1, IL-6, or tumor necrosis factor from human monocytes in culture medium or in whole blood. Our experiments do not support the hypothesis that either of these anti- lipid A mAbs function by neutralizing the toxic effects of LPS. PMID:8418211

Binding neutral information to emotional contexts: Brain dynamics of long-term recognition memory.

PubMed

Ventura-Bort, Carlos; Löw, Andreas; Wendt, Julia; Moltó, Javier; Poy, Rosario; Dolcos, Florin; Hamm, Alfons O; Weymar, Mathias

2016-04-01

There is abundant evidence in memory research that emotional stimuli are better remembered than neutral stimuli. However, effects of an emotionally charged context on memory for associated neutral elements is also important, particularly in trauma and stress-related disorders, where strong memories are often activated by neutral cues due to their emotional associations. In the present study, we used event-related potentials (ERPs) to investigate long-term recognition memory (1-week delay) for neutral objects that had been paired with emotionally arousing or neutral scenes during encoding. Context effects were clearly evident in the ERPs: An early frontal ERP old/new difference (300-500 ms) was enhanced for objects encoded in unpleasant compared to pleasant and neutral contexts; and a late central-parietal old/new difference (400-700 ms) was observed for objects paired with both pleasant and unpleasant contexts but not for items paired with neutral backgrounds. Interestingly, objects encoded in emotional contexts (and novel objects) also prompted an enhanced frontal early (180-220 ms) positivity compared to objects paired with neutral scenes indicating early perceptual significance. The present data suggest that emotional--particularly unpleasant--backgrounds strengthen memory for items encountered within these contexts and engage automatic and explicit recognition processes. These results could help in understanding binding mechanisms involved in the activation of trauma-related memories by neutral cues.

Measurement of heterophil antibody and antibodies to EB viral capsid antigen IgG and IgM in suspected cases of infectious mononucleosis.

PubMed

Blake, J M; Edwards, J M; Fletcher, W; McSwiggan, D A; Pereira, M S

1976-09-01

The EBV IgG titres in acute and convalescent specimens from 97 cases of infectious mononucleosis were compared with titres from acute and convalescent sera from 96 students with illnesses resembling infectious mononucleosis but without heterophil antibody, EB IgM or EB IgG seroconversion; and also with titres from 91 healthy students known to have had EB IgG antibody for at least six months. These titres were related to the titre of the Research Standard A.66/235 for infectious mononucleosis serum prepared by the National Institute for Biological Standards and Control. Serial sera were tested for heterophil antibody and EBVCA specific IgG and IgM from 61 university students with infectious mononucleosis. The period of persistence of heterophil antibody and EBV IgM after illness was outlined from the results of the tests. Single sera from 406 patients in hospital or general practice sent to the diagnostic laboratory for heterophil antibody tests were also tested for EBV antibodies without prior knowledge of the heterophil antibody result. The close agreement between heterophil antibody and EBV IgM results is shown. False positive EB IgM results were correlated with the presence of rheumatoid factor.

Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.

PubMed

MacLeod, Daniel T; Choi, Nancy M; Briney, Bryan; Garces, Fernando; Ver, Lorena S; Landais, Elise; Murrell, Ben; Wrin, Terri; Kilembe, William; Liang, Chi-Hui; Ramos, Alejandra; Bian, Chaoran B; Wickramasinghe, Lalinda; Kong, Leopold; Eren, Kemal; Wu, Chung-Yi; Wong, Chi-Huey; Kosakovsky Pond, Sergei L; Wilson, Ian A; Burton, Dennis R; Poignard, Pascal

2016-05-17

The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ∼11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity

PubMed Central

Grönwall, Caroline; Clancy, Robert M.; Getu, Lelise; Lloyd, Katy A.; Siegel, Don L.; Reed, Joanne H.; Buyon, Jill; Silverman, Gregg J.

2016-01-01

At birth, the human immune system already contains substantial levels of polymeric IgM, with autoantibodies to neo-epitopes on apoptotic cells (ACs) that are proposed to play homeostatic and anti-inflammatory roles. Yet the biologic origins and developmental regulation of these naturally arising antibodies remain poorly understood. Herein, we report that levels of IgM-antibodies to malondialdehyde (MDA) protein adducts, a common type of in vivo generated oxidative stress-related neoepitope, directly correlate with the relative binding of neonatal-IgM to ACs. While levels of IgM to phosphorylcholine (PC), a natural antibody prevalent in adults, were relatively scant in cord blood, there was significantly greater relative representation of IgM anti-MDA antibodies in newborns compared to adults. To investigate the potential interrelationships between neonatal IgM with pathogenic IgG-autoantibodies, we studied 103 newborns born to autoimmune mothers with IgG anti-Ro (i.e., 70 with neonatal lupus and 33 without neonatal lupus). In these subjects the mean levels of IgM anti-Ro60 were significantly higher than in the newborns from non-autoimmune mothers. In contrast, levels of IgM anti-MDA in IgG anti-Ro exposed neonates were significantly lower than in neonates from non-autoimmune mothers. The presence or absence of neonatal lupus did not influence the total levels of IgM in the anti-Ro exposed newborns. Taken together, our studies provide evidence that the immune development of the natural IgM-repertoire may be affected, and become imprinted by, the transfer of maternal IgG into the fetus. PMID:27289167

Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity.

PubMed

Grönwall, Caroline; Clancy, Robert M; Getu, Lelise; Lloyd, Katy A; Siegel, Don L; Reed, Joanne H; Buyon, Jill P; Silverman, Gregg J

2016-09-01

At birth, the human immune system already contains substantial levels of polymeric IgM, that include autoantibodies to neo-epitopes on apoptotic cells (ACs) that are proposed to play homeostatic and anti-inflammatory roles. Yet the biologic origins and developmental regulation of these naturally arising antibodies remain poorly understood. Herein, we report that levels of IgM-antibodies to malondialdehyde (MDA) protein adducts, a common type of in vivo generated oxidative stress-related neoepitope, directly correlate with the relative binding of neonatal-IgM to ACs. Levels of IgM to phosphorylcholine (PC), a natural antibody prevalent in adults, were relatively scant in cord blood, while there was significantly greater relative representation of IgM anti-MDA antibodies in newborns compared to adults. To investigate the potential interrelationships between neonatal IgM with pathogenic IgG-autoantibodies, we studied 103 newborns born to autoimmune mothers with IgG anti-Ro (i.e., 70 with neonatal lupus and 33 without neonatal lupus). In these subjects the mean levels of IgM anti-Ro60 were significantly higher than in the newborns from non-autoimmune mothers. In contrast, levels of IgM anti-MDA in IgG anti-Ro exposed neonates were significantly lower than in neonates from non-autoimmune mothers. The presence or absence of neonatal lupus did not appear to influence the total levels of IgM in the anti-Ro exposed newborns. Taken together, our studies provide evidence that the immune development of the natural IgM-repertoire may be affected, and become imprinted by, the transfer of maternal IgG into the fetus. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of monoclonal antibodies against IgM of sea bass (Lateolabrax japonicus) and analysis of phagocytosis by mIgM+ lymphocytes.

PubMed

Yang, Shun; Tang, Xiaoqian; Sheng, Xiuzhen; Xing, Jing; Zhan, Wenbin

2018-07-01

B cells in some fish were recently found to have potent phagocytic activities. Sea bass (Lateolabrax japonicus) as an important economical marine fish species, it could be used as an appropriate model to study the functions of B cells in phagocytosis. In the paper, three positive hybridomas designated as 1E11, 2H4 and 3F3 secreting monoclonal antibodies (MAbs) against sea bass immunoglobulin M (IgM) were produced and used as research tools. Indirect enzyme-linked immunosorbent assay showed that all the three MAbs had a high binding capacity with sea bass serum IgM. Western blotting analysis showed that all the three MAbs were specific for the heavy chain of sea bass IgM. Indirect immunofluorescence assay (IFA) analysis suggested that both MAbs 1E11 and 2H4 could recognize membrane-bound IgM (mIgM) molecule of sea bass. Specificity analysis showed that three MAbs had no cross-reactions with other six teleosts IgMs. Flow cytometric analysis exhibited that the percentages of sea bass mIgM + lymphocytes in peripheral blood, spleen and pronephros were 25.6%, 21.1%, and 17.5%, respectively. Moreover, we found that the mIgM + lymphocytes of sea bass could phagocytose fluorescence microspheres and Lactococcus lactis, but lower phagocytosis rates of L. lactis was observed. These results demonstrated that the MAbs produced in this paper could be used as tools to study secretory IgM and mIgM + lymphocytes of sea bass, and mIgM + lymphocytes might also play an important role in innate immunity of sea bass. Copyright © 2018 Elsevier Ltd. All rights reserved.

Formalin-Inactivated Coxiella burnetii Phase I Vaccine-Induced Protection Depends on B Cells To Produce Protective IgM and IgG

PubMed Central

Peng, Ying; Schoenlaub, Laura; Elliott, Alexandra; Mitchell, William; Zhang, Yan

2013-01-01

To further understand the mechanisms of formalin-inactivated Coxiella burnetii phase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell, CD4+ T cell, or CD8+ T cell deficiency in mice significantly affects the ability of PIV to confer protection against a C. burnetii infection. Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels of protection in CD4+ T cell- or CD8+ T cell-deficient mice and partial protection in T cell-deficient mice but did not provide measurable protection in B cell-deficient mice. These results suggest that PIV-induced protection depends on B cells. In addition, anti-PI-specific IgM was the major detectable antibody (Ab) in immune sera from PIV-vaccinated CD4+ T cell-deficient mice, and passive transfer of immune sera from PIV-vaccinated CD4+ T cell-deficient mice conferred significant protection. These results suggest that T cell-independent anti-PI-specific IgM may contribute to PIV-induced protection. Our results also suggested that PIV-induced protection may not depend on complement activation and Fc receptor-mediated effector functions. Furthermore, our results demonstrated that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibit C. burnetii infection in vivo, but only IgM from PIV-vaccinated CD4+ T cell-deficient mouse sera inhibited C. burnetii infection. Collectively, these findings suggest that PIV-induced protection depends on B cells to produce protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play a critical role in PIV-induced protection against C. burnetii infection. PMID:23545296

Acute inflammatory neuropathy with monoclonal anti-GM2 IgM antibodies, IgM-κ paraprotein and additional autoimmune processes in association with a diffuse large B-cell non-Hodgkin's lymphoma.

PubMed

Milnik, Annette; Roggenbuck, Dirk; Conrad, Karsten; Bartels, Claudius

2013-01-21

Lymphoproliferative disorders are often associated with autoimmune processes preceding or following the occurrence of a lymphoma. Here, we describe a patient with a history of recurrent diffuse large B-cell non-Hodgkin's lymphoma who suffered from an acute inflammatory neuropathy with specific monoclonal anti-GM2 IgM antibodies and associated IgM-κ paraprotein. It was possible in this case to prove that both, anti-GM2 IgM antibodies and IgM-κ paraprotein, share the same binding characteristic. In addition, the patient possibly suffered from an immune thrombocytopenia and an early-stage bullous pemphigoid with anti-BP-230 IgG antibodies. Intravenous immunoglobulin and plasmapheresis alleviated the acute neuropathy and thrombocytopenia, while the bullous pemphigoid has been aggravated. In summary, the simultaneous occurrence of multiple autoimmune processes was a sign of a dysfunctional immune system preceding the relapse of a B-cell non-Hodgkin's lymphoma.

Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.

PubMed

Hessell, Ann J; Jaworski, J Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F; Hammond, Katherine B; Cheever, Tracy A; Barnette, Philip T; Legasse, Alfred W; Planer, Shannon; Stanton, Jeffrey J; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S; Axthelm, Michael K; Lewis, Anne; Hirsch, Vanessa M; Graham, Barney S; Mascola, John R; Sacha, Jonah B; Haigwood, Nancy L

2016-04-01

Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8(+) T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.

Human monoclonal IgM with autoantibody activity against two gangliosides (GM1 and GD1b) in a patient with motor neuron syndrome.

PubMed Central

Jauberteau, M O; Gualde, N; Preud'Homme, J L; Rigaud, M; Gil, R; Vallat, J M; Baumann, N

1990-01-01

Small amounts of oligoclonal immunoglobulins were detected by Western blotting in the serum from a patient with motor neuron syndrome. The prominent one, a monoclonal IgM lambda, reacted strongly with the gangliosides GM1 and GD1b and more weakly with asialo GM1, as shown by immunoenzymatic staining of thin-layer chromatograms of gangliosides, ELISA on purified glycolipid coats and immunoadsorption with purified GM1. Affinity-chromatography with purified GM1 resulted in the purification of monoclonal IgM lambda. This purified IgM and its Fab fragments showed the same pattern of reactivity with gangliosides as that observed with whole serum. Such monoclonal IgM could be responsible for motor neuron diseases in some patients with overt or barely detectable monoclonal gammopathies. Images Fig. 2 Fig. 3 PMID:2357844

Identical IgM antibodies recognizing a glycine-alanine epitope are induced during acute infection with Epstein-Barr virus and cytomegalovirus.

PubMed

Rhodes, G; Smith, R S; Rubin, R E; Vaughan, J; Horwitz, C A

1990-01-01

We studied antibody production in serial serum samples from patients with acute Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Sera were analyzed both by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide (P62) derived from the glycine-alanine repeating region of the Epstein-Barr nuclear antigen (EBNA-1) and by immunoblotting. In prior studies, we have shown that patients with acute EBV infection make IgM antibodies that react with this peptide, that recognize a viral-specific protein (EBNA-1), and that bind with a number of proteins present in uninfected cells; however, antibody binding to these autoantigens was inhibited by the peptide. IgG antibodies reactive with the peptide did not appear until months after the disease and were specific for the EBNA-1 protein. We now find that patients with acute CMV infection but not those with acute infections from a variety of other nonherpes organisms also produce IgM antibodies that recognize the EBV-derived peptide P62. These antibodies also appear to recognize the same cellular proteins as the EBV-induced IgM antibodies. The IgM antibodies appeared in all acutely infected CMV patients studied and occurred both in patients with previous EBV infections and in one patient studied who had not previously been exposed to EBV. It appears that infection with EBV or CMV can induce the synthesis of a very similar or identical set of IgM antibodies.

The Neutral Gas Properties of Extremely Isolated Early-type Galaxies. II.

NASA Astrophysics Data System (ADS)

Ashley, Trisha; Marcum, Pamela M.; Fanelli, Michael N.

2018-01-01

As part of an ongoing study of isolated early-type galaxies (IEG), we present neutral hydrogen (H I) observations of six IEGs obtained with the Green Bank Telescope. Two of the six IEGs presented in this paper have detected H I emission (KIG 870 and SDSS J102145.89+383249.8). KIG 870 has an H I emission profile that is strongly asymmetric about the optical systemic velocity with a redshifted double-horned profile and a blueshifted single-peaked component. KIG 870 is likely an advanced merger system. SDSS J102145.89+383249.8 has a Gaussian-like profile, indicating that the H I is not strongly rotating, is in a face-on disk, or is in a thick-disk similar to a dwarf galaxy. Our parent sample of H I observations is composed of 12 IEGs, 7 of which have now been detected in H I. The dwarf and luminous IEGs in our parent sample have median H I-mass-to-blue-luminosity ratios that are each three times larger than that of their non-cluster ETG counterparts, indicating that IEGs in our sample are significantly more gas rich than non-cluster ETGs.

[IgM class antibodies against hepatitis A viruses in the differentiation of viral hepatitis].

PubMed

Zivanović-Marinković, V; Stanković, D; Parabucki, S; Lazarov, A; Marinković, V; Krstić, L; Letica, Z

1982-01-01

The sera of 64 patients with acute viral hepatitis which were previously HbsAG negative by rPHA were tested by RIA methods for the presence of HBsAG and anti-HBc, by EIA method for HBc and anti-HBc and also by RIA method for the presence of IgM antibodies against hepatitis A virus. The pairs of sera were tested also for the presence of antibodies against cytomegalovirus and EB viruses. Of the total of 64 patients, markers of fresh HB viral infection were proved in 5 patients, sera positive to IgM antibodies to hepatitis A virus were found in 51 and no positive tests to any of the tested viruses were found in 8. The authors consider that they belonged to "non-A, non-B" viral hepatitis.

Surveying the CGM and IGM across 4 orders of magnitude in environmental density

NASA Astrophysics Data System (ADS)

Burchett, Joseph

2017-08-01

Environment matters when it comes to galaxy evolution, and the mechanisms driving this evolution are reflected in the diffuse gas residing within the large-scale structures enveloping the cosmic galaxy population. QSO absorption lines effectively probe the circumgalactic medium (CGM) and intragroup and intracluster media, and work thus far hints at profound environmental effects on the CGM. However, sample sizes remain small, and a unifying picture of the gas characteristics across diverse environments has yet to emerge. Within the Sloan Digital Sky Survey, we have identified a sample volume containing a remarkable diversity in large-scale environment with an array of voids, >10,000 groups, several filaments, and 5 clusters, including the Coma Supercluster and CfA Great Wall. Leveraging the Hubble Spectroscopic Legacy Archive (HSLA), we propose a study using >360 background QSOs probing this volume to study the effects of large-scale environment on CGM and intergalactic medium (IGM) gas. The z = 0.019-0.028 spectroscopic galaxy sample is uniformly complete to galaxies L > 0.03 L* and, with the HSLA, produces 200 galaxy/sightline pairs within 300-kpc impact parameters across a wide range of environmental densities and structures.Upon quantifying the galaxy environment and identifying/measuring the QSO absorption lines at z = 0.019-0.028, we will pursue the following primary science goals:1. Constrain the CGM/IGM physical conditions across four orders of magnitude in galaxy density2. Compare ionic abundances and ionization states in the CGM of galaxies in filaments vs. voids3. Statistically investigate the IGM/CGM gas properties from structure to structure

DC-SIGN–expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma

PubMed Central

Amin, Rada; Mourcin, Frédéric; Uhel, Fabrice; Pangault, Céline; Ruminy, Philippe; Dupré, Loic; Guirriec, Marion; Marchand, Tony; Fest, Thierry; Lamy, Thierry

2015-01-01

Follicular lymphoma (FL) results from the accumulation of malignant germinal center (GC) B cells leading to the development of an indolent and largely incurable disease. FL cells remain highly dependent on B-cell receptor (BCR) signaling and on a specific cell microenvironment, including T cells, macrophages, and stromal cells. Importantly, FL BCR is characterized by a selective pressure to retain surface immunoglobulin M (IgM) BCR despite an active class-switch recombination process, and by the introduction, in BCR variable regions, of N-glycosylation acceptor sites harboring unusual high-mannose oligosaccharides. However, the relevance of these 2 FL BCR features for lymphomagenesis remains unclear. In this study, we demonstrated that IgM+ FL B cells activated a stronger BCR signaling network than IgG+ FL B cells and normal GC B cells. BCR expression level and phosphatase activity could both contribute to such heterogeneity. Moreover, we underlined that a subset of IgM+ FL samples, displaying highly mannosylated BCR, efficiently bound dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN), which could in turn trigger delayed but long-lasting BCR aggregation and activation. Interestingly, DC-SIGN was found within the FL cell niche in situ. Finally, M2 macrophages induced a DC-SIGN–dependent adhesion of highly mannosylated IgM+ FL B cells and triggered BCR-associated kinase activation. Interestingly, pharmacologic BCR inhibitors abolished such crosstalk between macrophages and FL B cells. Altogether, our data support an important role for DC-SIGN–expressing infiltrating cells in the biology of FL and suggest that they could represent interesting therapeutic targets. PMID:26272216

Spinal cord dysmyelination caused by an anti-PLP IgM antibody: implications for the mechanism of CNS myelin formation

PubMed Central

Rosenbluth, J.; Schiff, R.

2008-01-01

Antiglycolipid IgM antibodies are known to induce formation of ‘wide-spaced’ or ‘expanded’ myelin, a distinctive form of dysmylination characterized by a repeat period ~2X or 3X normal, seen also in diseases including multiple sclerosis. To determine whether an antibody directed against a myelin protein would cause equivalent pathology, we implanted O10 hybridoma cells into the spinal cord of adult or juvenile rats. O10 produces an IgM directed against PLP, the major protein of CNS myelin. Subsequent examination of the cords showed focal demyelination and remyelination. In addition, however, some juvenile cords, but none of the adults, displayed wide-spaced myelin with lamellae separated by an extracellular material comprised of elements consistent with IgM molecules in appearance. Wide spacing tended to involve the outer layers of the sheath and in some cases alternated with normally spaced lamellae. A feature not seen previously consists of multiple expanded myelin lamellae in one sector of a sheath continuous with normally spaced lamellae in another, resulting in variation in sheath thickness around the axonal circumference. This uneven distribution of wide-spaced lamellae is most simply explained based on incorporation of IgM molecules into immature sheaths during myelin formation and implies a model of CNS myelinogenesis more complex than simple spiraling. The periaxonal space never displays widening of this kind, but the interface with adjacent myelin sheaths or oligodendrocytes may. Thus, wide spacing appears to require that IgM molecules bridge between two PLP-containing membranes and does not reflect the mere presence of immunoglobulin within the extracellular space. PMID:18951490

Inadequacy of IgM antibody tests for diagnosis of Rocky Mountain Spotted Fever.

PubMed

McQuiston, Jennifer H; Wiedeman, Caleb; Singleton, Joseph; Carpenter, L Rand; McElroy, Kristina; Mosites, Emily; Chung, Ida; Kato, Cecilia; Morris, Kevin; Moncayo, Abelardo C; Porter, Susan; Dunn, John

2014-10-01

Among 13 suspected Rocky Mountain spotted fever (RMSF) cases identified through an enhanced surveillance program in Tennessee, antibodies to Rickettsia rickettsii were detected in 10 (77%) patients using a standard indirect immunofluorescent antibody (IFA) assay. Immunoglobulin M (IgM) antibodies were observed for 6 of 13 patients (46%) without a corresponding development of IgG, and for 3 of 10 patients (30%) at least 1 year post-onset. However, recent infection with a spotted fever group rickettsiae could not be confirmed for any patient, based on a lack of rising antibody titers in properly timed acute and convalescent serologic specimens, and negative findings by polymerase chain reaction testing. Case definitions used in national surveillance programs lack specificity and may capture cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other spotted fever group rickettsiae in the United States. © The American Society of Tropical Medicine and Hygiene.

Inadequacy of IgM Antibody Tests for Diagnosis of Rocky Mountain Spotted Fever

PubMed Central

McQuiston, Jennifer H.; Wiedeman, Caleb; Singleton, Joseph; Carpenter, L. Rand; McElroy, Kristina; Mosites, Emily; Chung, Ida; Kato, Cecilia; Morris, Kevin; Moncayo, Abelardo C.; Porter, Susan; Dunn, John

2014-01-01

Among 13 suspected Rocky Mountain spotted fever (RMSF) cases identified through an enhanced surveillance program in Tennessee, antibodies to Rickettsia rickettsii were detected in 10 (77%) patients using a standard indirect immunofluorescent antibody (IFA) assay. Immunoglobulin M (IgM) antibodies were observed for 6 of 13 patients (46%) without a corresponding development of IgG, and for 3 of 10 patients (30%) at least 1 year post-onset. However, recent infection with a spotted fever group rickettsiae could not be confirmed for any patient, based on a lack of rising antibody titers in properly timed acute and convalescent serologic specimens, and negative findings by polymerase chain reaction testing. Case definitions used in national surveillance programs lack specificity and may capture cases that do not represent current rickettsial infections. Use of IgM antibodies should be reconsidered as a basis for diagnosis and public health reporting of RMSF and other spotted fever group rickettsiae in the United States. PMID:25092818

A survey of interstellar neutral potassium. I - Abundances and physical conditions in clouds toward 188 early-type stars

NASA Technical Reports Server (NTRS)

Chaffee, F. H., Jr.; White, R. E.

1982-01-01

Observations of interstellar absorption in the resonance doublet 7664, 7698 A of neutral potassium toward 188 early-type stars at a spectral resolution of 8 km/s are reported. The 7664 A line is successfully separated from nearly coincident telluric O2 absorption for all but a few of the 165 stars for which K I absorption is detected, making possible an abundance analysis by the doublet ratio method. The relationships between the potassium abundances and other atomic abundances, the abundance of molecular hydrogen, and interstellar reddening are investigated.

Hexons from adenovirus serotypes 5 and 48 differentially protect adenovirus vectors from neutralization by mouse and human serum

PubMed Central

Harmon, Andrew W.; Moitra, Rituparna; Xu, Zhili

2018-01-01

Adenovirus vectors are widely used in gene therapy clinical trials, and preclinical studies with these vectors are often conducted in mice. It is therefore critical to understand whether mouse studies adequately predict the behavior of adenovirus vectors in humans. The most commonly-used adenovirus vectors are derived from adenovirus serotype 5 (Ad5). The Ad5 hexon protein can bind coagulation factor X (FX), and binding of FX has a major impact on vector interactions with other blood proteins. In mouse serum, FX protects Ad5 vectors from neutralization by natural antibodies and complement. In the current study, we similarly find that human FX inhibits neutralization of Ad5 vectors by human serum, and this finding is consistent among individual human sera. We show that human IgM and human IgG can each induce complement-mediated neutralization when Ad5 vectors are not protected by FX. Although mouse and human serum had similar effects on Ad5 vectors, we found that this was not true for a chimeric Ad5 vector that incorporated hexon regions from adenovirus serotype 48. Interestingly, this hexon-chimeric vector was neutralized by human serum, but not by mouse serum. These findings indicate that studies in mouse serum accurately predict the behavior of Ad5 vectors in human serum, but mouse serum is not an accurate model system for all adenovirus vectors. PMID:29401488

Efficient cold outflows driven by cosmic rays in high-redshift galaxies and their global effects on the IGM

NASA Astrophysics Data System (ADS)

Samui, Saumyadip; Subramanian, Kandaswamy; Srianand, Raghunathan

2018-05-01

We present semi-analytical models of galactic outflows in high-redshift galaxies driven by both hot thermal gas and non-thermal cosmic rays. Thermal pressure alone may not sustain a large-scale outflow in low-mass galaxies (i.e. M ˜ 108 M⊙), in the presence of supernovae feedback with large mass loading. We show that inclusion of cosmic ray pressure allows outflow solutions even in these galaxies. In massive galaxies for the same energy efficiency, cosmic ray-driven winds can propagate to larger distances compared to pure thermally driven winds. On an average gas in the cosmic ray-driven winds has a lower temperature which could aid detecting it through absorption lines in the spectra of background sources. Using our constrained semi-analytical models of galaxy formation (that explains the observed ultraviolet luminosity functions of galaxies), we study the influence of cosmic ray-driven winds on the properties of the intergalactic medium (IGM) at different redshifts. In particular, we study the volume filling factor, average metallicity, cosmic ray and magnetic field energy densities for models invoking atomic cooled and molecular cooled haloes. We show that the cosmic rays in the IGM could have enough energy that can be transferred to the thermal gas in presence of magnetic fields to influence the thermal history of the IGM. The significant volume filling and resulting strength of IGM magnetic fields can also account for recent γ-ray observations of blazars.

Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM.

PubMed

Goetz, Lindsey; Laskowski, Jennifer; Renner, Brandon; Pickering, Matthew C; Kulik, Liudmila; Klawitter, Jelena; Stites, Erik; Christians, Uwe; van der Vlag, Johan; Ravichandran, Kameswaran; Holers, V Michael; Thurman, Joshua M

2018-05-01

Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM-mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild-type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Early activation of teleost B cells in response to rhabdovirus infection.

PubMed

Abós, Beatriz; Castro, Rosario; González Granja, Aitor; Havixbeck, Jeffrey J; Barreda, Daniel R; Tafalla, Carolina

2015-02-01

demonstrated that VHSV infection provoked immediate transcriptional effects on B cells, at least partially mediated by intracellular PRR signaling. VHSV also activated NF-κB and increased IgM(+) cell survival. Interestingly, VHSV activated B lymphocytes toward an antigen-presenting profile, suggesting an important role of IgM(+) cells in VHSV presentation. Our results provide a first description of the effects provoked by fish rhabdoviruses through their early interaction with teleost B cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

IgG and IgM autoantibody differences in discoid and systemic lupus patients.

PubMed

Chong, Benjamin F; Tseng, Lin-chiang; Lee, Thomas; Vasquez, Rebecca; Li, Quan Z; Zhang, Song; Karp, David R; Olsen, Nancy J; Mohan, Chandra

2012-12-01

Systemic lupus erythematosus (SLE) patients with discoid lupus erythematosus (DLE) were reported to have milder disease. To test this observation, we used sandwich arrays containing 98 autoantigens to compare autoantibody profiles of SLE subjects without DLE (DLE-SLE+) (N=9), SLE subjects with DLE (DLE+SLE+) (N=10), DLE subjects without SLE (DLE+SLE-) (N=11), and healthy controls (N=11). We validated differentially expressed autoantibodies using immunoassays in DLE-SLE+ (N=18), DLE+SLE+ (N=17), DLE+SLE- (N=23), and healthy subjects (N=22). Arrays showed 15 IgG autoantibodies (10 against nuclear antigens) and 4 IgM autoantibodies that were differentially expressed (q-value<0.05). DLE-SLE+ subjects had higher IgG autoantibodies against double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), double-stranded RNA (dsRNA), histone H2A and H2B, and SS-A (52 kDa) compared with all other groups including DLE+SLE+ subjects (P<0.05). Immunoassays measuring anti-dsDNA, -ssDNA, and -SS-A (52 kDa) IgG autoantibodies showed similar trends (P<0.05). Healthy and DLE+SLE- subjects expressed higher IgM autoantibodies against alpha beta crystallin, lipopolysaccharide, heat-shock cognate 70, and desmoglein-3 compared with DLE+SLE+ and DLE-SLE+ subjects. IgG:IgM ratios of autoantibodies against nuclear antigens progressively rose from healthy to DLE-SLE+ subjects. In conclusion, lower IgG autoantibodies against nuclear antigens in DLE+SLE+ versus DLE-SLE+ subjects suggest that DLE indicates lower disease severity. Higher IgM autoantibodies against selected antigens in healthy and DLE+SLE- subjects may be nonpathogenic.

Translocalized IgA mediates neutralization and stimulates innate immunity inside infected cells

PubMed Central

Bidgood, Susanna R.; Tam, Jerry C. H.; McEwan, William A.; Mallery, Donna L.; James, Leo C.

2014-01-01

IgA is the most prevalent antibody type on mucosal surfaces and the second most prevalent antibody in circulation, yet its role in immune defense is not fully understood. Here we show that IgA is carried inside cells during virus infection, where it activates intracellular virus neutralization and innate immune signaling. Cytosolic IgA–virion complexes colocalize with the high-affinity antibody receptor tripartite motif-containing protein 21 (TRIM21) and are positive for lysine-48 ubiquitin chains. IgA neutralizes adenovirus infection in a TRIM21- and proteasome-dependent manner in both human and mouse cells. Translocated IgA also potently activates NF-κB signaling pathways in cells expressing TRIM21, whereas viral infection in the absence of antibody or TRIM21 is undetected. TRIM21 recognizes an epitope in IgG Fc that is not conserved in IgA; however, fluorescence anisotropy experiments demonstrate that direct binding to IgA is maintained. We use molecular modeling to show that TRIM21 forms a nonspecific hydrophobic seal around a β-loop structure that is present in IgG, IgM, and IgA, explaining how TRIM21 achieves such remarkable broad antibody specificity. The findings demonstrate that the antiviral protection afforded by IgA extends to the intracellular cytosolic environment. PMID:25169018

Translocalized IgA mediates neutralization and stimulates innate immunity inside infected cells.

PubMed

Bidgood, Susanna R; Tam, Jerry C H; McEwan, William A; Mallery, Donna L; James, Leo C

2014-09-16

IgA is the most prevalent antibody type on mucosal surfaces and the second most prevalent antibody in circulation, yet its role in immune defense is not fully understood. Here we show that IgA is carried inside cells during virus infection, where it activates intracellular virus neutralization and innate immune signaling. Cytosolic IgA-virion complexes colocalize with the high-affinity antibody receptor tripartite motif-containing protein 21 (TRIM21) and are positive for lysine-48 ubiquitin chains. IgA neutralizes adenovirus infection in a TRIM21- and proteasome-dependent manner in both human and mouse cells. Translocated IgA also potently activates NF-κB signaling pathways in cells expressing TRIM21, whereas viral infection in the absence of antibody or TRIM21 is undetected. TRIM21 recognizes an epitope in IgG Fc that is not conserved in IgA; however, fluorescence anisotropy experiments demonstrate that direct binding to IgA is maintained. We use molecular modeling to show that TRIM21 forms a nonspecific hydrophobic seal around a β-loop structure that is present in IgG, IgM, and IgA, explaining how TRIM21 achieves such remarkable broad antibody specificity. The findings demonstrate that the antiviral protection afforded by IgA extends to the intracellular cytosolic environment.

Evaluation of Commercially Available Diagnostic Tests for the Detection of Dengue Virus NS1 Antigen and Anti-Dengue Virus IgM Antibody

PubMed Central

Hunsperger, Elizabeth A.; Yoksan, Sutee; Buchy, Philippe; Nguyen, Vinh Chau; Sekaran, Shamala Devi; Enria, Delia A.; Vazquez, Susana; Cartozian, Elizabeth; Pelegrino, Jose L.; Artsob, Harvey; Guzman, Maria G.; Olliaro, Piero; Zwang, Julien; Guillerm, Martine; Kliks, Susie; Halstead, Scott; Peeling, Rosanna W.; Margolis, Harold S.

2014-01-01

Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60–75% and specificity 71–80%; NS1 RDT sensitivity was 38–71% and specificity 76–80%; the IgM anti-DENV RDTs sensitivity was 30–96%, with a specificity of 86–92%, and IgM anti-DENV ELISA sensitivity was 96–98% and specificity 78–91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88–94%. PMID:25330157

Acne conglobata in a long-term survivor with trisomy 13, accompanied by selective IgM deficiency.

PubMed

Inoue, Chiyoko N; Tanaka, Yoshiko; Tabata, Nobuko

2017-05-07

Trisomy 13 (T13) is a congenital chromosomal disorder that is usually fatal within 2 years of birth, and only a few patients have been reported to reach adolescence. Here, we report a male long-term survivor of T13, currently 15 years of age, with a several-year history of extensive acne conglobata (AC) with abscesses on the face and neck. Methicillin-resistant Staphylococcus aureus was consistently isolated from the pustular lesions. Serum IgM levels were extremely low at 10 mg/dl. There were no abnormalities in neutrophil and total B cell number, or in serum IgA and IgG levels. Increased CD8+ T cell counts and inversion of the CD4/CD8 ratio were observed repeatedly. The patient's clinical features and laboratory data support a diagnosis of selective IgM deficiency (SIgMD) with concurrent AC. Immunoglobulin replacement therapy elevated serum IgM levels to the normal range and reduced the severity of AC. We suggest that T13 may represent a syndromic disorder associated with multiple organ malformation and a risk of developing immunodeficiency involving SIgMD. Because pediatric SIgMD is rare and an immunological abnormality in T13 patients has not previously been reported, we describe the patient's clinical course. © 2017 Wiley Periodicals, Inc.

Experiences Integrating Transmission and Distribution Simulations for DERs with the Integrated Grid Modeling System (IGMS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmintier, Bryan; Hale, Elaine; Hodge, Bri-Mathias

2016-08-11

This paper discusses the development of, approaches for, experiences with, and some results from a large-scale, high-performance-computer-based (HPC-based) co-simulation of electric power transmission and distribution systems using the Integrated Grid Modeling System (IGMS). IGMS was developed at the National Renewable Energy Laboratory (NREL) as a novel Independent System Operator (ISO)-to-appliance scale electric power system modeling platform that combines off-the-shelf tools to simultaneously model 100s to 1000s of distribution systems in co-simulation with detailed ISO markets, transmission power flows, and AGC-level reserve deployment. Lessons learned from the co-simulation architecture development are shared, along with a case study that explores the reactivemore » power impacts of PV inverter voltage support on the bulk power system.« less

IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate

PubMed Central

Noviski, Mark; Mueller, James L; Satterthwaite, Anne; Garrett-Sinha, Lee Ann; Brombacher, Frank

2018-01-01

Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions. IgM but not IgD is downregulated on autoreactive B cells. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. IgD-only Lyn−/− B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1+ SLPC responses to T-dependent immunization. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells. PMID:29521626

Early diagnosis of dengue in travelers: comparison of a novel real-time RT-PCR, NS1 antigen detection and serology.

PubMed

Huhtamo, Eili; Hasu, Essi; Uzcátegui, Nathalie Y; Erra, Elina; Nikkari, Simo; Kantele, Anu; Vapalahti, Olli; Piiparinen, Heli

2010-01-01

The increased traveling to dengue endemic regions and the numerous epidemics have led to a rise in imported dengue. The laboratory diagnosis of acute dengue requires several types of tests and often paired samples are needed for obtaining reliable results. Although several diagnostic methods are available, proper comparative data on their performance are lacking. To compare the performance of novel methods including a novel pan-DENV real-time RT-PCR and a commercially available NS1 capture-EIA in regard to IgM detection for optimizing the early diagnosis of DENV in travelers. A panel of 99 selected early phase serum samples of dengue patients was studied by real-time RT-PCR, NS1 antigen ELISA, IgM-EIA, IgG-IFA and cell culture virus isolation. The novel real-time RT-PCR was shown specific and sensitive for detection of DENV-1-4 RNA and suitable for diagnostic use. The diagnostic rate using combination of RNA and IgM detection was 99% and using NS1 and IgM detection 95.9%. The results of RNA and NS1 antigen detection disagreed in 15.5% of samples that had only RNA or NS1 antigen detected. The diagnostic rates of early samples are higher when either RNA or NS1 antigen detection is combined with IgM detection. Besides the differences in the RNA and NS1 detection assays, the observed discrepancy of results could suggest individual variation or differences in timing of these markers in patient serum. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Production and characterization of monoclonal antibodies to IgM of Pacific herring (Clupea pallasii)

USGS Publications Warehouse

Purcell, Maureen K.; Bromage, Erin S.; Silva, Jessica; Hansen, John D.; Badil, Samantha M.; Woodson, James C.; Hershberger, Paul K.

2012-01-01

Pacific herring (Clupea pallasii) have a central role in the North Pacific ecosystem as a forage fish species and are natural reservoirs of several important finfish pathogens, including Viral hemorrhagic septicemia virus (VHSV). Here, we report the identification of the gene encoding the immunoglobulin mu (IgM) heavy chain, as well as the development and characterization of monoclonal antibodies (MAbs) that specifically react with Pacific herring IgM. Pacific herring immunoglobulin was purified and consisted of heavy and light chains of approximately 80 and 25 kDa. Three hybridoma clones were initially identified by ELISA as reactive with purified immunoglobulin but only one clone was able to detect an 80 kDa protein in Pacific and Atlantic herring (Clupea harengus) whole plasma by denaturing western blot. However, all three MAbs were able to precipitate an 80 kDa protein from Pacific herring and LCMS sequencing of peptide fragments derived from this protein matched the predicted amino acid sequence of the cloned, heavy chain gene. In addition, two of the MAbs stained cells within the putative lymphocyte gates for the spleen, anterior kidney and posterior kidney but were not reactive for myeloid/granulocyte gates, which is consistent with these MAbs reacting with surface IgM+ B-cells. To our knowledge, this is the first report of IgM-related gene sequences and anti-IgM monoclonal antibodies from any member of the family Clupeidae. The antibodies produced in this study are critical for achieving our long-term goal of conducting serological surveillance to assess pathogen exposure in natural populations of Pacific herring.

The epoch of cosmic heating by early sources of X-rays

NASA Astrophysics Data System (ADS)

Eide, Marius B.; Graziani, Luca; Ciardi, Benedetta; Feng, Yu; Kakiichi, Koki; Di Matteo, Tiziana

2018-05-01

Observations of the 21 cm line from neutral hydrogen indicate that an epoch of heating (EoH) might have preceded the later epoch of reionization. Here we study the effects on the ionization state and the thermal history of the intergalactic medium (IGM) during the EoH induced by different assumptions on ionizing sources in the high-redshift Universe: (i) stars; (ii) X-ray binaries (XRBs); (iii) thermal bremsstrahlung of the hot interstellar medium (ISM); and (iv) accreting nuclear black holes (BHs). To this aim, we post-process outputs from the (100 h-1 comoving Mpc)3 hydrodynamical simulation MassiveBlack-II with the cosmological 3D radiative transfer code CRASH, which follows the propagation of ultraviolet and X-ray photons, computing the thermal and ionization state of hydrogen and helium through the EoH. We find that stars determine the fully ionized morphology of the IGM, while the spectrally hard XRBs pave way for efficient subsequent heating and ionization by the spectrally softer ISM. With the seeding prescription in MassiveBlack-II, BHs do not contribute significantly to either ionization or heating. With only stars, most of the IGM remains in a cold state (with a median T = 11 K at z = 10), however, the presence of more energetic sources raises the temperature of regions around the brightest and more clustered sources above that of the cosmic microwave background, opening the possibility to observing the 21 cm signal in emission.

Apparent hyperthyroidism caused by biotin-like interference from IgM anti-streptavidin antibodies.

PubMed

Lam, Leo; Bagg, Warwick; Smith, Geoff; Chiu, Weldon; Middleditch, Martin James; Lim, Julie Ching-Hsia; Kyle, Campbell Vance

2018-05-29

Exclusion of analytical interference is important when there is discrepancy between clinical and laboratory findings. However, interferences on immunoassays are often mistaken as isolated laboratory artefacts. We characterized and report the mechanism of a rare cause of interference in two patients that caused erroneous thyroid function tests, and also affects many other biotin dependent immunoassays. Patient 1 was a 77 y female with worsening fatigue while taking carbimazole over several years. Her thyroid function tests however, were not suggestive of hypothyroidism. Patient 2 was a 25 y female also prescribed carbimazole for apparent primary hyperthyroidism. Despite an elevated FT4, the lowest TSH on record was 0.17mIU/L. In both cases, thyroid function tests performed by an alternative method were markedly different. Further characterization of both patients' serum demonstrated analytical interference on many immunoassays using the biotin-streptavidin interaction. Sandwich assays (e.g. TSH, FSH, TNT, beta-HCG) were falsely low, while competitive assays (e.g. FT4, FT3, TBII) were falsely high. Pre-incubation of serum with streptavidin microparticles removed the analytical interference, initially suggesting the cause of interference was biotin, however, neither patient had been taking biotin. Instead, a ~100kDa IgM immunoglobulin with high affinity to streptavidin was isolated from each patient's serum. The findings confirm IgM anti-streptavidin antibodies as the cause of analytical interference. We describe two patients with apparent hyperthyroidism as a result of analytical interference caused by IgM anti-streptavidin antibodies. Analytical interference identified on one immunoassay should raise the possibility of other affected results. Characterization of interference may help to identify other potentially affected immunoassays. In the case of anti-streptavidin antibodies, the pattern of interference mimics that due to biotin ingestion; however, the degree of

Unveiling the nature of dark matter with high redshift 21 cm line experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evoli, C.; Mesinger, A.; Ferrara, A., E-mail: carmelo.evoli@desy.de, E-mail: andrei.mesinger@sns.it, E-mail: andrea.ferrara@sns.it

2014-11-01

Observations of the redshifted 21 cm line from neutral hydrogen will open a new window on the early Universe. By influencing the thermal and ionization history of the intergalactic medium (IGM), annihilating dark matter (DM) can leave a detectable imprint in the 21 cm signal. Building on the publicly available 21cmFAST code, we compute the 21 cm signal for a 10 GeV WIMP DM candidate. The most pronounced role of DM annihilations is in heating the IGM earlier and more uniformly than astrophysical sources of X-rays. This leaves several unambiguous, qualitative signatures in the redshift evolution of the large-scale (k ≅ 0.1more » Mpc{sup -1}) 21 cm power amplitude: (i) the local maximum (peak) associated with IGM heating can be lower than the other maxima; (ii) the heating peak can occur while the IGM is in emission against the cosmic microwave background (CMB); (iii) there can be a dramatic drop in power (a global minimum) corresponding to the epoch when the IGM temperature is comparable to the CMB temperature. These signatures are robust to astrophysical uncertainties, and will be easily detectable with second generation interferometers. We also briefly show that decaying warm dark matter has a negligible role in heating the IGM.« less

The important role of early diagnosis and preventive management during a large-scale outbreak of hepatitis A in Thailand

PubMed Central

Poovorawan, Kittiyod; Chattakul, Paiboon; Chattakul, Sirirat; Thongmee, Thanunrat; Theamboonlers, Apiradee; Komolmit, Piyawat; Poovorawan, Yong

2013-01-01

Introduction Acute hepatitis A is a worldwide public health problem especially in developing countries. Recently, a large, community-wide outbreak of hepatitis A occurred in the northeast part of Thailand. Methods Demographic and clinical data as well as blood samples were collected and analyzed from patients with acute hepatitis who attended the Buengkan Provincial Hospital from June to September 2012. About 1619 patients with clinical symptoms of hepatitis A visited the hospital during the outbreak which manifested in three waves. Blood samples were collected from 205 patients. Results One hundred and seventy eight patients had hepatitis A confirmed by the presence of anti-hepatitis A virus (HAV) IgM and/or HAV-RNA. The sensitivities for anti-HAV IgM and HAV-RNA were 95.5% (170/178) and 61.8% (110/178), respectively. When HAV-RNA was combined with anti-HAV IgM test, this increased the diagnostic yield by 7.2% (8/111) in the early phase of the acute infection (less than 5 days). Investigation of the molecular structure of the detected viruses indicated that all of the infections were caused by HAV genotype IA. There were no fatalities from this outbreak. Rapid detection, health education, sanitation campaigns, and vaccination offered on a voluntary basis have steadily reduced the number of infected patients and stopped the outbreak. Conclusion Occasionally a large-scale outbreak of HAV genotype IA can occur. A combination of HAV-RNA and anti-HAV IgM tests can increase the diagnostic yield during the early phase of the acute infection. Early diagnosis and preventive management campaigns can slow down and stop the outbreak. PMID:24392680

Development and Characterization of Monoclonal Antibodies to Yellow Fever Virus and Application in Antigen Detection and IgM Capture Enzyme-Linked Immunosorbent Assay

PubMed Central

Adungo, Ferdinard; Kamau, David; Inoue, Shingo; Hayasaka, Daisuke; Posadas-Herrera, Guillermo; Sang, Rosemary; Mwau, Matilu

2016-01-01

Yellow fever (YF) is an acute hemorrhagic viral infection transmitted by mosquitoes in Africa and South America. The major challenge in YF disease detection and confirmation of outbreaks in Africa is the limited availability of reference laboratories and the persistent lack of access to diagnostic tests. We used wild-type YF virus sequences to generate recombinant envelope protein in an Escherichia coli expression system. Both the recombinant protein and sucrose gradient-purified YF vaccine virus 17D (YF-17D) were used to immunize BALB/c mice to generate monoclonal antibodies (MAbs). Eight MAbs were established and systematically characterized by indirect enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and immunofluorescence assay (IFA). The established MAbs showed strong reactivity with wild-type YF virus and recombinant protein with no detectable cross-reactivity to dengue virus or Japanese encephalitis virus. Epitope mapping showed strong binding of three MAbs to amino acid positions 1 to 51, while two MAbs mapped to amino acid positions 52 to 135 of the envelope protein. The remaining three MAbs did not show reactivity to envelope fragments. The established MAbs exert no neutralization against wild-type YF and 17D viruses (titer of <10 for both strains). The applicability of MAbs 8H3 and 3F4 was further evaluated using IgM capture ELISA. A total of 49 serum samples were analyzed, among which 12 positive patient and vaccinee samples were correctly identified. Using serum samples that were 2-fold serially diluted, the IgM capture ELISA was able to detect all YF-positive samples. Furthermore, MAb-based antigen detection ELISA enabled the detection of virus in culture supernatants containing titers of about 1,000 focus-forming units. PMID:27307452

Differentiation of Strains of Infectious Bovine Rhinotracheitis Virus by Neutralization Kinetics with Late 19S Rabbit Antibodies

PubMed Central

Potgieter, Leon N. D.; Maré, C. John

1974-01-01

Two vaccine, two respiratory (infectious bovine rhinotracheitis [IBR]), and two genital (infectious pustular vulvovaginitis [IPV]) strains of infectious bovine rhinotracheitis virus were compared by neutralization kinetics using late 19S antibody (AB). The two vaccine strains were indistinguishable from one another, but were neutralized far more rapidly than the other four strains when either anti-IBR or anti-IPV 19S AB was used. The two IPV strains were indistinguishable from one another, but were neutralized significantly more rapidly than the two IBR strains when anti-IBR 19S AB was used. The 2 IBR strains were neutralized at a similar rate with the latter globulin preparation. Almost identical results were obtained with anti-IPV 19S AB, except that one IPV strain was neutralized at a rate similar to the IBR strains. However, when early and late rabbit 7S AB were used, IBR strains could not be distinguished from IPV strains by neutralization kinetics. Preliminary experiments indicated that both early and late 19S rabbit antibodies neutralized the homologous strain more rapidly than the heterologous strain, but the difference was more noticeable with late 19S AB. It was also determined that neutralization of IBR-IPV virus by specific early and late 19S rabbit AB and early 7S rabbit AB was markedly enhanced by guinea pig complement. Neutralization of this virus by late 7S AB, however, was only slightly enhanced by complement. These results suggest that vaccine strains of IBR-IPV virus may be distinguished by neutralization kinetics with late 19S rabbit AB, and that genital and respiratory strains may possibly also be distinguishable with some 19S AB preparations. Images PMID:4372173

Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice

PubMed Central

Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A

2015-01-01

The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγnull mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. PMID:25125497

IgM antibodies to oxidized phosphatidylserine as protection markers in cardiovascular disease among 60-year olds

PubMed Central

Frostegård, Johan; Su, Jun; Sing, Sudhir; Hua, Xiang; Vikström, Max; Leander, Karin; Gigante, Bruna; de Faire, Ulf; Frostegård, Anna G.

2017-01-01

Objective Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). Methods Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected. Odds ratios (OR) with 95% intervals (CI) were calculated by conditional logistic regression. IgM anti-OxPS was measured by ELISA. Phagocytosis of apoptotic Jurkat-cells by macrophages was studied by flow cytometry. Results Anti-OxPS levels were lower among cases (median (interquartile range): 80.7 (60.9–101.0 vs. 84.6 (65.8–109.6); p = 0.047); among men (76.6 (55.8–99.2) vs. 82.0 (63.1–105.1); p = 0.022) and among women 89.6 (72.3–110.1) vs. 89.8 (69.9–114.4); p = 0.79). After adjustment for smoking, BMI, diabetes mellitus type II, hypercholesterolaemia and hypertension, and dividing into quartiles, using the highest quartile (quartile 4) as reference, quartile 3 was associated with a OR of 1.74 (CI 1.08–2.81). Quartiles 2 and 1 had similar associations, the later reaching statistical significance. Among men associations were stronger whereas no significant associations were observed in women. The OR of MI/angina comparing quartile 3 with quartile 4 was 2.31 (CI 1.30–4.11). The OR for quartile 2 and 1, respectively, were similar as for quartile 3. Total IgM increased uptake of apoptotic cells, which was reversed if incubated with OxPS. Conclusions IgM anti-OxPS is a novel potential protection marker for CVD, in particular in men. Increased phagocytosis of dying/dead cells could be one potential underlying mechanism. PMID:28430795

Modulation of thymus-leukemia antigens on mouse leukemia cells induced by IgG, but not IgM, antibody.

PubMed

Stackpole, C W

1980-04-01

Exposure of mouse leukemia cells bearing thymus-leukemia (TL) surface antigens to whole TL alloantiserum has previously been shown to desensitize the cells to subsequent lysis by guinea pig complement (C) and fresh antiserum (antigenic modulation) and to correlate with the ability of cells to escape immune destruction in mice immunized against TL antigens. Tested in vitro, IgG of TL.1,2,3,5 antiserum modulated RADA1 leukemia cells (TL.1,2,3,5) completely within 2 hours at 37 degrees C when fully sensitizing amounts were used, with normal mouse serum as a source of C3. Similar results were obtained with IgG1, IgG2a, and IgG2b fractions of TL antiserum. An IgG2a monoclonal TL.3 antibody also completely modulated TL.3 antigens and partially modulated all antigens detected with TL.1,2,3,5 antiserum. IgM anti-TL.1,2,3,5 failed to modulate RADA1 cells even after 6 hours in vitro when fully sensitizing amounts of antibody were used. An IgM monoclonal TL antibody also failed to induce modulation. Modulation did occur on cells incubated with fully sensitizing amounts of IgG and IgM TL.1,2,3,5 antibody simultaneously, and nearly all cell-bound immunoglobulins were IgG. In mice passively immunized with IgG TL antibody, RADA1 cells modulated completely within 24 hours, whereas no modulation occurred during 4 days in mice immunized with IgM antibody. However, in both instances, tumor cells grew actively, which indicated that tumor escape did not depend on achievement of a modulated state.

A flow cytometry-based strategy to identify and express IgM from VH1-69+ clonal peripheral B cells.

PubMed

Charles, Edgar D; Orloff, Michael I M; Dustin, Lynn B

2011-01-05

Pathologic rheumatoid factor (RF) levels are hallmarks of several human diseases. Production of monoclonal RF in vitro is essential for studies of the antigenic specificities of RF, as well as for a dissection of the mechanisms of aberrant RF+ B cell activation. We have expanded upon previous methods to develop a flow cytometry-based method to efficiently clone monoclonal antibodies (mAbs) from humans with expansions of RF-like, immunoglobulin heavy chain variable region (IgVH) 1-69 gene segment-containing B cells. The cloned variable regions are expressed as IgM and produced during culture at concentrations between 5 and 20 μg/ml. Using this system, we show that clonal Igs from patients with HCV-related mixed cryoglobulinemia, when expressed as IgM, have RF activity. We anticipate that this system will be useful for the cloning and expression of mAbs partially encoded by VH1-69 and for determination of the reactivity patterns of polyspecific, low-affinity IgMs of human pathogenic importance. Copyright © 2010 Elsevier B.V. All rights reserved.

Plasma exchanges for severe acute neurological deterioration in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) neuropathy.

PubMed

Baron, M; Lozeron, P; Harel, S; Bengoufa, D; Vignon, M; Asli, B; Malphettes, M; Parquet, N; Brignier, A; Fermand, J P; Kubis, N; Arnulf, Bertrand

2017-06-01

Monoclonal IgM anti-myelin-associated glycoprotein (MAG) antibody-related peripheral neuropathy (anti-MAG neuropathy) is predominantly a demyelinating sensory neuropathy with ataxia and distal paresthesia. The clinical course of anti-MAG neuropathy is usually slowly progressive making difficult the identification of clear criteria to start a specific treatment. Although no consensus treatment is yet available, a rituximab-based regimen targeting the B-cell clone producing the monoclonal IgM may be proposed, alone or in combination with alkylating agents or purine analogs. However, in some rare cases, an acute and severe neurological deterioration can occur in few days leading to a rapid loss of autonomy. In these cases, a treatment rapidly removing the monoclonal IgM from the circulation might be useful before initiating a specific therapy. We report successful treatment with plasma exchanges (PE) in four patients presenting with acute neurological deterioration. PE allowed a dramatic and rapid neurological improvement in all patients. PE are safe and may be useful at the initial management of these cases of anti-MAG neuropathy.

[The Quality Analysis of National Supervising Sampling for Rubella Virus IgM Diagnostic Kits in 2014].

PubMed

Yu, Tina; Qu, Shoufang; Zhang, Xiaoyan; Sun, Nan; Gao, Shangxian; Li, Haining; Huang, Jie

2015-07-01

To evaluate the quality status of rubella virus IgM diagnostic kits by national supervising sampling. Using legal inspection combining with exploratory study, the positive and negative coincidence rate, detection limit and repeatability of kits were verified. The results showed that 15 of 16 batches of kits were qualified using legal inspection, and the passing rate was 93.8%. The unqualified item was negative coincidence rate. In exploratory study, only 11 batches (68.8%) complied with industry standard. The unqualified items were negative coincidence rate, detection limit and repeatability. At present, rubella virus IgM diagnostic Kits have some quality problems in the market. It is recommended that we adopt industry standard and national reference panel in the registration inspection for the future, which will prompt enterprises to improve quality.

A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid.

PubMed

Warrener, Lenesha; Slibinskas, Rimantas; Chua, Kaw Bing; Nigatu, Wondatir; Brown, Kevin E; Sasnauskas, Kestutis; Samuel, Dhanraj; Brown, David

2011-09-01

To evaluate the performance of a newly developed point-of-care test (POCT) for the detection of measles-specific IgM antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used POCT strips. The POCT was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in Ethiopia, Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were positive for both. Also tested were 282 oral fluid specimens from the measles, mumps and rubella (MMR) surveillance programme of the United Kingdom of Great Britain and Northern Ireland. The Microimmune measles IgM capture enzyme immunoassay was the gold standard for comparison. A panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N) genes could be amplified by polymerase chain reaction directly from used POCT strips. With serum POCT showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N genes were reliably detected in POCT strips and the N genes could be sequenced for genotyping. Measles virus genes could be recovered from POCT strips after storage for 5 weeks at 20-25 °C. The POCT has the sensitivity and specificity required of a field-based test for measles diagnosis. However, its role in global measles control programmes requires further evaluation.

Le profil clinique et immunologique de 15 patients Marocains atteints de syndrome hyper IgM

PubMed Central

Ouair, Hind; Benhsaien, Ibtihal; Jeddane, Leila; El Bakkouri, Jalila; Elhafidi, Naima; Rada, Noureddine; Najib, Jilali; Ailal, Fatima; Alj, Hanane Salih; Bousfiha, Ahmed Aziz

2017-01-01

Le Syndrome hyper IgM est un déficit immunitaire héréditaire bien connu, décrit pour la première fois en 1961. Il est causé par un défaut au niveau des lymphocytes B, caractérisé par un taux sérique normal ou élevé des IgM et un taux bas ou nul des IgG, IgA, IgE résultant d'une déficience de la commutation isotypique. Ses manifestations cliniques sont dominées par les infections à répétition, surtout du tube digestif, de la sphère ORL et des poumons. Le syndrome est causé par un défaut de commutation de classe d'immunoglobuline dans les cellules B, et une diminution de la capacité des monocytes à induire la prolifération des lymphocytes T. Le résultat net de tous ces défauts est la susceptibilité accrue aux infections opportunistes à Pneumocystis jiroveci, Cryptosporidium spp et d'autres organismes intracellulaires, ainsi qu'une fréquence élevée d'infections bactériennes et virales. L'intérêt de ce projet est d'illustrer l'importance de la compréhension des mécanismes physiopathologiques associés à cette susceptibilité accrue aux infections, ce qui permettra une meilleure prise en charge diagnostique et thérapeutique des patients atteint du Syndrome hyper IgM (SHIM). PMID:28690727

Evaluation of Antigen-Specific IgM and IgG Production during an In Vitro Peripheral Blood Mononuclear Cell Culture Assay.

PubMed

Matsuda, Yoshiko; Imamura, Ryoichi; Takahara, Shiro

2017-01-01

The recent attention given to diseases associated with memory B-cell (mBC)-produced antibodies (Abs) suggests the need for a similar in vitro assay to evaluate the functions of mBCs. Here, we cultured peripheral blood mononuclear cells (PBMCs) with the intent to collect mBC-derived Abs in vitro and maintain their cell-cell contact-dependent interactions with helper T-cells. PBMCs were cultured with interleukin (IL)-21, CpG-oligodeoxynucleotides (ODN), phorbol myristate acetate (PMA), and phytohemagglutinin/leucoagglutinin (PHA-L) in 24-well flat-bottom plates (5 × 10 5  cells/well). A culture supernatant analysis of PBMCs from healthy donors ( n  = 10) indicated that antigen-specific IgM Ab levels in a PBMC culture supernatant might be better able to demonstrate the antigen sensitization status in a smaller peripheral blood sample, compared to IgG because Epstein-Barr virus-specific IgM mBCs circulate peripherally at a significantly higher frequency once antiviral humoral immunity has stabilized. Thus, our in vitro assay demonstrated the potential significance of antigen-specific IgM Ab production in the culture supernatants. Furthermore, an analysis of cultured PBMCs from allograft kidney recipients ( n  = 16) sensitized with de novo donor-specific human leukocyte antigen (HLA)-specific Abs (DSAs) showed that IgM-type HLA-specific Abs were detected mainly from the culture supernatants from PBMCs of patients with stable graft function, whereas IgG isotype HLA Abs were detectable only from patients with biopsy-proven antibody-mediated rejection. In other words, these IgG isotype Abs also represented an activated humoral immune response in vivo . Additionally, IgM- and IgG-expressing mBCs from healthy donors ( n  = 5) were cultured with IL-21, CpG-ODN, and a supernatant produced by stimulating CD19 + B-cell-depleted PBMCs with PHA-L and PMA in 24-well flat-bottom plates (1 × 10 5  cells/well), and the resulting in vitro analysis provided

Electrochemical immunoassay for the detection of IgM antibodies using polydopamine particles loaded with PbS quantum dots as labels.

PubMed

Ortega, Greter A; Zuaznabar-Gardona, Julio C; Reguera, Edilso

2018-09-30

Here, we report for the first time, an electrochemical immunoassay to detect IgM antibodies using lead sulfide quantum dots (PbS QDs) as electrochemical labels. In this sense, dendritic-like polydopamine particles loaded with PbS QDs were synthesized by the self-polymerization of dopamine in basic media in the presence of QDs (PbS@PDA) and further tagged with anti-IgM antibodies, dengue specific antigens, and streptavidin moieties. The analytical features of the sandwich immunoassay on ELISA microplate were carried out with the PbS@PDA-labeled anti-IgM as secondary antibody. The system was interrogated by acid dissolution of PbS@PDA, followed by differential pulse anodic stripping voltammetry in the presence of Bi(III) ions using carbon screen-printed electrodes. The results indicate that the voltammetric current increased with the increasing of the concentration of target IgM within a range of 0-0.5 mg mL -1 . The limit of detection of this electrochemical immunoassay was evaluated to 130 ng. The measures of satisfactory recoveries from 88.5% to 114% of spiked samples indicate that such a method has good specificity and is applicable to the quantification of IgM antibodies in complex biological samples. No significant differences at the 0.05 significance level were encountered in the analysis of IgM samples between the electrochemical immunoassay and a Bradford assay. Copyright © 2018 Elsevier B.V. All rights reserved.

2-tiered antibody testing for early and late Lyme disease using only an immunoglobulin G blot with the addition of a VlsE band as the second-tier test.

PubMed

Branda, John A; Aguero-Rosenfeld, Maria E; Ferraro, Mary Jane; Johnson, Barbara J B; Wormser, Gary P; Steere, Allen C

2010-01-01

Standard 2-tiered immunoglobulin G (IgG) testing has performed well in late Lyme disease (LD), but IgM testing early in the illness has been problematic. IgG VlsE antibody testing, by itself, improves early sensitivity, but may lower specificity. We studied whether elements of the 2 approaches could be combined to produce a second-tier IgG blot that performs well throughout the infection. Separate serum sets from LD patients and control subjects were tested independently at 2 medical centers using whole-cell enzyme immunoassays and IgM and IgG immunoblots, with recombinant VlsE added to the IgG blots. The results from both centers were combined, and a new second-tier IgG algorithm was developed. With standard 2-tiered IgM and IgG testing, 31% of patients with active erythema migrans (stage 1), 63% of those with acute neuroborreliosis or carditis (stage 2), and 100% of those with arthritis or late neurologic involvement (stage 3) had positive results. Using new IgG criteria, in which only the VlsE band was scored as a second-tier test among patients with early LD (stage 1 or 2) and 5 of 11 IgG bands were required in those with stage 3 LD, 34% of patients with stage 1, 96% of those with stage 2, and 100% of those with stage 3 infection had positive responses. Both new and standard testing achieved 100% specificity. Compared with standard IgM and IgG testing, the new IgG algorithm (with VlsE band) eliminates the need for IgM testing; it provides comparable or better sensitivity, and it maintains high specificity.

Distinct Differentiation Programs Triggered by IL-6 and LPS in Teleost IgM(+) B Cells in The Absence of Germinal Centers.

PubMed

Abós, Beatriz; Wang, Tiehui; Castro, Rosario; Granja, Aitor G; Leal, Esther; Havixbeck, Jeffrey; Luque, Alfonso; Barreda, Daniel R; Secombes, Chris J; Tafalla, Carolina

2016-08-02

Although originally identified as a B cell differentiation factor, it is now known that mammalian interleukin-6 (IL-6) only regulates B cells committed to plasma cells in response to T-dependent (TD) antigens within germinal centers (GCs). Even though adaptive immunity is present in teleost fish, these species lack lymph nodes and GCs. Thus, the aim of the present study was to establish the role of trout IL-6 on B cells, comparing its effects to those induced by bacterial lipopolysaccharide (LPS). We demonstrate that the effects of teleost IL-6 on naïve spleen B cells include proliferation, activation of NF-κB, increased IgM secretion, up-regulation of Blimp1 transcription and decreased MHC-II surface expression that point to trout IL-6 as a differentiation factor for IgM antibody-secreting cells (ASCs). However, LPS induced the secretion of IgM without up-regulating Blimp1, driving the cells towards an intermediate activation state in which antigen presenting mechanisms are elicited together with antibody secretion and expression of pro-inflammatory genes. Our results reveal that, in trout, IL-6 is a differentiation factor for B cells, stimulating IgM responses in the absence of follicular structures, and suggest that it was after follicular structures appeared that this cytokine evolved to modulate TD responses within the GC.

Isotype- and subclass-specific responses to infection and reinfection with parainfluenza-3 virus: comparison of the diagnostic potential of ELISAs detecting seroconversion and specific IgM and IgA.

PubMed

Graham, D A; Mawhinney, K A; German, A; Foster, J C; Adair, B M; Merza, M

1999-03-01

Isotype- and subclass-specific indirect enzyme-linked immunosorbent assays were developed to detect parainfluenza-3 virus-specific IgG1, IgG2, IgM, and IgA responses. Sera were treated with protein G-agarose prior to testing for specific IgM and IgA to eliminate the possibility of false-positive results due to IgM-rheumatoid factor and to remove interisotypic competition due to specific IgG. IgM and IgA absorbance values were expressed as a percentage of the absorbance values of positive reference sera included on each plate (S/P%), and respective positive/negative threshold values of 15.0% and 28.0% were determined. The mean interval between experimental infection of 3 calves and initial detection of specific IgG1 and IgG2 responses was 8.0 and 9.3 days respectively, rising rapidly to an initial plateau 13.7 and 11.0 days postinfection (dpi). Reinfection of these calves at 30 dpi resulted in further rapid increases, with higher plateau values reached 13.0 (IgG1) and 13.7 (IgG2) days later. The mean interval between infection and the first positive IgM and IgA responses was 6.7 and 12.3 days, respectively. IgM S/P% values peaked at 13.0 dpi, with all 3 calves showing a secondary anamnestic response to reinfection, peaking 4.7 days later. The IgA response to initial infection was weak, with only 2 calves showing an obvious peak response at 15.0 dpi. A strong anamnestic IgA response to reinfection occurred in 2 calves, with a peak response 9.5 days later. Apparent biphasic and triphasic IgM and IgA responses were evident in some calves. Acute and convalescent serum samples from 80 calves involved in 17 outbreaks of respiratory disease were tested for specific IgM and IgA. Positive IgM results were detected in 15 outbreaks, with 71 sera from 44 calves testing positive. Although IgA-positive results were detected in the same 15 outbreaks, only 42 sera from 31 calves were positive. In a previous study, seroconversion was detected in 21 of these calves from 10 outbreaks

Detection of bacterial-reactive natural IgM antibodies in desert bighorn sheep populations

PubMed Central

Palmer, Amy L.; Zielke, Ryszard A.; Sikora, Aleksandra E.; Beechler, Brianna R.; Jolles, Anna E.; Epps, Clinton W.

2017-01-01

Ecoimmunology is a burgeoning field of ecology which studies immune responses in wildlife by utilizing general immune assays such as the detection of natural antibody. Unlike adaptive antibodies, natural antibodies are important in innate immune responses and often recognized conserved epitopes present in pathogens. Here, we describe a procedure for measuring natural antibodies reactive to bacterial antigens that may be applicable to a variety of organisms. IgM from desert bighorn sheep plasma samples was tested for reactivity to outer membrane proteins from Vibrio coralliilyticus, a marine bacterium to which sheep would have not been exposed. Immunoblotting demonstrated bighorn sheep IgM could bind to a variety of bacterial cell envelope proteins while ELISA analysis allowed for rapid determination of natural antibody levels in hundreds of individual animals. Natural antibody levels were correlated with the ability of plasma to kill laboratory strains of E. coli bacteria. Finally, we demonstrate that natural antibody levels varied in two distinct populations of desert bighorn sheep. These data demonstrate a novel and specific measure of natural antibody function and show that this varies in ecologically relevant ways. PMID:28662203

Role of Serum Mycoplasma pneumoniae IgA, IgM, and IgG in the Diagnosis of Mycoplasma pneumoniae-Related Pneumonia in School-Age Children and Adolescents

PubMed Central

Lee, Wei-Ju; Huang, Eng-Yen; Tsai, Chih-Min; Kuo, Kuang-Che; Huang, Yi-Chuan; Hsieh, Kai-Sheng; Niu, Chen-Kuang

2016-01-01

ABSTRACT Mycoplasma pneumoniae is an important causative pathogen of community-acquired pneumonia in children. Rapid and reliable laboratory diagnosis of M. pneumoniae infection is important so that appropriate antibiotic treatment can be initiated to reduce the misuse of drugs and resistance rates. Anti-M. pneumoniae immunoglobulin M (IgM) is an indicator of recent primary infection but can persist for several months after initial infection. It has been suggested that anti-M. pneumoniae immunoglobulin A (IgA) can be a reliable indicator for recent M. pneumoniae infection in adults. We investigated the clinical diagnostic value of M. pneumoniae IgA in school-age children and adolescents with M. pneumoniae-related pneumonia. Eighty children with pneumonia and seropositive for M. pneumoniae IgM or with a 4-fold increase of anti-M. pneumoniae immunoglobulin G (IgG) were enrolled from May 2015 to March 2016. The titers of M. pneumoniae IgA, IgM, and IgG, the clinical features, and laboratory examinations of blood, C-reactive protein, and liver enzymes were analyzed. The initial positivity rates for M. pneumoniae IgM and IgA upon admission to the hospital were 63.6 and 33.8%, respectively. One week after admission, the cumulative positivity rates for M. pneumoniae IgM and IgA increased to 97.5 and 56.3%, respectively. Detection of M. pneumoniae IgM was more sensitive than detection of M. pneumoniae IgA for the diagnosis of M. pneumoniae-related pneumonia in school-age children and adolescents; however, paired sera are necessary for a more accurate diagnosis. PMID:27760779

Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody

PubMed Central

Ramsland, Paul A.; Terzyan, Simon S.; Cloud, Gwendolyn; Bourne, Christina R.; Farrugia, William; Tribbick, Gordon; Geysen, H. Mario; Moomaw, Carolyn R.; Slaughter, Clive A.; Edmundson, Allen B.

2006-01-01

The 2.6 Å (1 Å=0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenström's macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The three-dimensional structure of the branched N-linked oligosaccharide associated with the CH1 domain (first constant domain of heavy chain) is reported. The carbohydrate may act to shield part of the lateral surface of the CH1 domain and crowd the junction between the CH1 and CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611–39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024–14032]. The Yvo protein displayed the ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of serine protease substrates and the gp120 coat protein of HIV. An atypical serine, arginine and glutamate motif is located in the middle of the Yvo antigen-binding site and displays an overall geometry that mimics the classical serine, histidine and aspartate catalytic triad of serine proteases. Our present findings indicate that pre-existing or natural antibodies can utilize at least one novel strategy for the cleavage of peptide bonds. PMID:16422668

Antigenic modulation of the cytophilic binding of guinea-pig IgG and IgM antibodies to homologous macrophages.

PubMed Central

Webster, R O; Lawrence, D A

1979-01-01

The cytophilic binding of immune complexes by peritoneal exudate cells (PEC) from adjuvant-stimulated guinea-pigs was studied using 125I-labelled guinea-pig IgG1, IgG2 and IgM antibodies to the dinitrophenyl (DNP) group. The influence of hapten density upon cytophilic activity was studied by the addition of DNP-conjugated antigens to antibody in 2-200 molar ratios of DNP:antibody. Only IgG2 binding was enhanced by immune complex formation, and the increased binding of IgG2 anti-DNP was dependent on the number of DNP determinants per antigen molecule. Cytophilic activity with epsilon-DNP-L-lysine (DNP-LYS), alpha,epsilon-di-DNP-L-lysine (DNP-LYS-DNP), or DNP1-8-BSA was no greater than that seen in the absence of hapten. Increased cytophilic binding was noted only with DNP20-41-BSA. The binding of IgG2 and IgG2 anti-DNP:DNP-bovine serum albumin (BSA) complexes was inhibited by monomeric IgG2. The relative cytophilic capacities of guinea-pig immunoglobulins appeared as follows: IgG greater than IgG1 greater than IgM. IgG1 and IgM binding of DNP conjugates did not enhance their cytophilic activity; therefore, IgG1 and IgM cytophilic binding to PEC was considered biologically insignificant. This investigation provides further evidence that cytophilic binding of immune complexes to macrophages is due to the co-operative action of multiple Fc sites rather than a conformational change in the IgG2 antibodies, and serum proteins, notably complement components, can alter the binding and/or phagocytosis of IgG2 anti-DNP:DNP-BSA complexes. PMID:86509

The utility of measles and rubella IgM serology in an elimination setting, Ontario, Canada, 2009-2014.

PubMed

Bolotin, Shelly; Lim, Gillian; Dang, Vica; Crowcroft, Natasha; Gubbay, Jonathan; Mazzulli, Tony; Schabas, Richard

2017-01-01

In Canada, measles was eliminated in 1998 and rubella in 2000. Effective measles and rubella surveillance is vital in elimination settings, hinging on reliable laboratory methods. However, low-prevalence settings affect the predictive value of laboratory tests. We conducted an analysis to determine the performance of measles and rubella IgM testing in a jurisdiction where both infections are eliminated. 21,299 test results were extracted from the Public Health Ontario Laboratories database and 1,239 reports were extracted from the Ontario Integrated Public Health Information System (iPHIS) from 2008 and 2010 for measles and rubella, respectively, to 2014. Deterministic linkage resulted in 658 linked measles records (2009-2014) and 189 linked rubella records (2010-2014). Sixty-six iPHIS measles entries were classified as confirmed cases, of which 53 linked to laboratory data. Five iPHIS rubella entries were classified as confirmed, all linked to IgM results. The positive predictive value was 17.4% for measles and 3.6% for rubella. Sensitivity was 79.2% for measles and 100.0% for rubella. Specificity was 65.7% for measles and 25.8% for rubella. Our study confirms that a positive IgM alone does not confirm a measles case in elimination settings. This has important implications for countries that are working towards measles and rubella elimination.

Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease

PubMed Central

Weiner, Zachary P.; Crew, Rebecca M.; Brandt, Kevin S.; Ullmann, Amy J.; Schriefer, Martin E.; Molins, Claudia R.

2015-01-01

Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. PMID:26376927

Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease.

PubMed

Weiner, Zachary P; Crew, Rebecca M; Brandt, Kevin S; Ullmann, Amy J; Schriefer, Martin E; Molins, Claudia R; Gilmore, Robert D

2015-11-01

Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

PubMed Central

Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

2016-01-01

In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

Cocoa and cocoa fibre differentially modulate IgA and IgM production at mucosal sites.

PubMed

Massot-Cladera, Malen; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

2016-05-01

Previous studies have shown that a 10 % cocoa (C10) diet, containing polyphenols and fibre among others, modifies intestinal and systemic Ig production. The present study aimed at evaluating the impact of C10 on IgA and IgM production in the intestinal and extra-intestinal mucosal compartments, establishing the involvement of cocoa fibre (CF) in such effects. Mechanisms by which C10 intake may affect IgA synthesis in the salivary glands were also studied. To this effect, rats were fed either a standard diet, a diet containing C10, CF or inulin. Intestinal (the gut wash (GW), Peyer's patches (PP) and mesenteric lymph nodes (MLN)) and extra-intestinal (salivary glands) mucosal tissues and blood samples were collected for IgA and IgM quantification. The gene expressions of IgA production- and homing-related molecules were studied in the salivary glands. The C10 diet decreased intestinal IgA and IgM production. Although the CF diet decreased the GW IgA concentration, it increased PP, MLN and serum IgA concentrations. Both the C10 and the CF diets produced a down-regulatory effect on IgA secretion in the extra-intestinal tissues. The C10 diet interacted with the mechanisms involved in IgA synthesis, whereas the CF showed particular effects on the homing and transcytosis of IgA across the salivary glands. Overall, CF was able to up-regulate IgA production in the intestinal-inductor compartments, whereas it down-regulated its production at the mucosal-effector ones. Further studies must be directed to ascertain the mechanisms involved in the effect of particular cocoa components on gut-associated lymphoid tissue.

Efficient IgM assembly and secretion require the plasma cell induced endoplasmic reticulum protein pERp1

PubMed Central

van Anken, Eelco; Pena, Florentina; Hafkemeijer, Nicole; Christis, Chantal; Romijn, Edwin P.; Grauschopf, Ulla; Oorschot, Viola M. J.; Pertel, Thomas; Engels, Sander; Ora, Ari; Lástun, Viorica; Glockshuber, Rudi; Klumperman, Judith; Heck, Albert J. R.; Luban, Jeremy; Braakman, Ineke

2009-01-01

Plasma cells daily secrete their own mass in antibodies, which fold and assemble in the endoplasmic reticulum (ER). To reach these levels, cells require pERp1, a novel lymphocyte-specific small ER-resident protein, which attains expression levels as high as BiP when B cells differentiate into plasma cells. Although pERp1 has no homology with known ER proteins, it does contain a CXXC motif typical for oxidoreductases. In steady state, the CXXC cysteines are locked by two parallel disulfide bonds with a downstream C(X)6C motif, and pERp1 displays only modest oxidoreductase activity. pERp1 emerged as a dedicated folding factor for IgM, associating with both heavy and light chains and promoting assembly and secretion of mature IgM. PMID:19805154

In Vivo-Expressed Proteins of Virulent Leptospira interrogans Serovar Autumnalis N2 Elicit Strong IgM Responses of Value in Conclusive Diagnosis.

PubMed

Raja, Veerapandian; Shanmughapriya, Santhanam; Kanagavel, Murugesan; Artiushin, Sergey C; Velineni, Sridhar; Timoney, John F; Natarajaseenivasan, Kalimuthusamy

2016-01-01

Leptospirosis is a serious zoonosis that is underdiagnosed because of limited access to laboratory facilities in Southeast Asia, Central and South America, and Oceania. Timely diagnosis of locally distributed serovars of high virulence is crucial for successful care and outbreak management. Using pooled patient sera, an expression gene library of a virulent Leptospira interrogans serovar Autumnalis strain N2 isolated in South India was screened. The identified genes were characterized, and the purified recombinant proteins were used as antigens in IgM enzyme-linked immunosorbent assay (ELISA) either singly or in combination. Sera (n = 118) from cases of acute leptospirosis along with sera (n = 58) from healthy subjects were tested for reactivity with the identified proteins in an ELISA designed to detect specific IgM responses. We have identified nine immunoreactive proteins, ArgC, RecA, GlpF, FliD, TrmD, RplS, RnhB, Lp28.6, and Lrr44.9, which were found to be highly conserved among pathogenic leptospires. Apparently, the proteins ArgC, RecA, GlpF, FliD, TrmD, and Lrr44.9 are expressed during natural infection of the host and undetectable in in vitro cultures. Among all the recombinant proteins used as antigens in IgM ELISA, ArgC had the highest sensitivity and specificity, 89.8% and 95.5%, respectively, for the conclusive diagnosis of leptospirosis. The use of ArgC and RecA in combination for IgM ELISA increased the sensitivity and specificity to 95.7% and 94.9%, respectively. ArgC and RecA thus elicited specific IgM responses and were therefore effective in laboratory confirmation of Leptospira infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

An Unmutated IgM Response to the Vi Polysaccharide of Salmonella Typhi Contributes to Protective Immunity in a Murine Model of Typhoid.

PubMed

Pandya, Kalgi D; Palomo-Caturla, Isabel; Walker, Justin A; K Sandilya, Vijay; Zhong, Zhijiu; Alugupalli, Kishore R

2018-06-15

T cell-dependent B cell responses typically develop in germinal centers. Abs generated during such responses are isotype switched and have a high affinity to the Ag because of somatic hypermutation of Ab genes. B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice. To test the extent to which unmutated polysaccharide-specific IgM confers protective immunity, we immunized wildtype and AID -/- mice with either heat-killed Salmonella enterica serovar Typhi ( S. Typhi) or purified Vi polysaccharide (ViPS). We found that wildtype and AID -/- mice immunized with heat-killed S. Typhi generated similar anti-ViPS IgM responses. As expected, wildtype, but not AID -/- mice generated ViPS-specific IgG. However, the differences in the Ab-dependent killing of S. Typhi mediated by the classical pathway of complement activation were not statistically significant. In ViPS-immunized wildtype and AID -/- mice, the ViPS-specific IgM levels and S. Typhi bactericidal Ab titers at 7 but not at 28 d postimmunization were also comparable. To test the protective immunity conferred by these immunizations, mice were challenged with a chimeric S. Typhimurium strain expressing ViPS. Compared with their naive counterparts, immunized wildtype and AID -/- mice exhibited significantly reduced bacterial burden regardless of the route of infection. These data indicate that an unmutated IgM response to ViPS contributes to protective immunity to S. Typhi. Copyright © 2018 by The American Association of Immunologists, Inc.

Enhancement of antibody synthesis in rats by feeding cis-9,trans-11 conjugated linoleic acid during early life.

PubMed

Ramírez-Santana, Carolina; Castellote, Cristina; Castell, Margarida; Moltó-Puigmartí, Carolina; Rivero, Montserrat; Pérez-Cano, Francisco J; Franch, Angels

2011-05-01

Previous studies have demonstrated that the intake of a 1% conjugated linoleic acid (CLA) diet in an 80:20 mixture of cis-9,trans-11 and trans-10,cis-12 exerts age-specific effects on the immune system: immunoglobulin enhancement and proliferative down-modulation in neonatal and adult rats, respectively. The present study evaluates the influence of the same diet on antibody synthesis of early infant Wistar rats during suckling and/or after weaning. Dietary supplementation was performed during suckling and early infancy (4 weeks), only during suckling (3 weeks), or only in early infancy (1 week). CLA content in plasma and serum immunoglobulin (Ig) G, IgM and IgA concentration were determined. Proliferation, cytokines and Ig production were evaluated on isolated splenocytes. Cis-9,trans-11- and trans-10,cis-12-CLA isomers were detected in the plasma of all CLA-supplemented animals, and the highest content was quantified in those rats supplemented over the longest period. These rats also exhibited higher concentrations of serum IgG, IgM and IgA. Moreover, splenocytes from CLA-supplemented rats showed the highest IgM and IgG synthesis and interleukin (IL)-6 production, whereas their proliferative ability was lower. In summary, in infant rats, we observed both the enhance antibody synthesis previously reported in neonates, and the reduced lymphoproliferation previously reported in adults. Copyright © 2011 Elsevier Inc. All rights reserved.

Spontaneous Development of IgM Anti-Cocaine Antibodies in Habitual Cocaine Users: Effect on IgG Antibody Responses to a Cocaine Cholera Toxin B Conjugate Vaccine

PubMed Central

Orson, Frank M.; Rossen, Roger D.; Shen, Xiaoyun; Lopez, Angel Y.; Wu, Yan; Kosten, Thomas R.

2014-01-01

Background and Objectives In cocaine vaccine studies, only a minority of subjects made strong antibody responses. To investigate this issue, IgG and IgM antibody responses to cocaine and to cholera toxin B (CTB—the carrier protein used to enhance immune responses to cocaine) were measured in sera from the 55 actively vaccinated subjects in a Phase IIb randomized double-blind placebo-controlled trial (TA-CD 109). Methods Isotype specific ELISAs were used to measure IgG and IgM anti-cocaine and anti-CTB antibody in serial samples collected prior to and at intervals after immunization. We assessed IgG anti-cocaine responses of patients with pre-vaccination IgM anti-cocaine antibodies. Competitive inhibition ELISA was used to evaluate antibody specificity. Results and Conclusions Before immunization, 36/55 subjects had detectable IgM antibodies to cocaine, and 9 had IgM levels above the 95% confidence limit of 11 µg/ml. These nine had significantly reduced peak IgG anti-cocaine responses at 16 weeks, and all were below the concentration (40 µg/ml) considered necessary to discourage recreational cocaine use. The IgG anti-CTB responses of these same subjects were also reduced. Scientific Significance Subjects who develop an IgM antibody response to cocaine in the course of repeated recreational exposure to this drug are significantly less likely to produce high levels of IgG antibodies from the cocaine conjugate vaccine. The failure may be due to recreational cocaine exposure induction of a type 2 T-cell independent immune response. Such individuals will require improved vaccines and are poor candidates for the currently available vaccine. PMID:23414504

Serological Diagnosis of Acute Scrub Typhus in Southern India: Evaluation of InBios Scrub Typhus Detect IgM Rapid Test and Comparison with other Serological Tests.

PubMed

Anitharaj, Velmurugan; Stephen, Selvaraj; Pradeep, Jothimani; Park, Sungman; Kim, Seung-Han; Kim, Young Jin; Kim, Eun-Ye; Kim, Yoon-Won

2016-11-01

Scrub Typhus (ST) is being reported from different parts of India in the recent past. However, the diagnosis and confirmation of ST cases require specific serological and molecular diagnostic tests. Both rapid and conventional ELISA tests need to be properly evaluated. Evaluation of a new ST IgM Immunochromatography (ICT) test kit (InBios Scrub Typhus Detect IgM Rapid Test) and compare it with another rapid kit, conventional ELISA kit and Weil-Felix (WF) test. This prospective study was carried out in Mahatma Gandhi Medical College and Research Institute, Puducherry, during November 2015 to June 2016. Clinically suspected 220 ST patients were examined by a new kit, InBios Scrub Typhus Detect IgM Rapid Test, taking the conventional InBios Scrub Typhus Detect IgM ELISA as reference. Additional comparison was made with ImmuneMed Scrub Typhus Rapid, and WF test (single OXK titers ≥1:320). Statistical analysis was performed (Chi-square, Spearman's correlation and Kappa) using IBM SPSS Statistics 17 for Windows (SPSS Inc; Chicago, USA). Percentage Sensitivity, Specificity, Positive Predictive and Negative Predictive Values for InBios, ImmuneMed and WF were 99.25, 93.02, 95.68, 98.77; 94.87, 94.19, 96.21, 92.05 and 50.38, 95.51, 94.29, 56.67 respectively. A total of 134 patients were positive in reference standard InBios IgM ELISA. This new rapid ST IgM kit validated for the first time in India, showed good sensitivity and specificity. As a Point-of-Care (PoC) test, the kit would be helpful in both urban and remote rural parts of India.

Serological Diagnosis of Acute Scrub Typhus in Southern India: Evaluation of InBios Scrub Typhus Detect IgM Rapid Test and Comparison with other Serological Tests

PubMed Central

Anitharaj, Velmurugan; Pradeep, Jothimani; Park, Sungman; Kim, Seung-Han; Kim, Young Jin; Kim, Eun-Ye; Kim, Yoon-Won

2016-01-01

Introduction Scrub Typhus (ST) is being reported from different parts of India in the recent past. However, the diagnosis and confirmation of ST cases require specific serological and molecular diagnostic tests. Both rapid and conventional ELISA tests need to be properly evaluated. Aim Evaluation of a new ST IgM Immunochromatography (ICT) test kit (InBios Scrub Typhus Detect IgM Rapid Test) and compare it with another rapid kit, conventional ELISA kit and Weil-Felix (WF) test. Materials and Methods This prospective study was carried out in Mahatma Gandhi Medical College and Research Institute, Puducherry, during November 2015 to June 2016. Clinically suspected 220 ST patients were examined by a new kit, InBios Scrub Typhus Detect IgM Rapid Test, taking the conventional InBios Scrub Typhus Detect IgM ELISA as reference. Additional comparison was made with ImmuneMed Scrub Typhus Rapid, and WF test (single OXK titers ≥1:320). Statistical analysis was performed (Chi-square, Spearman’s correlation and Kappa) using IBM SPSS Statistics 17 for Windows (SPSS Inc; Chicago, USA). Results Percentage Sensitivity, Specificity, Positive Predictive and Negative Predictive Values for InBios, ImmuneMed and WF were 99.25, 93.02, 95.68, 98.77; 94.87, 94.19, 96.21, 92.05 and 50.38, 95.51, 94.29, 56.67 respectively. A total of 134 patients were positive in reference standard InBios IgM ELISA. Conclusion This new rapid ST IgM kit validated for the first time in India, showed good sensitivity and specificity. As a Point-of-Care (PoC) test, the kit would be helpful in both urban and remote rural parts of India. PMID:28050364

Cosmic Reionization on Computers: Properties of the Post-reionization IGM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gnedin, Nickolay Y.; Becker, George D.; Fan, Xiaohui

Here, we present a comparison between several observational tests of the post-reionization IGM and the numerical simulations of reionization completed under the Cosmic Reionization On Computers (CROC) project. The CROC simulations match the gap distribution reasonably well, and also provide a good match for the distribution of peak heights, but there is a notable lack of wide peaks in the simulated spectra and the flux PDFs are poorly matched in the narrow redshift interval 5.5 < z < 5.7, with the match at other redshifts being significantly better, albeit not exact. Both discrepancies are related: simulations show more opacity thanmore » the data.« less

Cosmic Reionization on Computers: Properties of the Post-reionization IGM

DOE PAGES

Gnedin, Nickolay Y.; Becker, George D.; Fan, Xiaohui

2017-05-19

Here, we present a comparison between several observational tests of the post-reionization IGM and the numerical simulations of reionization completed under the Cosmic Reionization On Computers (CROC) project. The CROC simulations match the gap distribution reasonably well, and also provide a good match for the distribution of peak heights, but there is a notable lack of wide peaks in the simulated spectra and the flux PDFs are poorly matched in the narrow redshift interval 5.5 < z < 5.7, with the match at other redshifts being significantly better, albeit not exact. Both discrepancies are related: simulations show more opacity thanmore » the data.« less

Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies

PubMed Central

Klaus, Tomasz; Bzowska, Monika; Kulesza, Małgorzata; Kabat, Agnieszka Martyna; Jemioła-Rzemińska, Małgorzata; Czaplicki, Dominik; Makuch, Krzysztof; Jucha, Jarosław; Karabasz, Alicja; Bereta, Joanna

2016-01-01

Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce haemagglutination and are used worldwide for diagnostic blood typing. Contrary to the current belief that IgGs are too small to simultaneously bind antigens on two different erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing isotype that has the ability to form Fc-dependent oligomers. However, F(ab′)2 fragments of the IgG3 were sufficient to agglutinate type B red blood cells; therefore, IgG3-triggered agglutination did not require oligomerization. Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than other mouse IgG subclasses and that the unique properties of mouse IgG3 are likely due to the structure of its hinge region. With a focus on applications in diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood typing reagents using an accelerated storage approach and differential scanning calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid decrease in IgM activity was caused by aggregation of the molecules and a previously unknown posttranslational proteolytic processing of the μ heavy chain. Our data point to mouse IgG3 as a potent diagnostic tool. PMID:27484487

IGM CONSTRAINTS FROM THE SDSS-III/BOSS DR9 Lyα FOREST TRANSMISSION PROBABILITY DISTRIBUTION FUNCTION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Khee-Gan; Hennawi, Joseph F.; Spergel, David N.

2015-02-01

The Lyα forest transmission probability distribution function (PDF) is an established probe of the intergalactic medium (IGM) astrophysics, especially the temperature-density relationship of the IGM. We measure the transmission PDF from 3393 Baryon Oscillations Spectroscopic Survey (BOSS) quasars from Sloan Digital Sky Survey Data Release 9, and compare with mock spectra that include careful modeling of the noise, continuum, and astrophysical uncertainties. The BOSS transmission PDFs, measured at (z) = [2.3, 2.6, 3.0], are compared with PDFs created from mock spectra drawn from a suite of hydrodynamical simulations that sample the IGM temperature-density relationship, γ, and temperature at mean density,more » T {sub 0}, where T(Δ) = T {sub 0}Δ{sup γ} {sup –} {sup 1}. We find that a significant population of partial Lyman-limit systems (LLSs) with a column-density distribution slope of β{sub pLLS} ∼ – 2 are required to explain the data at the low-transmission end of transmission PDF, while uncertainties in the mean Lyα forest transmission affect the high-transmission end. After modeling the LLSs and marginalizing over mean transmission uncertainties, we find that γ = 1.6 best describes the data over our entire redshift range, although constraints on T {sub 0} are affected by systematic uncertainties. Within our model framework, isothermal or inverted temperature-density relationships (γ ≤ 1) are disfavored at a significance of over 4σ, although this could be somewhat weakened by cosmological and astrophysical uncertainties that we did not model.« less

Perceiving emotions in neutral faces: expression processing is biased by affective person knowledge.

PubMed

Suess, Franziska; Rabovsky, Milena; Abdel Rahman, Rasha

2015-04-01

According to a widely held view, basic emotions such as happiness or anger are reflected in facial expressions that are invariant and uniquely defined by specific facial muscle movements. Accordingly, expression perception should not be vulnerable to influences outside the face. Here, we test this assumption by manipulating the emotional valence of biographical knowledge associated with individual persons. Faces of well-known and initially unfamiliar persons displaying neutral expressions were associated with socially relevant negative, positive or comparatively neutral biographical information. The expressions of faces associated with negative information were classified as more negative than faces associated with neutral information. Event-related brain potential modulations in the early posterior negativity, a component taken to reflect early sensory processing of affective stimuli such as emotional facial expressions, suggest that negative affective knowledge can bias the perception of faces with neutral expressions toward subjectively displaying negative emotions. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Multiplex Detection of IgG and IgM to Rift Valley Fever Virus Nucleoprotein, Nonstructural Proteins, and Glycoprotein in Ovine and Bovine.

PubMed

Hossain, Mohammad M; Wilson, William C; Faburay, Bonto; Richt, Jürgen; McVey, David S; Rowland, Raymond R

2016-08-01

A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were assembled into a multiplex and tested in serum samples from infected wild-type RVFV or MP12, a modified live virus vaccine. As expected, the N protein was immunodominant and the best target for early detection of infection. Antibody activity against the other targets was also detected. The experimental results demonstrate the capabilities of FMIA for the detection of antibodies to RVFV structural and nonstructural proteins, which can be applied to future development and validation of diagnostic tests that can be used to differentiate vaccinated from infected animals.

[Diagnostic approach of an IgM monoclonal gammopathy and clinical importance of gene MYD88 L265P mutation].

PubMed

Cilla, N; Vercruyssen, M; Ameye, L; Paesmans, M; de Wind, A; Heimann, P; Meuleman, N; Bron, D

2018-05-30

An IgM monoclonal gammopathy points to a diagnosis of Waldenstrom's Macroglobulinemia. Other B lymphoproliferatives disorders should be ruled out but the limits are sometimes difficult to define. The discovery of the L265P mutation of the MYD88 gene simplified potentially the situation. 383 patients of the Jules Bordet Institute with an IgM level above 2 g/L were reviewed. For the 49 who had a monoclonal peak, we analysed the underlying pathology in termes of general, clinical and biological characteristics. We checked if the MYD88 mutation had been detected. The overall survival rate was studied. 5 histological groups were identified: Waldenstrom's Macroglobulinemia (MW, N = 27), lymphoplasmacytic lymphoma (LLP, N = 10), marginal zone lymphoma (LMZ, N = 7), monoclonal gammopathy of unknown significance and multiple myeloma (MGUS/MM, N = 5). The MW group was compared to the other groups. Regarding biological characteristics, the IgM level upon diagnosis was statistically higher in the MW group with a median level at 19.5 g/L (2.3-101 g/L) (p-value = 0,0001). Concerning the clinical characteristics, a splenomegaly was more frequent in the LMZ group (p-value = 0,04). The L265P mutation of the MYD88 gene was found in 77 % of patients in the MW group, 60 % of patients in the LLP group and 67 % in the LMZ group (p-value = 0,38). For the 49 patients, the 10-yearoverall survival was 85 % (CI 95 %, 67 % to 94 %) and the 15-year-overall survival was 65 % (CI 95 %, 41 % to 81 %). A monoclonal IgM peak suggests a MW but other B lymphoproliferatives disorders should be excluded. Even if the L265P mutation is frequent in the LLP/MW, it is not specific. A precise diagnosis requires collating clinical, histological, immunophenotypical and genetical data.

Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice.

PubMed

Jaiswal, Smita; Smith, Kenneth; Ramirez, Alejandro; Woda, Marcia; Pazoles, Pamela; Shultz, Leonard D; Greiner, Dale L; Brehm, Michael A; Mathew, Anuja

2015-01-01

The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. © 2014 by the Society for Experimental Biology and Medicine.

Detection of MYD88 L265P and WHIM-like CXCR4 mutation in patients with IgM monoclonal gammopathy related disease.

PubMed

Cao, Xin-Xin; Meng, Qi; Cai, Hao; He, Tian-Hua; Zhang, Cong-Li; Su, Wei; Sun, Jian; Li, Yue; Xu, Wei; Zhou, Dao-Bin; Li, Jian

2017-06-01

A broad spectrum of diseases are associated with IgM monoclonal gammopathy, including Waldenstrom macroglobulinemia (WM), various types of B cell non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), primary amyloidosis (AL), and monoclonal gammopathy of undetermined significance (MGUS); these are called IgM monoclonal gammopathy related diseases (IgM-RD). We investigated MYD88 L265P and WHIM-like CXCR4 mutations in various IgM-RD. Patients with serum immunofixation electrophoresis confirmed IgM monoclonal gammopathy who had enough material for DNA extraction and presented between January 2008 and October 2016 at Peking Union Medical College Hospital were enrolled in this cohort. We performed real-time allele-specific-polymerase chain reaction and Sanger sequencing to explore the presence of MYD88 L265P and WHIM-like CXCR4 mutations. One hundred and twelve patients (64 male and 48 female patients) were included in this retrospective study. The median age at diagnosis was 62 years (range, 30-84 years). In total, 64 patients (57.1%) carried the MYD88 L265P mutation and 14 patients (12.5%) carried the CXCR4 WHIM-like mutation. We identified the MYD88 L265P somatic variant in cases with WM (39/42), MGUS (8/18), NHL (14/41, including 4/13 diffuse large B cell lymphoma (DLBCL), 1/8 mucosa-associated lymphoid tissue, 3/6 splenic marginal zone lymphoma (SMZL), 1/4 chronic lymphocytic leukemia, 2/3 nodal marginal zone lymphoma (NMZL), 1/2 mantle cell lymphoma, 1 Burkitt lymphoma, and 1 B cell NHL that could not be classified), primary AL (2/2), and IgM-PN (1/1). The mutation was absent in five patients with Cryoglobulinemia, two with primary cold agglutinin disease and one with MM. The CXCR4 WHIM-like mutation was present in 10/42 patients with WM, 3/41 with NHL (1 DLBCL, 1 SMZL, and 1 NMZL), and 1/18 patients with IgM MGUS. Among the patients with NHL, those with the mutated MYD88 L265P genotype were younger and had lower level of IgG and IgA than the patients with the

Seroprevalence of parvovirus B19 IgG and IgM antibodies among pregnant women in Oyo State, Nigeria.

PubMed

Abiodun, Iyanda; Opaleye, Oluyinka Oladele; Ojurongbe, Olusola; Fagbami, Ademola Hezekiah

2013-12-15

Human parvovirus B19 causes a wide range of complications in pregnant women including abortion, severe fetal anemia, non-immune hydrops fetalis, and even intrauterine fetal death. However, there is a dearth of information on the prevalence of the virus among pregnant women in southwestern Nigeria. Blood samples were collected from 231 pregnant women and screened for antibodies to human parvovirus B19 IgM and IgG using an enzyme immunosorbent assay kits. Of the 231 women, 31 were in their first trimester, 146 were in their second trimester, and 54 were in their third trimester. Forty-five (20%) were positive for parvovirus B19 IgG antibodies, 10 (4%) were positive for parvovirus B19 IgM antibodies, and 176 (76%) had no detectable parvovirus B19 antibodies. Twenty-eight (19%) of the 146 pregnant women in their second trimester were positive for parvovirus B19 IgG antibody while three (2%) of the 146 were positive for parvovirus B19 IgM antibody. It is evident that there is a high prevalence of human parvovirus B19 among pregnant women in south-western Nigeria. This suggests that there is an active transmission of the virus in the community; it is therefore necessary to conduct more studies on the virus in pregnant women in Nigeria to ascertain its effect on the fetus.

Gravity changes during animal development affect IgM heavy-chain transcription and probably lymphopoiesis.

PubMed

Huin-Schohn, Cécile; Guéguinou, Nathan; Schenten, Véronique; Bascove, Matthieu; Koch, Guillemette Gauquelin; Baatout, Sarah; Tschirhart, Eric; Frippiat, Jean-Pol

2013-01-01

Our previous research demonstrated that spaceflight conditions affect antibody production in response to an antigenic stimulation in adult amphibians. Here, we investigated whether antibody synthesis is affected when animal development occurs onboard a space station. To answer this question, embryos of the Iberian ribbed newt, Pleurodeles waltl, were sent to the International Space Station (ISS) before the initiation of immunoglobulin heavy-chain expression. Thus, antibody synthesis began in space. On landing, we determined the effects of spaceflight on P. waltl development and IgM heavy-chain transcription. Results were compared with those obtained using embryos that developed on Earth. We find that IgM heavy-chain transcription is doubled at landing and that spaceflight does not affect P. waltl development and does not induce inflammation. We also recreated the environmental modifications encountered by the embryos during their development onboard the ISS. This strategy allowed us to demonstrate that gravity change is the factor responsible for antibody heavy-chain transcription modifications that are associated with NF-κB mRNA level variations. Taken together, and given that the larvae were not immunized, these data suggest a modification of lymphopoiesis when gravity changes occur during ontogeny.

About Climate Neutral Research Campuses | Climate Neutral Research Campuses

Science.gov Websites

| NREL About Climate Neutral Research Campuses About Climate Neutral Research Campuses Research an example of climate neutrality. To better understand the concept of climate neutral research

The role of sulfoglucuronosyl glycosphingolipids in the pathogenesis of monoclonal IgM paraproteinemia and peripheral neuropathy

PubMed Central

ARIGA, Toshio

2011-01-01

In IgM paraproteinemia and peripheral neuropathy, IgM M-protein secretion by B cells leads to a T helper cell response, suggesting that it is antibody-mediated autoimmune disease involving carbohydrate epitopes in myelin sheaths. An immune response against sulfoglucuronosyl glycosphingolipids (SGGLs) is presumed to participate in demyelination or axonal degeneration in the peripheral nervous system (PNS). SGGLs contain a 3-sulfoglucuronic acid residue that interacts with anti-myelin-associated glycoprotein (MAG) and the monoclonal antibody anti-HNK-1. Immunization of animals with sulfoglucuronosyl paragloboside (SGPG) induced anti-SGPG antibodies and sensory neuropathy, which closely resembles the human disease. These animal models might help to understand the disease mechanism and lead to more specific therapeutic strategies. In an in vitro study, destruction or malfunction of the blood-nerve barrier (BNB) was found, resulting in the leakage of circulating antibodies into the PNS parenchyma, which may be considered as the initial key step for development of disease. PMID:21785257

Optical trapping and manipulation of neutral particles using lasers

PubMed Central

Ashkin, Arthur

1997-01-01

The techniques of optical trapping and manipulation of neutral particles by lasers provide unique means to control the dynamics of small particles. These new experimental methods have played a revolutionary role in areas of the physical and biological sciences. This paper reviews the early developments in the field leading to the demonstration of cooling and trapping of neutral atoms in atomic physics and to the first use of optical tweezers traps in biology. Some further major achievements of these rapidly developing methods also are considered. PMID:9144154

Effect of the Various Steps in the Processing of Human Milk in the Concentrations of IgA, IgM, and Lactoferrin.

PubMed

Arroyo, Gerardo; Ortiz Barrientos, Kevin Alexander; Lange, Karla; Nave, Federico; Miss Mas, Gabriela; Lam Aguilar, Pamela; Soto Galindo, Miguel Angel

2017-09-01

Human milk immune components are unique and important for the development of the newborn. Milk processing at the Human Milk Banks (HMB), however, causes partial destruction of immune proteins. The objective of this study was to determine the effects that heating during the milk processing procedure at the HMB had on the concentrations of IgA, IgM, and lactoferrin at three critical points in time. Fifty milk samples (150 mL) were collected from voluntary donors at the HMB at the Hospital Nacional Pedro de Bethancourt, located in Antigua Guatemala. Samples from three critical points in time during the milk processing procedure were selected for analysis: freezing/thawing I, freezing/thawing II, and pasteurization. IgA, IgM, and lactoferrin concentrations were determined during each critical point and compared with a baseline concentration. After milk processing, IgA, IgM, and lactoferrin mean concentrations were reduced by 30.0%, 36.0%, and 70.0%, respectively (p < 0.001). Reduction of biological activity was mainly attributed to pasteurization for IgA and lactoferrin (p < 0.001); the first freezing/thawing processes before pasteurization showed no significant reduction difference between mean concentrations of IgA (p = 0.160) and lactoferrin (p = 0.345) but showed a significant effect on IgM concentration (p = 0.016), and the second freezing/thawing procedure only showed a significant effect on IgA (p < 0.001). The effects of milk processing on the immune proteins that were evaluated in this study demonstrated a significant reduction.

A monoclonal antibody distinguishes between two IgM heavy chain isotypes in Atlantic salmon and brown trout: protein characterization, 3D modeling and epitope mapping.

PubMed

Kamil, Atif; Falk, Knut; Sharma, Animesh; Raae, Arnt; Berven, Frode; Koppang, Erling Olaf; Hordvik, Ivar

2011-09-01

Atlantic salmon (Salmo salar) and brown trout (Salmo trutta) possess two distinct subpopulations of IgM which can be separated by anion exchange chromatography. Accordingly, there are two isotypic μ genes in these species, related to ancestral tetraploidy. In the present work it was verified by mass spectrometry that IgM of peak 1 (subpopulation 1) have heavy chains previously designated as μB type whereas IgM of peak 2 (subpopulation 2) have heavy chains of μA type. Two adjacent cysteine residues are present near the C-terminal part of μB, in contrast to one cysteine residue in μA. Salmon IgM of both peak 1 and peak 2 contain light chains of the two most common isotypes: IgL1 and IgL3. In contrast to salmon and brown trout, IgM of rainbow trout (Oncorhynchus mykiss) is eluted in a single peak when subjected to anion exchange chromatography. Surprisingly, a monoclonal antibody MAb4C10 against rainbow trout IgM, reacted with μA in salmon, whereas in brown trout it reacted with μB. It is plausible to assume that DNA has been exchanged between the paralogous A and B loci during evolution while maintaining the two sub-variants, with and without the extra cysteine. MAb4C10 was conjugated to magnetic beads and used to separate cells, demonstrating that μ transcripts residing from captured cells were primarily of A type in salmon and B type in brown trout. An analysis of amino acid substitutions in μA and μB of salmon and brown trout indicated that the third constant domain is essential for MAb4C10 binding. This was supported by 3D modeling and was finally verified by studies of MAb4C10 reactivity with a series of recombinant μ3 constructs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cooperation between Strain-Specific and Broadly Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the Broadly Neutralizing Epitope

PubMed Central

Anthony, Colin; York, Talita; Bekker, Valerie; Matten, David; Selhorst, Philippe; Ferreria, Roux-Cil; Garrett, Nigel J.; Karim, Salim S. Abdool; Morris, Lynn; Wood, Natasha T.; Moore, Penny L.

2017-01-01

ABSTRACT V3-glycan-targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep-sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan-directed bNAbs compared to overlapping early strain-specific neutralizing antibody (ssNAb) responses to the V3/C3 region in donor CAP177. Escape from the ssNAb response occurred rapidly via an N334-to-N332 glycan switch, which took just 7.5 weeks to reach >50% frequency. In contrast, escape from the bNAbs was mediated via multiple pathways and took longer, with escape first occurring through an increase in V1 loop length, which took 46 weeks to reach 50% frequency, followed by an N332-to-N334 reversion, which took 66 weeks. Importantly, bNAb escape was incomplete, with contemporaneous neutralization observed up to 3 years postinfection. Both the ssNAb response and the bNAb response were modulated by the presence/absence of the N332 glycan, indicating an overlap between the two epitopes. Thus, selective pressure by ssNAbs to maintain the N332 glycan may have constrained the bNAb escape pathway. This slower and incomplete viral escape resulted in prolonged exposure of the bNAb epitope, which may in turn have aided the maturation of the bNAb lineage. IMPORTANCE The development of an HIV-1 vaccine is of paramount importance, and broadly neutralizing antibodies are likely to be a key component of a protective vaccine. The V3-glycan-targeting bNAb responses are among the most promising vaccine targets, as they are commonly elicited during infection. Understanding the interplay between viral evolution and the development of these antibodies provides insights that may guide immunogen design. Our work contrasted the dynamics of the early strain-specific antibodies and the later broadly neutralizing

Research and development at the Marshall Space Flight Center Neutral Buoyancy Simulator

NASA Technical Reports Server (NTRS)

Kulpa, Vygantas P.

1987-01-01

The Neutral Buoyancy Simulator (NBS), a facility designed to imitate zero-gravity conditions, was used to test the Experimental Assembly of Structures in Extravehicular Activity (EASE) and the Assembly Concept for Construction of Erectable Space Structures (ACCESS). Neutral Buoyancy Simulator applications and operations; early space structure research; development of the EASE/ACCESS experiments; and improvement of NBS simulation are summarized.

On becoming neutral: effects of experimental neutralizing reconsidered.

PubMed

van den Hout, M; van Pol, M; Peters, M

2001-12-01

Behaviour Research and Therapy 34 (1996) 889-898 found that writing out a negative thought produced anxiety and an urge to neutralize the thought, that instructing participants to neutralize the thought reduced anxiety/neutralization urge in the short run (i.e. within 2 min), but that in the control group 20 min without instruction was attended by the same reduction in anxiety/urge to neutralize ("natural decay"). The observations were made with pariticipants who scored high on "thought action fusion" and the experiment was set up as exerimental model of obsessions. We repeated the study with participants that were not selected on thought action fusion. All the findings reported by Behaviour Research and Therapy 34 (1996) 889-898 were replicated. Correlational analysis indicated that the strength of the effect was not related to scores on scales measuring "thought action fusion". Behaviour Research and Therapy 34 (1996) 889-898 did not assess whether non-neutralizing was followed by immediate reductions in distress. We did assess this and found that the larger part of the immediate reduction of distress after neutralization also occurs when no neutralization instruction is given. The effects of neutralization instructions in the present type of experiment are considerably less powerful than suggested earlier.

HLA-DQBl*0402 alleles polymorphisms detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM

NASA Astrophysics Data System (ADS)

Sari, Yulia; Haryati, Sri; Prasetyo, Afiono Agung; Hartono, Adnan, Zainal Arifin

2017-02-01

The human leukocyte antigen (HLA)-DQB1 gene polymorphisms may associated with the infection risk of Toxoplasma gondii in HIV patients. The HLA-DQB1*0402 in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasma encephalitis. However, the HLA-DQB1*0402 gene polymorphisms status in the Javanese HIV patients is unknown. This study evaluated the prevalence of HLA-DQB*0402 alleles polymorphisms in Javanese HIV patients with positive anti-Toxoplasma gondii IgM status. Since 2009 our research group performing a molecular epidemiology of blood borne viruses in Central Java Indonesia, by collecting the epidemiological and clinical data from the high risk communities. All blood samples were screened for blood borne pathogens by serological and molecular assays including for HIV and Toxoplasma gondii. The genomic DNA was isolated from the whole blood samples. Genetic polymorphisms of HLA-DQB1*0402 alleles were detected with polymerase chain reaction-sequence-specific primers (PCR-SSPs) technique. The genotypes were defined according to generated fragment patterns in the agarose gel electrophoresis analysis of PCR products. All of the samples were tested at least in duplicate. HLA-DQB1*0402 alleles were detected in 20.8% (16/77) patients and not detected in all HIV positive samples with negative anti-Toxoplasma gondii IgM status (n= 200). The HLA-DQB1*0402 alleles polymorphisms were detected in Javanese HIV patients with positive anti-Toxoplasma gondii IgM. The polymorphisms found may have association with the infection risk of Toxoplasma gondii in HIV patients.

Comparison of six commercial tick-borne encephalitis IgM and IgG ELISA kits and the molecular characterization of their antigenic design.

PubMed

Velay, Aurélie; Solis, Morgane; Barth, Heidi; Sohn, Véronique; Moncollin, Anne; Neeb, Amandine; Wendling, Marie-Josée; Fafi-Kremer, Samira

2018-04-01

Tick-borne encephalitis virus (TBEV) diagnosis is mainly based on the detection of viral-specific antibodies in serum. Several commercial assays are available, but published data on their performance remain unclear. We assessed six IgM and six IgG commercial enzyme-linked immunosorbent assay (ELISA) kits (ELISA-1 through ELISA-6) using 94 samples, including precharacterized TBEV-positive samples (n=50) and -negative samples (n=44). The six manufacturers showed satisfactory sensitivity and specificity and high overall agreement for both IgM and IgG. Three manufacturers showed better reproducibility and were the most sensitive (100%) and specific (95.5-98.1%) for both IgM and IgG. Two of them were also in agreement with the clinical interpretation in more than 90% of the cases. All the assays use inactivated virus as antigen, with strains showing approximately 94% homology at the amino acid level. The antigenic format of the assays was discussed to further improve this TBEV diagnostic tool. Copyright © 2017 Elsevier Inc. All rights reserved.

Determining the IgM and IgG antibodies titer against HSV1, HSV2 and CMV in the serum of schizophrenia patients.

PubMed

Mohagheghi, Masome; Eftekharian, Mohammad Mahdi; Taheri, Mohammad; Alikhani, Mohammad Yousef

2018-02-05

Schizophrenia is a destructive clinical syndrome with diverse mental pathologies. Different mechanisms and factors have a role in this disease. A possible mechanism is that teratogenic viruses cause brain changes and results in the disease appearance. The schizophrenia patients were diagnosed by psychologists and with the consent of patients, five CC of venous blood was drawn. Than Serum samples were isolated and immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2) and cytomegalovirus (CMV) were quantified by ELISA sandwich kit. The Results showed that anti-CMV and anti-HSV1 and anti-HSV2 IgG antibodies in schizophrenia patients were increased significantly (p< 0.05). The increasing of the anti-HSV2 IgM was also observed but increasing amount of the anti-HSV1 IgM was not statistically significant (p< 0.05). Therefore, as a result of this study CMV and HSV1 and HSV2 infection can probably intensify the symptoms in schizophrenia patients.

Depressive, anxiety and hypomanic symptoms in schizophrenia may be driven by tryptophan catabolite (TRYCAT) patterning of IgA and IgM responses directed to TRYCATs.

PubMed

Kanchanatawan, Buranee; Sirivichayakul, Sunee; Carvalho, André F; Anderson, George; Galecki, Piotr; Maes, Michael

2018-01-03

The aim of this study was to delineate the associations between the tryptophan catabolite (TRYCAT) pathway and affective symptoms in schizophrenia. Towards this end we measured immunoglobulin (Ig)A and IgM responses to relatively noxious TRYCATs, namely quinolinic (QA), xanthurenic (XA), picolinic (PA) acid and 3-OH-kynurenine (3HK), and generally protective TRYCATs, namely anthranilic (AA) and kynurenic (KA) acid in 80 patients with schizophrenia and 40 healthy controls. The Hamilton Rating Scale for Depression (HDRS) and anxiety (HAMA), Young Mania Rating Scale (YMRS) as well as the Positive and Negative Symptoms Scale of Schizophrenia (PANSS) were measured. Depression, anxiety and hypomanic as well as negative and positive symptoms were associated with increased IgA responses to PA. Increased IgA responses to XA were associated with anxiety, hypomanic and negative symptoms. Moreover, depressive, anxiety, hypomanic and negative symptoms were characterized by increased IgA responses to the noxious (XA+3HK+QA+PA)/protective (AA+KA) TRYCAT ratio. All symptom dimensions were associated with increased IgM responses to QA, while depressive, anxiety, positive and negative symptoms were accompanied by lowered IgM responses to 3HK. Hypomanic symptoms were additionally accompanied by lowered IgM responses to AA, and negative symptoms by increased IgM responses to KA. In conclusion, both shared and distinct alterations in the activity of the TRYCAT pathway, as well as its regulatory factors and consequences, may underpin affective and classical psychotic symptoms of schizophrenia. Increased mucosa-generated production of noxious TRYCATs, especially PA, and specific changes in IgM-mediated regulatory activities may be associated with the different symptom dimensions of schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Lunar Neutral Exposphere Properties from Pickup Ion Analysis

NASA Technical Reports Server (NTRS)

Hartle, R. E.; Sarantos, M.; Killen, R.; Sittler, E. C. Jr.; Halekas, J.; Yokota, S.; Saito, Y.

2009-01-01

Composition and structure of neutral constituents in the lunar exosphere can be determined through measurements of phase space distributions of pickup ions borne from the exosphere [1]. An essential point made in an early study [ 1 ] and inferred by recent pickup ion measurements [2, 3] is that much lower neutral exosphere densities can be derived from ion mass spectrometer measurements of pickup ions than can be determined by conventional neutral mass spectrometers or remote sensing instruments. One approach for deriving properties of neutral exospheric source gasses is to first compare observed ion spectra with pickup ion model phase space distributions. Neutral exosphere properties are then inferred by adjusting exosphere model parameters to obtain the best fit between the resulting model pickup ion distributions and the observed ion spectra. Adopting this path, we obtain ion distributions from a new general pickup ion model, an extension of a simpler analytic description obtained from the Vlasov equation with an ion source [4]. In turn, the ion source is formed from a three-dimensional exospheric density distribution, which can range from the classical Chamberlain type distribution to one with variable exobase temperatures and nonthermal constituents as well as those empirically derived. The initial stage of this approach uses the Moon's known neutral He and Na exospheres to deriv e He+ and Na+ pickup ion exospheres, including their phase space distributions, densities and fluxes. The neutral exospheres used are those based on existing models and remote sensing studies. As mentioned, future ion measurements can be used to constrain the pickup ion model and subsequently improve the neutral exosphere descriptions. The pickup ion model is also used to estimate the exosphere sources of recently observed pickup ions on KAGUYA [3]. Future missions carrying ion spectrometers (e.g., ARTEMIS) will be able to study the lunar neutral exosphere with great sensitivity

Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies

PubMed Central

McCoy, Laura E.; Falkowska, Emilia; Doores, Katie J.; Le, Khoa; Sok, Devin; van Gils, Marit J.; Euler, Zelda; Burger, Judith A.; Seaman, Michael S.; Sanders, Rogier W.; Schuitemaker, Hanneke; Poignard, Pascal; Wrin, Terri; Burton, Dennis R.

2015-01-01

The broadly neutralizing HIV monoclonal antibodies (bnMAbs) PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4) assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high-mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs) Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC)-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design. PMID:26267277

Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies.

PubMed

McCoy, Laura E; Falkowska, Emilia; Doores, Katie J; Le, Khoa; Sok, Devin; van Gils, Marit J; Euler, Zelda; Burger, Judith A; Seaman, Michael S; Sanders, Rogier W; Schuitemaker, Hanneke; Poignard, Pascal; Wrin, Terri; Burton, Dennis R

2015-08-01

The broadly neutralizing HIV monoclonal antibodies (bnMAbs) PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4) assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high-mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs) Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC)-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design.

Evaluation of the LDBIO point of care test for the combined detection of toxoplasmic IgG and IgM.

PubMed

Chapey, Emmanuelle; Wallon, Martine; Peyron, François

2017-01-01

The toxoplasma ICT IgG-IgM rapid diagnostic test for the simultaneous detection of specific toxoplasmic immunoglobulin (Ig) G and IgM was compared with the Architect fully automated chemiluminescence test. Four hundred sera were included, among which 248 scored negative in Architect. The cassettes were easily read with the naked eye. Diagnostic sensitivity and specificity were 97% and 96%, respectively. The test scored 8 false-positive IgG and yielded negative results in 3 sera displaying unspecific IgM in Architect. The LDBIO appears to be a reliable first line test, although the false-positive results for IgG deserve further investigation. Such an easily performed test could be used advantageously for screening for toxoplasmosis in pregnant women. Copyright © 2016 Elsevier B.V. All rights reserved.

Sin Nombre virus-specific immunoglobulin M and G kinetics in hantavirus pulmonary syndrome and the role played by serologic responses in predicting disease outcome.

PubMed

MacNeil, Adam; Comer, James A; Ksiazek, Thomas G; Rollin, Pierre E

2010-07-15

Sin Nombre virus (SNV) is the primary cause of hantavirus pulmonary syndrome (HPS) in the United States. Although other studies have demonstrated a possible association between neutralizing antibody titers and the severity of HPS, the exact nature of serologic responses and their association with outcomes have not been fully characterized. We examined immunoglobulin M (IgM) and immunoglobulin G (IgG) serologic responses in 94 clinical samples from 81 patients with confirmed HPS. We further compared a subset of 31 patients with fatal HPS and 20 surviving patients for whom samples were available within a week after the onset of HPS. SNV-specific IgM antibodies displayed a trend suggesting an early peak, whereas IgG antibody values peaked later. Among individuals with samples from the first week after the onset of HPS, all surviving patients had SNV-specific IgG responses, compared with <50% of patients with fatal HPS, and the distribution of IgG responses was significantly higher in surviving patients. Production of SNV-specific IgM antibodies occurs early during the clinical course of HPS, whereas production of IgG antibodies may be more protracted. The presence and overall distribution of higher IgG antibody titers in surviving patients with HPS suggests that production of SNV-specific IgG may be a strong predictor of favorable outcomes.

Immune Deficiency State in a Girl with Eczema and Low Serum IgM

PubMed Central

Evans, D. I. K.; Holzel, A.

1970-01-01

This report concerns an immune deficiency disorder in a girl with eczema. She has had recurrent infections including three severe attacks of herpes simplex and five attacks of pneumococcal meningitis. There is a moderate lymphopenia, dysgammaglobulinaemia with high IgG, high IgA, and low IgM; lymphocyte transformation with phytohaemagglutinin is impaired. Production of circulating antibody is abnormal, as are delayed hypersensitivity reactions. Although there is no thrombocytopenia, the resemblance to the Wiskott-Aldrich syndrome is discussed. ImagesFIG. 1.FIG. 2.FIG. 3 PMID:5506938

PAPER-64 Constraints On Reionization. II. The Temperature of the z =8.4 Intergalactic Medium

NASA Astrophysics Data System (ADS)

Pober, Jonathan C.; Ali, Zaki S.; Parsons, Aaron R.; McQuinn, Matthew; Aguirre, James E.; Bernardi, Gianni; Bradley, Richard F.; Carilli, Chris L.; Cheng, Carina; DeBoer, David R.; Dexter, Matthew R.; Furlanetto, Steven R.; Grobbelaar, Jasper; Horrell, Jasper; Jacobs, Daniel C.; Klima, Patricia J.; Kohn, Saul A.; Liu, Adrian; MacMahon, David H. E.; Maree, Matthys; Mesinger, Andrei; Moore, David F.; Razavi-Ghods, Nima; Stefan, Irina I.; Walbrugh, William P.; Walker, Andre; Zheng, Haoxuan

2015-08-01

We present constraints on both the kinetic temperature of the intergalactic medium (IGM) at z = 8.4, and on models for heating the IGM at high-redshift with X-ray emission from the first collapsed objects. These constraints are derived using a semi-analytic method to explore the new measurements of the 21 cm power spectrum from the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER), which were presented in a companion paper, Ali et al. Twenty-one cm power spectra with amplitudes of hundreds of mK2 can be generically produced if the kinetic temperature of the IGM is significantly below the temperature of the cosmic microwave background (CMB); as such, the new results from PAPER place lower limits on the IGM temperature at z = 8.4. Allowing for the unknown ionization state of the IGM, our measurements find the IGM temperature to be above ≈5 K for neutral fractions between 10% and 85%, above ≈7 K for neutral fractions between 15% and 80%, or above ≈10 K for neutral fractions between 30% and 70%. We also calculate the heating of the IGM that would be provided by the observed high redshift galaxy population, and find that for most models, these galaxies are sufficient to bring the IGM temperature above our lower limits. However, there are significant ranges of parameter space that could produce a signal ruled out by the PAPER measurements; models with a steep drop-off in the star formation rate density at high redshifts or with relatively low values for the X-ray to star formation rate efficiency of high redshift galaxies are generally disfavored. The PAPER measurements are consistent with (but do not constrain) a hydrogen spin temperature above the CMB temperature, a situation which we find to be generally predicted if galaxies fainter than the current detection limits of optical/NIR surveys are included in calculations of X-ray heating.

PAPER-64 CONSTRAINTS ON REIONIZATION. II. THE TEMPERATURE OF THE z = 8.4 INTERGALACTIC MEDIUM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pober, Jonathan C.; Ali, Zaki S.; Parsons, Aaron R.

We present constraints on both the kinetic temperature of the intergalactic medium (IGM) at z = 8.4, and on models for heating the IGM at high-redshift with X-ray emission from the first collapsed objects. These constraints are derived using a semi-analytic method to explore the new measurements of the 21 cm power spectrum from the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER), which were presented in a companion paper, Ali et al. Twenty-one cm power spectra with amplitudes of hundreds of mK{sup 2} can be generically produced if the kinetic temperature of the IGM ismore » significantly below the temperature of the cosmic microwave background (CMB); as such, the new results from PAPER place lower limits on the IGM temperature at z = 8.4. Allowing for the unknown ionization state of the IGM, our measurements find the IGM temperature to be above ≈5 K for neutral fractions between 10% and 85%, above ≈7 K for neutral fractions between 15% and 80%, or above ≈10 K for neutral fractions between 30% and 70%. We also calculate the heating of the IGM that would be provided by the observed high redshift galaxy population, and find that for most models, these galaxies are sufficient to bring the IGM temperature above our lower limits. However, there are significant ranges of parameter space that could produce a signal ruled out by the PAPER measurements; models with a steep drop-off in the star formation rate density at high redshifts or with relatively low values for the X-ray to star formation rate efficiency of high redshift galaxies are generally disfavored. The PAPER measurements are consistent with (but do not constrain) a hydrogen spin temperature above the CMB temperature, a situation which we find to be generally predicted if galaxies fainter than the current detection limits of optical/NIR surveys are included in calculations of X-ray heating.« less

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

PubMed Central

Vojdani, Aristo

2009-01-01

Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity. PMID:19435515

Estimating Collisionally-Induced Escape Rates of Light Neutrals from Early Mars

NASA Astrophysics Data System (ADS)

Gacesa, M.; Zahnle, K. J.

2016-12-01

Collisions of atmospheric gases with hot oxygen atoms constitute an important non-thermal mechanism of escape of light atomic and molecular species at Mars. In this study, we present revised theoretical estimates of non-thermal escape rates of neutral O, H, He, and H2 based on recent atmospheric density profiles obtained from the NASA Mars Atmosphere and Volatile Evolution (MAVEN) mission and related theoretical models. As primary sources of hot oxygen, we consider dissociative recombination of O2+ and CO2+ molecular ions. We also consider hot oxygen atoms energized in primary and secondary collisions with energetic neutral atoms (ENAs) produced in charge-exchange of solar wind H+ and He+ ions with atmospheric gases1,2. Scattering of hot oxygen and atmospheric species of interest is modeled using fully-quantum reactive scattering formalism3. This approach allows us to construct distributions of vibrationally and rotationally excited states and predict the products' emission spectra. In addition, we estimate formation rates of excited, translationally hot hydroxyl molecules in the upper atmosphere of Mars. The escape rates are calculated from the kinetic energy distributions of the reaction products using an enhanced 1D model of the atmosphere for a range of orbital and solar parameters. Finally, by considering different scenarios, we estimate the influence of these escape mechanisms on the evolution of Mars's atmosphere throughout previous epochs and their impact on the atmospheric D/H ratio. M.G.'s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Ames Research Center, administered by Universities Space Research Association under contract with NASA. 1N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere", Astroph. J., 790, 98 (2014) 2M. Gacesa, N. Lewkow, and V. Kharchenko, "Non-thermal production and escape of OH from the upper atmosphere of Mars", arXiv:1607

A non-equilibrium neutral model for analysing cultural change.

PubMed

Kandler, Anne; Shennan, Stephen

2013-08-07

Neutral evolution is a frequently used model to analyse changes in frequencies of cultural variants over time. Variants are chosen to be copied according to their relative frequency and new variants are introduced by a process of random mutation. Here we present a non-equilibrium neutral model which accounts for temporally varying population sizes and mutation rates and makes it possible to analyse the cultural system under consideration at any point in time. This framework gives an indication whether observed changes in the frequency distributions of a set of cultural variants between two time points are consistent with the random copying hypothesis. We find that the likelihood of the existence of the observed assemblage at the end of the considered time period (expressed by the probability of the observed number of cultural variants present in the population during the whole period under neutral evolution) is a powerful indicator of departures from neutrality. Further, we study the effects of frequency-dependent selection on the evolutionary trajectories and present a case study of change in the decoration of pottery in early Neolithic Central Europe. Based on the framework developed we show that neutral evolution is not an adequate description of the observed changes in frequency. Copyright © 2013 Elsevier Ltd. All rights reserved.

Total immunoglobulin G and IgG1 subclass levels specific for the MSP-1(19) of Plasmodium falciparum are different in individuals with either processing-inhibitory, blocking or neutral antibodies.

PubMed

Omosun, Y O; Adoro, S; Anumudu, C I; Odaibo, A; Holder, A A; Nwagwu, M; Nwuba, R I

2010-06-01

Some MSP-1(19) specific antibodies that inhibit merozoite invasion also inhibit the secondary processing of MSP-1. However the binding of these inhibitory antibodies can be blocked by another group of antibodies, called blocking antibodies, which recognize adjacent or overlapping epitopes, but themselves have no effect on either MSP-1 processing or merozoite invasion. These antibodies have been reported to be present in individuals living in a malaria endemic area. Blood samples were obtained from children shown to have processing inhibitory, blocking, and neutral antibodies in a previous study. Enzyme linked immunosorbent assay (ELISA), was used to determine the total IgG, IgM and IgG subtypes. There was a significant difference in anti-MSP-1(19) IgG, while there was no significant difference in the anti-MSP-1(19) IgM. Only anti MSP-1(19) IgG1, amongst the IgG subtypes was significantly different between the groups. This study shows that antibodies against MSP-1 are different not only in specificity and function but also in the amount of total IgG and IgG subtype produced.

IgG and IgM anti-snRNP reactivity in sequentially obtained serum samples from patients with connective tissue diseases.

PubMed Central

Nyman, U; Lundberg, I; Hedfors, E; Wahren, M; Pettersson, I

1992-01-01

Sequentially obtained serum samples from 30 patients with connective tissue disease positive for antibody to ribonucleoprotein (RNP) were examined to determine the specificities of IgG and IgM antibodies to snRNP during the disease course using immunoblotting of nuclear extracts. The antibody patterns were correlated with disease activity. The patterns of antibody to snRNP of individual patients were mainly stable during the study but changes in levels of antibody to snRNP were seen corresponding to changes in clinical activity. These results indicate that increased reactivity of serum IgM antibodies against the B/B' proteins seems to precede a clinically evident exacerbation of disease whereas IgG antibody reactivity to the 70 K protein peaks at the time of a disease flare. Images PMID:1485812

Ocular sarcoidosis masked by positive IgM for toxoplasmosis.

PubMed

Peres, Murilo Bertazzo; Sousa, Jacqueline Martins de; Nascimento, Heloisa

2017-01-01

We report a case of ocular sarcoidosis with positive immunoglobulin (Ig) M and IgG serology for toxoplasmosis. The patient was a young female with red painful eyes, bilateral eyelid edema, and panuveitis with periphlebitis. In laboratory testing, she was IgM and IgG positive for toxoplasmosis and anergic in the tuberculin test. Topical treatment for anterior uveitis and oral antibiotics for toxoplasmosis were started, without improvement. Orbit tomography showed increased lacrimal glands bilaterally, and chest X-ray radiographic findings were consistent with pulmonary sarcoidosis, which supported the presumed ocular sarcoidosis diagnosis. The patient was treated with oral prednisone and methotrexate without antibiotics. She showed clinical and vision improvement without recurrences during the 1-year follow-up. Ocular sarcoidosis is an important differential diagnosis requiring careful anamnesis and ophthalmological examinations. Ancillary tests, such as X-ray radiography, tomography, and clinical and laboratory evaluations may help rule out other causes. Treatment mainly consists of corticosteroids and immunosuppression.

Association with emotional information alters subsequent processing of neutral faces

PubMed Central

Riggs, Lily; Fujioka, Takako; Chan, Jessica; McQuiggan, Douglas A.; Anderson, Adam K.; Ryan, Jennifer D.

2014-01-01

The processing of emotional as compared to neutral information is associated with different patterns in eye movement and neural activity. However, the ‘emotionality’ of a stimulus can be conveyed not only by its physical properties, but also by the information that is presented with it. There is very limited work examining the how emotional information may influence the immediate perceptual processing of otherwise neutral information. We examined how presenting an emotion label for a neutral face may influence subsequent processing by using eye movement monitoring (EMM) and magnetoencephalography (MEG) simultaneously. Participants viewed a series of faces with neutral expressions. Each face was followed by a unique negative or neutral sentence to describe that person, and then the same face was presented in isolation again. Viewing of faces paired with a negative sentence was associated with increased early viewing of the eye region and increased neural activity between 600 and 1200 ms in emotion processing regions such as the cingulate, medial prefrontal cortex, and amygdala, as well as posterior regions such as the precuneus and occipital cortex. Viewing of faces paired with a neutral sentence was associated with increased activity in the parahippocampal gyrus during the same time window. By monitoring behavior and neural activity within the same paradigm, these findings demonstrate that emotional information alters subsequent visual scanning and the neural systems that are presumably invoked to maintain a representation of the neutral information along with its emotional details. PMID:25566024

IgA, IgM and IgG anti-M. leprae antibodies in babies of leprosy mothers during the first 2 years of life.

PubMed Central

Melsom, R; Harboe, M; Duncan, M E

1982-01-01

IgA, IgM and IgG anti-M. leprae antibody activity was estimated by solid phase radioimmunoassay in repeated serum samples from cord sera to sera taken 2 years after birth from 29 babies of mothers with lepromatous leprosy (Group 1) and 16 babies of mothers with tuberculoid leprosy and non-leprosy control mothers (Group 2). IgA anti-M. leprae antibody activity could be detected in 30% and IgM anti-M. leprae antibody activity in 50% of cord sera from Group 1, but not in any of the cord sera from Group 2. After birth, there was a significantly higher increase of IgA and IgM anti-M. leprae antibody activity in sera taken 3-6 months after birth from babies of Group 1 compared to Group 2, but the IgA and IgM activity in sera taken after 6 months of age showed the same increase in the two groups. IgG anti-M. leprae antibody activity showed a marked decrease in sera from both Groups 1 and 2 taken 3-6 and 6-9 months after birth compared to the activity in the cord sera. No increase of the IgG activity could be demonstrated even in sera taken 15-24 months after birth in any of the two groups. These findings are discussed in relation to possible transfer of M. leprae bacilli across the placenta, the influence of M. leprae and other mycobacteria exposure on the antibody activity, the poor IgG anti-M. leprae antibody response and subclinical leprosy infection in babies exposed to leprosy below 2 years of age. PMID:6756719

Neutral beam monitoring

DOEpatents

Fink, Joel H.

1981-08-18

Method and apparatus for monitoring characteristics of a high energy neutral beam. A neutral beam is generated by passing accelerated ions through a walled cell containing a low energy neutral gas, such that charge exchange neutralizes the high energy ion beam. The neutral beam is monitored by detecting the current flowing through the cell wall produced by low energy ions which drift to the wall after the charge exchange. By segmenting the wall into radial and longitudinal segments various beam conditions are further identified.

From "Below Dignity" to "Above It All": Origins and Early History of Underwater Neutral Buoyancy Simulation of Weightlessness for EVA Procedures Development and Training

NASA Technical Reports Server (NTRS)

Charles, John B.

2013-01-01

An attempt to clarify some vague memories of underwater studies of astronaut capabilities in space led Dr. John Charles to become acquainted with Sam Mattingly, one of the pioneers in the field, and to greater insights into Mattingly's work simulating Gemini EVAs in the mid-1960s. Charles recounted major accomplishments by Environmental Research Associates (ERA), Mattingly's company for contracting with NASA Langley on several early studies. ERA's work was considered within the context of contemporary efforts to simulate weightlessness and the widespread development of neutral buoyancy facilities after ERA's successful demonstration for Gemini 12.

Sociodemographic factors associated with IgG and IgM seroprevalence for human cytomegalovirus infection in adult populations of Pakistan: a seroprevalence survey.

PubMed

Ibrahim, Saira; Siddiqui, Anwar A; Siddiqui, Amna R; Ahmed, Waquaruddin; Moss, Paul A H; Lalani, El-Nasir M A

2016-10-22

The seroprevalence of human cytomegalovirus (HCMV) infection ranges from 30 to 90 % in developed countries. Reliable estimates of HCMV seroprevalence are not available for Pakistan. This study determined the seroprevalence and sociodemographic factors associated with HCMV infection in adult populations of Karachi, Pakistan. A seroprevalence survey was conducted on 1000 adults, including residents of two semi-urban communities, and visitors to a government and a private hospital. Questionnaire-based interviews were conducted. Sera were analysed for HCMV-specific IgG and IgM. Chi-square or Fisher's exact test was used for comparing sociodemographic variables against seropositivity of HCMV-IgG or IgM. Multiple logistic regression modeling was performed for IgG seroprevalence and adjusted odds ratios were computed. The seroprevalence of HCMV-IgG and IgM was 93.2 and 4.3 % respectively. 95.3 % of individuals who were IgM seropositive were also seropositive for IgG. Around 6 % (15/250) of women of childbearing age remained uninfected and were therefore susceptible to primary infection. HCMV-IgG seroprevalence was associated with being female (p = 0.001), increasing age (p = 0.002) and crowding index (p = 0.003) and also with lower levels of both education (p < 0.001) and income (p = 0.008). Seroprevalence also differed significantly by marital status (p = 0.008) and sampling location (p < 0.001). A logistic regression model for HCMV-IgG seroprevalence showed associations with being female (OR = 1.89; 95 % CI: 1.10-3.25), increasing age (OR = 3.95; 95 % CI: 1.79-8.71) and decreasing income (OR = 0.72; 95 % CI: 0.54-0.96). A strong association was observed between increased seroprevalence of HCMV-IgM and decreasing household size (p = 0.008). Seroprevalence of HCMV is very high in Pakistan, although 6 % of women of childbearing age remain at risk of primary infection. The IgM seropositivity observed in some individuals

Neonatal screening for congenital toxoplasmosis in the Poznań region of Poland by analysis of Toxoplasma gondii-specific IgM antibodies eluted from filter paper blood spots.

PubMed

Paul, M; Petersen, E; Pawlowski, Z S; Szczapa, J

2000-01-01

The aims of the study were to determine the prevalence of congenital toxoplasmosis at birth in the Poznań region of Poland, the value of the serologic examination of filter paper blood specimens collected from newborns for the diagnosis of congenital Toxoplasma infection and the duration of anti-Toxoplasma-specific IgM antibodies in infants' sera. All neonates born in the maternity wards of the University Hospital of Gynaecology and Obstetrics in Poznań and in 10 selected obstetrics wards in the district hospitals were included. Blood samples were collected on filter paper cards, between the first and sixth day of life, screened for anti-Toxoplasma-specific IgM antibodies by an immunocapture enzyme-linked immunosorbent assay and if positive further analyzed for specific IgG and IgA antibodies. Between June, 1996, and October, 1998, filter paper samples from 27,516 liveborn infants were tested, which constituted approximately 75% of all births and 83% of liveborn neonates from the Poznań region. Anti-T. gondii-specific IgM antibodies were found in 13 newborns, equivalent to a prevalence of Toxoplasma-specific IgM in newborns of 1 per 2,117 liveborn children (0.47 per 1,000) or 1 per 870 children (1.15 per 1,000) born to seronegative women at risk of primary T. gondii infection during pregnancy. We identified two congenitally infected infants who were IgM-negative at birth, had a classic triad of clinical symptoms during the first year of life and had high levels of specific IgG. The birth prevalence of congenital toxoplasmosis in the Poznań region was at least 1 per 1,834 live births (0.55 per 1,000) or 1 per 754 live neonates born to seronegative women (1.33 per 1,000). The sensitivity of the IgM assay on eluate from filter paper was not more than 86.7%, and the mean duration of IgM detectable by enzyme-linked immunosorbent assay in serum samples was the first 4.8 weeks of life. In Poland the screening for congenital toxoplasmosis detecting one case per each 2

Early Diagnosis of Scrub Typhus with a Rapid Flow Assay Using Recombinant Major Outer Membrane Protein Antigen (r56) of Orientia tsutsugamushi

PubMed Central

Ching, W.-M.; Rowland, D.; Zhang, Z.; Bourgeois, A. L.; Kelly, D.; Dasch, G. A.; Devine, P. L.

2001-01-01

The variable 56-kDa major outer membrane protein of Orientia tsutsugamushi is the immunodominant antigen in human scrub typhus infections. We developed a rapid immunochromatographic flow assay (RFA) for the detection of immunoglobulin M (IgM) and IgG antibodies to O. tsutsugamushi. The RFA employs a truncated recombinant 56-kDa protein from the Karp strain as the antigen. The performance of the RFA was evaluated with a panel of 321 sera (serial bleedings of 85 individuals suspected of scrub typhus) which were collected in the Pescadore Islands, Taiwan, from 1976 to 1977. Among these 85 individuals, IgM tests were negative for 7 cases by both RFA and indirect fluorescence assay (IFA) using Karp whole-cell antigen. In 29 cases specific responses were detected by the RFA earlier than by IFA, 44 cases had the same detection time, and 5 cases were detected earlier by IFA than by RFA. For IgG responses, 4 individuals were negative with both methods, 37 cases exhibited earlier detection by RFA than IFA, 42 cases were detected at the same time, and 2 cases were detected earlier by IFA than by RFA. The sensitivities of RFA detection of antibody in sera from confirmed cases were 74 and 86% for IgM and IgG, respectively. When IgM and IgG results were combined, the sensitivity was 89%. A panel of 78 individual sera collected from patients with no evidence of scrub typhus was used to evaluate the specificity of the RFA. The specificities of the RFA were 99% for IgM and 97% for IgG. The sensitivities of IFA were 53 and 73% for IgM and IgG, respectively, and were 78% when the results of IgM and IgG were combined. The RFA test was significantly better than the IFA test for the early detection of antibody to scrub typhus in primary infections, while both tests were equally sensitive with reinfected individuals. PMID:11238230

Diagnosis of Barmah Forest Virus Infection by a Nested Real-Time SYBR Green RT-PCR Assay

PubMed Central

Hueston, Linda; Toi, Cheryl S.; Jeoffreys, Neisha; Sorrell, Tania; Gilbert, Gwendolyn

2013-01-01

Barmah Forest virus (BFV) is a mosquito borne (+) ssRNA alphavirus found only in Australia. It causes rash, myalgia and arthralgia in humans and is usually diagnosed serologically. We developed a real-time PCR assay to detect BFV in an effort to improve diagnosis early in the course of infection. The limit of detection was 16 genome equivalents with a specificity of 100%. Fifty five serum samples from BFV-infected patients were tested by the PCR. 52 of 53 antibody-positive samples were PCR negative. Two culture-positive (neutralizing antibody negative) samples were positive on first round PCR, while one sample (IgM and neutralizing antibody strongly positive, IgG negative) was positive on second round PCR, suggesting that viral RNA is detectable and transiently present in early infection. PCR can provide results faster than culture, is capable of high throughput and by sequencing the PCR product strain variants can be characterized. PMID:23935816

Color Superconductivity and Charge Neutrality in Yukawa Theory

NASA Astrophysics Data System (ADS)

Alford, Mark G.; Pangeni, Kamal; Windisch, Andreas

2018-02-01

It is generally believed that when Cooper pairing occurs between two different species of fermions, their Fermi surfaces become locked together so that the resultant state remains "neutral," with equal number densities of the two species, even when subjected to a chemical potential that couples to the difference in number densities. This belief is based on mean-field calculations in models with a zero-range interaction, where the anomalous self-energy is independent of energy and momentum. Following up on an early report of a deviation from neutrality in a Dyson-Schwinger calculation of color-flavor-locked quark matter, we investigate the neutrality of a two-species condensate using a Yukawa model which has a finite-range interaction. In a mean field calculation we obtain the full energy-momentum dependence of the self-energy and find that the energy dependence leads to a population imbalance in the Cooper-paired phase when it is stressed by a species-dependent chemical potential. This gives some support to the suggestion that the color-flavor-locked phase of quark matter might not be an insulator.

IgM nephropathy; can we still ignore it

PubMed Central

Vanikar, Aruna

2013-01-01

Context:IgM nephropathy (IgMN) is a relatively less recognized clinico-immunopathological entity in the domain of glomerulonephritis , often thought to be a bridge between minimal change disease and focal segmental glomerulosclerosis. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. Results: IgM nephropathy can present as nephritic syndrome or less commonly with subnephrotic proteinuria or rarely hematuria. About 30% patients respond to steroids whereas others are steroid dependent / resistant. They should be given a trial of Rituximab or stem cell therapy. Conclusions:IgM nephropathy (IgMN) is an important and rather neglected pathology responsible for renal morbidity in children and adults in developing countries as compared to developed nations with incidence of 2-18.5% of native biopsies. Abnormal T-cell function with hyperfunctioning suppressor T-cells are believed to be responsible for this disease entity. Approximately one third of the patients are steroid responders where as the remaining two thirds are steroid resistant or dependent. Therapeutic trials including cell therapies targeting suppressor T-cells are required. PMID:24475434

Immunohistochemical detection of IgM and IgG in lung tissue of dogs with leptospiral pulmonary haemorrhage syndrome (LPHS)

USDA-ARS?s Scientific Manuscript database

Leptospiral pulmonary haemorrhage syndrome (LPHS) is a severe form of leptospirosis. Pathogenic mechanisms are poorly understood. Lung tissues from 26 dogs with LPHS, 5 dogs with pulmonary haemorrhage due to other causes and 6 healthy lungs were labelled for IgG, IgM and leptospiral antigens. Three ...

What Can Galaxies Tell Us About The Epoch of Reionization?

NASA Astrophysics Data System (ADS)

Mason, Charlotte; GLASS, BoRG

2018-01-01

The reionization of neutral hydrogen in the intergalactic medium (IGM) in the universe's first billion years (z>6) was likely driven by the first stars and galaxies, and its history encodes information about their properties. But the timeline of reionization is not well-measured and it is still unclear whether galaxies alone can produce the required ionizing photons. I will describe two key ways in which galaxies at our current observational frontiers can constrain reionization.One tool is the UV luminosity function (LF), which traces the evolution of star-forming galaxies and their ionizing photons. I will describe a Bayesian technique to account for gravitational lensing magnification bias in galaxy surveys to produce accurate LFs. I will then describe a simple, but powerful, model for LF evolution and its implications for reionization and z>10 galaxy surveys with JWST. Secondly, Lyman alpha (Lya) emission from galaxies is a potential probe of the IGM ionization state as Lya photons are strongly attenuated by neutral hydrogen, but requires disentangling physics on pc to Gpc scales. I will introduce a new forward-modeling Bayesian framework which combines cosmological IGM simulations with models of interstellar medium conditions to infer the IGM neutral fraction from observations of Lya emission. I will present our new measurement of the neutral fraction at z~7 and place it in the context of other constraints of the reionization history. I will describe ongoing efforts to build larger samples of Lya emitting galaxies for more accurate measurements with the HST survey GLASS, and will describe future prospects with JWST.

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

PubMed

Collins, Matthew H; McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A; Baric, Ralph S; Lazear, Helen M; de Silva, Aravinda M

2017-05-01

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection

PubMed Central

McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A.; Baric, Ralph S.; Lazear, Helen M.

2017-01-01

Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus–specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity. PMID:28418292

Neutral-neutral and neutral-ion collision integrals for Y2O3-Ar plasma system

NASA Astrophysics Data System (ADS)

Dhamale, Gayatri D.; Nath, Swastik; Mathe, Vikas L.; Ghorui, Srikumar

2017-06-01

A detailed investigation on the neutral-neutral and neutral-ion collision integrals is reported for Y2O3-Ar plasma, an important system of functional material with unique properties having a wide range of processing applications. The calculated integrals are indispensible pre-requisite for the estimation of transport properties needed in CFD modelling of associated plasma processes. Polarizability plays an important role in determining the integral values. Ambiguity in selecting appropriate polarizability data available in the literature and calculating effective number of electrons in the ionized species contributing to the polarizability are addressed. The integrals are evaluated using Lennard-Jones like phenomenological potential up to (l,s) = (4,4). Used interaction potential is suitable for both neutral-neutral and neutral-ion interactions. For atom-parent ion interactions, contribution coming from the inelastic resonant charge transfer process has been accounted properly together with that coming from the elastic counterpart. A total of 14 interacting species and 60 different interactions are considered. Key contributing factors like basic electronic properties of the interacting species and associated polarizability values are accounted carefully. Adopted methodology is first benchmarked against data reported in the literature and then applied to the Y2O3-Ar plasma system for estimating the collision integrals. Results are presented in the temperature range of 100 K-100 000 K.

CD22 serves as a receptor for soluble IgM.

PubMed

Adachi, Takahiro; Harumiya, Satoru; Takematsu, Hiromu; Kozutsumi, Yasunori; Wabl, Matthias; Fujimoto, Manabu; Tedder, Thomas F

2012-01-01

CD22 (Siglec-2) is a B-cell membrane-bound lectin that recognizes glycan ligands containing α2,6-linked sialic acid (α2,6Sia) and negatively regulates signaling through the B-cell Ag receptor (BCR). Although CD22 has been investigated extensively, its precise function remains unclear due to acting multiple phases. Here, we demonstrate that CD22 is efficiently activated in trans by complexes of Ag and soluble IgM (sIgM) due to the presence of glycan ligands on sIgM. This result strongly suggests sIgM as a natural trans ligand for CD22. Also, CD22 appears to serve as a receptor for sIgM, which induces a negative feedback loop for B-cell activation similar to the Fc receptor for IgG (FcγRIIB). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood.

PubMed

Tran, Thanh Nga T; de Vries, Peter J; Hoang, Lan Phuong; Phan, Giao T; Le, Hung Q; Tran, Binh Q; Vo, Chi Mai T; Nguyen, Nam V; Kager, Piet A; Nagelkerke, Nico; Groen, Jan

2006-01-25

The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots were tested with ELISA for dengue IgG and IgM. 74 serum pairs were tested again in another laboratory with similar methods, after a mean of 252 days. Cases were classified as no dengue (10 %), past dengue (55%) acute primary (7%) or secondary (28%) dengue. Significant differences between the two laboratories' results were found leading to different diagnostic classification (kappa 0.46, p < 0.001). Filter paper results correlated poorly to serum values, being more variable and lower with a mean (95% CI) difference of 0.82 (0.36 to 1.28) for IgMt3, 0.94 (0.51 to 1.37) for IgGt0 and 0.26 (-0.20 to 0.71) for IgGt3. This also led to differences in diagnostic classification (kappa value 0.44, p < 0.001) The duration of storage of frozen serum and dried filter papers, sealed in nylon bags in an air-conditioned room, had no significant effect on the ELISA results. Dengue virus IgG antibodies in serum and filter papers was not affected by duration of storage, but was subject to inter-laboratory variability. Dengue virus IgM antibodies measured in serum reconstituted from blood spots on filter papers were lower than in serum, in particular in the acute phase of disease. Therefore this method limits its value for diagnostic confirmation of individual patients with dengue virus infections. However the detection of dengue virus IgG antibodies eluted from filter paper can be used for sero-prevalence cross sectional studies.

Enzyme-linked immunoassay for dengue virus IgM and IgG antibodies in serum and filter paper blood

PubMed Central

Tran, Thanh Nga T; de Vries, Peter J; Hoang, Lan Phuong; Phan, Giao T; Le, Hung Q; Tran, Binh Q; Vo, Chi Mai T; Nguyen, Nam V; Kager, Piet A; Nagelkerke, Nico; Groen, Jan

2006-01-01

Background The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. Methods 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots were tested with ELISA for dengue IgG and IgM. 74 serum pairs were tested again in another laboratory with similar methods, after a mean of 252 days. Results Cases were classified as no dengue (10 %), past dengue (55%) acute primary (7%) or secondary (28%) dengue. Significant differences between the two laboratories' results were found leading to different diagnostic classification (kappa 0.46, p < 0.001). Filter paper results correlated poorly to serum values, being more variable and lower with a mean (95% CI) difference of 0.82 (0.36 to 1.28) for IgMt3, 0.94 (0.51 to 1.37) for IgGt0 and 0.26 (-0.20 to 0.71) for IgGt3. This also led to differences in diagnostic classification (kappa value 0.44, p < 0.001) The duration of storage of frozen serum and dried filter papers, sealed in nylon bags in an air-conditioned room, had no significant effect on the ELISA results. Conclusion Dengue virus IgG antibodies in serum and filter papers was not affected by duration of storage, but was subject to inter-laboratory variability. Dengue virus IgM antibodies measured in serum reconstituted from blood spots on filter papers were lower than in serum, in particular in the acute phase of disease. Therefore this method limits its value for diagnostic confirmation of individual patients with dengue virus infections. However the detection of dengue virus IgG antibodies eluted from filter paper can be used for sero-prevalence cross sectional studies. PMID:16436203

IgM anti-myeloperoxidase antibody-secreting lymphocytes are present in the peripheral repertoire of lupus mice but rarely differentiate into IgG-producing cells

PubMed Central

Vittecoq, O; Brard, F; Jovelin, F; Le Loet, X; Tron, F; Gilbert, D

1999-01-01

Two IgM, κ anti-myeloperoxidase (MPO) monoclonal antibodies, 6D6 and 9B5, bound to MPO in a solid-phase enzyme-linked immunosorbent assay were derived from the splenocytes of (NZB × NZW) F1 and MRL/lpr-lpr mice, respectively. 6D6 gave a characteristic perinuclear immunofluorescence staining pattern on ethanol-fixed human neutrophils, bound to the native form of MPO by immunoblotting and had a high constant affinity for MPO as demonstrated by real-time specific interaction. 9B5 produced a cytoplasmic immunofluorescence staining pattern, reacted with the heavy chain of MPO and had a low constant affinity for MPO. The heavy-and light-chain variable region genes of monoclonal antibodies (mAb) 6D6 and 9B5 were sequenced and found to be highly homologous to germline genes and to contain negatively charged amino acids in the complementarity determining regions. IgM MPO-binding activity was observed in most BW and MRL/lpr-lpr mouse sera, which may correspond to polyclonal activation of B cells, whereas IgG anti-MPO antibodies could be rarely detected. Thus, this study indicates that (i) BW and MRL/lpr-lpr mice do not delete IgM anti-MPO secreting B cells, do not maintain these B cells in a state of anergy, but most individuals are not able to spontaneously induce the class-switching of this autoantibody population; (ii) IgM anti-MPO antibodies can recognize different epitopes on MPO and produce different immunofluorescence staining pattern on ethanol-fixed human neutrophils, as demonstrated by the immunochemical properties of the two lupus-mouse derived mAb. PMID:10540169

Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shedlock, Devon J., E-mail: shedlock@mail.med.upenn.ed; Bailey, Michael A., E-mail: mike.bailey@taurigroup.co; Popernack, Paul M.

2010-06-05

Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished bymore » reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.« less

IgA and IgM protein primarily drive plasma corona-induced adhesion reduction of PLGA nanoparticles in human blood flow.

PubMed

Sobczynski, Daniel J; Eniola-Adefeso, Omolola

2017-06-01

The high abundance of immunoglobulins (Igs) in the plasma protein corona on poly(lactic-co-glycolic) acid (PLGA)-based vascular-targeted carriers (VTCs) has previously been shown to reduce their adhesion to activated endothelial cells (aECs) in human blood flow. However, the relative role of individual Ig classes (e.g., IgG, IgA, and IgM) in causing adhesion reduction remains largely unknown. Here, we characterized the influence of specific Ig classes in prescribing the binding efficiency of PLGA nano-sized VTCs in blood flow. Specifically, we evaluated the flow adhesion to aECs of PLGA VTCs with systematic depletion of various Igs in their corona. Adhesion reduction was largely eliminated for PLGA VTCs when all Igs were removed from the corona. Furthermore, re-addition of IgA or IgM to the Igs-depleted corona reinstated the low adhesion of PLGA VTCs, as evidenced by ∼40-70% reduction relative to particles with an Igs-deficient corona. However, re-addition of a high concentration of IgG to the Igs-depleted corona did not cause significant adhesion reduction. Overall, the presented results reveal that PLGA VTC adhesion reduction in blood flows is primarily driven by high adsorption of IgA and IgM in the particle corona. Pre-coating of albumin on PLGA VTCs mitigated the extent of adhesion reduction in plasma for some donors but was largely ineffective in general. Overall, this work may shed light into effective control of protein corona composition, thereby enhancing VTC functionality in vivo for eventual clinical use.

IgA and IgM protein primarily drive plasma corona‐induced adhesion reduction of PLGA nanoparticles in human blood flow

PubMed Central

Sobczynski, Daniel J.

2017-01-01

Abstract The high abundance of immunoglobulins (Igs) in the plasma protein corona on poly(lactic‐co‐glycolic) acid (PLGA)‐based vascular‐targeted carriers (VTCs) has previously been shown to reduce their adhesion to activated endothelial cells (aECs) in human blood flow. However, the relative role of individual Ig classes (e.g., IgG, IgA, and IgM) in causing adhesion reduction remains largely unknown. Here, we characterized the influence of specific Ig classes in prescribing the binding efficiency of PLGA nano‐sized VTCs in blood flow. Specifically, we evaluated the flow adhesion to aECs of PLGA VTCs with systematic depletion of various Igs in their corona. Adhesion reduction was largely eliminated for PLGA VTCs when all Igs were removed from the corona. Furthermore, re‐addition of IgA or IgM to the Igs‐depleted corona reinstated the low adhesion of PLGA VTCs, as evidenced by ∼40–70% reduction relative to particles with an Igs‐deficient corona. However, re‐addition of a high concentration of IgG to the Igs‐depleted corona did not cause significant adhesion reduction. Overall, the presented results reveal that PLGA VTC adhesion reduction in blood flows is primarily driven by high adsorption of IgA and IgM in the particle corona. Pre‐coating of albumin on PLGA VTCs mitigated the extent of adhesion reduction in plasma for some donors but was largely ineffective in general. Overall, this work may shed light into effective control of protein corona composition, thereby enhancing VTC functionality in vivo for eventual clinical use. PMID:28932819

The amino-terminal domain of ORF149 of koi herpesvirus is preferentially targeted by IgM from carp populations surviving infection.

PubMed

Torrent, F; Villena, A; Lee, P A; Fuchs, W; Bergmann, S M; Coll, J M

2016-10-01

Recombinantly expressed fragments of the protein encoded by ORF149 (pORF149), a structural protein from the common- and koi-carp-infecting cyprinid herpesvirus-3 (CyHV-3) that was previously shown to be antigenic, were used to obtain evidence that its amino-terminal part contains immunodominant epitopes in fish populations that survived the infection. To obtain such evidence, nonspecific binding of carp serum tetrameric IgM had to be overcome by a novel ELISA protocol (rec2-ELISA). Rec2-ELISA involved pre-adsorption of carp sera with a heterologous recombinant fragment before incubation with pORF149 fragments and detection with anti-carp IgM monoclonal antibodies. Only in this way was it possible to distinguish between sera from uninfected and survivor carp populations. Although IgM from survivors recognised pORF149 fragments to a lesser degree than whole virus, specificity was confirmed by correlation of rec2- and CyHV-3-ELISAs, inhibition of rec2-ELISA by an excess of frgIIORF149, ELISA using IgM-capture, Western blotting, and reduction of reactivity in CyHV-3-ELISA by pre-adsorption of sera with frgIIORF149. The similarity of IgM-binding profiles between frgIORF149 (amino acid residues 42-629) and frgIIORF149 (42-159) and their reactivities with previously described anti-CyHV-3 monoclonal antibodies confirmed that most pORF149 epitopes were localised in its amino-terminal part.

The Neutral Islands during the Late Epoch of Reionization

NASA Astrophysics Data System (ADS)

Xu, Yidong; Yue, Bin; Chen, Xuelei

2018-05-01

The large-scale structure of the ionization field during the epoch of reionization (EoR) can be modeled by the excursion set theory. While the growth of ionized regions during the early stage are described by the ``bubble model'', the shrinking process of neutral regions after the percolation of the ionized region calls for an ``island model''. An excursion set based analytical model and a semi-numerical code (islandFAST) have been developed. The ionizing background and the bubbles inside the islands are also included in the treatment. With two kinds of absorbers of ionizing photons, i.e. the large-scale under-dense neutral islands and the small-scale over-dense clumps, the ionizing background are self-consistently evolved in the model.

EVA Development and Verification Testing at NASA's Neutral Buoyancy Laboratory

NASA Technical Reports Server (NTRS)

Jairala, Juniper C.; Durkin, Robert; Marak, Ralph J.; Sipila, Stepahnie A.; Ney, Zane A.; Parazynski, Scott E.; Thomason, Arthur H.

2012-01-01

As an early step in the preparation for future Extravehicular Activities (EVAs), astronauts perform neutral buoyancy testing to develop and verify EVA hardware and operations. Neutral buoyancy demonstrations at NASA Johnson Space Center's Sonny Carter Training Facility to date have primarily evaluated assembly and maintenance tasks associated with several elements of the International Space Station (ISS). With the retirement of the Shuttle, completion of ISS assembly, and introduction of commercial players for human transportation to space, evaluations at the Neutral Buoyancy Laboratory (NBL) will take on a new focus. Test objectives are selected for their criticality, lack of previous testing, or design changes that justify retesting. Assembly tasks investigated are performed using procedures developed by the flight hardware providers and the Mission Operations Directorate (MOD). Orbital Replacement Unit (ORU) maintenance tasks are performed using a more systematic set of procedures, EVA Concept of Operations for the International Space Station (JSC-33408), also developed by the MOD. This paper describes the requirements and process for performing a neutral buoyancy test, including typical hardware and support equipment requirements, personnel and administrative resource requirements, examples of ISS systems and operations that are evaluated, and typical operational objectives that are evaluated.

Multiplexed Anti-Toxoplasma IgG, IgM, and IgA Assay on Plasmonic Gold Chips: towards Making Mass Screening Possible with Dye Test Precision

PubMed Central

Li, Xiaoyang; Pomares, Christelle; Gonfrier, Géraldine; Koh, Byumseok; Zhu, Shoujun; Gong, Ming

2016-01-01

Toxoplasmosis is an infection caused by the protozoan parasite Toxoplasma gondii that can lead to severe sequelae in the fetus during pregnancy. Definitive serologic diagnosis of the infection during gestation is made mostly by detecting T. gondii-specific antibodies, including IgG and IgM, individually in a single serum sample by using commercially available kits. The IgA test is used by some laboratories as an additional marker of acute infection. Most of the commercial tests have failed to reach 100% correlation with the reference method, the Sabin-Feldman dye test for the detection of Toxoplasma IgG antibodies. For Toxoplasma IgM and IgA antibodies, there is no reference method and their evaluation is done by comparing the results of one assay to those of another. There is a need for multiplexed assay platforms, as the serological diagnosis of T. gondii infection does not rely on the detection of a single Ig subtype. Here we describe the development of a plasmonic gold chip with vast fluorescence enhancement in the near-infrared region for simultaneous detection of IgG, IgM, and IgA antibodies against T. gondii in an ∼1-μl serum or whole-blood sample. When 168 samples were tested on this platform, IgG antibody detection sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. IgM antibody detection achieved 97.6% sensitivity and 96.9% specificity with a 90.9% PPV and a 99.2% NPV. Thus, the nanoscience-based plasmonic gold platform enables a high-performance, low-cost, multiplexed assay requiring ultrasmall blood volumes, paving the way for the implementation of universal screening for toxoplasmosis infection during gestation. PMID:27008879

CD73 expression identifies a subset of IgM+ antigen-experienced cells with memory attributes that is T cell and CD40 signalling dependent.

PubMed

D'Souza, Lucas; Gupta, Sneh Lata; Bal, Vineeta; Rath, Satyajit; George, Anna

2017-12-01

B-cell memory was long characterized as isotype-switched, somatically mutated and germinal centre (GC)-derived. However, it is now clear that the memory pool is a complex mixture that includes unswitched and unmutated cells. Further, expression of CD73, CD80 and CD273 has allowed the categorization of B-cell memory into multiple subsets, with combinatorial expression of the markers increasing with GC progression, isotype-switching and acquisition of somatic mutations. We have extended these findings to determine whether these markers can be used to identify IgM memory phenotypically as arising from T-dependent versus T-independent responses. We report that CD73 expression identifies a subset of antigen-experienced IgM + cells that share attributes of functional B-cell memory. This subset is reduced in the spleens of T-cell-deficient and CD40-deficient mice and in mixed marrow chimeras made with mutant and wild-type marrow, the proportion of CD73 + IgM memory is restored in the T-cell-deficient donor compartment but not in the CD40-deficient donor compartment, indicating that CD40 ligation is involved in its generation. We also report that CD40 signalling supports optimal expression of CD73 on splenic T cells and age-associated B cells (ABCs), but not on other immune cells such as neutrophils, marginal zone B cells, peritoneal cavity B-1 B cells and regulatory T and B cells. Our data indicate that in addition to promoting GC-associated memory generation during B-cell differentiation, CD40-signalling can influence the composition of the unswitched memory B-cell pool. They also raise the possibility that a fraction of ABCs may represent T-cell-dependent IgM memory. © 2017 John Wiley & Sons Ltd.

Neutral particle beam intensity controller

DOEpatents

Dagenhart, William K.

1986-01-01

A neutral beam intensity controller is provided for a neutral beam generator in which a neutral beam is established by accelerating ions from an ion source into a gas neutralizer. An amplitude modulated, rotating magnetic field is applied to the accelerated ion beam in the gas neutralizer to defocus the resultant neutral beam in a controlled manner to achieve intensity control of the neutral beam along the beam axis at constant beam energy. The rotating magnetic field alters the orbits of ions in the gas neutralizer before they are neutralized, thereby controlling the fraction of neutral particles transmitted out of the neutralizer along the central beam axis to a fusion device or the like. The altered path or defocused neutral particles are sprayed onto an actively cooled beam dump disposed perpendicular to the neutral beam axis and having a central open for passage of the focused beam at the central axis of the beamline. Virtually zero therough 100% intensity control is achieved by varying the magnetic field strength without altering the ion source beam intensity or its species yield.

Hepatitis C Virus Evasion Mechanisms from Neutralizing Antibodies

PubMed Central

Di Lorenzo, Caterina; Angus, Allan G. N.; Patel, Arvind H.

2011-01-01

Hepatitis C virus (HCV) represents a major public health problem, affecting 3% of the world’s population. The majority of infected individuals develop chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. To date, a vaccine is not available and current therapy is limited by resistance, adverse effects and high costs. Although it is very well established that cell-mediated immunity is necessary for viral clearance, the importance of host antibodies in clearing HCV infection is being increasingly recognized. Indeed, recent studies indicate that neutralizing antibodies are induced in the early phase of infection by patients who subsequently clear viral infection. Conversely, patients who do not clear the virus develop high titers of neutralizing antibodies during the chronic stage. Surprisingly, these antibodies are not able to control HCV infection. HCV has therefore developed mechanisms to evade immune elimination, allowing it to persist in the majority of infected individuals. A detailed understanding of the mechanisms by which the virus escapes immune surveillance is therefore necessary if novel preventive and therapeutic treatments have to be designed. This review summarizes the current knowledge of the mechanisms used by HCV to evade host neutralizing antibodies. PMID:22163345

EVA Development and Verification Testing at NASA's Neutral Buoyancy Laboratory

NASA Technical Reports Server (NTRS)

Jairala, Juniper; Durkin, Robert

2012-01-01

As an early step in preparing for future EVAs, astronauts perform neutral buoyancy testing to develop and verify EVA hardware and operations. To date, neutral buoyancy demonstrations at NASA JSC’s Sonny Carter Training Facility have primarily evaluated assembly and maintenance tasks associated with several elements of the ISS. With the retirement of the Space Shuttle, completion of ISS assembly, and introduction of commercial participants for human transportation into space, evaluations at the NBL will take on a new focus. In this session, Juniper Jairala briefly discussed the design of the NBL and, in more detail, described the requirements and process for performing a neutral buoyancy test, including typical hardware and support equipment requirements, personnel and administrative resource requirements, examples of ISS systems and operations that are evaluated, and typical operational objectives that are evaluated. Robert Durkin discussed the new and potential types of uses for the NBL, including those by non-NASA external customers.

EVA Development and Verification Testing at NASA's Neutral Buoyancy Laboratory

NASA Technical Reports Server (NTRS)

Jairala, Juniper; Durkin, Robert

2012-01-01

As an early step in preparing for future EVAs, astronauts perform neutral buoyancy testing to develop and verify EVA hardware and operations. To date, neutral buoyancy demonstrations at NASA JSC's Sonny Carter Training Facility have primarily evaluated assembly and maintenance tasks associated with several elements of the ISS. With the retirement of the Space Shuttle, completion of ISS assembly, and introduction of commercial participants for human transportation into space, evaluations at the NBL will take on a new focus. In this session, Juniper Jairala briefly discussed the design of the NBL and, in more detail, described the requirements and process for performing a neutral buoyancy test, including typical hardware and support equipment requirements, personnel and administrative resource requirements, examples of ISS systems and operations that are evaluated, and typical operational objectives that are evaluated. Robert Durkin discussed the new and potential types of uses for the NBL, including those by non-NASA external customers.

Relational Associative Learning Induces Cross-Modal Plasticity in Early Visual Cortex

PubMed Central

Headley, Drew B.; Weinberger, Norman M.

2015-01-01

Neurobiological theories of memory posit that the neocortex is a storage site of declarative memories, a hallmark of which is the association of two arbitrary neutral stimuli. Early sensory cortices, once assumed uninvolved in memory storage, recently have been implicated in associations between neutral stimuli and reward or punishment. We asked whether links between neutral stimuli also could be formed in early visual or auditory cortices. Rats were presented with a tone paired with a light using a sensory preconditioning paradigm that enabled later evaluation of successful association. Subjects that acquired this association developed enhanced sound evoked potentials in their primary and secondary visual cortices. Laminar recordings localized this potential to cortical Layers 5 and 6. A similar pattern of activation was elicited by microstimulation of primary auditory cortex in the same subjects, consistent with a cortico-cortical substrate of association. Thus, early sensory cortex has the capability to form neutral stimulus associations. This plasticity may constitute a declarative memory trace between sensory cortices. PMID:24275832

[Serum levels of antibodies for IgG, IgA, and IgM against the fungi antigen in psoriasis vulgaris].

PubMed

Liang, Yun-sheng; Wen, Hai-quan; Xiao, Rong

2003-12-01

To detect the serum levels of antibodies against Malassezia further and Candida albicans in patients with psoriasis vulgaris (PV), and to investigate the relationship between Malassezia furfur or Candida albicans and pathogenesis of PV. The serum levels of antibodies for IgG, IgA, and IgM against the whole cell antigen Wag and soluble antigen (Sag) of Malassezia fufur and Candida albicans in 40 PV patients and 20 healthy controls were detected by indirect-ELISA, RESULTS: The serum levels of IgG against Wag of Malassezia furfur and Candida albicans were significantly higher in PV patients than those in the healthy controls (P < 0.01, P < 0.05, respectively), The serum levels of IgM against Sag of Malassezia furfur and Candida albican, IgA against Sag of Candida albicans were significantly lower in PV patients than those in the healthy controls (P < 0.05). There are some humoral immunity abnormalties in PV patients. Malassezia furfur and Candida albicans may be related to the pathogenesis of PV.

The imprint of the cosmic supermassive black hole growth history on the 21 cm background radiation

NASA Astrophysics Data System (ADS)

Tanaka, Takamitsu L.; O'Leary, Ryan M.; Perna, Rosalba

2016-01-01

The redshifted 21 cm transition line of hydrogen tracks the thermal evolution of the neutral intergalactic medium (IGM) at `cosmic dawn', during the emergence of the first luminous astrophysical objects (˜100 Myr after the big bang) but before these objects ionized the IGM (˜400-800 Myr after the big bang). Because X-rays, in particular, are likely to be the chief energy courier for heating the IGM, measurements of the 21 cm signature can be used to infer knowledge about the first astrophysical X-ray sources. Using analytic arguments and a numerical population synthesis algorithm, we argue that the progenitors of supermassive black holes (SMBHs) should be the dominant source of hard astrophysical X-rays - and thus the primary driver of IGM heating and the 21 cm signature - at redshifts z ≳ 20, if (I) they grow readily from the remnants of Population III stars and (II) produce X-rays in quantities comparable to what is observed from active galactic nuclei and high-mass X-ray binaries. We show that models satisfying these assumptions dominate over contributions to IGM heating from stellar populations, and cause the 21 cm brightness temperature to rise at z ≳ 20. An absence of such a signature in the forthcoming observational data would imply that SMBH formation occurred later (e.g. via so-called direct collapse scenarios), that it was not a common occurrence in early galaxies and protogalaxies, or that it produced far fewer X-rays than empirical trends at lower redshifts, either due to intrinsic dimness (radiative inefficiency) or Compton-thick obscuration close to the source.

Heliospheric Neutral Atom Spectra Between 0.01 and 6 keV fom IBEX

NASA Technical Reports Server (NTRS)

Fuselier, S. A.; Allegrini, F.; Bzowski, M.; Funsten, H. O.; Ghielmetti, A. G.; Gloeckler, G.; Heirtzler, D.; Janzen, P.; Kubiak, M.; Kucharek, H.;

IgM nephropathy in India: a single centre experience.

PubMed

Vanikar, Aruna V; Kanodia, Kamal V; Patel, Rashmi D; Suthar, Kamlesh S; Patel, Himanshu V; Gumber, Manoj R; Trivedi, Hargovind L

2012-08-01

To find out the incidence and natural history of IgMN in India. Renal biopsies of children ≤12 y age of last 6 y were retrospectively evaluated. Their clinical and biochemical presentation were correlated. Patients with systemic diseases/disorders were excluded from the study. Immunoglobulin M nephropathy (IgMN) constituted 11.9% (n = 28) of 236 renal biopsies. Mean age was 10 y, predominant in boys (n = 24), most of the patients presented with proteinuria and edema. The most common associated histopathological finding was mesangial proliferative glomerulonephritis (MePGN) in 60.7% (n = 17) followed by minimal change disease (MCD) in 28.6% (n = 8) and focal segmental glomerulosclerosis (FSGS) in 10.7% (n = 3). In 85.7%, IgM appeared as the sole immunoglobulin deposit mainly in mesangial regions, followed by accompanied C3 in 3.6% (n = 1) and C1q + C3 in 10.7% (n = 3) biopsies. IgMN was observed in 11.9% biopsies with commonest morphology of MePGN followed by MCD and FSGS; proteinuria was bad prognosticator in addition to FSGS and co-deposition of other immunoglobulins had no significance.

The Nature of the Association between Moral Neutralization and Aggression: A Systematic Test of Causality in Early Adolescence

ERIC Educational Resources Information Center

Ribeaud, Denis; Eisner, Manuel

2015-01-01

This article examines possible causal linkages between moral neutralization--a generic term for the related concepts of neutralization techniques, moral disengagement, and self-serving cognitive distortions--and aggressive behavior by using a set of repeated measures in a culturally diverse urban sample at ages 11.4 and 13.7 (N = 1,032). First,…

A retrospective analysis of sera collected by the Hemorrhagic Fever Commission during the Korean Conflict.

PubMed

LeDuc, J W; Ksiazek, T G; Rossi, C A; Dalrymple, J M

1990-11-01

More than 600 sera from 245 patients with a clinical diagnosis of hemorrhagic fever were preserved by the Hemorrhagic Fever Commission during the Korean Conflict, 1951-1954. These sera were tested for IgM- and IgG-specific antibodies to Hantaan virus by enzyme immunoassay and for hantaviral antigen by immunoassay; one serum from each patient was tested by plaque reduction neutralization using both Hantaan and Seoul viruses. Only 15 patients failed to develop antihantaviral antibodies; most sera contained high titered IgM antibody on admission, and all were IgM-seropositive by day 7 after onset. Attempts to detect hantaviral antigen were unsuccessful. All seropositive patients had highest plaque reduction neutralization titers to Hantaan virus, suggesting that this virus was responsible for the disease seen. These results confirm that hemorrhagic fever of the Korean Conflict was due to Hantaan virus and demonstrate that measurement of specific IgM antibody is the method of choice for diagnosis of acute disease.

Development and evaluation of a Sarcocystis neurona-specific IgM capture enzyme-linked immunosorbent assay.

PubMed

Murphy, J E; Marsh, A E; Reed, S M; Meadows, C; Bolten, K; Saville, W J A

2006-01-01

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of horses caused primarily by the protozoal parasite Sarcocystis neurona. Currently available antemortem diagnostic testing has low specificity. The hypothesis of this study was that serum and cerebrospinal fluid (CSF) of horses experimentally challenged with S neurona would have an increased S neurona-specific IgM (Sn-IgM) concentration after infection, as determined by an IgM capture enzyme linked immunoassay (ELISA). The ELISA was based on the S neurona low molecular weight protein SNUCD-1 antigen and the monoclonal antibody 2G5 labeled with horseradish peroxidase. The test was evaluated using serum and CSF from 12 horses experimentally infected with 1.5 million S neurona sporocysts and 16 horses experimentally infected with varying doses (100 to 100,000) of S neurona sporocysts, for which results of histopathologic examination of the central nervous system were available. For horses challenged with 1.5 million sporocysts, there was a significant increase in serum Sn-IgM concentrations compared with values before infection at weeks 2-6 after inoculation (P < .0001). For horses inoculated with lower doses of S neurona, there were significant increases in serum Sn-IgM concentration at various points in time after inoculation, depending on the challenge dose (P < .01). In addition, there was a significant increase between the CSF Sn-IgM concentrations before and after inoculation (P < .0001). These results support further evaluation of the assay as a diagnostic test during the acute phase of EPM.

[Antibody responses in Japanese volunteers after immunization with yellow fever vaccine].

PubMed

Taga, Kenichiro; Imura, Shunro; Hayashi, Akihiro; Kamakura, Kazumasa; Hashimoto, Satoru; Takasaki, Tomohiko; Kurane, Ichiro; Uchida, Yukinori

2002-09-01

To monitor the development of specific and cross-reactive antibody response in twenty Japanese volunteers after vaccination with live yellow fever vaccine. Serum samples were collected on various days after vaccination and examined for hemagglutination inhibition (HI) antibodies against yellow fever virus (YFV), Japanese encephalitis virus (JEV) and dengue virus (DV), neutralizing antibodies against YFV and JEV, and IgM antibodies against YFV. None of the volunteers had been previously immunized with this vaccine. Fifteen of 20 had pre-vaccinated with JEV 7 to 40 years before. Ten of the 20 had neutralizing antibodies against JEV before immunization. None of the 20 had detectable antibodies against YFV or DV before vaccination. On day 10th after the vaccination, neutralizing antibodies to YFV were detected in 6 of 19 volunteers and IgM antibodies against YFV were detected in 7 of 19. On day 14th, HI, neutralizing, and IgM antibodies against YFV were detected in all the tested sera. Neutralizing antibodies against JEV were developed in 2 volunteers and HI antibodies against JEV were increased in 3 of 6 volunteers respectively. On day 29th, cross-reactive HI antibodies for JEV and DV were detected in all the tested sera. The results indicate that YF vaccine induces YFV-specific antibodies in all the tested volunteers and that it also induces HI antibodies cross-reactive for JEV and DV. The YF vaccine has a strong immunogenicity because it is a live vaccine, and induces antibody against YFV predominantly. The international certificate of yellow fever vaccination becomes valid 10 days after vaccination. On day 14th after vaccination, we detected neutralizing antibodies against YFV from all tested volunteers, however, only 6 of 19 volunteers had detectable neutralizing antibody on the 10th day after vaccination. Therefore, the vaccine may not be perfectly effective on day 10th after the vaccination.

Differential Decline in Leishmania Membrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy

PubMed Central

Anam, Khairul; Afrin, Farhat; Banerjee, Dwijadas; Pramanik, Netai; Guha, Subhasis K.; Goswami, Rama P.; Saha, Shiben K.; Ali, Nahid

1999-01-01

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar. PMID:10569788

Neutral particle beam intensity controller

DOEpatents

Dagenhart, W.K.

1984-05-29

The neutral beam intensity controller is based on selected magnetic defocusing of the ion beam prior to neutralization. The defocused portion of the beam is dumped onto a beam dump disposed perpendicular to the beam axis. Selective defocusing is accomplished by means of a magnetic field generator disposed about the neutralizer so that the field is transverse to the beam axis. The magnetic field intensity is varied to provide the selected partial beam defocusing of the ions prior to neutralization. The desired focused neutral beam portion passes along the beam path through a defining aperture in the beam dump, thereby controlling the desired fraction of neutral particles transmitted to a utilization device without altering the kinetic energy level of the desired neutral particle fraction. By proper selection of the magnetic field intensity, virtually zero through 100% intensity control of the neutral beam is achieved.

Is dispersal neutral?

PubMed

Lowe, Winsor H; McPeek, Mark A

2014-08-01

Dispersal is difficult to quantify and often treated as purely stochastic and extrinsically controlled. Consequently, there remains uncertainty about how individual traits mediate dispersal and its ecological effects. Addressing this uncertainty is crucial for distinguishing neutral versus non-neutral drivers of community assembly. Neutral theory assumes that dispersal is stochastic and equivalent among species. This assumption can be rejected on principle, but common research approaches tacitly support the 'neutral dispersal' assumption. Theory and empirical evidence that dispersal traits are under selection should be broadly integrated in community-level research, stimulating greater scrutiny of this assumption. A tighter empirical connection between the ecological and evolutionary forces that shape dispersal will enable richer understanding of this fundamental process and its role in community assembly. Copyright © 2014 Elsevier Ltd. All rights reserved.

46 CFR 502.404 - Neutrals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... resolution proceeding. A neutral shall have no official, financial, or personal conflict of interest with... Dispute Resolution § 502.404 Neutrals. (a) A neutral may be a permanent or temporary officer or employee... Maritime Commission Dispute Resolution Specialist will seek to provide a neutral in dispute resolution...

Multiplex detection of IgG and IgM to Rift Valley fever virus nucleoprotein, nonstructural proteins, and glycoprotein in ovine and bovine

USDA-ARS?s Scientific Manuscript database

A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were...

Identification of high-mannose and multiantennary complex-type N-linked glycans containing alpha-galactose epitopes from Nurse shark IgM heavy chain.

PubMed

Harvey, David J; Crispin, Max; Moffatt, Beryl E; Smith, Sylvia L; Sim, Robert B; Rudd, Pauline M; Dwek, Raymond A

2009-11-01

MALDI-TOF mass spectrometry, negative ion nano-electrospray MS/MS and exoglycosidase digestion were used to identify 36 N-linked glycans from 19S IgM heavy chain derived from the nurse shark (Ginglymostoma cirratum). The major glycan was the high-mannose compound, Man(6)GlcNAc(2) accompanied by small amounts of Man(5)GlcNAc(2), Man(7)GlcNAc(2) and Man(8)GlcNAc(2). Bi- and tri-antennary (isomer with a branched 3-antenna) complex-type glycans were also abundant, most contained a bisecting GlcNAc residue (beta1-->4-linked to the central mannose) and with varying numbers of alpha-galactose residues capping the antennae. Small amounts of monosialylated glycans were also found. This appears to be the first comprehensive study of glycosylation in this species of animal. The glycosylation pattern has implications for the mechanism of activation of the complement system by nurse shark IgM.

Emotional contexts modulate intentional memory suppression of neutral faces: Insights from ERPs.

PubMed

Pierguidi, Lapo; Righi, Stefania; Gronchi, Giorgio; Marzi, Tessa; Caharel, Stephanie; Giovannelli, Fabio; Viggiano, Maria Pia

2016-08-01

The main goal of present work is to gain new insight into the temporal dynamics underlying the voluntary memory control for neutral faces associated with neutral, positive and negative contexts. A directed forgetting (DF) procedure was used during the recording of EEG to answer the question whether is it possible to forget a face that has been encoded within a particular emotional context. A face-scene phase in which a neutral face was showed in a neutral or emotional scene (positive, negative) was followed by the voluntary memory cue (cue phase) indicating whether the face had to-be remember or to-be-forgotten (TBR and TBF). Memory for faces was then assessed with an old/new recognition task. Behaviorally, we found that it is harder to suppress faces-in-positive-scenes compared to faces-in-negative and neutral-scenes. The temporal information obtained by the ERPs showed: 1) during the face-scene phase, the Late Positive Potential (LPP), which indexes motivated emotional attention, was larger for faces-in-negative-scenes compared to faces-in-neutral-scenes. 2) Remarkably, during the cue phase, ERPs were significantly modulated by the emotional contexts. Faces-in-neutral scenes showed an ERP pattern that has been typically associated to DF effect whereas faces-in-positive-scenes elicited the reverse ERP pattern. Faces-in-negative scenes did not show differences in the DF-related neural activities but larger N1 amplitude for TBF vs. TBR faces may index early attentional deployment. These results support the hypothesis that the pleasantness or unpleasantness of the contexts (through attentional broadening and narrowing mechanisms, respectively) may modulate the effectiveness of intentional memory suppression for neutral information. Copyright © 2016 Elsevier B.V. All rights reserved.

Sudden appearance of anti-protein IgG1-forming cell precursors early during primary immunization.

PubMed

Nossal, G J; Riedel, C

1989-06-01

that the anti-KLH IgG1 precursors that suddenly emerge are the results of early variable region gene (V) mutations in B cells. Moreover, it is not excluded that they represent products of a subset of B cells different from those that give rise to the primary in vitro anti-KLH IgM response. The findings have implications for theories of B-cell tolerance.

Development of a serodiagnostic IgM-ELISA for tick-borne encephalitis virus using subviral particles with strep-tag.

PubMed

Nakayasu, Miki; Hirano, Minato; Muto, Memi; Kobayashi, Shintaro; Kariwa, Hiroaki; Yoshii, Kentaro

2018-06-23

Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis in humans. IgM antibody detection is useful for the serological diagnosis of TBEV infection, because IgM has high specificity for each flavivirus and indicates a recent infection. Commercial IgM-ELISA kits are somewhat expensive and difficulties in their sensitivity have been suggested due to their format and formalin-inactivated antigens. Therefore, the development of an inexpensive IgM-ELISA with high specificity and sensitivity is needed. In this study, a μ-capture ELISA was developed to detect TBEV-specific IgM antibodies using subviral particles (SPs) with strep-tag (strep-SP-IgM-ELISA). The results of our strep-SP-IgM-ELISA were highly correlated with diagnoses made by the neutralization test (sensitivity: 94.1%), and our strep-SP-IgM-ELISA could detect anti-TBEV IgM antibodies in patients who could not be diagnosed with the neutralization test. Besides, 51 of 52 positive samples by a commercial IgM-ELISA were also diagnosed as positive by our strep-SP-IgM-ELISA (98.1%), and our strep-SP-IgM-ELISA could detect anti-TBEV IgM antibodies in all samples that were inconclusive based on the commercial IgM-ELISA. Our strep-SP-IgM-ELISA will be useful for diagnoses in TBE-endemic areas. Copyright © 2018 Elsevier GmbH. All rights reserved.

Concepts for the magnetic design of the MITICA neutral beam test facility ion accelerator.

PubMed

Chitarin, G; Agostinetti, P; Marconato, N; Marcuzzi, D; Sartori, E; Serianni, G; Sonato, P

2012-02-01

The megavolt ITER injector concept advancement neutral injector test facility will be constituted by a RF-driven negative ion source and by an electrostatic Accelerator, designed to produce a negative Ion with a specific energy up to 1 MeV. The beam is then neutralized in order to obtain a focused 17 MW neutral beam. The magnetic configuration inside the accelerator is of crucial importance for the achievement of a good beam efficiency, with the early deflection of the co-extracted and stripped electrons, and also of the required beam optic quality, with the correction of undesired ion beamlet deflections. Several alternative magnetic design concepts have been considered, comparing in detail the magnetic and beam optics simulation results, evidencing the advantages and drawbacks of each solution both from the physics and engineering point of view.

Labs21 Approach to Climate Neutral Campuses | Climate Neutral Research

Science.gov Websites

Campuses | NREL Labs21 Approach to Climate Neutral Campuses Labs21 Approach to Climate Neutral included a whole-building approach to energy efficiency in laboratory buildings. This website takes that approach a step further in carrying out campus-wide energy- and carbon-reduction strategies. The

Neutralization tiers of HIV-1

PubMed Central

Montefiori, David C.; Roederer, Mario; Morris, Lynn; Seaman, Michael S.

2018-01-01

Purpose of review HIV-1 isolates are often classified on the basis of neutralization ‘tier’ phenotype. Tier classification has important implications for the monitoring and interpretation of vaccine-elicited neutralizing antibody responses. The molecular basis that distinguishes the multiple neutralization phenotypes of HIV-1 has been unclear. We present a model based on the dynamic nature of the HIV-1 envelope glycoproteins and its impact on epitope exposure. We also describe a new approach for ranking HIV-1 vaccine-elicited neutralizing antibody responses. Recent findings The unliganded trimeric HIV-1 envelope glycoprotein spike spontaneously transitions through at least three conformations. Neutralization tier phenotypes correspond to the frequency by which the trimer exists in a closed (tiers 2 and 3), open (tier 1A), or intermediate (tier 1B) conformation. An increasing number of epitopes become exposed as the trimer opens, making the virus more sensitive to neutralization by certain antibodies. The closed conformation is stabilized by many broadly neutralizing antibodies. Summary The tier 2 neutralization phenotype is typical of most circulating strains and is associated with a predominantly closed Env trimer configuration that is a high priority to target with vaccines. Assays with tier 1A viruses should be interpreted with caution and with the understanding that they detect many antibody specificities that do not neutralize tier 2 viruses and do not protect against HIV-1 infection. PMID:29266013

ALEX neutral beam probe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pourrezaei, K.

1982-01-01

A neutral beam probe capable of measuring plasma space potential in a fully 3-dimensional magnetic field geometry has been developed. This neutral beam was successfully used to measure an arc target plasma contained within the ALEX baseball magnetic coil. A computer simulation of the experiment was performed to refine the experimental design and to develop a numerical model for scaling the ALEX neutral beam probe to other cases of fully 3-dimensional magnetic field. Based on this scaling a 30 to 50 keV neutral cesium beam probe capable of measuring space potential in the thermal barrier region of TMX Upgrade wasmore » designed.« less

Three IgH isotypes, IgM, IgA and IgY are expressed in Gentoo penguin and zebra finch.

PubMed

Han, Binyue; Li, Yan; Han, Haitang; Zhao, Yaofeng; Pan, Qingjie; Ren, Liming

2017-01-01

Previous studies on a limited number of birds suggested that the IgD-encoding gene was absent in birds. However, one of our recent studies showed that the gene was definitely expressed in the ostrich and emu. Interestingly, we also identified subclass diversification of IgM and IgY in these two birds. To better understand immunoglobulin genes in birds, in this study, we analyzed the immunoglobulin heavy chain genes in the zebra finch (Taeniopygia guttata) and Gentoo penguin (Pygoscelis papua), belonging respectively to the order Passeriformes, the most successful bird order in terms of species diversity and numbers, and Sphenisciformes, a relatively primitive avian order. Similar to the results obtained in chickens and ducks, only three genes encoding immunoglobulin heavy chain isotypes, IgM, IgA and IgY, were identified in both species. Besides, we detected a transcript encoding a short membrane-bound IgA lacking the last two CH exons in the Gentoo penguin. We did not find any evidence supporting the presence of IgD gene or subclass diversification of IgM/IgY in penguin or zebra finch. The obtained data in our study provide more insights into the immunoglobulin heavy chain genes in birds and may help to better understand the evolution of immunoglobulin genes in tetrapods.

Spatial calibration of a tokamak neutral beam diagnostic using in situ neutral beam emission

DOE PAGES

Chrystal, Colin; Burrell, Keith H.; Grierson, Brian A.; ...

2015-10-20

Neutral beam injection is used in tokamaks to heat, apply torque, drive non-inductive current, and diagnose plasmas. Neutral beam diagnostics need accurate spatial calibrations to benefit from the measurement localization provided by the neutral beam. A new technique has been developed that uses in-situ measurements of neutral beam emission to determine the spatial location of the beam and the associated diagnostic views. This technique was developed to improve the charge exchange recombination diagnostic (CER) at the DIII-D tokamak and uses measurements of the Doppler shift and Stark splitting of neutral beam emission made by that diagnostic. These measurements contain informationmore » about the geometric relation between the diagnostic views and the neutral beams when they are injecting power. This information is combined with standard spatial calibration measurements to create an integrated spatial calibration that provides a more complete description of the neutral beam-CER system. The integrated spatial calibration results are very similar to the standard calibration results and derived quantities from CER measurements are unchanged within their measurement errors. Lastly, the methods developed to perform the integrated spatial calibration could be useful for tokamaks with limited physical access.« less

Spatial calibration of a tokamak neutral beam diagnostic using in situ neutral beam emission

NASA Astrophysics Data System (ADS)

Chrystal, C.; Burrell, K. H.; Grierson, B. A.; Pace, D. C.

2015-10-01

Neutral beam injection is used in tokamaks to heat, apply torque, drive non-inductive current, and diagnose plasmas. Neutral beam diagnostics need accurate spatial calibrations to benefit from the measurement localization provided by the neutral beam. A new technique has been developed that uses in situ measurements of neutral beam emission to determine the spatial location of the beam and the associated diagnostic views. This technique was developed to improve the charge exchange recombination (CER) diagnostic at the DIII-D tokamak and uses measurements of the Doppler shift and Stark splitting of neutral beam emission made by that diagnostic. These measurements contain information about the geometric relation between the diagnostic views and the neutral beams when they are injecting power. This information is combined with standard spatial calibration measurements to create an integrated spatial calibration that provides a more complete description of the neutral beam-CER system. The integrated spatial calibration results are very similar to the standard calibration results and derived quantities from CER measurements are unchanged within their measurement errors. The methods developed to perform the integrated spatial calibration could be useful for tokamaks with limited physical access.

Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees.

PubMed Central

Nara, P L; Smit, L; Dunlop, N; Hatch, W; Merges, M; Waters, D; Kelliher, J; Gallo, R C; Fischinger, P J; Goudsmit, J

1990-01-01

Emergence in two chimpanzees of human immunodeficiency virus type 1 (HIV-1) IIIB variants resistant to neutralization by the preexisting antibody is described. Viruses isolated from the HIV-1 IIIB gp120-vaccinated and -challenged animal were more resistant to neutralization by the chimpanzee's own serum than viruses isolated from the naive infected animal, indicating immune pressure as the selective mechanism. However, all reisolated viruses were 16- to 256-fold more neutralization resistant than the inoculum virus to antibodies binding to the third variable domain (V3) of the HIV-1 external envelope. Early chimpanzee serum samples that neutralized the inoculum strain but not the reisolated viruses were found to bind an HIV-1 IIIB common nonapeptide (IQRGPGRAF) derived from the gp120 isolate-specific V3 domain shown to induce isolate-specific neutralization in other animals. Amplification of the V3 coding sequence by polymerase chain reaction and subsequent sequence analysis of the neutralization-resistant variants obtained from in vivo-infected animals indicated that early resistance to neutralization by an HIV-1 IIIB monoclonal antibody (0.5 beta) was conferred by changes outside the direct binding site for the selective neutralizing antibody. The reisolated neutralization-resistant isolates consisted of the lower-replication-competent virus subpopulations of the HIV-1 IIIB stock, as confirmed by biological and sequence analyses. In vitro passage of the HIV-1 IIIB stock through chimpanzee and human peripheral blood mononuclear cell cultures void of HIV-specific antibody resulted in homogenic amplification of the more-replication-competent subpopulation preexisting in the original viral stock, suggesting a role for the immune system in suppressing the more-replication-competent viruses. Images PMID:2370681

Plasma/Neutral-Beam Etching Apparatus

NASA Technical Reports Server (NTRS)

Langer, William; Cohen, Samuel; Cuthbertson, John; Manos, Dennis; Motley, Robert

1989-01-01

Energies of neutral particles controllable. Apparatus developed to produce intense beams of reactant atoms for simulating low-Earth-orbit oxygen erosion, for studying beam-gas collisions, and for etching semiconductor substrates. Neutral beam formed by neutralization and reflection of accelerated plasma on metal plate. Plasma ejected from coaxial plasma gun toward neutralizing plate, where turned into beam of atoms or molecules and aimed at substrate to be etched.

Neutral theory and the species abundance distribution: recent developments and prospects for unifying niche and neutral perspectives

PubMed Central

Matthews, Thomas J; Whittaker, Robert J

2014-01-01

Published in 2001, The Unified Neutral Theory of Biodiversity and Biogeography (UNTB) emphasizes the importance of stochastic processes in ecological community structure, and has challenged the traditional niche-based view of ecology. While neutral models have since been applied to a broad range of ecological and macroecological phenomena, the majority of research relating to neutral theory has focused exclusively on the species abundance distribution (SAD). Here, we synthesize the large body of work on neutral theory in the context of the species abundance distribution, with a particular focus on integrating ideas from neutral theory with traditional niche theory. First, we summarize the basic tenets of neutral theory; both in general and in the context of SADs. Second, we explore the issues associated with neutral theory and the SAD, such as complications with fitting and model comparison, the underlying assumptions of neutral models, and the difficultly of linking pattern to process. Third, we highlight the advances in understanding of SADs that have resulted from neutral theory and models. Finally, we focus consideration on recent developments aimed at unifying neutral- and niche-based approaches to ecology, with a particular emphasis on what this means for SAD theory, embracing, for instance, ideas of emergent neutrality and stochastic niche theory. We put forward the argument that the prospect of the unification of niche and neutral perspectives represents one of the most promising future avenues of neutral theory research. PMID:25360266

Neutral theory and the species abundance distribution: recent developments and prospects for unifying niche and neutral perspectives.

PubMed

Matthews, Thomas J; Whittaker, Robert J

2014-06-01

Published in 2001, The Unified Neutral Theory of Biodiversity and Biogeography (UNTB) emphasizes the importance of stochastic processes in ecological community structure, and has challenged the traditional niche-based view of ecology. While neutral models have since been applied to a broad range of ecological and macroecological phenomena, the majority of research relating to neutral theory has focused exclusively on the species abundance distribution (SAD). Here, we synthesize the large body of work on neutral theory in the context of the species abundance distribution, with a particular focus on integrating ideas from neutral theory with traditional niche theory. First, we summarize the basic tenets of neutral theory; both in general and in the context of SADs. Second, we explore the issues associated with neutral theory and the SAD, such as complications with fitting and model comparison, the underlying assumptions of neutral models, and the difficultly of linking pattern to process. Third, we highlight the advances in understanding of SADs that have resulted from neutral theory and models. Finally, we focus consideration on recent developments aimed at unifying neutral- and niche-based approaches to ecology, with a particular emphasis on what this means for SAD theory, embracing, for instance, ideas of emergent neutrality and stochastic niche theory. We put forward the argument that the prospect of the unification of niche and neutral perspectives represents one of the most promising future avenues of neutral theory research.

Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments

DOE PAGES

Hraber, Peter; Rademeyer, Cecilia; Williamson, Carolyn; ...

2017-07-26

In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus panels, chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses from early infection. All 200 Envs were expressed as a single round of replication pseudoviruses and were tested to quantify neutralization titers by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C infections. We selected large panels of 50 and 100 Envsmore » either to characterize cross-reactive breadth for sera identified as having potent neutralization activity based on initial screening or to evaluate neutralization magnitude-breadth distributions of newly isolated antibodies. We identified these panels by downselection after hierarchical clustering of bnAb neutralization titers. The resulting panels represent the diversity of neutralization profiles throughout the range of virus sensitivities identified in the original panel of 200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials or natural-infection studies for neutralization responses. We considered panels selected by previously described methods but favored a computationally informed method that enabled selection of viruses representing diverse neutralization sensitivity patterns, given that we do nota prioriknow what the neutralization-response profile of vaccine sera will be relative to that of sera from infected individuals. The resulting 12-Env panel complements existing panels. Use of standardized panels enables direct comparisons of data from different trials and study sites testing HIV-1 clade C-specific products. HIV-1 group M includes nine clades and many recombinants. Clade C is the most common lineage, responsible for roughly half

Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hraber, Peter; Rademeyer, Cecilia; Williamson, Carolyn

In the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus panels, chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses from early infection. All 200 Envs were expressed as a single round of replication pseudoviruses and were tested to quantify neutralization titers by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C infections. We selected large panels of 50 and 100 Envsmore » either to characterize cross-reactive breadth for sera identified as having potent neutralization activity based on initial screening or to evaluate neutralization magnitude-breadth distributions of newly isolated antibodies. We identified these panels by downselection after hierarchical clustering of bnAb neutralization titers. The resulting panels represent the diversity of neutralization profiles throughout the range of virus sensitivities identified in the original panel of 200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials or natural-infection studies for neutralization responses. We considered panels selected by previously described methods but favored a computationally informed method that enabled selection of viruses representing diverse neutralization sensitivity patterns, given that we do nota prioriknow what the neutralization-response profile of vaccine sera will be relative to that of sera from infected individuals. The resulting 12-Env panel complements existing panels. Use of standardized panels enables direct comparisons of data from different trials and study sites testing HIV-1 clade C-specific products. HIV-1 group M includes nine clades and many recombinants. Clade C is the most common lineage, responsible for roughly half

Detection of Human Papillomavirus 16-Specific IgG and IgM Antibodies in Patient Sera: A Potential Indicator of Oral Squamous Cell Carcinoma Risk Factor

PubMed Central

Kerishnan, Jesinda P.; Gopinath, Subash C.B.; Kai, Sia Bik; Tang, Thean-Hock; Ng, Helen Lee-Ching; Rahman, Zainal Ariff Abdul; Hashim, Uda; Chen, Yeng

2016-01-01

The association between human papillomavirus type 16 (HPV16) and oral cancer has been widely reported. However, detecting anti-HPV antibodies in patient sera to determine risk for oral squamous cell carcinoma (OSCC) has not been well studied. In the present investigation, a total of 206 OSCC serum samples from the Malaysian Oral Cancer Database & Tissue Bank System, with 134 control serum samples, were analyzed by enzyme-linked immunosorbant assay (ELISA) to detect HPV16-specific IgG and IgM antibodies. In addition, nested PCR analysis using comprehensive consensus primers (PGMY09/11 and GP5+/6+) was used to confirm the presence of HPV. Furthermore, we have evaluated the association of various additional causal factors (e.g., smoking, alcohol consumption, and betel quid chewing) in HPV-infected OSCC patients. Statistical analysis of the Malaysian population indicated that OSCC was more prevalent in female Indian patients that practices betel quid chewing. ELISA revealed that HPV16 IgG, which demonstrates past exposure, could be detected in 197 (95.6%) OSCC patients and HPV16-specific IgM was found in a total of 42 (20.4%) OSCC patients, indicating current exposure. Taken together, our study suggest that HPV infection may play a significant role in OSCC (OR: 13.6; 95% CI: 3.89-47.51) and HPV16-specific IgG and IgM antibodies could represent a significant indicator of risk factors in OSCC patients. PMID:27279791

Detection of Human Papillomavirus 16-Specific IgG and IgM Antibodies in Patient Sera: A Potential Indicator of Oral Squamous Cell Carcinoma Risk Factor.

PubMed

Kerishnan, Jesinda P; Gopinath, Subash C B; Kai, Sia Bik; Tang, Thean-Hock; Ng, Helen Lee-Ching; Rahman, Zainal Ariff Abdul; Hashim, Uda; Chen, Yeng

2016-01-01

The association between human papillomavirus type 16 (HPV16) and oral cancer has been widely reported. However, detecting anti-HPV antibodies in patient sera to determine risk for oral squamous cell carcinoma (OSCC) has not been well studied. In the present investigation, a total of 206 OSCC serum samples from the Malaysian Oral Cancer Database & Tissue Bank System, with 134 control serum samples, were analyzed by enzyme-linked immunosorbant assay (ELISA) to detect HPV16-specific IgG and IgM antibodies. In addition, nested PCR analysis using comprehensive consensus primers (PGMY09/11 and GP5(+)/6(+)) was used to confirm the presence of HPV. Furthermore, we have evaluated the association of various additional causal factors (e.g., smoking, alcohol consumption, and betel quid chewing) in HPV-infected OSCC patients. Statistical analysis of the Malaysian population indicated that OSCC was more prevalent in female Indian patients that practices betel quid chewing. ELISA revealed that HPV16 IgG, which demonstrates past exposure, could be detected in 197 (95.6%) OSCC patients and HPV16-specific IgM was found in a total of 42 (20.4%) OSCC patients, indicating current exposure. Taken together, our study suggest that HPV infection may play a significant role in OSCC (OR: 13.6; 95% CI: 3.89-47.51) and HPV16-specific IgG and IgM antibodies could represent a significant indicator of risk factors in OSCC patients.

Acute suppression of serum IgM and IgA in tank workers exposed to benzene.

PubMed

Kirkeleit, J; Ulvestad, E; Riise, T; Bråtveit, M; Moen, B E

2006-12-01

We investigated associations between benzene exposure and alterations of proteins and cells of the immune system among workers maintaining cargo tanks containing crude oil residues. Individual exposure to benzene, benzene in blood and urine, peripheral blood lymphocytes (total lymphocytes, lymphocytes in subpopulations CD3, CD4, CD8, CD19, CD56 and CD4/CD8 ratio), complement factors C3 and C4 and serum concentration of immunoglobulins (IgG, IgA, IgM and IgE) were analysed among 13 tank workers and nine unexposed referents (catering section). Benzene exposure was measured during three consecutive 12-h work days. Blood and urine samples were collected pre-shift on the first day (baseline), post-shift on the third day, and pre-next shift on the following morning. The time spent in the cargo tank was logged. The individual geometric mean benzene exposure in the breathing zone of tank workers over 3 days was 0.15 p.p.m. (range 0.01-0.62 p.p.m.) (n = 26). The geometric mean benzene concentration in blood post-shift was 12.3 nmol/l among tank workers versus 0.7 nmol/l among the referents. Tank workers showed a decline (versus referents) in IgM from baseline to post-shift (t-test, P = 0.04) and IgA from baseline to pre-next shift (t-test, P = 0.01). They also showed a decline in CD4 T cells from baseline to post-shift (t-test, P = 0.04). Suppression correlated with benzene exposure, benzene concentrations in blood and urine and time spent in the tank. The groups did not differ significantly in the change in other immune parameters. The clinical significance is unknown and warrants further studies.

Single or combined effects of Lactobacillus sakei and inulin on growth, non-specific immunity and IgM expression in leopard grouper (Mycteroperca rosacea).

PubMed

Reyes-Becerril, Martha; Ascencio, Felipe; Gracia-Lopez, Vicente; Macias, Ma Esther; Roa, Marcos Cadena; Esteban, María Ángeles

2014-08-01

The aim of this study was to evaluate the single or combined effects of Lactobacillus sakei with inulin suitable for immunological in vivo studies in farmed fish. By in vitro assays, L. sakei strain 5-4 showed antibacterial activities against all assayed fish pathogens (except the Vibrio harveyi strain CAIM-1793). L. sakei was able to survive at high fish bile concentrations. Fermentation of the agave inulin resulted in a large increase in number of lactobacilli. For the in vivo study, fish were fed for 8 weeks four practical diets: control diet (control), L. sakei 5-4 (10(7) CFU/g), inulin (1% or 10 g/kg) and L. sakei + inulin (10(7) CFU/g + 10 g/kg). The weight gain showed clearly the synergistic effect of L. sakei 5-4 and inulin at 6 and 8 weeks of treatments. Leopard grouper fed with L. sakei alone or combined with inulin have significantly increased the assayed physiological and humoral immune parameters. By real-time PCR assays, the mRNA transcripts of immunoglobulin M (IgM) were found to be higher expressed in intestine, head kidney, mucus, gill, spleen and skin. Moreover, mRNA expression levels of IgM in head kidney and anterior intestine were measured by real-time PCR. L. sakei 5-4 and L. sakei + inulin supplemented diet up-regulated the expression of IgM at week 4 and 8 in intestine and head kidney, respectively. These results support the idea that the L. sakei 5-4 alone or combined with agave inulin improved growth performance and stimulates the immune system of leopard grouper.

Origins and Early History of Underwater Neutral Buoyancy Simulation of Weightlessness for EVA Procedures Development and Training. Part 2; Winnowing and Regrowth

NASA Technical Reports Server (NTRS)

Charles, John B.

2013-01-01

The technique of neutral buoyancy during water immersion was applied to a variety of questions pertaining to human performance factors in the early years of the space age. It was independently initiated by numerous aerospace contractors at nearly the same time, but specific applications depended on the problems that the developers were trying to solve. Those problems dealt primarily with human restraint and maneuverability and were often generic across extravehicular activity (EVA) and intravehicular activity (IVA) worksites. The same groups often also considered fractional gravity as well as weightless settings and experimented with ballasting to achieve lunar and Mars-equivalent loads as part of their on-going research and development. Dr. John Charles reviewed the association of those tasks with contemporary perceptions of the direction of NASA's future space exploration activities and with Air Force assessments of the military value of man in space.

Modeling the neutral hydrogen distribution in the post-reionization Universe: intensity mapping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villaescusa-Navarro, Francisco; Viel, Matteo; Datta, Kanan K.

We model the distribution of neutral hydrogen (HI) in the post-reionization era and investigate its detectability in 21 cm intensity mapping with future radio telescopes like the Square Kilometer array (SKA). We rely on high resolution hydrodynamical N-body simulations that have a state-of-the-art treatment of the low density photoionized gas in the inter-galactic medium (IGM). The HI is assigned a-posteriori to the gas particles following two different approaches: a halo-based method in which HI is assigned only to gas particles residing within dark matter halos; a particle-based method that assigns HI to all gas particles using a prescription based onmore » the physical properties of the particles. The HI statistical properties are then compared to the observational properties of Damped Lyman-α Absorbers (DLAs) and of lower column density systems and reasonable good agreement is found for all the cases. Among the halo-based method, we further consider two different schemes that aim at reproducing the observed properties of DLAs by distributing HI inside halos: one of this results in a much higher bias for DLAs, in agreement with recent observations, which boosts the 21 cm power spectrum by a factor ∼ 4 with respect to the other recipe. Furthermore, we quantify the contribution of HI in the diffuse IGM to both Ω{sub HI} and the HI power spectrum finding to be subdominant in both cases. We compute the 21 cm power spectrum from the simulated HI distribution and calculate the expected signal for both SKA1-mid and SKA1-low configurations at 2.4 ≤ z ≤ 4. We find that SKA will be able to detect the 21 cm power spectrum, in the non-linear regime, up to k ∼ 1 h/Mpc for SKA1-mid and k ∼ 5 h/Mpc for SKA1-low with 100 hours of observations. We also investigate the perspective of imaging the HI distribution. Our findings indicate that SKA1-low could detect the most massive HI peaks with a signal to noise ratio (SNR) higher than 5 for an observation time of

Communication: Classical threshold law for ion-neutral-neutral three-body recombination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pérez-Ríos, Jesús; Greene, Chris H.

2015-07-28

A very recently method for classical trajectory calculations for three-body collision [Pérez-Ríos et al., J. Chem. Phys. 140, 044307 (2014)] has been applied to describe ion-neutral-neutral ternary processes for low energy collisions: 0.1 mK–10 mK. As a result, a threshold law for the three-body recombination cross section is obtained and corroborated numerically. The derived threshold law predicts the formation of weakly bound dimers, with binding energies comparable to the collision energy of the collisional partners. In this low energy range, this analysis predicts that molecular ions should dominate over molecular neutrals as the most products formed.

Neutral evolution of mutational robustness

PubMed Central

van Nimwegen, Erik; Crutchfield, James P.; Huynen, Martijn

1999-01-01

We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population’s limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network’s adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. These results quantify the extent to which populations evolve mutational robustness—the insensitivity of the phenotype to mutations—and thus reduce genetic load. Because the average neutrality is independent of evolutionary parameters—such as mutation rate, population size, and selective advantage—one can infer global statistics of neutral network topology by using simple population data available from in vitro or in vivo evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions. PMID:10449760

Analysis of the Fc Gamma Receptor-Dependent Component of Neutralization Measured by Anthrax Toxin Neutralization Assays▿

PubMed Central

Verma, Anita; Ngundi, Miriam M.; Meade, Bruce D.; De Pascalis, Roberto; Elkins, Karen L.; Burns, Drusilla L.

2009-01-01

Anthrax toxin neutralization assays are used to measure functional antibody levels elicited by anthrax vaccines in both preclinical and clinical studies. In this study, we investigated the magnitude and molecular nature of Fc gamma (Fcγ) receptor-dependent toxin neutralization observed in commonly used forms of the anthrax toxin neutralization assay. Significantly more Fcγ receptor-dependent neutralization was observed in the J774A.1 cell-based assay than in the RAW 264.7 cell-based assay, a finding that could be due to the larger numbers of Fcγ receptors that we found on J774A.1 cells by using flow cytometry. Thus, the extent to which Fcγ receptor-dependent neutralization contributes to the total neutralization measured by the assay depends on the specific cell type utilized in the assay. Using Fcγ receptor blocking monoclonal antibodies, we found that at least three murine Fcγ receptor classes, IIB, III, and IV, can contribute to Fcγ receptor-dependent neutralization. When antibodies elicited by immunization of rabbits with protective-antigen-based anthrax vaccines were analyzed, we found that the magnitude of Fcγ receptor-dependent neutralization observed in the J774A.1 cell-based assay was dependent on the concentration of protective antigen utilized in the assay. Our results suggest that the characteristics of the antibodies analyzed in the assay (e.g., species of origin, isotype, and subclass), as well as the assay design (e.g., cell type and protective antigen concentration), could significantly influence the extent to which Fcγ receptor-dependent neutralization contributes to the total neutralization measured by anthrax toxin neutralization assays. These findings should be considered when interpreting anthrax toxin neutralization assay output. PMID:19656993

Studies on the diagnostic value of an immunofluorescence test for EB virus-specific IgM.

PubMed

Edwards, J M; McSwiggan, D A

1974-08-01

A modification of the test for EB virus/IgM introduced by Schmitz and Scherer (1972) is described. It is simple and gives reproducible results.EB virus/IgM was demonstrated in all but one case of infectious mononucleosis and in students with minor illness shown to have acquired EB virus/IgG recently. Unlike the EB virus/IgG, the IgM disappears within a few months. Although the Paul-Bunnell-Davidsohn test is still the test of choice for the diagnosis of infectious mononucleosis, the EB virus/IgM test could be useful to establish a diagnosis of current or recent EB virus infection where the Paul-Bunnell-Davidsohn test was negative or equivocal.

Emotional words facilitate lexical but not early visual processing.

PubMed

Trauer, Sophie M; Kotz, Sonja A; Müller, Matthias M

2015-12-12

Emotional scenes and faces have shown to capture and bind visual resources at early sensory processing stages, i.e. in early visual cortex. However, emotional words have led to mixed results. In the current study ERPs were assessed simultaneously with steady-state visual evoked potentials (SSVEPs) to measure attention effects on early visual activity in emotional word processing. Neutral and negative words were flickered at 12.14 Hz whilst participants performed a Lexical Decision Task. Emotional word content did not modulate the 12.14 Hz SSVEP amplitude, neither did word lexicality. However, emotional words affected the ERP. Negative compared to neutral words as well as words compared to pseudowords lead to enhanced deflections in the P2 time range indicative of lexico-semantic access. The N400 was reduced for negative compared to neutral words and enhanced for pseudowords compared to words indicating facilitated semantic processing of emotional words. LPC amplitudes reflected word lexicality and thus the task-relevant response. In line with previous ERP and imaging evidence, the present results indicate that written emotional words are facilitated in processing only subsequent to visual analysis.

The Formation of Fe/Mg Smectite Under Mildly Acidic Conditions on Early Mars

NASA Technical Reports Server (NTRS)

Sutter, B.; Golden, D. C.; Ming, Douglas W.; Niles, P. B.

2011-01-01

The detection of Fe/Mg smectites and carbonate in Noachian and early Hesperian terrain of Mars suggests that neutral to mildly alkaline conditions prevailed during the early history of Mars. If early Mars surface geochemical conditions were neutral to moderately alkaline with a denser CO2 atmosphere than today, then large carbonates deposits should be more widely detected in Noachian terrain. Why have so few carbonate deposits been detected compared to Fe/Mg smectites? Fe/Mg smectites on early Mars formed under mildly acidic conditions, which would preclude the extensive formation of carbonate deposits. The goal of the proposed work is to evaluate the formation of Fe/Mg smectites under mildly acidic conditions.

Are You Neutral About Net Neutrality

DTIC Science & Technology

2007-06-20

Alaska War on Terrorism Universal Service Reform Streamlining Franchising Process Video Content Municipal Broadband Wireless Innovation Networks Digital...Chair, Joe Barton (R), Texas National Video Franchising Network Neutrality/Enforcement of Broadband Policy VoIP/E9ll Municipal Provision of Services

Toxicological Effects of Nickel Chloride on IgA+ B Cells and sIgA, IgA, IgG, IgM in the Intestinal Mucosal Immunity in Broilers

PubMed Central

Wu, Bangyuan; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Huang, Jianying

2014-01-01

The objective of this study was to investigate the toxicological effects of dietary NiCl2 on IgA+ B cells and the immunoglobulins including sIgA, IgA, IgG and IgM in the small intestine and cecal tonsil of broilers by the methods of immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Two hundred and forty one-day-old avian broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg NiCl2 for 42 days. Compared with the control group, the IgA+ B cell number and the sIgA, IgA, IgG, and IgM contents in the NiCl2-treated groups were significantly decreased (p < 0.05 or p < 0.01). It was concluded that dietary NiCl2 in the excess of 300 mg/kg had negative effects on the IgA+ B cell number and the abovementioned immunoglobulin contents in the small intestine and the cecal tonsil. NiCl2-reduced sIgA, IgA, IgG and IgM contents is due to decrease in the population and/or the activation of B cell. The results suggest that NiCl2 at high levels has intestinal mucosal humoral immunotoxicity in animals. PMID:25116637

[Detection of split products of the immunoglobulins IgG, IgA and IgM during chronic otitis media (author's transl)].

PubMed

Kastenbauer, E R; Hochgesand, K; Hochstrasser, K; Tappermann, G

1975-07-01

Proteolytic enzymes such as pepsine or papaine are able to split IgG antibodies into large fragments in vitro. These immunoglobulin fragments (IgG, IgA, IgM) were now detected in vivo from the purulent secretions of cholesteatoma, chronic otitis media and radical mastoid cavities. During chronic otitis media the intact immunoglobulins are split due to the proteolytic activity of neutral proteinases. These fragments were qualitatively and quantitatively investigated by means of various immunological procedures. After the immunoelectrophoretic separation of the purulent middle-ear-secretions and after diffusion against anti-IgG-, anti-IgA- and anti-IgM- serum double precipitate lines could be observed especially in middle-ear-secretion with a bacterial flora of pseudomonas aeruginosa (pyocyanea) and of the proteus-providencia-group. This was the first proof of the presence of split products of the immunoglobulins. The exact demonstration of these split products could be carried out by gel-filtration and fractionation of the intact and split immunoglobulins. During chronic otitis media intact immunoglobulins are split by leucocytic and extracellular bacterial proteinases into fragments of different molecular weight. The most malignant extracellular proteinases with the greatest proteolytic activity against intact immunoglobulins are the bacterial proteinases of pseudomonas aeruginosa. These proteinases can not be inhibited by the other serum proteinaseinhibitors except for alpha-2-macroglobulin of the human blood serum. This inhibitor has a very high molecular weight so that we can not find it in a higher concentration in the middle-ear-secretion. We can liberate this inhibitor by injuring the blood vessels during a tympanoplasty. In this way we get an inhibitory effect against these proteinases and combined with an appropriate antibiotic therapy we can cure a chronic otitis media.

Neutral face classification using personalized appearance models for fast and robust emotion detection.

PubMed

Chiranjeevi, Pojala; Gopalakrishnan, Viswanath; Moogi, Pratibha

2015-09-01

Facial expression recognition is one of the open problems in computer vision. Robust neutral face recognition in real time is a major challenge for various supervised learning-based facial expression recognition methods. This is due to the fact that supervised methods cannot accommodate all appearance variability across the faces with respect to race, pose, lighting, facial biases, and so on, in the limited amount of training data. Moreover, processing each and every frame to classify emotions is not required, as user stays neutral for majority of the time in usual applications like video chat or photo album/web browsing. Detecting neutral state at an early stage, thereby bypassing those frames from emotion classification would save the computational power. In this paper, we propose a light-weight neutral versus emotion classification engine, which acts as a pre-processer to the traditional supervised emotion classification approaches. It dynamically learns neutral appearance at key emotion (KE) points using a statistical texture model, constructed by a set of reference neutral frames for each user. The proposed method is made robust to various types of user head motions by accounting for affine distortions based on a statistical texture model. Robustness to dynamic shift of KE points is achieved by evaluating the similarities on a subset of neighborhood patches around each KE point using the prior information regarding the directionality of specific facial action units acting on the respective KE point. The proposed method, as a result, improves emotion recognition (ER) accuracy and simultaneously reduces computational complexity of the ER system, as validated on multiple databases.

Neutrality between Government and Religion.

ERIC Educational Resources Information Center

Mawdsley, Ralph D.

1996-01-01

The overall guiding principle of neutrality between government and religion masks a tension that exists between free exercise of religion and establishment of religion. Reviews the development and current status of "Lemon" as a test for neutrality; proposes a new test for neutrality, evenhandedness, that is common to both the Free…

LANL - Neutral - TTU

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosovic, Branko

This dataset includes large-eddy simulation (LES) output from a neutrally stratified atmospheric boundary layer (ABL) simulation of observations at the SWIFT tower near Lubbock, Texas on Aug. 17, 2012. The dataset was used to assess LES models for simulation of canonical neutral ABL. The dataset can be used for comparison with other LES and computational fluid dynamics model outputs.

Are we witnessing the epoch of reionisation at z = 7.1 from the spectrum of J1120+0641?

NASA Astrophysics Data System (ADS)

Greig, Bradley; Mesinger, Andrei; Haiman, Zoltán; Simcoe, Robert A.

2017-04-01

We quantify the presence of Lyα damping wing absorption from a partially neutral intergalactic medium (IGM) in the spectrum of the z = 7.08 QSO, ULASJ1120+0641. Using a Bayesian framework, we simultaneously account for uncertainties in: (I) the intrinsic QSO emission spectrum; and (II) the distribution of cosmic H I patches during the epoch of reionization (EoR). For (I), we use a new intrinsic Lyα emission line reconstruction method, sampling a covariance matrix of emission line properties built from a large data base of moderate-z QSOs. For (II), we use the Evolution of 21-cm Structure (EOS; Mesinger et al.) simulations, which span a range of physically motivated EoR models. We find strong evidence for the presence of damping wing absorption redward of Lyα (where there is no contamination from the Lyα forest). Our analysis implies that the EoR is not yet complete by z = 7.1, with the volume-weighted IGM neutral fraction constrained to \\bar{x}_{H I} = 0.40^{+0.21 }_{ -0.19} at 1σ (\\bar{x}_{H I} = 0.40^{+0.41 }_{ -0.32} at 2σ). This result is insensitive to the EoR morphology. Our detection of significant neutral H I in the IGM at z = 7.1 is consistent with the latest Planck 2016 measurements of the CMB Thompson scattering optical depth.

Neutral-current x-distributions

DOE R&D Accomplishments Database

Friedman, J. I.; Kendall, H. W.; Bogert, D.; Burnstein, R.; Fisk, R.; Fuess, S.; Bofill, J.; Busza, W.; Eldridge, T.; Abolins, M.; Brock, R.; et al.

1984-06-01

The role of the semi leptonic neutral current interaction as a probe of nucleon structure is examined. Previous measurements of neutral current x-distributions are reviewed, and new results from the Fermilab - MIT - MSU collaboration are presented.

Neutral atom imaging at Mercury

NASA Astrophysics Data System (ADS)

Mura, A.; Orsini, S.; Milillo, A.; Di Lellis, A. M.; De Angelis, E.

2006-02-01

The feasibility of neutral atom detection and imaging in the Hermean environment is discussed in this study. In particular, we consider those energetic neutral atoms (ENA) whose emission is directly related to solar wind entrance into Mercury's magnetosphere. In fact, this environment is characterised by a weak magnetic field; thus, cusp regions are extremely large if compared to the Earth's ones, and intense proton fluxes are expected there. Our study includes a model of H + distribution in space, energy and pitch angle, simulated by means of a single-particle, Monte-Carlo simulation. Among processes that could generate neutral atom emission, we focus our attention on charge-exchange and ion sputtering, which, in principle, are able to produce directional ENA fluxes. Simulated neutral atom images are investigated in the frame of the neutral particle analyser-ion spectrometer (NPA-IS) SERENA experiment, proposed to fly on board the ESA mission BepiColombo/MPO. The ELENA (emitted low-energy neutral atoms) unit, which is part of this experiment, will be able to detect such fluxes; instrumental details and predicted count rates are given.

Elimination of falsely reactive results in a commercially-available West Nile virus IgM capture enzyme-linked immunosorbent assay by heterophilic antibody blocking reagents.

PubMed

Prince, Harry E; Lapé-Nixon, Mary; Givens, Tara S; Bradshaw, Tiffany; Nowicki, Marek J

2017-05-01

All sera initially reactive in the Focus Diagnostics West Nile virus IgM capture enzyme-linked immunosorbent assay (WNV IgM ELISA) must be retested with background subtraction to identify falsely-reactive (FR) samples due to antibodies that bind to immunoglobulins of other animal species (heterophilic antibodies). In some settings, such as pre-transplant testing of organ donors, the reporting delay associated with retesting can have an adverse impact on donor procurement and organ placement. We sought to determine if inclusion of heterophilic antibody blockers in assay conjugate could eliminate the nonspecific reactivity of FR samples. Of 6 blocking reagents evaluated using a well-characterized FR sample, immunoglobulin inhibiting reagent from Bioreclamation (IIR) and blocker from Fitzgerald Industries (BFI) were superior in their ability to inhibit false reactivity; these 2 blockers were then used to evaluate 20 additional FR and 21 truly-reactive (TR) samples. Both blockers eliminated the reactivity of 20/21 FR samples, whereas all 21 TR samples remained reactive; further, all 13 truly non-reactive (NR) samples evaluated remained non-reactive when using blocker-containing conjugate. A subset of 22 samples were tested in parallel using the initial lot and a second lot of IIR and BFI; with one exception, all samples showed the same qualitative result using both lots of a given blocker. These findings demonstrate that modification of the Focus WNV IgM screening ELISA to include heterophilic antibody blocker IIR or BFI in assay conjugate eliminates the reactivity of most FR samples, markedly reducing the number of samples requiring further testing by background subtraction. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective Effect of Vaccine Promoted Neutralizing Antibodies against the Intracellular Pathogen Chlamydia trachomatis.

PubMed

Olsen, Anja Weinreich; Lorenzen, Emma Kathrine; Rosenkrands, Ida; Follmann, Frank; Andersen, Peter

2017-01-01

There is an unmet need for a vaccine to control Chlamydia trachomatis ( C.t .) infections. We have recently designed a multivalent heterologous immuno-repeat 1 (Hirep1) vaccine construct based on major outer membrane protein variable domain (VD) 4 regions from C.t . serovars (Svs) D-F. Hirep1 administered in the Cationic Adjuvant Formulation no. 1 (CAF01) promoted neutralizing antibodies in concert with CD4 + T cells and protected against genital infection. In the current study, we examined the protective role of the antibody (Ab) response in detail. Mice were vaccinated with either Hirep1 or a vaccine construct based on a homologous multivalent construct of extended VD4's from SvF (extVD4 F *4), adjuvanted in CAF01. Hirep1 and extVD4 F *4 induced similar levels of Ab and cell-mediated immune responses but differed in the fine specificity of the B cell epitopes targeted in the VD4 region. Hirep1 induced a strong response toward a neutralizing epitope (LNPTIAG) and the importance of this epitope for neutralization was demonstrated by competitive inhibition with the corresponding peptide. Immunization with extVD4 F *4 skewed the response to a non-neutralizing epitope slightly upstream in the sequence. Vaccination with Hirep1 as opposed to extVD4 F *4 induced significant protection against infection in mice both in short- and long-term vaccination experiments, signifying a key role for Hirep1 neutralizing antibodies during protection against C.t . Finally, we show that passive immunization of Rag1 knockout mice with Hirep1 antibodies completely prevented the establishment of infection in 48% of the mice, demonstrating an isolated role for neutralizing antibodies in controlling infection. Our data emphasize the role of antibodies in early protection against C.t . and support the inclusion of neutralizing targets in chlamydia vaccines.

Protective Effect of Vaccine Promoted Neutralizing Antibodies against the Intracellular Pathogen Chlamydia trachomatis

PubMed Central

Olsen, Anja Weinreich; Lorenzen, Emma Kathrine; Rosenkrands, Ida; Follmann, Frank; Andersen, Peter

2017-01-01

There is an unmet need for a vaccine to control Chlamydia trachomatis (C.t.) infections. We have recently designed a multivalent heterologous immuno-repeat 1 (Hirep1) vaccine construct based on major outer membrane protein variable domain (VD) 4 regions from C.t. serovars (Svs) D–F. Hirep1 administered in the Cationic Adjuvant Formulation no. 1 (CAF01) promoted neutralizing antibodies in concert with CD4+ T cells and protected against genital infection. In the current study, we examined the protective role of the antibody (Ab) response in detail. Mice were vaccinated with either Hirep1 or a vaccine construct based on a homologous multivalent construct of extended VD4’s from SvF (extVD4F*4), adjuvanted in CAF01. Hirep1 and extVD4F*4 induced similar levels of Ab and cell-mediated immune responses but differed in the fine specificity of the B cell epitopes targeted in the VD4 region. Hirep1 induced a strong response toward a neutralizing epitope (LNPTIAG) and the importance of this epitope for neutralization was demonstrated by competitive inhibition with the corresponding peptide. Immunization with extVD4F*4 skewed the response to a non-neutralizing epitope slightly upstream in the sequence. Vaccination with Hirep1 as opposed to extVD4F*4 induced significant protection against infection in mice both in short- and long-term vaccination experiments, signifying a key role for Hirep1 neutralizing antibodies during protection against C.t. Finally, we show that passive immunization of Rag1 knockout mice with Hirep1 antibodies completely prevented the establishment of infection in 48% of the mice, demonstrating an isolated role for neutralizing antibodies in controlling infection. Our data emphasize the role of antibodies in early protection against C.t. and support the inclusion of neutralizing targets in chlamydia vaccines. PMID:29312283

grid-model: Semi-numerical reionization code

NASA Astrophysics Data System (ADS)

Hutter, Anne

2018-05-01

grid-model computes the time and spatially dependent ionization of neutral hydrogen (HI), neutral (HeI) and singly ionized helium (HeII) in the intergalactic medium (IGM). It accounts for recombinations and provides different descriptions for the photoionization rate that are used to calculate the residual HI fraction in ionized regions. The ionizing emissivity is directly derived from the RT simulation spectra.

Comparison of early and late treatment with a recombinant endotoxin neutralizing protein in a rat model of Escherichia coli sepsis.

PubMed

Weiner, D L; Kuppermann, N; Saladino, R A; Thompson, C M; Novitsky, T J; Siber, G R; Fleisher, G R

1996-09-01

To test the efficacy of a recombinant endotoxin neutralizing protein as compared with saline in rats with Escherichia coli sepsis. Prospective, controlled animal trial. Hospital animal research laboratory. Male Wistar rats challenged with intraperitoneal E. coli, O18ac K1, and treated 1 hr later with ceftriaxone and gentamicin. Recombinant endotoxin neutralizing protein, 50 mg/kg, was administered to rats 1, 2, or 3 hrs after E. coli challenge; saline was administered to control animals. Quantitative bacteremia, 1 hr after challenge and before antibiotic administration, was not significantly different between treatment groups (range geometric mean 451 to 621 colony-forming units [cfu]/mL). The endotoxin concentration, measured immediately before recombinant endotoxin neutralizing protein administration, was significantly higher in animals sampled and treated at 2 hrs (geometric mean 260 EU/mL; 95% confidence interval 140 to 480 EU/mL), or 3 hrs (geometric mean 697 EU/mL; 95% confidence interval 307 to 1585 EU/mL) after E. coli challenge, compared with animals sampled and treated at 1 hr (geometric mean 17 EU/mL; 95% confidence interval 7 to 69 EU/ mL). Survival rate was significantly greater in rats treated with recombinant endotoxin neutralizing protein at 1 hr (23/27; p < .001) or 2 hrs (8/30; p < .01) after E. coli challenge than in controls (1/32). Administration of recombinant endotoxin neutralizing protein delayed up to 2 hrs after challenge with E. coli improves survival in antibiotic-treated rats with Gram-negative sepsis.

Molecular clock on a neutral network.

PubMed

Raval, Alpan

2007-09-28

The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

Molecular Clock on a Neutral Network

NASA Astrophysics Data System (ADS)

Raval, Alpan

2007-09-01

The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

Is a neutral expression also a neutral stimulus? A study with functional magnetic resonance.

PubMed

Carvajal, Fernando; Rubio, Sandra; Serrano, Juan M; Ríos-Lago, Marcos; Alvarez-Linera, Juan; Pacheco, Lara; Martín, Pilar

2013-08-01

Although neutral faces do not initially convey an explicit emotional message, it has been found that individuals tend to assign them an affective content. Moreover, previous research has shown that affective judgments are mediated by the task they have to perform. Using functional magnetic resonance imaging in 21 healthy participants, we focus this study on the cerebral activity patterns triggered by neutral and emotional faces in two different tasks (social or gender judgments). Results obtained, using conjunction analyses, indicated that viewing both emotional and neutral faces evokes activity in several similar brain areas indicating a common neural substrate. Moreover, neutral faces specifically elicit activation of cerebellum, frontal and temporal areas, while emotional faces involve the cuneus, anterior cingulated gyrus, medial orbitofrontal cortex, posterior superior temporal gyrus, precentral/postcentral gyrus and insula. The task selected was also found to influence brain activity, in that the social task recruited frontal areas while the gender task involved the posterior cingulated, inferior parietal lobule and middle temporal gyrus to a greater extent. Specifically, in the social task viewing neutral faces was associated with longer reaction times and increased activity of left dorsolateral frontal cortex compared with viewing facial expressions of emotions. In contrast, in the same task emotional expressions distinctively activated the left amygdale. The results are discussed taking into consideration the fact that, like other facial expressions, neutral expressions are usually assigned some emotional significance. However, neutral faces evoke a greater activation of circuits probably involved in more elaborate cognitive processing.

Measuring Alignments between Galaxies and the Cosmic Web at z ˜ 2-3 Using IGM Tomography

NASA Astrophysics Data System (ADS)

Krolewski, Alex; Lee, Khee-Gan; Lukić, Zarija; White, Martin

2017-03-01

Many galaxy formation models predict alignments between galaxy spin and the cosmic web (I.e., directions of filaments and sheets), leading to an intrinsic alignment between galaxies that creates a systematic error in weak-lensing measurements. These effects are often predicted to be stronger at high redshifts (z ≳ 1) that are inaccessible to massive galaxy surveys on foreseeable instrumentation, but IGM tomography of the Lyα forest from closely spaced quasars and galaxies is starting to measure the z ˜ 2-3 cosmic web with requisite fidelity. Using mock surveys from hydrodynamical simulations, we examine the utility of this technique, in conjunction with coeval galaxy samples, to measure alignment between galaxies and the cosmic web at z ˜ 2.5. We show that IGM tomography surveys with ≲5 h -1 Mpc sightline spacing can accurately recover the eigenvectors of the tidal tensor, which we use to define the directions of the cosmic web. For galaxy spins and shapes, we use a model parameterized by the alignment strength, {{Δ }}< \\cos θ > , with respect to the tidal tensor eigenvectors from the underlying density field, and also consider observational effects such as errors in the galaxy position angle, inclination, and redshift. Measurements using the upcoming ˜1 deg2 CLAMATO tomographic survey and 600 coeval zCOSMOS-Deep galaxies should place 3σ limits on extreme alignment models with {{Δ }}< \\cos θ > ˜ 0.1, but much larger surveys encompassing >10,000 galaxies, such as Subaru PFS, will be required to constrain models with {{Δ }}< \\cos θ > ˜ 0.03. These measurements will constrain models of galaxy-cosmic web alignment and test tidal torque theory at z ˜ 2, improving our understanding of the physics of intrinsic alignments.

Measuring Alignments between Galaxies and the Cosmic Web at z ~ 2–3 Using IGM Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krolewski, Alex; Lee, Khee-Gan; Luki?, Zarija

Many galaxy formation models predict alignments between galaxy spin and the cosmic web (i.e., directions of filaments and sheets), leading to an intrinsic alignment between galaxies that creates a systematic error in weak-lensing measurements. These effects are often predicted to be stronger at high redshifts (z ≳ 1) that are inaccessible to massive galaxy surveys on foreseeable instrumentation, but IGM tomography of the Lyα forest from closely spaced quasars and galaxies is starting to measure the z ~ 2-3 cosmic web with requisite fidelity. Using mock surveys from hydrodynamical simulations, we examine the utility of this technique, in conjunction withmore » coeval galaxy samples, to measure alignment between galaxies and the cosmic web at z ~ 2.5. We show that IGM tomography surveys with ≲ 5 h -1 Mpc sightline spacing can accurately recover the eigenvectors of the tidal tensor, which we use to define the directions of the cosmic web. For galaxy spins and shapes, we use a model parameterized by the alignment strength, Δ (cos θ), with respect to the tidal tensor eigenvectors from the underlying density field, and also consider observational effects such as errors in the galaxy position angle, inclination, and redshift. Measurements using the upcoming ~ 1 deg 2 CLAMATO tomographic survey and 600 coeval zCOSMOS-Deep galaxies should place 3σ limits on extreme alignment models with Δ (cos θ) ~ 0.1, but much larger surveys encompassing > 10,000 galaxies, such as Subaru PFS, will be required to constrain models with Δ (cos θ) ~ 0.3. These measurements will constrain models of galaxy-cosmic web alignment and test tidal torque theory at z ~ 2, improving our understanding of the physics of intrinsic alignments.« less

Measuring Alignments between Galaxies and the Cosmic Web at z ~ 2–3 Using IGM Tomography

DOE PAGES

Krolewski, Alex; Lee, Khee-Gan; Luki?, Zarija; ...

2017-02-28

Many galaxy formation models predict alignments between galaxy spin and the cosmic web (i.e., directions of filaments and sheets), leading to an intrinsic alignment between galaxies that creates a systematic error in weak-lensing measurements. These effects are often predicted to be stronger at high redshifts (z ≳ 1) that are inaccessible to massive galaxy surveys on foreseeable instrumentation, but IGM tomography of the Lyα forest from closely spaced quasars and galaxies is starting to measure the z ~ 2-3 cosmic web with requisite fidelity. Using mock surveys from hydrodynamical simulations, we examine the utility of this technique, in conjunction withmore » coeval galaxy samples, to measure alignment between galaxies and the cosmic web at z ~ 2.5. We show that IGM tomography surveys with ≲ 5 h -1 Mpc sightline spacing can accurately recover the eigenvectors of the tidal tensor, which we use to define the directions of the cosmic web. For galaxy spins and shapes, we use a model parameterized by the alignment strength, Δ (cos θ), with respect to the tidal tensor eigenvectors from the underlying density field, and also consider observational effects such as errors in the galaxy position angle, inclination, and redshift. Measurements using the upcoming ~ 1 deg 2 CLAMATO tomographic survey and 600 coeval zCOSMOS-Deep galaxies should place 3σ limits on extreme alignment models with Δ (cos θ) ~ 0.1, but much larger surveys encompassing > 10,000 galaxies, such as Subaru PFS, will be required to constrain models with Δ (cos θ) ~ 0.3. These measurements will constrain models of galaxy-cosmic web alignment and test tidal torque theory at z ~ 2, improving our understanding of the physics of intrinsic alignments.« less

Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site

PubMed Central

Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J.

2016-01-01

ABSTRACT Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. IMPORTANCE We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. PMID:26764003

Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site.

PubMed

Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J; Hogle, James M

2016-01-13

Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

New synthesis method for 4-MAPBA monomer and using for the recognition of IgM and mannose with MIP-based QCM sensors.

PubMed

Diltemiz, Sibel Emir; Hür, Deniz; Keçili, Rüstem; Ersöz, Arzu; Say, Rıdvan

2013-03-07

Quartz crystal microbalance (QCM) sensors coated with molecularly imprinted polymers (MIP) have been developed for the recognition of immunoglobulin M (IgM) and mannose. In this method, methacryloylamidophenylboronic acid (MAPBA) was used as a monomer and mannose was used as a template. For this purpose, initially, QCM electrodes were modified with 2-propene-1-thiol to form mannose-binding regions on the QCM sensor surface. In the second step, the methacryloylamidophenylboronic acid-mannose [MAPBA-mannose], pre-organized monomer system, was prepared using the MAPBA monomer. Then, a molecularly imprinted film was coated on to the QCM electrode surface under UV light using ethylene glycol dimethacrylate (EDMA), and azobisisobutyronitrile (AIBN) as a cross-linking agent and an initiator, respectively. The mannose can be simultaneously bound to MAPBA and fitted into the shape-selective cavities. The binding affinity of the mannose-imprinted sensors was investigated using the Langmuir isotherm. The mannose-imprinted QCM electrodes have shown homogeneous binding sites for mannose (K(a): 3.3 × 10(4) M(-1)) and heterogeneous binding sites for IgM (K(a1): 1.0 × 10(4) M(-1); K(a2): 3.3 × 10(3) M(-1)).

Neutral beamline with improved ion energy recovery

DOEpatents

Kim, Jinchoon

1984-01-01

A neutral beamline employing direct energy recovery of unneutralized residual ions is provided which enhances the energy recovery of the full energy ion component of the beam exiting the neutralizer cell, and thus improves the overall neutral beamline efficiency. The unneutralized full energy ions exiting the neutralizer are deflected from the beam path and the electrons in the cell are blocked by a magnetic field applied transverse to the beam direction in the neutral izer exit region. The ions which are generated at essentially ground potential and accelerated through the neutralizer cell by a negative acceleration voltage are collected at ground potential. A neutralizer cell exit end region is provided which allows the magnetic and electric fields acting on the exiting ions to be loosely coupled. As a result, the fractional energy ions exiting the cell are reflected onto and collected at an interior wall of the neutralizer formed by the modified end geometry, and thus do not detract from the energy recovery efficiency of full energy ions exiting the cell. Electrons within the neutralizer are prevented from exiting the neutralizer end opening by the action of crossed fields drift (ExB) and are terminated to a collector collar around the downstream opening of the neutralizer. The correct combination of the extended neutralizer end structure and the magnet region is designed so as to maximize the exit of full energy ions and to contain the fractional energy ions.

Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients

PubMed Central

Aw-Yong, Kam Leng; Sam, I-Ching; Koh, Mia Tuang

2016-01-01

Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4), and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142–156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41–55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates. PMID:27806091

IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.

PubMed Central

Procaccia, S; Lazzarin, A; Colucci, A; Gasparini, A; Forcellini, P; Lanzanova, D; Foppa, C U; Novati, R; Zanussi, C

1987-01-01

To investigate some humoral aspects which may reflect the involvement of B lymphocytes in the acquired immunodeficiency syndrome (AIDS), we used an enzyme-linked immunoassay (ELISA) to determine the levels of IgM, IgG and IgA rheumatoid factors (RF) in 16 patients suffering from full-blown AIDS and 32 patients with AIDS-related complex (ARC), in the clinical form of lymphoadenopathy syndrome (LAS), compared with 40 healthy, young heterosexual subjects. Both AIDS and ARC patients showed a greater incidence of high IgM RF levels, with mean values significantly higher than controls, but with no differences between the two pathological groups. IgG RF behaviour was similar in the two patient populations and the healthy subjects. IgA RF were significantly raised in AIDS and ARC. Further information on RF was obtained by determination of the immunoglobulin levels of the respective isotypes in the same patients. Mean IgG levels were above normal in AIDS and ARC patients, but the latter group showed a higher incidence of increased values and higher mean levels. The IgA isotype was significantly increased mainly in AIDS patients. The behaviour of IgM was virtually the same in the three groups studied. A difference between AIDS and ARC patients was established by the detection of circulating immune-complexes (IC) by the C1q-binding and CIC-conglutinin assays. IC were significantly high, by both methods, only in the ARC group, but normal or very low in AIDS. These overall findings suggest once again the impairment of B cell function in AIDS, with prevalent hyperactivation in ARC and exhaustion in full-blown AIDS, and apparent preservation, in the latter group, of the antibody responses which are more closely related to the activity of subsets of T helper cells. PMID:3608224

Varied presentations of early congenital syphilis.

PubMed

Basu, Sriparna; Kumar, Ashok

2013-06-01

In spite of availability of cost-effective preventive measures and treatment, a resurgence of congenital syphilis has currently been noted. During the past 4 years, we came across five low birth weight neonates with unusual symptoms, which subsequently proved to be manifestations of early congenital syphilis. All the mothers had apparently uneventful antenatal period. No investigation was done during pregnancy. They were unaware about their disease and were found to be positive for syphilis by Venereal Disease Research Laboratory Test and fluorescent treponemal antibody (absorbed) IgM test only after childbirth. Screening for other congenital infections was negative. All the neonates were positive for Venereal Disease Research Laboratory Test. They were treated with intravenous crystalline penicillin G for 10 days. Recovery was uneventful. We reemphasize the importance of raising public awareness, routine antenatal screening and treatment for all pregnant mothers to avoid such a potentially treatable condition.

Estimating the Stoichiometry of HIV Neutralization

PubMed Central

Magnus, Carsten; Regoes, Roland R.

2010-01-01

HIV-1 virions infect target cells by first establishing contact between envelope glycoprotein trimers on the virion's surface and CD4 receptors on a target cell, recruiting co-receptors, fusing with the cell membrane and finally releasing the genetic material into the target cell. Specific experimental setups allow the study of the number of trimer-receptor-interactions needed for infection, i.e., the stoichiometry of entry and also the number of antibodies needed to prevent one trimer from engaging successfully in the entry process, i.e., the stoichiometry of (trimer) neutralization. Mathematical models are required to infer the stoichiometric parameters from these experimental data. Recently, we developed mathematical models for the estimations of the stoichiometry of entry [1]. In this article, we show how our models can be extended to investigate the stoichiometry of trimer neutralization. We study how various biological parameters affect the estimate of the stoichiometry of neutralization. We find that the distribution of trimer numbers—which is also an important determinant of the stoichiometry of entry—influences the estimated value of the stoichiometry of neutralization. In contrast, other parameters, which characterize the experimental system, diminish the information we can extract from the data about the stoichiometry of neutralization, and thus reduce our confidence in the estimate. We illustrate the use of our models by re-analyzing previously published data on the neutralization sensitivity [2], which contains measurements of neutralization sensitivity of viruses with different envelope proteins to antibodies with various specificities. Our mathematical framework represents the formal basis for the estimation of the stoichiometry of neutralization. Together with the stoichiometry of entry, the stoichiometry of trimer neutralization will allow one to calculate how many antibodies are required to neutralize a virion or even an entire population of

Ion-Neutral Coupling in Solar Prominences

NASA Technical Reports Server (NTRS)

Gilbert, Holly

2011-01-01

Interactions between ions and neutrals in a partially ionized plasma are important throughout heliophysics, including near the solar surface in prominences. Understanding how ion-neutral coupling affects formation, support, structure, and dynamics of prominences will advance our physical understanding of magnetized systems involving a transition from a weakly ionized dense gas to a fully ionized tenuous plasma. We address the fundamental physics of prominence support, which is normally described in terms of a magnetic force on the prominence plasma that balances the solar gravitational force, and the implications for observations. Because the prominence plasma is only partially ionized, it is necessary to consider the support of the both the ionized and neutral components. Support of the neutrals is accomplished through a frictional interaction between the neutral and ionized components of the plasma, and its efficacy depends strongly on the degree of ionization of the plasma. More specifically, the frictional force is proportional to the relative flow of neutral and ion species, and for a sufficiently weakly ionized plasma, this flow must be relatively large to produce a frictional force that balances gravity. A large relative flow, of course, implies significant draining of neutral particles from the prominence. We evaluate the importance of this draining effect for a hydrogen-helium plasma, and consider the observational evidence for cross-field diffusion of neutral prominence material.

Benchmark of 3D halo neutral simulation in TRANSP and FIDASIM and application to projected neutral-beam-heated NSTX-U plasmas

NASA Astrophysics Data System (ADS)

Liu, D.; Medley, S. S.; Gorelenkova, M. V.; Heidbrink, W. W.; Stagner, L.

2014-10-01

A cloud of halo neutrals is created in the vicinity of beam footprint during the neutral beam injection and the halo neutral density can be comparable with beam neutral density. Proper modeling of halo neutrals is critical to correctly interpret neutral particle analyzers (NPA) and fast ion D-alpha (FIDA) signals since these signals strongly depend on local beam and halo neutral density. A 3D halo neutral model has been recently developed and implemented inside TRANSP code. The 3D halo neutral code uses a ``beam-in-a-box'' model that encompasses both injected beam neutrals and resulting halo neutrals. Upon deposition by charge exchange, a subset of the full, one-half and one-third beam energy components produce thermal halo neutrals that are tracked through successive halo neutral generations until an ionization event occurs or a descendant halo exits the box. A benchmark between 3D halo neural model in TRANSP and in FIDA/NPA synthetic diagnostic code FIDASIM is carried out. Detailed comparison of halo neutral density profiles from two codes will be shown. The NPA and FIDA simulations with and without 3D halos are applied to projections of plasma performance for the National Spherical Tours eXperiment-Upgrade (NSTX-U) and the effects of halo neutral density on NPA and FIDA signal amplitude and profile will be presented. Work supported by US DOE.

Modeling Neutral Densities Downstream of a Gridded Ion Thruster

NASA Technical Reports Server (NTRS)

Soulas, George C.

2010-01-01

The details of a model for determining the neutral density downstream of a gridded ion thruster are presented. An investigation of the possible sources of neutrals emanating from and surrounding a NEXT ion thruster determined that the most significant contributors to the downstream neutral density include discharge chamber neutrals escaping through the perforated grids, neutrals escaping from the neutralizer, and vacuum facility background neutrals. For the neutral flux through the grids, near- and far-field equations are presented for rigorously determining the neutral density downstream of a cylindrical aperture. These equations are integrated into a spherically-domed convex grid geometry with a hexagonal array of apertures for determining neutral densities downstream of the ion thruster grids. The neutrals escaping from an off-center neutralizer are also modeled assuming diffuse neutral emission from the neutralizer keeper orifice. Finally, the effect of the surrounding vacuum facility neutrals is included and assumed to be constant. The model is used to predict the neutral density downstream of a NEXT ion thruster with and without neutralizer flow and a vacuum facility background pressure. The impacts of past simplifying assumptions for predicting downstream neutral densities are also examined for a NEXT ion thruster.

Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.

PubMed

Hessell, Ann J; Malherbe, Delphine C; Pissani, Franco; McBurney, Sean; Krebs, Shelly J; Gomes, Michelle; Pandey, Shilpi; Sutton, William F; Burwitz, Benjamin J; Gray, Matthew; Robins, Harlan; Park, Byung S; Sacha, Jonah B; LaBranche, Celia C; Fuller, Deborah H; Montefiori, David C; Stamatatos, Leonidas; Sather, D Noah; Haigwood, Nancy L

2016-04-01

Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B-infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements. Copyright © 2016 by The American Association of Immunologists, Inc.

Comparison of a recombinant endotoxin-neutralizing protein with a human monoclonal antibody to endotoxin for the treatment of Escherichia coli sepsis in rats.

PubMed

Kuppermann, N; Nelson, D S; Saladino, R A; Thompson, C M; Sattler, F; Novitsky, T J; Fleisher, G R; Siber, G R

1994-09-01

A recombinant endotoxin-neutralizing protein (ENP) from Limulus polyphemus and a monoclonal IgM anti-lipid A antibody (HA-1A) were compared in a rat model of Escherichia coli sepsis. One hour after intraperitoneal challenge with 10(6) cfu of E. coli O18ac K1, animals were sensitized to endotoxin with lead acetate and treated with ENP, HA-1A, or saline, followed by ceftriaxone and gentamicin. Before treatment, 95% of rats had high-grade bacteremia and high serum endotoxin concentrations, which were similar in all treatment groups (P > .60). One hour after treatment, there was no bacterial growth in any blood sample, and endotoxin concentrations were significantly lower in the ENP group than in the HA-1A and saline groups (P < .01). At 24 h after challenge, survival in the ENP group was significantly higher than in the HA-1A saline group (P < .001). ENP improved survival in a rat model of E. coli sepsis with high mortality despite effective antibiotic therapy.

Neutrality, abstinence, and the therapeutic alliance.

PubMed

Meissner, W W

1998-01-01

Concepts of neutrality and abstinence are discussed in terms of the variant opinions about them, pro and con, with particular reference to efforts to dispense with them based on the unavoidable role of the analyst's personal influence and subjectivity in the analytic process. Stereotypes of both neutrality and abstinence are examined, and the therapeutic alliance established as the most appropriate context within which to articulate the essential and constructive role of effective analytic neutrality and abstinence. The alliance is not possible without the persistent exercise of both neutrality and abstinence; conversely, other components of the alliance are intended to facilitate and preserve neutrality and abstinence on the part of both analyst and analysand. These elements are essential factors in effective analytic practice.

Probing the end of reionization with the near zones of z ≳ 6 QSOs

NASA Astrophysics Data System (ADS)

Keating, Laura C.; Haehnelt, Martin G.; Cantalupo, Sebastiano; Puchwein, Ewald

2015-11-01

QSO near zones are an important probe of the ionization state of the intergalactic medium (IGM) at z ˜ 6-7, at the end of reionization. We present here high-resolution cosmological 3D radiative transfer simulations of QSO environments for a wide range of host halo masses, 1010-12.5 M⊙. Our simulated near zones reproduce both the overall decrease of observed near-zone sizes at 6 < z < 7 and their scatter. The observable near-zone properties in our simulations depend only very weakly on the mass of the host halo. The size of the H II region expanding into the IGM is generally limited by (super-)Lyman Limit systems loosely associated with (low-mass) dark matter haloes. This leads to a strong dependence of near-zone size on direction and drives the large observed scatter. In the simulation centred on our most massive host halo, many sightlines show strong red damping wings even for initial volume averaged neutral hydrogen fractions as low as ˜10-3. For QSO lifetimes long enough to allow growth of the central supermassive black hole while optically bright, we can reproduce the observed near zone of ULAS J1120+0641 only with an IGM that is initially neutral. Our results suggest that larger samples of z > 7 QSOs will provide important constraints on the evolution of the neutral hydrogen fraction and thus on how late reionization ends.

Effects of (Anti) Androgenic Endocrine Disruptors (DEHP and Butachlor) on Immunoglobulin M (IgM) and Leukocytes Counts of Male Rainbow Trout (Oncorhynchus mykiss).

PubMed

Ahmadivand, Sohrab; Farahmand, Hamid; Mirvaghefi, Alireza; Eagderi, Soheil; Zargar, Ashkan

2015-06-01

The effect of two anti-androgenic endocrine disrupting compounds, i.e. the plasticizer di (2-ethylhexyl) phthalate (DEHP) and herbicide butachlor, were evaluated for their effects on immunoglobulin M (IgM) and leukocytes in male rainbow trout. Also, plasma testosterone (T) concentration was measured to confirm their anti-androgenic effects. In the first experiment, trout were treated with 50 mg/kg (body weight) DEHP intraperitoneally, and in the second one, fish were exposed to 0.39 mg/L butachlor for 10 days. The results showed that T concentrations and white blood cells were significantly lower in fish exposed to either DEHP or butachlor compared to control fish (p < 0.05). Fish showed significantly elevated neutrophil levels and decreased lymphocyte levels in the butachlor (p < 0.05); however, no significant difference was observed in lymphocyte and neutrophils values in the DEHP treatment (p > 0.05). In addition, no significant differences were found in IgM, eosinophil and monocyte parameters in either DEHP or butachlor treatments (p > 0.05). These results confirmed that leukocytes counts can be considered as a novel marker of immunotoxicity triggered by (anti) androgenic endocrine disruptors.

Monitoring of early humoral immunity to identify lung recipients at risk for development of serious infections: A multicenter prospective study.

PubMed

Sarmiento, Elizabeth; Cifrian, Jose; Calahorra, Leticia; Bravo, Carles; Lopez, Sonia; Laporta, Rosalia; Ussetti, Piedad; Sole, Amparo; Morales, Carmen; de Pablos, Alicia; Jaramillo, Maria; Ezzahouri, Ikram; García, Sandra; Navarro, Joaquin; Lopez-Hoyos, Marcos; Carbone, Javier

2018-04-06

Infection is still a leading cause of death during the first year after lung transplantation. We performed a multicenter study among teaching hospitals to assess monitoring of early humoral immunity as a means of identifying lung recipients at risk of serious infections. We prospectively analyzed 82 adult lung recipients at 5 centers in Spain. Data were collected before transplantation and at 7 and 30 days after transplantation. Biomarkers included IgG, IgM, IgA, complement factors C3 and C4, titers of antibodies to pneumococcal polysaccharide antigens (IgG, IgA, IgM) and antibodies to cytomegalovirus (IgG), and serum B-cell activating factor (BAFF) levels. The clinical follow-up period lasted 6 months. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. We found that 33 patients (40.2%) developed at least 1 serious bacterial infection, 8 patients (9.8%) had CMV disease, and 10 patients (12.2%) had fungal infections. Lower IgM antibody levels against pneumococcal polysaccharide antigens at Day 7 (defined as <5 mg/dl) were a risk factor for serious bacterial infection (adjusted odds ratio [OR] 3.96; 95% confidence interval [CI] 1.39 to 11.26; p = 0.0099). At Day 7 after transplantation, IgG hypogammaglobulinemia (defined as IgG <600 mg/dl) was associated with a higher risk of CMV disease (after adjustment for CMV mismatch: OR 8.15; 95% CI 1.27 to 52.55; p = 0.028) and fungal infection (adjusted OR 8.03, 95% CI 1.51 to 42.72; p = 0.015). Higher BAFF levels before transplantation were associated with a higher rate of development of serious bacterial infection and acute cellular rejection. Early monitoring of specific humoral immunity parameters proved useful for the identification of lung recipients who are at risk of serious infections. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights

Description of a Prospective 17DD Yellow Fever Vaccine Cohort in Recife, Brazil

PubMed Central

de Melo, Andréa Barbosa; da Silva, Maria da Paz C.; Magalhães, Maria Cecília F.; Gonzales Gil, Laura Helena Vega; Freese de Carvalho, Eduardo M.; Braga-Neto, Ulisses M.; Bertani, Giovani Rota; Marques, Ernesto T. A.; Cordeiro, Marli Tenório

2011-01-01

From September 2005 to March 2007, 238 individuals being vaccinated for the first time with the yellow fever (YF) -17DD vaccine were enrolled in a cohort established in Recife, Brazil. A prospective study indicated that, after immunization, anti-YF immunoglobulin M (IgM) and anti-YF IgG were present in 70.6% (IgM) and 98.3% (IgG) of the vaccinated subjects. All vaccinees developed protective immunity, which was detected by the plaque reduction neutralization test (PRNT) with a geometric mean titer of 892. Of the 238 individuals, 86.6% had IgG antibodies to dengue virus; however, the presence of anti-dengue IgG did not interfere significantly with the development of anti-YF neutralizing antibodies. In a separate retrospective study of individuals immunized with the 17DD vaccine, the PRNT values at 5 and 10 years post-vaccination remained positive but showed a significant decrease in neutralization titer (25% with PRNT titers < 100 after 5 years and 35% after 10 years). PMID:21976581

Energetic neutral particles from Jupiter and Saturn

NASA Astrophysics Data System (ADS)

Cheng, A. F.

1986-04-01

The Voyager 1 spacecraft has detected energetic neutral particles escaping from the magnetospheres of Jupiter and Saturn. These energetic neutrals are created in charge exchange reactions between radiation belt ions and ambient atoms or molecules in the magnetosphere. If the Io torus is assumed to be the dominant Jovian source region for energetic neutrals, the Voyager observations can be used to infer upper limits to the average ion intensities there below about 200 keV. No readily interpretable in-situ measurements are available in the Io torus at these energies. The middle and outer Jovian magnetospheres may also be a significant source of energetic neutrals. At Saturn, the observed neutral particle count rates are too high to be explained by charge exchange between fast protons and H atoms of the Titan torus. Most of the energetic neutrals may be produced by charge exchanges between heavy ions and a neutral cloud containing H2O in Saturn's inner magnetosphere. If so, the Voyager measurements of energetic neutral fluxes would be the first detected emissions from this region of Saturn's magnetosphere.

Atomic and Molecular Spectroscopic Studies of the DIII-D Neutral Beam Ion Source and Neutralizer

NASA Astrophysics Data System (ADS)

Crowley, B.; Rauch, J.; Scoville, J. T.; Sharma, S. K.; Choksi, B.

2015-11-01

The neutral beam system is interesting in that it comprises two distinct low temperature plasmas. Firstly, the ion source is typically a filament or RF driven plasma from which ions are extracted by a high voltage accelerator grid system. Secondly the neutralizer is essentially a low temperature plasma system with the beam serving as the primary ionization source and the neutralizer walls serving as conducting boundaries. Atomic spectroscopy of Doppler shifted D-alpha light emanating from the fast atoms is studied to determine the composition of the source and the divergence of the beam. Molecular spectroscopy involves measuring fine structure in electron-vibrational rotational bands. The technique has applications in low temperature plasmas and here it is used to determine gas temperature in the neutralizer. We describe the experimental set-up and the physics model used to relate the spectroscopic data to the plasma parameters and we present results of recent experiments exploring how to increase neutralization efficiency. Supported by the US DOE under DE-FC02-04ER54698.

Ion Neutral Mass Spectrometer Measurements from Titan

NASA Technical Reports Server (NTRS)

Waite, J. H., Jr.; Niemann, H.; Yelle, R. V.; Kasprzak, W.; Cravens, T.; Luhmann, J.; McNutt, R.; Ip, W.-H.; Gell, D.; Muller-Wordag, I. C. F.

2005-01-01

Introduction: The Ion Neutral Mass Spectrometer (INMS) aboard the Cassini orbiter has obtained the first in situ composition measurements of the neutral densities of molecular nitrogen, methane, argon, and a host of stable carbon-nitrile compounds in its first flyby of Titan. The bulk composition and thermal structure of the moon s upper atmosphere do not appear to be changed since the Voyager flyby in 1979. However, the more sensitive techniques provided by modern in-situ mass spectrometry also give evidence for large-spatial-scale large-amplitude atmospheric waves in the upper atmosphere and for a plethora of stable carbon-nitrile compounds above 1174 km. Furthermore, they allow the first direct measurements of isotopes of nitrogen, carbon, and argon, which provide interesting clues about the evolution of the atmosphere. The atmosphere was first accreted as ammonia and ammonia ices from the Saturn sub-nebula. Subsequent photochemistry likely converted the atmosphere into molecular nitrogen. The early atmosphere was 1.5 to 5 times more substantial and was lost via escape over the intervening 4.5 billion years due to the reduced gravity associated with the relatively small mass of Titan. Carbon in the form of methane has continued to outgas over time from the interior with much of it being deposited in the form of complex hydrocarbons on the surface and some of it also being lost to space.

The Net Neutrality Debate: The Basics

ERIC Educational Resources Information Center

Greenfield, Rich

2006-01-01

Rich Greenfield examines the basics of today's net neutrality debate that is likely to be an ongoing issue for society. Greenfield states the problems inherent in the definition of "net neutrality" used by Common Cause: "Network neutrality is the principle that Internet users should be able to access any web content they choose and…

Predicting HIV-1 broadly neutralizing antibody epitope networks using neutralization titers and a novel computational method

PubMed Central

2014-01-01

Background Recent efforts in HIV-1 vaccine design have focused on immunogens that evoke potent neutralizing antibody responses to a broad spectrum of viruses circulating worldwide. However, the development of effective vaccines will depend on the identification and characterization of the neutralizing antibodies and their epitopes. We developed bioinformatics methods to predict epitope networks and antigenic determinants using structural information, as well as corresponding genotypes and phenotypes generated by a highly sensitive and reproducible neutralization assay. 282 clonal envelope sequences from a multiclade panel of HIV-1 viruses were tested in viral neutralization assays with an array of broadly neutralizing monoclonal antibodies (mAbs: b12, PG9,16, PGT121 - 128, PGT130 - 131, PGT135 - 137, PGT141 - 145, and PGV04). We correlated IC50 titers with the envelope sequences, and used this information to predict antibody epitope networks. Structural patches were defined as amino acid groups based on solvent-accessibility, radius, atomic depth, and interaction networks within 3D envelope models. We applied a boosted algorithm consisting of multiple machine-learning and statistical models to evaluate these patches as possible antibody epitope regions, evidenced by strong correlations with the neutralization response for each antibody. Results We identified patch clusters with significant correlation to IC50 titers as sites that impact neutralization sensitivity and therefore are potentially part of the antibody binding sites. Predicted epitope networks were mostly located within the variable loops of the envelope glycoprotein (gp120), particularly in V1/V2. Site-directed mutagenesis experiments involving residues identified as epitope networks across multiple mAbs confirmed association of these residues with loss or gain of neutralization sensitivity. Conclusions Computational methods were implemented to rapidly survey protein structures and predict epitope

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

DOE PAGES

Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.; ...

2015-09-09

The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses.

PubMed

Moody, M Anthony; Gao, Feng; Gurley, Thaddeus C; Amos, Joshua D; Kumar, Amit; Hora, Bhavna; Marshall, Dawn J; Whitesides, John F; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey E; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Finzi, Andrés; Vandergrift, Nathan A; Alam, S Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia D; Kamanga, Gift; Cohen, Myron S; Sam, Noel E; Kapiga, Saidi; Gray, Elin S; Tumba, Nancy L; Morris, Lynn; Zolla-Pazner, Susan; Gorny, Miroslaw K; Mascola, John R; Hahn, Beatrice H; Shaw, George M; Sodroski, Joseph G; Liao, Hua-Xin; Montefiori, David C; Hraber, Peter T; Korber, Bette T; Haynes, Barton F

2015-09-09

The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses. Copyright © 2015 Elsevier Inc. All rights reserved.

Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.

The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

NREL - SOWFA - Neutral - TTU

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosovic, Branko

This dataset includes large-eddy simulation (LES) output from a neutrally stratified atmospheric boundary layer (ABL) simulation of observations at the SWIFT tower near Lubbock, Texas on Aug. 17, 2012. The dataset was used to assess LES models for simulation of canonical neutral ABL. The dataset can be used for comparison with other LES and computational fluid dynamics model outputs.

Neutrality and curiosity: elements of technique.

PubMed

Nersessian, Edward; Silvan, Matthew

2007-07-01

In the past three decades, neutrality has come under increasing criticism. The idea that a psychoanalyst can leave himself out of the therapeutic exchange has come to be seen as either an impossible dream or a myth. We propose that examining neutrality through the lens of curiosity allows for a new appreciation of the ongoing and vital importance of this psychoanalytic attitude. Our hypothesis is that curiosity and neutrality are linked, and that to maintain a neutral stance, the analyst must be able to direct a relatively conflict-free curiosity toward the workings of the analysand's mind as well as his own.

A layer of neutrally buoyant olivine in the early stages of a deep lunar magma ocean and a possible consecutive overturn

NASA Astrophysics Data System (ADS)

Krättli, G.; Schmidt, M. W.

2017-12-01

The moon is thought to have undergone a completely molten stage during its accretion, the lunar magma ocean. In order to understand the evolution and first differentiation of the lunar magma ocean, we performed a series of consecutive liquidus experiments at pressures of the lower half of the lunar magma ocean. In these experiments, we determined the liquidus, crystallized some amount of minerals (typically 10-20%) and then stepped to a new bulk composition representing the residual liquid after fractionation of these minerals. Mineral and melt densities were then calculated in order to decide whether minerals would float or sink. The bulk lunar composition used in this study (Taylor 1982) results in extensive early olivine crystallization with high XMg (94-90) for all experimental pressures, the liquidus temperature slightly decreasing from 1900 to 1850°C from 4.5 to 3.5 GPa. Crystallization begins at the core-mantle boundary, but calculations indicate that olivine initially floats and becomes neutrally buoyant at 3.5-3.7 GPa, leading to a stable olivine layer of several 100 km thickness at this depth. This layer should rapidly compact yielding two chemically separated magma reservoirs. Olivine crystallization is followed by orthopyroxene (1650°C, twm_fr2), minor garnet (1600°C, twm_fr3), clinopyroxene and spinel (1550°C, twm_fr3) in the lower magma ocean. Despite continuously decreasing XMg and increasing Ca/Al, further experiments indicate that the more extensively fractionated lower magma should become finally buoyant, possibly causing an overturn of the previously layered structure. Additionally, few centrifuge assisted experiments at 2.5-3.5 GPa were performed showing decreasing olivine-melt density contrasts with increasing pressure. Slightly higher pressures would be necessary to positively prove the neutral buoyancy of olivine at 3.6 GPa, currently we are improving the piston cylinder on the centrifuge to reach 4 GPa. Taylor, Stuart Ross. Planetary

Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies

PubMed Central

Zhu, Zhongyu; Chakraborti, Samitabh; He, Yuxian; Roberts, Anjeanette; Sheahan, Tim; Xiao, Xiaodong; Hensley, Lisa E.; Prabakaran, Ponraj; Rockx, Barry; Sidorov, Igor A.; Corti, Davide; Vogel, Leatrice; Feng, Yang; Kim, Jae-Ouk; Wang, Lin-Fa; Baric, Ralph; Lanzavecchia, Antonio; Curtis, Kristopher M.; Nabel, Gary J.; Subbarao, Kanta; Jiang, Shibo; Dimitrov, Dimiter S.

2007-01-01

The severe acute respiratory syndrome coronavirus (SARS-CoV) caused a worldwide epidemic in late 2002/early 2003 and a second outbreak in the winter of 2003/2004 by an independent animal-to-human transmission. The GD03 strain, which was isolated from an index patient of the second outbreak, was reported to resist neutralization by the human monoclonal antibodies (hmAbs) 80R and S3.1, which can potently neutralize isolates from the first outbreak. Here we report that two hmAbs, m396 and S230.15, potently neutralized GD03 and representative isolates from the first SARS outbreak (Urbani, Tor2) and from palm civets (SZ3, SZ16). These antibodies also protected mice challenged with the Urbani or recombinant viruses bearing the GD03 and SZ16 spike (S) glycoproteins. Both antibodies competed with the SARS-CoV receptor, ACE2, for binding to the receptor-binding domain (RBD), suggesting a mechanism of neutralization that involves interference with the SARS-CoV–ACE2 interaction. Two putative hot-spot residues in the RBD (Ile-489 and Tyr-491) were identified within the SARS-CoV spike that likely contribute to most of the m396-binding energy. Residues Ile-489 and Tyr-491 are highly conserved within the SARS-CoV spike, indicating a possible mechanism of the m396 cross-reactivity. Sequence analysis and mutagenesis data show that m396 might neutralize all zoonotic and epidemic SARS-CoV isolates with known sequences, except strains derived from bats. These antibodies exhibit cross-reactivity against isolates from the two SARS outbreaks and palm civets and could have potential applications for diagnosis, prophylaxis, and treatment of SARS-CoV infections. PMID:17620608

A neutral lithium beam source

NASA Astrophysics Data System (ADS)

Zhang, XiaoDong; Wang, ZhengMin; Hu, LiQun

1994-04-01

A low energy neutral lithium beam source with energy about 6 keV and a neutral beam equivalent current of 20 μA/cm2 has been developed in ASIPP in order to measure the density gradient and the fluctuations in the edge plasma of the HT-6M tokamak. In the source, lithium ions are extracted from a solid emitter (β-eucryptite), focused in a two-tube immersion lens, and neutralized in a charge-exchange cell with sodium. This source operates in pulsed mode. The pulse length is adjustable from 10 to 100 ms.

Adaptive Immune Responses following Senecavirus A Infection in Pigs.

PubMed

Maggioli, Mayara F; Lawson, Steve; de Lima, Marcelo; Joshi, Lok R; Faccin, Tatiane C; Bauermann, Fernando V; Diel, Diego G

2018-02-01

Senecavirus A (SVA), an emerging picornavirus of swine, causes vesicular disease (VD) that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Many aspects of SVA interactions with the host and the host immune responses to infection, however, remain unknown. In the present study, humoral and cellular immune responses to SVA were evaluated following infection in pigs. We show that SVA infection elicited an early and robust virus-neutralizing (VN) antibody response, which coincided and was strongly correlated with VP2- and VP3-specific IgM responses. Notably, the neutralizing antibody (NA) responses paralleled the reduction of viremia and resolution of the disease. Analysis of the major porcine T-cell subsets revealed that during the acute/clinical phase of SVA infection (14 days postinfection [p.i.]), T-cell responses were characterized by an increased frequency of αβ T cells, especially CD4 + T cells, which were first detected by day 7 p.i. and increased in frequency until day 14 p.i. Additionally, the frequency of CD8 + and double-positive CD4 + CD8 + T cells (effector/memory T cells) expressing interferon gamma (IFN-γ) or proliferating in response to SVA antigen stimulation increased after day 10 p.i. Results presented here show that SVA elicits B- and T-cell activation early upon infection, with IgM antibody levels being correlated with early neutralizing activity against the virus and peak B- and T-cell responses paralleling clinical resolution of the disease. The work provides important insights into the immunological events that follow SVA infection in the natural host. IMPORTANCE Senecavirus A (SVA) has recently emerged in swine, causing outbreaks of vesicular disease (VD) in major swine-producing countries around the world, including the United States, Brazil, China, Thailand, and Colombia. Notably, SVA-induced disease is clinically indistinguishable from other high-consequence VDs of swine, such as FMD, swine vesicular disease

Structural and functional properties of antibodies to the superantigen TSST-1 and their relationship to menstrual toxic shock syndrome.

PubMed

Kansal, Rita; Davis, Catherine; Hansmann, Melanie; Seymour, Jon; Parsonnet, Jeffrey; Modern, Paul; Gilbert, Steve; Kotb, Malak

2007-05-01

Menstrual toxic shock syndrome (mTSS) is an acute febrile disease accompanied by hypotension and multiple organ involvement. Infection with Staphylococcus aureus producing the superantigen toxic shock syndrome toxin-1 (TSST-1) vaginally is necessary; however, only a small fraction of those infected with TSST-1 producing bacteria actually develop mTSS, suggesting that host factors modulate disease susceptibility. Serum antibodies to the toxin protect against development of the syndrome, but not all antibodies can neutralize the toxin. We set out to determine whether risk of developing the syndrome is related to the absence of neutralizing antibody and if antibody isotypes influence the neutralization capacity. In healthy subjects, TSST-1-binding serum antibodies were exclusively of the IgG and IgM classes; however, toxin-neutralizing capacity was correlated to the TSST-1-specific IgG1 and IgG4 antibodies (r (2)=0.88, p<0.0001 and 0.33, p<0.0086, respectively) but not with IgM antibodies. Specific IgA was not detectable. Compared to healthy matched controls who were colonized vaginally with S. aureus, IgG1 anti-TSST-1 antibodies and toxin neutralizing activity was lacking in all of the acute phases and in the majority of convalescent sera, suggesting that these patients may be incapable of generating TSST-1 neutralizing antibodies. These new findings support the hypothesis that host factors are important in the development of mTSS and that the anti-toxin isotype impacts antibody functionality.

Neutral ISM, Ly α , and Lyman-continuum in the Nearby Starburst Haro 11

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivera-Thorsen, T. Emil; Östlin, Göran; Hayes, Matthew

2017-03-01

Star-forming galaxies are believed to be a major source of Lyman continuum (LyC) radiation responsible for reionizing the early universe. Direct observations of escaping ionizing radiation have however been sparse and with low escape fractions. In the local universe, only 10 emitters have been observed, with typical escape fractions of a few percent. The mechanisms regulating this escape need to be strongly evolving with redshift in order to account for the epoch of reionization. Gas content and star formation feedback are among the main suspects, known to both regulate neutral gas coverage and evolve with cosmic time. In this paper,more » we reanalyze Hubble Space Telescope ( HST )-Cosmic Origins Spectrograph (COS) spectrocopy of the first detected local LyC leaker, Haro 11. We examine the connection between LyC leakage and Ly α line shape, and feedback-influenced neutral interstellar medium (ISM) properties like kinematics and gas distribution. We discuss the two extremes of an optically thin, density bounded ISM and a riddled, optically thick, ionization bounded ISM, and how Haro 11 fits into theoretical predictions. We find that the most likely ISM model is a clumpy neutral medium embedded in a highly ionized medium with a combined covering fraction of unity and a residual neutral gas column density in the ionized medium high enough to be optically thick to Ly α , but low enough to be at least partly transparent to LyC and undetected in Si ii. This suggests that star formation feedback and galaxy-scale interaction events play a major role in opening passageways for ionizing radiation through the neutral medium.« less

Campus Climate Neutrality--Yes We Can! It's a Big Challenge, but Here's How to Do It

ERIC Educational Resources Information Center

Simpson, Walter

2009-01-01

Everyone knows climate change is real, it's happening quickly, its risks are great, and it is not too late to do something about it. Indicative of change is the fact that as of early 2009 over 600 colleges and universities have pledged to achieve climate neutrality through the American College & University Presidents Climate Commitment. Presidents…

ION SOURCE WITH SPACE CHARGE NEUTRALIZATION

DOEpatents

Flowers, J.W.; Luce, J.S.; Stirling, W.L.

1963-01-22

This patent relates to a space charge neutralized ion source in which a refluxing gas-fed arc discharge is provided between a cathode and a gas-fed anode to provide ions. An electron gun directs a controlled, monoenergetic electron beam through the discharge. A space charge neutralization is effected in the ion source and accelerating gap by oscillating low energy electrons, and a space charge neutralization of the source exit beam is effected by the monoenergetic electron beam beyond the source exit end. The neutralized beam may be accelerated to any desired energy at densities well above the limitation imposed by Langmuir-Child' s law. (AEC)

ExoCube INMS with Neutral Hydrogen Mode

NASA Astrophysics Data System (ADS)

Jones, S.; Paschalidis, N.; Rodriguez, M.; Sittler, E. C., Jr.; Chornay, D. J.; Cameron, T.; Uribe, P.; Nanan, G.; Noto, J.; Waldrop, L.; Mierkiewicz, E. J.; Gardner, D.; Nossal, S. M.; Puig-Suari, J.; Bellardo, J.

2015-12-01

The ExoCube mission launched on Jan 31 2015 into a polar orbit to acquire global knowledge of in situ densities of neutral and ionized H, He, and O in the upper ionosphere and lower exosphere. The CubeSat platform is used in combination with incoherent scatter radar and optical ground stations distributed throughout the Americas. ExoCube seeks to obtain the first in situ measurement of neutral exospheric hydrogen and will measure in situ atomic oxygen for the first time in decades. The compact Ion and Neutral Mass Spectrometer (INMS) developed by GSFC uses the gated Time of Flight technique for in situ measurements of ions and neutrals (H, He, N, O, N2, O2) with M/dM of approximately 10. The compact sensor has a dual symmetric configuration with ion and neutral sensor heads. Neutral particles are ionized by electron impact using a thermionic emitter. In situ measurements of neutral hydrogen are notoriously difficult as historically the signal has been contaminated by hydrogen outgassing which persists even years after commissioning. In order to obtain neutral atmospheric hydrogen fluxes, either the atmospheric peak and outgassing peak must be well resolved, or the outgassing component subtracted off. The ExoCube INMS employs a separate mode, specifically for measuring neutral Hydrogen. The details of this mode and lessons learned will be presented as well as in flight instrument validation data for the neutral channel and preliminary flight ion spectra. At the time of abstract submission, the ExoCube spacecraft is currently undergoing attitude control maneuvers to orient INMS in the ram direction for science operations.

Contribution of IgG avidity and PCR for the early diagnosis of toxoplasmosis in pregnant women from the North-Eastern region of Algeria.

PubMed

Berredjem, Hajira; Aouras, Hayette; Benlaifa, Meriem; Becheker, Imène; Djebar, Mohamed Reda

2017-09-01

Acute toxoplasmosis in pregnant women presents a high risk of Toxoplasma transmission to the fetus. Early diagnosis is difficult, especially when serological testing for IgG/IgM antibodies fail to differentiate between a recent and a past infection. In this case, we rely on IgG avidity or PCR assays. The aim of this study was to compare conventional ELISA and IgG avidity, with PCR using B1 and P30 primers for the early diagnosis of toxoplasmosis in pregnant women. Sera were collected from 143 pregnant women and measured by ELISA for anti- Toxoplasma IgG, IgM, IgA and IgG avidity. DNA was extracted from 57 peripheral blood and 14 amniotic fluid samples for PCR amplification. A total of 57 out 143 women were seropositive: 30 (52.6%) were IgG+/IgM- and 27 (43.8%) were IgG+/IgM+; IgA antibodies were positive in 7 (12.2%) cases. IgG avidity was low in 9 women suggesting an acute infection; 3 women presented an intermediate avidity. PCR detected Toxoplasma DNA in 9 women presenting low avidity and was negative for the intermediate avidity cases. PCR combined to avidity IgG performed better than ELISA IgG, IgM and/or IgA assays alone. PCR was useful in the case of intermediate avidity.

Neutral pion production in solar flares

NASA Technical Reports Server (NTRS)

Forrest, D. J.; Vestrand, W. T.; Chupp, E. L.; Rieger, E.; Cooper, J. F.; Share, G. H.

1985-01-01

The Gamma-Ray Spectrometer (GRS) on SMM has detected more than 130 flares with emission approx 300 keV. More than 10 of these flares were detected at photon energies 10 MeV. Although the majority of the emission at 10 MeV must be from electron bremsstrahlung, at least two of the flares have spectral properties 40 MeV that require gamma rays from the decay of neutral pions. It is found that pion production can occur early in the impulsive phase as defined by hard X-rays near 100 keV. It is also found in one of these flares that a significant portion of this high-energy emission is produced well after the impulsive phase. This extended production phase, most clearly observed at high energies, may be a signature of the acceleration process which produces solar energetic particles (SEP's) in space.

The Transient High Energy Sky and Early Universe Surveyor (THESEUS)

NASA Astrophysics Data System (ADS)

Amati, Lorenzo; O'Brien, Paul T.; Götz, Diego

2016-07-01

The Transient High Energy Sky and Early Universe Surveyor (THESEUS) is a mission concept under development by a large international collaboration aimed at exploiting gamma-ray bursts for investigating the early Universe. The main scientific objectives of THESEUS include: investigating the star formation rate and metallicity evolution of the ISM and IGM up to redshift 9-10, detecting the first generation (pop III) of stars, studying the sources and physics of re-ionization, detecting the faint end of galaxies luminosity function. These goals will be achieved through a unique combination of instruments allowing GRB detection and arcmin localization over a broad FOV (more than 1sr) and an energy band extending from several MeVs down to 0.3 keV with unprecedented sensitivity, as well as on-board prompt (few minutes) follow-up with a 0.6m class IR telescope with both imaging and spectroscopic capabilities. Such instrumentation will also allow THESEUS to unveil and study the population of soft and sub-energetic GRBs, and, more in general, to perform monitoring and survey of the X-ray sky with unprecedented sensitivity.

[Early form of toxoplasmosis with accompanying enlargement of lymph nodes].

PubMed

Małafiej, Eugeniusz; Spiewak, Ewa; Frankowska, Joanna; Maciejewska, Ewa

2004-05-01

The paper describes a case of a 42-year-old female presented rapidly increasing enlargement of lymph nodes. Initially it was believed to be an effect of proliferous systemic changes. The diagnostic procedures did not confirm the initial diagnosis but they evoked a lot of stress of the patient as well as her psychic discomfort resulting from a number of biopsies. Serological tests carried out in the further course of the diagnostic procedure showed that the increased nodular reaction should be attributed to Toxoplasma gondii invasion, which was indicated by the presence of IgM and IgA antibodies and low avidity of IgG. The early administration of specific treatment with spiramycin led to the regression of the clinical symptoms and gradual normalization of the serological test. The case is worth attention for several reasons: 1. it indicates that it is necessary to consider T. gondii infection in basic clinical practice, which is frequently ignored, 2. it illustrates the effectiveness of early specific treatment, 3. it demonstrates the importance of well selected and properly interpreted microbiological tests.

New insights on the collisional escape of light neutrals from Mars

NASA Astrophysics Data System (ADS)

Gacesa, Marko; Zahnle, Kevin

2017-04-01

Photodissociative recombination (PDR) of atmospheric molecules on Mars is a major mechanism of production of hot (suprathermal) atoms with sufficient kinetic energy to either directly escape to space or to eject other atmospheric species. This collisional ejection mechanism is important for evaluating the escape rates of all light neutrals that are too heavy to escape via Jeans escape. In particular, it plays a role in estimating the total volume of escaped water constituents (i.e., O and H) from Mars, as well as influences evolution of the atmospheric [D]/[H] ratio1. We present revised estimates of total collisional escape rates of neutral light elements including H, He, and H2, based on recent (years 2015-2016) atmospheric density profiles obtained from the NASA Mars Atmosphere and Volatile Evolution (MAVEN) mission. We also estimate the contribution to the collisional escape from Energetic Neutral Atoms (ENAs) produced in charge-exchange of solar wind H+ and He+ ions with atmospheric gases2,3. Scattering of hot oxygen and atmospheric species of interest is modeled using fully-quantum reactive scattering formalism1,3. The escape rates are evaluated using a 1D model of the atmosphere supplemented with MAVEN measurements of the neutrals. Finally, new estimates of contributions of these non-thermal mechanisms to the estimated PDR escape rates from young Mars4 are presented. [1] M. Gacesa and V. Kharchenko, "Non-thermal escape of molecular hydrogen from Mars", Geophys. Res. Lett., 39, L10203 (2012). [2] N. Lewkow and V. Kharchenko, "Precipitation of Energetic Neutral Atoms and Escape Fluxes induced from the Mars Atmosphere", Astroph. J., 790, 98 (2014). [3] M. Gacesa, N. Lewkow, and V. Kharchenko, "Non-thermal production and escape of OH from the upper atmosphere of Mars", Icarus 284, 90 (2017). [4] J. Zhao, F. Tian, Y. Ni, and X. Huang, "DR-induced escape of O and C from early Mars", Icarus 284, 305 (2017).

Relative contributions of neutral and non-neutral genetic differentiation to inform conservation of steelhead trout across highly variable landscapes

PubMed Central

Matala, Andrew P; Ackerman, Michael W; Campbell, Matthew R; Narum, Shawn R

2014-01-01

Mounting evidence of climatic effects on riverine environments and adaptive responses of fishes have elicited growing conservation concerns. Measures to rectify population declines include assessment of local extinction risk, population ecology, viability, and genetic differentiation. While conservation planning has been largely informed by neutral genetic structure, there has been a dearth of critical information regarding the role of non-neutral or functional genetic variation. We evaluated genetic variation among steelhead trout of the Columbia River Basin, which supports diverse populations distributed among dynamic landscapes. We categorized 188 SNP loci as either putatively neutral or candidates for divergent selection (non-neutral) using a multitest association approach. Neutral variation distinguished lineages and defined broad-scale population structure consistent with previous studies, but fine-scale resolution was also detected at levels not previously observed. Within distinct coastal and inland lineages, we identified nine and 22 candidate loci commonly associated with precipitation or temperature variables and putatively under divergent selection. Observed patterns of non-neutral variation suggest overall climate is likely to shape local adaptation (e.g., potential rapid evolution) of steelhead trout in the Columbia River region. Broad geographic patterns of neutral and non-neutral variation demonstrated here can be used to accommodate priorities for regional management and inform long-term conservation of this species. PMID:25067950

Early preschool environments and gender: Effects of gender pedagogy in Sweden.

PubMed

Shutts, Kristin; Kenward, Ben; Falk, Helena; Ivegran, Anna; Fawcett, Christine

2017-10-01

To test how early social environments affect children's consideration of gender, 3- to 6-year-old children (N=80) enrolled in gender-neutral or typical preschool programs in the central district of a large Swedish city completed measures designed to assess their gender-based social preferences, stereotypes, and automatic encoding. Compared with children in typical preschools, a greater proportion of children in the gender-neutral school were interested in playing with unfamiliar other-gender children. In addition, children attending the gender-neutral preschool scored lower on a gender stereotyping measure than children attending typical preschools. Children at the gender-neutral school, however, were not less likely to automatically encode others' gender. The findings suggest that gender-neutral pedagogy has moderate effects on how children think and feel about people of different genders but might not affect children's tendency to spontaneously notice gender. Copyright © 2017 Elsevier Inc. All rights reserved.

Neutral Pion Production in MINERvA

NASA Astrophysics Data System (ADS)

Palomino, Jose

2012-03-01

MINERνA is a neutrino-nucleus scattering experiment employing multiple nuclear targets. The experiment is searching for neutral pion production, both in charged current and neutral current, from coherent, resonant and deep-inelastic processes off these targets. Neutral pions are detected through the 2 photon decay that then produce electromagnetic showers. We will describe how we isolate and reconstruct the electromagnetic showers to calculate the invariant mass of the photon pair.

Nitrogen-neutrality: a step towards sustainability

NASA Astrophysics Data System (ADS)

Leip, Adrian; Leach, Allison; Musinguzi, Patrick; Tumwesigye, Trust; Olupot, Giregon; Tenywa, John Stephen; Mudiope, Joseph; Hutton, Olivia; Cordovil, Claudia M. d. S.; Bekunda, Mateete; Galloway, James

2014-11-01

We propose a novel indicator measuring one dimension of the sustainability of an entity in modern societies: Nitrogen-neutrality. N-neutrality strives to offset Nr releases an entity exerts on the environment from the release of reactive nitrogen (Nr) to the environment by reducing it and by offsetting the Nr releases elsewhere. N-neutrality also aims to increase awareness about the consequences of unintentional releases of nitrogen to the environment. N-neutrality is composed of two quantified elements: Nr released by an entity (e.g. on the basis of the N footprint) and Nr reduction from management and offset projects (N offset). It includes management strategies to reduce nitrogen losses before they occur (e.g., through energy conservation). Each of those elements faces specific challenges with regard to data availability and conceptual development. Impacts of Nr releases to the environment are manifold, and the impact profile of one unit of Nr release depends strongly on the compound released and the local susceptibility to Nr. As such, N-neutrality is more difficult to conceptualize and calculate than C-neutrality. We developed a workable conceptual framework for N-neutrality which was adapted for the 6th International Nitrogen Conference (N2013, Kampala, November 2013). Total N footprint of the surveyed meals at N2013 was 66 kg N. A total of US 3050 was collected from the participants and used to offset the conference’s N footprint by supporting the UN Millennium Village cluster Ruhiira in South-Western Uganda. The concept needs further development in particular to better incorporate the spatio-temporal variability of impacts and to standardize the methods to quantify the required N offset to neutralize the Nr releases impact. Criteria for compensation projects need to be sharply defined to allow the development of a market for N offset certificates.

Determination by enzyme-linked immunosorbent assay of immunoglobulin G (IgG), IgM, and IgA to Brucella melitensis major outer membrane proteins and whole-cell heat-killed antigens in sera of patients with brucellosis.

PubMed Central

Araj, G F; Kaufmann, A F

1989-01-01

An enzyme-linked immunosorbent assay was used to compare Brucella melitensis major outer membrane proteins (MOMP) and whole-cell heat-killed antigens (HK) in measuring antibrucella immunoglobulin G (IgG), IgM, and IgA in sera of brucellosis patients and controls. Antibodies to MOMP were generally similar to those against HK, and the correlation coefficients between the two antigens and IgG, IgM, and IgA in patients varied between 0.73 and 0.94. Both antigens are comparably suitable in detecting antibrucella immunoglobulin isotypes for the serologic diagnosis of patients with brucellosis, with high (greater than or equal to 95%) sensitivity and specificity. PMID:2768476

The Phobos neutral and ionized torus

NASA Astrophysics Data System (ADS)

Poppe, A. R.; Curry, S. M.; Fatemi, S.

2016-05-01

Charged particle sputtering, micrometeoroid impact vaporization, and photon-stimulated desorption are fundamental processes operating at airless surfaces throughout the solar system. At larger bodies, such as Earth's Moon and several of the outer planet moons, these processes generate tenuous surface-bound exospheres that have been observed by a variety of methods. Phobos and Deimos, in contrast, are too gravitationally weak to keep ejected neutrals bound and, thus, are suspected to generate neutral tori in orbit around Mars. While these tori have not yet been detected, the distribution and density of both the neutral and ionized components are of fundamental interest. We combine a neutral Monte Carlo model and a hybrid plasma model to investigate both the neutral and ionized components of the Phobos torus. We show that the spatial distribution of the neutral torus is highly dependent on each individual species (due to ionization rates that span nearly 4 orders of magnitude) and on the location of Phobos with respect to Mars. Additionally, we present the flux distribution of torus pickup ions throughout the Martian system and estimate typical pickup ion fluxes. We find that the predicted pickup ion fluxes are too low to perturb the ambient plasma, consistent with previous null detections by spacecraft around Mars.

Collisional spreading of Enceladus’ neutral cloud

NASA Astrophysics Data System (ADS)

Cassidy, T. A.; Johnson, R. E.

2010-10-01

We describe a direct simulation Monte Carlo (DSMC) model of Enceladus' neutral cloud and compare its results to observations of OH and O orbiting Saturn. The OH and O are observed far from Enceladus (at 3.95 R S), as far out as 25 R S for O. Previous DSMC models attributed this breadth primarily to ion/neutral scattering (including charge exchange) and molecular dissociation. However, the newly reported O observations and a reinterpretation of the OH observations (Melin, H., Shemansky, D.E., Liu, X. [2009] Planet. Space Sci., 57, 1743-1753, PS&S) showed that the cloud is broader than previously thought. We conclude that the addition of neutral/neutral scattering (Farmer, A.J. [2009] Icarus, 202, 280-286), which was underestimated by previous models, brings the model results in line with the new observations. Neutral/neutral collisions primarily happen in the densest part of the cloud, near Enceladus' orbit, but contribute to the spreading by pumping up orbital eccentricity. Based on the cloud model presented here Enceladus maybe the ultimate source of oxygen for the upper atmospheres of Titan and Saturn. We also predict that large quantities of OH, O and H 2O bombard Saturn's icy satellites.

Immunoglobulin M (IgM)-Glycoinositolphospholipid Enzyme-Linked Immunosorbent Assay: an Immunoenzymatic Assay for Discrimination between Patients with Acute Toxoplasmosis and Those with Persistent Parasite-Specific IgM Antibodies

PubMed Central

Giraldo, Mónica; Portela, Ricardo W. D.; Snege, Mirian; Leser, Paulo G.; Camargo, Mário E.; Mineo, José Roberto; Gazzinelli, Ricardo T.

2002-01-01

In the present study we developed an enzyme-linked immunosorbent assay (ELISA) to measure immunoglobulin M (IgM) specific for glycoinositolphospholipids (GIPL) derived from tachyzoite membrane (IgM-GIPL ELISA). The sensitivity and specificity of the assay were compared with those of commercially available Toxoplasma-specific IgM serological tests, namely, immunofluorescence assay (IFA) with fixed tachyzoites and capture ELISA employing tachyzoite extracts. Our results show that all patients with acute toxoplasmosis, as determined by clinical data and conventional serological tests, were also positive by the IgM-GIPL ELISA. Interestingly, many patients that were classified as indeterminate, who had IgG with high avidity but positive results in the IgM-specific IFA and capture ELISA, were negative by the IgM-GIPL ELISA. Finally, we tested the sera from patients with rheumatoid arthritis and various parasitic infections and found no evidence of false positives in the IgM-GIPL ELISA. PMID:11923364

On implicit abstract neutral nonlinear differential equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernández, Eduardo, E-mail: lalohm@ffclrp.usp.br; O’Regan, Donal, E-mail: donal.oregan@nuigalway.ie

2016-04-15

In this paper we continue our developments in Hernández and O’Regan (J Funct Anal 261:3457–3481, 2011) on the existence of solutions for abstract neutral differential equations. In particular we extend the results in Hernández and O’Regan (J Funct Anal 261:3457–3481, 2011) for the case of implicit nonlinear neutral equations and we focus on applications to partial “nonlinear” neutral differential equations. Some applications involving partial neutral differential equations are presented.

Survey parameters for detecting 21cm - Lyα emitter cross correlations with the Square Kilometre Array

NASA Astrophysics Data System (ADS)

Hutter, Anne; Trott, Cathryn M.; Dayal, Pratika

2018-06-01

Detections of the cross correlation signal between the 21cm signal during reionization and high-redshift Lyman Alpha emitters (LAEs) are subject to observational uncertainties which mainly include systematics associated with radio interferometers and LAE selection. These uncertainties can be reduced by increasing the survey volume and/or the survey luminosity limit, i.e. the faintest detectable Lyman Alpha (Lyα) luminosity. We use our model of high-redshift LAEs and the underlying reionization state to compute the uncertainties of the 21cm-LAE cross correlation function at z ≃ 6.6 for observations with SKA1-Low and LAE surveys with Δz = 0.1 for three different values of the average IGM ionization state (⟨χHI⟩≃ 0.1, 0.25, 0.5). At z ≃ 6.6, we find SILVERRUSH type surveys, with a field of view of 21 deg2 and survey luminosity limits of Lα ≥ 7.9 × 1042erg s-1, to be optimal to distinguish between an inter-galactic medium (IGM) that is 50%, 25% and 10% neutral, while surveys with smaller fields of view and lower survey luminosity limits, such as the 5 and 10 deg2 surveys with WFIRST, can only discriminate between a 50% and 10% neutral IGM.

Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site.

PubMed

Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S; Mkhize, Nonhlanhla N; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D; Labuschagne, Phillip; Louder, Mark K; Bailer, Robert T; Abdool Karim, Salim S; Mascola, John R; Williamson, Carolyn; Moore, Penny L; Kwong, Peter D; Morris, Lynn

2016-11-15

All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive

Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.

ABSTRACT All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report themore » isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. IMPORTANCEThe conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to

Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

PubMed Central

Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.; Mkhize, Nonhlanhla N.; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D.; Labuschagne, Phillip; Louder, Mark K.; Bailer, Robert T.; Abdool Karim, Salim S.; Mascola, John R.; Williamson, Carolyn; Moore, Penny L.

2016-01-01

ABSTRACT All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. IMPORTANCE The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site

Unreliability of three commercial Coxiella burnetii phase II IgM ELISA kits for the seroscreening of acute Q fever in human cases.

PubMed

Stephen, Selvaraj; Ambroise, Stanley; Pradeep, Jothimani; Gunasekaran, Dhandapany; Sangeetha, Balakrishnan; Sarangapani, Kengamuthu

2017-09-01

Seroprevalence of Q fever (QF) caused by Coxiella burnetii has been reported from different parts of India. Usually serological/molecular tests are employed for detection of infection. The present study was undertaken to verify the validity of three different QF phase II IgM ELISA kits for acute QF diagnosis by comparing with the gold standard indirect fluorescent antibody assay (IFA). Fifty eight serum samples collected from 42 patients (26 patients provided acute sample only and 16 both acute and convalescent samples) which were examined by all three commercial kits, were cross-checked with QF Phase II IgM IFA for confirmation. Eleven patients were positive for C. burnetii antibodies by IFA in acute and/or convalescent serum samples. Taking IFA as a reference, percentages of sensitivity, specificity, positive predictive value and negative predictive value for Virion-Serion/Vircell/NovaTec were 36.36, 61.29, 25.00, 73.08; 81.82, 35.48, 31.03, 84.62 and 100, 25.81, 32.35, 100 per cent, respectively. The three different ELISA kits exhibited poor agreement amongst them and unacceptable level of false positivity. IFA remains to be the only option for diagnosing acute QF. Discrepancy between the clinical findings and IFA/ELISA results needs confirmation by C. burnetii DNA detection in real-time polymerase chain reaction.

Unreliability of three commercial Coxiella burnetii phase II IgM ELISA kits for the seroscreening of acute Q fever in human cases

PubMed Central

Stephen, Selvaraj; Ambroise, Stanley; Pradeep, Jothimani; Gunasekaran, Dhandapany; Sangeetha, Balakrishnan; Sarangapani, Kengamuthu

2017-01-01

Background & objectives: Seroprevalence of Q fever (QF) caused by Coxiella burnetii has been reported from different parts of India. Usually serological/molecular tests are employed for detection of infection. The present study was undertaken to verify the validity of three different QF phase II IgM ELISA kits for acute QF diagnosis by comparing with the gold standard indirect fluorescent antibody assay (IFA). Methods: Fifty eight serum samples collected from 42 patients (26 patients provided acute sample only and 16 both acute and convalescent samples) which were examined by all three commercial kits, were cross-checked with QF Phase II IgM IFA for confirmation. Results: Eleven patients were positive for C. burnetii antibodies by IFA in acute and/or convalescent serum samples. Taking IFA as a reference, percentages of sensitivity, specificity, positive predictive value and negative predictive value for Virion-Serion/Vircell/NovaTec were 36.36, 61.29, 25.00, 73.08; 81.82, 35.48, 31.03, 84.62 and 100, 25.81, 32.35, 100 per cent, respectively. Interpretation & conclusions: The three different ELISA kits exhibited poor agreement amongst them and unacceptable level of false positivity. IFA remains to be the only option for diagnosing acute QF. Discrepancy between the clinical findings and IFA/ELISA results needs confirmation by C. burnetii DNA detection in real-time polymerase chain reaction. PMID:29355147

Priming Effects for Affective vs. Neutral Faces

ERIC Educational Resources Information Center

Burton, Leslie A.; Rabin, Laura; Wyatt, Gwinne; Frohlich, Jonathan; Vardy, Susan B.; Dimitri, Diana

2005-01-01

Affective and Neutral Tasks (faces with negative or neutral content, with different lighting and orientation) requiring reaction time judgments of poser identity were administered to 32 participants. Speed and accuracy were better for the Affective than Neutral Task, consistent with literature suggesting facilitation of performance by affective…

Shielding of a lipooligosaccharide IgM epitope allows evasion of neutrophil-mediated killing of an invasive strain of nontypeable Haemophilus influenzae.

PubMed

Langereis, Jeroen D; Weiser, Jeffrey N

2014-07-22

Nontypeable Haemophilus influenzae is a frequent cause of noninvasive mucosal inflammatory diseases but may also cause invasive diseases, such as sepsis and meningitis, especially in children and the elderly. Infection by nontypeable Haemophilus influenzae is characterized by recruitment of neutrophilic granulocytes. Despite the presence of a large number of neutrophils, infections with nontypeable Haemophilus influenzae are often not cleared effectively by the antimicrobial activity of these immune cells. Herein, we examined how nontypeable Haemophilus influenzae evades neutrophil-mediated killing. Transposon sequencing (Tn-seq) was used on an isolate resistant to neutrophil-mediated killing to identify genes required for its survival in the presence of human neutrophils and serum, which provided a source of complement and antibodies. Results show that nontypeable Haemophilus influenzae prevents complement-dependent neutrophil-mediated killing by expression of surface galactose-containing oligosaccharide structures. These outer-core structures block recognition of an inner-core lipooligosaccharide epitope containing glucose attached to heptose HepIII-β1,2-Glc by replacement with galactose attached to HepIII or through shielding HepIII-β1,2-Glc by phase-variable attachment of oligosaccharide chain extensions. When the HepIII-β1,2-Glc-containing epitope is expressed and exposed, nontypeable Haemophilus influenzae is opsonized by naturally acquired IgM generally present in human serum and subsequently phagocytosed and killed by human neutrophils. Clinical nontypeable Haemophilus influenzae isolates containing galactose attached to HepIII that are not recognized by this IgM are more often found to cause invasive infections. Importance: Neutrophils are white blood cells that specialize in killing pathogens and are recruited to sites of inflammation. However, despite the presence of large numbers of neutrophils in the middle ear cavity and lungs of patients with

46 CFR 111.05-15 - Neutral grounding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Neutral grounding. 111.05-15 Section 111.05-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL... propulsion, power, lighting, or distribution system having a neutral bus or conductor must have the neutral...

46 CFR 111.05-15 - Neutral grounding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Neutral grounding. 111.05-15 Section 111.05-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL... propulsion, power, lighting, or distribution system having a neutral bus or conductor must have the neutral...

46 CFR 111.05-15 - Neutral grounding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Neutral grounding. 111.05-15 Section 111.05-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL... propulsion, power, lighting, or distribution system having a neutral bus or conductor must have the neutral...

46 CFR 111.05-15 - Neutral grounding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Neutral grounding. 111.05-15 Section 111.05-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL... propulsion, power, lighting, or distribution system having a neutral bus or conductor must have the neutral...

46 CFR 111.05-15 - Neutral grounding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Neutral grounding. 111.05-15 Section 111.05-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL... propulsion, power, lighting, or distribution system having a neutral bus or conductor must have the neutral...

26Al Production in the Early Solar Nebula by Neutral High-Energy Plasma Winds

NASA Astrophysics Data System (ADS)

Spergel, M. S.

1995-09-01

In the light of recent observations, I believe that the sources for the presence of ^26Al within the solar nebula must be reconsidered [2,3]. Recent low observational estimates of the probability of encounters between mass-losing evolved stars and molecular clouds [4] for the production of ^26Al and the observed low production [5] of 26 Al from AGB (Asymptotic Giant Branch stars) along with the predicted low abundance of cosmic ray induced local production [6] in the early solar nebula all support continued investigation for additional sources of the solar nebula ^26Al presence. It is suggested based on the presences of new cross section data [7], that an important source of this ^26Al presence might be from enhanced interactions from the collisions of the local "T. Tauri" like plasma winds with the atomic and molecular Early Solar Nebula (ESN). Interactions like ^26Mg (p,n) ^26Al in this "neutral" electrical setting may provide the needed selective production. The ESN provides an environment where plasma winds can lead to such nucleosynthesis. Stellar winds of 300-700 km/s (about 3x10^7 K) are seen to T. Tauri like stars, presumed precursor to solar like stars, and also within the Solar heliosphere [8.9]. These winds provide the source of Solar High Energy Particles which can interact with such in situ targets such as ^26Mg to produce the ^26Al. The presence of the atomic and molecular environments, will enhance [10] nucleosynthesis over that seen in scattering of protons off bare nuclei. Such enhancement has been recently observed in low energy scattering on electrically shield targets [7]. There it was also suggested that in stellar convective zones, electron clouds of the plasma shield may also shield bare target nuclei. Measured values of low energy proton scattered on atomic and molecular targets indicated [7] that fusion cross sections are enlarged and elastic cross sections are reduced, therefore simple extrapolation of accelerator data can lead to an

A Statistical Model of the Magnetotail Neutral Sheet

NASA Astrophysics Data System (ADS)

Xiao, Sudong; Zhang, Tielong; Baumjohann, Wolfgang; Nakamura, Rumi; Ge, Yasong; Du, Aimin; Wang, Guoqiang; Lu, Quanming

2015-04-01

The neutral sheet of the magnetotail is characterized by weak magnetic field, strong cross tail current, and a reversal of the magnetic field direction across it. The dynamics of the earth's magnetosphere is greatly influenced by physical processes that occur near the neutral sheet. However, the exact position of the neutral sheet is variable in time. It is therefore essential to have a reliable estimate of the average position of the neutral sheet. Magnetic field data from ten years of Cluster, nineteen years of Geotail, four years of TC 1, and seven years of THEMIS observations have been incorporated to obtain a model of the magnetotail neutral sheet. All data in aberrated GSM (Geocentric Solar Magnetospheric) coordinate system are normalized to the same solar wind pressure condition. The shape and position of the neutral sheet, illustrated directly by the separator of positive and negative Bx on the YZ cross sections, are fitted with a displaced ellipse model. It is consistent with previous studies that the neutral sheet becomes curvier in the YZ cross section when the dipole tilt increases, yet our model shows the curviest neutral sheet compared with previous models. The new model reveals a hinging distance very close to 10 RE at a reference solar wind dynamic pressure of 2 nPa. We find that the earth dipole tilt angle not only affects the neutral sheet configuration in the YZ cross section but also in the XZ cross section. The neutral sheet becomes more tilting in the XZ cross section when the dipole tilt increases. The effect of an interplanetary magnetic field (IMF) penetration is studied, and an IMF By-related twisting of about 3° is found. Anticlockwise twisting of the neutral sheet is observed, looking along the downtail direction, for a positive IMF By, and clockwise twisting of the neutral sheet for a negative IMF By.

Modeling thermospheric neutral density

NASA Astrophysics Data System (ADS)

Qian, Liying

Satellite drag prediction requires determination of thermospheric neutral density. The NCAR Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIEGCM) and the global-mean Thermosphere-Ionosphere-Mesosphere-Electrodynamics General Circulation Model (TIMEGCM) were used to quantify thermospheric neutral density and its variations, focusing on annual/semiannual variation, the effect of using measured solar irradiance on model calculations of solar-cycle variation, and global change in the thermosphere. Satellite drag data and the MSIS00 empirical model were utilized to compare to the TIEGCM simulations. The TIEGCM simulations indicated that eddy diffusion and its annual/semiannual variation is a mechanism for annual/semiannual density variation in the thermosphere. It was found that eddy diffusion near the turbopause can effectively influence thermospheric neutral density. Eddy diffusion, together with annual insolation variation and large-scale circulation, generated global annual/semiannual density variation observed by satellite drag. Using measured solar irradiance as solar input for the TIEGCM improved the solar-cycle dependency of the density calculation shown in F10.7 -based thermospheric empirical models. It has been found that the empirical models overestimate density at low solar activity. The TIEGCM simulations did not show such solar-cycle dependency. Using historic measurements of CO2 and F 10.7, simulations of the global-mean TIMEGCM showed that thermospheric neutral density at 400 km had an average long-term decrease of 1.7% per decade from 1970 to 2000. A forecast of density decrease for solar cycle 24 suggested that thermospheric density will decrease at 400 km from present to the end of solar cycle 24 at a rate of 2.7% per decade. Reduction in thermospheric density causes less atmospheric drag on earth-orbiting space objects. The implication of this long-term decrease of thermospheric neutral density is that it will increase the

This person is saying bad things about you: The influence of physically and socially threatening context information on the processing of inherently neutral faces.

PubMed

Klein, Fabian; Iffland, Benjamin; Schindler, Sebastian; Wabnitz, Pascal; Neuner, Frank

2015-12-01

Recent studies have shown that the perceptual processing of human faces is affected by context information, such as previous experiences and information about the person represented by the face. The present study investigated the impact of verbally presented information about the person that varied with respect to affect (neutral, physically threatening, socially threatening) and reference (self-referred, other-referred) on the processing of faces with an inherently neutral expression. Stimuli were presented in a randomized presentation paradigm. Event-related potential (ERP) analysis demonstrated a modulation of the evoked potentials by reference at the EPN (early posterior negativity) and LPP (late positive potential) stage and an enhancing effect of affective valence on the LPP (700-1000 ms) with socially threatening context information leading to the most pronounced LPP amplitudes. We also found an interaction between reference and valence with self-related neutral context information leading to more pronounced LPP than other related neutral context information. Our results indicate an impact of self-reference on early, presumably automatic processing stages and also a strong impact of valence on later stages. Using a randomized presentation paradigm, this study confirms that context information affects the visual processing of faces, ruling out possible confounding factors such as facial configuration or conditional learning effects.

The effects of gender and self-insight on early semantic processing.

PubMed

Xu, Xu; Kang, Chunyan; Guo, Taomei

2014-01-01

This event-related potential (ERP) study explored individual differences associated with gender and level of self-insight in early semantic processing. Forty-eight Chinese native speakers completed a semantic judgment task with three different categories of words: abstract neutral words (e.g., logic, effect), concrete neutral words (e.g., teapot, table), and emotion words (e.g., despair, guilt). They then assessed their levels of self-insight. Results showed that women engaged in greater processing than did men. Gender differences also manifested in the relationship between level of self-insight and word processing. For women, level of self-insight was associated with level of semantic activation for emotion words and abstract neutral words, but not for concrete neutral words. For men, level of self-insight was related to processing speed, particularly in response to abstract and concrete neutral words. These findings provide electrophysiological evidence for the effects of gender and self-insight on semantic processing and highlight the need to take into consideration subject variables in related research.

West Nile virus--neutralizing antibodies in humans in Greece.

PubMed

Papa, Anna; Perperidou, Parthena; Tzouli, Anisa; Castilletti, Concetta

2010-10-01

Serum samples collected during March-May 2007 from 392 residents of Imathia prefecture, Northern Greece, were tested by indirect immunofluorescence assay and enzyme-linked immunosorbent assay for IgG antibodies against West Nile virus (WNV). Microneutralization assay was applied in six positive samples. Four (4/392, 1.02%) were found positive for WNV-neutralizing antibodies. None of the positive individuals had a history of travel in endemic area or flavivirus vaccination, suggesting that WNV, or an antigenically related flavivirus, circulates in an endemic sylvatic cycle, at least locally, in rural areas in Greece. Human, animal, and vector surveillance systems have to be implemented to provide an early detection of WNV activity in Greece.

The ratio of neutral hydrogen to neutral helium in the local interstellar medium

NASA Astrophysics Data System (ADS)

Green, James Carswell

The results are described from a sounding rocket borne EUV spectrometer that was designed and built. This instrument operated from 400 to 1150A with a spectral resolution of approx. 15A. The instrument effective area was about 1 sq cm. The instrument was successfully launched, and observed the nearby DA white dwarf G191-B2B. From this observation, it was determined that the stellar effective temperature is 61,000 + or -4000 to 6000K, and the ratio of helium to hydrogen in the stellar photosphere is 1.0 + or -0.68 to 2.2 x 10-4. Additionally, the neutral column densities of helium and hydrogen were measured to the star. The neutral helium column density was determined from the first observation of the interstellar absorption edge at 504A. The ratio of neutral helium to neutral hydrogen constrains the mean ionization of the warm gas along the line of sight to G191-B2B. The fractional ionization of hydrogen (H II/H) is approx. less than 20 percent, unless significant helium ionization is present as well. The scenario where the fractional ionization of hydrogen is high (H II/H) approx. less than 40 percent and the helium is neutral is ruled out with 99 percent certainty. This result is consistent with some recent theoretical calculations. Using these results, a self-consistent model of the local interstellar medium along the line of sight to G191-B2B is developed. In addition, an unexpected emission feature at 584A was detected in this observation with a high level of significance. Possible sources of this emission are examined, including the companion K dwarf G191-B2A, and an emission nebula near or around G191-B2B.

Impaired glucose metabolism in subjects with the Williams-Beuren syndrome: A five-year follow-up cohort study

PubMed Central

Lunati, Maria Elena; Bedeschi, Maria Francesca; Resi, Veronica; Grancini, Valeria; Palmieri, Eva; Salera, Simona; Lalatta, Faustina; Pugliese, Giuseppe

2017-01-01

Objective The Williams-Beuren syndrome (WS) is associated with impaired glucose metabolism (IGM) early in adulthood. However, the pathophysiology of IGM remains poorly defined, due to the lack of longitudinal studies investigating the contribution of β-cell dysfunction and impaired insulin sensitivity. This study aimed at assessing incidence of IGM and the underlying mechanisms in WS adults. Methods This observational, longitudinal (5-year), cohort study enrolled thirty-one consecutive WS subjects attending a tertiary referral center. An oral glucose tolerance test (OGTT) was performed yearly and used to classify patients as normal or IGM, including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and diabetes mellitus (DM), and to calculate surrogate measures of insulin secretion and/or sensitivity. Results IGM patients were 18 (58.1%, three DM) at baseline and 19 (61.3%, five DM) at end-of-follow-up. However, 13 individuals changed category of glucose homeostasis in both directions during follow-up (8 progressors, 5 regressors) and 18 did not (8 non-progressors, 10 non-regressors). New cases of IGM and DM were 11.1 and 2.53 per 100 persons-year, respectively, and were treated non-pharmacologically. In the whole cohort and, to a higher extent, in progressors, indices of early-phase insulin secretion and insulin sensitivity decreased significantly from baseline to end-of-follow-up, with concurrent reduction of the oral disposition index and insulin secretion-sensitivity index-2 (ISSI-2), compensating insulin secretion for the level of insulin resistance. No baseline measure independently predicted progression, which correlated with change from baseline in ISSI-2. Compared with patients with normal glucose homeostasis, IGT subjects had impaired insulin sensitivity, whereas insulin secretion was reduced only in those with IFG+IGT or DM. Conclusions IGM incidence is high in young adults with WS, suggesting the need of early screening and timed

Optimization of a Plaque Neutralization Test (PNT) to identify the exposure history of Pacific Herring to viral hemorrhagic septicemia virus (VHSV)

USGS Publications Warehouse

Hart, Lucas; Mackenzie, Ashley; Purcell, Maureen; Thompson, Rachel L.; Hershberger, Paul

2017-01-01

Methods for a plaque neutralization test (PNT) were optimized for the detection and quantification of viral hemorrhagic septicemia virus (VHSV) neutralizing activity in the plasma of Pacific Herring Clupea pallasii. The PNT was complement dependent, as neutralizing activity was attenuated by heat inactivation; further, neutralizing activity was mostly restored by the addition of exogenous complement from specific-pathogen-free Pacific Herring. Optimal methods included the overnight incubation of VHSV aliquots in serial dilutions (starting at 1:16) of whole test plasma containing endogenous complement. The resulting viral titers were then enumerated using a viral plaque assay in 96-well microplates. Serum neutralizing activity was virus-specific as plasma from viral hemorrhagic septicemia (VHS) survivors demonstrated only negligible reactivity to infectious hematopoietic necrosis virus, a closely related rhabdovirus. Among Pacific Herring that survived VHSV exposure, neutralizing activity was detected in the plasma as early as 37 d postexposure and peaked at approximately 64 d postexposure. The onset of neutralizing activity was slightly delayed in fish reared at 7.4°C relative to those in warmer temperatures (9.9°C and 13.1°C); however, neutralizing activity persisted for at least 345 d postexposure in all temperature treatments. It is anticipated that this novel ability to assess VHSV neutralizing activity in Pacific Herring will enable retrospective comparisons between prior VHS infections and year-class recruitment failures. Additionally, the optimized PNT could be employed as a forecasting tool capable of identifying the potential for future VHS epizootics in wild Pacific Herring populations.

Ideological reactivity: Political conservatism and brain responsivity to emotional and neutral stimuli.

PubMed

Tritt, Shona M; Peterson, Jordan B; Page-Gould, Elizabeth; Inzlicht, Michael

2016-12-01

Conservatives are often thought to have a negativity bias-responding more intensely to negative than positive information. Yet, recent research has found that greater endorsement of conservative beliefs follows from both positive and negative emotion inductions. This suggests that the role of affect in political thought may not be restricted to negative valence, and more attention should be given to how conservatives and liberals respond to a wider range of stimulation. In this vein, we examined neural responses to a full range of affective stimuli, allowing us to examine how self-reported ideology moderated these responses. Specifically, we explored the relationship between political orientation and 2 event-related potentials (1 late and 1 early) previously shown to covary with the subjective motivational salience of stimuli-in response to photographs with standardized ratings of arousal and valence. At late time points, conservatives exhibited sustained heightened reactivity, compared with liberals, specifically in response to relatively unarousing and neutral stimuli. At early time points, conservatives exhibited somewhat enhanced neural activity in response to all stimulus types compared with liberals. These results may suggest that conservatives experience a wide variety of stimuli in their environment with increased motivational salience, including positive, neutral, and low-arousal stimuli. No effects of valence were found in this investigation. Such findings have implications for the development and refinement of psychological conceptions of political orientation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Autonomous mine detection system (AMDS) neutralization payload module

NASA Astrophysics Data System (ADS)

Majerus, M.; Vanaman, R.; Wright, N.

2010-04-01

The Autonomous Mine Detection System (AMDS) program is developing a landmine and explosive hazards standoff detection, marking, and neutralization system for dismounted soldiers. The AMDS Capabilities Development Document (CDD) has identified the requirement to deploy three payload modules for small robotic platforms: mine detection and marking, explosives detection and marking, and neutralization. This paper addresses the neutralization payload module. There are a number of challenges that must be overcome for the neutralization payload module to be successfully integrated into AMDS. The neutralizer must meet stringent size, weight, and power (SWaP) requirements to be compatible with a small robot. The neutralizer must be effective against a broad threat, to include metal and plastic-cased Anti-Personnel (AP) and Anti-Tank (AT) landmines, explosive devices, and Unexploded Explosive Ordnance (UXO.) It must adapt to a variety of threat concealments, overburdens, and emplacement methods, to include soil, gravel, asphalt, and concrete. A unique neutralization technology is being investigated for adaptation to the AMDS Neutralization Module. This paper will describe review this technology and how the other two payload modules influence its design for minimizing SWaP. Recent modeling and experimental efforts will be included.

Implementation of a plasma-neutral model in NIMROD

NASA Astrophysics Data System (ADS)

Taheri, S.; Shumlak, U.; King, J. R.

2016-10-01

Interaction between plasma fluid and neutral species is of great importance in the edge region of magnetically confined fusion plasmas. The presence of neutrals can have beneficial effects such as fueling burning plasmas and quenching the disruptions in tokamaks, as well as deleterious effects like depositing high energy particles on the vessel wall. The behavior of edge plasmas in magnetically confined systems has been investigated using computational approaches that utilize the fluid description for the plasma and Monte Carlo transport for neutrals. In this research a reacting plasma-neutral model is implemented in NIMROD to study the interaction between plasma and neutral fluids. This model, developed by E. T. Meier and U. Shumlak, combines a single-fluid magnetohydrodynamic (MHD) plasma model with a gas dynamic neutral fluid model which accounts for electron-impact ionization, radiative recombination, and resonant charge exchange. Incorporating this model into NIMROD allows the study of the interaction between neutrals and plasma in a variety of plasma science problems. An accelerated plasma moving through a neutral gas background in a coaxial electrode configuration is modeled, and the results are compared with previous calculations from the HiFi code.

Towards Universal Screening for Toxoplasmosis: Rapid, Cost-effective and Simultaneous Detection of Toxoplasma Anti-IgG, IgM and IgA Antibodies Using Very Small Serum Volumes

EPA Pesticide Factsheets

No dataset associated with this publication.This dataset is associated with the following publication:Augustine, S. Towards Universal Screening for Toxoplasmosis: Rapid, Cost-effective and Simultaneous Detection of Toxoplasma Anti-IgG, IgM and IgA Antibodies Using Very Small Serum Volumes. JOURNAL OF CLINICAL MICROBIOLOGY. American Society for Microbiology, Washington, DC, USA, 56(7): 1-2, (2016).

Neutral Gas Properties of Extremely Isolated Early-type Galaxies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashley, Trisha; Marcum, Pamela M.; Fanelli, Michael N., E-mail: trisha.l.ashley@nasa.gov, E-mail: pamela.m.marcum@nasa.gov, E-mail: michael.n.fanelli@nasa.gov

We present the results of single-dish atomic hydrogen (H i) observations of six highly isolated early-type galaxies. These objects are a representative subset of galaxies previously studied at optical wavelengths and selected to be separated by at least 2.5 Mpc from companions brighter than M{sub V}  = −16.5 mag. Each galaxy was observed with a single pointing using the NRAO Green Bank Telescope L -band receiver. Five of these systems were strongly detected in H i. These five galaxies exhibit H i profiles with a range of properties: single Gaussian-like peaks, separate double peaks, and double horn-like profiles. The four bluestmore » galaxies ( B − V < 0.54) all contain significant gas with H i masses ranging from 1.1 × 10{sup 8} to 1.4 × 10{sup 9}.« less

Ion-Neutral Coupling in Solar Prominence

NASA Technical Reports Server (NTRS)

Gilbert, H.; DeVore, C. R.; Karpen, J.; Kucera, T.; Antiochos, S.; Kawashima, R.

2011-01-01

Coupling between ions and neutrals in magnetized plasmas is fundamentally important to many aspects of heliophysics, including our ionosphere, the solar chromosphere, the solar wind interaction with planetary atmospheres, and the interface between the heliosphere and the interstellar medium. Ion-neutral coupling also plays a major role in the physics of solar prominences. By combining theory, modeling, and observations we are working toward a better understanding of the structure and dynamics of partially ionized prominence plasma. Two key questions are addressed in the present work: 1) what physical mechanism(s) sets the cross-field scale of prominence threads? 2) Are ion-neutral interactions responsible for the vertical flows and structure in prominences? We present initial results from a study investigating what role ion-neutral interactions play in prominence dynamics and structure. This research was supported by NASA.

Neutral and Non-Neutral Evolution of Duplicated Genes with Gene Conversion

PubMed Central

Fawcett, Jeffrey A.; Innan, Hideki

2011-01-01

Gene conversion is one of the major mutational mechanisms involved in the DNA sequence evolution of duplicated genes. It contributes to create unique patters of DNA polymorphism within species and divergence between species. A typical pattern is so-called concerted evolution, in which the divergence between duplicates is maintained low for a long time because of frequent exchanges of DNA fragments. In addition, gene conversion affects the DNA evolution of duplicates in various ways especially when selection operates. Here, we review theoretical models to understand the evolution of duplicates in both neutral and non-neutral cases. We also explain how these theories contribute to interpreting real polymorphism and divergence data by using some intriguing examples. PMID:24710144

LLNL - WRF-LES - Neutral - TTU

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosovic, Branko

This dataset includes large-eddy simulation (LES) output from a neutrally stratified atmospheric boundary layer (ABL) simulation of observations at the SWIFT tower near Lubbock, Texas on Aug. 17, 2012. The dataset was used to assess LES models for simulation of canonical neutral ABL. The dataset can be used for comparison with other LES and computational fluid dynamics model outputs.

ANL - WRF-LES - Neutral - TTU

DOE Data Explorer

Kosovic, Branko

2018-06-20

This dataset includes large-eddy simulation (LES) output from a neutrally stratified atmospheric boundary layer (ABL) simulation of observations at the SWIFT tower near Lubbock, Texas on Aug. 17, 2012. The dataset was used to assess LES models for simulation of canonical neutral ABL. The dataset can be used for comparison with other LES and computational fluid dynamics model outputs.

LANL - WRF-LES - Neutral - TTU

DOE Data Explorer

Kosovic, Branko

2018-06-20

This dataset includes large-eddy simulation (LES) output from a neutrally stratified atmospheric boundary layer (ABL) simulation of observations at the SWIFT tower near Lubbock, Texas on Aug. 17, 2012. The dataset was used to assess LES models for simulation of canonical neutral ABL. The dataset can be used for comparison with other LES and computational fluid dynamics model outputs.

Enzyme-linked immunosorbent assay for Potomac horse fever disease.

PubMed

Pretzman, C I; Rikihisa, Y; Ralph, D; Gordon, J C; Bech-Nielsen, S

1987-01-01

An enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) and IgM in natural and experimental infections of equids with Ehrlichia risticii was developed. Ehrlichial organisms purified from an infected mouse macrophage cell line were used as the antigen. IgM was separated from serum IgG by the expedient of spun-column chromatography, allowing the use of an indirect ELISA for quantitation of both IgG and IgM in the test sera. Among 16 paired sera from horses exhibiting clinical signs of Potomac horse fever, 8 were positive by the indirect fluorescent-antibody test (IFA), 11 were positive by the IgG ELISA, and 8 were positive by the IgM ELISA. All IFA-positive specimens were positive by the IgG ELISA, which appeared to be more sensitive than the IFA. In all cases, the IgG ELISA alone would have sufficed for diagnosis when acute- and convalescent-phase sera were available. When 26 single acute- or convalescent-phase serum samples were tested, the IFA detected 8, the IgG ELISA detected 10, and the IgM ELISA detected 6 positive serum specimens. The kinetics of IgG and IgM responses as determined by ELISA in two experimentally infected ponies which survived infection and challenges revealed that specific IgM was short-lived, falling to undetectable levels by day 60 postinoculation, whereas specific IgG persisted for more than 1 year. IgM and IgG were detected as early as days 1 and 10, respectively, postinoculation. The results suggest that the ELISA is more sensitive than the IFA and that the IgM ELISA may provide a means for early diagnosis of Potomac horse fever at or before the onset of clinical signs.

Optimization of incubation conditions of Plasmodium falciparum antibody multiplex assays to measure IgG, IgG1-4, IgM and IgE using standard and customized reference pools for sero-epidemiological and vaccine studies.

PubMed

Ubillos, Itziar; Jiménez, Alfons; Vidal, Marta; Bowyer, Paul W; Gaur, Deepak; Dutta, Sheetij; Gamain, Benoit; Coppel, Ross; Chauhan, Virander; Lanar, David; Chitnis, Chetan; Angov, Evelina; Beeson, James; Cavanagh, David; Campo, Joseph J; Aguilar, Ruth; Dobaño, Carlota

2018-06-01

The quantitative suspension array technology (qSAT) is a useful platform for malaria immune marker discovery. However, a major challenge for large sero-epidemiological and malaria vaccine studies is the comparability across laboratories, which requires the access to standardized control reagents for assay optimization, to monitor performance and improve reproducibility. Here, the Plasmodium falciparum antibody reactivities of the newly available WHO reference reagent for anti-malaria human plasma (10/198) and of additional customized positive controls were examined with seven in-house qSAT multiplex assays measuring IgG, IgG 1-4 subclasses, IgM and IgE against a panel of 40 antigens. The different positive controls were tested at different incubation times and temperatures (4 °C overnight, 37 °C 2 h, room temperature 1 h) to select the optimal conditions. Overall, the WHO reference reagent had low IgG2, IgG4, IgM and IgE, and also low anti-CSP antibody levels, thus this reagent was enriched with plasmas from RTS,S-vaccinated volunteers to be used as standard for CSP-based vaccine studies. For the IgM assay, another customized plasma pool prepared with samples from malaria primo-infected adults with adequate IgM levels proved to be more adequate as a positive control. The range and magnitude of IgG and IgG 1-4 responses were highest when the WHO reference reagent was incubated with antigen-coupled beads at 4 °C overnight. IgG levels measured in the negative control did not vary between incubations at 37 °C 2 h and 4 °C overnight, indicating no difference in unspecific binding. With this study, the immunogenicity profile of the WHO reference reagent, including seven immunoglobulin isotypes and subclasses, and more P. falciparum antigens, also those included in the leading RTS,S malaria vaccine, was better characterized. Overall, incubation of samples at 4 °C overnight rendered the best performance for antibody measurements against the antigens tested

Edge momentum transport by neutrals: an interpretive numerical framework

NASA Astrophysics Data System (ADS)

Omotani, J. T.; Newton, S. L.; Pusztai, I.; Viezzer, E.; Fülöp, T.; The ASDEX Upgrade Team

2017-06-01

Due to their high cross-field mobility, neutrals can contribute to momentum transport even at the low relative densities found inside the separatrix and they can generate intrinsic rotation. We use a charge-exchange dominated solution to the neutral kinetic equation, coupled to neoclassical ions, to evaluate the momentum transport due to neutrals. Numerical solutions to the drift-kinetic equation allow us to cover the full range of collisionality, including the intermediate levels typical of the tokamak edge. In the edge there are several processes likely to contribute to momentum transport in addition to neutrals. Therefore, we present here an interpretive framework that can evaluate the momentum transport through neutrals based on radial plasma profiles. We demonstrate its application by analysing the neutral angular momentum flux for an L-mode discharge in the ASDEX Upgrade tokamak. The magnitudes of the angular momentum fluxes we find here due to neutrals of 0.6-2 \\text{N} \\text{m} are comparable to the net torque on the plasma from neutral beam injection, indicating the importance of neutrals for rotation in the edge.

Evaluation of a commercial IgE ELISA in comparison with IgA and IgM ELISAs, IgG avidity assay and complement fixation for the diagnosis of acute toxoplasmosis.

PubMed

Kodym, P; Machala, L; Rohácová, H; Sirocká, B; Malý, M

2007-01-01

A panel of sera from patients with known case histories representative of acute toxoplasmosis (primarily lymphadenopathy, n = 106), latent toxoplasmosis (asymptomatic, n = 368) and negative samples (n = 54) was used to evaluate the capacity of five serological tests to differentiate among patients with acute or latent toxoplasmosis and non-infected individuals. Positive IgA, IgE and IgM ELISA results and low IgG avidity and complement fixation test (CFT) titres of >or=256 were considered to be indicative of acute toxoplasmosis. The most sensitive methods were IgM ELISA (98.1%) and CFT (97.1%), albeit with low specificity (65.0% and 64.5%, respectively) and positive predictive values (43.3% and 42.7%, respectively). IgG avidity assay and IgE ELISA had the highest specificity (97.7% and 91.7%, respectively) and the highest positive predictive values (89.4% and 75.6%, respectively). The best association between serological results and clinical findings was obtained with IgE ELISA (86%, as expressed via Youden's index). In a subset of 259 samples categorised by the period between the onset of clinical symptoms and sampling, >50% of patients had enlarged lymph nodes for <4 months, despite a broad range of differences. However, IgM remained positive for 12-18 months, IgA for 6-9 months and IgE for 4-6 months. IgG avidity remained low for a maximum of 4 months, after which avidity increased despite the persistence of enlarged lymph nodes and a positive IgE assay. Detection of IgE appears to be a highly specific test for confirming the acute nature of Toxoplasma infections that have been detected by other sensitive methods.

A Ly{alpha} GALAXY AT REDSHIFT z = 6.944 IN THE COSMOS FIELD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rhoads, James E.; Hibon, Pascale; Malhotra, Sangeeta

2012-06-20

Ly{alpha} emitting galaxies can be used to study cosmological reionization, because a neutral intergalactic medium (IGM) scatters Ly{alpha} photons into diffuse halos whose surface brightness falls below typical survey detection limits. Here, we present the Ly{alpha} emitting galaxy LAE J095950.99+021219.1, identified at redshift z = 6.944 in the COSMOS field using narrowband imaging and follow-up spectroscopy with the IMACS instrument on the Magellan I Baade telescope. With a single object spectroscopically confirmed so far, our survey remains consistent with a wide range of IGM neutral fraction at z Almost-Equal-To 7, but further observations are planned and will help clarify themore » situation. Meantime, the object we present here is only the third Ly{alpha}-selected galaxy to be spectroscopically confirmed at z {approx}> 7, and is {approx}2-3 times fainter than the previously confirmed z Almost-Equal-To 7 Ly{alpha} galaxies.« less

Characterization of specific anti-Candida IgM, IgA and IgE: diagnostic value in deep-seated infections.

PubMed

Aubert, D; Puygauthier-Toubas, D; Leon, P; Pignon, B; Foudrinier, F; Marnef, F; Boulant, J; Pinon, J M

1996-01-01

The proposed serological diagnosis of systemic Candida infections is based on a microplate immunocapture technique detecting IgM, IgA and IgE anti-Candida antibodies. Activity is revealed with a suspension of human erythrocytes sensitized with somatic antigen of Candida albicans, and is quantified on an automated plate reader. The sera were obtained from patients with deep-seated (n = 56) and superficial (n = 193) candidosis. We compared this immunological method with a combination of indirect immunofluorescence and co-immunoelectrodiffusion. The immunocapture method was more sensitive (80.4% vs. 48.2% with indirect immunofluorescence and 58.9% with co-immunoelectrodiffusion), and often provided the diagnosis at an earlier stage, with clear therapeutic advantages. The IgA isotype was a particularly valuable marker of deep-seated Candida infections.

An ER protein functionally couples neutral lipid metabolism on lipid droplets to membrane lipid synthesis in the ER.

PubMed

Markgraf, Daniel F; Klemm, Robin W; Junker, Mirco; Hannibal-Bach, Hans K; Ejsing, Christer S; Rapoport, Tom A

2014-01-16

Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation

PubMed Central

2012-01-01

Background Alkaline phosphatase (AP) is a ubiquitously expressed enzyme which can neutralize endotoxin as well as adenosine triphosphate (ATP), an endogenous danger signal released during brain injury. In this study we assessed a potential therapeutic role for AP in inhibiting neuroinflammation using three complementary approaches. Methods Mice were immunized to induce experimental autoimmune encephalomyelitis (EAE) and treated with AP for seven days during different phases of disease. In addition, serological assays to determine AP activity, endotoxin levels and endotoxin-reactive antibodies were performed in a cohort of multiple sclerosis (MS) patients and controls. Finally, the expression of AP and related enzymes CD39 and CD73 was investigated in brain tissue from MS patients and control subjects. Results AP administration during the priming phase, but not during later stages, of EAE significantly reduced neurological signs. This was accompanied by reduced proliferation of splenocytes to the immunogen, myelin oligodendrocyte glycoprotein peptide. In MS patients, AP activity and isoenzyme distribution were similar to controls. Although endotoxin-reactive IgM was reduced in primary-progressive MS patients, plasma endotoxin levels were not different between groups. Finally, unlike AP and CD73, CD39 was highly upregulated on microglia in white matter lesions of patients with MS. Conclusions Our findings demonstrate that: 1) pre-symptomatic AP treatment reduces neurological signs of EAE; 2) MS patients do not have altered circulating levels of AP or endotoxin; and 3) the expression of the AP-like enzyme CD39 is increased on microglia in white matter lesions of MS patients. PMID:23231745

Association of X-ray arches with chromospheric neutral lines

NASA Technical Reports Server (NTRS)

Mcintosh, P. S.; Krieger, A. S.; Nolte, J. T.; Vaiana, G.

1976-01-01

Daily maps of magnetic neutral lines derived from H-alpha observations have been superimposed on solar X-ray images for the period from June 15 to 30, 1973. Nearly all X-ray-emitting structures consist of systems of arches covering chromospheric neutral lines. Areas of low emissivity, coronal holes, appear as the areas between arcades of arches. The presence of a coronal hole, therefore, is determined by the spacing between neutral lines and the scale of the arches over those neutral lines. X-ray emissivity on the solar disk extends from neutral lines in proportion to the vertical and horizontal scale of the arches over those neutral lines. Increasing scale of arches corresponds with increasing age of magnetic fields associated with the neutral line. All X-ray filament cavities coincided with neutral lines, but filaments appeared under cavities for only part of their length and for only a fraction of the disk passage.

Neutral depletion and the helicon density limit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magee, R. M.; Galante, M. E.; Carr, J. Jr.

2013-12-15

It is straightforward to create fully ionized plasmas with modest rf power in a helicon. It is difficult, however, to create plasmas with density >10{sup 20} m{sup −3}, because neutral depletion leads to a lack of fuel. In order to address this density limit, we present fast (1 MHz), time-resolved measurements of the neutral density at and downstream from the rf antenna in krypton helicon plasmas. At the start of the discharge, the neutral density underneath the antenna is reduced to 1% of its initial value in 15 μs. The ionization rate inferred from these data implies that the electronmore » temperature near the antenna is much higher than the electron temperature measured downstream. Neutral density measurements made downstream from the antenna show much slower depletion, requiring 14 ms to decrease by a factor of 1/e. Furthermore, the downstream depletion appears to be due to neutral pumping rather than ionization.« less

Infection with non-lethal West Nile virus Eg101 strain induces immunity that protects mice against the lethal West Nile virus NY99 strain.

PubMed

Kumar, Mukesh; O'Connell, Maile; Namekar, Madhuri; Nerurkar, Vivek R

2014-06-06

Herein we demonstrate that infection of mice with West Nile virus (WNV) Eg101 provides protective immunity against lethal challenge with WNV NY99. Our data demonstrated that WNV Eg101 is largely non-virulent in adult mice when compared to WNV NY99. By day 6 after infection, WNV-specific IgM and IgG antibodies, and neutralizing antibodies were detected in the serum of all WNV Eg101 infected mice. Plaque reduction neutralization test data demonstrated that serum from WNV Eg101 infected mice neutralized WNV Eg101 and WNV NY99 strains with similar efficiency. Three weeks after infection, WNV Eg101 immunized mice were challenged subcutaneously or intracranially with lethal dose of WNV NY99 and observed for additional three weeks. All the challenged mice were protected against disease and no morbidity and mortality was observed in any mice. In conclusion, our data for the first time demonstrate that infection of mice with WNV Eg101 induced high titers of WNV specific IgM and IgG antibodies, and cross-reactive neutralizing antibodies, and the resulting immunity protected all immunized animals from both subcutaneous and intracranial challenge with WNV NY99. These observations suggest that WNV Eg101 may be a suitable strain for the development of a vaccine in humans against virulent strains of WNV.

Fiscal Neutrality and Local Choice in Public Education.

ERIC Educational Resources Information Center

Weber, William L.

1991-01-01

Extends Feldstein's notion of wealth neutrality to embrace fiscal neutrality, using a representative consumer context. Employs an "ideal" demand system to model school district expenditures in a general equilibrium framework. Rejects constant price and income elasticity demand models. Supports the fiscally neutral elasticity model…

The Relationship between Neutralization Techniques and Induced Abortion

PubMed Central

Kalateh Sadati, Ahmad; Tabei, Seyed Ziaaddin; Salehzadeh, Hamzeh; Rahnavard, Farnaz; Namavar Jahromi, Bahia; Hemmati, Soroor

2014-01-01

Background: Induced abortion is not only a serious threat for women’s health, but also a controversial topic for its ethical and moral problems. We aimed to evaluate the relationship between neutralization techniques and attempting to commit abortion in married women with unintended pregnancy. Methods: After in-depth interviews with some women who had attempted abortion, neutralization themes were gathered. Next, to analyze the data quantitatively, a questionnaire was created including demographic and psychosocial variables specifically related to neutralization. The participants were divided into two groups (abortion and control) of unintended pregnancy and were then compared. Results: Analysis of psychosocial variables revealed a significant difference in the two groups at neutralization, showing that neutralization in the control group (56.97±10.24) was higher than that in the abortion group (44.19±12.44). To evaluate the findings more accurately, we examined the causal factors behind the behaviors of the abortion group. Binary logistic regression showed that among psychosocial factors, neutralization significantly affected abortion (95% CI=1.07-1.35). Conclusion: Despite the network of many factors affecting induced abortion, neutralization plays an important role in reinforcing the tendency to attempt abortion. Furthermore, the decline of religious beliefs, as a result of the secular context of the modern world, seems to have an important role in neutralizing induced abortion. PMID:25349851

Optimal combinations of broadly neutralizing antibodies for prevention and treatments of HIV-1 clade C infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn

In this study, the identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and themore » gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP). By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.« less

Optimal combinations of broadly neutralizing antibodies for prevention and treatments of HIV-1 clade C infection

DOE PAGES

Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn; ...

2016-03-30

In this study, the identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct epitopes on the viral envelope (Env) will likely be required to overcome the extraordinary diversity of HIV-1, a key outstanding question is which bnAbs, and how many, will be needed to achieve optimal clinical benefit. We assessed the neutralizing activity of 15 bnAbs targeting four distinct epitopes of Env, including the CD4-binding site (CD4bs), the V1/V2-glycan region, the V3-glycan region, and themore » gp41 membrane proximal external region (MPER), against a panel of 200 acute/early clade C HIV-1 Env pseudoviruses. A mathematical model was developed that predicted neutralization by a subset of experimentally evaluated bnAb combinations with high accuracy. Using this model, we performed a comprehensive and systematic comparison of the predicted neutralizing activity of over 1,600 possible double, triple, and quadruple bnAb combinations. The most promising bnAb combinations were identified based not only on breadth and potency of neutralization, but also other relevant measures, such as the extent of complete neutralization and instantaneous inhibitory potential (IIP). By this set of criteria, triple and quadruple combinations of bnAbs were identified that were significantly more effective than the best double combinations, and further improved the probability of having multiple bnAbs simultaneously active against a given virus, a requirement that may be critical for countering escape in vivo. These results provide a rationale for advancing bnAb combinations with the best in vitro predictors of success into clinical trials for both the prevention and treatment of HIV-1 infection.« less

Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

PubMed

Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

2015-01-01

Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESN<3 yr, and HIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode

The early universe history from contraction-deformation of the Standard Model

NASA Astrophysics Data System (ADS)

Gromov, N. A.

2017-03-01

The elementary particles evolution in the early Universe from Plank time up to several milliseconds is presented. The developed theory is based on the high-temperature (high-energy) limit of the Standard Model which is generated by the contractions of its gauge groups. At the infinite temperature all particles lose masses. Only massless neutral -bosons, massless Z-quarks, neutrinos and photons are survived in this limit. The weak interactions become long-range and are mediated by neutral currents, quarks have only one color degree of freedom.

6 CFR 27.305 - Neutral adjudications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 6 Domestic Security 1 2012-01-01 2012-01-01 false Neutral adjudications. 27.305 Section 27.305 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Orders and Adjudications § 27.305 Neutral adjudications. (a) Any facility or other person who has...

6 CFR 27.305 - Neutral adjudications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 6 Domestic Security 1 2013-01-01 2013-01-01 false Neutral adjudications. 27.305 Section 27.305 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY CHEMICAL FACILITY ANTI-TERRORISM STANDARDS Orders and Adjudications § 27.305 Neutral adjudications. (a) Any facility or other person who has...