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Sample records for subclass levels specific

  1. Temporal variation in HIV-specific IgG subclass Abs during acute infection differentiates spontaneous controllers from chronic progressors.

    Science.gov (United States)

    Sadanand, Saheli; Das, Jishnu; Chung, Amy W; Schoen, Matthew K; Lane, Sophie; Suscovich, Todd J; Streeck, Hendrik; Smith, Davey; Little, Susan; Lauffenburger, Douglas A; Richman, Douglas; Alter, Galit

    2017-12-12

    Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between subjects who ultimately became controllers versus those who became progressors. IgG was purified from plasma from nine acutely infected subjects who subsequently controlled HIV spontaneously (controllers) and ten acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 post-infection. Levels of clade B gp120-, gp140-and gp41-specific IgG antibody subclasses were measured. Additionally, gp120-specific antibody-dependent cellular phagocytosis (ADCP), rapid fluorescent antibody-dependent cellular cytotoxicity (RFADCC), and antibody-dependent cellular viral inhibition (ADCVI) were all assessed. While no single Ab-related measurement was significantly associated with long-term HIV control, combinations of Ab-associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 Abs and losses in Env-specific IgG3 Abs. Moreover, progressors, but not controllers, lost ADCVI function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection. This study suggests that the temporal variation and maintenance of Env-specific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir.

  2. The Challenge of Immunoglobulin-G Subclass Deficiency and Specific Polysaccharide Antibody Deficiency--a Dutch Pediatric Cohort Study.

    Science.gov (United States)

    Schatorjé, Ellen J H; de Jong, Everieke; van Hout, Roeland W N M; García Vivas, Yumely; de Vries, Esther

    2016-02-01

    Immunoglobulin(Ig)G-subclass deficiency and specific polysaccharide antibody deficiency (SPAD) are among the most frequent causes of recurrent respiratory infections in children. Little is known about their prevalence, clinical presentation and prognosis. No study has been published in a Western-European nor in a mainly non-tertiary cohort until now. Therefore, we performed this observational cohort study in children recruited from secondary and tertiary pediatric practices all over The Netherlands. Dutch pediatricians were monthly asked to report patients with IgG-subclass deficiency and/or SPAD. Demographic, clinical and laboratory characteristics were collected. Separate informed consent was asked from parents and children (≥ 12 years of age) for annual update of the medical status. 49 children with confirmed IgG-subclass deficiency and/or SPAD were included. The majority of children (69%) was reported by four (out of 12) secondary hospitals with a pediatric immunologist in the staff. 45 children had ≥ 1 low IgG-subclass level and 11 had SPAD. IgG2 deficiency was the most prevalent IgG-subclass deficiency (37/49;76%). 10% of these children already showed bronchiectasis. Two-thirds were male (33/49;67%, p = 0.015). From 10 years of age, only boys were left and only boys showed progressive immunodeficiency during follow-up (11/24; 46%). This is the first Western-European mainly non-tertiary cohort of children with IgG-subclass deficiency and/or SPAD. The disease course is not always benign, especially in boys. Most children were reported and managed in secondary hospitals with a pediatric immunologist in the staff. To identify more patients, the awareness of these diseases among general pediatricians should increase.

  3. IgG subclass and vaccination stimulus determine changes in antigen specific antibody glycosylation in mice.

    Science.gov (United States)

    Kao, Daniela; Lux, Anja; Schaffert, Anja; Lang, Roland; Altmann, Friedrich; Nimmerjahn, Falk

    2017-08-02

    Immunoglobulin G (IgG) glycosylation can modulate antibody effector functions. Depending on the precise composition of the sugar moiety attached to individual IgG glycovariants either pro- or anti-inflammatory effector pathways can be initiated via differential binding to type I or type II Fc-receptors. However, an in depth understanding of how individual IgG subclasses are glycosylated during the steady state and how their glycosylation pattern changes during vaccination is missing. To monitor IgG subclass glycosylation during the steady state and upon vaccination of mice with different T-cell dependent and independent antigens, tryptic digests of serum, and antigen-specific IgG preparations were analyzed by reversed phase-liquid chromatography-mass spectrometry. We show that there is a remarkable difference with respect to how individual IgG subclasses are glycosylated during the steady state. More importantly, upon T-cell dependent and independent vaccinations, individual antigen-specific IgG subclasses reacted differently with respect to changes in individual glycoforms, suggesting that the IgG subclass itself is a major determinant of restricting or allowing alterations in specific IgG glycovariants. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Subclass restriction pattern of antigen-specific antibodies in donors with defective expression of IgG or IgA subclass heavy chain constant region genes

    NARCIS (Netherlands)

    Hammerström, L.; Carbonara, A.O.; DeMarchi, M.; LeFranc, G.; Möller, G.; Smith, C.I.E.; Zegers, B.J.M.

    1987-01-01

    We have developed a method for the measurement of the IgG and IgA subclass distribution of antigen-specific human antibodies. The controls for the specificity of the assay include the use of a number of monoclonal human antibodies and sera from individuals with deletions of particular immunoglobulin

  5. Quantification of serum IgG subclasses by use of subclass-specific tryptic peptides and liquid chromatography--tandem mass spectrometry.

    Science.gov (United States)

    Ladwig, Paula M; Barnidge, David R; Snyder, Melissa R; Katzmann, Jerry A; Murray, David L

    2014-08-01

    Measurement of IgG subclasses is a useful tool for investigation of humoral immune deficiency in the presence of total IgG within reference intervals and IgG4-related disease. Nephelometry has been the method of choice for quantification. We describe an LC-MS/MS method that can multiplex all 4 subclasses along with total IgG by use of either IgG subclass-specific peptide stable isotope-labeled internal standards or a surrogate digest standard for quantification and does not rely on antigen/antibody reactions. We combined serum with labeled internal peptide standards and intact purified horse IgG. Samples were denatured, reduced, alkylated, and digested. We analyzed the digested serum by LC-MS/MS for IgG subclasses 1-4 and total IgG. We assayed 112 patient sera by LC-MS/MS and immunonephelometry. The mean of the slopes and R(2) values for IgG1, IgG2, IgG3, IgG4, and IgG were 1.18 and 0.93, respectively. Interassay imprecision for the LC-MS/MS method was IgG and subclasses and was slightly improved by use of a calibrator peptide from an exogenous horse IgG. Summed total IgG correlated with the measured total IgG within 10%. Reference intervals and analytical measuring range were all similar to our previous validation data for the immunonephelometry assays. Total IgG and IgG subclasses 1, 2, 3, and 4 can be quantified by LC-MS/MS with performance comparable to nephelometry. © 2014 American Association for Clinical Chemistry.

  6. In-depth analysis of subclass-specific conformational preferences of IgG antibodies

    DEFF Research Database (Denmark)

    Tian, Xinsheng; Vestergaard, Bente; Thorolfsson, Matthias

    2015-01-01

    with identical variable regions, were thoroughly analysed by the ensemble optimization method. The extended analysis of the optimized ensembles through shape clustering reveals distinct subclass-specific conformational preferences, which provide new insights for understanding the variations in physical....../chemical stability and biological function of therapeutic antibodies. Importantly, the way that specific differences in the linker region correlate with the solution structure of intact antibodies is revealed, thereby visualizing future potential for the rational design of antibodies with designated physicochemical...

  7. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications.

    Science.gov (United States)

    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michele; Alfano, Christian

    2016-01-27

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.

  8. Kinetics of dengue virus-specific serum immunoglobulin classes and subclasses correlate with clinical outcome of infection.

    NARCIS (Netherlands)

    P. Koraka (Penelope); C. Suharti (Catarina); T.E. Setiati (Tatty); A.T.A. Mairuhu; E.C.M. van Gorp (Eric); C.E. Hack (Erik); M. Juffrie; J. Sutaryo; G.M. van der Meer; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    2001-01-01

    textabstractThe kinetics of dengue virus (DEN)-specific serum immunoglobulin classes (immunoglobulin M [IgM] and IgA) and subclasses (IgG1 to IgG4) were studied in patients suffering from dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Serum samples from non-DEN

  9. The Challenge of Immunoglobulin-G Subclass Deficiency and Specific Polysaccharide Antibody Deficiency--a Dutch Pediatric Cohort Study

    NARCIS (Netherlands)

    Schatorjé, Ellen J H; de Jong, Everieke; van Hout, Roeland W N M; García Vivas, Yumely; de Vries, Esther

    PURPOSE: Immunoglobulin(Ig)G-subclass deficiency and specific polysaccharide antibody deficiency (SPAD) are among the most frequent causes of recurrent respiratory infections in children. Little is known about their prevalence, clinical presentation and prognosis. No study has been published in a

  10. The challenge of Immunoglobulin-G Subclass Deficiency and Specific Polysaccharide Antibody Deficiency : A Dutch pediatric cohort study

    NARCIS (Netherlands)

    Schatorjé, E.J.H.; de Jong, E.; van Hout, R.; García Vivas, Y.; de Vries, E.

    2016-01-01

    Purpose Immunoglobulin(Ig)G-subclass deficiency and specific polysaccharide antibody deficiency (SPAD) are among the most frequent causes of recurrent respiratory infections in children. Little is known about their prevalence, clinical presentation and prognosis. No study has been published in a

  11. Rotavirus-specific subclass antibody and cytokine responses in Bangladeshi children with rotavirus diarrhoea.

    Science.gov (United States)

    Azim, Tasnim; Zaki, M Hasan; Podder, Goutam; Sultana, Novera; Salam, M Abdus; Rahman, S Moshfiqur; Sefat-e-Khuda; Sack, David A

    2003-02-01

    Rotavirus-specific subclass antibody responses and cytokines, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-8 (IL-8), and IL-10, were measured in children 7-24 months of age with rotavirus diarrhoea (n = 29); the responses were compared with children with watery diarrhoea from whom no enteric pathogens were isolated (controls; n = 11). All children had diarrhoea for or = 4-fold rise in antibody titre between the acute and convalescent stages were considered to have a response. The numbers of children with rotavirus-specific IgA and IgA1 responses in stool were similar in the two groups of children. In the plasma, more children with rotavirus diarrhoea had rotavirus-specific IgA, IgA1, IgG, IgG1, and IgG3 responses than did control children (P = 0.049, 0.007, 0.001, 0.002, and 0.012, respectively). IgA2 was not detectable. Among cytokines measured in supernatants from peripheral blood mononuclear cells (PBMCs) cultured for 6 and 24 hr, IFN-gamma was the only cytokine that was higher in children with rotavirus diarrhoea compared with controls (P = 0.013). Severity of illness did not correlate with nutritional status or antibody titres, but severity did correlate with TNF-alpha during the acute stage of illness. IFN-gamma correlated positively with IgG1 titres. These findings suggest a role for IFN-gamma in the pathogenesis of rotavirus infection, but this needs confirmation by other studies. The immune responses described are relevant to future vaccine trials, as immune responses in vaccinees should mimic those in natural infection.

  12. The Essence of Subclassing

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann; Møller-Pedersen, Birger

    The essence of subclassing is the ability to represent classification hierarchies reflecting domain concepts. With the right class mechanism there is no need for a separate type/subtype mechanism, and general classes may have behavior specifications so that subclassing also implies code reuse....... Sometimes the application is so well defined (known) that developers may readily start out with classes that represent domain concepts. Singular objects have been around for some time, so a new kind of language with equal support for both objects and classes would simply ask for tool support for objects...

  13. Increases in serum immunoglobulins to age-related normal levels in children with IgA and/or IgG subclass deficiency.

    Science.gov (United States)

    Kutukculer, Necil; Karaca, Neslihan Edeer; Demircioglu, Ozlem; Aksu, Guzide

    2007-03-01

    Immunoglobulins (Ig) A and G subclass deficiencies are common immune system disorders which cause morbidity especially between 2 and 6 yr of age. Prognosis of these defects and therapeutic approach is unclear. The aim of the present retrospective study was to review the clinical and laboratory records of 87 children with IgA and/or IgG subclass deficiency to determine whether these patients experience changes in serum Ig concentrations during follow-up and to give more clinic and laboratory information to the families about the course of these diseases. Among 87 patients studied, the most frequent defect was partial IgA deficiency combined with IgG3 subclass deficiency (41%). The other groups were as follows; partial IgA deficiency (32%), selective IgA deficiency (8%), partial IgA combined with IgG2-G4 subclass deficiency (6%), and IgG subclass deficiency (13%). The commonest clinical presentations were recurrent upper respiratory tract infections (76%), pneumonia (14%), acute gastroenteritis (3%), urinary tractus infection (3%), sinusitis (2%), and acute otitis media (2%). Atopy was widely represented in the patients studied (24%). The number of patients who were given prophylactic treatment with benzathine penicilline, prophylactic oral antibiotic, or oral bacterial extract to prevent infections was 68 (78%). Frequency of recurrent infections decreased from 7.9 +/- 4.9 per year to 2.5 +/- 2.3 in 68 patients receiving any prophylactic regimen; however, decrease in frequency of infections did not show any significant difference between different prophylactic groups. None of the patients in the selective IgA deficiency group had reached normal serum levels of IgA. At the age of 58.3 +/- 21.4 months, 52% of patients in partial IgA deficiency group and 51% of patients in partial IgA + IgG subclass deficiency group, serum IgA increased to normal ranges. Serum IgG subclass levels increased to normal range for age in 67% of patients in partial IgA + IgG subclass

  14. The blocking activity of birch pollen-specific immunotherapy-induced IgG4 is not qualitatively superior to that of other IgG subclasses

    DEFF Research Database (Denmark)

    Ejrnaes, Anne M; Bødtger, Uffe; Larsen, Jørgen N

    2004-01-01

    Allergen-specific IgG antibodies induced by specific immunotherapy (SIT) interfere with the allergen-IgE interaction, and act as blocking antibodies in vitro. It has been hypothesised that IgG4, as opposed to other IgG subclasses, is particularly important in this function, which may play a role...

  15. Immunological studies on bee-keepers: specific IgG and subclass typing IgG against bee venom and bee venom components.

    Science.gov (United States)

    Urbanek, R; Forster, J; Ziupa, J; Karitzky, D

    1980-11-17

    Specific IgE antibodies against bee venom and its components were studied in 23 bee-keepers. The highest IgG serum levels were observed for whole bee venom followed by phospholipase A. The serum levels of specific IgG antibodies against melittin and MCD-peptide were lower, the lowest serum levels being observed for apamin. After a 5 month absence from bee-keeping a fall in the serum levels of IgG antibodies was observed in all the bee-keepers studied. The investigation of the IgG subclass antibodies 1-4 against bee venom and phospholipase A demonstrated the highest serum levels for IgG 4 and IgG 2, the lowest levels were observed for IgG 1. The lowest IgG serum levels were associated with the least effective protection to bee stings. These findings support the concept that specific IgG antibodies prevent the development of allergic symptoms after bee sting.

  16. Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI.

    Science.gov (United States)

    Radinsky, Olga; Edri, Avishay; Brusilovsky, Michael; Fedida-Metula, Shlomit; Sobarzo, Ariel; Gershoni-Yahalom, Orly; Lutwama, Julius; Dye, John; Lobel, Leslie; Porgador, Angel

    2017-07-20

    Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors' sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

  17. Serum IGG subclass levels in healthy infants of 13-62 weeks of age

    NARCIS (Netherlands)

    Zegers, B. J. M.; van der Giessen, M.; Reerink-Brongers, E. E.; Stoop, J. W.

    1980-01-01

    The levels of IgGl, IgG2, IgG3, and IgG4 were determined in serum samples of 160 infants aged 13-62 weeks, and of their mothers. In addition the serum IgM, IgG, IgA, and IgD levels of the infants are presented. The results show that IgM, IgGl, and IgG3 slightly increase during the first year of

  18. The serum igg subclass levels in healthy infants of 13–62 weeks of age

    NARCIS (Netherlands)

    Zegers, B.J.M.; Giessen, M. van der; Reerink-Brongers, E.E.; Stoop, J.W.

    1980-01-01

    The levels of IgG1, IgG2, IgG3, and IgG4 were determined in serum samples of 160 infants aged 13–62 weeks, and of their mothers. In addition the serum IgM, IgG, IgA, and IgD levels of the infants are presented. The results show that IgM, IgG1, and IgG3 slightly increase during the first year of

  19. The serum igg subclass levels in healthy infants of 13–62 weeks of age

    OpenAIRE

    Zegers, B.J.M.; van der Giessen, M; Reerink-Brongers, E.E.; Stoop, J.W.

    1980-01-01

    The levels of IgG1, IgG2, IgG3, and IgG4 were determined in serum samples of 160 infants aged 13–62 weeks, and of their mothers. In addition the serum IgM, IgG, IgA, and IgD levels of the infants are presented. The results show that IgM, IgG1, and IgG3 slightly increase during the first year of life, whereas IgG2, IgG4, IgA, and IgD hardly do. This difference in the development of the various immunoglobulin isotypes reflects differences in the terminal maturation of subsets of B-lymphocytes i...

  20. Determination of levels of salivary IgA subclasses in patients with minor recurrent aphthous ulcer.

    Science.gov (United States)

    Saluja, Ramandeep; Kale, Alka; Hallikerimath, Seema

    2012-01-01

    Recurrent Aphthous Ulcer (RAU) is an inflammatory disease characterized by recurrent, painful oral ulcers. It is of multifactorial etiology. Salivary immunoglobulins have important role in the protection of mucosal surfaces. The aim of this study was to determine salivary immunoglobulin A1 (IgA1) and IgA2 in acute and remission phases of the disease. Thirty clinically confirmed cases of RAU and 30 age-and sex-matched controls were included in the study. After detailed case history and thorough clinical examination, 2 mL of saliva was collected in both acute and remission phases of the disease. The obtained saliva samples were subjected to quantification of IgA1 and IgA2 levels using RID kit. The mean IgA2 level was significantly higher (Pacute and remission phase of the study group. The mean IgA1 level also showed a significant increase in the acute phase compared to remission as well as controls (Pacute phase for IgA1 and in both phases for IgA2 (Pacute phase is characterized with increase in IgA2 that might reflect increased immune response as a possible result of the microbial stimulation seen in the acute phase in comparison to the remission period. IgA plays an important role in the pathogenesis of RAU and it can be used as a parameter to assess the mucosal immune status.

  1. Are serum levels of immunoglobulin classes and IgG subclasses involved in delayed pulmonary complications induced by sulfur mustard? Sardasht-Iran Cohort Study.

    Science.gov (United States)

    Ghazanfari, Tooba; Mostafaie, Ali; Yaraee, Roya; Pourfarzam, Shahryar; Faghihzadeh, Soghrat; Rezaei, Abbas; Mahmoudi, Mahmoud; Vaez-Mahdavi, Mohammad R; Moaiedmohseni, Sakine; Soroush, Mohammad R; Naghizadeh, Mohammad M; Faghihzadeh, Elham; Hassan, Zuhair M

    2013-11-01

    Respiratory complications are the foremost long term debilitating effects after sulfur mustard toxicity. The underlying immunological mechanisms of sulfur mustard induced lung damage are still poorly understood. The question of the involvement of immunoglobulin classes and subclasses in delayed pulmonary complications induced by SM was addressed in this study as a part of Sardasht-Iran Cohort Study (SICS).In SICS, 372 male participants who were exposed to SM 20 years earlier were compared with 128 unexposed age-matched controls. At the time of study (2007), the clinical evaluations and spirometry was performed for all subjects according to the American Thoracic Society Criteria, and at the same time, the sera were isolated, labeled and aliquots were kept frozen in -80°C. Serum immunoglobulin (Ig) levels including IgM, IgA, IgE, IgG, and IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were measured using quantitative Elisa method. It was found that among immunoglobulin classes and IgG subclasses only IgM and IgG4 were significantly decreased in the peripheral blood of exposed cases. IgM level also positively correlated with FEV1 only in the SM exposed group. These results indicated a weak but significant role for IgA in control of the delayed pulmonary complications. There were no strong correlations between other immunoglobulin classes or IgG subclasses with pulmonary disease severity in sulfur mustard intoxicated subjects. The authors proposed that systemic levels of immunoglobulins do not exert essential roles in severity of delayed pulmonary complications following SM toxicity. However, more studies on local and systemic levels of immunoglobulins in more severe groups are suggested. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Malaria resistance genes are associated with the levels of IgG subclasses directed against Plasmodium falciparum blood-stage antigens in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Afridi Sarwat

    2012-09-01

    Full Text Available Abstract Background HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. Furthermore, HBB, IL4, TNF, and FCGR2A have been associated with both malaria resistance and IgG levels. This suggests that some malaria resistance genes influence the levels of IgG subclass antibodies. Methods In this study, the effect of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the levels of IgG responses against Plasmodium falciparum blood-stage extract was investigated in 220 individuals living in Burkina Faso. The Pearson’s correlation coefficient among IgG subclasses was determined. A family-based approach was used to assess the association of polymorphisms with anti-P. falciparum IgG, IgG1, IgG2, IgG3 and IgG4 levels. Results After applying a multiple test correction, several polymorphisms were associated with IgG subclass or IgG levels. There was an association of i haemoglobin C with IgG levels; ii the FcγRIIa H/R131 with IgG2 and IgG3 levels; iii TNF-863 with IgG3 levels; iv TNF-857 with IgG levels; and, v TNF1304 with IgG3, IgG4, and IgG levels. Conclusion Taken together, the results support the hypothesis that some polymorphisms affect malaria resistance through their effect on the acquired immune response, and pave the way towards further comprehension of genetic control of an individual’s humoral response against malaria.

  3. Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy

    DEFF Research Database (Denmark)

    Høst, A; Husby, S; Gjesing, B

    1992-01-01

    Prospectively, serum levels of IgE, specific IgE antibodies (AB) to whole cow milk protein (CMP), bovine se-albumin, bovine immunoglobulin, bovine lactoferrin, bovine lactalbumin and beta-lactoglobulin (BLG), IgG and IgG subclass antibodies to ovalbumin (OA) and BLG, and IgG4 RAST to CMP (bovine...

  4. Characteristics of HPV-specific antibody responses induced by infection and vaccination: cross-reactivity, neutralizing activity, avidity and IgG subclasses.

    Directory of Open Access Journals (Sweden)

    Mirte Scherpenisse

    Full Text Available OBJECTIVES: In order to assess HPV-specific IgG characteristics, we evaluated multiple aspects of the humoral antibody response that will provide insight in the HPV humoral immune response induced by HPV infection and vaccination. METHODS: Cross-reactivity of HPV-specific antibodies induced by infection or vaccination was assessed with VLP16 or 18 inhibition using a VLP-based multiplex immunoassay (MIA for HPV16, 18, 31, 33, 45, 52 and 58. HPV16/18 specific IgG1-4 subclasses and avidity were determined with the VLP-MIA in sera after HPV infection and after vaccination. Neutralizing antibodies were determined in a small subset of single-seropositive and multi-seropositive naturally derived antibodies. RESULTS: Naturally derived antibodies from single-positive sera were highly genotype-specific as homologue VLP-inhibition percentages varied between 78-94%. In multi-positive sera, cross-reactive antibodies were observed both within and between α7 and α9 species. After vaccination, cross-reactive antibodies were mainly species-specific. Avidity of vaccine-derived HPV-specific antibodies was 3 times higher than that of antibodies induced by HPV infection (p<0.0001. IgG1 and IgG3 were found to be the predominant subclasses observed after HPV infection and vaccination. In the small subset tested, the number of single-positive sera with neutralizing capacity was higher than of multi-positive sera. CONCLUSION: Naturally derived HPV-specific antibodies from single-positive samples showed different characteristics in terms of cross-reactivity and neutralizing capacity compared with antibodies from multi-positive sera. Post-vaccination, HPV antibody avidity was approximately 3 times higher than antibody avidity induced by HPV infection. Therefore, antibody avidity might be a potential surrogate of protection.

  5. Probing the specificity of the subclass B3 FEZ-1 metallo-beta-lactamase by site-directed mutagenesis.

    Science.gov (United States)

    Mercuri, Paola Sandra; García-Sáez, Isabel; De Vriendt, Kris; Thamm, Iris; Devreese, Bart; Van Beeumen, Jozef; Dideberg, Otto; Rossolini, Gian Maria; Frère, Jean-Marie; Galleni, Moreno

    2004-08-06

    The subclass B3 FEZ-1 beta-lactamase produced by Fluoribacter (Legionella) gormanii is a Zn(II)-containing enzyme that hydrolyzes the beta-lactam bond in penicillins, cephalosporins, and carbapenems. FEZ-1 has been extensively studied using kinetic, computational modeling and x-ray crystallography. In an effort to probe residues potentially involved in substrate binding and zinc binding, five site-directed mutants of FEZ-1 (H121A, Y156A, S221A, N225A, and Y228A) were prepared and characterized using metal analyses and steady state kinetics. The activity of H121A is dependent on zinc ion concentration. The H121A monozinc form is less active than the dizinc form, which exhibits an activity similar to that of the wild type enzyme. Tyr156 is not essential for binding and hydrolysis of the substrate. Substitution of residues Ser221 and Asn225 modifies the substrate profile by selectively decreasing the activity against carbapenems. The Y228A mutant is inhibited by the product formed upon hydrolysis of cephalosporins. A covalent bond between the side chain of Cys200 and the hydrolyzed cephalosporins leads to the formation of an inactive and stable complex.

  6. A computational approach to the description of individual immune responses. IgE and IgG-subclass allergen-specific antibodies formed during immunotherapy

    DEFF Research Database (Denmark)

    Søndergaard, I; Poulsen, L K; Osterballe, O

    1991-01-01

    Detailed evaluation of the IgE and IgG-subclass immune response during immunotherapy can now be performed by crossed radio immunoelectrophoresis (CRIE). Some new concepts are introduced facilitating the handling of the vast amount of data obtained by quantitating the immune response. These concepts...... are "distance" between antibody responses and "immune response width". The 20 patients included in this study were pollen-allergic patients who underwent specific immunotherapy in a 3-year prospective study. It was found that the immune response during immunotherapy was restricted to IgG1 and IgG4 antibodies...... and decreased towards six. For the IgG4 antibodies the number of reactions increased towards 15 antigens and decreased towards four. The increase is generally paralleled by an increase in quantitative immune response as well. For some of the antigens a rise in the IgE antibodies is contrasted by a fall...

  7. High prevalence of subclass-specific binding and neutralizing antibodies against Clostridium difficile toxins in adult cystic fibrosis sera: possible mode of immunoprotection against symptomatic C. difficile infection

    Directory of Open Access Journals (Sweden)

    Monaghan TM

    2017-07-01

    Full Text Available Tanya M Monaghan,1 Ola H Negm,2,3 Brendon MacKenzie,4 Mohamed R Hamed,2,3 Clifford C Shone,5 David P Humphreys,4 K Ravi Acharya,6 Mark H Wilcox7 1Nottingham Digestive Diseases Centre, NIHR Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham, Nottingham, 2Breast Surgery Group, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham, UK; 3Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 4Antibody Biology, UCB-New Medicines, UCB Celltech, Slough, UK; 5Toxins Group, National Infection Service, Public Health England, Salisbury, UK; 6Department of Biology and Biochemistry, University of Bath, Bath, UK; 7Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK Objectives: Despite multiple risk factors and a high rate of colonization for Clostridium difficile, the occurrence of C. difficile infection in patients with cystic fibrosis is rare. The aim of this study was to compare the prevalence of binding C. difficile toxin-specific immunoglobulin (IgA, IgG and anti-toxin neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic C. difficile infection (without cystic fibrosis and healthy controls. Methods: Subclass-specific IgA and IgG responses to highly purified whole C. difficile toxins A and B (toxinotype 0, strain VPI 10463, ribotype 087, toxin B from a C. difficile toxin-B-only expressing strain (CCUG 20309 and precursor form of B fragment of binary toxin, pCDTb, were determined by protein microarray. Neutralizing antibodies to C. difficile toxins A and B were evaluated using a Caco-2 cell-based neutralization assay. Results: Serum IgA anti-toxin A and B levels and neutralizing antibodies against toxin A were significantly higher in adult cystic fibrosis patients (n=16 compared with healthy controls (n=17 and

  8. IgG antibody subclasses, tumor necrosis factor and IFN-gamma levels in patients with type II lepra reaction on thalidomide treatment.

    Science.gov (United States)

    Partida-Sanchez, S; Favila-Castillo, L; Pedraza-Sanchez, S; Gomez-Melgar, M; Saul, A; Estrada-Parra, S; Estrada-Garcia, I

    1998-05-01

    A group of 9 Mexican lepromatous leprosy patients was studied at the beginning of a type II reaction (erythema nodosum leprosum, ENL) and after 1 or 2 months of thalidomide treatment. ENL patients at the onset of the reaction had slightly higher amounts of anti-Mycobacterium leprae IgG1 and IgG2 antibodies, compared to similar lepromatous patients that did not develop ENL. Neither these antibody levels nor IgM and the other IgG subclasses were importantly modified after thalidomide treatment. Serum TNF was significantly higher in the patients that developed ENL compared to those that did not develop the reaction. TNF levels were slightly decreased after 1 month of thalidomide treatment and significantly decreased after 2 months of treatment. Serum IFN-gamma was significantly lower in patients at the onset of ENL and was increased after 1 and 2 months of thalidomide treatment.

  9. Characteristics of HPV-specific antibody responses induced by infection and vaccination: cross-reactivity, neutralizing activity, avidity and IgG subclasses.

    Science.gov (United States)

    Scherpenisse, Mirte; Schepp, Rutger M; Mollers, Madelief; Meijer, Chris J L M; Berbers, Guy A M; van der Klis, Fiona R M

    2013-01-01

    In order to assess HPV-specific IgG characteristics, we evaluated multiple aspects of the humoral antibody response that will provide insight in the HPV humoral immune response induced by HPV infection and vaccination. Cross-reactivity of HPV-specific antibodies induced by infection or vaccination was assessed with VLP16 or 18 inhibition using a VLP-based multiplex immunoassay (MIA) for HPV16, 18, 31, 33, 45, 52 and 58. HPV16/18 specific IgG1-4 subclasses and avidity were determined with the VLP-MIA in sera after HPV infection and after vaccination. Neutralizing antibodies were determined in a small subset of single-seropositive and multi-seropositive naturally derived antibodies. Naturally derived antibodies from single-positive sera were highly genotype-specific as homologue VLP-inhibition percentages varied between 78-94%. In multi-positive sera, cross-reactive antibodies were observed both within and between α7 and α9 species. After vaccination, cross-reactive antibodies were mainly species-specific. Avidity of vaccine-derived HPV-specific antibodies was 3 times higher than that of antibodies induced by HPV infection (pHPV infection and vaccination. In the small subset tested, the number of single-positive sera with neutralizing capacity was higher than of multi-positive sera. Naturally derived HPV-specific antibodies from single-positive samples showed different characteristics in terms of cross-reactivity and neutralizing capacity compared with antibodies from multi-positive sera. Post-vaccination, HPV antibody avidity was approximately 3 times higher than antibody avidity induced by HPV infection. Therefore, antibody avidity might be a potential surrogate of protection.

  10. Common carp have two subclasses of bonyfish specific antibody IgZ showing differential expression in response to infection

    NARCIS (Netherlands)

    Ryo, S.; Wijdeven, R.H.M.; Tyagi, A.; Hermsen, G.J.; Kono, T.; Karunasagar, I.; Rombout, J.H.W.M.; Sakai, H.; Verburg-van Kemenade, B.M.L.; Savan, R.

    2010-01-01

    Immunoglobulin heavy chains identified in bony fish are broadly classified into three classes namely IgM, IgD and IgZ. The most recently described isotype is IgZ, a teleosts-fish specific isotype that shows variations in gene structure across teleosts. In this study we have identified two IgZ

  11. Evaluation of cysticercus-specific IgG (total and subclasses and IgE antibody responses in cerebrospinal fluid samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies

    Directory of Open Access Journals (Sweden)

    Lisandra Akemi Suzuki

    Full Text Available In the present study, an enzyme-linked immunosorbent assay (ELISA standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses and IgE antibodies in cerebrospinal fluid (CSF samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA=1.17 and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49 and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46 and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12 and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85 and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60 and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.

  12. Immunoglobulin G (IgG) subclass deficiency in Thai children.

    Science.gov (United States)

    Visitsunthorn, Nualanong; Hengcrawit, Wiriya; Jirapongsananuruk, Orathai; Luangwedchakam, Voravich

    2011-12-01

    Patients with Immunoglobulin G (IgG) subclass deficiency may suffer from recurrent infections, mainly sino-pulmonary infection. To determine the epidemiology of IgG subclass deficiency in Thai children at a tertiary care hospital and to compare the differences between children who were diagnosed with IgG subclass deficiency by using low level criteria [less than 2 standard deviation (SD) of normal levels for age] and by using low percentage criteria (proportion of each IgG subclasses/total IgG). The study was a descriptive study of 55 children up to 15 years old with recurrent infections diagnosed as having IgG subclass deficiency but no acquired or other primary immune deficiencies except for IgA and/or IgM deficiency. Isolated IgG3 subclass deficiency was the most common IgG subclass deficiency (56.4%). IgG3 subclass deficiency, either isolated or combined with other IgG subclass deficiency, was found in 85.5% of the cases. The common age of onset was between birth and five years of age. The most common presenting symptom was recurrent sinusitis (83.6%). Majority of the cases (89.3%) were diagnosed by low percentage criteria while 12.7% were diagnosed by low level criteria. All cases with low levels of IgG subclass antibodies also had low percentages. There were no statistically significant differences in the clinical manifestations and management methods between the children who were diagnosed by low level and low percentage. IgG3 subclass deficiency was the most common IgG subclass deficiency in Thai children. The most common presenting symptom was recurrent sinusitis. Although the diagnosis could be made in the patients with recurrent upper respiratory infection by using low level criteria, but the diagnosis should be considered when the low percentage criteria are met.

  13. Validation and evaluation of VapA-specific IgG and IgG subclass enzyme-linked immunosorbent assays (ELISAs) to identify foals with Rhodococcus equi pneumonia.

    Science.gov (United States)

    Sanz, M G; Oliveira, A F; Loynachan, A; Page, A; Svansson, V; Giguère, S; Horohov, D W

    2016-01-01

    Rhodococcus equi (Rhodococcus hoagii/Prescottella equi) is a common cause of foal pneumonia, but its diagnosis remains a challenge for equine veterinarians. While the VapA-specific (virulence-associated protein A) immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) has low sensitivity and specificity for detecting pneumonic foals, little is known about VapA-specific IgG subclasses. To evaluate the performance of VapA-specific ELISA for IgG and its subclasses IgGa, IgGb and IgG(T) in the early diagnosis of pneumonia caused by R. equi. Assay validation followed by assessment of diagnostic performance using archived samples from animals of known status. Serum samples from exposed (n = 125) and nonexposed adult horses (n = 10) and from experimentally challenged and naturally infected foals were used for ELISA validation. Post mortem and tissue culture records of the last 24 years from the Institute for Experimental Pathology at the University of Iceland in Keldur, Iceland laboratory were evaluated to confirm the absence of R. equi cases in Iceland. The diagnostic performance of VapA-specific IgG and its subclasses was evaluated using banked serum samples from pneumonic (n = 21) and healthy foals (n = 80). To evaluate each IgG assay, a cut-off value was selected based on receiver operating characteristic curve analysis and used to calculate sensitivity and specificity. The intra- and interassay coefficients of variation were calculated for each ELISA. Using sera from Iceland, where R. equi infection has not been reported, the VapA-specific IgG ELISA differentiated exposed from nonexposed horses. When used to identify infected foals, VapA-specific IgG, IgGa and IgGb had no diagnostic value. In contrast, IgG(T) had high sensitivity and specificity. Horses from Iceland are not exposed to VapA(+) R. equi and can serve as negative controls. VapA-specific IgG subclasses, with the exception of IgG(T), are poor predictors of disease. Further

  14. Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

    Directory of Open Access Journals (Sweden)

    Andrew R Dalby

    Full Text Available Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

  15. Serum cholesterol and triglyceride reference ranges of twenty lipoprotein subclasses for healthy Japanese men and women.

    Science.gov (United States)

    Furusyo, Norihiro; Ai, Masumi; Okazaki, Mitsuyo; Ikezaki, Hiroaki; Ihara, Takeshi; Hayashi, Takeo; Hiramine, Satoshi; Ura, Kazuya; Kohzuma, Takuji; Schaefer, Ernst J; Hayashi, Jun

    2013-12-01

    This epidemiological study was done to generate normal ranges for the cholesterol and triglyceride levels in serum lipoprotein subclasses isolated from healthy adults based on gender and menopausal status. Cholesterol and triglyceride levels in 20 lipoprotein subclasses as separated by high performance liquid chromatography were measured in serum obtained from 825 fasting healthy subjects (267 men, 558 women). For serum cholesterol, 13.7% was found in very low density lipoprotein (VLDL) subclasses, 55.6% in low density lipoprotein (LDL) subclasses, and 30.4% in high density lipoprotein (HDL) subclasses. For serum triglycerides, these values were 52.1%, 27.9%, and 17.4%, respectively. Levels of cholesterol in some VLDL subclasses were inversely correlated with the levels of some HDL subclasses, while for triglycerides, elevated levels in any one subclass were generally strongly associated with elevated levels in all other subclasses. Men had significantly higher large VLDL-cholesterol levels than women (P cholesterol levels than men (P cholesterol levels than men (P cholesterol levels, and significantly higher all VLDL, LDL, and HDL-triglyceride levels than premenopausal women (P cholesterol and triglyceride subclass levels, as well as significant correlations between values in the various serum lipoprotein subclasses. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Identification of pediatric septic shock subclasses based on genome-wide expression profiling

    Directory of Open Access Journals (Sweden)

    Monaco Marie

    2009-07-01

    Full Text Available Abstract Background Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling. Methods Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization. Results Three putative subclasses (subclasses A, B, and C were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, P Conclusion Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.

  17. Antibody isotypes, including IgG subclasses, in Ecuadorian patients with pulmonary Paragonimiasis

    Directory of Open Access Journals (Sweden)

    Angel Guevara E.

    1995-08-01

    Full Text Available An ELISA test was developed to detect Paragonimus-specific antibodies, including IgG subclasses, using P. mexicanus crude water-soluble antigens. The test was standardized to detect antibodies in sera of Ecuadorian patients with pulmonary paragonimiasis and negative controls from the endemic area. The detected mean levels of IgG (0.753, SEM: 0.074 and IgM (0.303, SEM: 0.033 were significantly elevated (P<0.05. Within the IgG subclasses, IgG4 showed the highest detected mean level (0.365, SEM: 0.116 and the other three subclasses showed considerably lower mean levels (IgG1, 0.186 SEM: 0.06; IgG2, 0.046 SEM: 0.01; IgG3, 0.123 SEM: 0.047. The number of P. mexicanus eggs found in sputum of infected individuals showed a positive correlation with the level of antibodies detected for IgM, IgG and its subclasses (P<0.001. The relevance of these findings in Ecuadorian patients suffering from pulmonary paragonimiasis is discussed.

  18. Chronic glomerulonephritis associated with IgG subclass deficiency.

    Science.gov (United States)

    Kamei, Koichi; Nakagawa, Atsuko; Otsuka, Yasufumi; Nakayama, Makiko; Kobayashi, Shinichi; Matsuoka, Kentaro; Iijima, Kazumoto

    2007-08-01

    We experienced two patients with IgG subclass deficiency who suffered from chronic glomerulonephritis (GN). Patient 1 was a 17-year-old girl with IgG subclass deficiency (combined deficiency of IgG2 and IgG4). Renal biopsy was performed when she was aged 16 years, and she was diagnosed with membranoproliferative GN. Patient 2 was a 16-year-old girl with IgG subclass deficiency (combined deficiency of IgG2, IgG3, and IgG4). Renal biopsy was performed when she was aged 15 years, and she was diagnosed with membranous nephropathy. We examined the glomerular deposition patterns of their IgG subclasses. Furthermore, we compared their clinical and laboratory findings with those of three patients with IgG subclass deficiency without GN. Patients with GN suffered infections more frequently than those without GN. The serum levels of IgG (especially IgG1) and IgM were higher in patients with GN than in those without GN. In patient 1 IgG1 and IgG3 were deposited in a mesangiocapillary pattern, but, in patient 2, only IgG1 was deposited in a capillary pattern. Thus, the different patterns of IgG subclass deficiency between the two patients may be responsible for their different glomerular pathologies. To the best of our knowledge, this is the first report of chronic GN in patients with IgG subclass deficiency.

  19. The subclass distribution of IgG autoantibodies in cicatricial pemphigoid and epidermolysis bullosa acquisita.

    Science.gov (United States)

    Bernard, P; Prost, C; Aucouturier, P; Durepaire, N; Denis, F; Bonnetblanc, J M

    1991-08-01

    To study the subclass distribution of autoantibodies and their complement-fixing capacity in cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) we studied the sera from 23 patients by both indirect immunofluorescence (IIF) on 4-microns cryostat sections of normal human skin and immunoblotting of epidermal or dermal extracts. Monoclonal antibodies of strict specificity for human IgG subclasses were used. Sera from 20 patients with BP served as controls. In addition, total IgG subclass levels were determined by indirect competitive ELISA in all sera. Complement binding capacity was studied by IIF using antibodies to C3 after incubation of skin section with autoantibodies and source of fresh complement. CP autoantibodies reacting with the 230-240 kD and/or the 180-kD epidermal bands showed an IgG4/IgG1 subclass restriction, with a predominance of IgG4 in 10 cases, of IgG1 in four. In BP sera, IgG4 and IgG1 autoantibodies were detected with a similar frequency (100% and 83%, respectively). In EBA sera, autoantibodies reacting with the 290 kD and 145 kD dermal bands also showed an IgG1/IgG4 restriction. Concordant results were obtained by IIF. However, the IIF method had a lower sensitivity for the detection of IgG4 CP antibodies and IgG1 EBA antibodies than immunoblotting. Finally, when CP antibodies were analyzed for their complement-binding activity, it was found that sera containing IgG4 autoantibodies alone never fixed complement whereas all complement-fixing CP sera had IgG1 autoantibodies, suggesting that only this subclass of antibodies is capable of fixing complement.

  20. Anti-food and anti-microbial IgG subclass antibodies in inflammatory bowel disease.

    Science.gov (United States)

    Jansen, Anke; Mandić, Ana D; Bennek, Eveline; Frehn, Lisa; Verdier, Julien; Tebrügge, Irene; Lutz, Holger; Streetz, Konrad; Trautwein, Christian; Sellge, Gernot

    2016-12-01

    Inflammatory bowel disease (IBD), particularly Crohn's disease (CD), is associated with increased microbial-specific IgG and IgA antibodies, whereas alterations of anti-food antibodies are still disputed. The knowledge about IgG subclass antibodies in IBD is limited. In this study we analysed IgG subclass antibodies specific for nutritional and commensal antigens in IBD patients and controls. Serum IgG1, IgG2, IgG3 and IgG4 specific for wheat and milk extracts, purified ovalbumin, Escherichia coli and Bacteroides fragilis lysates and mannan from Saccharomyces cerevisiae were analysed by ELISA in patients with CD (n = 56), ulcerative colitis (UC; n = 29), acute gastroenteritis/colitis (n = 12) as well as non-inflammatory controls (n = 62). Anti-Saccharomyces cerevisiae antibodies (ASCA) of all IgG subclasses and anti-B. fragilis IgG1 levels were increased in CD patients compared to UC patients and controls. The discriminant validity of ASCA IgG2 and IgG4 was comparable with that of ASCA pan-IgG and IgA, whereas it was inferior for ASCA IgG1/IgG3 and anti-B. fragilis IgG1. Complicated CD defined by the presence of perianal, stricturing or penetrating disease phenotypes was associated with increased ASCA IgG1/IgG3/IgG4, anti-B. fragilis IgG1 and anti-E. coli IgG1 levels. Anti-food IgG subclass levels were not different between IBD patients and controls and did not correlate with food intolerance. In contrast to anti-microbial Abs, food-specific IgG responses were predominately of the IgG4 isotype and all food-specific IgG subclass levels correlated negatively with age. Our study supports the notion that the adaptive immune recognition of food and commensal antigens are differentially regulated.

  1. Comparison and Characterization of Immunoglobulin G Subclasses among Primate Species

    OpenAIRE

    Shearer, Michael H.; Dark, Robyn D.; Chodosh, James; Kennedy, Ronald C.

    1999-01-01

    Little information is available on the immunoglobulin G (IgG) subclasses expressed in the sera of nonhuman primate species. To address this issue, we compared the IgG subclasses found in humans (IgG1, IgG2, IgG3, and IgG4) to those of nonhuman primates, such as baboons and macaques. Cross-reactive antihuman IgG subtype-specific reagents were identified and used to analyze purified IgG from sera by solid-phase enzyme-linked immunosorbent assay. Protein A-purified human ...

  2. Effects of pregnancy and intensity of Plasmodium falciparum transmission on immunoglobulin G subclass responses to variant surface antigens

    DEFF Research Database (Denmark)

    Megnekou, Rosette; Staalsoe, Trine; Taylor, Diane W

    2005-01-01

    , the levels of VSA(PAM)-specific antibodies either were very low or negative or were very high, whereas the levels of the antibodies specific for non-PAM type VSA were uniformly high. Interestingly, the levels of VSA(PAM)-specific IgG1 increased with increasing gestational age, while the levels...... status, parity, gestational age, and parasite transmission intensity, whereas only the parasite transmission intensity influenced the levels of IgG specific for non-PAM type VSA. For both types of VSA, the responses were dominated by the cytophilic subclass IgG1, followed by IgG3. In pregnant women...

  3. Anion exchange chromatographic distribution of human monoclonal immunoglobulin G is determined by heavy chain subclass and level of sialic acid expression

    Directory of Open Access Journals (Sweden)

    Ilić Vesna

    2012-01-01

    Full Text Available Anion exchange chromatography is widely accepted method for purification of immunoglobulins. In this work, we used human monoclonal immunoglobulin G (IgG with structure and solubility of normal human IgG as a model for studying chromatographic behavior of particular molecular forms of IgG. Human sera with monoclonal IgG were fractionated on strong anion exchanger, Q Sepharose Fast Flow. With 20 mM Tris pH 7.5 as a start buffer, 42% of human monoclonal IgG passed through column, and 58% of them remained adsorbed. Bound monoclonal IgG were eluted from the exchanger by linear increasing of concentration of NaCl from 0 to 0.5 M. Chromatographic distribution of human monoclonal IgG correlated with their electrophoretic mobility in agarose gels, and it was dependent on γ heavy chain isotype. Light chain type, as well as serum concentration of monoclonal IgG did not influence their chromatographic behavior. The level of heavy chain sialic acid expression, but not of galactose and N-acetylglucosamine, significantly determined chromatographic distribution of serum monoclonal IgG. Additionally to the information on the chromatographic behavior of human monoclonal IgG, we believe that presented data could provide useful information about the possible use of Q Sepharose Fast Flow matrix for the isolation of specific molecular forms of human IgG.

  4. Retinal vasculitis revealing immunoglobulin G subclass deficiency.

    Science.gov (United States)

    Hassani, Rachid Tahiri Joutei; Rousseau, Antoine; de Monchy, Ivan; el Sanharawi, Mohamed; Gendron, Gael; Barreau, Emmanuel; Goujard, Cécile; Labetoulle, Marc

    2013-01-01

    Immunoglobulin G (IgG) subclass deficiency is a rare primary immunodeficiency syndrome characterized by recurrent infections and autoimmune disorders. However, there have been no reports of ocular involvement, either inflammatory or infectious, in association with IgG subclass deficiency. The authors report the first case of retinal vasculitis that led to the diagnosis of IgG subclass deficiency, in a patient with a history of inflammatory bowel disease and recurrent infections of previously unknown origin.

  5. Lipoprotein subclasses in genetic studies: The Berkeley Data Set

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.; Williams, P.T.; Blanche, P.J.; Cavanaugh, A.; Holl, L.G. [Lawrence Berkeley Lab., CA (United States); Austin, M.A. [Washington Univ., Seattle, WA (United States). Dept. of Epidemiology

    1992-10-01

    Data from the Berkeley Data Set was used to investigate familial correlations of HDL-subclasses. Analysis of the sibling intraclass correlation coefficient by HDL particle diameter showed that sibling HDL levels were significantly correlated for HDL{sub 2b}, HDL{sub 3a} and HDL{sub 3b} subclasses. The percentage of the offsprings` variance explained by their two parents. Our finding that parents and offspring-have the highest correlation for HDL{sub 2b} is consistent with published reports that show higher heritability estimates for HDL{sub 2} compared with HDL{sub 3}{minus} cholesterol.

  6. Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass.

    Science.gov (United States)

    Teichert, Russell W; Memon, Tosifa; Aman, Joseph W; Olivera, Baldomero M

    2014-02-11

    Change is intrinsic to nervous systems; change is required for learning and conditioning and occurs with disease progression, normal development, and aging. To better understand mammalian nervous systems and effectively treat nervous-system disorders, it is essential to track changes in relevant individual neurons. A critical challenge is to identify and characterize the specific cell types involved and the molecular-level changes that occur in each. Using an experimental strategy called constellation pharmacology, we demonstrate that we can define a specific somatosensory neuronal subclass, cold thermosensors, across different species and track changes in these neurons as a function of development. Cold thermosensors are uniformly responsive to menthol and innocuous cool temperature (17 °C), indicating that they express TRPM8 channels. A subset of cold thermosensors expressed α7 nicotinic acetylcholine receptors (nAChRs) but not other nAChR subtypes. Differences in temperature threshold of cold thermosensors correlated with functional expression of voltage-gated K channels Kv1.1/1.2: Relatively higher expression of KV1.1/1.2 channels resulted in a higher threshold response to cold temperature. Other signaling components varied during development and between species. In cold thermosensors of neonatal mice and rats, ATP receptors were functionally expressed, but the expression disappeared with development. This developmental change occurred earlier in low-threshold than high-threshold cold thermosensors. Most rat cold thermosensors expressed TRPA1 channels, whereas mouse cold thermosensors did not. The broad implications of this study are that it is now feasible to track changes in receptor and ion-channel expression in individual neuronal subclasses as a function of development, learning, disease, or aging.

  7. VHDL Specification Methodology from High-level Specification

    OpenAIRE

    Benmohammed, M.; S. Merniz

    2005-01-01

    Design complexity has been increasing exponentially this last decade. In order to cope with such an increase and to keep up designers' productivity, higher level specifications were required. Moreover new synthesis systems, starting with a high level specification, have been developed in order to automate and speed up processor design. This study presents a VHDL specification methodology aimed to extend structured design methodologies to the behavioral level. The goal is t...

  8. IgG subclasses in previously healthy adult patients with acute ...

    African Journals Online (AJOL)

    has been known for more than 20 years that certain patients with IgG subclass deficiencies may develop recurrent respiratory tract infections, including pneumonia.I...; However, there are few studies of IgG subclass levels in previously healthy adult patients with acute community-acquired pneumonia,~ particularly of patients ...

  9. Separability-Oriented Subclass Discriminant Analysis.

    Science.gov (United States)

    Wan, Huan; Wang, Hui; Guo, Gongde; Wei, Xin

    2018-02-01

    Linear discriminant analysis (LDA) is a classical method for discriminative dimensionality reduction. The original LDA may degrade in its performance for non-Gaussian data, and may be unable to extract sufficient features to satisfactorily explain the data when the number of classes is small. Two prominent extensions to address these problems are subclass discriminant analysis (SDA) and mixture subclass discriminant analysis (MSDA). They divide every class into subclasses and re-define the within-class and between-class scatter matrices on the basis of subclass. In this paper we study the issue of how to obtain subclasses more effectively in order to achieve higher class separation. We observe that there is significant overlap between models of the subclasses, which we hypothesise is undesirable. In order to reduce their overlap we propose an extension of LDA, separability oriented subclass discriminant analysis (SSDA), which employs hierarchical clustering to divide a class into subclasses using a separability oriented criterion, before applying LDA optimisation using re-defined scatter matrices. Extensive experiments have shown that SSDA has better performance than LDA, SDA and MSDA in most cases. Additional experiments have further shown that SSDA can project data into LDA space that has higher class separation than LDA, SDA and MSDA in most cases.

  10. Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

    DEFF Research Database (Denmark)

    Olesen, Cathrine Holm; Brahimi, Karima; Vandahl, Brian

    2010-01-01

    then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. METHODS: Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P...

  11. Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome.

    Science.gov (United States)

    Löbel, Madlen; Mooslechner, Agnes Anna; Bauer, Sandra; Günther, Sabrina; Letsch, Anne; Hanitsch, Leif G; Grabowski, Patricia; Meisel, Christian; Volk, Hans-Dieter; Scheibenbogen, Carmen

    2015-08-14

    Chronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients suffer from sustained exhaustion, cognitive impairment and an increased sensitivity to pain and sensory stimuli. A subset of patients has frequent respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous system and an association with genetic variations in the catechol-O-methyltransferase (COMT) and glucocorticoid receptor genes influencing sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed the prevalence of SNPs of COMT and glucocorticoid receptor-associated genes in CFS patients and correlated them to immunoglobulin levels and susceptibility to RRTI. We analyzed blood cells of 74 CFS patients and 76 healthy controls for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum immunoglobulins were determined by immunoturbidimetric technique, cortisol levels by ECLIA. Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced cortisol levels providing evidence for its functional relevance. Both enhanced IgE and diminished IgG3 levels and an increased susceptibility to RRTI were observed in CFS patients with the Met/Met variant. Such an association was not observed in 68 non-CFS patients with RRTI. Our results indicate a relationship of COMT polymorphism rs4680 with immune dysregulation in CFS providing a potential link for the association between stress and infection susceptibility in CFS.

  12. The N-Glycosylation of Mouse Immunoglobulin G (IgG)-Fragment Crystallizable Differs Between IgG Subclasses and Strains.

    Science.gov (United States)

    de Haan, Noortje; Reiding, Karli R; Krištić, Jasminka; Hipgrave Ederveen, Agnes L; Lauc, Gordan; Wuhrer, Manfred

    2017-01-01

    N-linked glycosylation of the fragment crystallizable (Fc)-region of immunoglobulin G (IgG) is known to have a large influence on the activity of the antibody, an effect reported to be IgG subclass specific. This situation applies both to humans and mice. The mouse is often used as experimental animal model to study the effects of Fc-glycosylation on IgG effector functions, and results are not uncommonly translated back to the human situation. However, while human IgG Fc-glycosylation has been extensively characterized in both health and disease, this is not the case for mice. To characterize the glycosylation profile of murine IgG-Fc and in addition evaluate the systematic glycosylation differences between mouse strains, sexes, and IgG subclasses, we used nanoliquid chromatography mass spectrometry (nanoLC-MS(/MS)) to look at the subclass-specific IgG Fc-glycopeptides of male and female mice from the strains BALB/c, C57BL/6, CD-1, and Swiss Webster. The structural analysis revealed the presence of predominantly fucosylated, diantennary glycans, with varying amounts of galactosylation and α2,6-sialylation. In addition, we report glycosylation features not previously reported in an Fc-specific way on murine IgG, including monoantennary, hybrid, and high mannose structures, as well as diantennary structures without a core fucose, with a bisecting N-acetylglucosamine, or with α1,3-galactosylation. Pronounced differences were detected between strains and the IgG subclasses within each strain. Especially the large spread in galactosylation and sialylation levels found between both strains and subclasses may vastly influence IgG effector functions. Mouse strain-based and subclass-specific glycosylation differences should be taken into account when designing and interpreting immunological and glycobiological mouse studies involving IgG effector functions.

  13. The N-Glycosylation of Mouse Immunoglobulin G (IgG-Fragment Crystallizable Differs Between IgG Subclasses and Strains

    Directory of Open Access Journals (Sweden)

    Noortje de Haan

    2017-05-01

    Full Text Available N-linked glycosylation of the fragment crystallizable (Fc-region of immunoglobulin G (IgG is known to have a large influence on the activity of the antibody, an effect reported to be IgG subclass specific. This situation applies both to humans and mice. The mouse is often used as experimental animal model to study the effects of Fc-glycosylation on IgG effector functions, and results are not uncommonly translated back to the human situation. However, while human IgG Fc-glycosylation has been extensively characterized in both health and disease, this is not the case for mice. To characterize the glycosylation profile of murine IgG-Fc and in addition evaluate the systematic glycosylation differences between mouse strains, sexes, and IgG subclasses, we used nanoliquid chromatography mass spectrometry (nanoLC-MS(/MS to look at the subclass-specific IgG Fc-glycopeptides of male and female mice from the strains BALB/c, C57BL/6, CD-1, and Swiss Webster. The structural analysis revealed the presence of predominantly fucosylated, diantennary glycans, with varying amounts of galactosylation and α2,6-sialylation. In addition, we report glycosylation features not previously reported in an Fc-specific way on murine IgG, including monoantennary, hybrid, and high mannose structures, as well as diantennary structures without a core fucose, with a bisecting N-acetylglucosamine, or with α1,3-galactosylation. Pronounced differences were detected between strains and the IgG subclasses within each strain. Especially the large spread in galactosylation and sialylation levels found between both strains and subclasses may vastly influence IgG effector functions. Mouse strain-based and subclass-specific glycosylation differences should be taken into account when designing and interpreting immunological and glycobiological mouse studies involving IgG effector functions.

  14. Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Freeman, Jane A; Crassini, Kyle R; Best, O Giles; Forsyth, Cecily J; Mackinlay, Naomi J; Han, Ping; Stevenson, William; Mulligan, Stephen P

    2013-01-01

    Hypogammaglobulinemia is a common complication of chronic lymphocytic leukemia (CLL), but the significance of immunoglobulin G (IgG) subclass deficiency is unknown. We analyzed the prevalence of immunoglobulins G, A and M, IgG subclass deficiency and infection in 150 patients with CLL. Low IgG, IgA and IgM levels were observed in 27.3%, 30.7% and 56.7% of patients, respectively. IgG subclass deficiency was frequent, with reduced IgG1, IgG2, IgG3 and IgG4 in 28%, 19.3%, 52% and 22.7% of patients, respectively. IgG subclass deficiency (total 64.6%) and hypogammaglobulinemia (27.3%) were more prevalent than clinically significant infection (16%). Recurrent or significant infections were seen in 24 patients (16%), of whom 50% had hypogammaglobulinemia but 100% had at least one IgG subclass deficiency, indicating that half the patients with infection had IgG subclass deficiency but normal total IgG level. Deficiencies of IgG3 and IgG4 were statistically associated with infection risk. Normal immunoglobulin and IgG subclass levels were seen in 26 patients (17%) and none had infections. IgG subclass deficiency is commonly observed in patients with CLL with both normal and reduced total IgG levels, and is associated with infection. Screening patients with CLL for IgG subclass deficiency may be a useful adjunct in stratifying their infection risk.

  15. Characterization of two neuronal subclasses through constellation pharmacology.

    Science.gov (United States)

    Teichert, Russell W; Raghuraman, Shrinivasan; Memon, Tosifa; Cox, Jeffrey L; Foulkes, Tucker; Rivier, Jean E; Olivera, Baldomero M

    2012-07-31

    Different types of neurons diverge in function because they express their own unique set or constellation of signaling molecules, including receptors and ion channels that work in concert. We describe an approach to identify functionally divergent neurons within a large, heterogeneous neuronal population while simultaneously investigating specific isoforms of signaling molecules expressed in each. In this study we characterized two subclasses of menthol-sensitive neurons from cultures of dissociated mouse dorsal-root ganglia. Although these neurons represent a small fraction of the dorsal-root ganglia neuronal population, we were able to identify them and investigate the cell-specific constellations of ion channels and receptors functionally expressed in each subclass, using a panel of selective pharmacological tools. Differences were found in the functional expression of ATP receptors, TRPA1 channels, voltage-gated calcium-, potassium-, and sodium channels, and responses to physiologically relevant cold temperatures. Furthermore, the cell-specific responses to various stimuli could be altered through pharmacological interventions targeted to the cell-specific constellation of ion channels expressed in each menthol-sensitive subclass. In fact, the normal responses to cold temperature could be reversed in the two neuronal subclasses by the coapplication of the appropriate combination of pharmacological agents. This result suggests that the functionally integrated constellation of signaling molecules in a particular type of cell is a more appropriate target for effective pharmacological intervention than a single signaling molecule. This shift from molecular to cellular targets has important implications for basic research and drug discovery. We refer to this paradigm as "constellation pharmacology."

  16. Formal specification level concepts, methods, and algorithms

    CERN Document Server

    Soeken, Mathias

    2015-01-01

    This book introduces a new level of abstraction that closes the gap between the textual specification of embedded systems and the executable model at the Electronic System Level (ESL). Readers will be enabled to operate at this new, Formal Specification Level (FSL), using models which not only allow significant verification tasks in this early stage of the design flow, but also can be extracted semi-automatically from the textual specification in an interactive manner.  The authors explain how to use these verification tasks to check conceptual properties, e.g. whether requirements are in conflict, as well as dynamic behavior, in terms of execution traces. • Serves as a single-source reference to a new level of abstraction for embedded systems, known as the Formal Specification Level (FSL); • Provides a variety of use cases which can be adapted to readers’ specific design flows; • Includes a comprehensive illustration of Natural Language Processing (NLP) techniques, along with examples of how to i...

  17. Evaluation of cysticercus-specific IgG (total and subclasses and IgE antibody responses in cerebrospinal fluid samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies Avaliação das respostas de anticorpos anti-cisticercos IgG (total e subclasses e IgE em amostras de líquido cefalorraquidiano de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG

    Directory of Open Access Journals (Sweden)

    Lisandra Akemi Suzuki

    2013-01-01

    Full Text Available In the present study, an enzyme-linked immunosorbent assay (ELISA standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses and IgE antibodies in cerebrospinal fluid (CSF samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA=1.17 and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49 and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46 and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12 and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85 and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60 and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.No presente estudo, uma reação imunoenzimática (ELISA padronizada com o fluido vesicular de cisticercos de Taenia solium foi utilizada para avaliar as respostas de anticorpos anti-cisticercos IgG (total e subclasses e IgE em amostras de líquido cefalorraquidiano (LCR de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG e pacientes com outras desordens neurológicas. Os seguintes resultados foram obtidos: ELISA-IgG: 100% de sensibilidade (mediana das absorbâncias das reações ELISA (MAE=1,17 e especificidade 100%; ELISA-IgG1: sensibilidade 72,7% (MAE=0,49 e especificidade 100%; ELISA-IgG2

  18. Clinical significance of serum immunoglobulin G subclass deficiency in patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Svensson, Tobias; Höglund, Martin; Cherif, Honar

    2013-07-01

    Patients with chronic lymphocytic leukemia (CLL) and hypogammaglobulinemia who suffer from recurrent infections can be offered prophylactic intravenous immunoglobulin (Ig) substitution. Our aim was to assess the prevalence of pure IgG subclass deficiency (with normal Ig levels), its correlation to risk of infection, and the clinical value of routine measurement of serum IgG subclass levels in patients with CLL. Serum levels of Ig and IgG subclasses were determined in patients with CLL at Uppsala University Hospital. Clinical data were collected through patient records and questionnaires. Hypogammaglobulinemia occurred in 52.3% out of 111 patients. These patients did not have a higher annual risk of infection than patients without hypogammaglobulinemia (79.5% vs 79.1%, p = 0.706 for all infections; 13.4% vs 11.2%, p = 0.394 for severe infection; and 1.7% vs 3.4%, p = 0.083 for sepsis). Pure subclass deficiency was uncommon and occurred in 6 patients (5.4%). The annual overall risk of infection, of severe infection, and of sepsis for these patients did not differ as compared to patients with no hypogammaglobulinemia and no subclass deficiency (70.8% vs 80.7%, p = 0.334; 11.8% vs 11.1%, p = 0.497; and 8.9% vs 2.3%, p = 0.067, respectively). Pure IgG subclass deficiency is rare in patients with CLL. In this heterogeneous cohort of patients, neither hypogammaglobulinemia nor pure IgG subclass deficiency were significant risk factors for infectious complications. Measurement of serum levels of Ig may be justified in patients with recurrent severe infections, but routine analysis of IgG subclass levels in patients with CLL is probably not warranted.

  19. The Clinical Utility of Measuring IgG Subclass Immunoglobulins During Immunological Investigation for Suspected Primary Antibody Deficiencies.

    Science.gov (United States)

    Parker, Antony R; Skold, Markus; Ramsden, David B; Ocejo-Vinyals, J Gonzalo; López-Hoyos, Marcos; Harding, Stephen

    2017-11-08

    Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is clinically important when total IgG is within the normal age-specific reference range. The measurement is useful for diagnosis of IgG subclass deficiency, to aid the diagnosis of specific antibody deficiency, as a supporting test for the diagnosis of common variable immunodeficiency, as well as for risk stratification of patients with low IgA. The measurement of IgG subclasses may also help determine a revaccination strategy for patients and support patient management. In certain circumstances, the measurement of IgG subclasses may be used to monitor a patient's humoral immune system. In this review, we discuss the utility of measuring IgG subclass concentrations. © The Author 2017. Published by Oxford University Press on behalf of American Society for Clinical Pathology.

  20. The DAL10 gene from Norway spruce (Picea abies) belongs to a potentially gymnosperm-specific subclass of MADS-box genes and is specifically active in seed cones and pollen cones.

    Science.gov (United States)

    Carlsbecker, Annelie; Sundström, Jens; Tandre, Karolina; Englund, Marie; Kvarnheden, Anders; Johanson, Urban; Engström, Peter

    2003-01-01

    Transcription factors encoded by different members of the MADS-box gene family have evolved central roles in the regulation of reproductive organ development in the flowering plants, the angiosperms. Development of the stamens and carpels, the pollen- and seed-bearing organs, involves the B- and C-organ-identity MADS-box genes. B- and C-type gene orthologs with activities specifically in developing pollen- and seed-bearing organs are also present in the distantly related gymnosperms: the conifers and the gnetophytes. We now report on the characterization of DAL10, a novel MADS-box gene from the conifer Norway spruce, which unlike the B- and C-type conifer genes shows no distinct orthology relationship to any angiosperm gene or clade in phylogenetic analyses. Like the B- and C-type genes, it is active specifically in developing pollen cones and seed cones. In situ RNA localization experiments show DAL10 to be expressed in the cone axis, which carry the microsporophylls of the young pollen cone. In contrast, in the seed cone it is expressed both in the cone axis and in the bracts, which subtend the ovuliferous scales. Expression data and the phenotype of transgenic Arabidopsis plants expressing DAL10 suggest that the gene may act upstream to or in concert with the B- and C-type genes in the establishment of reproductive identity of developing cones.

  1. Clinical and laboratory evaluation of periodically monitored Turkish children with IgG subclass deficiencies.

    Science.gov (United States)

    Karaca, Neslihan Edeer; Karadeniz, Cem; Aksu, Guzide; Kutukculer, Necil

    2009-03-01

    IgG subclass deficiencies are common immune system disorders during childhood. The aim of this retrospective study was to review clinical findings and laboratory results of patients with IgG subclass deficiencies in order to determine the changes in serum IgG subclass levels during follow-up, the percentage and time span until normalization of the IgG subclass levels to age-corresponding normal levels, the type of infections incurred and the benefits of prophylaxis. Among the 59 pediatric patients reviewed, the most frequent defect was an IgG3 subclass deficiency (77%). Nine percent of the patients had an isolated IgG2 deficiency and 14% had an IgG2+G3 deficiency. The most common clinical presentations were recurrent upper respiratory tract infections, followed by pneumonia, acute gastroenteritis and urinary tract infections. Atopy was present in 15% of the patients. Ninety percent of the patients were given a prophylactic treatment (benzathine penicillin, oral antibiotics, oral bacterial lysate or intravenous immunoglobulin). The frequency of recurrent infections decreased from 13.4 +/- 7.4 per year to 5.7 +/- 3.9 in patients receiving a prophylactic regimen. Serum IgG subclass levels reached normal ranges in 30% of the patients in the IgG3 deficiency group and in 35.7% of the patients in the IgG2+G3 deficiency group. Patients with an isolated IgG2 deficiency did not reach age-related normal levels during the study period. Our study shows that IgG subclass levels may normalize in 30 to 40% of patients at about 6 years of age. We emphasize the need of monitoring IgG levels together with the clinical symptomatology in affected individuals and initiate preventive measures when appropriate.

  2. On Certain Subclasses of Analytic Functions Defined by Differential Subordination

    Directory of Open Access Journals (Sweden)

    Hesam Mahzoon

    2011-01-01

    Full Text Available We introduce and study certain subclasses of analytic functions which are defined by differential subordination. Coefficient inequalities, some properties of neighborhoods, distortion and covering theorems, radius of starlikeness, and convexity for these subclasses are given.

  3. The relationship between high density lipoprotein subclass profile and plasma lipids concentrations

    Directory of Open Access Journals (Sweden)

    Tian Li

    2010-10-01

    Full Text Available Abstract HDL particles posses multiple antiatherogenic activities and the identification and differentiation of individual HDL subclasses may be useful in documentation and understanding of metabolic changes of different HDL subclasses. The major plasma lipids exist and are transported in the form of lipoprotein complexes. Hence, alterations in plasma lipids levels can interfere with the composition, content, and distribution of plasma lipoprotein subclasses that affect atherosclerosis risk. The research review major discussed the relationship between plasma lipids levels and HDL subclasses distribution. The general shift toward smaller size of HDL particle size in HTG, HCL and MHL subjects, and the changes were more prominent with the elevation of TG and TC levels which imply that HDL maturation might be abnormal and RCT pathway might be weaken, and these changes were more seriously in MHL subjects. Plasma contents of small sized HDL particles significantly higher, whereas those of large sized HDL particles were significantly lower with elevation of TG/HDL-C and TC/HDL-C ratios. Increased in the TC/HDL-C ratio alone did not influence the distributions of HDL subclasses significantly when the TG/HDL-C ratio was low (TG/HDL-C ≤ 2.5. Hence, the TG/HDL-C ratio might be more sensitive to reflect the alteration of HDL subclass distribution than the TC/HDL-C ratio. In LDL-C/HDL-C ≤ 2.3 group, the pattern of distribution in HDL subclass was in agreement with the normolipidemic subjects. Moreover, considering the relative ease of measuring TC/HDL-C, TG/HDL-C and LDL-C/HDL-C ratios, as opposed to measuring HDL subclasses, these 3 ratios together may be a good indicator of HDL subclass distribution. The protective effect of increased apoA-I levels against the reduction of HDL2b caused by elevated TG concentration. On one hand, plasma HDL-C and apoA-I appear to play a coordinated role in the assembly of HDL particles and the determination of their

  4. IgG subclass deficiencies in children: Facts and fiction.

    Science.gov (United States)

    Wahn, Volker; von Bernuth, Horst

    2017-09-01

    The chance to analyse the four IgG subclasses arose with the publication of Terry and Fahey(1) . Since then, a lot of new information on the role of subclasses and their deficiency states in humans has been obtained. This review tries to analyse critically our current knowledge of subclass deficiencies in children. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  5. Molecular characterization and expression analysis of three subclasses of IgT in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Zhang, Nu; Zhang, Xu-Jie; Chen, Dan-Dan; Oriol Sunyer, J; Zhang, Yong-An

    2017-05-01

    As the teleost specific immunoglobulin, IgT plays important roles in systemic and mucosal immunity. In the current study, in rainbow trout, we have cloned the heavy chain (Igτ) genes of a secretory form of IgT2 as well as the membrane and secretory forms of a third IgT subclass, termed IgT3. Conserved cysteine and tryptophan residues that are crucial for the folding of the immunoglobulin domain as well as hydrophobic and hydrophilic residues within CART motif were identified in all IgT subclasses. Through analysis of the rainbow trout genome assembly, Igτ3 gene was found localized upstream of Igτ1 gene, while Igτ2 gene situated on another scaffold. At the transcriptional level, Igτ1 was mainly expressed in both systemic and mucosal lymphoid tissues, while Igτ2 was largely expressed in systemic lymphoid organs. After LPS and poly (I:C) treatment, Igτ1 and Igτ2 genes exhibited different expression profiles. Interestingly the transcriptional level of Igτ3 was negligible, although its protein product could be identified in trout serum. Importantly, a previously reported monoclonal antibody directed against trout IgT1 was able to recognize IgT2 and IgT3. These data demonstrate that there exist three subclasses of IgT in rainbow trout, and that their heavy chain genes display different expression patterns during stimulation. Overall, our data reflect the diversity and complexity of immunoglobulin in trout, thus provide a better understanding of the IgT system in the immune response of teleost fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Coefficient estimates for certain subclass of bi-univalent functions

    Science.gov (United States)

    Omar, Rashidah; Halim, Suzeini Abdul; Janteng, Aini

    2017-08-01

    In this paper, a subclass of bi-univalent functions is introduced using subordination. Estimates on the initial coefficients and the Fekete-Szegö inequality are determined for functions in this subclass. The results would generalize the previous related works of several earlier authors.

  7. IgG subclasses determine pathways of anaphylaxis in mice.

    Science.gov (United States)

    Beutier, Héloïse; Gillis, Caitlin M; Iannascoli, Bruno; Godon, Ophélie; England, Patrick; Sibilano, Riccardo; Reber, Laurent L; Galli, Stephen J; Cragg, Mark S; Van Rooijen, Nico; Mancardi, David A; Bruhns, Pierre; Jönsson, Friederike

    2017-01-01

    Animal models have demonstrated that allergen-specific IgG confers sensitivity to systemic anaphylaxis that relies on IgG Fc receptors (FcγRs). Mouse IgG2a and IgG2b bind activating FcγRI, FcγRIII, and FcγRIV and inhibitory FcγRIIB; mouse IgG1 binds only FcγRIII and FcγRIIB. Although these interactions are of strikingly different affinities, these 3 IgG subclasses have been shown to enable induction of systemic anaphylaxis. We sought to determine which pathways control the induction of IgG1-, IgG2a-, and IgG2b-dependent passive systemic anaphylaxis. Mice were sensitized with IgG1, IgG2a, or IgG2b anti-trinitrophenyl mAbs and challenged with trinitrophenyl-BSA intravenously to induce systemic anaphylaxis that was monitored by using rectal temperature. Anaphylaxis was evaluated in mice deficient for FcγRs injected with mediator antagonists or in which basophils, monocytes/macrophages, or neutrophils had been depleted. FcγR expression was evaluated on these cells before and after anaphylaxis. Activating FcγRIII is the receptor primarily responsible for all 3 models of anaphylaxis, and subsequent downregulation of this receptor was observed. These models differentially relied on histamine release and the contribution of mast cells, basophils, macrophages, and neutrophils. Strikingly, basophil contribution and histamine predominance in mice with IgG1- and IgG2b-induced anaphylaxis correlated with the ability of inhibitory FcγRIIB to negatively regulate these models of anaphylaxis. We propose that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier

  8. Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in type 1 diabetes.

    Science.gov (United States)

    Zhang, Ying; Jenkins, Alicia J; Basu, Arpita; Stoner, Julie A; Lopes-Virella, Maria F; Klein, Richard L; Lyons, Timothy J

    2016-02-01

    Our objective is to define differences in circulating lipoprotein subclasses between intensive versus conventional management of type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). NMR-determined lipoprotein subclass profiles (NMR-LSPs), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of 5 years (interquartile range: 4-6 years) of randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSPs between treatment groups. Standard total, LDL, and HDL cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSPs showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, P = 0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, P = 0.007), total IDL/LDL (mean: 1,000 vs. 1,053 nmol/l, P = 0.01), and small HDL (mean: 17.3 vs. 18.6 μmol/l, P intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications.

  9. A case of IgG subclass deficiency with the initial presentation of transient hypogammaimmuno-globulinemia of infancy and a review of IgG subclass deficiencies.

    Science.gov (United States)

    Nettagul, R; Visitsunthorn, N; Vichyanond, P

    2003-07-01

    Primary immunodeficiency diseases are not common in children. The possibility of an immunological defect should be considered in any individual with repeated infections. A definite diagnosis for immodeficiency is sometimes difficult to achieve because of overlapping clinical manifestations. Immunoglobulin subclass deficiency is an immunological deficiency disease with which, one or more IgG subclasses are deficient. T cell immunity is normal. Patients may develop recurrent bacterial and respiratory infections or could remain asymptomatic. The authors report a case of immunoglobulin G subclass deficiency presenting initially as transient hypogammaglobulinemia of infancy. A 2 month-old boy presented to Siriraj Hospital with a history of chronic protracted diarrhea, disseminated scabies and sepsis. On presentation, he had generalized scaly and maculopapular rash with no palpable lymph nodes. CBC revealed WBC 22,100 cells/cm3 with PMN 42 per cent, lymphocytes 38 per cent, Eosinophils 4 per cent, Basophil 2 per cent and platelets 254,000/cm3. The immunoglobulin levels were as follows: IgG 181 mg/dl, IgA IgG became normal at 2 years of age (after 12 months of IVIG). IVIG was stopped and the diagnosis was changed to transient hypogammaglobulinemia of infancy (THI). Nevertheless, during his 4 month follow-up he developed recurrent sinopulmonary infections (i.e, otitis media and pneumonia). Repeated immunoglobulin profile showed IgG 1,200 mg/dl, IgA 135 mg/dl, IgM 26 mg/dl, IgG subclass were IgG, 1,030 mg/dl (N 280-830), IgG2 30 mg/dl (N 40-2,400), IgG3 22 mg/dl (N 6-130), IgG4 3 mg/dl (N 3-120). A diagnosis of IgG2 subclass deficiency presenting early as transient hypogammaglobulinemia of infancy was then made. Treatment with monthly IVIG was reinitiated and the patient is currently doing well. The authors present a case of IgG subclass deficiency presenting as transient hypogammaglbulinemia of infancy. Follow-up of the immune profile and clinical manifestation is

  10. Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response to HIV gp140 Vaccination

    Directory of Open Access Journals (Sweden)

    Sven Kratochvil

    2017-12-01

    Full Text Available Antibody subclasses exhibit extensive polymorphisms (allotypes that could potentially impact the quality of HIV-vaccine induced B cell responses. Allotypes of immunoglobulin (Ig G1, the most abundant serum antibody, have been shown to display altered functional properties in regard to serum half-life, Fc-receptor binding and FcRn-mediated mucosal transcytosis. To investigate the potential link between allotypic IgG1-variants and vaccine-generated humoral responses in a cohort of 14 HIV vaccine recipients, we developed a novel protocol for rapid IgG1-allotyping. We combined PCR and ELISA assays in a dual approach to determine the IgG1 allotype identity (G1m3 and/or G1m1 of trial participants, using human plasma and RNA isolated from PBMC. The IgG1-allotype distribution of our participants mirrored previously reported results for caucasoid populations. We observed elevated levels of HIV gp140-specific IgG1 and decreased IgG2 levels associated with the G1m1-allele, in contrast to G1m3 carriers. These data suggest that vaccinees homozygous for G1m1 are predisposed to develop elevated Ag-specific IgG1:IgG2 ratios compared to G1m3-carriers. This elevated IgG1:IgG2 ratio was further associated with higher FcγR-dimer engagement, a surrogate for potential antibody-dependent cellular cytotoxicity (ADCC and antibody-dependent cellular phagocytosis (ADCP function. Although preliminary, these results suggest that IgG1 allotype may have a significant impact on IgG subclass distribution in response to vaccination and associated Fc-mediated effector functions. These results have important implications for ongoing HIV vaccine efficacy studies predicated on engagement of FcγR-mediated cellular functions including ADCC and ADCP, and warrant further investigation. Our novel allotyping protocol provides new tools to determine the potential impact of IgG1 allotypes on vaccine efficacy.

  11. Frequent IgG subclass and mannose binding lectin deficiency in patients with chronic fatigue syndrome.

    Science.gov (United States)

    Guenther, Sabrina; Loebel, Madlen; Mooslechner, Agnes A; Knops, Michael; Hanitsch, Leif G; Grabowski, Patricia; Wittke, Kirsten; Meisel, Christian; Unterwalder, Nadine; Volk, Hans-Dieter; Scheibenbogen, Carmen

    2015-10-01

    Chronic fatigue syndrome (CFS) is a severe disease characterized by various symptoms of immune dysfunction. CFS onset is typically with an infection and many patients suffer from frequently recurrent viral or bacterial infections. Immunoglobulin and mannose binding lectin (MBL) deficiency are frequent causes for increased susceptibility to infections. In this study we retrospectively analysed 300 patients with CFS for immunoglobulin and MBL levels, and B-cell subset frequencies. 25% of the CFS patients had decreased serum levels of at least one antibody class or subclass with IgG3 and IgG4 subclass deficiencies as most common phenotypes. However, we found elevated immunoglobulin levels with an excess of IgM and IgG2 in particular in another 25% of patients. No major alteration in numbers of B cells and B-cell subsets was seen. Deficiency of MBL was found in 15% of the CFS patients in contrast to 6% in a historical control group. In a 2nd cohort of 168 patients similar frequencies of IgG subclass and MBL deficiency were found. Thus, humoral immune defects are frequent in CFS patients and are associated with infections of the respiratory tract. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  12. Objective Evaluation of Subclass Characteristics on Breech Face Marks.

    Science.gov (United States)

    Riva, Fabiano; Hermsen, Rob; Mattijssen, Erwin; Pieper, Pascal; Champod, Christophe

    2017-03-01

    Subclass characteristics can be found on the breech face marks left on spent cartridge cases. Even if they are assumed to be rare and their reported number is small, they can potentially lead to false associations. Subclass characteristics have been studied empirically allowing examiners to recognize them and to understand in which conditions they are produced. Until now, however, their influence on the identification process has not been studied from a probabilistic point of view. In this study, we aim at measuring the effect of these features on the strength of association derived from examinations involving subclass characteristics. The study takes advantage of a 3D automatic comparison system allowing the calculation of likelihood ratios (LRs). The similarities between cartridge case specimens fired by thirteen S&W .40S&W Sigma pistols are quantified, and their respective LRs are computed. The results show that the influence of subclass characteristics on the LRs is limited, even when these features are prevalent among the potential sources considered in a case. We show that the proportion of firearms sharing subclass characteristics should be larger than 40% of the pool of potential firearms for the effect to be significant. © 2016 American Academy of Forensic Sciences.

  13. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  14. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode re...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...

  15. Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution.

    Science.gov (United States)

    Woudberg, Nicholas J; Goedecke, Julia H; Blackhurst, Dee; Frias, Miguel; James, Richard; Opie, Lionel H; Lecour, Sandrine

    2016-05-11

    Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.

  16. Post-prandial alterations in LDL size and subclasses in patients with growth hormone deficiency.

    Science.gov (United States)

    Rizzo, Manfredi; Trepp, Roman; Berneis, Kaspar; Christ, Emanuel R

    2008-06-01

    Several studies have suggested that lipoproteins generated during the post-prandial phase are highly atherogenic, with modifications in low-density lipoproteins (LDL) size and density. In the present study we assessed post-prandial variations in LDL size and subclasses in patients with growth hormone deficiency (GHD). We studied in 12 hypopituitary patients with GHD and 10 healthy control subjects matched for gender, age and body mass index (BMI) post-prandial variations after a standardized meal consisting of 35% fat, 45% carbohydrate and 20% of protein (Clinutren Mix, Nestlé) and containing calories corresponding to 1/3 of estimated basal metabolic rate. Blood samples were collected at baseline and after 2 and 4h to measure plasma lipids and LDL size and subclasses by nondenaturing polyacrylamide gradient gel electrophoresis. At baseline patients had similar plasma lipids than controls, with the exception of higher triglycerides (1.2+/-0.8 vs. 0.7+/-0.4mmol/L, p=.0024). Baseline LDL size was similar between the two groups and LDL subclass analysis revealed a small increase in LDL-IIIA (p=.0046). During post-prandial phase no significant differences were found in LDL size and subclasses in patients vs. controls with the sole exception of increased levels of LDL-IVB after 2h (p=.0295) and LDL-IIIB after 4h (p=.0478). It is, therefore, unlikely that a post-prandial variation in levels of small, dense LDL may significantly contribute to the atherogenic potential in hypopituitary patients with GHD.

  17. Isolation and characterization of a monoclonal anti CK-2 alpha subunit antibody of the IgG1 subclass

    DEFF Research Database (Denmark)

    Schmidt-Spaniol, I; Boldyreff, B; Issinger, O G

    1992-01-01

    A monoclonal antibody was produced against the recombinant human alpha subunit of CK-2. The antibody was of the IgG1 subclass and it was isolated from serum-free cell culture media and purified by affinity chromatography on Protein G Sepharose. The antibody can be used to detect specifically the ...

  18. Immunization of humans with polysaccharide vaccines induces systemic, predominantly polymeric IgA2-subclass antibody responses.

    Science.gov (United States)

    Tarkowski, A; Lue, C; Moldoveanu, Z; Kiyono, H; McGhee, J R; Mestecky, J

    1990-05-15

    Ig class- and IgA subclass-specific immune responses to protein and polysaccharide Ag were studied in serum, external secretions, and at the single cell level in peripheral blood of systemically immunized adults. Immunization with tetanus toxoid induced predominantly IgG antibody responses in serum and in the PBMC. The IgA antibody response was low, and was mostly of the IgA1 subclass. In contrast, immunization with polysaccharide Ag (Haemophilus influenzae type b, Neisseria meningitidis serogroup A, C, Y, W-135, and Streptococcus pneumoniae capsular polysaccharides) elicited a major IgA response predominantly of the IgA2 isotype. Analysis of the molecular forms of secreted IgA antibodies indicated that polymers were produced early after immunization, irrespective of the nature of the Ag. When compared with serum antibody and to PBMC cell responses, systemic immunization with polysaccharides induced a minor salivary response dominated by IgG and IgM antibodies. In contrast, the presence of antipolysaccharide antibodies in bile, irrespective of their isotype, paralleled the serum response 14 days after the immunization with polysaccharide Ag. These results suggest that biliary Ig were mostly derived from serum. Different patterns of the expression of MHC class II Ag on T cells, B cells, and monocytes during the course of immunization with protein or polysaccharide Ag were observed: whereas protein Ag induced a high frequency of HLA-DP- and HLA-DR-expressing cells early in the course of immunization, polysaccharide vaccines elicited low and protracted increases of HLA-DP+ T cells. Polysaccharide vaccine covalently coupled to a protein carrier induced a higher frequency of antipolysaccharide antibody-secreting cells in peripheral blood and increased the IgG to IgA ratio among polysaccharide-specific antibody-secreting cells.

  19. Detection of herbicide subclasses by an optical multibiosensor based on an array of photosystem II mutants.

    Science.gov (United States)

    Giardi, Maria Teresa; Guzzella, Licia; Euzet, Pierre; Rouillon, Regis; Esposito, Dania

    2005-07-15

    Massive use of herbicides in agriculture over the last few decades has become a serious environmental problem. The residual concentration of these compounds frequently exceeds the maximum admissible concentration in drinking water for human consumption and is a real environmental risk for the aquatic ecosystem. Herbicides inhibiting photosynthesis via targeting photosystem II function still represent the basic means of weed control. A multibiosensor was constructed for detecting herbicides using as biosensing elements photosynthetic preparations coupled to an optical fluorescence transduction system (Giardi et al. EU patent EP1134585, 01830148.1-2204); this paper is about its application in the detection of herbicide subclasses in river water. Photosynthetic material was immobilized on a silicio septum inside a series of flow cells, close to diodes so as to activate photosystem II (PSII) fluorescence. The principle of the detection was based on the factthat herbicides selectively modify PSII fluorescence activity. The multibiosensor has the original feature of being able to distinguish the subclasses of the photosynthetic herbicides by using specific immobilized biomediators isolated from mutated organisms. This setup resulted in a reusable, portable multibiosensor for the detection of herbicide subclasses with a half-life of 54 h for spinach thylakoids and limit of detection of 3 x 10(-9) M for herbicides present in river water.

  20. Skill level-specific differences in snowboarding-related injuries.

    Science.gov (United States)

    Ogawa, Hiroyasu; Sumi, Hiroshi; Sumi, Yasuhiko; Shimizu, Katsuji

    2010-03-01

    Snowboarding-related injuries have been associated with specific snowboarding skill levels, but differences in specific skill level have not been identified. Injury patterns are different among skill levels. Descriptive epidemiology study. The subjects were 19 539 snowboarders from the Oku-Mino region in Gifu Prefecture, Japan, who were admitted to our hospital during the 12 snowboarding seasons from 1996 to 2008. They were asked to complete a questionnaire regarding age, gender, self-estimated skill level, injury location, injury type, mechanism of injury, and protective gear. Physicians documented diagnostic variables and injury severity score; these variables were compared among the self-estimated skill levels. Of the total 19 539 injured snowboarders, 1204 (6.2%) were novices, 6409 (32.8%) were beginners, 9260 (47.4%) were intermediates, 1918 (9.8%) were experts, and the skill level was not known in 748 (3.8%). Proportions of the trunk and multiple injuries increased with increases in skill level; however, the number of head/face injuries decreased with increase in skill level. Upper extremity injuries also decreased with increase in skill level, except in novices. Dislocations and multiple injuries increased with increase in skill level, while lacerations/contusions, fractures, and bruises decreased. The mean overall injury severity score was 3.28 + or - 0.02, and the value increased significantly with increase in skill level. The proportion of collision and isolated fall injuries significantly decreased with increase in skill level, but that of jump injuries significantly increased. The percentage of protective gear use increased with the increase in skill level. Prevalence of injury type, injury location, mechanism of injury, and percentage of protective gear use varied according to skill level, and the severity of the injury increased with increase in skill level. On the basis of our observations, we believe that snowboarding injury prevention strategies

  1. Highly specific fiber optic immunosensor coupled with immunomagnetic separation for detection of low levels of Listeria monocytogenes and L. ivanovii

    Science.gov (United States)

    2012-01-01

    Background Immunomagnetic separation (IMS) and immunoassays are widely used for pathogen detection. However, novel technology platforms with highly selective antibodies are essential to improve detection sensitivity, specificity and performance. In this study, monoclonal antibodies (MAbs) against Internalin A (InlA) and p30 were generated and used on paramagnetic beads of varying diameters for concentration, as well as on fiber-optic sensor for detection. Results Anti-InlA MAb-2D12 (IgG2a subclass) was specific for Listeria monocytogenes and L. ivanovii, and p30-specific MAb-3F8 (IgM) was specific for the genus Listeria. At all bacterial concentrations (103–108 CFU/mL) tested in the IMS assay; the 1-μm diameter MyOne beads had significantly higher capture efficiency (P Listeria antibody (9 %). Furthermore, capture efficiency for MyOne-2D12 was highly specific for L. monocytogenes and L. ivanovii. Subsequently, we captured L. monocytogenes by MyOne-2D12 and MyOne-3F8 from hotdogs inoculated with mono- or co-cultures of L. monocytogenes and L. innocua (10–40 CFU/g), enriched for 18 h and detected by fiber-optic sensor and confirmed by plating, light-scattering, and qPCR assays. The detection limit for L. monocytogenes and L. ivanovii by the fiber-optic immunosensor was 3 × 102 CFU/mL using MAb-2D12 as capture and reporter antibody. Selective media plating, light-scattering, and qPCR assays confirmed the IMS and fiber-optic results. Conclusions IMS coupled with a fiber-optic sensor using anti-InlA MAb is highly specific for L. monocytogenes and L. ivanovii and enabled detection of these pathogens at low levels from buffer or food. PMID:23176167

  2. Highly specific fiber optic immunosensor coupled with immunomagnetic separation for detection of low levels of Listeria monocytogenes and L. ivanovii.

    Science.gov (United States)

    Mendonça, Marcelo; Conrad, Neida L; Conceição, Fabricio R; Moreira, Angela N; da Silva, Wladimir P; Aleixo, José Ag; Bhunia, Arun K

    2012-11-23

    Immunomagnetic separation (IMS) and immunoassays are widely used for pathogen detection. However, novel technology platforms with highly selective antibodies are essential to improve detection sensitivity, specificity and performance. In this study, monoclonal antibodies (MAbs) against Internalin A (InlA) and p30 were generated and used on paramagnetic beads of varying diameters for concentration, as well as on fiber-optic sensor for detection. Anti-InlA MAb-2D12 (IgG2a subclass) was specific for Listeria monocytogenes and L. ivanovii, and p30-specific MAb-3F8 (IgM) was specific for the genus Listeria. At all bacterial concentrations (10³-10⁸ CFU/mL) tested in the IMS assay; the 1-μm diameter MyOne beads had significantly higher capture efficiency (P Listeria antibody (9 %). Furthermore, capture efficiency for MyOne-2D12 was highly specific for L. monocytogenes and L. ivanovii. Subsequently, we captured L. monocytogenes by MyOne-2D12 and MyOne-3F8 from hotdogs inoculated with mono- or co-cultures of L. monocytogenes and L. innocua (10-40 CFU/g), enriched for 18 h and detected by fiber-optic sensor and confirmed by plating, light-scattering, and qPCR assays. The detection limit for L. monocytogenes and L. ivanovii by the fiber-optic immunosensor was 3 × 10² CFU/mL using MAb-2D12 as capture and reporter antibody. Selective media plating, light-scattering, and qPCR assays confirmed the IMS and fiber-optic results. IMS coupled with a fiber-optic sensor using anti-InlA MAb is highly specific for L. monocytogenes and L. ivanovii and enabled detection of these pathogens at low levels from buffer or food.

  3. Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy.

    Science.gov (United States)

    Decewicz, David J; Neatrour, David M; Burke, Amy; Haberkorn, Mary Jane; Patney, Heather L; Vernalis, Marina N; Ellsworth, Darrell L

    2009-06-29

    Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients. The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p lifestyle change program were not confounded by lipid-lowering medications. In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

  4. Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy

    Directory of Open Access Journals (Sweden)

    Patney Heather L

    2009-06-01

    Full Text Available Abstract Background Low-density lipoprotein (LDL cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD to improve our understanding of lipoprotein management in cardiac patients. Results The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p Conclusion In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to women.

  5. Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass.

    Science.gov (United States)

    Neergaard, Martin S; Nielsen, Anders D; Parshad, Henrik; Van De Weert, Marco

    2014-01-01

    Few studies have so far directly compared the impact of antibody subclass on protein stability. This case study investigates two mAbs (one IgG1 and one IgG4 ) with identical variable region. Investigations of mAbs that recognize similar epitopes are necessary to identify possible differences between the IgG subclasses. Both physical and chemical stability were evaluated by applying a range of methods to measure formation of protein aggregates [size-exclusion chromatography (SEC)-HPLC and UV340 nm], structural integrity (circular dichroism and FTIR), thermodynamic stability (differential scanning calorimetry), colloidal interactions (dynamic light scattering), and fragmentation and deamidation (SEC-HPLC and capillary isoelectric focusing). The impact of pH (4-9) and ionic strength (10 and 150 mM) was investigated using highly-concentrated (150 mg/mL) mAb formulations. Lower conformational stability was identified for the IgG4 resulting in increased levels of soluble aggregates. The IgG1 was chemically less stable as compared with the IgG4 , presumably because of the higher flexibility in the IgG1 hinge region. The thermodynamic stability of individual mAb domains was also addressed in detail. The stability of our mAb molecules is clearly affected by the IgG framework, and this study suggests that subclass switching may alter aggregation propensity and aggregation pathway and thus potentially improve the overall formulation stability while retaining antigen specificity. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. Anti-inflammatory and antioxidant functions of high-density lipoprotein subclasses in patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Ying TAN

    2013-02-01

    Full Text Available Objective  To assess the anti-inflammatory and antioxidant functions of high-density lipoprotein (HDL subclasses (HDL2 and HDL3 in patients with acute coronary syndrome (ACS, and to elucidate whether incapacitation of HDL subclasses occurred in ACS patients. Methods  Forty ACS patients hospitalized in Nanfang Hospital from Jan. 2011 to Jan. 2012 (ACS group, and 40 subjects simultaneously receiving health examination (control group were enrolled in present study. Plasma lipid and hypersensitive C reactive protein (hs-CRP levels, HDL subclasses inflammatory index (HII, paraoxonase-1 (PON1 activity and lipid hydroperoxide (LOOH levels in both groups were measured. Results  The low-density lipoprotein cholesterol (LDL-C and hs-CRP levels were higher in ACS group than in control group (P0.05. Conclusions  The incapacitation of HDL subclasses may occur in ACS patients, with an attenuated antioxidant ability and accentuated proinflammatory function. Mature HDL2 possesses better anti-inflammatory and antioxidant function than HDL3, thus playing a better cardioprotective effect.

  7. On a Subclass of Harmonic Convex Functions of Complex Order

    Directory of Open Access Journals (Sweden)

    N. Magesh

    2012-01-01

    Full Text Available We introduce and study a subclass of harmonic convex functions of complex order. Coefficient bounds, extreme points, distortion bounds, convolution conditions, and convex combination are determined for functions in this class. Further, we obtain the closure property of this class under integral operator.

  8. Lipid subclasses profiles and oxidative stress in aggressive periodontitis before and after treatment.

    Science.gov (United States)

    Nibali, L; Rizzo, M; Li Volti, G; D'Aiuto, F; Giglio, R V; Barbagallo, I; Pelekos, G; Donos, N

    2015-12-01

    Associations between dyslipidaemia, oxidative stress and periodontitis have emerged in recent years. However, there is a lack of studies investigating these associations in aggressive periodontitis (AgP) cases. The aim of this study was to investigate the lipid and oxidative stress profiles in patients with AgP, and to relate them to clinical variables and interleukin (IL)-6 genetic variants. Twelve non-smoking Caucasian patients with AgP selected based on their IL6 haplotypes underwent periodontal non-surgical and surgical treatment. Peripheral blood samples taken at baseline and at six different time-points after treatment were processed to determine IL-6 circulating levels, lipid profiles (cholesterol, triglycerides, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] subclasses) and oxidative stress markers (glutathione and total lipid hydroperoxide levels). HDLs were the most prevalent lipoproteins, followed by intermediate-density lipoprotein, very-low-density lipoprotein and LDL. The LDL subclasses consisted mainly of the less atherogenic large LDL. The lipid profile did not consistently change after treatment up to 3 mo after surgery. Periodontal disease severity was associated with LDL levels and size. The IL6 haplotypes were associated with total cholesterol, triglycerides, HDL and LDL subclasses after adjusting for confounders. IL-6 circulating levels were associated with both very-low-density lipoprotein and lipid hydroperoxide levels. Based on these data, we conclude that both periodontal disease severity and IL6 haplotypes may influence lipid profiles in AgP. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis.

    Science.gov (United States)

    Rigopoulou, Eirini I; Davies, Edward T; Bogdanos, Dimitrios-Petrou; Liaskos, Christos; Mytilinaiou, Maria; Koukoulis, George K; Dalekos, George N; Vergani, Diego

    2007-11-01

    Primary biliary cirrhosis (PBC) is characterised by the presence of immunoglobulin (Ig) G antimitochondrial antibodies (AMA), which are routinely detected by indirect immunofluorescence (IFL) using composite rodent tissue substrate. The IgG subclass distribution and clinical significance of IFL-detected AMA in patients with PBC have not been previously studied in detail. We have examined IgG subclass-specific AMA detected by IFL on rodent liver, kidney and stomach tissue substrate using affinity-purified IgG subclass monospecific antisera as revealing reagents in 95 AMA-positive PBC patients from Greece. AMA of any of the IgG1, IgG2 or IgG3 subclasses were present in 89/95 (93.7%) patients. Among those 89, 55 (61.8%) had IgG1, 2, 3 AMA positivity; eight (9%) had IgG1, 2; seven (7.9%) had IgG2, 3; eight (9%) had IgG1, 3; nine (10.1%) had IgG1 subclass and two (2.2%) single IgG3 AMA reactivity. IgG4 AMA was absent. IgG3 titres were higher than IgG2 and IgG1 (P<0.001) and IgG1 higher than IgG2 (P<0.001). IgG3 AMA-positive patients had a histologically more advanced disease (P<0.01) and were more frequently cirrhotic compared with those who were negative (P<0.01). There was a positive correlation between AMA IgG3 titre and Mayo risk score (r=0.55, P=0.009, Spearman's correlation). Our findings suggest that AMA are not restricted to a specific IgG subclass. AMA of the IgG3 subclass are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.

  10. Coefficient Estimates for Certain Subclasses of Biunivalent Functions Defined by Convolution

    Directory of Open Access Journals (Sweden)

    R. Vijaya

    2016-01-01

    Full Text Available We introduce two new subclasses of the function class Σ of biunivalent functions in the open disc defined by convolution. Estimates on the coefficients a2 and a3 for the two subclasses are obtained. Moreover, we verify Brannan and Clunie’s conjecture a2≤2 for our subclasses.

  11. Level and appraisal of fatigue are not specific in burnout.

    Science.gov (United States)

    Van Dam, Arno; Keijsers, Ger; Verbraak, Marc; Eling, Paul; Becker, Eni

    2015-01-01

    Fatigue is a main feature of the burnout syndrome but also very common in other psychiatric disorders such as major depression and anxiety disorders. This raises the question of whether the level and appraisal of fatigue is experienced differently by individuals suffering from burnout than by those exhibiting anxiety disorders and major depression. If fatigue is experienced differently in burnout compared with other disorders, this may clarify why fatigue is the main feature of the burnout syndrome. This knowledge may lead to the application of specific therapeutic interventions aimed at the experience of fatigue in burnout. In the present study, we investigated whether fatigue is experienced differently in burnout patients than in patients suffering from anxiety disorders or major depression. We presented 73 burnout patients, 67 depressed patients, 57 patients with an anxiety disorder and 127 healthy participants with a rating scale containing statements about the fatigue-performance relationship, and we assessed the level of fatigue, depression and anxiety. The level of fatigue reported by burnout patients was high but did not differ from that of the other patient groups. The appraisal of fatigue also did not differ among the patient groups. The burnout patients did not appraise their fatigue as a result of unrewarding activities nor did they catastrophize fatigue in an exceptional way. Thus, the level of fatigue and the appraisal of fatigue may be less relevant to the understanding of the specific pathological processes associated with burnout than is often presumed. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Combining Unsupervised and Supervised Learning for Discovering Disease Subclasses

    OpenAIRE

    Tucker, A; Bosoni, P; Bellazzi, R; Nihtyanova, S; Denton, C

    2016-01-01

    Diseases are often umbrella terms for many subcategories of disease. The identification of these subcategories is vital if we are to develop personalised treatments that are better focussed on individual patients. In this short paper, we explore the use of a combination of unsupervised learning to identify potential subclasses, and supervised learning to build models for better predicting a number of different health outcomes for patients that suffer from systemic sclerosis, a rare chronic co...

  13. Nasal polyposis and immunoglobulin-G subclass deficiency.

    Science.gov (United States)

    Tran Khai Hoan, N; Karmochkine, M; Laccourreye, O; Bonfils, P

    2014-06-01

    Study of the association between immunoglobulin-G (IgG) subclass deficiency and nasal polyposis. Longitudinal study (5 years) in a prospective cohort of 161 nasal polyposis patients. Analysis of the association between humoral immunodeficiency, rhinologic symptoms, endoscopy score and prescribed doses of local and systemic corticosteroids. The prevalence of IgG subclass deficiency was 13.7% (22/161). One patient was diagnosed with common variable immunodeficiency (CVID). No significant differences were observed between the groups with and without pre-treatment deficiency for symptom severity, endoscopic score or local or systemic corticosteroid regimens at baseline or during the 5 years, following initiation of medical and surgical treatment. Only the Lund-Mackay CT score was significantly higher in the pre-treatment deficiency group. There was no correlation between the presence of humoral deficiency and either symptom evolution after medical and surgical treatment or the dose of corticosteroids needed to control disease. Thus, a link between IgG subclass deficiency and nasal polyposis seems unlikely. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Subclasses of Normal Helly Circular-Arc Graphs

    CERN Document Server

    Lin, Min Chih; Szwarcfiter, Jayme L

    2011-01-01

    A Helly circular-arc model M = (C,A) is a circle C together with a Helly family \\A of arcs of C. If no arc is contained in any other, then M is a proper Helly circular-arc model, if every arc has the same length, then M is a unit Helly circular-arc model, and if there are no two arcs covering the circle, then M is a normal Helly circular-arc model. A Helly (resp. proper Helly, unit Helly, normal Helly) circular-arc graph is the intersection graph of the arcs of a Helly (resp. proper Helly, unit Helly, normal Helly) circular-arc model. In this article we study these subclasses of Helly circular-arc graphs. We show natural generalizations of several properties of (proper) interval graphs that hold for some of these Helly circular-arc subclasses. Next, we describe characterizations for the subclasses of Helly circular-arc graphs, including forbidden induced subgraphs characterizations. These characterizations lead to efficient algorithms for recognizing graphs within these classes. Finally, we show how do these ...

  15. Heavy metals and specific porphyrine levels in children with autism

    Directory of Open Access Journals (Sweden)

    Marta Macedoni-Lukšič

    2014-06-01

    Full Text Available Background: The aim of our study was to determine the levels of heavy metals in blood (zinc, copper, aluminium, lead, mercury, as well as the specific porphyrin levels in the urine of patients with ASD compared with patients with other neurological disorders.Methods: The study was performed in a group of children with ASD (N = 52, average age = 6.2y and control group of children with other neurological disorders (N = 22, average age = 6.6y, matched in terms of intellectual abilities (Mann-Whitney U = 565.0, p = .595. Measurement of heavy metals in blood was performed by atomic absorption spectrometry, while the HPLC method by means of a fluorescence detector was used to test urinary porphyrin levels. Results were compared across groups using a multivariate analysis of covariance (MANCOVA. In addition, a generalized linear model was used to establish the impact of group membership on the blood Cu/Zn ratio.Results: In terms of heavy metal blood levels, no significant difference between the groups was found. However, compared to the control group, ASD group had significantly elevated blood Cu/Zn ratio (Wald χ2 = 6.6, df = 1, p = .010. Additionaly, no significant difference between the groups was found in terms of Uroporphyrin I, Heptacarboxyporphyrin I, Hexacarboxyporphyrin and Pentacarboxyporphyrin I. However, the levels of Coproporphyrin I and Coproporphyrin III were lower in the ASD group compared to the controls.Conclusions: Due to the observed higher Cu/Zn ratio we’d suggest that blood levels of zinc and cupper should be tested in all children with ASD and a Zn supplement should be given as needed.

  16. Subclass-based Multi-task Learning for Alzheimer's Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    Heung-Il eSuk

    2014-08-01

    Full Text Available In this work, we propose a novel subclass-based multi-task learning method for feature selection in computer-aided Alzheimer's Disease (AD or Mild Cognitive Impairment (MCI diagnosis. Unlike the previous methods that often assumed a unimodal data distribution, we take into account the underlying multipeak distribution of classes. The rationale for our approach is that it is highly likely for neuroimaging data to have multiple peaks or modes in distribution, e.g., mixture of Gaussians, due to the inter-subject variability. In this regard, we use a clustering method to discover the multipeak distributional characteristics and define subclasses based on the clustering results, in which each cluster covers a peak in the underlying multipeak distribution. Specifically, after performing clustering for each class, we encode the respective subclasses, i.e., clusters, with their unique codes. In encoding, we impose the subclasses of the same original class close to each other and those of different original classes distinct from each other. By setting the codes as new label vectors of our training samples, we formulate a multi-task learning problem in a l21-penalized regression framework, through which we finally select features for classification. In our experimental results on the ADNI dataset, we validated the effectiveness of the proposed method by improving the classification accuracies by 1% (AD/Normal Control: NC, 3.25% (MCI/NC, 5.34% (AD/MCI, and 7.4% (MCI Converter: MCI-C/MCI Non-Converter: MCI-NC compared to the competing single-task learning method. It is remarkable for the performance improvement in MCI-C/MCI-NC classification, which is the most important for early diagnosis and treatment. It is also noteworthy that with the strategy of modality-adaptive weights by means of a multi-kernel support vector machine, we maximally achieved the classification accuracies of 96.18% (AD/NC, 81.45% (MCI/NC, 73.21% (AD/MCI, and 74.04% (MCI

  17. Chronic rhinosinusitis and recurrent nasal polyps in two children with IgG subclass deficiency and review of the literature.

    Science.gov (United States)

    Chinratanapisit, Sasawan; Tunsuriyawong, Prayuth; Vichyanond, Pakit; Visitsunthorn, Nualanong; Luangwedchakarn, Voravich; Jirapongsananuruk, Orathai

    2005-11-01

    Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder of mucosa of the nose and the paranasal sinuses. Two major forms of CRS can be differentiated; CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The pathophysiology and etiology of nasal polyps (NPs) are partly understood. IgG subclass deficiency was shown to be associated with an increased susceptibility to infections. However the association between NPs and IgG subclass deficiency has never been reported. To report two cases of recalcitrant CRS and recurrent NPs with IgG subclass deficiency. Two children (6 and 8 year-old boys) were referred to the Pediatric Allergy/Immunology Clinic, Siriraj Hospital due to a prolonged history of CRS and recurrent NPs. Both of them were treated with aggressive medical (topical and systemic corticosteroids, antibiotics, leukotriene antagonist, nasal irrigation) as well as surgical therapy, without significant improvement. Immunologic investigation in both patients showed that IgG, IgA, and IgM level were normal. IgG subclasses level in patient No. 1 were IgG1 1,235 (280-1120) mg/dl (79%), IgG2 235 (30-630) mg/dl (23.5%), IgG3 27.3 (40-250) mg/dl (1.74%), and IgG4 92.4 (11-620) mg/dl (5.9%). IgG subclasses level in patient No. 2 were IgG1 1,139 (280-1120) mg/dl (82.5%), IgG2 170 (30-630) mg/dl (12.3%), IgG3 5.6 (40-250) mg/dl (0.4%), IgG4 65.7 (11-620) mg/dl (4.8%). The diagnosis of CRS and recurrent NPs with IgG3 subclass deficiency in the first patient and IgG2/IgG3 subclass deficiency in the second patient were made. Patient No. 1 was given monthly IVIG therapy for the total of 7 courses and medications were gradually tapered. Currently, the patient is doing well after the cessation of IVIG therapy for 3 months. Patient No. 2 denied the IVIG treatment and was lost to follow up. We reported two cases of recalcitrant CRS and recurrent NPs in children. Immunologic work up revealed IgG subclass deficiency. The treatment with monthly IVIG improved

  18. Highly specific fiber optic immunosensor coupled with immunomagnetic separation for detection of low levels of Listeria monocytogenes and L. ivanovii

    Directory of Open Access Journals (Sweden)

    Mendonça Marcelo

    2012-11-01

    Full Text Available Abstract Background Immunomagnetic separation (IMS and immunoassays are widely used for pathogen detection. However, novel technology platforms with highly selective antibodies are essential to improve detection sensitivity, specificity and performance. In this study, monoclonal antibodies (MAbs against Internalin A (InlA and p30 were generated and used on paramagnetic beads of varying diameters for concentration, as well as on fiber-optic sensor for detection. Results Anti-InlA MAb-2D12 (IgG2a subclass was specific for Listeria monocytogenes and L. ivanovii, and p30-specific MAb-3F8 (IgM was specific for the genus Listeria. At all bacterial concentrations (103–108 CFU/mL tested in the IMS assay; the 1-μm diameter MyOne beads had significantly higher capture efficiency (P 5 CFU/mL was significantly higher (P Listeria antibody (9 %. Furthermore, capture efficiency for MyOne-2D12 was highly specific for L. monocytogenes and L. ivanovii. Subsequently, we captured L. monocytogenes by MyOne-2D12 and MyOne-3F8 from hotdogs inoculated with mono- or co-cultures of L. monocytogenes and L. innocua (10–40 CFU/g, enriched for 18 h and detected by fiber-optic sensor and confirmed by plating, light-scattering, and qPCR assays. The detection limit for L. monocytogenes and L. ivanovii by the fiber-optic immunosensor was 3 × 102 CFU/mL using MAb-2D12 as capture and reporter antibody. Selective media plating, light-scattering, and qPCR assays confirmed the IMS and fiber-optic results. Conclusions IMS coupled with a fiber-optic sensor using anti-InlA MAb is highly specific for L. monocytogenes and L. ivanovii and enabled detection of these pathogens at low levels from buffer or food.

  19. Global Projections of River Flood Risk at Specific Warming Levels

    Science.gov (United States)

    Alfieri, L.; Feyen, L.; Dottori, F.; Naumann, G.; Bianchi, A.; De Roo, A. P. J.; Bernard, B.; Hirpa, F. A.; Salamon, P.

    2016-12-01

    The ongoing rise in global average temperature has put increasing pressure on understanding the links between atmospheric warming and the occurrence of natural hazards. While the Paris Agreement has set the ambitious target to limit global warming to 1.5°C compared to pre-industrial levels, scientist are urged to explore scenarios for different warming thresholds and quantify ranges of socio-economic impact. In this work, we present a framework to estimate the economic damage and population affected by river floods. It is based on a modeling cascade involving hydrological, hydraulic and socio-economic impact simulations. The modeling framework is designed to perform global scale simulations with hazard and risk mapping at 1 km spatial resolution. Furthermore, it relies on state-of-the-art exposure and vulnerability information. We forced the global hydrological model with an ensemble of seven high-resolution climate projections based on RCP8.5 to derive a streamflow climatology of up to 160 years of daily data starting in 1971. This was used to assess the frequency and magnitude of river floods over time slices centered on the years of exceeding specific warming levels of 1.5, 2, and 4 °C. Results indicate a clear positive correlation between atmospheric warming and future flood risk at global scale. Changes in flood risk appear unevenly distributed, with the largest increases in Asia, America and Europe. On the other hand, changes are statistically not significant in most countries in Africa and Oceania for all considered warming levels.

  20. Anxiety levels in mothers of children with specific learning disability

    Directory of Open Access Journals (Sweden)

    Karande S

    2009-01-01

    Full Text Available Background : Parents of children with specific learning disability (SpLD undergo stress in coping with their child′s condition. Aim : To measure the levels of anxiety and find out the cause of anxiety in mothers of children with SpLD at time of diagnosis. Settings and Design : Prospective rating-scale and interview-based study conducted in our clinic. Materials and Methods : One hundred mothers of children (70 boys, 30 girls with SpLD were interviewed using the Hamilton anxiety rating scale (HAM-A and a semi-structured questionnaire. Detailed clinical and demographic data of mothers were noted. Statistical Analysis : Chi-square test or unpaired student′s t-test was applied wherever applicable. Results : The mean age of mothers was 40.14 years (±SD 4.94, range 25.07-54.0, 73% belonged to upper or upper middle socioeconomic strata of society, 67% were graduates or postgraduates, 58% were full-time home-makers, and 33% lived in joint families. Levels of anxiety were absent in 24%, mild in 75%, and moderate in 1% of mothers. Their mean total anxiety score was 5.65 (±SD 4.75, range 0-21, mean psychic anxiety score was 3.92 (±SD 3.11, range 0-13, and mean somatic anxiety score was 1.76 (±SD 2.05, range 0-10. Their common worries were related to child′s poor school performance (95%, child′s future (90%, child′s behavior (51%, and visits to our clinic (31%. Conclusion : Most mothers of children with SpLD have already developed mild anxiety levels by the time this hidden disability is diagnosed. These anxieties should be addressed by counseling to ensure optimum rehabilitation of these children.

  1. Physical activity versus sedentary behavior: associations with lipoprotein particle subclass concentrations in healthy adults.

    Directory of Open Access Journals (Sweden)

    Eivind Aadland

    Full Text Available BACKGROUND: Physical activity (PA and sedentary behavior (SED may have independent effects on health and disease. This might be due to PA and SED having distinct effects on lipoprotein metabolism. The aim of this study was to determine associations between lipoprotein subclass particle concentrations (-P and accelerometer-measured SED and moderate-to-vigorous PA (MVPA in a sample of healthy adult subjects. METHODS: Lipoprotein subclass particle concentrations were determined by proton nuclear magnetic resonance spectroscopy, whereas SED and MVPA were measured using Agtigraph GT1M and GT3X+ accelerometers. We obtained valid data in 73 subjects (30 men and 43 women, age 40.5 ± 10.6 years; body mass index 24.0 ± 2.8. Multiple regression analysis was used to determine associations (partial correlations with lipoproteins. RESULTS: Positive associations were detected between SED and small VLDL-P, large LDL-P and TG (partial r = 0.24 to 0.25, p .355. On the contrary, MVPA was positively associated with large HDL-P, average HDL size, Apo A1 and HDL-cholesterol (partial r = 0.28 to 0.50, p .607. CONCLUSION: There might be a specific effect of SED versus MVPA on lipoprotein metabolism. However, our results must be interpreted carefully due to possible effect-modification by gender and a low sample size. Thus, our findings should be viewed as preliminary.

  2. Effects of adjuvants on IgG subclasses elicited by virus-like Particles

    Directory of Open Access Journals (Sweden)

    Visciano Maria Luisa

    2012-01-01

    Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

  3. Different IgG-subclass distributions after whole-cell and acellular pertussis infant primary vaccinations in healthy and pertussis infected children.

    Science.gov (United States)

    Hendrikx, Lotte H; Schure, Rose-Minke; Oztürk, Kemal; de Rond, Lia G H; de Greeff, S C; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-09-16

    The distribution of IgG-subclasses provides insight in the immunological mechanisms of protection against whooping cough. We investigated the effect of Dutch whole-cell pertussis and acellular pertussis vaccines administered in infancy on the IgG-subclass distributions in healthy children aged 12 months, 4 years and 9 years as well as in children who have been infected with Bordetella pertussis. A fluorescent bead-based multiplex immunoassay was used for the measurement of IgG1, IgG2, IgG3 and IgG4 responses against pertussis toxin, filamentous heamagglutinin and pertactin. Although IgG1 was the predominant subclass for all pertussis antigens in both healthy and infected children, elevated IgG4 levels were only present in children who had received repeated number of acellular pertussis vaccinations. IgG2 and IgG3 antibodies did not contribute to the IgG response. No differences in IgG-subclasses between healthy vaccinated or infected children were found. The pertussis vaccine used for priming seems to determine the IgG-subclass composition elicited after a secondary antibody response either induced by pertussis vaccination or infection. The pronounced anti-pertussis IgG4 response might reflect the Th2-skewing of the immune response after aP vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  5. Kernel Subclass Support Vector Description for Face and Human Action Recognition

    OpenAIRE

    Mygdalis, Vasileios; Iosifidis, Alexandros; Tefas, Anastasios; Pitas, Ioannis

    2016-01-01

    In this paper, we present the Kernel Subclass Support Vector Data Description classifier. We focus on face recognition and human action recognition applications, where we argue that sub-classes are formed within the training class. We modify the standard SVDD optimization problem, so that it exploits subclass information in its optimization process. We extend the proposed method to work in feature spaces of arbitrary dimensionality. We evaluate the proposed method in publicly available face r...

  6. Specification for procurement of water-level sensing instrumentation, specification number HIF-I-1

    Science.gov (United States)

    Rapp, D.H.

    1982-01-01

    This specification is to communicate to instrument manufacturers the U.S. Geological Survey 's requirements. It covers systems for sensing the elevation of the water surface on open channels, rivers, lakes, reservoirs, storm-sewer pipes, and observation wells at Survey data-collection sites. The signal output (mechanical or electrical) must meet the signal input requirements of analog to digital and digital input recorders in use by the Survey. A classification of stage-sensing systems by common characteristics is used to aid Survey people making system selections. These characteristics are (1) system type (contact or noncontact), (2) sensor type and sensing distance, (3) accuracy, (4) range, (5) power requirements, (6) system size and weight, and (7) data output signal. Acceptable system requirements cover system configurations, signal outputs, materials, operation manuals, detailed environmental conditions, calibration procedures, system accuracy, power requirements, installation limitations, maintainability, safety, and workmanship. An outline of the qualification test procedures and failure criteria are also given. The Hydrologic Instrumentation Facility at NSTL Station, Mississippi will test available systems to determine if they meet the specification in this report for inclusion in the Survey 's 'Qualified Products List'. This list will be used for future procurement of water-level sensing systems by the Survey. (USGS)

  7. Development of a fluorescent-bead-based multiplex immunoassay to determine immunoglobulin G subclass responses to Neisseria meningitidis serogroup A and C polysaccharides

    NARCIS (Netherlands)

    de Voer, Richarda M.; van der Klis, Fiona R. M.; Engels, Carla W. A. M.; Rijkers, Ger T.; Sanders, Elisabeth A.; Berbers, Guy A. M.

    A fluorescent-particle-based multiplex flow cytometric immunoassay (MIA) for the detection of serum immunoglobulin G (IgG) and two IgG subclasses, IgG1 and IgG2, specific for Neisseria meningitidis serogroup A ( MenA) and C (MenC) polysaccharides ( PS) was developed. The assay comprised three

  8. [Multicenter study of commercial kits for the determination of human IgG subclasses, using the ELISA technique].

    Science.gov (United States)

    Pontet, F; Pressac, M; Musset, L; Tapon-Bretaudière, J; Jehl, C; Cailliez, M; Bienvenu, F

    1994-01-01

    We evaluated two commercially available sandwich type Elisa procedures for the measurement of IgG subclasses in human serum. Assay kits from The Binding Site and the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service were tested in six laboratories. The performance of spectrophotometers, pipettes and dilutors were assessed at each center. Within-run precision was estimated according to the Valtec method (Société Française de Biologie Clinique). The overall coefficient of variation ranged from 4 to 50% depending on subclass and kit. We also evaluated the IgG2 and IgG4 specificity using four sera containing a monoclonal IgG2 or IgG4 (kappa or lambda type). Using total IgG and immunoelectrophoresis as a comparative technique, IgG2 kappa and IgG4 kappa were both underestimated, IgG2 lambda was overestimated while IgG4 lambda compared favorably. Polyclonal IgG subclasses were frequently overestimated in these sera suggesting cross-reactions with either monoclonal IgG or other polyclonal IgG. Antigen excess was investigated and not encountered with either kit. Our results demonstrate that these procedures are insufficiently accurate or precise for routine clinical use.

  9. Serum prostate specific antigen levels in men with benign prostatic ...

    African Journals Online (AJOL)

    Objective: To determine the sensitivity, specificity and positive predictive value of the PSA test at the conventional cut-off value of 4 ng/ml. Design: Retrospective study. Setting: Nairobi Hospital Laboratory, Nairobi. Data Source: Results of serum Prostate specific Antigen (PSA), estimation and prostate histology specimens at ...

  10. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros

    2015-11-01

    Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

  11. Level and Appraisal of Fatigue are Not Specific in Burnout

    NARCIS (Netherlands)

    Dam, A. van; Keijsers, G.P.J.; Verbraak, M.J.P.M.; Eling, P.A.T.M.; Becker, E.S.

    2015-01-01

    Fatigue is a main feature of the burnout syndrome but also very common in other psychiatric disorders such as major depression and anxiety disorders. This raises the question of whether the level and appraisal of fatigue is experienced differently by individuals suffering from burnout than by those

  12. Early diagnosis of congenital toxoplasmosis in newborn infants using IgG subclasses against two Toxoplasma gondii recombinant proteins

    Directory of Open Access Journals (Sweden)

    Carlos Henryque de Souza e Silva

    2012-05-01

    Full Text Available The aim of this work was to evaluate the utility of ELISA-based testing of total IgG (IgGt antibodies and its subclasses (IgG1, IgG2, IgG3 and IgG4 against soluble (STAg and recombinant (rSAG1 and rMIC3 antigens of Toxoplasma gondii for diagnosing congenital toxoplasmosis. Sera from 217 newborns initially testing positive for specific IgM in filter paper dried blood spots were tested for specific IgM and IgG by ELFA-VIDAS®. Congenital toxoplasmosis was confirmed in 175 and ruled out in 42 infants. The validity of the ELISA tests was determined using the persistence of IgG antibodies (ELFA-VIDAS® kit at the end of 12 months, which is considered the reference test for the diagnosis of congenital toxoplasmosis. The frequency of positivity with IgGt against STAg, rSAG1 and rMIC3 was found in 97.2%, 96.3% and 80.2%, respectively, of the newborns with confirmed congenital toxoplasmosis. IgG1 reacted with all three antigens, while IgG3 and IgG4 reacted preferentially with rMIC3. Higher mean values of reactivity (sample optical density/cut-off were found for all subclasses when using rMIC3. All of the antigens showed high sensitivity and low specificity in detecting anti-T. gondii IgGt and IgG1 and low sensitivity and high specificity in detecting IgG3 and IgG4. In conclusion, the combined detection of IgG antibody subclasses against recombinant toxoplasmic antigens may be useful for the early diagnosis of congenital toxoplasmosis.

  13. Reprogrammable Controller Design From High-Level Specification

    OpenAIRE

    Benmohammed, M.; M. Bourahla; S. Merniz

    2003-01-01

    Existing techniques in high-level synthesis mostly assume a simple controller architecture model in the form of a single FSM. However, in reality more complex controller architectures are often used. On the other hand, in the case of programmable processors, the controller architecture is largely defined by the available control-flow instructions in the instruction set. With the wider acceptance of behavioral synthesis, the application of these methods for the design of programmable contr...

  14. Application-specific protocols for user-level shared memory

    Energy Technology Data Exchange (ETDEWEB)

    Falsafi, B.; Lebeck, A.R.; Reinhardt, S.K.; Schoinas, I.; Hill, M.D.; Larus, J.R.; Rogers, A.; Wood, D.A. [Univ. of Wisconsin, Madison, WI (United States). Computer Sciences Dept.

    1994-12-31

    Recent distributed shared memory (DSM) systems and proposed shared-memory machines have implemented some or all of their cache coherence protocols in software. One way to exploit the flexibility of this software is to tailor a coherence protocol to match an application`s communication patterns and memory semantics. This paper presents evidence that this approach can lead to large performance improvements. It shows that application-specific protocols substantially improved the performance of three application programs--appbt, em3d, and barnes--over carefully tuned transparent shared memory implementations. The speed-ups were obtained on Blizzard, a fine-grained DSM system running on a 32-node Thinking Machines CM-5.

  15. Reprogrammable Controller Design From High-Level Specification

    Directory of Open Access Journals (Sweden)

    M. Benmohammed

    2003-10-01

    Full Text Available Existing techniques in high-level synthesis mostly assume a simple controller architecture model in the form of a single FSM. However, in reality more complex controller architectures are often used. On the other hand, in the case of programmable processors, the controller architecture is largely defined by the available control-flow instructions in the instruction set. With the wider acceptance of behavioral synthesis, the application of these methods for the design of programmable controllers is of fundamental importance in embedded system technology. This paper describes an important extension of an existing architectural synthesis system targeting the generation of ASIP reprogrammable architectures. The designer can then generate both style of architecture, hardwired and programmable, using the same synthesis system and can quickly evaluate the trade-offs of hardware decisions.

  16. IgA and/or IgG subclass deficiency in children with recurrent respiratory infections and its relationship with chronic pulmonary damage.

    Science.gov (United States)

    Ozkan, H; Atlihan, F; Genel, F; Targan, S; Gunvar, T

    2005-01-01

    Most patients with IgA and/or IgG subclass deficiency are asymptomatic but some may suffer from frequent mainly respiratory infections. The aim of our study was to determine the frequency of IgA and/or IgG subclass deficiencies and the rate of chronic pulmonary damage secondary to recurrent pulmonary infections in these children. Serum IgA and IgG subclass levels were measured in 225 children aged 6 months to 6 years with recurrent sinopulmonary infections (44 with recurrent upper respiratory tract infections, 100 with recurrent pulmonary infections and 81 with recurrent bronchiolitis). In order to determine chronic pulmonary damage due to recurrent infections in patients with recurrent pulmonary infections CT scans of thorax were also obtained. The overall frequency of antibody defects was found to be 19.1%. IgA deficiency was observed in 9.3%, IgG subclass deficiency in 8.4% and IgA + IgG subclass deficiency in 1.4%. The prevalance of IgA and/or IgG subclass deficiency was 25% in patients with recurrent upper respiratory tract infections, 22% in patients with recurrent pulmonary infections and 12.3% in patients with recurrent bronchiolitis (p>0.05). Chronic pulmonary damage in lungs was determined radiologically in 17 of 100 cases with recurrent pulmonary infection. In IgG subclass deficiencies sequel changes, although not statistically significant, were observed five times more frequently than that of IgA deficiencies. CT scans revealed pulmonary sequels in 5 of the 22 (22.7%) patients with recurrent pulmonary infections and immunodeficiency (bronchiectasis in 2 patients with IgG3 deficiency, fibrotic changes in one with IgA deficiency and in one with IgG3 deficiency, bronchiolitis obliterans in one with IgG2 + IgG3 deficiency). On the other hand, pulmonary sequels were observed in 12 patients (15.4%) with normal immunoglobulin levels. Eight of them were bronchiolitis obliterans, 2 of them were atelectasia and 1 of them was bronchiectasia. We therefore suggest

  17. Subclass mapping: identifying common subtypes in independent disease data sets.

    Directory of Open Access Journals (Sweden)

    Yujin Hoshida

    Full Text Available Whole genome expression profiles are widely used to discover molecular subtypes of diseases. A remaining challenge is to identify the correspondence or commonality of subtypes found in multiple, independent data sets generated on various platforms. While model-based supervised learning is often used to make these connections, the models can be biased to the training data set and thus miss inherent, relevant substructure in the test data. Here we describe an unsupervised subclass mapping method (SubMap, which reveals common subtypes between independent data sets. The subtypes within a data set can be determined by unsupervised clustering or given by predetermined phenotypes before applying SubMap. We define a measure of correspondence for subtypes and evaluate its significance building on our previous work on gene set enrichment analysis. The strength of the SubMap method is that it does not impose the structure of one data set upon another, but rather uses a bi-directional approach to highlight the common substructures in both. We show how this method can reveal the correspondence between several cancer-related data sets. Notably, it identifies common subtypes of breast cancer associated with estrogen receptor status, and a subgroup of lymphoma patients who share similar survival patterns, thus improving the accuracy of a clinical outcome predictor.

  18. Human IgG subclass antibodies to the 19 kilodalton carboxy ...

    African Journals Online (AJOL)

    Human IgG subclass antibodies to the 19 kilodalton carboxy terminal fragment of Plasmodium Falciparum merozoite surface protein 1 (MSP1 19 ) and predominance of the MAD20 allelic type of MSP1 in Uganda.

  19. Discovery of a new subclass of alpha-conotoxins in the venom of Conus australis

    Digital Repository Service at National Institute of Oceanography (India)

    Lebbe, E.K.M.; Peigneur, S.; Maiti, M.; Mille, B.G.; Prabhadevi; Ravichandran, S.; Lescrinier, E.; Waelkens, E.; DeSouza, L.; Herdewijn, P.; Tytgat, J.

    -conotoxins, acts on nicotinic acetylcholine receptors (nAChRs) which dysfunctions play important roles in pathologies such as epilepsy, myasthenic syndromes, schizophrenia, Parkinson's disease and Alzheimer's disease. Here we define a new subclass of the alpha...

  20. Fractal analysis reveals subclasses of neurons and suggests an explanation of their spontaneous activity.

    Science.gov (United States)

    Favela, Luis H; Coey, Charles A; Griff, Edwin R; Richardson, Michael J

    2016-07-28

    The present work used fractal time series analysis (detrended fluctuation analysis; DFA) to examine the spontaneous activity of single neurons in an anesthetized animal model, specifically, the mitral cells in the rat main olfactory bulb. DFA bolstered previous research in suggesting two subclasses of mitral cells. Although there was no difference in the fractal scaling of the interspike interval series at the shorter timescales, there was a significant difference at longer timescales. Neurons in Group B exhibited fractal, power-law scaled interspike intervals, whereas neurons in Group A exhibited random variation. These results raise questions about the role of these different cells within the olfactory bulb and potential explanations of their dynamics. Specifically, self-organized criticality has been proposed as an explanation of fractal scaling in many natural systems, including neural systems. However, this theory is based on certain assumptions that do not clearly hold in the case of spontaneous neural activity, which likely reflects intrinsic cell dynamics rather than activity driven by external stimulation. Moreover, it is unclear how self-organized criticality might account for the random dynamics observed in Group A, and how these random dynamics might serve some functional role when embedded in the typical activity of the olfactory bulb. These theoretical considerations provide direction for additional experimental work. Published by Elsevier Ireland Ltd.

  1. The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients.

    Science.gov (United States)

    van Delft, Myrthe A M; Verheul, Marije K; Burgers, Leonie E; Derksen, Veerle F A M; van der Helm-van Mil, Annette H M; van der Woude, Diane; Huizinga, Tom W J; Toes, René E M; Trouw, Leendert A

    2017-08-15

    Anti-carbamylated protein (anti-CarP) antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties. At present, the breadth and molecular make-up of the anti-CarP antibody response is ill defined. To understand the anti-CarP antibody immune response and potential immune effector mechanisms it can recruit, we determined the anti-CarP antibody isotype and IgG-subclass usage in RA patients. Anti-CarP antibody IgM, IgA, and IgG or IgG subclasses were detected by enzyme-linked immunosorbent assay (ELISA) in sera from 373 unselected RA patients and 196 healthy controls. An additional 114 anti-citrullinated protein antibody (ACPA) and anti-CarP IgG double-positive patients were selected to study the concomitant presence of both antibody systems. Anti-CarP IgG was present in around 45% of the patients and comprised all anti-CarP IgG subclasses. The presence of anti-CarP IgG1 particularly associates with radiological damage. Anti-CarP IgM was detected in 16% of RA patients, even in anti-CarP IgG-positive individuals, and is indicative of an actively ongoing immune response. Around 45% of the patients were positive for IgA which included ACPA-positive cases but also 24% of the ACPA-negative cases. In ACPA and anti-CarP double-positive patients, the distribution and number of isotypes and IgG subclasses was similar for both autoantibodies at the group level, but substantial variation was observed within individual patient samples. In RA, the anti-CarP antibody response uses a broad spectrum of isotypes and seems to be an actively ongoing immune reaction. Furthermore, the anti-CarP and ACPA autoantibody responses seems to be differentially regulated.

  2. Taxonomic resolutions based on 18S rRNA genes: a case study of subclass copepoda.

    Directory of Open Access Journals (Sweden)

    Shu Wu

    Full Text Available Biodiversity studies are commonly conducted using 18S rRNA genes. In this study, we compared the inter-species divergence of variable regions (V1-9 within the copepod 18S rRNA gene, and tested their taxonomic resolutions at different taxonomic levels. Our results indicate that the 18S rRNA gene is a good molecular marker for the study of copepod biodiversity, and our conclusions are as follows: 1 18S rRNA genes are highly conserved intra-species (intra-species similarities are close to 100%; and could aid in species-level analyses, but with some limitations; 2 nearly-whole-length sequences and some partial regions (around V2, V4, and V9 of the 18S rRNA gene can be used to discriminate between samples at both the family and order levels (with a success rate of about 80%; 3 compared with other regions, V9 has a higher resolution at the genus level (with an identification success rate of about 80%; and 4 V7 is most divergent in length, and would be a good candidate marker for the phylogenetic study of Acartia species. This study also evaluated the correlation between similarity thresholds and the accuracy of using nuclear 18S rRNA genes for the classification of organisms in the subclass Copepoda. We suggest that sample identification accuracy should be considered when a molecular sequence divergence threshold is used for taxonomic identification, and that the lowest similarity threshold should be determined based on a pre-designated level of acceptable accuracy.

  3. Recurrent meningitis in a child with IgG3 subclass deficiency.

    Science.gov (United States)

    Vehapoglu, Aysel; Ozgurhan, Gamze; Demir, Aysegul Dogan; Uzuner, Selcuk; Nursoy, Mustafa Atilla; Turkmen, Serdar

    2014-08-01

    Recurrent meningitis is an uncommon life-threatening condition. Here, the case of a 6-year-old boy is reported who had two episodes of meningitis with an IgG3 subclass deficiency. The boy had aseptic meningitis at the age of 3 years, followed by bacterial meningitis at the age of 4 years. Primary immunoglobulin deficiencies are a group of disorders associated with an increased incidence and/or severity of infection. Recurrent infections, sinusitis, bronchitis, and pneumonia are the most frequently observed illnesses in patients with IgG subclass deficiencies, of which an IgG3 subclass deficiency is the most common, especially in adults. Although cases of recurrent viral or bacterial meningitis have been reported, herein a patient is presented with recurrence of aseptic and bacterial meningitis 1 year after the initial episode. Some researchers recommend that all children with episodes of recurrent meningitis should be screened for primary immunoglobulin or complement deficiencies.

  4. [Sinonasal polyposis associated with a deficiency subclass immunoglobulin G: Place of substitution immunoglobulins].

    Science.gov (United States)

    Hoan, Nhung Tran Khai; Karmochkine, M; Laccourreye, O; Bonfils, P

    2014-01-01

    To study the effect of the introduction of a substitution by intravenous Immunoglobulins (Ig IV) at patients with immunoglobulins G (IgG) subclasses deficiency and nasal polyposis. Prospective study concerning five patients with IgG subclasses deficiency and nasal polyposis treated by Ig IV. Rhinologic, otologic and pulmonary symptoms, exacerbations of nasal polyposis, chronic otitis and asthma as well as the number of antibiotics and corticoids treatments were counted during the Ig IV substitution. To study the association between IgIV substitution and the number of exacerbations of nasal polyposis, chronic otitis, asthma and the number of antibiotics and corticoids treatments in patients with IgG subclasses deficiency and nasal polyposis. Five patients with a IgG subclass deficiency and nasal polyposis were substituted. The number of antibiotics and corticoids cures increased at one patient and remained stable at four others. The number of sinus, ear and lung infections as well as the global rhinologic score of symptoms and the endoscopic stage of the nasal polyposis remained stable. In the absence of efficiency of the treatment, this one was interrupted at the end of 6 months for patients n° 1 and n° 3, 24 months for patient n° 4 and 42 months for patient n° 5. The current study failed to highlight clinical improvement in patients wih IgG subclasses deficiency and nasal polyposis treated by Ig IV. A previous study had not allowed to find a link between IgG subclasses deficiency and severity of nasal polyposis, what seems to be confirmed by the absence of improvement brought during the substitution of this deficit in the current study.

  5. A two-level formal specification of a defense communications system

    Energy Technology Data Exchange (ETDEWEB)

    Chisholm, G.H. [Argonne National Lab., IL (United States). Decision and Information Sciences Div.; Kemmerer, R.A. [Univ. of California, Santa Barbara, CA (United States). Reliable Software Group

    1994-04-01

    Computer systems are being used in critical situations with sensitive data, which makes it very important to ensure that these systems perform as desired. The defense communications system contains particularly sensitive data. A two-level ASLAN formal specification of a defense communications system is presented. The ASLAN model is designed to enhance the understanding of critical requirements and demands of the defense communications system. For the top-level (high-level) specifications, the structural details of the actual network are actual network are abstracted to allow more time for examining the interactions between the sites and the network. At this level, DataGrams move through the network, although the actual routing decisions are not specified. More details are added in the second-level specification. At this level, structure is added to the network.

  6. On some subclasses of the family of Darboux Baire 1 functions

    Directory of Open Access Journals (Sweden)

    Gertruda Ivanova

    2014-01-01

    Full Text Available We introduce a subclass of the family of Darboux Baire 1 functions \\(f:\\mathbb{R}\\rightarrow\\mathbb{R}\\ modifying the Darboux property analogously as it was done by Z. Grande in [On a subclass of the family of Darboux functions, Colloq. Math. 17 (2009, 95-104], and replacing approximate continuity with \\(\\mathcal{I}\\-approximate continuity, i.e. continuity with respect to the \\(\\mathcal{I}\\-density topology. We prove that the family of all Darboux quasi-continuous functions from the first Baire class is a strongly porous set in the space \\(\\mathcal{DB}_1\\ of Darboux Baire 1 functions, equipped with the supremum metric.

  7. Is Fc gamma receptor IIA (FcγRIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?

    Science.gov (United States)

    Cherif, Mariama K; Sanou, Guillaume S; Bougouma, Edith C; Diarra, Amidou; Ouédraogo, Alphonse; Dolo, Amagana; Troye-Blomberg, Marita; Cavanagh, David R; Theisen, Michael; Modiano, David; Sirima, Sodiomon B; Nebié, Issa

    2015-02-01

    In the present study, the influences of FcγRIIA polymorphism on susceptibility to malaria and antibody responses to Plasmodium falciparum antigens were analyzed in children. We recruited 96 healthy children between 3 and 10 years at the beginning of the high transmission season and we followed up for 5 months through the high transmission season to assess the parasitological, immunological and genetic endpoints in relation to clinical malaria status. There was a similar distribution of homozygous and heterozygous individuals carrying the FcγRIIA-131R/R and FcγRIIA-131R/H allele, whereas the number of FcγRIIA-131H/H homozygous individuals was lower. P. falciparum infection frequency was not associated with the FcγRIIa-131R/H polymorphism. Only IgG antibody responses to GLURP R0 showed a significant association between antibody levels and FcγRIIA polymorphism (p=0.02). IgG levels to MSP2a were significantly higher in children who did not experience any clinical malaria episode compared to those who experienced at least one malaria episode (p=0.019). Cytophilic and non-cytophylic IgG subclass levels were higher in children without malaria than those who experienced at least one malaria episode. This difference was statistically significant for IgG1 to MSP3 (p=0.003) and to MSP2a (p=0.006); IgG3 to MSP2a (p=0.007) and to GLURP R0 (p=0.044); IgG2 to MSP2b (p=0.007) and IgG4 to MSP3 (p=0.051) and to MSP2a (p=0.049). In this study, homozygous carriers of the FcγRIIA-131R/R allele had higher malaria-specific antibody levels compare to the heterozygous carriers FcγRIIA-131R/H alleles and to homozygous carriers of FcγRIIA-131H/H alleles. The pre-existing antibodies responses were related to a reduced subsequent risk of clinical malaria. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Predictors of shingles reports at diagnosis of common variable immunodeficiency and selective immunoglobulin G subclass deficiency in 212 Alabama adults

    Directory of Open Access Journals (Sweden)

    James C. Barton

    2012-07-01

    Full Text Available We sought to determine predictors of shingles reports in adults with common variable immunodeficiency or immunoglobulin (Ig G subclass deficiency (CVID/IgGSD. We tabulated observations at diagnosis of CVID/IgGSD in 212 white adult index patients (165 women, 47 men who responded to a question about having had shingles. None had been vaccinated for herpes zoster. We analyzed age, sex, and shingles reports; blood levels of CD19+, CD4+, CD8+, and CD56+ mononuclear cells; serum levels of IgG subclasses, IgA, and IgM; and positivity for human leukocyte antigen (HLA-A and -B haplotypes. Cell counts and immunoglobulin levels were normalized with loge (ln transformation for analyses. Thirty-one patients (14.6% reported shingles; 11 reported recurrent or disseminated shingles. Patients with shingles reports had greater mean age at diagnosis of CVID/IgGSD [54±13 (standard deviation years vs. 47±12 years; P=0.0130] and a greater prevalence of HLA-A*01, B*08 positivity (35.5% vs. 17.7%; P=0.0227. In a 13-factor logistic regression model, there was a positive association of age with shingles reports [P=0.0151; odds ratio (1.05, 95% confidence interval 1.01, 1.08]. HLA-A*01, B*08 positivity was also positively associated with shingles reports [P=0.0480; odds ratio 2.61 (1.00, 6.81]. During a mean followup interval of 7.5 years after CVID/IgGSD diagnosis, the prevalence of recurrent shingles was almost five-fold greater in patients with previous shingles reports. In conclusion, in white adults at CVID/IgGSD diagnosis, age at diagnosis and positivity for HLA-A*01, B*08 have significant positive associations with reports of previous shingles.

  9. Affinity separation of immunoglobulin G subclasses on dye attached poly(hydroxypropyl methacrylate) beads.

    Science.gov (United States)

    Yavuz, Handan; Akgöl, Sinan; Say, Ridvan; Denizli, Adil

    2006-11-15

    Poly(hydroxypropyl methacrylate) [poly(HPMA)] gel beads with an average size of 150-200 micro m were prepared by suspension polymerization of hydroxypropyl methacrylate (HPMA). The poly(HPMA) gel beads were characterized by swelling studies, surface area measurements, scanning electron microscopy (SEM) and elemental analysis. Poly(HPMA) gel beads had a specific surface area of 88.6 m(2)/g. The dye Reactive Green HE 4BD was chemically attached to yield dye-poly(HPMA) gel beads at an average concentration of 44.3 micro mol dye/g bead with a swelling ratio of 75%. These dye attached gel beads were used in the separation of immunoglobulin-G (IgG) through adsorption-elution studies. The non-specific adsorption of IgG on the poly(HPMA) gel beads was 0.5 mg/g. The attachment of Reactive Green HE 4BD significantly increased the adsorption of IgG up to 71 mg/g. The Langmuir adsorption model was found to be applicable in interpretation of data pertaining to the adsorption studies of IgG with Reactive Green HE 4BD attached to the poly(HPMA) gel beads. The adsorption of IgG was found to be optimal at pH 7.0. The adsorption of IgG was observed to decrease by about 76% as the NaCl concentration was increased from 0.001 to 0.1 M. The IgG adsorption capacity of the dye attached poly(HPMA) gel beads was determined for a commercially available IgG solution to be 4.2 mg/g for IgG(1), 64.5 mg/g for IgG(2), 7.1 mg/g for IgG(3) and 10.8 mg/g for IgG(4). The Reactive Green HE 4BD attached poly(HPMA) gel beads have a significant adsorption capacity for IgG(2). The quantity of adsorbed IgG(2) is three times higher than the quantity of the other subclasses, IgG(1), IgG(3) and IgG(4). A similar adsorption behaviour was observed when the albumin free human plasma was used. The quantity of adsorbed IgG(2) is higher than the quantity of the other subclasses, IgG(1), IgG(3) and IgG(4). Adsorption capacities for albumin free human plasma were obtained as 6.4 mg/g for IgG(1), 67.8 mg/g for IgG(2

  10. Designing Peace and Conflict Exercises: Level of Analysis, Scenario, and Role Specification

    Science.gov (United States)

    Bartels, Elizabeth; McCown, Margaret; Wilkie, Timothy

    2013-01-01

    Attentiveness to and transparency about the methodological implications of the level of analysis selected for peace and conflict exercises constitute essential elements of good game design. The article explores the impact of level of analysis choices in the context of two key portions of exercises, scenario construction and role specification. It…

  11. Effects of Immunoglobulin Replacement on Asthma Exacerbation in Adult Asthmatics with IgG Subclass Deficiency.

    Science.gov (United States)

    Kim, Joo Hee; Ye, Young Min; Ban, Ga Young; Shin, Yoo Seob; Lee, Hyun Young; Nam, Young Hee; Lee, Soo Keol; Cho, You Sook; Jang, Seung Hun; Jung, Ki Suck; Park, Hae Sim

    2017-11-01

    Recurrent respiratory tract infection is a common manifestation of primary immunodeficiency disease, and respiratory viruses or bacteria are important triggers of asthma exacerbations. Asthma often coexists with humoral immunodeficiency in adults, and some asthmatics with immunoglobulin (Ig) G subclass deficiency (IgGSCD) suffer from recurrent exacerbations. Although some studies suggest a benefit from Ig replacement, others have failed to support its use. This study aimed to assess the effect of Ig replacement on asthma exacerbation caused by respiratory infection as well as the asthma control status of adult asthmatics with IgGSCD. This is a multi-center, open-label study of adult asthmatics with IgGSCD. All patients received monthly intravenous immunoglobulin (IVIG) for 6 months and were evaluated regarding asthma exacerbation related to infection, asthma control status, quality of life, and lung function before and after IVIG infusion. A total of 30 patients were enrolled, and 24 completed the study. Most of the patients had a moderate degree of asthma severity with partly (52%) or uncontrolled (41%) status at baseline. IVIG significantly reduced the proportion of patients with asthma exacerbations, lowered the number of respiratory infections, and improved asthma control status, compared to the baseline values (P<0.001). The mean asthma-specific quality of life and asthma control test scores were improved significantly (P=0.009 and P=0.053, respectively); however, there were no significant changes in lung function. IVIG reduced the frequency of asthma exacerbations and improved asthma control status in adult asthmatics with IgGSCD, suggesting that IVIG could be an effective treatment option in this population.

  12. Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

    Science.gov (United States)

    Boesch, Austin W.; Osei-Owusu, Nana Yaw; Crowley, Andrew R.; Chu, Thach H.; Chan, Ying N.; Weiner, Joshua A.; Bharadwaj, Pranay; Hards, Rufus; Adamo, Mark E.; Gerber, Scott A.; Cocklin, Sarah L.; Schmitz, Joern E.; Miles, Adam R.; Eckman, Joshua W.; Belli, Aaron J.; Reimann, Keith A.; Ackerman, Margaret E.

    2016-01-01

    Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies. PMID:28018355

  13. Influence of immunoglobulin G-glycan and subclass variation on antibody effector functions

    NARCIS (Netherlands)

    Dekkers, G.

    2017-01-01

    Antibodies signal to other parts of the immune system by binding of their constant domain (Fc) to receptors, such as Fc gamma receptors (FcγR) or C1q of the complement system in the case of immunoglobulin G (IgG). For these interactions the Fc-structure, influenced by subclasses or

  14. Fekete-Szegö Inequalities of a Subclass of Multivalent Analytic Functions

    Directory of Open Access Journals (Sweden)

    Selvaraj C.

    2016-07-01

    Full Text Available The main object of this paper is to study Fekete-Szegö problem for a certain subclass of p - valent analytic functions. Fekete-Szegö inequality of several classes are obtained as special cases from our results. Applications of the result are also obtained on the class defined by convolution.

  15. Separation of human immunoglobulin G subclasses on a protein A monolith column.

    Science.gov (United States)

    Leblebici, Pelin; Leblebici, M Enis; Ferreira-da-Silva, Frederico; Rodrigues, Alírio E; Pais, Luís S

    2014-07-01

    Monolithic columns have attracted significant attention for the purification of large biomolecules. In the present study, a step gradient elution method was evaluated for the separation of human immunoglobulin G (hIgG) into its subclasses on CIM (convective interaction media) r-protein A (recombinant protein A) monolithic column. hIgG was loaded onto the column and bound protein was eluted with a pH gradient. The subclass content of the eluted fractions was analyzed by enzyme-linked immunosorbent assay (ELISA). Results showed that separation of IgG3 from the other three subclasses can be successfully achieved with high selectivity (100%) and throughput on monolithic media. It was also revealed that enriched fractions of IgG1 and IgG2 could be obtained from purified hIgG in a 28min long chromatographic run. Three fractions with high IgG1 content (89.1%, 94.3% and 88.8%) were recovered. Furthermore, IgG2 was enriched to 64% successfully. A rapid step gradient elution scheme without any additives in buffers was proven to obtain enriched preparations of the two important subclasses with high throughput. The separation time can be reduced even more by increasing the flow rate without any loss in selectivity, which will be beneficial in industrial scale applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Integrative Transcriptome Analysis Reveals Common Molecular Subclasses of Human Hepatocellular Carcinoma

    Science.gov (United States)

    Hoshida, Yujin; Nijman, Sebastian M.B.; Kobayashi, Masahiro; Chan, Jennifer A.; Brunet, Jean-Philippe; Chiang, Derek Y.; Villanueva, Augusto; Newell, Philippa; Ikeda, Kenji; Hashimoto, Masaji; Watanabe, Goro; Gabriel, Stacey; Friedman, Scott L.; Kumada, Hiromitsu; Llovet, Josep M.; Golub, Todd R.

    2009-01-01

    Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and prior attempts to develop genomics-based classification for HCC have yielded highly divergent results, indicating difficulty to identify unified molecular anatomy. We performed a meta-analysis of gene expression profiles in datasets from 8 independent patient cohorts across the world. In addition, aiming to establish the real world applicability of a classification system, we profiled 118 formalin-fixed, paraffin-embedded tissues from an additional patient cohort. A total of 603 patients were analyzed, representing the major etiologies of HCC (hepatitis B and C) collected from Western and Eastern countries. We observed 3 robust HCC subclasses (termed S1, S2, and S3), each correlated with clinical parameters such as tumor size, extent of cellular differentiation, and serum alpha-fetoprotein levels. An analysis of the components of the signatures indicated that S1 reflected aberrant activation of the WNT signaling pathway, S2 was characterized by proliferation as well as MYC and AKT activation, and S3 was associated with hepatocyte differentiation. Functional studies indicated that the WNT pathway activation signature characteristic of S1 tumors was not simply the result of beta-catenin mutation, but rather was the result of TGF-beta activation, thus representing a new mechanism of WNT pathway activation in HCC. These experiments establish the first consensus classification framework for HCC based on gene-expression profiles, and highlight the power of integrating of multiple datasets to define a robust molecular taxonomy of the disease. PMID:19723656

  17. Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts.

    Science.gov (United States)

    Nimptsch, Katharina; Zhang, Xuehong; Cassidy, Aedín; Song, Mingyang; O'Reilly, Éilis J; Lin, Jennifer H; Pischon, Tobias; Rimm, Eric B; Willett, Walter C; Fuchs, Charles S; Ogino, Shuji; Chan, Andrew T; Giovannucci, Edward L; Wu, Kana

    2016-01-01

    Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses' Health Study. During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer.

  18. IDH mutation and neuroglial developmental features define clinically distinct subclasses of lower grade diffuse astrocytic glioma.

    Science.gov (United States)

    Gorovets, Daniel; Kannan, Kasthuri; Shen, Ronglai; Kastenhuber, Edward R; Islamdoust, Nasrin; Campos, Carl; Pentsova, Elena; Heguy, Adriana; Jhanwar, Suresh C; Mellinghoff, Ingo K; Chan, Timothy A; Huse, Jason T

    2012-05-01

    Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma [World Health Organization (WHO) IV], its most malignant subtype, lower grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notable clinical heterogeneity. Accordingly, we sought to identify and characterize clinically relevant molecular subclasses of lower grade diffuse astrocytic gliomas. We conducted multidimensional molecular profiling, including global transcriptional analysis, on 101 lower grade diffuse astrocytic gliomas collected at our own institution and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, platelet-derived growth factor receptor (PDGFR)A overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone. This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. We have elucidated molecularly distinct subclasses of lower grade diffuse astrocytic glioma that dictate clinical behavior and show fundamental associations with both IDH mutational status and neuroglial developmental stage. ©2012 AACR.

  19. Association between habitual dietary intake and lipoprotein subclass profile in healthy young adults.

    Science.gov (United States)

    Bogl, L H; Pietiläinen, K H; Rissanen, A; Kangas, A J; Soininen, P; Rose, R J; Ala-Korpela, M; Kaprio, J

    2013-11-01

    Nutritional epidemiology is increasingly shifting its focus from studying single nutrients to the exploration of the whole diet utilizing dietary pattern analysis. We analyzed associations between habitual diet (including macronutrients, dietary patterns, biomarker of fish intake) and lipoprotein particle subclass profile in young adults. Complete dietary data (food-frequency questionnaire) and lipoprotein subclass profile (via nuclear magnetic resonance spectroscopy) were available for 663 subjects from the population-based FinnTwin12 study (57% women, age: 21-25 y). The serum docosahexaenoic to total fatty acid ratio was used as a biomarker of habitual fish consumption. Factor analysis identified 5 dietary patterns: "Fruit and vegetables", "Meat", "Sweets and desserts", "Junk food" and "Fish". After adjustment for sex, age, body mass index, waist circumference, physical activity, smoking status and alcohol intake, the "Junk food" pattern was positively related to serum triglycerides (r = 0.12, P = 0.002), a shift in the subclass distribution of VLDL toward larger particles (r = 0.12 for VLDL size, P < 0.001) and LDL toward smaller particles (r = -0.15 for LDL size, P < 0.001). In addition, higher scores on this pattern were positively correlated with concentrations of small, dense HDL (r = 0.16, P < 0.001). Habitual fish intake associated negatively with VLDL particle diameter ("Fish" pattern and biomarker) and positively with HDL particle diameter (biomarker). Our results suggest that in young adults, higher habitual fish consumption is related to favorable subclass distributions of VLDL and HDL, while junk food intake is associated with unfavorable alterations in the distribution of all lipoprotein subclasses independent of adiposity and other lifestyle factors. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

    Science.gov (United States)

    McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

    2016-01-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  1. Structural Basis for Binding Specificity between Subclasses of Modular Polyketide Synthase Docking Domains

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, Tonia J.; Geders, Todd W.; Bartley, III, Frank E.; Reynolds, Kevin A.; Smith, Janet L.; Sherman, David H.; (Michigan); (Portland SU)

    2009-04-02

    Bacterial type I polyketide synthases (PKSs) assemble structurally diverse natural products of significant clinical value from simple metabolic building blocks. The synthesis of these compounds occurs in a processive fashion along a large multiprotein complex. Transfer of the acyl intermediate across interpolypeptide junctions is mediated, at least in large part, by N- and C-terminal docking domains. We report here a comprehensive analysis of the binding affinity and selectivity for the complete set of discrete docking domain pairs in the pikromycin and erythromycin PKS systems. Despite disconnection from their parent module, each cognate pair of docking domains retained exquisite binding selectivity. Further insights were obtained by X-ray crystallographic analysis of the PikAIII/PikAIV docking domain interface. This new information revealed a series of key interacting residues that enabled development of a structural model for the recently proposed H2-T2 class of polypeptides involved in PKS intermodular molecular recognition.

  2. Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies.

    Science.gov (United States)

    Latrofa, F; Ricci, D; Montanelli, L; Piaggi, P; Mazzi, B; Bianchi, F; Brozzi, F; Santini, P; Fiore, E; Marinò, M; Tonacchera, M; Vitti, P

    2014-12-01

    The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine ((131)I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before (131) I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to (125-) (I) Tg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0.024). TgAb κ chains did not change (P = 0.052), whereas TgAb λ chains increased significantly (P = 0.001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after (131)I (P = 0.008 and P = 0.006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after (131)I. We conclude that (131)I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern. © 2014 British Society for Immunology.

  3. Influence of catheterization on the prostate specific antigen level in patient suffering from prostate disorder

    OpenAIRE

    Osman Sianipar, Osman Sianipar

    2015-01-01

    Background: The increase of life expectancy may increase the number of patients suffered from prostate disorder. In Indonesia prostate cancer is in the top ten malignancies in men and is the second most frequent malignancies in urology clinics. Early detection may decreasies its fatality rate and increase the quality of life. Prostate specific antigen (PSA) is clinically the most useful tumor marker; its serum level has positive correlation with the prostate cancer. Serum PSA level will also ...

  4. Sensitivity and specificity of fluid-blood levels for coagulopathy in acute intracerebral hematomas

    Energy Technology Data Exchange (ETDEWEB)

    Pfleger, M.J.; Hardee, E.P.; Hayman, L.A.; Contant, C.F. Jr. (Baylor College of Medicine, Houston, TX (United States))

    1994-02-01

    To characterize the imaging features of intracerebral hemorrhages in patients with coagulopathies that alter prothrombin time or partial thromboplastin time. A fluid-blood level was defined as a horizontal interface between hypodense bloody serum layered above hyperdense settled blood. The prevalence of fluid-blood levels in acute intracerebral hemorrhages was determined on third-generation CT scans in 32 patients with elevation in prothrombin time or partial thromboplastin time. This was compared with the frequency of fluid-blood levels in 185 patients with intracerebral hemorrhage in which there was no laboratory evidence of coagulopathy. The probability of finding a fluid-blood level in an intracerebral hemorrhage of a patient with abnormal prothrombin time or partial thromboplastin time was 59% (sensitivity). The probability that there will be no fluid-blood level in a patient with a normal prothrombin time and partial thromboplastin time was 98% (specificity). Fluid-blood levels in acute intracerebral hemorrhage are moderately sensitive to the presence of coagulopathy (i.e., abnormal prothrombin time and partial thromboplastin time) and highly specific for this condition. Thus, an intracerebral hemorrhage with a fluid-blood level should prompt a thorough search for coagulopathy because early treatment of this condition may improve the 40% mortality in these patients. Caution should be used to distinguish the horizontal interface of a fluid-blood level from a clot with a flat top. A decubitus CT is useful in these rare instances. 20 refs., 5 figs., 2 tabs.

  5. Lipoprotein particle subclasses, cardiovascular disease and HIV infection

    DEFF Research Database (Denmark)

    Duprez, Daniel A; Kuller, Lewis H; Tracy, Russell

    2009-01-01

    OBJECTIVE: To study the association of lipoprotein particles with CVD in a subgroup of HIV-infected patients who were enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART was a trial of intermittent use of ART (drug conservation [DC]) versus continuous of ART......-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer. Latest levels of total HDL-p were also significantly inversely associated with CVD; treatment interruption led to decrease of total HDL-p; adjusting for latest HDL-p did not explain the greater risk of CVD that was observed in the DC versus VS group....... CONCLUSIONS: Lipoprotein particles, especially lower levels of small and large HDL-p identify HIV-infected patients at increased risk of CVD independent of other CVD risk factors....

  6. Domain-Specific Creativity in Relation to the Level of Empathy and Systemizing

    Science.gov (United States)

    Dostál, Daniel; Plháková, Alena; Záškodná, Tereza

    2017-01-01

    This study aimed to explore self-reported domain-specific creativity in relation to the level of empathy, systemizing, and the Big Five personality dimensions. The research sample consisted of 1112 college students to whom the Kaufman Domains of Creativity Scale (K-DOCS), the Creative Achievement Questionnaire (CAQ), Baron-Cohen's empathy and…

  7. Response to Specific Training for Students with Different Levels of Mathematical Difficulties

    Science.gov (United States)

    Re, Anna Maria; Pedron, Martina; Tressoldi, Patrizio Emanuele; Lucangeli, Daniela

    2014-01-01

    The purpose of this study was to determine the efficacy of specific, individualized training for students with different levels of mathematical difficulties. Fifty-four students, with either severe or mild math difficulties, were assigned to individualized training or to a control condition. Ten students with severe math difficulties…

  8. Decision Level Fusion of Domain Specific Regions for Facial Action Recognition

    NARCIS (Netherlands)

    Jiang, Bihan; Martinez, Brais; Valstar, Michel F.; Pantic, Maja

    In this paper we propose a new method for the detection of action units that relies on a novel region-based face representation and a mid-level decision layer that combines region-specific information. Different from other approaches, we do not represent the face as a regular grid based on the face

  9. Diagnostic value of free prostate-specific antigen among men with a prostate-specific antigen level of liter.

    Science.gov (United States)

    Finne, Patrik; Auvinen, Anssi; Määttänen, Liisa; Tammela, Teuvo L; Ruutu, Mirja; Juusela, Harri; Martikainen, Paula; Hakama, Matti; Stenman, Ulf-Håkan

    2008-08-01

    The percentage of free prostate-specific antigen (%fPSA) improves the diagnostic accuracy for prostate cancer when the serum level of total PSA (tPSA) is elevated. Approximately 14% of men with a tPSA below 3 microg/l have prostate cancer on biopsy, but the diagnostic value of %fPSA in such men is rather unknown. The purpose was to estimate the impact of %fPSA on future prostate cancer risk among men with a normal tPSA in prostate cancer screening. The first round of the Finnish arm of the European Randomized Trial for Screening of Prostate Cancer in 1996 to 1999 comprised 20,793 men aged 55-67 yr. Screen-negative men (tPSA level below 3.0 microg/l, n=17,680) were followed up until the end of 2003. Cumulative risk of prostate cancer was calculated as a function of %fPSA. During the median follow-up of 5.8 yr (range, 0-7.7 yr), 327 men were diagnosed with prostate cancer and 25% of them had a Gleason score of 7 or higher. Five years after the first screening, cumulative risk of prostate cancer was 1.7% (95%CI, 1.5-1.9%). Men with a %fPSA in the lowest quartile (23.7%). In men with a low serum tPSA, a low %fPSA is a strong predictor of later diagnosis of prostate cancer.

  10. Gene-specific correlation of RNA and protein levels in human cells and tissues

    DEFF Research Database (Denmark)

    Edfors, Fredrik; Danielsson, Frida; Hallström, Björn M.

    2016-01-01

    to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP......An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring...... copies per mRNA molecule for others. In conclusion, our data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell, thus forming an attractive link between the field of genomics and proteomics....

  11. Hypertriglyceridemia and unusual lipoprotein subclass distributions associated with late pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Forte, T.M.; Kretchmer, N.; Silliman, K. (Lawrence Berkeley Lab., CA (United States))

    1991-03-15

    In the human adult population elevated plasma triglyceride (TG) levels are associated with decreased high density lipoprotein-cholesterol (HDL-C) levels and decreased HDL and LDL particle sizes. Late pregnancy is a hypertriglyceridemic state where little is known about LDL and HDL subpopulation distribution. Plasma lipids, apolipoproteins (apo) and lipoprotein subpopulations were examined in 36 pregnant women at 36 wk pregnancy and 6 wk postpartum and correlated with HDL and LDL size. There was a significant decrease in LDL diameter at 36 wk pre, 25 {plus minus} 0.7 nm compared, with 6 wk post, 26.4 {plus minus} 0.8 nm. A total of 97% of the 36 wk pre subjects had small dense LDL which paralleled increases in apoB concentration. Unlike LDL HDL at 36 wks pre showed a significant increase in larger sized particles where HDL{sub 2b} predominated. There was a positive correlation between HDL{sub 2b} mass and apoAl and HDL-C concentrations. Late pregnancy is a metabolic state where the predominance of large, HDL{sub 2b} particles is discordant with the predominance of small LDL and elevated TG. This annual metabolic pattern may in part be due to hormonal changes occurring in late pregnancy.

  12. Temporal Processing Capacity in High-Level Visual Cortex Is Domain Specific.

    Science.gov (United States)

    Stigliani, Anthony; Weiner, Kevin S; Grill-Spector, Kalanit

    2015-09-09

    Prevailing hierarchical models propose that temporal processing capacity--the amount of information that a brain region processes in a unit time--decreases at higher stages in the ventral stream regardless of domain. However, it is unknown if temporal processing capacities are domain general or domain specific in human high-level visual cortex. Using a novel fMRI paradigm, we measured temporal capacities of functional regions in high-level visual cortex. Contrary to hierarchical models, our data reveal domain-specific processing capacities as follows: (1) regions processing information from different domains have differential temporal capacities within each stage of the visual hierarchy and (2) domain-specific regions display the same temporal capacity regardless of their position in the processing hierarchy. In general, character-selective regions have the lowest capacity, face- and place-selective regions have an intermediate capacity, and body-selective regions have the highest capacity. Notably, domain-specific temporal processing capacities are not apparent in V1 and have perceptual implications. Behavioral testing revealed that the encoding capacity of body images is higher than that of characters, faces, and places, and there is a correspondence between peak encoding rates and cortical capacities for characters and bodies. The present evidence supports a model in which the natural statistics of temporal information in the visual world may affect domain-specific temporal processing and encoding capacities. These findings suggest that the functional organization of high-level visual cortex may be constrained by temporal characteristics of stimuli in the natural world, and this temporal capacity is a characteristic of domain-specific networks in high-level visual cortex. Significance statement: Visual stimuli bombard us at different rates every day. For example, words and scenes are typically stationary and vary at slow rates. In contrast, bodies are dynamic

  13. The GLAS Standard Data Products Specification--Level 2, Version 9. Volume 14

    Science.gov (United States)

    Lee, Jeffrey E.

    2013-01-01

    The Geoscience Laser Altimeter System (GLAS) is the primary instrument for the ICESat (Ice, Cloud and Land Elevation Satellite) laser altimetry mission. ICESat was the benchmark Earth Observing System (EOS) mission for measuring ice sheet mass balance, cloud and aerosol heights, as well as land topography and vegetation characteristics. From 2003 to 2009, the ICESat mission provided multi-year elevation data needed to determine ice sheet mass balance as well as cloud property information, especially for stratospheric clouds common over polar areas. It also provided topography and vegetation data around the globe, in addition to the polar-specific coverage over the Greenland and Antarctic ice sheets.This document defines the Level-2 GLAS standard data products. This document addresses the data flow, interfaces, record and data formats associated with the GLAS Level 2 standard data products. The term standard data products refers to those EOS instrument data that are routinely generated for public distribution. The National Snow and Ice Data Center (NSDIC) distribute these products. Each data product has a unique Product Identification code assigned by the Senior Project Scientist. The Level 2 Standard Data Products specifically include those derived geophysical data values (i.e., ice sheet elevation, cloud height, vegetation height, etc.). Additionally, the appropriate correction elements used to transform the Level 1A and Level 1B Data Products into Level 2 Data Products are included. The data are packaged with time tags, precision orbit location coordinates, and data quality and usage flags.

  14. Preliminary level 2 specification for the nested, fixed-depth sampling system

    Energy Technology Data Exchange (ETDEWEB)

    BOGER, R.M.

    1999-02-08

    This preliminary Level 2 Component Specification establishes the performance, design, development, and test requirements for the in-tank sampling system which will support the BNFL contract in the final disposal of Hanford's High Level Wastes (HLW) and Low Activity Wastes (LAW). The PHMC will provide Low Activity Wastes (LAW) tank wastes for final treatment by BNFL from double-shell feed tanks. Concerns about the inability of the baseline ''grab'' sampling to provide large volume samples within time constraints has led to the development of a nested, fixed-depth sampling system. This sampling system will provide large volume? representative samples without the environmental, radiation exposure, and sample volume Impacts of the current base-line ''grab'' sampling method. This preliminary Level 2 Component Specification is not a general specification for tank sampling, but is based on a ''record of decision'', AGA (HNF-SD-TWR-AGA-001 ), the System Specification for the Double Shell Tank System (HNF-SD-WM-TRD-O07), and the BNFL privatization contract.

  15. Sex bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR.

    Science.gov (United States)

    Keng, Vincent W; Sia, Daniela; Sarver, Aaron L; Tschida, Barbara R; Fan, Danhua; Alsinet, Clara; Solé, Manel; Lee, Wai L; Kuka, Timothy P; Moriarity, Branden S; Villanueva, Augusto; Dupuy, Adam J; Riordan, Jesse D; Bell, Jason B; Silverstein, Kevin A T; Llovet, Josep M; Largaespada, David A

    2013-01-01

    Hepatocellular carcinoma (HCC) is one of the deadliest solid cancers and is the third leading cause of cancer-related death. There is a universal estimated male/female ratio of 2.5, but the reason for this is not well understood. The Sleeping Beauty (SB) transposon system was used to elucidate candidate oncogenic drivers of HCC in a forward genetics screening approach. Sex bias occurrence was conserved in our model, with male experimental mice developing liver tumors at reduced latency and higher tumor penetrance. In parallel, we explored sex differences regarding genomic aberrations in 235 HCC patients. Liver cancer candidate genes were identified from both sexes and genotypes. Interestingly, transposon insertions in the epidermal growth factor receptor (Egfr) gene were common in SB-induced liver tumors from male mice (10/10, 100%) but infrequent in female mice (2/9, 22%). Human single-nucleotide polymorphism data confirmed that polysomy of chromosome 7, locus of EGFR, was more frequent in males (26/62, 41%) than females (2/27, 7%) (P = 0.001). Gene expression-based Poly7 subclass patients were predominantly male (9/9) compared with 67% males (55/82) in other HCC subclasses (P = 0.02), and this subclass was accompanied by EGFR overexpression (P < 0.001). Sex bias occurrence of HCC associated with EGFR was confirmed in experimental animals using the SB transposon system in a reverse genetic approach. This study provides evidence for the role of EGFR in sex bias occurrences of liver cancer and as the driver mutational gene in the Poly7 molecular subclass of human HCC. Copyright © 2012 American Association for the Study of Liver Diseases.

  16. Associations of Apgar score and size at birth with lipoprotein subclasses in juvenile obesity

    Science.gov (United States)

    Bekhet, Osama H.; Vekic, Jelena; Zeljkovic, Aleksandra; Parıpovıc, Dusan; Gojkovıc, Tamara; Janac, Jelena; Spasojevıc-Kalımanovska, Vesna; Peco-Antıc, Amira; Mılosevskı-Lomıc, Gordana; Jelıc-Ivanovıc, Zorana; Stefanovıc, Aleksandra

    2017-12-19

    Background/aim: Juvenile obesity is associated with several metabolic abnormalities, one of them being atherogenic dyslipidemia. Suboptimal fetal growth is associated with obesity risk in childhood, but also with increased rate of metabolic diseases in later life. This study investigated associations of neonatal data (Apgar score, birth weight and birth length) with low-density lipoprotein and high-density lipoprotein (LDL and HDL) subclasses in a group of obese children, as well as a possible impact of breastfeeding duration on obesity-associated lipoprotein subclasses distributions.Materials and methods: We included 42 obese children, aged 14.2 ± 2.1 years. LDL and HDL subfractions were separated by gradient gel electrophoresis and biochemical parameters were assessed by routine methods.Results: Compared with obese children with Apgar ≥ 9, the group with Apgar < 9 had significantly higher percentages of small, dense LDL particles (P < 0.05), due to reduced LDL I (P < 0.01) and increased LDL III subclasses (P < 0.05). Birth weight was positively associated with the proportions of LDL I particles (P < 0.001), whereas birth height positively correlated with the amount of HDL 2b subclasses (P < 0.05). The group of never or less than 3 months breastfed children had significantly smaller LDL size (P < 0.01) and lower proportion of HDL 2a particles (P < 0.05) than their ≥3 months breastfed peers.Conclusion: The results showed significant associations of neonatal characteristics with LDL and HDL particle distributions in obese children. In addition, our results point toward positive aspects of longer breastfeeding duration on lipoprotein particle distributions in obese children.

  17. Phrase Structure Patterning and Licensing for English and Serbian Speaker-Oriented Adverb Subclasses

    Directory of Open Access Journals (Sweden)

    Dimković-Telebaković Gordana

    2016-12-01

    Full Text Available This paper attempts to set phrase structure rules for English and Serbian speaker-oriented adverb subclasses. Adverbs are looked at here as specifiers licensed by the semantic feature [ILLOCUTIONARY FORCE]. The results suggest that illocutionary, evaluative and evidential adverbs normally merge within the complementizer layer and the inflectional layer, and that English epistemic adverbs are in most cases preferably integrated into the inflectional layer, whereas Serbian epistemic adverbs tend to occur in the sentence-initial position.

  18. A subclass of harmonic univalent functions with positive coefficients associated with fractional calculus operator

    Directory of Open Access Journals (Sweden)

    R. Agarwal

    2012-09-01

    Full Text Available In the present paper, we are defining a subclass of harmonic univalent functions with positive coefficients in unit disc $U$ by using fractional calculus operator. Further we obtain distortion bounds, extreme points and radii of convexity for functions belonging to this class and discuss a class preserving integral operator. Here we also determine that the class studied in this paper is closed under convolution and convex combinations.

  19. Subclasses of Starlike Functions Associated with Fractional q-Calculus Operators

    Directory of Open Access Journals (Sweden)

    G. Murugusundaramoorthy

    2013-01-01

    Full Text Available Making use of fractional q-calculus operators, we introduce a new subclass ℳq(λ,γ,k of starlike functions and determine the coefficient estimate, extreme points, closure theorem, and distortion bounds for functions in ℳq(λ,γ,k. Furthermore we discuss neighborhood results, subordination theorem, partial sums, and integral means inequalities for functions in ℳq(λ,γ,k.

  20. The effects of exercise on the lipoprotein subclass profile: A meta-analysis of 10 interventions.

    Science.gov (United States)

    Sarzynski, Mark A; Burton, Jeffrey; Rankinen, Tuomo; Blair, Steven N; Church, Timothy S; Després, Jean-Pierre; Hagberg, James M; Landers-Ramos, Rian; Leon, Arthur S; Mikus, Catherine R; Rao, D C; Seip, Richard L; Skinner, James S; Slentz, Cris A; Thompson, Paul D; Wilund, Kenneth R; Kraus, William E; Bouchard, Claude

    2015-12-01

    The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. The effects of exercise on the lipoprotein subclass profile: a meta-analysis of 10 interventions

    Science.gov (United States)

    Sarzynski, Mark A.; Burton, Jeffrey; Rankinen, Tuomo; Blair, Steven N.; Church, Timothy S.; Després, Jean-Pierre; Hagberg, James M.; Landers-Ramos, Rian; Leon, Arthur S.; Mikus, Catherine R.; Rao, D.C.; Seip, Richard L.; Skinner, James S.; Slentz, Cris A.; Thompson, Paul D.; Wilund, Kenneth R.; Kraus, William E.; Bouchard, Claude

    2015-01-01

    Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1,555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N=106), DREW (N=385), GERS (N=79), HERITAGE (N=715), STRRIDE I (N=168) and II (N=102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk. PMID:26520888

  2. Immunoglobulin G subclass deficiency is the major phenotype of primary immunodeficiency in a Korean adult cohort.

    Science.gov (United States)

    Kim, Joo-Hee; Park, Han-Jung; Choi, Gil-Soon; Kim, Jeong-Eun; Ye, Young-Min; Nahm, Dong-Ho; Park, Hae-Sim

    2010-06-01

    Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases.

  3. Circulating Blood Monocyte Subclasses and Lipid-Laden Adipose Tissue Macrophages in Human Obesity.

    Science.gov (United States)

    Pecht, Tal; Haim, Yulia; Bashan, Nava; Shapiro, Hagit; Harman-Boehm, Ilana; Kirshtein, Boris; Clément, Karine; Shai, Iris; Rudich, Assaf

    2016-01-01

    Visceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM) are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient. We preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM) lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65) undergoing elective abdominal surgery. Ex-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,plipid content (r = 0.303,plipid content, particularly in men. Collectively, although circulating blood NCM are unlikely direct functional precursor cells for adipose tissue foam cells, their increased percentage in the circulation may clinically reflect higher lipid content in visceral ATMs.

  4. The GLAS Standard Data Products Specification-Level 1, Version 9

    Science.gov (United States)

    Lee, Jeffrey E.

    2013-01-01

    The Geoscience Laser Altimeter System (GLAS) is the primary instrument for the ICESat (Ice, Cloud and Land Elevation Satellite) laser altimetry mission. ICESat was the benchmark Earth Observing System (EOS) mission for measuring ice sheet mass balance, cloud and aerosol heights, as well as land topography and vegetation characteristics. From 2003 to 2009, the ICESat mission provided multi-year elevation data needed to determine ice sheet mass balance as well as cloud property information, especially for stratospheric clouds common over polar areas. It also provided topography and vegetation data around the globe, in addition to the polar-specific coverage over the Greenland and Antarctic ice sheets.This document defines the Level-1 GLAS standard data products. This document addresses the data flow, interfaces, record and data formats associated with the GLAS Level 1 standard data products. GLAS Level 1 standard data products are composed of Level 1A and Level 1B data products. The term standard data products refers to those EOS instrument data that are routinely generated for public distribution. The National Snow and Ice Data Center (NSDIC) distribute these products. Each data product has a unique Product Identification code assigned by the Senior Project Scientist. GLAS Level 1A and Level 1B Data Products are composed from those Level 0 data that have been reformatted or transformed to corrected and calibrated data in physical units at the full instrument rate and resolution.

  5. Consonants, vowels and levels of specification in the phonological representations of the first lexicon: a review

    Directory of Open Access Journals (Sweden)

    Marta Ramon-Casas

    2014-05-01

    Full Text Available A review of the main studies on the format of lexical representation in the initial stages of language development is presented. Current investigations reveal a significant level of phonological specificity in the representation of words in the first lexicon, even before age two years. These results can be explained from a theoretical framework that posits the existence of multiple levels of encoding and suggests differences in accessing the represented information as a function of task demands or vocabulary size. The existence of possible differences in the degree of specification of vowels and consonants represented in the lexicon is an area of current debate. This article discusses the present state of this debate in the light of recent findings from research with different languages, in populations with different linguistic environments (monolingual and bilingual and from experimental approaches that involve varying degrees of cognitive demands.

  6. Comparing Domain-Specific Physical Activity Efficacy Level between Turkish Adolescent Girls and Boys

    Science.gov (United States)

    Çatikkas, Fatih

    2017-01-01

    The adolescence period is a very critical developmental period for personality, socializing and promotion of physical activity. In this regard, the aim of this study was to compare domain-specific physical activity efficacy level between adolescent boys and girls. A total of 219 girls (body weight: 57.50 ± 10.44 kg, height: 160.30 ± 7.40 cm, age…

  7. A population study of fasting time and serum prostate-specific antigen (PSA) level

    OpenAIRE

    Lau, Cheryl K; Maggie Guo; Viczko, Jeannine A; Naugler, Christopher T

    2014-01-01

    Prostate cancer is one of the most common cancers in men. Traditional screening and diagnostic methods include digital rectal examinations (DREs), biopsies and serum prostate-specific antigen (PSA) tests, with the latter being the more popular. PSA is a biomarker for prostate cancer; however, it is highly sensitive to external factors as well as other prostate diseases. As such, the reliability of of the serum PSA level as a sole screening and diagnostic tool for prostate cancer is controvers...

  8. A population study of fasting time and serum prostate-specific antigen (PSA) level

    Science.gov (United States)

    Lau, Cheryl K; Guo, Maggie; Viczko, Jeannine A; Naugler, Christopher T

    2014-01-01

    Prostate cancer is one of the most common cancers in men. Traditional screening and diagnostic methods include digital rectal examinations (DREs), biopsies and serum prostate-specific antigen (PSA) tests, with the latter being the more popular. PSA is a biomarker for prostate cancer; however, it is highly sensitive to external factors as well as other prostate diseases. As such, the reliability of of the serum PSA level as a sole screening and diagnostic tool for prostate cancer is controversial. Recently, it has been shown that fasting extremes can affect concentrations of serum chemistry analytes, thus raising the question of whether or not fasting has an effect on the highly sensitive PSA biomarker. Patients testing for serum PSA levels are often concomitantly submitting to other tests that require fasting, subjecting certain patients to a fasting PSA level while others not. The objective of this study was to investigate whether this discrepancy in fasting state translates into an effect on serum PSA levels. Serum PSA levels and fasting time records for 157 276 men who underwent testing at Calgary Laboratory Services (CLS; Calgary, Alberta, Canada) between 01 January 2010 and 31 March 2013 were accessed. Linear regression models of mean PSA levels and fasting times revealed a statistically important relationship at certain fasting times. Applying a dynamic mathematical model to explore the clinical effect of fasting suggests minimal impact on serum PSA result interpretation. Thus, patients can be tested for serum PSA levels regardless of their fasting state. PMID:24994780

  9. A population study of fasting time and serum prostate-specific antigen (PSA) level.

    Science.gov (United States)

    Lau, Cheryl K; Guo, Maggie; Viczko, Jeannine A; Naugler, Christopher T

    2014-01-01

    Prostate cancer is one of the most common cancers in men. Traditional screening and diagnostic methods include digital rectal examinations (DREs), biopsies and serum prostate-specific antigen (PSA) tests, with the latter being the more popular. PSA is a biomarker for prostate cancer; however, it is highly sensitive to external factors as well as other prostate diseases. As such, the reliability of of the serum PSA level as a sole screening and diagnostic tool for prostate cancer is controversial. Recently, it has been shown that fasting extremes can affect concentrations of serum chemistry analytes, thus raising the question of whether or not fasting has an effect on the highly sensitive PSA biomarker. Patients testing for serum PSA levels are often concomitantly submitting to other tests that require fasting, subjecting certain patients to a fasting PSA level while others not. The objective of this study was to investigate whether this discrepancy in fasting state translates into an effect on serum PSA levels. Serum PSA levels and fasting time records for 157 276 men who underwent testing at Calgary Laboratory Services (CLS; Calgary, Alberta, Canada) between 01 January 2010 and 31 March 2013 were accessed. Linear regression models of mean PSA levels and fasting times revealed a statistically important relationship at certain fasting times. Applying a dynamic mathematical model to explore the clinical effect of fasting suggests minimal impact on serum PSA result interpretation. Thus, patients can be tested for serum PSA levels regardless of their fasting state.

  10. Gender- and ethnic-specific associations with obesity: individual and neighborhood-level factors.

    Science.gov (United States)

    Zeigler-Johnson, Charnita; Weber, Anita; Glanz, Karen; Spangler, Elaine; Rebbeck, Timothy R

    2013-01-01

    Gender- and ethnicity-specific groups face different risks for obesity, but little is understood about the factors that predict group-specific risks. We evaluated individual and neighborhood factors in relation to obesity. Cross-sectional surveys of adults (ages 18-100 years) from southeastern Pennsylvania were analyzed. Individual- and neighborhood-level factors were included in fully-adjusted regression models to estimate relationships with obesity for specific gender-ethnic groups. The study included 679 Asian women, 655 Asian men, 4190 African-American women, 1568 African-American men, 1248 Hispanic women, 586 Hispanic men, 11791 European American women, and 6547 European American men. There were significant differences in the predictors of obesity by gender-ethnic groups. Obesity was differentially associated with age (p obesity (p gender-ethnic group. Inverse neighborhood effects on obesity prevalence were observed in most groups for higher neighborhood education and family income. Direct associations with obesity were observed for neighborhood poverty and neighborhood smoking. We observed that individual- and neighborhood-level variables are associated with obesity. Several individual-level effects differ by gender-ethnic group.

  11. Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development.

    Science.gov (United States)

    Wiebe, Chris; Rush, David N; Nevins, Thomas E; Birk, Patricia E; Blydt-Hansen, Tom; Gibson, Ian W; Goldberg, Aviva; Ho, Julie; Karpinski, Martin; Pochinco, Denise; Sharma, Atul; Storsley, Leroy; Matas, Arthur J; Nickerson, Peter W

    2017-11-01

    Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch. HLA-DR/DQ eplet mismatch was a significant multivariate predictor of dnDSA development. Recipients treated with a cyclosporin regimen had a 2.7-fold higher incidence of dnDSA development than recipients on a tacrolimus regimen. Recipients treated with tacrolimus who developed HLA-DR/DQ dnDSA had a higher proportion of tacrolimus trough levels tacrolimus trough levels in the 6 months before dnDSA development were significantly lower than the levels >6 months before dnDSA development in the same patients. Recipients with a high-risk HLA eplet mismatch score were less likely to tolerate low tacrolimus levels without developing dnDSA. We conclude that HLA-DR/DQ eplet mismatch and tacrolimus trough levels are independent predictors of dnDSA development. Recipients with high HLA alloimmune risk should not target tacrolimus levels <5 ng/ml unless essential, and monitoring for dnDSA may be advisable in this setting. Copyright © 2017 by the American Society of Nephrology.

  12. Tobacco-Specific Nitrosamines in Electronic Cigarettes: Comparison between Liquid and Aerosol Levels

    Directory of Open Access Journals (Sweden)

    Konstantinos E. Farsalinos

    2015-07-01

    Full Text Available Introduction: Although electronic cigarette (EC liquids contain low levels of tobacco-specific nitrosamines (TSNAs, studies evaluating the levels emitted to the aerosol are scarce. The purpose of this study was to compare the levels of TSNAs between liquids and generated aerosol. Methods: Three EC liquids were obtained from the market. An additional (spiked sample was prepared by adding known amounts of standard TSNAs solutions to one of the obtained liquids. N-nitrosonornicotine (NNN, N-nitrosoanatabine (NAT, N-nitrosoanabasine (NAB and 4-(methylnitrosamino1-(3-pyridyl-1-butanone (NNK were measured. Three 100-puff sets from each liquid were trapped in filter pads and were subsequently analyzed for the presence of TSNAs. The expected levels of TSNAs (calculated based on the liquid consumption were compared with the measured levels in the aerosol. Results: Only NAB was found at trace levels in two commercial liquids (1.2 and 2.3 ng/g, while the third contained 1.5 ng/g NAB and 7.7 ng/g NNN. The 100-puff sets resulted in 336–515 mg liquid consumption, with no TSNAs being detected in the aerosol. The spiked sample contained 42.0–53.9 ng/g of each of the TSNAs. All TSNAs were detected in the aerosol with the measured levels being statistically similar to the expected amounts. A significant correlation between expected and measured levels of TSNAs in the aerosol was found (r = 0.83, p < 0.001. Conclusion: The findings of this study show that exposure of EC users to TSNAs can be accurately assessed based on the levels present in the liquid, without the need to analyze the aerosol.

  13. Advanced prostatic carcinomas with low serum levels of prostate-specific antigen

    Directory of Open Access Journals (Sweden)

    Cerović Snežana J.

    2002-01-01

    Full Text Available The serum levels of prostate-specific antigen (PSA represent a significant diagnostic and monitoring parameter of prostatic carcinoma (PC. The aim of the study was to establish correlation of serum PSA level in addition to grade, histological type, and clinical stage of PC in patients with normal or intermediary PSA serum level. In 37 untreated PC patients with preoperative serum PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum samples were immunohistological studied and immunoassay for PSA was done. The most representative was poorly differentiated PC with D stage In serum samples from PC patients 27 (73.7% normal (≤ 4.0 ng/ml, and 10 (27.3% intermediate (4.1-10 ng/ml PSA levels were found Immunohistochemistry, in 36 PC (97.3% had demonstrated the expression of PSA. Our study results had shown low serum PSA levels in some patients with advanced poorly differentiated PC.

  14. Evaluation of different jumping tests in defining position-specific and performance-level differences in high level basketball players

    Science.gov (United States)

    Pehar, Miran; Sekulic, Damir; Sisic, Nedim; Spasic, Miodrag; Uljevic, Ognjen; Krolo, Ante; Sattler, Tine

    2017-01-01

    The importance of jumping ability in basketball is well known, but there is an evident lack of studies that have examined different jumping testing protocols in basketball players at advanced levels. The aim of this study was to assess the applicability of different tests of jumping capacity in identifying differences between (i) playing position and (ii) competitive levels of professional players. Participants were 110 male professional basketball players (height: 194.92±8.09 cm; body mass: 89.33±10.91 kg; 21.58±3.92 years of age; Guards, 49; Forwards, 22; Centres, 39) who competed in the first (n = 58) and second division (n = 52). The variables included anthropometrics and jumping test performance. Jumping performances were evaluated by the standing broad jump (SBJ), countermovement jump (CMJ), reactive strength index (RSI), repeated reactive strength ability (RRSA) and four running vertical jumps: maximal jump with (i) take-off from the dominant leg and (ii) non-dominant leg, lay-up shot jump with take-off from the (iii) dominant leg and (iv) non-dominant leg. First-division players were taller (ES: 0.76, 95%CI: 0.35-1.16, moderate differences), heavier (0.69, 0.29-1.10), had higher maximal reach height (0.67, 0.26-1.07, moderate differences), and had lower body fat % (-0.87, -1.27-0.45, moderate differences) than second-division players. The playing positions differed significantly in three of four running jump achievements, RSI and RRSA, with Centres being least successful. The first-division players were superior to second-division players in SBJ (0.63, 0.23-1.03; 0.87, 0.26-1.43; 0.76, 0.11-1.63, all moderate differences, for total sample, Guards, and Forwards, respectively). Running vertical jumps and repeated jumping capacity can be used as valid measures of position-specific jumping ability in basketball. The differences between playing levels in vertical jumping achievement can be observed by assessing vertical jump scores together with differences

  15. Validated age-specific reference values for CSF total protein levels in children.

    Science.gov (United States)

    Kahlmann, V; Roodbol, J; van Leeuwen, N; Ramakers, C R B; van Pelt, D; Neuteboom, R F; Catsman-Berrevoets, C E; de Wit, M C Y; Jacobs, B C

    2017-07-01

    To define age-specific reference values for cerebrospinal fluid (CSF) total protein levels for children and validate these values in children with Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). Reference values for CSF total protein levels were determined in an extensive cohort of diagnostic samples from children (values were confirmed in children diagnosed with disorders unrelated to raised CSF total protein level and validated in children with GBS, ADEM and MS. The test results of 6145 diagnostic CSF samples from 3623 children were used to define reference values. The reference values based on the upper limit of the 95% CI (i.e. upper limit of normal) were for 6 months-2 years 0.25 g/L, 2-6 years 0.25 g/L, 6-12 years 0.28 g/L, 12-18 years 0.34 g/L. These reference values were confirmed in a subgroup of 378 children diagnosed with disorders that are not typically associated with increased CSF total protein. In addition, the CSF total protein levels in these children in the first 6 months after birth were highly variable (median 0.47 g/L, IQR 0.26-0.65). According to these new reference values, CSF total protein level was elevated in 85% of children with GBS, 66% with ADEM and 23% with MS. More accurate age-specific reference values for CSF total protein levels in children were determined. These new reference values are more sensitive than currently used values for diagnosing GBS and ADEM in children. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. Polarity-specific high-level information propagation in neural networks.

    Science.gov (United States)

    Lin, Yen-Nan; Chang, Po-Yen; Hsiao, Pao-Yueh; Lo, Chung-Chuan

    2014-01-01

    Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals.

  17. Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

    Directory of Open Access Journals (Sweden)

    Rachel S. Lee

    2011-01-01

    Full Text Available The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ.

  18. A specific association between facial disgust recognition and estradiol levels in naturally cycling women.

    Directory of Open Access Journals (Sweden)

    Sunjeev K Kamboj

    Full Text Available Subtle changes in social cognition are associated with naturalistic fluctuations in estrogens and progesterone over the course of the menstrual cycle. Using a dynamic emotion recognition task we aimed to provide a comprehensive description of the association between ovarian hormone levels and emotion recognition performance using a variety of performance metrics. Naturally cycling, psychiatrically healthy women attended a single experimental session during a follicular (days 7-13; n = 16, early luteal (days 15-19; n = 14 or late luteal phase (days 22-27; n = 14 of their menstrual cycle. Correct responses and reaction times to dynamic facial expressions were recorded and a two-high threshold analysis was used to assess discrimination and response bias. Salivary progesterone and estradiol were assayed and subjective measures of premenstrual symptoms, anxiety and positive and negative affect assessed. There was no interaction between cycle phase (follicular, early luteal, late luteal and facial expression (sad, happy, fearful, angry, neutral and disgusted on any of the recognition performance metrics. However, across the sample as a whole, progesterone levels were positively correlated with reaction times to a variety of facial expressions (anger, happiness, sadness and neutral expressions. In contrast, estradiol levels were specifically correlated with disgust processing on three performance indices (correct responses, response bias and discrimination. Premenstrual symptoms, anxiety and positive and negative affect were not associated with emotion recognition indices or hormone levels. The study highlights the role of naturalistic variations in ovarian hormone levels in modulating emotion recognition. In particular, progesterone seems to have a general slowing effect on facial expression processing. Our findings also provide the first behavioural evidence of a specific role for estrogens in the processing of disgust in humans.

  19. Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

    Science.gov (United States)

    Grisendi, Valentina; Spada, Elena; Argento, Cindy; Plebani, Maddalena; Milani, Silvano; Seracchioli, Renato; Volpe, Annibale; La Marca, Antonio

    2014-06-01

    High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

  20. Patient-Specific Classification of ICU Sedation Levels From Heart Rate Variability.

    Science.gov (United States)

    Nagaraj, Sunil B; Biswal, Siddharth; Boyle, Emily J; Zhou, David W; McClain, Lauren M; Bajwa, Ednan K; Quraishi, Sadeq A; Akeju, Oluwaseun; Barbieri, Riccardo; Purdon, Patrick L; Westover, M Brandon

    2017-07-01

    To develop a personalizable algorithm to discriminate between sedation levels in ICU patients based on heart rate variability. Multicenter, pilot study. Several ICUs at Massachusetts General Hospital, Boston, MA. We gathered 21,912 hours of routine electrocardiogram recordings from a heterogenous group of 70 adult ICU patients. All patients included in the study were mechanically ventilated and were receiving sedatives. As "ground truth" for developing our method, we used Richmond Agitation Sedation Scale scores grouped into four levels denoted "comatose" (-5), "deeply sedated" (-4 to -3), "lightly sedated" (-2 to 0), and "agitated" (+1 to +4). We trained a support vector machine learning algorithm to calculate the probability of each sedation level from heart rate variability measures derived from the electrocardiogram. To estimate algorithm performance, we calculated leave-one-subject out cross-validated accuracy. The patient-independent version of the proposed system discriminated between the four sedation levels with an overall accuracy of 59%. Upon personalizing the system supplementing the training data with patient-specific calibration data, consisting of an individual's labeled heart rate variability epochs from the preceding 24 hours, accuracy improved to 67%. The personalized system discriminated between light- and deep-sedation states with an average accuracy of 75%. With further refinement, the methodology reported herein could lead to a fully automated system for depth of sedation monitoring. By enabling monitoring to be continuous, such technology may help clinical staff to monitor sedation levels more effectively and to reduce complications related to over- and under sedation.

  1. Muscle utilization patterns vary by skill levels of the practitioners across specific yoga poses (asanas).

    Science.gov (United States)

    Ni, Meng; Mooney, Kiersten; Balachandran, Anoop; Richards, Luca; Harriell, Kysha; Signorile, Joseph F

    2014-08-01

    To compare muscle activation patterns in 14 dominant side muscles during different yoga poses across three skill levels. Mixed repeated-measures descriptive study. University neuromuscular research laboratory, Miami, US. A group of 36 yoga practitioners (9 M/27 F; mean ± SD, 31.6 ± 12.6 years) with at least 3 months yoga practice experience. Each of the 11 surya namaskar poses A and B was performed separately for 15s and the surface electromyography for 14 muscles were recorded. Normalized root mean square of the electromyographic signal (NrmsEMG) for 14 muscles (5 upper body, 4 trunk, 5 lower body). There were significant main effects of pose for all fourteen muscles except middle trapezius (phead, anterior deltoid, medial deltoid, upper rectus abdominis and gastrocnemius lateralis; p<.05). Post hoc analyses using Bonferroni comparisons indicated that different poses activated specific muscle groups; however, this varied by skill level. Our results indicate that different poses can produce specific muscle activation patterns which may vary due to practitioners' skill levels. This information can be used in designing rehabilitation and training programs and for cuing during yoga training. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Polymorphisms of STAT6 and specific serum IgE levels in patients with penicillin allergy.

    Science.gov (United States)

    Huang, Chen-Zheng; Zou, Dan; Yang, Jing; Qiao, Hai-Ling

    2012-07-01

    Signal transducer and activator of transcription (STAT) 6 signaling pathway is required for mediating the biologic functions of interleukin (IL)-4 which is proved to play an important role in the pathogenesis of allergic diseases and the induction of specific immunoglobulin (Ig) E synthesis. The current studies are conducted to evaluate the relationship between polymorphisms of STAT6, specific IgE and penicillin allergy. In 242 patients with penicillin allergy and 220 controls, polymorphisms of STAT6 in2SNP3 and 3'UTRSNP3 were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Eight kinds of specific IgE to penicillins were detected with radioallergosorbent test (RAST). For STAT6 in2SNP3, the frequency of the CC genotype was significantly higher in all patients than in controls (60 vs. 47%, p = 0.005). A similar result was observed between patients of the urticaria group and controls (70 vs. 47%, p = 0.005). With respect to allele frequency, the C-allele occurred more frequently in all patients and in the urticaria group than in controls (78 vs. 69%, p = 0.002; 83 vs. 69%, p = 0.007). Our finding suggests that STAT6 in2SNP3 is associated with penicillin allergy, but has no effect on the specific IgE levels of patients with penicillin allergy.

  3. The influence of allotypes on the IgG subclass response to chromosomal beta-lactamase of Pseudomonas aeruginosa in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, O; Pressler, T; Pandey, J P

    1997-01-01

    Sera from 70 adult cystic fibrosis (CF) patients with chronic lung infection with Pseudomonas aeruginosa were typed for seven GM and two KM allotype determinants. IgG class and all four IgG subclasses of antibodies against chromosomal beta-lactamase of Ps. aeruginosa (a beta ab) were measured...... in all 70 CF patients in a cross-sectional study. The a beta ab IgG subclass response in sera collected during the first 11 years of chronic infection from 20 CF patients (10 patients with G3M*5 G1M*3/G3M*5 G1M*3 genotype and 10 patients with G3M*21 G1M*1/G3M*21 G1M*1 genotype) was analysed...... in a longitudinal study. Increased levels of IgG2 were associated with the presence of GM 23 allotype. IgG3 a beta ab levels were the lowest for subjects with the GM 1,2,3,17 23 5,21 and GM 1,3,17 21 phenotypes and the highest in subjects with GM 3,23,5 and GM 3,5. No significant differences in IgG1 and IgG4 a beta...

  4. Generating Safety-Critical PLC Code From a High-Level Application Software Specification

    Science.gov (United States)

    2008-01-01

    The benefits of automatic-application code generation are widely accepted within the software engineering community. These benefits include raised abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at Kennedy Space Center recognized the need for PLC code generation while developing the new ground checkout and launch processing system, called the Launch Control System (LCS). Engineers developed a process and a prototype software tool that automatically translates a high-level representation or specification of application software into ladder logic that executes on a PLC. All the computer hardware in the LCS is planned to be commercial off the shelf (COTS), including industrial controllers or PLCs that are connected to the sensors and end items out in the field. Most of the software in LCS is also planned to be COTS, with only small adapter software modules that must be developed in order to interface between the various COTS software products. A domain-specific language (DSL) is a programming language designed to perform tasks and to solve problems in a particular domain, such as ground processing of launch vehicles. The LCS engineers created a DSL for developing test sequences of ground checkout and launch operations of future launch vehicle and spacecraft elements, and they are developing a tabular specification format that uses the DSL keywords and functions familiar to the ground and flight system users. The tabular specification format, or tabular spec, allows most ground and flight system users to document how the application software is intended to function and requires little or no software programming knowledge or experience. A small sample from a prototype tabular spec application is

  5. Soil Moisture Active Passive (SMAP) Mission Level 4 Carbon (L4_C) Product Specification Document

    Science.gov (United States)

    Glassy, Joe; Kimball, John S.; Jones, Lucas; Reichle, Rolf H.; Ardizzone, Joseph V.; Kim, Gi-Kong; Lucchesi, Robert A.; Smith, Edmond B.; Weiss, Barry H.

    2015-01-01

    This is the Product Specification Document (PSD) for Level 4 Surface and Root Zone Soil Moisture (L4_SM) data for the Science Data System (SDS) of the Soil Moisture Active Passive (SMAP) project. The L4_SM data product provides estimates of land surface conditions based on the assimilation of SMAP observations into a customized version of the NASA Goddard Earth Observing System, Version 5 (GEOS-5) land data assimilation system (LDAS). This document applies to any standard L4_SM data product generated by the SMAP Project.

  6. Interleukin-4 and specific IgE to oranges levels study in persons with allergic anamnesis

    Directory of Open Access Journals (Sweden)

    A. S. Prilutskiy

    2014-04-01

    Full Text Available Introduction. Currently allergic diseases pose a global health concern. The connection between immunoglobulin E antibodies (IgE-Ab and allergic disorders is well established. However, the mechanisms through which IgE-Ab contribute to the pathogenesis of allergic diseases are yet to be elucidated. There are reports that highlight the crucial role of interleukins in the regulation of these processes. Thus, some authors pay attention to interleukin-4 (IL-4 which is important for the control of all aspects of the humoral response. Recent epidemiological studies show that oranges are largely consumed worldwide and commonly included in the diet in many countries being one of the main reasons of food allergy. So it was decided to investigate possible links between the levels of IL-4 and IgE-Ab both total and specific to the orange allergens. The aim of this study is to determine the levels of IL-4, total and specific orange IgE-Ab (sIgE-Ab concentrations in individuals with a history of allergic diseases and find some statistically significant links between these parameters. Materials and methods. We selected and investigated serums of 180 patients between 7 months and 78 years with a history of allergic diseases who complained on frequent development of various allergic reactions, mainly atopic dermatitis, urticaria, etc. Determination of the levels of IL-4, total and specific IgE-Ab to the orange allergens was carried out using the first national ELISA test systems of the fourth generation (“Ukrmed-Don”, Donetsk, Ukraine. Specific IgE and IL-4 levels were examined in 180 patients and total IgE levels were investigated in 161 patients. Statistical analysis was performed using the licensed program “MedStat” (Donetsk, Ukraine. The median, the median error, the left and right limits of 95% confidence interval were calculated for all of three samples (IL-4, total IgE-Ab, sIgE-Ab. Central tendencies of two subgroups of IL-4, which were

  7. Study of Vitamin D Level in Children with Non-specific Musculoskeletal Pain

    Directory of Open Access Journals (Sweden)

    Hashem Mahmoodzadeh

    2017-03-01

    Full Text Available BackgroundVitamin D deficiency is known as a one of the underlying causes of Idiopathic musculoskeletal pain (IMSP. This study aimed to evaluate the correlation between serum vitamin D (Cholecalciferol status in patient with Non-specific Musculoskeletal Pain and healthy children.Materials and MethodsSeventy-seven children (aged 3–14 years, with IMSP were included as cases and 90 healthy subjects were selected for control group. Demographic characteristics and biochemical levels of vitamin D and Parathyroid hormone (PTH, were obtained. Data were analysis using SPSS version 17.0 software.ResultsResults showed that vitamin D means levels of patients and healthy children were significantly different (19.5 + 8.84 ng/mL versus 12.7 + 11.89 ng/mL, respectively (P

  8. Age-specific fertility by educational level in the Finnish male cohort born 1940‒1950

    Directory of Open Access Journals (Sweden)

    Jessica Nisén

    2014-07-01

    Full Text Available Background: Education is positively associated with completed fertility rate (CFR among men in Nordic countries, but the age patterns of fertility by educational level are poorly documented. Moreover, it is not known what parities contribute to the higher CFR among more highly educated men. Objective: To describe men's fertility by age, parity, and education in Finland. Methods: The study is based on register data covering the male cohort born in 1940‒1950 (N=38,838. Education was measured at ages 30‒34 and classified as basic, lower secondary, upper secondary, and tertiary. Fertility was measured until ages 59‒69. We calculated completed and age-specific fertility rates, and decomposed the educational gradient in CFR into parity-specific contributions. Results: The more highly educated men had more children (CFR: basic 1.71 and tertiary 2.06, had them later (mean age at having the first child: basic 26.1 and tertiary 28.1, and had them within a shorter interval (interquartile range of age at having the first child: basic 5.8 and tertiary 5.2. The educational gradient in the cumulative fertility rate was negative at young ages but turned positive by the early thirties. High levels of childlessness among those with a basic education explained three-quarters of the CFR difference between the lowest and highest educational groups. Fertility at ages above 45 was low and did not widen the educational gradient in CFR. Conclusions: The fact that highly educated men have more children than their counterparts with less education is largely attributable to higher fertility levels at older ages and the lower probability of remaining childless. Variation in fertility timing and quantity is wider among men with a low level of education.

  9. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

    Science.gov (United States)

    You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

    2016-01-01

    Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

  10. Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

    Science.gov (United States)

    Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

    2009-11-01

    Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

  11. Catabolism of human γG-immunoglobulins of different heavy chain subclasses

    Science.gov (United States)

    Spiegelberg, Hans L.; Fishkin, Ben G.; Grey, Howard M.

    1968-01-01

    The rates of catabolism of human γG-immunoglobulins of subclasses γG1, γG2, γG3, and γG4 were studied by determining the rates of elimination from the circulation of pairs of 131I-and 125I-labeled γG-myeloma proteins in 57 patients suffering from cancer other than multiple myeloma. On the average, γG1-, γG2-, and γG4-myeloma proteins were catabolized at a rate similar to that of normal γG-immunoglobulin, whereas γG3-myeloma proteins were catabolized more rapidly than normal γG-immunoglobulin. The average half-lives for the myeloma proteins were 12.3 days for normal γG, 11.6 days for γG1, 12.4 days for γG2, 8.2 days for γG3, and 11.3 days for γG4. However, significant differences in catabolic rates were observed when individual myeloma proteins of a single subclass were compared. These individual variations were present within all four heavy chain subclasses. The extent of differences ranged from 10 to 47%. The catabolic rate of normal γG was in an intermediate range when compared with myeloma proteins of relatively long and short half-lives. The rate of catabolism of an individual myeloma protein did not correlate with its light chain type, Gm factor, carbohydrate content, or electrophoretic mobility. These findings indicate that the structure(s) related to the catabolism of γG-immunoglobulins are complex and differ from one immunoglobulin molecule to another. Images PMID:4175542

  12. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis.

    Science.gov (United States)

    Hua, Xiaoli; Yu, Lili; You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

    2016-01-01

    Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68-0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50-0.92) and flavonols (RR = 0.68, 95% CI = 0.58-0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71-1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger's test (p = 0.26). This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted.

  13. Manganese spread in Ursa Minor as a proof of sub-classes of type Ia supernovae

    Science.gov (United States)

    Cescutti, G.; Kobayashi, C.

    2017-10-01

    Context. Recently, new sub-classes of Type Ia supernovae (SNe Ia) were discovered, including SNe Iax. The suggested progenitors of SNe Iax are relatively massive, possibly hybrid C+O+Ne white dwarfs, which can cause white dwarf winds at low metallicities. There is another class that can potentially occur at low or zero metallicities; sub-Chandrasekhar mass explosions in single and/or double degenerate systems of standard C+O white dwarfs. These explosions have different nucleosynthesis yields compared to the normal, Chandrasekhar mass explosions. Aims: We test these SN Ia channels using their characteristic chemical signatures. Methods: The two sub-classes of SNe Ia are expected to be rarer than normal SNe Ia and do not affect the chemical evolution in the solar neighbourhood; however, because of the shorter delay time and/or weaker metallicity dependence, they could influence the evolution of metal-poor systems. Therefore, we have included both in our stochastic chemical evolution model for the dwarf spheroidal galaxy Ursa Minor. Results: The model predicts a butterfly-shape spread in [Mn/Fe] in the interstellar medium at low metallicity and - at the same time - a decrease of [α/Fe] ratios at lower [Fe/H] than in the solar neighbourhood, both of which are consistent with the observed abundances in stars of Ursa Minor. Conclusions: The surprising agreement between our models and available observations provides a strong indication of the origins of these new sub-classes of SNe Ia. This outcome requires confirmation by future abundance measurements of manganese in stars of other satellite galaxies of our Milky Way. It will be vital for this project to measure not the most extreme metal-poor tail, as more commonly happens, but the opposite; the metal-rich end of dwarf spheroidals.

  14. Gender bias occurrence of hepatocellular carcinoma in Poly7 molecular subclass is associated with EGFR

    Science.gov (United States)

    Keng, Vincent W.; Sia, Daniela; Sarver, Aaron L.; Tschida, Barbara R.; Fan, Danhua; Alsinet, Clara; Solé, Manel; Lee, Wai L.; Kuka, Timothy P.; Moriarity, Branden S.; Villanueva, Augusto; Dupuy, Adam J.; Riordan, Jesse D.; Bell, Jason B.; Silverstein, Kevin A.T.; Llovet, Josep M.; Largaespada, David A.

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the deadliest solid cancers and represents the third leading cause of cancer-related death. There is a universal HCC male to female estimated ratio of 2.5, but the reason for this is not well understood. The Sleeping Beauty (SB) transposon system was used to elucidate candidate oncogenic drivers of HCC in a forward genetics screening approach. Gender bias occurrence was conserved in our model, with male experimental mice developing liver tumors at reduced latency and higher tumor penetrance. In parallel, we explored gender differences regarding genomic aberrations in 235 HCC patients. Liver cancer candidate genes were identified from both genders and genotypes. Interestingly, transposon insertions in the epidermal growth factor receptor (Egfr) gene were common in SB-induced liver tumors from male mice (10/10, 100%) but infrequent in female animals (2/9, 22%). Human SNP data confirmed that polysomy of chromosome 7, locus of EGFR, was more frequent in males (26/62, 41%) than females (2/27, 7%) (P = 0.001). Gene expression based Poly7 subclass patients were predominantly males (9/9) compared with 67% males (55/82) in other HCC subclasses (P = 0.02) and was accompanied by EGFR overexpression (P < 0.001). Gender bias occurrence of HCC associated with EGFR was confirmed in experimental animals using the SB transposon system in a reverse genetic approach. This study provides evidence for the role of EGFR in gender bias occurrences of liver cancer and as the driver mutational gene in the Poly7 molecular subclass of human HCC. PMID:22899566

  15. Flavonoids, flavonoid subclasses and breast cancer risk: a meta-analysis of epidemiologic studies.

    Science.gov (United States)

    Hui, Chang; Qi, Xie; Qianyong, Zhang; Xiaoli, Peng; Jundong, Zhu; Mantian, Mi

    2013-01-01

    Studies have suggested the chemopreventive effects of flavonoids on carcinogenesis. Yet numbers of epidemiologic studies assessing dietary flavonoids and breast cancer risk have yielded inconsistent results. The association between flavonoids, flavonoid subclasses (flavonols, flavan-3-ols, etc.) and the risk of breast cancer lacks systematic analysis. We aimed to examine the association between flavonoids, each flavonoid subclass (except isoflavones) and the risk of breast cancer by conducting a meta-analysis. We searched for all relevant studies with a prospective cohort or case-control study design published before July 1(st), 2012, using Cochrane library, MEDLINE, EMBASE and PUBMED. Summary relative risks (RR) were calculated using fixed- or random-effects models. All analyses were performed using STATA version 10.0. Twelve studies were included, involving 9 513 cases and 181 906 controls, six of which were prospective cohort studies, and six were case-control studies. We calculated the summary RRs of breast cancer risk for the highest vs lowest categories of each flavonoid subclass respectively. The risk of breast cancer significantly decreased in women with high intake of flavonols (RR=0.88, 95% CI 0.80-0.98) and flavones (RR=0.83, 95% CI: 0.76-0.91) compared with that in those with low intake of flavonols and flavones. However, no significant association of flavan-3-ols (RR=0.93, 95% CI: 0.84-1.02), flavanones (summary RR=0.95, 95% CI: 0.88-1.03), anthocyanins (summary RR=0.97, 95% CI: 0.87-1.08) or total flavonoids (summary RR=0.98, 95% CI: 0.86-1.12) intake with breast cancer risk was observed. Furthermore, summary RRs of 3 case-control studies stratified by menopausal status suggested flavonols, flavones or flavan-3-ols intake is associated with a significant reduced risk of breast cancer in post-menopausal while not in pre-menopausal women. The present study suggests the intake of flavonols and flavones, but not other flavonoid subclasses or total

  16. Flavonoids, flavonoid subclasses and breast cancer risk: a meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Chang Hui

    Full Text Available BACKGROUND: Studies have suggested the chemopreventive effects of flavonoids on carcinogenesis. Yet numbers of epidemiologic studies assessing dietary flavonoids and breast cancer risk have yielded inconsistent results. The association between flavonoids, flavonoid subclasses (flavonols, flavan-3-ols, etc. and the risk of breast cancer lacks systematic analysis. OBJECTIVE: We aimed to examine the association between flavonoids, each flavonoid subclass (except isoflavones and the risk of breast cancer by conducting a meta-analysis. DESIGN: We searched for all relevant studies with a prospective cohort or case-control study design published before July 1(st, 2012, using Cochrane library, MEDLINE, EMBASE and PUBMED. Summary relative risks (RR were calculated using fixed- or random-effects models. All analyses were performed using STATA version 10.0. RESULTS: Twelve studies were included, involving 9 513 cases and 181 906 controls, six of which were prospective cohort studies, and six were case-control studies. We calculated the summary RRs of breast cancer risk for the highest vs lowest categories of each flavonoid subclass respectively. The risk of breast cancer significantly decreased in women with high intake of flavonols (RR=0.88, 95% CI 0.80-0.98 and flavones (RR=0.83, 95% CI: 0.76-0.91 compared with that in those with low intake of flavonols and flavones. However, no significant association of flavan-3-ols (RR=0.93, 95% CI: 0.84-1.02, flavanones (summary RR=0.95, 95% CI: 0.88-1.03, anthocyanins (summary RR=0.97, 95% CI: 0.87-1.08 or total flavonoids (summary RR=0.98, 95% CI: 0.86-1.12 intake with breast cancer risk was observed. Furthermore, summary RRs of 3 case-control studies stratified by menopausal status suggested flavonols, flavones or flavan-3-ols intake is associated with a significant reduced risk of breast cancer in post-menopausal while not in pre-menopausal women. CONCLUSIONS: The present study suggests the intake of flavonols

  17. Acute effects of interleukin-6 infusion on apo-B-containing lipoprotein subclasses in humans

    DEFF Research Database (Denmark)

    Bagdade, John; Pedersen, Bente K; Schwenke, Dawn

    2011-01-01

    IL-6 is believed to mediate the elevation in plasma TG and VLDL lipids in patients with sepsis. Previous studies of lipoprotein density fractions do not reveal the extent to which cytokines change the immunochemically distinct TG-rich (LpB:C, LpB:C:E, LpAII:B:C:D:E) and cholesterol-rich (LpB, Lp...... unchanged by IL-6, the distribution of TG-rich subclasses was significantly altered. Compared to baseline values, LpB:E + LpB:C:E increased significantly at 0.5 h (p

  18. Preliminary level 2 specification for the nested, fixed-depth sampling system

    Energy Technology Data Exchange (ETDEWEB)

    BOGER, R.M.

    1999-05-26

    This revision 1 Level 2 Specification establishes the performance, design, development, and test requirements for a sampling system and for an at-tank analysis system that will support the BNFL, Inc. privatization contract in the final disposal of Hanford's high level waste (HLW) and low activity waste (LAW). The sampling system will quickly provide large volume, representative waste samples for validating the chemical, radiological, and physical properties of the tank waste without the exposure and time concerns of the baseline grab sampling method. The on-line sensors of the at-tank analysis system will provide data from which the mixing or settling status of the waste can be assessed. This revision 1 document includes functions, requirement, and specifications for the at-tank analysis system, the results of the preliminary outline design, and the FY 1998 validation testing. The sample container filling system will comply with RCRA criteria for samples with volatile organic constituents, include empty container and swipe input ports, use Hanford's Steel Pig radioactive sample package, comply with Hanford's flammable gas criteria, and have the means to recover from broken sample containers.

  19. Emergence at the Fundamental Systems Level: Existence Conditions for Iterative Specifications

    Directory of Open Access Journals (Sweden)

    Bernard P. Zeigler

    2016-11-01

    Full Text Available Conditions under which compositions of component systems form a well-defined system-of-systems are here formulated at a fundamental level. Statement of what defines a well-defined composition and sufficient conditions guaranteeing such a result offers insight into exemplars that can be found in special cases such as differential equation and discrete event systems. For any given global state of a composition, two requirements can be stated informally as: (1 the system can leave this state, i.e., there is at least one trajectory defined that starts from the state; and (2 the trajectory evolves over time without getting stuck at a point in time. Considered for every global state, these conditions determine whether the resultant is a well-defined system and, if so, whether it is non-deterministic or deterministic. We formulate these questions within the framework of iterative specifications for mathematical system models that are shown to be behaviorally equivalent to the Discrete Event System Specification (DEVS formalism. This formalization supports definitions and proofs of the afore-mentioned conditions. Implications are drawn at the fundamental level of existence where the emergence of a system from an assemblage of components can be characterized. We focus on systems with feedback coupling where existence and uniqueness of solutions is problematic.

  20. Common variable immunodeficiency and IgG subclass deficiency in central Alabama hemochromatosis probands homozygous for HFE C282Y.

    Science.gov (United States)

    Barton, James C; Bertoli, Luigi F; Acton, Ronald T

    2003-01-01

    Eight hemochromatosis probands with HFE C282Y homozygosity had frequent, severe, or unusual infections and common variable immunodeficiency (CVID) or immunoglobulin (Ig) G subclass deficiency (IgGSD). Thus, we performed serum Ig isotyping and other characterization of 43 additional unselected probands, 5 human leukocyte antigen (HLA)-identical siblings, and 240 consecutive CVID or IgGSD index patients. C282Y allele frequencies were estimated in 58 CVID or IgGSD index patients without hemochromatosis phenotypes and in 341 controls. HLA-A and -B haplotypes and frequencies were determined in all 51 probands, 186 CVID or IgGSD index patients without hemochromatosis phenotypes, and 751 controls. Thirteen unselected probands (30%) had CVID or IgGSD. Among all 21 hemochromatosis probands with CVID (n = 4) or IgGSD (n = 17), Ig subclass deficiency patterns were IgG(1) (n = 5), IgG(1) and IgG(3) (n = 6), IgG(3) (n = 9), and IgG(1), IgG(3), and IgG(4) (n = 1). IgG(2) or IgA deficiency was not detected; one proband had IgM deficiency. Mean values of total IgG, IgG(1), and IgG(3) were significantly lower in probands with CVID or IgGSD. Mean values of age, transferrin saturation, and ferritin at diagnosis and phlebotomy units required to induce iron depletion were similar in probands with or without CVID or IgGSD; phlebotomy had no apparent effect on IgG levels. C282Y frequencies were similar in CVID or IgGSD index cases without hemochromatosis phenotypes and in controls. There was concordance of Ig and hemochromatosis phenotypes in probands and respective HLA-identical siblings. Eight of 240 CVID or IgGSD index patients had hemochromatosis phenotypes and C282Y homozygosity (3 vs 0.7% and 0.2% controls; P IgG abnormalities characteristic of CVID or IgGSD are common in hemochromatosis probands, and that the prevalence of hemochromatosis is increased in CVID and IgGSD index cases. These observations could be explained by the increased frequencies of HLA-A*03-B*07 in C282Y

  1. The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core.

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T; Hoops, Stefan; Keating, Sarah M; Sahle, Sven; Schaff, James C; Smith, Lucian P; Wilkinson, Darren J

    2015-09-04

    Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

  2. Correlations Between Allergen-Specific IgE Serum Levels in Patients With Ocular Allergy.

    Science.gov (United States)

    Polido, Júlia Gomes Fernandes; Cabral, Thiago; Perini, Paula de Resende Campos; Fernandes, Maria de Fátima Marcelos; de Freitas, Denise; dos Santos Araújo, Maria Emília Xavier; Serracarbassa, Pedro Durães

    2015-09-01

    To evaluate ocular allergies in patients at the Hospital do Servidor Publico Estadual de Sao Paulo (HSPE) and the correlations with serum allergen-specific immunoglobulin E levels. We performed a longitudinal study of patients with ocular allergies who were treated at the Cornea and Immunology and Allergy Department. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 4 groups. We conducted the following laboratory tests and measurements: blood count, eosinophil count, total serum IgE, and specific IgE. Among 61 patients, 16 (26.2%) had a clinical diagnosis of seasonal allergic conjunctivitis, 23 (37.7%) had perennial allergic conjunctivitis, 19 (31.1%) had vernal keratoconjunctivitis, and 3 (4.9%) had atopic keratoconjunctivitis. Mixed dust mites were positive in 94.9% of patients. Dermatophagoides pteronyssinus (dp) and Dermatophagoides farinae (df) antigens were positive in 93.2% of patients followed by Blattella germanica, Blomia tropicalis, and mixed animal epithelia (81%, 75.9%, and 25.8%, respectively). Perennial allergic conjunctivitis was the most prevalent disorder and demonstrated higher positivity in class V/VI for specific antigens (mixed dust mites, dp, and df), indicating high antigenicity. Dust mites, D. pteronyssinus, D. farinae, B. germanica, and B. tropicalis were the primary triggers of the studied ocular allergies.

  3. Frequency-specific modulation of population-level frequency tuning in human auditory cortex

    Directory of Open Access Journals (Sweden)

    Roberts Larry E

    2009-01-01

    Full Text Available Abstract Background Under natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random under auditory focused attention by means of magnetoencephalography (MEG. Results In total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands. Conclusion The present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

  4. The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T.; Hoops, Stefan; Keating, Sarah M.; Sahle, Sven; Schaff, James C.; Smith, Lucian P.; Wilkinson, Darren J.

    2017-01-01

    Summary Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/. PMID:26528564

  5. National-Level Wetland Policy Specificity and Goals Vary According to Political and Economic Indicators

    Science.gov (United States)

    Peimer, Alex W.; Krzywicka, Adrianna E.; Cohen, Dora B.; Van den Bosch, Kyle; Buxton, Valerie L.; Stevenson, Natalie A.; Matthews, Jeffrey W.

    2017-01-01

    Growing recognition of the importance of wetlands to human and ecosystem well-being has led countries worldwide to implement wetland protection policies. Different countries have taken different approaches to wetland protection by implementing various policies, including territorial exclusion, market-based offsetting, and incentive programs for land users. Our objective was to describe the relationship between components of national-level wetland protection policies and national characteristics, including natural resource, economic, social, and political factors. We compiled data on the wetland policies of all 193 countries recognized by the U.N. and described the relationships among wetland policy goals and wetland protection mechanisms using non-metric multidimensional scaling. The first non-metric multidimensional scaling axis strongly correlated with whether a country had a wetland-specific environmental policy in place. Adoption of a comprehensive, wetland-specific policy was positively associated with degree of democracy and a commitment to establishing protected areas. The second non-metric multidimensional scaling axis defined a continuum of policy goals and mechanisms by which wetlands are protected, with goals to protect wetland ecosystem services on one end of the spectrum and goals to protect biodiversity on the other. Goals for protecting ecosystem services were frequently cited in policy documents of countries with agriculture-based economies, whereas goals associated with wetland biodiversity tended to be associated with tourism-based economies. We argue that the components of a country's wetland policies reflect national-level resource and economic characteristics. Understanding the relationship between the type of wetland policy countries adopt and national-level characteristics is critical for international efforts to protect wetlands.

  6. Abnormal lactate levels in patients with polymyositis and dermatomyositis: the benefits of a specific rehabilitative program.

    Science.gov (United States)

    Bertolucci, F; Neri, R; Dalise, S; Venturi, M; Rossi, B; Chisari, C

    2014-04-01

    Polymyositis (PM) and Dermatomyositis (DM) are chronic, inflammatory and autoimmune skeletal muscle disorders characterized by reduced muscle strength, fatigue and myalgia. While inflammation causes muscle damage in the early phase, metabolic alterations such as an impairment of oxidative metabolism seem to be responsible for the disability in the chronic phase of the disease. To assess muscle oxidative efficiency and to test the effect of aerobic training in a group of PM/DM patients. A case-control study and a within-group comparison. SETTING. Outpatients of the Unit of Neurorehabilitation of the University Hospital of Pisa. 20 patients with myositis (15 PM and 5 DM) and 15 healthy subjects as a control group. The test consisted of an incremental, sub-maximal aerobic exercise on a treadmill; haematic lactate was assessed at rest and after 1', 5', 10' and 30' minutes from the end of the exercise. A within-group comparison was conducted on four of the PM patients (P group). They were subjected to six weeks aerobic training. Lactate curve and functional tests were assessed before and after the treatment. A precocious fatigability and significantly higher values of lactate at rest and after the exercise were observed in patients. In the P group mean lactate levels were significantly decreased after the treatment and an improvement of muscle performance was observed. Abnormal blood lactate levels suggested an impaired muscle oxidative efficiency in PM/DM patients. A specific aerobic training program reduced lactate levels and relieved fatigue symptoms in a within-group of four of the PM patients. Such a specific aerobic training program could be introduced in everyday practice for the rehabilitative treatment of PM/DM patients.

  7. National-Level Wetland Policy Specificity and Goals Vary According to Political and Economic Indicators.

    Science.gov (United States)

    Peimer, Alex W; Krzywicka, Adrianna E; Cohen, Dora B; Van den Bosch, Kyle; Buxton, Valerie L; Stevenson, Natalie A; Matthews, Jeffrey W

    2017-01-01

    Growing recognition of the importance of wetlands to human and ecosystem well-being has led countries worldwide to implement wetland protection policies. Different countries have taken different approaches to wetland protection by implementing various policies, including territorial exclusion, market-based offsetting, and incentive programs for land users. Our objective was to describe the relationship between components of national-level wetland protection policies and national characteristics, including natural resource, economic, social, and political factors. We compiled data on the wetland policies of all 193 countries recognized by the U.N. and described the relationships among wetland policy goals and wetland protection mechanisms using non-metric multidimensional scaling. The first non-metric multidimensional scaling axis strongly correlated with whether a country had a wetland-specific environmental policy in place. Adoption of a comprehensive, wetland-specific policy was positively associated with degree of democracy and a commitment to establishing protected areas. The second non-metric multidimensional scaling axis defined a continuum of policy goals and mechanisms by which wetlands are protected, with goals to protect wetland ecosystem services on one end of the spectrum and goals to protect biodiversity on the other. Goals for protecting ecosystem services were frequently cited in policy documents of countries with agriculture-based economies, whereas goals associated with wetland biodiversity tended to be associated with tourism-based economies. We argue that the components of a country's wetland policies reflect national-level resource and economic characteristics. Understanding the relationship between the type of wetland policy countries adopt and national-level characteristics is critical for international efforts to protect wetlands.

  8. Effect of Chitosan and Liposome Nanoparticles as Adjuvant Codelivery on the Immunoglobulin G Subclass Distribution in a Mouse Model.

    Science.gov (United States)

    Haryono, Agus; Salsabila, Korrie; Restu, Witta Kartika; Harmami, Sri Budi; Safari, Dodi

    2017-01-01

    We investigate the immunogenic properties of chitosan and liposome nanoparticles as adjuvant codelivery against a commercial pneumococcal conjugate vaccine (PCV) in an animal model. The chitosan and liposome nanoparticles were prepared by ionic gelation and dry methods, respectively. The PCV immunization was performed intradermally in the presence of adjuvants and booster injections which were given without an adjuvant. The Quil-A® was used as a control adjuvant. The ELISA was performed to measure the antibodies against pneumococcal type 14 polysaccharide (Pn14PS). The level of total antibodies against Pn14PS antigen was no different between the mouse groups with or without adjuvant codelivery. Codelivery of the PCV with chitosan nanoparticles as well as the Quil-A adjuvant elicited IgG1, IgG2a, IgG2b, and IgG3 antibodies. Meanwhile, codelivery of liposome nanoparticles elicited mainly IgG1 antibodies against the Pn14PS. The chitosan and liposome nanoparticles as adjuvant codelivery were successfully synthesized. These nanoparticles have different shapes in particle formation, liposome nanoparticle with their unilamellar shape and chitosan nanoparticles in large shape due to the aggregation of small-size particles. Codelivery of chitosan nanoparticles has more effect on the IgG subclass antibody production than that of liposome nanoparticles in a mouse model.

  9. IgA deficiency: clinical correlates with IgG subclass and mannan-binding lectin deficiencies.

    Science.gov (United States)

    Santaella, María L; Peredo, Rubén; Disdier, Orville M

    2005-06-01

    To characterize an IgA deficient population in terms of the incidence of IgG subclass and mannose-binding lectin (MBL) deficiencies and the type and severity of infections and other associated disorders. Selective IgA deficiency is probably the commonest of the primary immunodeficiency disorders and although it may lead to an increased risk for respiratory and gastrointestinal infections and associated to various autoimmune diseases, it may also be asymptomatic. Several studies have suggested the need of a concomitant defect in order for manifestation of its symptoms. A total of 27 patients fulfilling the diagnostic criteria of selective IgA deficiency were evaluated for IgG subclass and MBL deficiencies after a thorough medical history, physical examination and pertinent evaluation for concomitant medical conditions. The overall incidence of IgG subclass deficiency found in the IgA deficient group was 18.5%. MBL deficiency was found to be 3.7%. These frequencies may have been influenced by the age group evaluated and the size of the population studied. Severe infections were more common in patients with combined deficiencies, either IgA and any of the IgG subclasses or IgA and MBL deficiency. Atopy was widely represented in the patients studied. The observed relationship between combined deficiencies Ig A, IgG subclasses and MBL and the increased representation of severe infections needs to be corroborated in a larger sample of patients with an inclusion of pediatric patients.

  10. Low density lipoprotein subclasses and response to a low-fat diet in healthy men

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.; Dreon, D.M. [Lawrence Berkeley Lab., CA (United States). Life Sciences Div.

    1994-11-01

    Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-fat, 87 subjects had predominantly large, buoyant LDL as measured by gradient gel electrophoresis and confirmed by analytic ultracentrifugation (pattern A), while the remainder had primarily smaller, denser LDL (pattern B). On low-fat, 36 men changed from pattern A to B. Compared with the 51 men in the stable A group, men in the stable B group (n = 18) had a three-fold greater reduction in LDL cholesterol and significantly greater reductions in plasma apoB and mass of intermediate (LDL II) and small (LDL III) LDL subtractions measured by analytic ultracentrifugation. In both stable A and change groups, reductions in LDL-cholesterol were not accompanied by reduced plasma apoB, consistent with the observation of a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, without significant change in particle number. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in response to a low-fat diet.

  11. Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies.

    Science.gov (United States)

    Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

    2016-06-08

    Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49-0.74), flavanones (OR = 0.65, 95% CI: 0.49-0.86), and flavones (OR = 0.78, 95% CI 0.64-0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59-1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer.

  12. IgG Subclasses and Allotypes: From Structure to Effector Functions

    Science.gov (United States)

    Vidarsson, Gestur; Dekkers, Gillian; Rispens, Theo

    2014-01-01

    Of the five immunoglobulin isotypes, immunoglobulin G (IgG) is most abundant in human serum. The four subclasses, IgG1, IgG2, IgG3, and IgG4, which are highly conserved, differ in their constant region, particularly in their hinges and upper CH2 domains. These regions are involved in binding to both IgG-Fc receptors (FcγR) and C1q. As a result, the different subclasses have different effector functions, both in terms of triggering FcγR-expressing cells, resulting in phagocytosis or antibody-dependent cell-mediated cytotoxicity, and activating complement. The Fc-regions also contain a binding epitope for the neonatal Fc receptor (FcRn), responsible for the extended half-life, placental transport, and bidirectional transport of IgG to mucosal surfaces. However, FcRn is also expressed in myeloid cells, where it participates in both phagocytosis and antigen presentation together with classical FcγR and complement. How these properties, IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function will be the focus of the current review. PMID:25368619

  13. Specific calibration problems for gammaspectrometric measurements of low-level radioactivity in environmental samples

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, D. [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany); Wershofen, H. [Physikalisch-Technische Bundesanstalt, Braunschweig (Germany)

    1997-03-01

    Gammaspectrometric measurements of low-level radioactivity in environmental samples are always done in a close source detector geometry. This geometry causes coincidence-summing effects for measurements of multi-photon emitting nuclides. The measurements of radioactivity in environmental samples are also influenced by the absorption of photons in the materials which have to be analysed. Both effects must be taken into account by correction factors with respect to an energy-specific calibration of the detector system for a given geometry and a given composition of the calibration source. The importance of these corrections is emphasized. It is the aim of the present paper to compare different experimental and theoretical methods for the determination of these correction factors published by various authors and to report about efforts to refine them. (orig.)

  14. Psychological balance in high level athletes: gender-based differences and sport-specific patterns.

    Directory of Open Access Journals (Sweden)

    Karine Schaal

    Full Text Available OBJECTIVES: Few epidemiological studies have focused on the psychological health of high level athletes. This study aimed to identify the principal psychological problems encountered within French high level athletes, and the variations in their prevalence based on sex and the sport practiced. METHODS: Multivariate analyses were conducted on nationwide data obtained from the athletes' yearly psychological evaluations. RESULTS: A representative sample of 13% of the French athlete population was obtained. 17% of athletes have at least one ongoing or recent disorder, generalized anxiety disorder (GAD being the most prevalent (6%, followed by non-specific eating disorders (4.2%. Overall, 20.2% of women had at least one psychopathology, against 15.1% in men. This female predominance applied to anxiety and eating disorders, depression, sleep problems and self-harming behaviors. The highest rates of GAD appeared in aesthetic sports (16.7% vs. 6.8% in other sports for men and 38.9% vs. 10.3% for women; the lowest prevalence was found in high risk sports athletes (3.0% vs. 3.5%. Eating disorders are most common among women in racing sports (14% vs. 9%, but for men were found mostly in combat sports (7% vs. 4.8%. DISCUSSION: This study highlights important differences in psychopathology between male and female athletes, demonstrating that the many sex-based differences reported in the general population apply to elite athletes. While the prevalence of psychological problems is no higher than in the general population, the variations in psychopathology in different sports suggest that specific constraints could influence the development of some disorders.

  15. Psychological balance in high level athletes: gender-based differences and sport-specific patterns.

    Science.gov (United States)

    Schaal, Karine; Tafflet, Muriel; Nassif, Hala; Thibault, Valérie; Pichard, Capucine; Alcotte, Mathieu; Guillet, Thibaut; El Helou, Nour; Berthelot, Geoffroy; Simon, Serge; Toussaint, Jean-François

    2011-05-04

    Few epidemiological studies have focused on the psychological health of high level athletes. This study aimed to identify the principal psychological problems encountered within French high level athletes, and the variations in their prevalence based on sex and the sport practiced. Multivariate analyses were conducted on nationwide data obtained from the athletes' yearly psychological evaluations. A representative sample of 13% of the French athlete population was obtained. 17% of athletes have at least one ongoing or recent disorder, generalized anxiety disorder (GAD) being the most prevalent (6%), followed by non-specific eating disorders (4.2%). Overall, 20.2% of women had at least one psychopathology, against 15.1% in men. This female predominance applied to anxiety and eating disorders, depression, sleep problems and self-harming behaviors. The highest rates of GAD appeared in aesthetic sports (16.7% vs. 6.8% in other sports for men and 38.9% vs. 10.3% for women); the lowest prevalence was found in high risk sports athletes (3.0% vs. 3.5%). Eating disorders are most common among women in racing sports (14% vs. 9%), but for men were found mostly in combat sports (7% vs. 4.8%). This study highlights important differences in psychopathology between male and female athletes, demonstrating that the many sex-based differences reported in the general population apply to elite athletes. While the prevalence of psychological problems is no higher than in the general population, the variations in psychopathology in different sports suggest that specific constraints could influence the development of some disorders.

  16. Psychological Balance in High Level Athletes: Gender-Based Differences and Sport-Specific Patterns

    Science.gov (United States)

    Schaal, Karine; Tafflet, Muriel; Nassif, Hala; Thibault, Valérie; Pichard, Capucine; Alcotte, Mathieu; Guillet, Thibaut; El Helou, Nour; Berthelot, Geoffroy; Simon, Serge; Toussaint, Jean-François

    2011-01-01

    Objectives Few epidemiological studies have focused on the psychological health of high level athletes. This study aimed to identify the principal psychological problems encountered within French high level athletes, and the variations in their prevalence based on sex and the sport practiced. Methods Multivariate analyses were conducted on nationwide data obtained from the athletes' yearly psychological evaluations. Results A representative sample of 13% of the French athlete population was obtained. 17% of athletes have at least one ongoing or recent disorder, generalized anxiety disorder (GAD) being the most prevalent (6%), followed by non-specific eating disorders (4.2%). Overall, 20.2% of women had at least one psychopathology, against 15.1% in men. This female predominance applied to anxiety and eating disorders, depression, sleep problems and self-harming behaviors. The highest rates of GAD appeared in aesthetic sports (16.7% vs. 6.8% in other sports for men and 38.9% vs. 10.3% for women); the lowest prevalence was found in high risk sports athletes (3.0% vs. 3.5%). Eating disorders are most common among women in racing sports (14% vs. 9%), but for men were found mostly in combat sports (7% vs. 4.8%). Discussion This study highlights important differences in psychopathology between male and female athletes, demonstrating that the many sex-based differences reported in the general population apply to elite athletes. While the prevalence of psychological problems is no higher than in the general population, the variations in psychopathology in different sports suggest that specific constraints could influence the development of some disorders. PMID:21573222

  17. Cytokines, IgG subclasses and costimulation in a mouse model of thyroid autoimmunity induced by injection of fibroblasts co-expressing MHC class II and thyroid autoantigens

    Science.gov (United States)

    Yan, X-M; Guo, J; Pichurin, P; Tanaka, K; Jaume, J C; Rapoport, B; Mclachlan, S M

    2000-01-01

    AKR/N mice injected with fibroblasts expressing MHC class II (RT4.15HP cells) and the TSH receptor (TSHR) develop antibodies similar to those in Graves' disease. We were unable to analyse the subclass of these antibodies because of unexpectedly high non-specific binding by ELISA or flow cytometry. The non-specific binding reflected generalized immune activation which occurred even when the fibroblasts did not express the TSHR. However, the IgG subclasses were determined for thyroid peroxidase (TPO) antibodies induced using TPO-expressing RT4.14HP cells and found to be IgG2a > IgG1. This Th1 pattern is consistent with spontaneous secretion of interferon-gamma (but not IL-4 or IL-10) by splenocytes from injected mice. The Th1 bias was related to fibroblast injection because conventional immunization of the same mouse strain with purified TPO and adjuvant induced a Th2 response (IgG1 >> IgG2a). Further, untransfected fibroblasts themselves induced powerful, non-specific proliferative responses when used as antigen-presenting cells (APC) in vitro. Flow cytometry revealed that the RT4.15HP fibroblasts (and TSHR- and TPO-transfected derivatives) expressed B7-1. Unexpected constitutive expression of this key molecule may bypass the requirement for up-regulation of other costimulatory molecules involved in T cell stimulation. Our data support the concept that RT4.15HP fibroblasts present the TSHR (or TPO), at least for initiating the immune response. However, the accompanying generalized immune stimulation creates difficulties for analysis of TSHR-specific T and B lymphocytes. On the other hand, extension of the model to TPO, an easier antigen to study, will facilitate analysis of murine T cell responses likely to resemble those in human thyroid autoimmunity. PMID:11091271

  18. Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels.

    Science.gov (United States)

    Dai, Bo; Ye, Ding-Wei; Kong, Yun-Yi; Shen, Yi-Jin; Wang, Bo-Hua

    2008-03-01

    To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific antigen (PSA) levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% (6/90) in our patients (P 50 ng/mL (P sextant strategy is recommended for those with PSA > 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy = or > 10 years and the sextant strategy should be applied in those with life expectancy < 10 years.

  19. Prostate specific antigen level and Gleason score in predicting the stage of newly diagnosed prostate cancer.

    Science.gov (United States)

    Spencer, J A; Chng, W J; Hudson, E; Boon, A P; Whelan, P

    1998-11-01

    The purpose of this study was to determine the utility of prostate specific antigen (PSA) level and Gleason score in the prediction of disease stage in men with newly diagnosed prostate cancer. 102 consecutive men, newly diagnosed with prostate cancer and candidates for radical therapy, underwent contrast enhanced pelvic CT and skeletal scintigraphy. Staging examinations used the TNM classification and were reported prospectively with the radiologist blinded to the patient's Gleason score and level of PSA. Lymph node metastasis was confirmed by CT guided biopsy, lymphadenectomy or response to therapy in some cases of massive disease. There were significant differences between the mean PSA values of 18 men with and 84 men without skeletal metastases (p = 0.01) and between men with locally confined and non-confined disease (p = 0.02). There was no difference between PSA values of 13 men with and 89 men without lymph node metastasis (p = 0.9). Only one man with CT evidence of nodal metastasis (N + ve) had a PSA value below 20 ng ml-1. Two men with Gleason scores below 6 were N + ve and both had PSA values over 20 ng ml-1. One man with skeletal metastasis had a PSA value below 20 ng ml-1 but had bone pain. For this study group if only those men with PSA values over 20 ng ml-1 had been examined, sensitivity for lymphatic and skeletal metastasis would have been 92%. Using this threshold about one-third would have been spared imaging investigation. In conclusion, pelvic CT and skeletal scintigraphy are unlikely to show metastatic disease in a man newly diagnosed with prostate cancer who has no suggestive clinical features, a PSA level below 20 ng ml-1 and a Gleason score below 6.

  20. Toxoplasma gondii infection specifically increases the levels of key host microRNAs.

    Directory of Open Access Journals (Sweden)

    Gusti M Zeiner

    2010-01-01

    Full Text Available The apicomplexan parasite Toxoplasma gondii can infect and replicate in virtually any nucleated cell in many species of warm-blooded animals; thus, it has evolved the ability to exploit well-conserved biological processes common to its diverse hosts. Here we have investigated whether Toxoplasma modulates the levels of host microRNAs (miRNAs during infection.Using microarray profiling and a combination of conventional molecular approaches we report that Toxoplasma specifically modulates the expression of important host microRNAs during infection. We show that both the primary transcripts for miR-17 approximately 92 and miR-106b approximately 25 and the pivotal miRNAs that are derived from miR-17 approximately 92 display increased abundance in Toxoplasma-infected primary human cells; a Toxoplasma-dependent up-regulation of the miR-17 approximately 92 promoter is at least partly responsible for this increase. The abundance of mature miR-17 family members, which are derived from these two miRNA clusters, remains unchanged in host cells infected with the closely related apicomplexan Neospora caninum; thus, the Toxoplasma-induced increase in their abundance is a highly directed process rather than a general host response to infection.Altered levels of miR-17 approximately 92 and miR-106b approximately 25 are known to play crucial roles in mammalian cell regulation and have been implicated in numerous hyperproliferative diseases although the mechanisms driving their altered expression are unknown. Hence, in addition to the implications of these findings on the host-pathogen interaction, Toxoplasma may represent a powerful probe for understanding the normal mechanisms that regulate the levels of key host miRNAs.

  1. Dissecting the relationships of IgG subclasses and complements in membranous lupus nephritis and idiopathic membranous nephropathy.

    Science.gov (United States)

    Na, Woong; Yi, Kijong; Song, Young Soo; Park, Moon Hyang

    2017-01-01

    Membranous lupus nephritis (MLN) and idiopathic membranous nephropathy (IMN) are kidney diseases with similar morphology, but distinct etiologies, both producing glomeruli with immune deposits. Immunoglobulins and complements, the main components of the deposits, can be detected by immunofluorescence (IF) microscopy. Previous researches characterized the immune deposits only individually, but not the interactions between them. To study these relationships we analyzed an IF profile of IgG subclasses and complements (IgG1, IgG2, IgG3, IgG4, C3, C1q, and C4) in 53 and 95 cases of biopsy-confirmed MLNs and IMNs, respectively, mainly using information theory and Bayesian networks. We identified significant entropy differences between MLN and IMN for all markers except C3 and IgG1, but mutual information (a measure of mutual dependence) were not significantly different for all the pairs of markers. The entropy differences between MLN and IMN, therefore, were not attributable to the mutual information. These findings suggest that disease type directly and/or indirectly influences the glomerular deposits of most of IgG subclasses and complements, and that the interactions between any pair of the markers were similar between the two diseases. A Markov chain of IgG subclasses was derived from the mutual information about each pair of IgG subclass. Finally we developed an integrated disease model, consistent with the previous findings, describing the glomerular immune deposits of the IgG subclasses and complements based on a Bayesian network using the Markov chain of IgG subclasses as seed. The relationships between the markers were effectively explored by information theory and Bayesian network. Although deposits of IgG subclasses and complements depended on both disease type and the other markers, the interaction between the markers appears conserved, independent from the disease type. The disease model provided an integrated and intuitive representation of the

  2. Core Gene Set As the Basis of Multilocus Sequence Analysis of the Subclass Actinobacteridae

    Science.gov (United States)

    Adékambi, Toïdi; Butler, Ray W.; Hanrahan, Finnian; Delcher, Arthur L.; Drancourt, Michel; Shinnick, Thomas M.

    2011-01-01

    Comparative genomic sequencing is shedding new light on bacterial identification, taxonomy and phylogeny. An in silico assessment of a core gene set necessary for cellular functioning was made to determine a consensus set of genes that would be useful for the identification, taxonomy and phylogeny of the species belonging to the subclass Actinobacteridae which contained two orders Actinomycetales and Bifidobacteriales. The subclass Actinobacteridae comprised about 85% of the actinobacteria families. The following recommended criteria were used to establish a comprehensive gene set; the gene should (i) be long enough to contain phylogenetically useful information, (ii) not be subject to horizontal gene transfer, (iii) be a single copy (iv) have at least two regions sufficiently conserved that allow the design of amplification and sequencing primers and (v) predict whole-genome relationships. We applied these constraints to 50 different Actinobacteridae genomes and made 1,224 pairwise comparisons of the genome conserved regions and gene fragments obtained by using Sequence VARiability Analysis Program (SVARAP), which allow designing the primers. Following a comparative statistical modeling phase, 3 gene fragments were selected, ychF, rpoB, and secY with R2>0.85. Selected sets of broad range primers were tested from the 3 gene fragments and were demonstrated to be useful for amplification and sequencing of 25 species belonging to 9 genera of Actinobacteridae. The intraspecies similarities were 96.3–100% for ychF, 97.8–100% for rpoB and 96.9–100% for secY among 73 strains belonging to 15 species of the subclass Actinobacteridae compare to 99.4–100% for 16S rRNA. The phylogenetic topology obtained from the combined datasets ychF+rpoB+secY was globally similar to that inferred from the 16S rRNA but with higher confidence. It was concluded that multi-locus sequence analysis using core gene set might represent the first consensus and valid approach for

  3. Specific alterations in levels of mannose 6-phosphorylated glycoproteins in different neuronal ceroid lipofuscinoses.

    Science.gov (United States)

    Sleat, D E; Sohar, I; Pullarkat, P S; Lobel, P; Pullarkat, R K

    1998-01-01

    Mannose 6-phosphate (Man-6-P) is a carbohydrate modification that is generated on newly synthesized lysosomal proteins. This modification is specifically recognized by two Man-6-P receptors that direct the vesicular transport of the lysosomal enzymes from the Golgi to a prelysosomal compartment. The Man-6-P is rapidly removed in the lysosome of most cell types; however, in neurons the Man-6-P modification persists. In this study we have examined the spectrum of Man-6-P-containing glycoproteins in brain specimens from patients with different neuronal ceroid lipofuscinoses (NCLs), which are progressive neurodegenerative disorders with established links to defects in lysosomal catabolism. We find characteristic alterations in the Man-6-P glycoproteins in specimens from late-infantile (LINCL), juvenile (JNCL) and adult (ANCL) patients. Man-6-P glycoproteins in LINCL patients were similar to controls, with the exception that the band corresponding to CLN2, a recently identified lysosomal enzyme whose deficiency results in this disease, was absent. In an ANCL patient, two Man-6-P glycoproteins were elevated in comparison with normal controls, suggesting that this disease also results from a perturbation in lysosomal hydrolysis. In JNCL, total levels of Man-6-P glycoproteins were 7-fold those of controls. In general this was reflected by increased lysosomal enzyme activities in JNCL but three Man-6-P glycoproteins were elevated to an even greater degree. These are CLN2 and the unidentified proteins that are also highly elevated in the ANCL. PMID:9729460

  4. Comparison of specific-yield estimates for calculating evapotranspiration from diurnal groundwater-level fluctuations

    Science.gov (United States)

    Gribovszki, Zoltán

    2017-11-01

    Methods that use diurnal groundwater-level fluctuations are commonly used for shallow water-table environments to estimate evapotranspiration (ET) and recharge. The key element needed to obtain reliable estimates is the specific yield (Sy), a soil-water storage parameter that depends on unsaturated soil-moisture and water-table fluxes, among others. Soil-moisture profile measurement down to the water table, along with water-table-depth measurements, can provide a good opportunity to calculate Sy values even on a sub-daily scale. These values were compared with Sy estimates derived by traditional techniques, and it was found that slug-test-based Sy values gave the most similar results in a sandy soil environment. Therefore, slug-test methods, which are relatively cheap and require little time, were most suited to estimate Sy using diurnal fluctuations. The reason for this is that the timeframe of the slug-test measurement is very similar to the dynamic of the diurnal signal. The dynamic characteristic of Sy was also analyzed on a sub-daily scale (depending mostly on the speed of drainage from the soil profile) and a remarkable difference was found in Sy with respect to the rate of change of the water table. When comparing constant and sub-daily (dynamic) Sy values for ET estimation, the sub-daily Sy application yielded higher correlation, but only a slightly smaller deviation from the control ET method, compared with the usage of constant Sy.

  5. Levels of Intra-specific AFLP Diversity in Tuber-Bearing Potato Species with Different Breeding Systems and Ploidy Levels

    Directory of Open Access Journals (Sweden)

    Glenn J. Bryan

    2017-09-01

    Full Text Available DNA-based marker analysis of plant genebank material has become a useful tool in the evaluation of levels of genetic diversity and for the informed use and maintenance of germplasm. In this study, we quantify levels of amplified fragment length polymorphism (AFLP in representative accessions of wild and cultivated potato species of differing geographic origin, ploidy, and breeding system. We generated 449 polymorphic AFLP fragments in 619 plants, representing multiple plants (16–23 from 17 accessions of 14 potato taxa as well as single plants sampled from available accessions (from 3 to 56 of the same 14 taxa. Intra-accession diversities were compared to those of a synthetic ‘taxon-wide’ population comprising a single individual from a variable number of available accessions of each sampled taxon. Results confirm the expected considerably lower levels of polymorphism within accessions of self-compatible as compared to self-incompatible taxa. We observed broadly similar levels of ‘taxon-wide’ polymorphism among self-compatible and self-incompatible species, with self-compatible taxa showing only slightly lower rates of polymorphism. The most diverse accessions were the two cultivated potato accessions examined, the least diverse being the Mexican allohexaploids Solanum demissum and S. iopetalum. Generally allopolyploid self-compatible accessions exhibited lower levels of diversity. Some purported self-incompatible accessions showed relatively low levels of marker diversity, similar to the more diverse self-compatible material surveyed. Our data indicate that for self-compatible species a single plant is highly representative of a genebank accession. The situation for self-incompatible taxa is less clear, and sampling strategies used will depend on the type of investigation. These results have important implications for those seeking novel trait variation (e.g., disease resistance in gene banks as well as for the selection of individuals

  6. Lipoprotein subclass patterns in women with polycystic ovary syndrome (PCOS) compared with equally insulin-resistant women without PCOS.

    LENUS (Irish Health Repository)

    Phelan, N

    2012-02-01

    OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are more insulin resistant and display an atherogenic lipid profile compared with normal women of similar body mass index (BMI). Insulin resistance (IR) at least partially underlies the dyslipidemia of PCOS, but it is unclear whether PCOS status per se confers additional risk. RESEARCH DESIGN AND METHODS: Using a case-control design, we compared plasma lipids and lipoprotein subclasses (using polyacrylamide gel tube electrophoresis) in 70 women with PCOS (National Institutes of Health criteria) and 70 normal women pair matched for age, BMI, and IR (homeostasis model assessment-IR, quantitative insulin sensitivity check index, and the Avignon Index). Subjects were identified as having a (less atherogenic) type A pattern consisting predominantly of large low-density lipoprotein (LDL) subfractions or a (more atherogenic) non-A pattern consisting predominantly of small-dense LDL subfractions. RESULTS: Total, high-density lipoprotein, or LDL cholesterol, or triacylglycerol did not differ between the groups, but very low-density lipoprotein levels (P<0.05) were greater in women with PCOS, whereas a non-A LDL profile was seen in 12.9% compared with 2.9% of controls (P<0.05, chi2). Multiple regression analysis revealed homeostasis model assessment-IR and waist circumference to be independent predictors of very low-density lipoprotein together explaining 40.2% of the overall variance. Logistic regression revealed PCOS status to be the only independent determinant of a non-A LDL pattern (odds ratio 5.48 (95% confidence interval 1.082-27.77; P<0.05). CONCLUSIONS: Compared with women matched for BMI and IR, women with PCOS have potentially important differences in lipid profile with greater very low-density lipoprotein levels and increased rates of a more atherogenic non-A LDL pattern.

  7. IgG subclass distribution of autoantibodies differs between renal and extra-renal relapses in patients with systemic lupus erythematosus

    NARCIS (Netherlands)

    Bijl, M.; Dijstelbloem, H. M.; Oost, W. W.; Bootsma, H.; Derksen, R. H. W. M.; Aten, J.; Limburg, P. C.; Kallenberg, C. G. M.

    2002-01-01

    Background. IgG subclasses of autoantibodies differ in their potential to induce an inflammatory response as they interact differentially with complement and Fcgamma receptors. Methods. The IgG subclass distribution of anti-nucleohistone and anti-dsDNA antibodies was analysed longitudinally in

  8. Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients

    NARCIS (Netherlands)

    Westra, J.; van Assen, S.; Wilting, K. R.; Land, J.; Horst, G.; de Haan, A.; Bijl, M.

    2014-01-01

    Rituximab (RTX) treatment in rheumatoid arthritis (RA) patients severely hampers humoral response after influenza vaccination as determined by haemagglutination inhibition assay (HI). It is not known whether HI reflects both immunoglobulin (Ig)M and IgG (subclass) influenza response, and whether IgM

  9. Sex differences in the associations of visceral adiposity, HOMA-IR, and BMI with lipoprotein subclass analysis in obese adolescents

    Science.gov (United States)

    Hatch-Stein, Jacquelyn A; Kelly, Andrea; Gidding, Samuel S; Zemel, Babette S; Magge, Sheela N

    2016-01-01

    Background The relationship of lipoprotein particle subclasses to visceral adipose tissue area (VAT-area) in obese children has not been examined previously. Objectives The study aims were to compare the relationships of VAT-area, homeostatic model assessment of insulin resistance (HOMA-IR), and body mass index (BMI) with lipids and lipoprotein subclasses in obese adolescents, and to determine if these relationships vary by sex. Methods This cross-sectional study of obese adolescents (BMI≥95th percentile), ages 12-18y, measured VAT-area by dual energy x-ray absorptiometry (DXA), BMI, fasting lipids, lipoprotein subclasses, and HOMA-IR. Linear regression models evaluated the associations of VAT-area, HOMA-IR, and BMI with lipid cardiometabolic risk factors. Sex-stratified analyses further explored these associations. Results Included were 127 adolescents (age=14.4±1.5 years; 53.5% female; 88.2% African-American), mean BMI=34.0±5.1 kg/m2. VAT-area was negatively associated with LDL particle (−P) size (β=−0.28, p=0.0001), HDL-P size (β=−0.33, p<0.0001) and large HDL-P concentration (β=−0.29, p<0.0001), and positively associated with small LDL-P concentration (β=0.23, p=0.0005) and small HDL-P concentration (β=0.25, p=0.05). When VAT-area, HOMA-IR, and BMI associations were compared, VAT-area had the strongest associations with most of the lipoprotein subclasses. After sex-stratification, the associations of VAT-area with HDL cholesterol, LDL-P size, and large LDL-P concentration were significant only for females (all p<0.05). Conclusions In a cohort of largely African-American obese adolescents, VAT-area was associated with a more atherogenic lipoprotein subclass profile. When compared to HOMA-IR and BMI, VAT-area had the strongest associations with most lipoprotein subclasses. The relationships between VAT-area and certain lipoprotein subclasses are significantly different in males versus females. PMID:27578105

  10. Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy men-a randomized trial.

    Directory of Open Access Journals (Sweden)

    Heiner K Berthold

    Full Text Available CONTEXT AND OBJECTIVE: Investigating the effects of lipid-lowering drugs on HDL subclasses has shown ambiguous results. This study assessed the effects of ezetimibe, simvastatin, and their combination on HDL subclass distribution. DESIGN AND PARTICIPANTS: A single-center randomized parallel 3-group open-label study was performed in 72 healthy men free of cardiovascular disease with a baseline LDL-cholesterol of 111±30 mg/dl (2.9±0.8 mmol/l and a baseline HDL-cholesterol of 64±15 mg/dl (1.7±0.4 mmol/l. They were treated with ezetimibe (10 mg/day, n = 24, simvastatin (40 mg/day, n = 24 or their combination (n = 24 for 14 days. Blood was drawn before and after the treatment period. HDL subclasses were determined using polyacrylamide gel-tube electrophoresis. Multivariate regression models were used to determine the influence of treatment and covariates on changes in HDL subclass composition. RESULTS: Baseline HDL subclasses consisted of 33±10% large, 48±6% intermediate and 19±8% small HDL. After adjusting for baseline HDL subclass distribution, body mass index, LDL-C and the ratio triglycerides/HDL-C, there was a significant increase in large HDL by about 3.9 percentage points (P<0.05 and a decrease in intermediate HDL by about 3.5 percentage points (P<0.01 in both simvastatin-containing treatment arms in comparison to ezetimibe. The parameters obtained after additional adjustment for the decrease in LDL-C indicated that about one third to one half of these effects could be explained by the extent of LDL-C-lowering. CONCLUSIONS: In healthy men, treatment with simvastatin leads to favorable effects on HDL subclass composition, which was not be observed with ezetimibe. Part of these differential effects may be due to the stronger LDL-C-lowering effects of simvastatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00317993.

  11. Prostate specific antigen levels and prostate cancer detection rates in patients with end stage renal disease.

    Science.gov (United States)

    Chen, Catherine J; Heldt, Jonathan P; Anderson, Kirk M; Ruckle, Herbert C; Agarwal, Gautum; Smith, Damien L; Schlaifer, Amy E; Richards, Gideon D; Arnold, Don C; Baldwin, D Duane

    2012-06-01

    Patients with end stage renal disease plus prostate cancer are ineligible to receive a renal transplant at most centers until an acceptable cancer-free period is demonstrated. To our knowledge previously established prostate specific antigen reference ranges have not been validated in patients with end stage renal disease. We determined age stratified 95th percentile prostate specific antigen reference ranges and the prostate cancer detection rate at specific prostate specific antigen intervals for patients with end stage renal disease. We retrospectively reviewed the records of 775 male patients with end stage renal disease on the waiting list for a renal transplant who had undergone a serum prostate specific antigen test. Prostate specific antigen was stratified by age at the time of the blood test and 95th percentile reference ranges were calculated for each decade. A total of 80 patients underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination. The cancer detection rate was calculated for specific prostate specific antigen reference ranges. The age specific 95th percentile prostate specific antigen references ranges were 0 to 4.0 ng/ml for ages 40 to 49 in 137 patients, 0 to 5.3 ng/ml for ages 50 to 59 in 257, 0 to 10.5 ng/ml for ages 60 to 69 in 265 and 0 to 16.6 ng/ml for ages 70 to 79 years in 69. The cancer detection rate was 44%, 38% and 67% for prostate specific antigen 2.5 to 4.0, 4 to 10 and greater than 10 ng/ml, respectively. In our study population of patients with end stage renal disease age stratified prostate specific antigen was higher than in the general population. The cancer detection rate was increased in our patients with end stage renal disease compared to that in patients with normal renal function at specific prostate specific antigen intervals. Lower prostate specific antigen cutoffs may be appropriate to recommend prostate biopsy in patients with end stage renal disease. Copyright

  12. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  13. Affinity composite cryogel discs functionalized with Reactive Red 120 and Green HE 4BD dye ligands: Application on the separation of human immunoglobulin G subclasses

    Energy Technology Data Exchange (ETDEWEB)

    Huseynli, Sabina; Baydemir, Gözde; Sarı, Esma [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey); Elkak, Assem [Laboraory of “Valorisation des Ressources Naturelles et Produits de Santé (VRNPS)”, Doctoral School of Sciences and Technology, Lebanese University, Rafic Hariri University Campus, Hadath (Lebanon); Denizli, Adil, E-mail: denizli@hacettepe.edu.tr [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey)

    2015-01-01

    Naturally produced by the human immune system, immunoglobulin nowadays is widely used for in vivo and in vitro purposes. The increased needs for pure immunoglobulin have prompted researchers to find new immunoglobulin chromatographic separation processes. Cryogels as chromatographic adsorbents, congregate several mechanical features including good compatibility, large pore structure, flexibility, short diffusion pathway and stability. These different characteristics make them a good alternative to conventional chromatographic methods and allowing their potential use in separation technology. In the present study, two sets of poly(2-hydroxyethyl methacrylate) (PHEMA) based beads were prepared and functionalized with Reactive Red 120 (RR) and Reactive Green HE 4BD (RG) dyes, and then embedded into supermacroporous cryogels. The morphology, physical and chemical features of the prepared bead embedded composite cryogel discs (CCDs) were performed by scanning electron microscopy (SEM), swelling test, elemental analysis and Fourier transform infrared spectroscopy (FTIR). The results showed that the embedded composite cryogel discs have a specific surface area of 192.0 m{sup 2}/g with maximum adsorption capacity of HIgG 239.8 mg/g for the RR functionalized CCD and 170 mg/g for RG functionalized CCD columns, both at pH 6.2. - Highlights: • Dye attached composite cryogel discs were prepared to separate HIgG subclasses. • Composite cryogels characterized by swelling, FTIR, SEM and elemental analysis. • Reactive Green HE 4B and Reactive Red 120 dyes were used as the affinity ligand. • HIgG and subclasses were separate from both aqueous solution and human plasma.

  14. High-level HIV-1 viremia suppresses viral antigen-specific CD4+ T cell proliferation

    OpenAIRE

    McNeil, Andrew C.; Shupert, W. Lesley; Iyasere, Christiana A.; Hallahan, Claire W.; Mican, JoAnn; Davey, Richard T.; Connors, Mark

    2001-01-01

    In chronic viral infections of humans and experimental animals, virus-specific CD4+ T cell function is believed to be critical for induction and maintenance of host immunity that mediates effective restriction of viral replication. Because in vitro proliferation of HIV-specific memory CD4+ T cells is only rarely demonstrable in HIV-infected individuals, it is presumed that HIV-specific CD4+ T cells are killed upon encountering the virus, and maintenance of CD4+ T cell responses in some patien...

  15. The level 1 and 2 specification for parallel benchmark and a benchmark test of scalar-parallel computer SP2 based on the specifications

    Energy Technology Data Exchange (ETDEWEB)

    Orii, Shigeo [Japan Atomic Energy Research Inst., Tokyo (Japan)

    1998-06-01

    A benchmark specification for performance evaluation of parallel computers for numerical analysis is proposed. Level 1 benchmark, which is a conventional type benchmark using processing time, measures performance of computers running a code. Level 2 benchmark proposed in this report is to give the reason of the performance. As an example, scalar-parallel computer SP2 is evaluated with this benchmark specification in case of a molecular dynamics code. As a result, the main causes to suppress the parallel performance are maximum band width and start-up time of communication between nodes. Especially the start-up time is proportional not only to the number of processors but also to the number of particles. (author)

  16. Association of IL-10 level and IL-10 promoter SNPs with specific antibodies in penicillin-allergic patients.

    Science.gov (United States)

    Qiao, Hai-Ling; Wen, Qiang; Gao, Na; Tian, Xin; Jia, Lin-Jing

    2007-03-01

    Our aim was to investigate the hypothesis that the sera interleukin-10 (IL-10) level and polymorphic nucleotides within the IL-10 gene promoters would link to specific IgE and IgG production and the expression of penicillin allergy. One hundred and two patients and 86 healthy subjects were chosen for assay of serum IL-10 level by enzyme-linked immunosorbent assay (ELISA) and type -1082 G/A and -819 C/T alleles by sequence-specific primer polymerase chain reaction (SSP-PCR). Radioallergosorbent test (RAST) and ELISA were used to examine eight types of specific immunoglobulin-E (IgE) and IgG antibodies, respectively, which included four types of antibodies to major and minor antigenic determinants. Compared with control subjects and patients with negative-specific IgE, there were significantly lower levels of IL-10 in patients with positive-specific IgE (P allergic patients with negative-specific IgG (P allergic-history group. Compared with controls and patients with negative antibodies, a significantly decreased frequency of the -1082 G allele was present in patients with positive antibodies (P allergic reaction to penicillins. The distributions of genotype and frequency of allele at the -1082 G/A position may be associated with the production of both specific IgE and IgG antibodies.

  17. Repetition rates of specific interval patterns in single spike train reflect excitation level of specific receptor types, shown by high-speed favored-pattern detection method.

    Science.gov (United States)

    Ku, Yun-Hui; Wang, Ming; Li, Yao-Hua; Sun, Ze-Jin; Guo, Tao; Wu, Jin-Sheng

    2006-10-03

    Interval patterns in single spike train, e.g. "favored patterns (FPs, the FP is a sequence of successive intervals of action potentials that occur more often than what is reasonably expected at random.)", may represent neural codes containing information. The present study developed a "high-speed FP-detection method" which could qualitatively and quantitatively analyze FPs. By using this method, single spike trains of nucleus paraventricularis (NPV) and rostral ventrolateral medulla (RVL) having different firing patterns, being involved in regulation of arterial pressure, and controlled by different transmitters, were chosen for analysis. (1) Corticotropin releasing factor, substance P and agonists of alpha-, beta- and M-receptor microinjected into these brain areas, respectively, induced dominant change of specific FP. Repetition rates of specific FPs reflect excitation level of specific receptor types. It shows that chemical codes (different transmitters with their receptor types or subtypes) are transformed into electrical codes (different FPs). (2) When alpha-, beta- and M-receptors of RVL neurons were activated simultaneously by intrinsic excitatory transmitters released due to activation of input pathway, only repetition rate of the specific FP that represented the predominant activity of the receptor type (alpha-adrenergic receptor) markedly increased. The activities of other receptor types (beta- and M-receptors) were masked. (3) Intrinsic inhibitory transmitters (GABA, beta-endorphin) in the RVL all decreased specific FP repetition rate of dominant receptor type. These results may provide a new way to further explore how information in the CNS is conveyed and processed.

  18. Different levels of natural antibodies in chickens divergently selected for specific antibody responses

    NARCIS (Netherlands)

    Parmentier, H.K.; Lammers, A.; Hoekman, J.J.; Vries Reilingh, de G.; Zaanen, I.T.A.; Savelkoul, H.F.J.

    2004-01-01

    We studied the presence of Natural antibodies in plasma samples from individual birds from selected chicken lines at young and old age. Binding, specificity, and relative affinity to various antigens were determined in plasma from non-immunized female chickens at 5 weeks of age, and in plasma

  19. Classification of a Subclass of Two-Dimensional Lattices via Characteristic Lie Rings

    Science.gov (United States)

    Habibullin, Ismagil; Poptsova, Mariya

    2017-09-01

    The main goal of the article is testing a new classification algorithm. To this end we apply it to a relevant problem of describing the integrable cases of a subclass of two-dimensional lattices. By imposing the cut-off conditions u_{-1}=c_0 and u_{N+1}=c_1 we reduce the lattice u_{n,xy}=α(u_{n+1},u_n,u_{n-1})u_{n,x}u_{n,y} to a finite system of hyperbolic type PDE. Assuming that for each natural N the obtained system is integrable in the sense of Darboux we look for α. To detect the Darboux integrability of the hyperbolic type system we use an algebraic criterion of Darboux integrability which claims that the characteristic Lie rings of such a system must be of finite dimension. We prove that up to the point transformations only one lattice in the studied class passes the test. The lattice coincides with the earlier found Ferapontov-Shabat-Yamilov equation. The one-dimensional reduction x=y of this lattice passes also the symmetry integrability test.

  20. Synthesis of some members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family.

    Science.gov (United States)

    Padwa, Albert; Zhang, Hongjun

    2007-03-30

    The total synthesis of several members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family has been carried out. (+/-)-Lycoricidine and (+/-)-7-deoxypancratistatin were assembled through a one-pot Stille/intramolecular Diels-Alder cycloaddition cascade to construct the core skeleton. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone on further heating at 160 degrees C. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered vinyl group oriented exo with respect to the oxygen bridge. The resulting cycloadduct was used for the stereocontrolled installation of the remaining functionality present in the C-ring of the target molecules. Key features of the synthetic strategy include (1) a lithium hydroxide induced tandem hydrolysis/decarboxylation/elimination sequence to introduce the required pi-bond in the C-ring of (+/-)-lycoricidine, and (2) conversion of the initially formed Diels-Alder adduct into an aldehyde intermediate which then undergoes a stereospecific decarbonylation reaction mediated by Wilkinson's catalyst to set the trans-B-C ring junction of (+/-)-7-deoxypancratistatin.

  1. Dynamics of plasma levels of specific IgE in chlorhexidine allergic patients with and without accidental re-exposure

    DEFF Research Database (Denmark)

    Opstrup, Morten Schjørring; Poulsen, Lars K.; Malling, Hans Jørgen

    2016-01-01

    BACKGROUND: Chlorhexidine is an effective disinfectant, which may cause severe allergic reactions. Plasma level of specific IgE to chlorhexidine (ImmunoCAP(®) ) has high estimated sensitivity and specificity when measured within 6 months of allergic reaction, but knowledge of the dynamics over...... longer time periods is lacking and it is unknown whether levels fall below allergic patients...... with and without re-exposure. METHODS: All patients diagnosed with chlorhexidine allergy in the Danish Anaesthesia Allergy Centre January 1999 to March 2015 were invited to participate. The study included blood samples from the time of reaction and time of investigation and blood samples drawn prospectively over...

  2. Correlation of Age-Specific Phenylalanine Levels on Intellectual Outcome in Patients with Phenylketonuria

    OpenAIRE

    Viau, Krista S.

    2010-01-01

    It is widely appreciated by the medical community that subtle deficits in intellect, academic skills and executive functioning exist in early treated phenylketonuria (PKU). In this study, we described the relationship between intellectual outcome and concentration/variation in blood phenylalanine (Phe) during specific developmental periods (0-5 years, 6-10 years, >10 years). We also examined the association between mean number of blood Phe samples and maintenance of Phe within treatment ran...

  3. SPECIFIC SITES OF BONE EXPANSION DEPEND ON THE LEVEL OF VOLLEYBALL PRACTICE IN PREPUBESCENT BOYS

    Directory of Open Access Journals (Sweden)

    Hamada Chaari

    2013-06-01

    Full Text Available The purpose of this study was to investigate the effect of 18 months of high and low levels of volleyball practice on bone acquisition. 130 prepubescent boys (mean age 11.4 ± 0.7 were divided into a high-level training group (HLG, low-level training group (LLG, and controls. Bone mineral content (BMC and bone area at the whole body, lumbar spine L2-L4, femoral neck of the dominant leg, and right and left radius were measured using dual-photon X-ray absorptiometry. Enhanced BMC resulted from high-training volleyball activity in all measured sites except the third left and right distal radius, which is not modified by low-level training in prepubescent players but it was accompanied by a bone area expansion in radius and weight-bearing sites for the HLG, and in legs, whole right and left radius for the LLG. Significant improvement of skeletal tissues is associated with the intensity and duration of volleyball training.

  4. Plasma levels of beta-endorphin and serotonin in response to specific spinal based exercises

    Directory of Open Access Journals (Sweden)

    O. Sokunbi

    2008-02-01

    Full Text Available Exercises as the primary mode of treatment for low back disorders aim to achieve pain reduction, improvement in functional abilityand quality of life of for low back disorder sufferers. However the bio-chemical events associated with the use of these exercises in terms of theireffects on pain relieving neuropeptides have not been well established. Thisstudy was carried out to investigate the effects of spinal stabilisation, backextension and treadmill walking exercises on plasma levels of serotonin andbeta-endorphin.Twenty volunteers (10 males and 10 females without low back pain participated in the study. They were randomly allocated either to one of theexercise groups, where participants carried out one of the spinal stabilisation, back extension and treadmill walkingexercises or the control (no exercise group. The main outcome measures used in this study were plasma levels of serotonin and beta-endorphin measured with Enzyme linked immuno absorbent assay (ELISA technique.The results of this study showed that spinal stabilisation and treadmill walking exercises produced significantincrease in plasma serotonin levels (P < 0.05 however there were no significant changes in the plasma levels of beta-endorphin in all the exercise groups (P > 0.05.It could be that biochemical effects associated with stabilisation and treadmill walking exercises therefore mayinvolve production of serotonin and its release into the plasma.

  5. SPECIFIC SITES OF BONE EXPANSION DEPEND ON THE LEVEL OF VOLLEYBALL PRACTICE IN PREPUBESCENT BOYS

    Science.gov (United States)

    Zouch, M.; Zribi, A.; Bouajina, E.; Zaouali, M.; Tabka, Z.

    2013-01-01

    The purpose of this study was to investigate the effect of 18 months of high and low levels of volleyball practice on bone acquisition. 130 prepubescent boys (mean age 11.4 ± 0.7) were divided into a high-level training group (HLG), low-level training group (LLG), and controls. Bone mineral content (BMC) and bone area at the whole body, lumbar spine L2-L4, femoral neck of the dominant leg, and right and left radius were measured using dual-photon X-ray absorptiometry. Enhanced BMC resulted from high-training volleyball activity in all measured sites except the third left and right distal radius, which is not modified by low-level training in prepubescent players but it was accompanied by a bone area expansion in radius and weight-bearing sites for the HLG, and in legs, whole right and left radius for the LLG. Significant improvement of skeletal tissues is associated with the intensity and duration of volleyball training. PMID:24744493

  6. Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety

    NARCIS (Netherlands)

    Molendijk, M.L.; Bus, B.A.A.; Spinhoven, P.; Penninx, B.W.J.H.; Prickaerts, J.; Voshaar, R.C.O.; Elzinga, B.M.

    2012-01-01

    Objectives. Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as

  7. Confidence Level Based Approach to Total Dose Specification for Spacecraft Electronics

    Science.gov (United States)

    Xapsos, M. A.; Stauffer, C.; Phan, A.; McClure, S. S.; Ladbury, R. L.; Pellish, J. A.; Campola, M. J.; Label, K. A.

    2017-01-01

    A confidence level based approach to total dose radiation hardness assurance is presented for spacecraft electronics. It is applicable to both ionizing and displacement damage dose. Results are compared to the traditional approach that uses radiation design margin and advantages of the new approach are discussed.

  8. Clone-specific differences in Pragmites australis: Effects of ploidy level and geographic origin

    DEFF Research Database (Denmark)

    Hansen, D.; Lambertini, Carla; Jampeetong, Arunothai

    2007-01-01

    by the geographic origin, the euploidy level (4x, 6x, 8x and 12x), and to assess differences between native and introduced clones in North America. Growth, morphology, photosynthetic characteristics, photosynthetic pigments and enzymes were measured on 11 geographically distinct clones propagated in a common...

  9. Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location

    NARCIS (Netherlands)

    Leufkens, A.M.; Duijnhoven, van F.J.B.; Boshuizen, H.C.; Sierseman, P.D.; Kunst, A.E.; Mouw, T.; Tjonneland, A.; Olsen, A.; Overvad, K.; Boutron-Ruault, M.C.; Clavel-Chapelon, F.; Morois, S.; Krogh, V.; Tumino, R.; Panico, S.; Polidoro, S.; Palli, D.; Kaaks, R.; Teucher, B.; Pischon, T.; Trichopoulou, A.; Orfanos, P.; Goufa, I.; Peeters, P.H.; Skeie, G.; Braaten, T.; Rodriguez, L.; Lujan-Barroso, L.; Sanchez-Perez, M.J.; Navarro, C.; Barricarte, A.; Zackrisson, S.; Almquist, M.; Hallmans, G.; Palmqvist, R.; Tsilidis, K.K.; Khaw, K.T.; Wareham, N.; Gallo, V.; Jenab, M.; Riboli, E.; Bueno-de-Mesquita, H.B.

    2012-01-01

    Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational

  10. The relative effectiveness of segment specific level and non-specific level spinal joint mobilization on pain and range of motion: results of a systematic review and meta-analysis.

    Science.gov (United States)

    Slaven, Emily Joan; Goode, Adam P; Coronado, Rogelio A; Poole, Charles; Hegedus, Eric J

    2013-02-01

    Systematic literature review and meta-analysis. IN SYMPTOMATIC SUBJECTS TO: (1) examine the effects of a single session of joint mobilization on pain at rest and with most painful movement, and (2) compare the effects when joint mobilization is provided to a specific or non-specific spinal level. Joint mobilization is routinely used for treating spinal pain in conjunction with other interventions, but its unique effect is not well understood. Further, there is controversy about the role of 'specific level' techniques in producing benefit. Searches were performed for randomized controlled trials (RCTs) using electronic databases (MEDLINE, CINAHL, and PEDro) from 1966 through November 2010. Methodological quality was assessed using previously detailed criteria. Meta-analysis and meta-regression were conducted on eligible studies. Eight RCTs with a mean methodological score of 10/12 were included. Significant heterogeneity (P = 0.075) was found in the overall meta-analysis estimate. When stratified by body location, no significant individual effect was found for pain at rest. However, there was a statistical mean difference [0.71 (95% confidence interval: 0.13-1.28)] between pain at rest for the cervical and lumbar individual means. We found multiple studies which provided evidence that a single session of joint mobilization can lead to a reduction of pain at rest and with most painful movement. When using joint mobilization, the need for specific versus non-specific level mobilization may be influenced by anatomical region; the direction of effect in the cervical spine was toward specific mobilization and in the lumbar spine towards non-specific mobilization.

  11. A possible association between elevated serum levels of brain-specific auto-antibodies and reduced plasma levels of docosahexaenoic acid in autistic children.

    Science.gov (United States)

    Mostafa, Gehan A; El-Khashab, Heba Y; Al-Ayadhi, Laila Y

    2015-03-15

    Polyunsaturated fatty acids (PUFAs) are not only essential for energy production, but they also exhibit a range of immunomodulatory properties that progress through T cell mediated events. Autoimmunity may have a pathogenic role in a subgroup of autistic children. This study is the first to investigate the relationship between serum levels of anti-myelin basic protein (anti-MBP) brain-specific auto-antibodies and reduced plasma levels of PUFAs in autistic children. Plasma levels of PUFAs (including linoleic, alphalinolenic, arachidonic "AA" and docosahexaenoic "DHA" acids) and serum anti-MBP were measured in 80 autistic children, aged between 4 and 12 years, and 80 healthy-matched children. Autistic patients had significantly lower plasma levels of PUFAs than healthy children. On the other hand, ω6/ω3 ratio (AA/DHA) was significantly higher in autistic patients than healthy children. Low plasma DHA, AA, linolenic and linoleic acids were found in 67.5%, 50%, 40% and 35%, respectively of autistic children. On the other hand, 70% of autistic patients had elevated ω6/ω3 ratio. Autistic patients with increased serum levels of anti-MBP auto-antibodies (75%) had significantly lower plasma DHA (Pchildren have a significant positive association between reduced levels of plasma DHA and increased serum levels of anti-MBP brain-specific auto-antibodies. However, replication studies of larger samples are recommended to validate whether reduced levels of plasma PUFAs are a mere association or have a role in the induction of the production of anti-MBP in some autistic children. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Mercury contamination in human hair and fish from Cambodia: levels, specific accumulation and risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Agusa, Tetsuro [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Kunito, Takashi [Department of Environmental Sciences, Faculty of Science, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Iwata, Hisato [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Monirith, In [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Tana, Touch Seang [Social and Cultural Observation Unit (OBSES) of the Cabinet of the Council of Ministers, Phnom Penh (Cambodia); Subramanian, Annamalai [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan); Tanabe, Shinsuke [Center for Marine Environmental Studies (CMES), Ehime University, Bunkyo-cho 2-5, Matsuyama 790-8577 (Japan)]. E-mail: shinsuke@agr.ehime-u.ac.jp

    2005-03-01

    Mercury (Hg) concentrations in human hair and fish samples from Phnom Penh, Kien Svay, Tomnup Rolork and Batrong, Cambodia, collected in November 1999 and December 2000 were determined to understand the status of contamination, and age- and sex-dependent accumulation in humans and to assess the intake of mercury via fish consumption. Mercury concentrations in human hair ranged from 0.54 to 190 {mu}g/g dry wt. About 3% of the samples contained Hg levels exceeding the no observed adverse effects level (NOAEL) of WHO (50 {mu}g/g) and the levels in some hair samples of women also exceeded the NOAEL (10 {mu}g/g) associated with fetus neurotoxicity. A weak but significant positive correlation was observed between age and Hg levels in hair of residents. Mercury concentrations in muscle of marine and freshwater fish from Cambodia ranged from <0.01 to 0.96 {mu}g/g wet wt. Mercury intake rates were estimated on the basis of the Hg content in fish and daily fish consumption. Three samples of marine fish including sharp-tooth snapper and obtuse barracuda, and one sample of sharp-tooth snapper exceeded the guidelines by US EPA and by Joint FAO/WHO Expert Committee on Food Additives (JECFA), respectively, which indicates that some fish specimens examined (9% and 3% for US EPA and JECFA guidelines, respectively) were hazardous for consumption at the ingestion rate of Cambodian people (32.6 g/day). It is suggested that fish is probably the main source of Hg for Cambodian people. However, extremely high Hg concentrations were observed in some individuals and could not be explained by Hg intake from fish consumption, indicating some other contamination sources of Hg in Cambodia. - A source other than fish may be responsible for high Hg in some Cambodians.

  13. Region-Specific Dissociation between Cortical Noradrenaline Levels and the Sleep/Wake Cycle.

    Science.gov (United States)

    Bellesi, Michele; Tononi, Giulio; Cirelli, Chiara; Serra, Pier Andrea

    2016-01-01

    The activity of the noradrenergic system of the locus coeruleus (LC) is high in wake and low in sleep. LC promotes arousal and EEG activation, as well as attention, working memory, and cognitive flexibility. These functions rely on prefrontal cortex and are impaired by sleep deprivation, but the extent to which LC activity changes during wake remains unclear. Moreover, it is unknown whether noradrenergic neurons can sustain elevated firing during extended wake. Recent studies show that relative to LC neurons targeting primary motor cortex (M1), those projecting to medial prefrontal cortex (mPFC) have higher spontaneous firing rates and are more excitable. These results suggest that noradrenaline (NA) levels should be higher in mPFC than M1, and that during prolonged wake LC cells targeting mPFC may fatigue more, but direct evidence is lacking. We performed in vivo microdialysis experiments in adult (9-10 weeks old) C57BL/6 mice implanted for chronic electroencephalographic recordings. Cortical NA levels were measured during spontaneous sleep and wake (n = 8 mice), and in the course of sleep deprivation (n = 6). We found that absolute NA levels are higher in mPFC than in M1. Moreover, in both areas they decline during sleep and increase during wake, but these changes are faster in M1 than mPFC. Finally, by the end of sleep deprivation NA levels decline only in mPFC. Locus coeruleus (LC) neurons targeting prefrontal cortex may fatigue more markedly, or earlier, than other LC cells, suggesting one of the mechanisms underlying the cognitive impairment and the increased sleep presure associated with sleep deprivation. A commentary on this article appears in this issue on page 11. © 2016 Associated Professional Sleep Societies, LLC.

  14. Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location.

    Science.gov (United States)

    Leufkens, Anke M; Van Duijnhoven, Fränzel J B; Boshuizen, Hendriek C; Siersema, Peter D; Kunst, Anton E; Mouw, Traci; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Morois, Sophie; Krogh, Vittorio; Tumino, Rosario; Panico, Salvatore; Polidoro, Silvia; Palli, Domenico; Kaaks, Rudolf; Teucher, Birgit; Pischon, Tobias; Trichopoulou, Antonia; Orfanos, Philippos; Goufa, Ioulia; Peeters, Petra H M; Skeie, Guri; Braaten, Tonje; Rodríguez, Laudina; Lujan-Barroso, Leila; Sánchez-Pérez, Maria-José; Navarro, Carmen; Barricarte, Aurelio; Zackrisson, Sophia; Almquist, Martin; Hallmans, Goran; Palmqvist, Richard; Tsilidis, Konstantinos K; Khaw, Kay-Tee; Wareham, Nick; Gallo, Valentina; Jenab, Mazda; Riboli, Elio; Bueno-de-Mesquita, H Bas

    2012-02-01

    Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57-0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58-0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe. Copyright © 2011 UICC.

  15. A specific E3 ligase/deubiquitinase pair modulates TBP protein levels during muscle differentiation.

    Science.gov (United States)

    Li, Li; Martinez, Silvia Sanchez; Hu, Wenxin; Liu, Zhe; Tjian, Robert

    2015-09-22

    TFIID-a complex of TATA-binding protein (TBP) and TBP-associated factors (TAFs)-is a central component of the Pol II promoter recognition apparatus. Recent studies have revealed significant downregulation of TFIID subunits in terminally differentiated myocytes, hepatocytes and adipocytes. Here, we report that TBP protein levels are tightly regulated by the ubiquitin-proteasome system. Using an in vitro ubiquitination assay coupled with biochemical fractionation, we identified Huwe1 as an E3 ligase targeting TBP for K48-linked ubiquitination and proteasome-mediated degradation. Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation. We found that Huwe1 activity on TBP is antagonized by the deubiquitinase USP10, which protects TBP from degradation. Thus, modulating the levels of both Huwe1 and USP10 appears to fine-tune the requisite degradation of TBP during myogenesis. Together, our study unmasks a previously unknown interplay between an E3 ligase and a deubiquitinating enzyme regulating TBP levels during cellular differentiation.

  16. Site-specific changes in zinc levels in the epididymis of rats exposed to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Homma-Takeda, S. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan)]. E-mail: shino_ht@nirs.go.jp; Nishimura, Y. [Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan); Watanabe, Y. [Research Center for Radiation Protection, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan); Yukawa, M. [Fundamental Technology Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku Chiba 263-8555 (Japan)

    2007-07-15

    The epididymis is an accessory sex organ that plays an important role in sperm maturation and storage. Trace elements, such as copper (Cu), manganese (Mn), zinc (Zn) and selenium (Se), have a pivotal role in spermatogenesis. We studied the effects of radiation on trace element levels in the epididymis in male Wistar rats using inductively coupled plasma-mass spectrometry (ICP-MS). We determined trace element concentration in segment-dissected specimens and used micro-PIXE analysis to determine Zn in epididymal sections in situ. Zn concentrations in the caput and cauda epididymis of control rats were 37.7 {+-} 6.5 {mu}g/g wet weight and 18.7 {+-} 4.1 {mu}g/g wet weight, respectively. At 6 h after irradiation at a single dose of 5Gy, the Zn level decreased by 33% in the caput epididymis, whereas the level did not change in the cauda segment. Similar results were obtained for Se, but not both Cu and Mn. PIXE spot analysis revealed that Zn in the lumen of the epididymal tubules decreased after irradiation.

  17. Recent artificial selection in U.S. Jersey cattle impacts autozygosity levels of specific genomic regions.

    Science.gov (United States)

    Kim, Eui-Soo; Sonstegard, Tad S; Rothschild, Max F

    2015-04-16

    Genome signatures of artificial selection in U.S. Jersey cattle were identified by examining changes in haplotype homozygosity for a resource population of animals born between 1953 and 2007. Genetic merit of this population changed dramatically during this period for a number of traits, especially milk yield. The intense selection underlying these changes was achieved through extensive use of artificial insemination (AI), which also increased consanguinity of the population to a few superior Jersey bulls. As a result, allele frequencies are shifted for many contemporary animals, and in numerous cases to a homozygous state for specific genomic regions. The goal of this study was to identify those selection signatures that occurred after extensive use of AI since the 1960, using analyses of shared haplotype segments or Runs of Homozygosity. When combined with animal birth year information, signatures of selection associated with economically important traits were identified and compared to results from an extended haplotype homozygosity analysis. Overall, our results reveal that more recent selection increased autozygosity across the entire genome, but some specific regions increased more than others. A genome-wide scan identified more than 15 regions with a substantial change in autozygosity. Haplotypes found to be associated with increased milk, fat and protein yield in U.S. Jersey cattle also consistently increased in frequency. The analyses used in this study was able to detect directional selection over the last few decades when individual production records for Jersey animals were available.

  18. Radiative association processes to specific rovibrational levels in low-energy Na++Rb87 collisions

    Science.gov (United States)

    Yan, L. L.; Li, X. Y.; Wu, Y.; Wang, J. G.; Qu, Y. Z.

    2014-09-01

    The radiative association processes for Na+ colliding with Rb87(5s ) atoms have been investigated by using the quantum-mechanical method. The total and partial cross sections that associate to the specific rovibrational states are calculated rigorously in the energy range of 10-13-1.2×10-2eV. The association cross sections display rich resonance structures. The ratios of rotationally resolved cross sections to total association cross sections and the ratios of vibrationally resolved cross sections to rotationally resolved cross sections are calculated and presented. For energies less than 10-9eV, association to X2Σ+ (J=1) dominates over all other association states. As the energy increases, each resonance of the total cross sections is associated with the given angular component of specific bound states. In the energy range of 10-13-1.2×10-3eV, the vibrational states v=27 and v=28 are the most probable final states. The probability for the formation of molecular ion NaRb+ in the rovibrational states is discussed. The existence of Cooper minima in the radiative association cross sections is found and illustrated.

  19. A new subclass of intrinsic aminoglycoside nucleotidyltransferases, ANT(3")-II, is horizontally transferred among Acinetobacter spp. by homologous recombination

    Science.gov (United States)

    Zhang, Gang; Leclercq, Sébastien Olivier; Tian, Jingjing; Wang, Chao; Ai, Guomin; Liu, Shuangjiang

    2017-01-01

    The emergence and spread of antibiotic resistance among Acinetobacter spp. have been investigated extensively. Most studies focused on the multiple antibiotic resistance genes located on plasmids or genomic resistance islands. On the other hand, the mechanisms controlling intrinsic resistance are still not well understood. In this study, we identified the novel subclass of aminoglycoside nucleotidyltransferase ANT(3")-II in Acinetobacter spp., which comprised numerous variants distributed among three main clades. All members of this subclass can inactivate streptomycin and spectinomycin. The three ant(3")-II genes, encoding for the three ANT(3")-II clades, are widely distributed in the genus Acinetobacter and always located in the same conserved genomic region. According to their prevalence, these genes are intrinsic in Acinetobacter baumannii, Acinetobacter pittii, and Acinetobacter gyllenbergii. We also demonstrated that the ant(3")-II genes are located in a homologous recombination hotspot and were recurrently transferred among Acinetobacter species. In conclusion, our findings demonstrated a novel mechanism of natural resistance in Acinetobacter spp., identified a novel subclass of aminoglycoside nucleotidyltransferase and provided new insight into the evolutionary history of intrinsic resistance genes. PMID:28152054

  20. A new subclass of intrinsic aminoglycoside nucleotidyltransferases, ANT(3")-II, is horizontally transferred among Acinetobacter spp. by homologous recombination.

    Science.gov (United States)

    Zhang, Gang; Leclercq, Sébastien Olivier; Tian, Jingjing; Wang, Chao; Yahara, Koji; Ai, Guomin; Liu, Shuangjiang; Feng, Jie

    2017-02-01

    The emergence and spread of antibiotic resistance among Acinetobacter spp. have been investigated extensively. Most studies focused on the multiple antibiotic resistance genes located on plasmids or genomic resistance islands. On the other hand, the mechanisms controlling intrinsic resistance are still not well understood. In this study, we identified the novel subclass of aminoglycoside nucleotidyltransferase ANT(3")-II in Acinetobacter spp., which comprised numerous variants distributed among three main clades. All members of this subclass can inactivate streptomycin and spectinomycin. The three ant(3")-II genes, encoding for the three ANT(3")-II clades, are widely distributed in the genus Acinetobacter and always located in the same conserved genomic region. According to their prevalence, these genes are intrinsic in Acinetobacter baumannii, Acinetobacter pittii, and Acinetobacter gyllenbergii. We also demonstrated that the ant(3")-II genes are located in a homologous recombination hotspot and were recurrently transferred among Acinetobacter species. In conclusion, our findings demonstrated a novel mechanism of natural resistance in Acinetobacter spp., identified a novel subclass of aminoglycoside nucleotidyltransferase and provided new insight into the evolutionary history of intrinsic resistance genes.

  1. Relationship of baseline HDL subclasses, small dense LDL and LDL triglyceride to cardiovascular events in the AIM-HIGH clinical trial.

    Science.gov (United States)

    Albers, John J; Slee, April; Fleg, Jerome L; O'Brien, Kevin D; Marcovina, Santica M

    2016-08-01

    Previous results of the AIM-HIGH trial showed that baseline levels of the conventional lipid parameters were not predictive of future cardiovascular (CV) outcomes. The aims of this secondary analysis were to examine the levels of cholesterol in high density lipoprotein (HDL) subclasses (HDL2-C and HDL3-C), small dense low density lipoprotein (sdLDL-C), and LDL triglyceride (LDL-TG) at baseline, as well as the relationship between these levels and CV outcomes. Individuals with CV disease and low baseline HDL-C levels were randomized to simvastatin plus placebo or simvastatin plus extended release niacin (ERN), 1500 to 2000 mg/day, with ezetimibe added as needed in both groups to maintain an on-treatment LDL-C in the range of 40-80 mg/dL. The primary composite endpoint was death from coronary disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebrovascular revascularization. HDL-C, HDL3-C, sdLDL-C and LDL-TG were measured at baseline by detergent-based homogeneous assays. HDL2-C was computed by the difference between HDL-C and HDL3-C. Analyses were performed on 3094 study participants who were already on statin therapy prior to enrollment in the trial. Independent contributions of lipoprotein fractions to CV events were determined by Cox proportional hazards modeling. Baseline HDL3-C was protective against CV events (HR: 0.84, p = 0.043) while HDL-C, HDL2-C, sdLDL-C and LDL-TG were not event-related (HR: 0.96, p = 0.369; HR: 1.07, p = 0.373; HR: 1.05, p = 0.492; HR: 1.03, p = 0.554, respectively). The results of this secondary analysis of the AIM-HIGH Study indicate that levels of HDL3-C, but not other lipoprotein fractions, are predictive of CV events, suggesting that the HDL3 subclass may be primarily responsible for the inverse association of HDL-C and CV disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    Science.gov (United States)

    van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W.J.H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J.M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; Elbers, Clara C.; Francesco Palamara, Pier; Pe'er, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F.J.; Stoneking, Mark; de Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; van den Berg, Leonard H.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; van Setten, Jessica; Kattenberg, Mathijs; van Schaik, Barbera D.C.; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D.; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I.W.; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M.

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10−4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. PMID:25751400

  3. Axial level-specific regulation of neuronal development: lessons from PITX2.

    Science.gov (United States)

    Waite, Mindy R; Martin, Donna M

    2015-02-01

    Transcriptional regulation of gene expression is vital for proper control of proliferation, migration, differentiation, and survival of developing neurons. Pitx2 encodes a homeodomain transcription factor that is highly expressed in the developing and adult mammalian brain. In humans, mutations in PITX2 result in Rieger syndrome, characterized by defects in the development of the eyes, umbilicus, and teeth and variable abnormalities in the brain, including hydrocephalus and cerebellar hypoplasia. Alternative splicing of Pitx2 in the mouse results in three isoforms, Pitx2a, Pitx2b, and Pitx2c, each of which is expressed symmetrically along the left-right axis of the brain throughout development. Here, we review recent evidence for axial and brain region-specific requirements for Pitx2 during neuronal migration and differentiation, highlighting known isoform contributions. © 2014 Wiley Periodicals, Inc.

  4. Sleep Dependent Synaptic Down-Selection (II: Single Neuron Level Benefits for Matching, Selectivity, and Specificity

    Directory of Open Access Journals (Sweden)

    Atif eHashmi

    2013-10-01

    Full Text Available In a companion paper (Nere et al., this volume, we used computer simulations to show that a strategy of activity-dependent, on-line net synaptic potentiation during wake, followed by off-line synaptic depression during sleep, can provide a parsimonious account for several memory benefits of sleep at the systems level, including the consolidation of procedural and declarative memories, gist extraction, and integration of new with old memories. In this paper, we consider the theoretical benefits of this two-step process at the single neuron level and employ the theoretical notion of Matching between brain and environment to measure how this process increases the ability of the neuron to capture regularities in the environment and model them internally. We show that down-selection during sleep is beneficial for increasing or restoring Matching after learning, after integrating new with old memories, and after forgetting irrelevant material. By contrast, alternative schemes, such as additional potentiation in wake, potentiation in sleep, or synaptic renormalization in wake, decrease Matching. We also argue that, by selecting appropriate loops through the brain that tie feedforward synapses with feedback ones in the same dendritic domain, different subsets of neurons can learn to specialize for different contingencies and form sequences of nested perception-action loops. By potentiating such loops when interacting with the environment in wake, and depressing them when disconnected from the environment in sleep, neurons can learn to match the long-term statistical structure of the environment while avoiding spurious modes of functioning and catastrophic interference. Finally, such a two-step process has the additional benefit of desaturating the neuron's ability to learn and of maintaining cellular homeostasis. Thus, sleep-dependent synaptic renormalization offers a parsimonious account for both cellular and systems-level effects of sleep on learning

  5. Impact of induced levels of specific free radicals and malondialdehyde on chicken semen quality and fertility.

    Science.gov (United States)

    Rui, Bruno R; Shibuya, Fábio Y; Kawaoku, Allison J T; Losano, João D A; Angrimani, Daniel S R; Dalmazzo, Andressa; Nichi, Marcilio; Pereira, Ricardo J G

    2017-03-01

    Over the past decades, scientists endeavored to comprehend oxidative stress in poultry spermatozoa and its relationship with fertilizing ability, lipid peroxidation (LPO), free-radical scavenging systems, and antioxidant therapy. Although considerable progress has been made, further improvement is needed in understanding how specific reactive oxygen species (ROS) and malondialdehyde (MDA, a toxic byproduct of LPO) disrupt organelles in avian spermatozoon. Hence, this study examined functional changes in chicken spermatozoa after incubation with different ROS, and their implications for the fertility. First, semen samples from 14 roosters were individually diluted and aliquoted into five equal parts: control, superoxide anion, hydrogen peroxide (H2O2), hydroxyl radicals, and MDA. After incubation with these molecules, aliquots were analyzed for motility, plasma membrane and acrosome integrity, mitochondrial activity, and LPO and DNA damage. Hydrogen peroxide was more detrimental for sperm motility than hydroxyl radicals, whereas the superoxide anion and MDA exhibited no differences compared with controls. In turn, plasma membrane and acrosome integrity, mitochondrial activity, LPO and DNA integrity rates were only affected by hydroxyl radicals. Thereafter, semen aliquots were incubated under the same conditions and used for artificial insemination. In accordance to our in vitro observations, H2O2 and hydroxyl radicals sharply reduced egg fertility, whereas superoxide anion and MDA only induced slight declines. Thus, chicken sperm function was severely impaired by H2O2 and hydroxyl radicals, but their mechanisms of action seemingly comprise different pathways. Further analysis regarding susceptibility of spermatozoon organelles to specific radicals in other poultry will help us to understand the development of interspecific differences in scavenging systems and to outline more oriented antioxidant approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Specific and number of comorbidities are associated with increased levels of temporomandibular pain intensity and duration.

    Science.gov (United States)

    Dahan, Haissam; Shir, Yoram; Velly, Ana; Allison, Paul

    2015-01-01

    Temporomandibular pain disorder (TMD) is a common pain condition in the face. People with TMD report multiple pain comorbidities. The presence of fibromyalgia and migraine in people with TMD is associated with an increase in TMD pain intensity and duration. However, data on the relationship between increasing number of pain comorbidities and TMD pain are rare. The aims of this study were: firstly to evaluate the extent to which increasing number of comorbidities is associated with increasing TMD pain intensity and duration; and secondly to evaluate the extent to which the presence of specific comorbidities is associated with increasing TMD pain intensity and duration. The sample included 180 people seeking TMD treatment at Boston and Montreal clinics. TMD was diagnosed using the Research Diagnostic Criteria for TMD. A Numerical Pain Rating Scale assessed TMD pain intensity and participants provided their TMD pain duration in a study questionnaire. The comorbidities of migraine, chronic fatigue syndrome, irritable bowel syndrome, interstitial cystitis and restless leg syndrome were diagnosed by 5 validated diagnostic questionnaires. The associations were analyzed by linear regression, controlling for confounders. There was a positive association between the number of comorbidities present and TMD pain intensity (p comorbidities present and TMD pain duration (p pain intensity (p chronic fatigue syndrome was positively associated with TMD pain intensity (p pain duration (p pain group, whereas in the non-myofascial pain group, the relationship between number of comorbidities and TMD pain duration was the only one still present. This study shows that the number of comorbidities is positively associated with TMD pain duration and intensity. The presence of specific conditions, such as migraine and chronic fatigue syndrome, is associated with an increase in TMD intensity and duration.

  7. SPECIFIC ELEMENTS OF SOME COMPONENTS OF THE MANAGEMENT SYSTEM ON THE LEVEL OF THE TEAM

    OpenAIRE

    Prof. Daniela Popescu PhD.; Assoc. Prof. Adriana SCRIOTEANU PhD.

    2011-01-01

    This study analyses some management tools on the level of the team as: the „tree” diagram, the matrix diagram and the priority matrix. The study of this diagram is focused on the practical aspects of the diagrams and the analysis of the conditions of use in some branch of activity. At the same time some useful tools are pointed out for the practical activity. The problem of the study also deals with the matrix diagram. This tool allows the individuals from the team to identify and clarify the...

  8. Teachers' opinion about learning continuum based on student's level of competence and specific pedagogical material in classification topics

    Science.gov (United States)

    Andriani, Aldina Eka; Subali, Bambang

    2017-08-01

    This research discusses learning continuum development for designing a curriculum. The objective of this study is to gather the opinion of public junior and senior high school teachers about learning continuum based on student's level of competence and specific pedagogical material in classification topics. This research was conducted in Yogyakarta province from October 2016 to January 2017. This research utilizes a descriptive survey method. Respondents in this study consist of 281 science teachers at junior and senior high school in Yogyakarta city and 4 regencies namely Sleman, Bantul, Kulonprogo, and Gunung Kidul. The sample were taken using a census. The collection of data used questionnaire that had been validated from the aspects of construct validity and experts judgements. Data were analyzed using a descriptive analysis technique. The results of the analysis show that the opinions of teachers regarding specific pedagogical material in classification topics of living things at the junior high school taught in grade VII to the ability level of C2 (Understanding). At senior high school level, it is taught in grade X with the ability level C2 (Understanding). Based on these results, it can be concluded that the opinions of teachers still refer to the current syllabus and curriculum so that the teachers do not have pure opinions about the student's competence level in classification topics that should be taught at the level of the grade in accordance with the level of corresponding competency.

  9. Frequency of specific osteopathic manipulative treatment modalities used by candidates while taking COMLEX-USA Level 2-PE.

    Science.gov (United States)

    Langenau, Erik E; Dowling, Dennis J; Dyer, Caitlin; Roberts, William L

    2012-08-01

    As one of the key measures of clinical skills assessment, the Comprehensive Osteopathic Medical Licensing Examination-USA Level 2-Performance Evaluation (COMLEX-USA Level 2-PE) is used to rate candidates' performance of osteopathic manipulative treatment (OMT). To evaluate the frequency of specific OMT modalities used by COMLEX-USA Level 2-PE candidates and to report frequent use on the basis of clinical presentation. With enhanced scoring procedures in place, OMT physician-examiners identified and documented specific OMT techniques that were performed by candidates at the 28 colleges of osteopathic medicine and branch campuses that had eligible students at that time. A frequency analysis for OMT techniques, according to clinical content axis, was applied to all candidates (N=4757) for the 2010-2011 testing cycle. Students used a wide range of specific OMT techniques. Candidates performed 24,202 instances of specific OMT techniques, including 10,471 myofascial/soft tissue (43.3%), 3942 muscle energy (16.3%), 1676 sinus drainage (6.9%), 1476 inhibition (6.1%), 1221 fascial release (5.0%), 1171 rib raising (4.8%), 918 lymphatic (3.8%), and 866 counterstrain (3.6%). A few students (<0.01%) used high-velocity, low-amplitude (HVLA), a technique that is prohibited from use on the COMLEX-USA Level 2-PE because of the potential hazard of repeatedly treating a standardized patient with thrust technique to the same segment in a given day. Additional techniques included functional, facilitated positional release, balanced ligamentous tension, and visceral. Use of techniques also varied according to the clinical presentation of the standardized patient (ie, cardiovascular, respiratory, neuromusculoskeletal, gastrointestinal, or other) and chronicity (ie, acute or chronic). Findings contributed to a better understanding of the types of OMT techniques being used by candidates taking COMLEX-USA Level 2-PE. Frequency of use of specific OMT modalities varied according to clinical

  10. Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease.

    Directory of Open Access Journals (Sweden)

    David M Naeger

    2010-01-01

    Full Text Available In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence" in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.

  11. Monocyte Recruitment by HLA IgG‐Activated Endothelium: The Relationship Between IgG Subclass and FcγRIIa Polymorphisms

    National Research Council Canada - National Science Library

    Valenzuela, N. M; Trinh, K. R; Mulder, A; Morrison, S. L; Reed, E. F

    2015-01-01

    ...RIIa polymorphisms, the authors show the ability of different human IgG subclasses to cause endothelial activation and recruitment of monocytes, and evaluate therapeutic potential of IgG with two...

  12. An Asset Pricing Approach to Testing General Term Structure Models including Heath-Jarrow-Morton Specifications and Affine Subclasses

    DEFF Research Database (Denmark)

    Christensen, Bent Jesper; van der Wel, Michel

    We develop a new empirical approach to term structure analysis that allows testing for time-varying risk premia and for the absence of arbitrage opportunities based on the drift restriction within the Heath, Jarrow and Morton (1992) framework. As in the equity case, a zero intercept condition is ...

  13. Antibody response to the Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in healthy and infection-prone individuals with IgG3 subclass deficiency.

    Science.gov (United States)

    Hahn-Zoric, M; Ulanova, M; Friman, V; Björkander, J; Oxelius, V A; Lucas, A; Hanson, L A

    2004-09-01

    Searching for a possible explanation for the phenotypic heterogeneity in IgG3 deficiency, we studied the antibody response to a polysaccharide and a protein antigen in IgG3-deficient (IgG3d) adults after vaccination with Haemophilus influenzae type b capsular polysaccharide (Hib CP) conjugated to tetanus toxoid. Distribution of isotypes, idiotypes, clonotypes, and Gm allotypes were compared. All the vaccinated individuals, irrespective of the level of IgG3 and proneness to infections, developed protective levels of anti-Hib CP. Significantly lower prevaccination levels of IgG2 (p infection-prone compared to the healthy IgG3d individuals and/or controls. Seventy percent of the IgG3d patients and none of the controls had the low responding Gm(ga-n/ga-n) genotype, while the majority of the controls had the alternative Gm(bfn/bfn) genotype. The conjugate ACT-HIB vaccine efficiently overcomes the IgG3 subclass deficiency state and the genetic predisposition for lower responsiveness, providing protection against Hib and tetanus infections. The proneness to infection in some IgG3d individuals may relate to their low prevaccination antibody levels.

  14. Restoring Specific Lactobacilli Levels Decreases Inflammation and Muscle Atrophy Markers in an Acute Leukemia Mouse Model

    Science.gov (United States)

    Bindels, Laure B.; Beck, Raphaël; Schakman, Olivier; Martin, Jennifer C.; De Backer, Fabienne; Sohet, Florence M.; Dewulf, Evelyne M.; Pachikian, Barbara D.; Neyrinck, Audrey M.; Thissen, Jean-Paul; Verrax, Julien; Calderon, Pedro Buc; Pot, Bruno; Grangette, Corinne; Cani, Patrice D.; Scott, Karen P.; Delzenne, Nathalie M.

    2012-01-01

    The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis) in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L) in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay). These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle. PMID:22761662

  15. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.

    Directory of Open Access Journals (Sweden)

    Laure B Bindels

    Full Text Available The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl, characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay. These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle.

  16. Differential effects of calcium antagonist subclasses on markers of nephropathy progression.

    Science.gov (United States)

    Bakris, George L; Weir, Matthew R; Secic, Michelle; Campbell, Brett; Weis-McNulty, Annette

    2004-06-01

    Numerous studies suggest that the dihydropyridine calcium antagonists (DCAs) and nondihydropyridine calcium antagonists (NDCAs) have differential antiproteinuric effects. Proteinuria reduction is a correlate of the progression of renal disease. In an earlier systematic review, calcium antagonists were shown as effective antihypertensive drugs, but there was uncertainty about their renal benefits in patients with proteinuria and renal insufficiency. A systematic review was conducted to assess the differential effects of DCAs and NDCAs on proteinuria in hypertensive adults with proteinuria, with or without diabetes, and to determine whether these differential effects translate into altered progression of nephropathy. Studies included in the review had to be randomized clinical trials with at least 6 months of treatment, include a DCA or NDCA treatment arm, have one or more renal end points, and have been initiated after 1986. Summary data were extracted from 28 studies entered into two identical but separate databases, which were compared and evaluated by independent reviewers. The effects of each drug class on blood pressure (N= 1338) and proteinuria (N= 510) were assessed. After adjusting for sample size, study length, and baseline value, there were no statistically significant differences in the ability of either class of calcium antagonist to decrease blood pressure. The mean change in proteinuria was +2% for DCAs and -30% for NDCAs (95% CI, 10% to 54%, P= 0.01). Consistently greater reductions in proteinuria were associated with the use of NDCAs compared with DCAs, despite no significant differences in blood pressure reduction or presence of diabetes. This analysis supports (1) similar efficacy between subclasses of calcium antagonists to lower blood pressure, and (2) greater reductions in proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes. Based on these findings, NDCAs, alone or in combination with an angiotensin-converting enzyme

  17. Early dutasteride monotherapy in men with detectable serum prostate-specific antigen levels following radical prostatectomy: A prospective trial

    Directory of Open Access Journals (Sweden)

    Yu Seob Shin

    2017-03-01

    Full Text Available Purpose: To investigate the effects of early administration of dutasteride in patients with detectable serum prostate-specific antigen (PSA levels after radical prostatectomy (RP. Materials and Methods: A prospective open-label study, with a cumulative analysis of asymptomatic increase in PSA following RP, was conducted from January 2005 to December 2013. An early increase in PSA level was defined as detectable serum PSA level>0.04 ng/mL. Patients with PSA level>0.04 ng/mL were treated with dutasteride 0.5 mg daily. Serum PSA level and biochemical recurrence (BCR were monitored. We divided the patients into 2 groups based on the serum PSA response after dutasteride treatment. Results: Eighty patients were included in the study. At the median follow-up of 51.8 months, 56 patients (70.0% showed a decrease of greater than 10% in serum PSA level, and 24 showed increased PSA levels. Twelve of the 56 patients with PSA response showed subsequently increased PSA. Intergroup differences in preoperative PSA levels, PSA nadir levels, and Gleason score of 6 or less were significant (p=0.028, p=0.030, and p=0.035, respectively. A multivariate analysis revealed that Gleason score of 6 or less (p=0.018 and PSA nadir levels (p=0.011 were predictive factors for PSA response after early dutasteride treatment in men with increased PSA levels following RP. Conclusions: Early monotherapy of dutasteride showed a decline in serum PSA levels in men with lower nadir PSA levels, and a Gleason score 6, when the serum PSA was detected after RP.

  18. Evaluation of Basketball-Specific Agility: Applicability of Preplanned and Nonplanned Agility Performances for Differentiating Playing Positions and Playing Levels.

    Science.gov (United States)

    Sekulic, Damir; Pehar, Miran; Krolo, Ante; Spasic, Miodrag; Uljevic, Ognjen; Calleja-González, Julio; Sattler, Tine

    2017-08-01

    Sekulic, D, Pehar, M, Krolo, A, Spasic, M, Uljevic, O, Calleja-González, J, and Sattler, T. Evaluation of basketball-specific agility: applicability of preplanned and nonplanned agility performances for differentiating playing positions and playing levels. J Strength Cond Res 31(8): 2278-2288, 2017-The importance of agility in basketball is well known, but there is an evident lack of studies examining basketball-specific agility performances in high-level players. The aim of this study was to determine the reliability and discriminative validity of 1 standard agility test (test of preplanned agility [change-of-direction speed] over T course, T-TEST), and 4 newly developed basketball-specific agility tests, in defining playing positions and performance levels in basketball. The study comprised 110 high-level male basketball players (height: 194.92 ± 8.09 cm; body mass: 89.33 ± 10.91 kg; age: 21.58 ± 3.92 years). The variables included playing position (Guard, Forward, Center), performance level (first division vs. second division), anthropometrics (body height, body mass, and percentage of body fat), T-TEST, nonplanned basketball agility test performed on dominant (BBAGILdom) and nondominant sides (BBAGILnond), and a preplanned (change-of-direction speed) basketball agility test performed on dominant (BBCODSdom) and nondominant sides (BBCODSnond). The reliability of agility tests was high (intraclass correlation coefficient of 0.81-0.95). Forwards were most successful in the T-TEST (F test: 13.57; p = 0.01). Guards outperformed Centers in BBCODSdom, BBCODSndom, BBAGILdom, and BBAGILnond (F test: 5.06, p = 0.01; 6.57, 0.01; 6.26, 0.01; 3.37, 0.04, respectively). First division Guards achieved better results than second division Guards in BBCODSdom (t: 2.55; p = 0.02; moderate effect size differences), BBAGILdom, and BBAGILnond (t: 3.04 and 3.06, respectively; both p = 0.01 and moderate effect size differences). First division Centers outperformed second division

  19. Different levels of food restriction reveal genotype-specific differences in learning a visual discrimination task.

    Directory of Open Access Journals (Sweden)

    Kalina Makowiecki

    Full Text Available In behavioural experiments, motivation to learn can be achieved using food rewards as positive reinforcement in food-restricted animals. Previous studies reduce animal weights to 80-90% of free-feeding body weight as the criterion for food restriction. However, effects of different degrees of food restriction on task performance have not been assessed. We compared learning task performance in mice food-restricted to 80 or 90% body weight (BW. We used adult wildtype (WT; C57Bl/6j and knockout (ephrin-A2⁻/⁻ mice, previously shown to have a reverse learning deficit. Mice were trained in a two-choice visual discrimination task with food reward as positive reinforcement. When mice reached criterion for one visual stimulus (80% correct in three consecutive 10 trial sets they began the reverse learning phase, where the rewarded stimulus was switched to the previously incorrect stimulus. For the initial learning and reverse phase of the task, mice at 90%BW took almost twice as many trials to reach criterion as mice at 80%BW. Furthermore, WT 80 and 90%BW groups significantly differed in percentage correct responses and learning strategy in the reverse learning phase, whereas no differences between weight restriction groups were observed in ephrin-A2⁻/⁻ mice. Most importantly, genotype-specific differences in reverse learning strategy were only detected in the 80%BW groups. Our results indicate that increased food restriction not only results in better performance and a shorter training period, but may also be necessary for revealing behavioural differences between experimental groups. This has important ethical and animal welfare implications when deciding extent of diet restriction in behavioural studies.

  20. Adipose-derived stem cells express higher levels of type VII collagen under specific culture conditions.

    Science.gov (United States)

    Maeda, Yuichiro; Hasegawa, Toshio; Wada, Akino; Fukai, Tatsuo; Iida, Hideo; Sakamoto, Atsushi; Ikeda, Shigaku

    2017-12-01

    Type VII collagen (Col7) is a major component of the anchoring fibrils at the dermoepidermal junction. Adipose-derived stem cells (ADSCs) are a cell population highly useful in regenerative medicine because of their ease of isolation and their potential for multilineage differentiation. Based on the observations that K14 was expressed in undifferentiated ADSCs and the expression was downregulated after differentiation into adipocytes, we speculated that ADSCs are keratinocyte stem/progenitor cells. ADSCs were co-cultured with fibroblasts on type IV collagen in a medium containing all-trans retinoic acid and bone morphogenetic protein 4. At day 14 of culture in keratinocyte serum-free medium, the cells were harvested and subjected to immunofluorescence, flow cytometry, real-time PCR, and western blotting. Approximately, 45% of ADSCs were immunostained positively for anti-human cytokeratin 10, and approximately 80% were stained positively for Col7. Flow cytometry, real-time PCR, and western blotting also confirmed that differentiated ADSCs expressed higher levels of Col7. These findings support the therapeutic potential of ADSCs, not only for wound healing, but also for the correction of Col7 deficiencies.

  1. Different levels of visual perceptual skills are associated with specific modifications in functional connectivity and global efficiency.

    Science.gov (United States)

    Danti, Sabrina; Handjaras, Giacomo; Cecchetti, Luca; Beuzeron-Mangina, Helen; Pietrini, Pietro; Ricciardi, Emiliano

    2017-10-05

    The disembedding ability (i.e., the ability to identify a simple masked figure within a complex one) depends on attentional mechanisms, executive functions and working memory. Recent cognitive models ascribed different levels of disembedding task performance to the efficiency of the subtended mental processes engaged during visuo-spatial perception. Here we aimed at assessing whether different levels of the disembedding ability were associated to the functional signatures of neural efficiency, defined as a specific modulation in response magnitude and functional connectivity strength in task-related areas. Consequently, brain activity evoked by a visual task involving the disembedding ability was acquired using functional magnetic resonance imaging (fMRI) in a sample of 23 right-handed healthy individuals. Brain activity was analyzed at different levels of information processing, from local responses to connectivity interactions between brain nodes, as far as to network topological properties. All different levels of information processing were significantly modulated by individual behavioral performance. Specifically, single voxel response magnitude, connectivity strength of the right intrahemispheric and interhemispheric edges, and graph measures (i.e., local and global efficiency) were negatively associated to behavioral performance. Altogether, these results indicate that efficiency during a disembedding task cannot be merely attributed to a reduced neural recruitment of task-specific regions, but can be better characterized as an enhanced functional hemispherical asymmetry. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. A specific phospholipase C activity regulates phosphatidylinositol levels in lung surfactant of patients with acute respiratory distress syndrome.

    Science.gov (United States)

    Spyridakis, Spyros; Leondaritis, George; Nakos, George; Lekka, Marilena E; Galanopoulou, Dia

    2010-03-01

    Lung surfactant (LS) is a lipid-rich material lining the inside of the lungs. It reduces surface tension at the liquid/air interface and thus, it confers protection of the alveoli from collapsing. The surface-active component of LS is dipalmitoyl-phosphatidylcholine, while anionic phospholipids such as phosphatidylinositol (PtdIns) and primarily phosphatidylglycerol are involved in the stabilization of the LS monolayer. The exact role of PtdIns in this system is not well-understood; however, PtdIns levels change dramatically during the acute respiratory distress syndrome (ARDS) evolution. In this report we present evidence of a phosphoinositide-specific phospholipase C (PI-PLC) activity in bronchoalveolar lavage (BAL) fluid, which may regulate PtdIns levels. Characterization of this extracellular activity showed specificity for PtdIns and phosphatidylinositol 4,5-bisphosphate, sharing the typical substrate concentration-, pH-, and calcium-dependencies with mammalian PI-PLCs. Fractionation of BAL fluid showed that PI-PLC did not co-fractionate with large surfactant aggregates, but it was found mainly in the soluble fraction. Importantly, analysis of BAL samples from control subjects and from patients with ARDS showed that the PI-PLC specific activity was decreased by 4-fold in ARDS samples concurrently with the increase in BAL PtdIns levels. Thus, we have identified for the first time an extracellular PI-PLC enzyme activity that may be acutely involved in the regulation of PtdIns levels in LS.

  3. Estimated Infant Exposure to Enantiomer-Specific Methadone Levels in Breastmilk

    Science.gov (United States)

    Perel, James M.; Helsel, Joseph C.; Hanusa, Barbara H.; Thompson, Matthew; Wisner, Katherine L.

    2011-01-01

    Abstract Background and Objectives Breastfeeding, a public health priority, improves outcomes for infants. Methadone is dispensed as a racemic mixture; R-methadone is the active enantiomer. Pharmacologic data for R-methadone in breastmilk could improve risk–benefit decision-making for treatment of lactating women. This study estimated infant exposure to R- and S-methadone via breastmilk by theoretic infant dose (TID) and relative infant dose (RID) and reported the milk-to-maternal plasma (M/P) ratio. Methods Women treated with methadone doses of 40–200 mg/day (mean, 102 mg/day) provided concomitantly collected plasma and breastmilk samples 1–6 days after delivery. Most (16 of 20) samples were taken at the time of peak maternal plasma levels; thus infant exposure estimates are for maximum possible exposure. Concentrations of R- and S-methadone were measured in maternal plasma and breastmilk; M/P ratio, TID, and RID were calculated for each enantiomer and total methadone. Results The 20 participants were 18–38 years old and publicly insured; a quarter did not complete high school, and only one was not white. R-Methadone concentration was 1.3–3.0 times that of S-methadone in all breastmilk samples. The mean (SD) R-, S-, and total methadone M/P ratios were 0.52 (0.28), 0.28 (0.15), and 0.40 (0.21), respectively. Mean (range) R-, S-, and total methadone TID were 0.02 mg/kg/day (0.004–0.099), 0.013 mg/kg/day (0.002–0.071), and 0.033 mg/kg/day (0.006–0.170), respectively. Mean (range) RID of R-, S-, and total methadone were 2.7% (0.7–10.1%), 1.6% (0.3–7.2%), and 2.1% (0.52–8.8%), respectively. Conclusions R-Methadone is found in higher concentrations than S-methadone in breastmilk. Even at high methadone doses, breastmilk methadone concentrations were relatively low and support American Academy of Pediatrics recommendations that dose should not be a factor in determining whether women on methadone breastfeed. PMID:21348770

  4. Trimester-Specific Urinary Bisphenol A Concentrations and Blood Glucose Levels Among Pregnant Women From a Fertility Clinic.

    Science.gov (United States)

    Chiu, Yu-Han; Mínguez-Alarcón, Lidia; Ford, Jennifer B; Keller, Myra; Seely, Ellen W; Messerlian, Carmen; Petrozza, John; Williams, Paige L; Ye, Xiaoyun; Calafat, Antonia M; Hauser, Russ; James-Todd, Tamarra

    2017-04-01

    Women with a history of infertility are at increased risk of impaired glucose tolerance during pregnancy. Studies suggest higher urinary bisphenol A (BPA) concentrations are associated with diabetes in nonpregnant populations, but the association between BPA and glucose levels among pregnant women is unclear. To assess trimester-specific urinary BPA concentrations in relation to blood glucose levels among subfertile women. Environment and Reproductive Health Study, an ongoing prospective cohort study. A fertility center in a teaching hospital. A total of 245 women contributed at least one urine sample during first and/or second trimesters, delivered a singleton or twin pregnancy, and had available blood glucose data (2005 to 2015). Blood glucose levels after a nonfasting 50-g glucose challenge test at 24 to 28 weeks of gestation. The specific gravity-adjusted geometric mean urinary BPA concentrations during first and second trimesters were 1.39 and 1.27 µg/L, respectively. Second-trimester BPA concentrations were positively associated with blood glucose (P, trend = 0.01). Specifically, the adjusted mean glucose levels (95% confidence interval) for women in the highest quartile of second-trimester BPA concentrations was 119 (112, 126) mg/dL compared with 106 (100, 112) mg/dL for women in the lowest quartile. No associations were observed between first-trimester BPA concentrations and glucose levels. BPA exposure during the second trimester may have adverse effect on blood glucose levels among subfertile women. As the findings represent the first report suggesting a potential etiologically relevant window for BPA and glucose in humans, further studies are needed.

  5. High-level specification of a proposed information architecture for support of a bioterrorism early-warning system.

    Science.gov (United States)

    Berkowitz, Murray R

    2013-01-01

    Current information systems for use in detecting bioterrorist attacks lack a consistent, overarching information architecture. An overview of the use of biological agents as weapons during a bioterrorist attack is presented. Proposed are the design, development, and implementation of a medical informatics system to mine pertinent databases, retrieve relevant data, invoke appropriate biostatistical and epidemiological software packages, and automatically analyze these data. The top-level information architecture is presented. Systems requirements and functional specifications for this level are presented. Finally, future studies are identified.

  6. Sex-specific heritability of spontaneous lipid levels in an extended pedigree of Indian-origin rhesus macaques (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Amanda Vinson

    Full Text Available The rhesus macaque is an important model for human atherosclerosis but genetic determinants of relevant phenotypes have not yet been investigated in this species. Because lipid levels are well-established and heritable risk factors for human atherosclerosis, our goal was to assess the heritability of lipoprotein cholesterol and triglyceride levels in a single, extended pedigree of 1,289 Indian-origin rhesus macaques. Additionally, because increasing evidence supports sex differences in the genetic architecture of lipid levels and lipid metabolism in humans and macaques, we also explored sex-specific heritability for all lipid measures investigated in this study. Using standard methods, we measured lipoprotein cholesterol and triglyceride levels from fasted plasma in a sample of 193 pedigreed rhesus macaques selected for membership in large, paternal half-sib cohorts, and maintained on a low-fat, low cholesterol chow diet. Employing a variance components approach, we found moderate heritability for total cholesterol (h²=0.257, P=0.032, LDL cholesterol (h²=0.252, P=0.030, and triglyceride levels (h²=0.197, P=0.034 in the full sample. However, stratification by sex (N=68 males, N=125 females revealed substantial sex-specific heritability for total cholesterol (0.644, P=0.004, females only, HDL cholesterol (0.843, P=0.0008, females only, VLDL cholesterol (0.482, P=0.018, males only, and triglyceride levels (0.705, P=0.001, males only that was obscured or absent when sexes were combined in the full sample. We conclude that genes contribute to spontaneous variation in circulating lipid levels in the Indian-origin rhesus macaque in a sex-specific manner, and that the rhesus macaque is likely to be a valuable model for sex-specific genetic effects on lipid risk factors for human atherosclerosis. These findings are a first-ever report of heritability for cholesterol levels in this species, and support the need for expanded analysis of these traits in

  7. Level and specificity of antibodies evoked by crude and purified antigens of poliovirus I and echovirus 7.

    Science.gov (United States)

    Frommhagen, L H

    1965-11-01

    Preparations of poliovirus I and echovirus 7, purified by density gradient centrifugation, liquid-phase partition, and anion exchange (diethylaminoethyl) chromatography, have been shown to evoke high antibody levels of substantial specificity in the complement-fixation assay. Certain practical aspects of the three purification methods are discussed. These results argue for the use of purified viral antigens, particularly in view of the simplicity of the purification methods now available.

  8. Labeled experimental choice design for estimating attribute and availability cross effects with N attributes and specific brand attribute levels

    DEFF Research Database (Denmark)

    Nguyen, Thong Tien

    2011-01-01

    , orthogonal design is not available for every situation. Instead, efficient design based on computerized design algorithm is always available. This paper presents the method of efficient design for estimating brand models having attribute and availability cross effects. The paper gives a framework...... for implementing designs that is efficient enough to estimate model with N brands, each brand have K attributes, and brand attribute has specific levels. The paper also illustrates an example in food consumption study....

  9. Differences and Relationship Between Standard and Specific Throwing Test in Handball According to the Competitive and Professional Level

    OpenAIRE

    Rivilla García, Jesús; Grande Rodriguez, Ignacio; Chirosa, L.J.; Gómez Ortiz, María Jose; Sampedro Molinuevo, Javier

    2011-01-01

    The present study analyzed the differences in distance throwing with heavy and light medicine ball and throwing velocity between handball players of different competitive and professional level. Likewise, the relationship between the three throwing test of progressive specificity was analyzed: throwing with heavy medicinal ball (TH), throwing with light medicinal ball (TL) and throwing velocity (TV). For this purpose, sixty-five professional (P), semiprofessional (S) and non-professional (...

  10. Prostate cancer detection rate in patients with fluctuating prostate-specific antigen levels on the repeat prostate biopsy

    OpenAIRE

    Park, Yong Hyun; Lee, Jung Keun; Jung, Jin-Woo; Lee, Byung Ki; Lee, Sangchul; Jeong, Seong Jin; Hong, Sung Kyu; Byun, Seok-Soo; Lee, Sang Eun

    2014-01-01

    Purpose: To evaluate whether the risk of prostate cancer was different according to the pattern of fluctuation in prostate-specific antigen (PSA) levels in patients undergoing repeat transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Methods: From March 2003 to December 2012, 492 patients underwent repeat TRUS-Bx. The patients were stratified into 3 groups based on the PSA fluctuation pattern: group 1 (continuous elevation of PSA, n=169), group 2 (PSA fluctuation with PSA velocity [PSAV...

  11. Higher-level accumulation of foreign gene products in transgenic rice seeds by the callus-specific selection system.

    Science.gov (United States)

    Wakasa, Yuhya; Ozawa, Kenjirou; Takaiwa, Fumio

    2009-01-01

    Transgenic rice plants that accumulate the hypocholesterolemic pentapeptide lactostatin (IIAEK) as a fusion protein with the endosperm seed storage protein glutelin were developed. Plants were selected from Agrobacterium-mediated transformants using a mutated-rice acetolactate synthase (mALS) marker protein expressed under the control of the rice callus-specific promoter (CSP) (CSP:mALS). Lactostatin accumulation levels were compared in mature seeds of 78 independent transgenic rice lines selected for either the CSP:mALS gene cassette or hygromycin phosphotransferase (HPT) under the control of the CaMV 35S promoter (35S:HPT). Transgenic rice seeds harboring a CSP:mALS gene cassette accumulated more (approximately 120-200% on average) lactostatin than those with a 35S:HPT gene cassette, and accumulation was largely independent of transgene copy number. Furthermore, transgenic rice seeds that were selected by HPT under the control of CSP (CSP:HPT) also accumulated more lactostatin (approximately 160% on average) than transgenic rice seeds with the 35S:HPT gene cassette. These results indicate that high-value bioactive peptides such as lactostatin can be produced at higher levels using callus-specific selection than by conventional constitutive selection. Specific expression of a marker gene at the selection stage may thus result in increased target peptide accumulation levels in seeds.

  12. Urban Latino children's physical activity levels and performance in interactive dance video games: effects of goal difficulty and goal specificity.

    Science.gov (United States)

    Gao, Zan; Podlog, Leslie

    2012-10-01

    To examine the effects of different levels of goal specificity and difficulty on Latino children's performance and physical activity (PA) levels in an after-school program incorporating an interactive dance program (Dance Dance Revolution [DDR]; Konami Corporation). Comparison study. Rose Park Elementary School, Salt Lake City, Utah. Ninety-eight Latino children in the first through sixth grades, aged 7 to 13 years. After the pretest, the participants were randomly assigned into 1 of the following 3 goal-setting conditions: (1) easy, (2) difficult, and (3) best effort (hereinafter referred to as do-your-best goal). Participants' PA levels were measured using piezoelectric pedometers, and steps per minute were used as the outcome variable. Participants' total points for their dance on television screens were retrieved as their performance scores. These outcome variables were assessed again 8 weeks later (posttest score). The multivariate analysis of covariance yielded a significant main effect for the goal-setting condition. Follow-up tests revealed that children who set specific (easy or difficult) goals had significantly greater increased PA levels (mean scores, 10.34 for easy and 22.45 for difficult) and DDR performance (0.011 for easy and 0.67 for difficult) than those in the do-your-best group (0.83 for PA and 0.17 for performance). In addition, children's increased PA levels in the difficult-goal group were significantly higher than those in the easy-goal group. The easy- and difficult-goal groups show a significant improvement on DDR performance. The difficult- goal group also displays the highest improvement on PA levels. Strategies to enhance children's DDR performance and PA levels are discussed in relation to the extant goal-setting literature.

  13. Cause-specific mortality by occupational skill level in Canada: a 16-year follow-up study.

    Science.gov (United States)

    Tjepkema, M; Wilkins, R; Long, A

    2013-09-01

    Mortality data by occupation are not routinely available in Canada, so we analyzed census-linked data to examine cause-specific mortality rates across groups of occupations ranked by skill level. A 15% sample of 1991 Canadian Census respondents aged 25 years or older was previously linked to 16 years of mortality data (1991-2006). The current analysis is based on 2.3 million people aged 25 to 64 years at cohort inception, among whom there were 164 332 deaths during the follow-up period. Occupations coded according to the National Occupation Classification were grouped into five skill levels. Age-standardized mortality rates (ASMRs), rate ratios (RRs), rate differences (RDs) and excess mortality were calculated by occupational skill level for various causes of death. ASMRs were clearly graded by skill level: they were highest among those employed in unskilled jobs (and those without an occupation) and lowest for those in professional occupations. All-cause RRs for men were 1.16, 1.40, 1.63 and 1.83 with decreasing occupational skill level compared with professionals. For women the gradient was less steep: 1.23, 1.24, 1.32 and 1.53. This gradient was present for most causes of death. Rate ratios comparing lowest to highest skill levels were greater than 2 for HIV/AIDS, diabetes mellitus, suicide and cancer of the cervix as well as for causes of death associated with tobacco use and excessive alcohol consumption. Mortality gradients by occupational skill level were evident for most causes of death. These results provide detailed cause-specific baseline indicators not previously available for Canada.

  14. The relationship between solar UV exposure, serum vitamin D levels and serum prostate-specific antigen levels, in men from New South Wales, Australia: the CHAMP study.

    Science.gov (United States)

    Nair-Shalliker, Visalini; Smith, David P; Clements, Mark; Naganathan, Vasikaran; Litchfield, Melisa; Waite, Louise; Handelsman, David; Seibel, Markus J; Cumming, Robert; Armstrong, Bruce K

    2014-10-01

    We aim to determine the relationship between season, personal solar UV exposure, serum 25(OH)D and 1,25(OH)2D and serum prostate-specific antigen (PSA) levels. Questionnaire data and blood samples were collected at baseline from participants of the Concord Health and Ageing in Men Project (n = 1,705), aged 70 and above. They were grouped as men 'free of prostate disease' for those with no record of having prostate cancer, benign prostatic hyperplasia, or prostatitis and with serum PSA levels below 20 ng/mL, and 'with prostate disease' for those with a record of either of these diseases or with serum PSA levels 20 ng/mL or above. Personal solar UV exposure (sUV) was estimated from recalled hours of outdoor exposure and weighted against ambient solar UV radiation. Sera were analysed to determine levels of PSA, 25(OH)D and 1,25(OH)2D, and analysed using multiple regression, adjusting for age, BMI and region of birth. The association between sUV and serum PSA levels was conditional upon season (p interaction = 0.04). There was no direct association between serum PSA and 25(OH)D in both groups of men. There was a positive association between serum PSA and 1,25(OH)2D in men with prostate disease (mean = 110.6 pmol/L; p heterogeneity = 0.03), but there was no such association in men free of prostate disease (mean = 109.3 pmol/L; p heterogeneity = 0.8). The association between PSA and sUV may only be evident at low solar UV irradiance, and this effect may be independent of serum vitamin D levels.

  15. Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy.

    Science.gov (United States)

    Qiao, H-L; Liu, J-H; Yang, J; Dong, Z-M

    2005-08-01

    The aim of this study was to investigate the relationships between skin test, specific immunoglobulin (Ig) E and cytokines in penicillin allergy. We collected the sera of 259 patients with historical positive skin test to penicillins, with immediate positive skin test and with a negative skin test results. The positive rate of specific IgE antibodies in 259 patients was 62.2% (161) by using radioallergosorbent test (RAST). Of the eight kinds of antigenic determinants, the positive rates of specific IgE to major and minor determinants were 43.63% (113) and 52.51% (136), respectively (p test, when the degrees of skin test were +, 2+, 3+ and 4+, the positive rates of specific IgE were 45.7, 57.1, 85.2 and 100%, respectively. The levels of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma in the sera of patients with positive skin test were significantly increased with the degree of positive skin test (p RAST offers the better test for the detection of penicillin-specific IgE antibodies. IL-4, IL-13 and IFN-gamma play important roles in penicillin allergy.

  16. Comparison of parasite-specific immunoglobulin levels in two chicken lines during sustained infection with Ascaridia galli

    DEFF Research Database (Denmark)

    Norup, Liselotte Rothmann; Dalgaard, Tina S.; Pleidrup, Janne

    2013-01-01

    Increasingly large numbers of poultry are held in production systems with access to outdoor areas. In these systems intestinal helminths are found with flock prevalences of up to 100%. Helminth infections influence chicken health negatively, which is why the following investigation has been...... in chicken faeces were measured for a period of 81 weeks.The level of excreted A. galli eggs measured as eggs per gram chicken faeces (EPG) varied greatly between chickens in each line. Significant differences were found between the two lines and with the R5 chickens reaching the highest levels. Likewise......, the A. galli-specific IgG titres in serum differed significantly between the two lines, and an inverse relationship between infection level (EPG) and antibody titres was found. Although this inverse relationship suggests that humoral immunity may be involved in protection against A. galli infection...

  17. Teacher's opinions about learning continuum based on the student's level of competence and specific pedagogical materials on anatomical aspects

    Science.gov (United States)

    Astuti, Laili Dwi; Subali, Bambang

    2017-08-01

    This research deals with designing learning continuum for developing a curriculum. The objective of this study is to gather the opinion of public junior and high school teachers about Learning Continuum based on Student's Level of Competence and Specific Pedagogical Material on Anatomical Aspects. This is a survey research. The population of the research is natural science teachers at junior high school and biology teacher at senior high school in Yogyakarta Special Region. Data were collected using a questionnaire. Data were analyzed using a descriptive analysis technique. Based on the results of the survey, the teachers opinion are in accordance with the level of the students they teach. Junior high school teachers argued that anatomical aspects were taught in grade VII,VIII, IX and X on the level of C2 (understanding), the high school teacher argued that anatomical aspects were taught in grade VIII, X and XI on the level of C2 (understanding) and C3 (apply). While according to the opinions of primary school teachers about aspects of anatomy resulted from the research of Subali (2016), anatomy is mostly not taught at the elementary school level, only some of the materials that are taught in this school level. Therefore, the results of the survey can be inferred that the opinions of teachers is still based on the existing curriculum.

  18. Groundwater level and specific conductance monitoring at Marine Corps Base, Camp Lejeune, Onslow County, North Carolina, 2007-2008

    Science.gov (United States)

    McSwain, Kristen Bukowski

    2010-01-01

    The U.S. Geological Survey, in cooperation with the Marine Corps Base, Camp Lejeune, monitored water-resources conditions in the surficial, Castle Hayne, Peedee, and Black Creek aquifers in Onslow County, North Carolina, from November 2007 through September 2008. To comply with North Carolina Central Coastal Plain Capacity Use Area regulations, large-volume water suppliers in Onslow County must reduce their dependency on the Black Creek aquifer as a water-supply source and have, instead, proposed using the Castle Hayne aquifer as an alternative water-supply source. The Marine Corps Base, Camp Lejeune, uses water obtained from the unregulated surficial and Castle Hayne aquifers for drinking-water supply. Water-level data were collected and field measurements of physical properties were made at 19 wells at 8 locations spanning the Marine Corps Base, Camp Lejeune. These wells were instrumented with near real-time monitoring equipment to collect hourly measurements of water level. Additionally, specific conductance and water temperature were measured hourly in 16 of the 19 wells. Graphs are presented relating altitude of groundwater level to water temperature and specific conductance measurements collected during the study, and the relative vertical gradients between aquifers are discussed. The period-of-record normal (25th to 75th percentile) monthly mean groundwater levels at two well clusters were compared to median monthly mean groundwater levels at these same well clusters for 2008 to determine groundwater-resources conditions. In 2008, water levels were below normal in the 3 wells at one of the well clusters and were normal in 4 wells at the other cluster.

  19. Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.

    Science.gov (United States)

    López, Sonia; Buil, Alfonso; Souto, Juan Carlos; Casademont, Jordi; Blangero, John; Martinez-Perez, Angel; Fontcuberta, Jordi; Lathrop, Mark; Almasy, Laura; Soria, Jose Manuel

    2012-01-01

    Altered mitochondrial DNA (mtDNA) levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT). We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs) involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p=1.82e-05). We identified a QTL on Chromosome 2 (LOD=2.21) using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD=3.09), indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD=2.67), whereas in males a QTL was identified on Chromosome 1 (LOD=2.81). These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene MRPL37, involved in mitochondrial protein translation. The rs2140855 on Chromosome 2 showed association in the analysis using all of the subjects. It was near the gene CMPK2, which encodes a mitochondrial enzyme of the salvage pathway of deoxyribonucleotide synthesis. Our results provide evidence of a sex-specific genetic mechanism for the control of mtDNA levels and provide a framework to identify new genes that influence mtDNA levels.

  20. Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.

    Directory of Open Access Journals (Sweden)

    Sonia López

    Full Text Available Altered mitochondrial DNA (mtDNA levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT. We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p=1.82e-05. We identified a QTL on Chromosome 2 (LOD=2.21 using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD=3.09, indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD=2.67, whereas in males a QTL was identified on Chromosome 1 (LOD=2.81. These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene MRPL37, involved in mitochondrial protein translation. The rs2140855 on Chromosome 2 showed association in the analysis using all of the subjects. It was near the gene CMPK2, which encodes a mitochondrial enzyme of the salvage pathway of deoxyribonucleotide synthesis. Our results provide evidence of a sex-specific genetic mechanism for the control of mtDNA levels and provide a framework to identify new genes that influence mtDNA levels.

  1. Correlation of symptoms with total IgE and specific IgE levels in patients presenting with allergic rhinitis.

    Science.gov (United States)

    Karli, Rifat; Balbaloglu, Evrim; Uzun, Lokman; Cinar, Fikret; Ugur, Mehmet Birol

    2013-04-01

    The objective of this study was to investigate the correlation of symptoms in patients with presumed allergic rhinitis on the basis of their medical history and physical examination with the levels of total immunoglobulin E (IgE) and specific IgE, and to question the necessity of these tests in diagnosis. The records of 295 patients, who had at least two complaints of nasal itching, nasal obstruction, runny discharge and sneezing, and/or presumed as allergic rhinitis on physical examination findings were retrospectively screened. The correlation between the levels of IgE, specific inhalant IgE, and food-specific serum IgE were evaluated in these patients. A total of 70 cases (23.7%) were determined to have a total value of IgE under 20 U/ml, 113 cases (38.3%) with IgE values between 20 U/ml and 100 U/ml, and 100 cases with IgE values above 100 U/ml. Results of total IgE could not be obtained in 12 (4.06%) patients. Dermatophagoides farinae was the most common allergy in this group with 74 (68.5%) cases. The determination of IgE in allergic rhinitis is a supportive method. However, it cannot be recommended for routine use because of the time loss and high cost.

  2. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies

    OpenAIRE

    Lewis, Melanie J.; Wagner, Bettina; Woof, Jenny M.

    2008-01-01

    Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1 > I...

  3. Insights from native mass spectrometry approaches for top- and middle- level characterization of site-specific antibody-drug conjugates.

    Science.gov (United States)

    Botzanowski, Thomas; Erb, Stéphane; Hernandez-Alba, Oscar; Ehkirch, Anthony; Colas, Olivier; Wagner-Rousset, Elsa; Rabuka, David; Beck, Alain; Drake, Penelope M; Cianférani, Sarah

    2017-07-01

    Antibody-drug conjugates (ADCs) have emerged as a family of compounds with promise as efficient immunotherapies. First-generation ADCs were generated mostly via reactions on either lysine side-chain amines or cysteine thiol groups after reduction of the interchain disulfide bonds, resulting in heterogeneous populations with a variable number of drug loads per antibody. To control the position and the number of drug loads, new conjugation strategies aiming at the generation of more homogeneous site-specific conjugates have been developed. We report here the first multi-level characterization of a site-specific ADC by state-of-the-art mass spectrometry (MS) methods, including native MS and its hyphenation to ion mobility (IM-MS). We demonstrate the versatility of native MS methodologies for site-specific ADC analysis, with the unique ability to provide several critical quality attributes within one single run, along with a direct snapshot of ADC homogeneity/heterogeneity without extensive data interpretation. The capabilities of native IM-MS to directly access site-specific ADC conformational information are also highlighted. Finally, the potential of these techniques for assessing an ADC's heterogeneity/homogeneity is illustrated by comparing the analytical characterization of a site-specific DAR4 ADC to that of first-generation ADCs. Altogether, our results highlight the compatibility, versatility, and benefits of native MS approaches for the analytical characterization of all types of ADCs, including site-specific conjugates. Thus, we envision integrating native MS and IM-MS approaches, even in their latest state-of-the-art forms, into workflows that benchmark bioconjugation strategies.

  4. Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet-derived growth factor receptor alpha.

    Science.gov (United States)

    Shah, Gaurav D; Loizos, Nick; Youssoufian, Hagop; Schwartz, Jonathan D; Rowinsky, Eric K

    2010-02-15

    A large body of evidence suggests that the platelet-derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC-3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor alpha (PDGFRalpha) with high affinity and blocks PDGF ligand binding and PDGFRalpha activation. The results of preclinical studies and the frequent expression of PDGFRalpha in many types of cancer and in cancer-associated stroma support a rationale for the clinical development of IMC-3G3. Currently, IMC-3G3 is being evaluated in early clinical development for patients with several types of solid malignancies. (c) 2010 American Cancer Society.

  5. Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1

    Science.gov (United States)

    Orthwein, Alexandre; Zahn, Astrid; Methot, Stephen P; Godin, David; Conticello, Silvestro G; Terada, Kazutoyo; Di Noia, Javier M

    2012-01-01

    The enzyme activation-induced deaminase (AID) deaminates deoxycytidine at the immunoglobulin genes, thereby initiating antibody affinity maturation and isotype class switching during immune responses. In contrast, off-target DNA damage caused by AID is oncogenic. Central to balancing immunity and cancer is AID regulation, including the mechanisms determining AID protein levels. We describe a specific functional interaction between AID and the Hsp40 DnaJa1, which provides insight into the function of both proteins. Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. Conversely, DnaJa1, but not DnaJa2, depletion reduces AID levels, stability and isotype switching. In vivo, DnaJa1-deficient mice display compromised response to immunization, AID protein and isotype switching levels being reduced by half. Moreover, DnaJa1 farnesylation is required to maintain, and farnesyltransferase inhibition reduces, AID protein levels in B cells. Thus, DnaJa1 is a limiting factor that plays a non-redundant role in the functional stabilization of AID. PMID:22085931

  6. Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels.

    Science.gov (United States)

    Koo, Kyo Chul; Park, Sang Un; Kim, Ki Hong; Rha, Koon Ho; Hong, Sung Joon; Yang, Seung Choul; Chung, Byung Ha

    2015-03-01

    Prostate-specific antigen (PSA) is a surrogate marker of disease progression; however, its predictive ability in the extreme ranges is unknown. We determined the predictors of survival in patients with bone metastatic prostate cancer (BMPCa) and with extremely high PSA levels. Treatment-naïve patients (n = 248) diagnosed with BMPCa between December 2002 and June 2012 were retrospectively analyzed. Clinicopathological features at diagnosis, namely age, body mass index, serum alkaline phosphatase (ALP) and PSA levels, PSA nadir, time to PSA nadir and its maintenance period, PSA declining velocity, Gleason grade, clinical T stage, pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), and the number of bone metastases were assessed. The patients were stratified according to PSA ranges of bone lesions (P < 0.001). During the follow-up period (median, 39.9 months; interquartile range, 21.5-65.9 months), there were no differences between the groups in terms of the survival endpoints. High ALP levels, shorter time to PSA nadir, and pain were associated with an increased risk of progression to CRPC, and high ALP levels, ECOG PS ≥ 1, and higher PSA nadir independently predicted CSS. PSA response to androgen deprivation therapy and serum ALP are reliable predictors of survival in patients with BMPCa presenting with extremely high PSA levels. These patients should not be deterred from active treatment based on baseline PSA values.

  7. Are age-specific high serum IgE levels associated with worse symptomatology in children with atopic dermatitis?

    Science.gov (United States)

    Hon, Kam-Lun Ellis; Lam, Man-Ching Adrian; Leung, Ting-Fan; Wong, Kin-Yee; Chow, Chung-Mo; Fok, Tai-Fai; Ng, Pak-Cheung

    2007-12-01

    Atopic dermatitis (AD) is a distressing disease associated with excoriations, pruritus, sleep disturbance, and elevation of serum total immunoglobulin E (IgE) levels. To evaluate whether serum IgE levels correlate with the symptomatology and plasma chemokine levels in children with AD. AD patients aged younger than 18 years were recruited from the pediatric dermatology clinic of a university teaching hospital, and the AD severity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index. Concentrations of serum total IgE, eosinophil count, and plasma AD-associated chemokines [cutaneous T-cell-attracting cytokine (CTACK), thymus and activation-regulated chemokine (TARC)] were measured. One hundred and seventeen Chinese children with AD (64 boys and 53 girls), with an age (mean +/- standard deviation) of 10.7 +/- 4.4 years, were recruited. Their overall SCORAD index (mean +/- standard deviation) was 51.1 +/- 22.8. The total serum IgE level divided by the age-specific upper limit (AE) correlated well with the extent and intensity of AD, except for oozing/crusting, which was significant only in males. There was a significant correlation between AE and pruritus or sleep loss only in females. Levels of IgE, CTACK, and TARC, and eosinophil count, differed significantly between patients with mild, moderate, and severe disease. AE correlated well with TARC (r = 0.50, P clinical scores and chemokine markers of AD, and is a useful indicator for predicting moderate to severe AD in children.

  8. Plasma Levels of the Cerebral Biomarker, Neuron-Specific Enolase, are Elevated During Pregnancy in Women Developing Preeclampsia.

    Science.gov (United States)

    Bergman, Lina; Åkerud, Helena

    2016-03-01

    Neuron-specific enolase (NSE) is considered to be a peripheral biomarker of central nervous system injury. The aim of this study was to compare levels of NSE throughout pregnancy, in healthy pregnant women and in women developing preeclampsia. A nested case-control study within a longitudinal study cohort was performed. Four hundred sixty nine healthy pregnant women were enrolled, and plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. Levels of NSE were analyzed in 16 women with preeclampsia and 36 controls throughout pregnancy with an enzyme-linked immunosorbent assay. In gestational week 37, women who developed preeclampsia had significantly higher plasma levels of NSE than healthy pregnant controls (P preeclampsia, but the levels decreased significantly in healthy pregnant controls (P preeclampsia, the levels of NSE remained high throughout pregnancy, whereas in healthy women, these tended to decline over time, especially at the 2 last time points. The result might be confounded in early pregnancy by extracerebral sources of NSE, such as the corpus luteum. Findings need to be confirmed in a larger prospective study. © The Author(s) 2015.

  9. Our Prostate Biopsy Results in The Patients with Prostate Specific Antigen Levels Below 4 ng/ml

    Directory of Open Access Journals (Sweden)

    Huseyin Aydemir

    2014-03-01

    Full Text Available Aim: The aim of this study is to evaluate the re¬sults of prostate biopsy of patients who had the prostate-specific antigen (PSA levels below 4 ng/ml. Material and Method: The medical records of 524 pa¬tients who underwent transrectal prostate biopsy be¬tween January 2010 and February 2013 in our clinic, due to suspi¬cion of prostate cancer were evaluated and histopathologic results of 43 patients whose PSA levels under 4 ng/ml were retrospectively revieved. Results: The mean age of patients was 64.63 ±7:42 and the mean level of PSA was 2.89 ±0.88ng /ml. A digital rectal examination (DRE had suspicious findings in 41(95.34% patients. Prostate adenocarcinoma was determined in 13 of (30.23% patients according to the biopsy result. The mean PSA value of these patients was 2.89 ±0.88 ng/ml and the mean gleason score of these patients was 6.41 ±0.87. The mean prostate volume of these patients was 41.46 ±11.95 cm3. Discussion: In our study, prostate cancer was identified in 30.3% of patients whose PSA levels were below 4 ng/ml. DRE, is still important for the evaluation of the prostate. According to our results, significant number of cancers can be detected in PSA below 4 ng/ml levels.

  10. Metastatic Prostatic Adenocarcinoma in an Inguinal Hernia Sac in a Patient with Undetectable Serum Prostate Specific Antigen Level

    Directory of Open Access Journals (Sweden)

    Shiu-Dong Chung

    2007-05-01

    Full Text Available Metastatic prostate cancer found within the hernia sac contents is a rare clinical manifestation. We report a 64-year-old male patient who presented with rare clinical features of prostate cancer. A focal metastasis of prostate cancer was incidentally found in an incised inguinal hernia sac 5 years after radical prostatectomy. The serum prostate specific antigen (PSA level remained undetectable (< 0.01 ng/mL prior to herniorrhaphy without any adjuvant therapy. In addition, serial studies performed right after herniorrhaphy disclosed no evidence of overt clinical metastasis. However, his serum PSA level started rising 12 months later and bladder invasion as well as a mass in the cul-de-sac was identified subsequently. The serum PSA level was 2.45 ng/mL at his latest visit, which was 5 years after herniorrhaphy. This case implies that physicians should be more alert in patients with a low preoperative serum PSA level during the period of follow-up. Both serum PSA and digital rectal examination may be important in patients with low preoperative PSA level after radical prostatectomy.

  11. The learning continuum based on student's level of competence and specific pedagogical learning material on physiological aspects from teachers's opinions

    Science.gov (United States)

    Hadi, Ria Fitriyani; Subali, Bambang

    2017-08-01

    The scope of learning continuum at the conceptual knowledge is formulated based on the student's level of competence and specific pedagogical learning material. The purpose of this study is to develop a learning continuum of specific pedagogical material aspects of physiology targeted for students in primary and secondary education. This research was conducted in Province of Yogyakarta Special Region from October 2016 to January 2017. The method used in this study was survey method. The data were collected using questionnaire that had been validated from the aspects of construct validity and experts judgements. Respondents in this study consist of 281 Science/Biology teachers at Public Junior and Senior High Schools in the Province of Yogyakarta Special Region which spread in Yogyakarta city and 4 regencies namely Sleman, Bantul, Kulonprogo, and Gunungkidul. The data were taken using a census. Data were analyzed using a descriptive analysis technique. The results show the learning continuum of physiology based on teachers's opinion from grade VII, VIII, and IX are taught in grade VII, VIII, IX and X on level of C2 (understanding) and the learning continuum of physiology based on teachers's opinion from grade X, XI and XII are taught in grade X and XI on level of C2 (understanding), C3 (applying), and C4 (analyzing) based on teachers's opinions. The conclusion is that many teachers refer to the existing curriculum rather than their own original idea for developing learning continuum.

  12. An Approach for the High-Level Specification of QoS-Aware Grid Workflows Considering Location Affinity

    Directory of Open Access Journals (Sweden)

    Ivona Brandic

    2006-01-01

    Full Text Available Many important scientific and engineering problems may be solved by combining multiple applications in the form of a Grid workflow. We consider that for the wide acceptance of Grid technology it is important that the user has the possibility to express requirements on Quality of Service (QoS at workflow specification time. However, most of the existing workflow languages lack constructs for QoS specification. In this paper we present an approach for high level workflow specification that considers a comprehensive set of QoS requirements. Besides performance related QoS, it includes economical, legal and security aspects. For instance, for security or legal reasons the user may express the location affinity regarding Grid resources on which certain workflow tasks may be executed. Our QoS-aware workflow system provides support for the whole workflow life cycle from specification to execution. Workflow is specified graphically, in an intuitive manner, based on a standard visual modeling language. A set of QoS-aware service-oriented components is provided for workflow planning to support automatic constraint-based service negotiation and workflow optimization. For reducing the complexity of workflow planning, we introduce a QoS-aware workflow reduction technique. We illustrate our approach with a real-world workflow for maxillo facial surgery simulation.

  13. Association of DNA Methylation Levels with Tissue-specific Expression of Adipogenic and Lipogenic Genes in Muscle of Korean Cattle

    Directory of Open Access Journals (Sweden)

    M. Baik

    2014-10-01

    Full Text Available Epigenetic factors, such as DNA methylation status, may regulate adipogenesis and lipogenesis, thus affecting intramuscular fat (IMF deposition in longissimus dorsi muscle (LM of beef cattle. In Korean cattle steers, the LM consists mainly of muscle tissue. However, the LM tissue also contains IMF. We compared the gene expression levels between the IMF and muscle portions of the LM after tissue separation. Real-time polymerase chain reaction analysis showed that the mRNA levels of both adipogenic peroxisome proliferator-activated receptor gamma isoform 1 (PPARG1 and lipogenic fatty acid binding protein 4 (FABP4 were higher (p<0.01 in the IMF than in the muscle portion of the LM. We determined DNA methylation levels of regulatory regions of the PPARG1 and FABP4 genes by pyrosequencing of genomic DNA. DNA methylation levels of two of three CpG sites in the PPARG1 gene promoter region were lower (p<0.05 in the IMF than in the muscle portion of the LM. DNA methylation levels of all five CpG sites from the FABP4 gene promoter region were also lower (p<0.001 in the IMF than in the muscle portion. Thus, mRNA levels of both PPARG1 and FABP4 genes were inversely correlated with DNA methylation levels in regulatory regions of CpG sites of the corresponding gene. Our findings suggest that DNA methylation status regulates tissue-specific expression of adipogenic and lipogenic genes in the IMF and muscle portions of LM tissue in Korean cattle.

  14. Are Total, Intensity- and Domain-Specific Physical Activity Levels Associated with Life Satisfaction among University Students?

    Science.gov (United States)

    Pedišić, Željko; Greblo, Zrinka; Phongsavan, Philayrath; Milton, Karen; Bauman, Adrian E.

    2015-01-01

    Background Thorough information about the relationship between physical activity (PA) and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO) moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity), domain-specific PA (work, transport-related, domestic, and leisure-time), and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI), and self-rated health. Methods The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years), using the International Physical Activity Questionnaire — long form and the Satisfaction with Life Scale. Results Higher life satisfaction was associated with female gender (β = 0.13; p = life satisfaction and size of community (p = 0.567), smoking status (p = 0.056), alcohol consumption (p = 0.058), or BMI (p = 0.508). Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045). Conclusions This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the relationship between PA and life satisfaction based on total PA levels only may be misleading. PMID:25695492

  15. Gene-specific DNA methylation association with serum levels of C-reactive protein in African Americans.

    Directory of Open Access Journals (Sweden)

    Yan V Sun

    Full Text Available A more thorough understanding of the differences in DNA methylation (DNAm profiles in populations may hold promise for identifying molecular mechanisms through which genetic and environmental factors jointly contribute to human diseases. Inflammation is a key molecular mechanism underlying several chronic diseases including cardiovascular disease, and it affects DNAm profile on both global and locus-specific levels. To understand the impact of inflammation on the DNAm of the human genome, we investigated DNAm profiles of peripheral blood leukocytes from 966 African American participants in the Genetic Epidemiology Network of Arteriopathy (GENOA study. By testing the association of DNAm sites on CpG islands of over 14,000 genes with C-reactive protein (CRP, an inflammatory biomarker of cardiovascular disease, we identified 257 DNAm sites in 240 genes significantly associated with serum levels of CRP adjusted for age, sex, body mass index and smoking status, and corrected for multiple testing. Of the significantly associated DNAm sites, 80.5% were hypomethylated with higher CRP levels. The most significant Gene Ontology terms enriched in the genes associated with the CRP levels were immune system process, immune response, defense response, response to stimulus, and response to stress, which are all linked to the functions of leukocytes. While the CRP-associated DNAm may be cell-type specific, understanding the DNAm association with CRP in peripheral blood leukocytes of multi-ethnic populations can assist in unveiling the molecular mechanism of how the process of inflammation affects the risks of developing common disease through epigenetic modifications.

  16. Utility of free prostate specific antigen serum level and its related parameters in the diagnosis of prostate cancer

    Directory of Open Access Journals (Sweden)

    Azmi A Haroun

    2011-01-01

    Full Text Available We evaluated the role of free prostate specific antigen (f-PSA serum level and its related parameters in detecting prostate cancer. This retrospective study was conducted between January 2006 and March 2008. Trans-rectal ultrasound guided prostate biopsy was performed for 107 patients who had total PSA (t-PSA level of either >4 ng/mL with or without palpable nodule or ≤4 ng/mL with palpable nodule on digital rectal examination. The perfor-mance measurements for f-PSA, percent free PSA (%f-PSA and free PSA density (f-PSAD were determined and compared with those for t-PSA and total PSA density (t-PSAD. Descriptive statistics for all variables of interest were calculated, and receiver operating characteristic curves were generated. Nine patients (8.4% had normal histology, 69 patients (64.4% had benign disease and 29 patients (27.1% had prostate cancer. The performance of f-PSA in PCa detection was better than other evaluated parameters. The largest area under the curve for patients in the gray area (t-PSA range 4.1-10 ng/mL was for f-PSA, with a value of 0.64 and a sensitivity and specificity of 44% and 87%, respectively. For %f-PSA, these values were 0.59, 63% and 62%, respectively. For patients with a t-PSA level of 10.1-20 ng/mL, they were 0.68, 67%, and 81%, respectively, for f-PSA, and 0.64, 67%, and 76%, respectively, for %f-PSA. In conclusion, f-PSA serum levels performed better than free to total PSA ratio and t-PSA for prostate cancer screening. It is of clinical value which could affect the biopsy decision avoiding unnecessary interventions.

  17. Utility of free prostate specific antigen serum level and its related parameters in the diagnosis of prostate cancer.

    Science.gov (United States)

    Haroun, Azmi A; Hadidy, Azmy S; Awwad, Ziad M; Nimri, Caramella F; Mahafza, Waleed S; Tarawneh, Emad S

    2011-03-01

    We evaluated the role of free prostate specific antigen (f-PSA) serum level and its related parameters in detecting prostate cancer. This retrospective study was conducted between January 2006 and March 2008. Transrectal ultrasound guided prostate biopsy was performed for 107 patients who had total PSA (t-PSA) level of either >4 ng/mL with or without palpable nodule or ≤4 ng/mL with palpable nodule on digital rectal examination. The performance measurements for f-PSA, percent free PSA (%f-PSA) and free PSA density (f-PSAD) were determined and compared with those for t-PSA and total PSA density (t-PSAD). Descriptive statistics for all variables of interest were calculated, and receiver operating characteristic curves were generated. Nine patients (8.4%) had normal histology, 69 patients (64.4%) had benign disease and 29 patients (27.1%) had prostate cancer. The performance of f-PSA in PCa detection was better than other evaluated parameters. The largest area under the curve for patients in the gray area (t-PSA range 4.1-10 ng/mL) was for f-PSA, with a value of 0.64 and a sensitivity and specificity of 44% and 87%, respectively. For %f-PSA, these values were 0.59, 63% and 62%, respectively. For patients with a t-PSA level of 10.1-20 ng/mL, they were 0.68, 67%, and 81%, respectively, for f-PSA, and 0.64, 67%, and 76%, respectively, for %f-PSA. In conclusion, f-PSA serum levels performed better than free to total PSA ratio and t-PSA for prostate cancer screening. It is of clinical value which could affect the biopsy decision avoiding unnecessary interventions.

  18. Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects.

    Science.gov (United States)

    Wu, Dong-Feng; Yin, Rui-Xing; Aung, Lynn Htet Htet; Li, Qing; Yan, Ting-Ting; Zeng, Xiao-Na; Huang, Ke-Ke; Huang, Ping; Wu, Jin-Zhen; Pan, Shang-Ling

    2012-01-13

    Acyl-CoA:cholesterol acyltransferase (ACAT) is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP) and serum lipid levels in the hyperlipidemic subjects. A total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345) aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. There was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC), HDL-C and apolipoprotein (Apo) AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (P ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male)-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.

  19. Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects

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    Wu Dong-Feng

    2012-01-01

    Full Text Available Abstract Background Acyl-CoA:cholesterol acyltransferase (ACAT is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP and serum lipid levels in the hyperlipidemic subjects. Methods A total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345 aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results There was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC, HDL-C and apolipoprotein (Apo AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (P Conclusions The present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.

  20. Prostate-specific antigen levels in men aged 70 years and over: findings from the CHAMP study.

    Science.gov (United States)

    Litchfield, Melisa J; Cumming, Robert G; Smith, David P; Naganathan, Vasi; Le Couteur, David G; Waite, Louise M; Blyth, Fiona M; Handelsman, David J

    2012-04-02

    To describe values of serum prostate-specific antigen (PSA) in older men without diagnosed prostate cancer, categorised by age and country of birth, and to describe self-reported prostate cancer screening. A cohort study (the Concord Health and Ageing in Men Project) involving a representative sample of 1434 eligible community-dwelling men with no diagnosis of prostate cancer who were aged 70 years and over and living in a defined geographic area in Sydney, with baseline data collected between 28 January 2005 and 4 June 2007. Serum PSA levels and self-reported prostate cancer screening. 11% of men (155) had a PSA level of ≥6.5 ng/mL, increasing from 7.5% of men aged 70-74 years to 31.4% of men aged≥90 years. PSA levels varied with ethnicity, with Australian-born men (695) having the highest levels (median, 2.3 ng/mL; 5th-95th percentile, 0.4-10.1 ng/mL), followed by men born in China (n=42; 2.1 ng/mL; 0.4-12.4 ng/mL), United Kingdom and Ireland (n=70; 1.9 ng/mL; 0.3-8.9 ng/mL), Greece (n=59; 1.5 ng/mL; 0.2-6.1 ng/mL), and Italy (n=293; 1.4 ng/mL; 0.3-7.2 ng/mL). A PSA test in the previous 2 years was reported by 48% of participants, and a digital rectal examination (DRE) in the previous 2 years by 37%. A significant number of men aged over 70 years reported recent prostate cancer tests. The PSA level ranges reported in this cohort will help with interpreting serum PSA level findings in men aged over 70 years.

  1. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

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    Pino, Jessica M. V.; da Luz, Marcio H. M.; Antunes, Hanna K. M.; Giampá, Sara Q. de Campos; Martins, Vilma R.; Lee, Kil S.

    2017-01-01

    Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC) and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR) or with normal diet (CTL) for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA) was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological disorders. Our

  2. Iron-Restricted Diet Affects Brain Ferritin Levels, Dopamine Metabolism and Cellular Prion Protein in a Region-Specific Manner

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    Jessica M. V. Pino

    2017-05-01

    Full Text Available Iron is an essential micronutrient for several physiological functions, including the regulation of dopaminergic neurotransmission. On the other hand, both iron, and dopamine can affect the folding and aggregation of proteins related with neurodegenerative diseases, such as cellular prion protein (PrPC and α-synuclein, suggesting that deregulation of iron homeostasis and the consequential disturbance of dopamine metabolism can be a risk factor for conformational diseases. These proteins, in turn, are known to participate in the regulation of iron and dopamine metabolism. In this study, we evaluated the effects of dietary iron restriction on brain ferritin levels, dopamine metabolism, and the expression levels of PrPC and α-synuclein. To achieve this goal, C57BL/6 mice were fed with iron restricted diet (IR or with normal diet (CTL for 1 month. IR reduced iron and ferritin levels in liver. Ferritin reduction was also observed in the hippocampus. However, in the striatum of IR group, ferritin level was increased, suggesting that under iron-deficient condition, each brain area might acquire distinct capacity to store iron. Increased lipid peroxidation was observed only in hippocampus of IR group, where ferritin level was reduced. IR also generated discrete results regarding dopamine metabolism of distinct brain regions: in striatum, the level of dopamine metabolites (DOPAC and HVA was reduced; in prefrontal cortex, only HVA was increased along with the enhanced MAO-A activity; in hippocampus, no alterations were observed. PrPC levels were increased only in the striatum of IR group, where ferritin level was also increased. PrPC is known to play roles in iron uptake. Thus, the increase of PrPC in striatum of IR group might be related to the increased ferritin level. α-synuclein was not altered in any regions. Abnormal accumulation of ferritin, increased MAO-A activity or lipid peroxidation are molecular features observed in several neurological

  3. Phylogenetic relationships of the Subclass Peniculia (Oligohymenophorea, Ciliophora) inferred from small subunit rRNA gene sequences.

    Science.gov (United States)

    Strüder-Kypke, M C; Wright, A D; Fokin, S I; Lynn, D H

    2000-01-01

    Peniculine ciliates have been recognized as a distinct higher taxon of ciliates for almost 50 years. However, phylogenetic relationships within the Subclass Peniculia are still unsettled. To contribute to our understanding of their phylogeny and provide evidence for the position of Urocentrum turbo, we sequenced its small subunit (SS) rRNA gene and the SSrRNA genes from Lembadion bullinum, Frontonia sp., Paramecium caudatum, Paramecium multimicronucleatum, Paramecium putrinum, and Paramecium woodruffi. Urocentrum turbo was the only one of these species not to exhibit a shortened Helix E10_1, which we conclude characterizes the "higher" peniculines. Except for U. turbo, the peniculines are strongly supported as a monophyletic clade with Lembadion, Frontonia, and Paramecium species forming separate and strongly supported clades by bootstrap analysis using distance matrix, maximum parsimony, and maximum likelihood methods. Urocentrum turbo is associated with different lineages, depending upon the analysis used. The Paramecium species form at least four clades with the Paramecium aurelia subgroup being the most derived. We conclude that the Subclass Peniculia should be divided into two orders, the Order Urocentrida and Order Peniculida, with the latter order having two suborders, the Suborder Frontoniina and Peniculina. We place U. turbo with the peniculines because of shared morphological and stomatogenetic features.

  4. Impact of liver fat on the differential partitioning of hepatic triacylglycerol into VLDL subclasses on high and low sugar diets.

    Science.gov (United States)

    Umpleby, A Margot; Shojaee-Moradie, Fariba; Fielding, Barbara; Li, Xuefei; Marino, Andrea; Alsini, Najlaa; Isherwood, Cheryl; Jackson, Nicola; Ahmad, Aryati; Stolinski, Michael; Lovegrove, Julie A; Johnsen, Sigurd; Jeewaka R Mendis, A S; Wright, John; Wilinska, Malgorzata E; Hovorka, Roman; Bell, Jimmy D; Thomas, E Louise; Frost, Gary S; Griffin, Bruce A

    2017-11-01

    Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD ( n = 11) and low liver fat 'controls' ( n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL 1 -triacylglycerol (TAG) after the high ( P liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars. © 2017 The Author(s).

  5. Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

    Science.gov (United States)

    Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

    2017-03-01

    Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (pcholesterol absorption had increased proportion of LDL IVB (pcholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

  6. Species-specific control of external superoxide levels by the coral holobiont during a natural bleaching event

    Science.gov (United States)

    Diaz, Julia M.; Hansel, Colleen M.; Apprill, Amy; Brighi, Caterina; Zhang, Tong; Weber, Laura; McNally, Sean; Xun, Liping

    2016-12-01

    The reactive oxygen species superoxide (O2.-) is both beneficial and detrimental to life. Within corals, superoxide may contribute to pathogen resistance but also bleaching, the loss of essential algal symbionts. Yet, the role of superoxide in coral health and physiology is not completely understood owing to a lack of direct in situ observations. By conducting field measurements of superoxide produced by corals during a bleaching event, we show substantial species-specific variation in external superoxide levels, which reflect the balance of production and degradation processes. Extracellular superoxide concentrations are independent of light, algal symbiont abundance and bleaching status, but depend on coral species and bacterial community composition. Furthermore, coral-derived superoxide concentrations ranged from levels below bulk seawater up to ~120 nM, some of the highest superoxide concentrations observed in marine systems. Overall, these results unveil the ability of corals and/or their microbiomes to regulate superoxide in their immediate surroundings, which suggests species-specific roles of superoxide in coral health and physiology.

  7. Mirror Visual Feedback Training Improves Intermanual Transfer in a Sport-Specific Task: A Comparison between Different Skill Levels

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    Fabian Steinberg

    2016-01-01

    Full Text Available Mirror training therapy is a promising tool to initiate neural plasticity and facilitate the recovery process of motor skills after diseases such as stroke or hemiparesis by improving the intermanual transfer of fine motor skills in healthy people as well as in patients. This study evaluated whether these augmented performance improvements by mirror visual feedback (MVF could be used for learning a sport-specific skill and if the effects are modulated by skill level. A sample of 39 young, healthy, and experienced basketball and handball players and 41 novices performed a stationary basketball dribble task at a mirror box in a standing position and received either MVF or direct feedback. After four training days using only the right hand, performance of both hands improved from pre- to posttest measurements. Only the left hand (untrained performance of the experienced participants receiving MVF was more pronounced than for the control group. This indicates that intermanual motor transfer can be improved by MVF in a sport-specific task. However, this effect cannot be generalized to motor learning per se since it is modulated by individuals’ skill level, a factor that might be considered in mirror therapy research.

  8. Generic versus specific competencies of entry-level public health graduates: employers' perceptions in Poland, the UK, and the Netherlands.

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    Biesma, Regien G; Pavlova, Milena; Vaatstra, Rina; van Merode, Godefridus G; Czabanowska, Katarzyna; Smith, Tony; Groot, Wim

    2008-08-01

    Constant changes in society and the public health domain force public health professionals into new roles and the development of new competencies. Public health professionals will need to be trained to respond to this challenge. The aim of this comparative study among Poland, the UK and the Netherlands is to identify competence needs for Master of Public Health graduates entering the labour market from a European perspective. A self-administered questionnaire was sent to employers in the three countries, rating the importance of competency in public health on a master's level. In all three countries, interpersonal competencies, like team working and communication skills, are rated as highly important. However, employers in the UK and Poland generally rate public health specific competencies as much more important than their Dutch colleagues. It is concluded that while public health specific knowledge is providing a useful starting point for entry-level public health professionals, employers increasingly recognise the value of generic competencies such as communication and team working skills. The results suggest a stronger emphasis on teaching methods that encourage active learning and the integration of skills, which is crucial for enhancing graduates' employability, and foster an open attitude to multidisciplinary working, which is essential in modern health care.

  9. Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1

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    Cornelia Kilchert

    2015-12-01

    Full Text Available In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation.

  10. Transforming pluripotency: an exon-level study of malignancy-specific transcripts in human embryonal carcinoma and embryonic stem cells.

    Science.gov (United States)

    Alagaratnam, Sharmini; Harrison, Neil; Bakken, Anne Cathrine; Hoff, Andreas M; Jones, Mark; Sveen, Anita; Moore, Harry D; Andrews, Peter W; Lothe, Ragnhild A; Skotheim, Rolf I

    2013-04-01

    To circumvent difficulties of isolating pure populations of cancer stem cells (CSCs) for the purpose of identifying malignancy-specific gene expression, we have compared exon-resolution transcriptomic profiles of 5 embryonal carcinoma (EC) cell lines, a histological subtype of germ cell tumor (GCT), to their nonmalignant caricature, specifically 6 human embryonic stem (ES) cell lines. Both cell types are readily accessible, and were purified for undifferentiated cells only. We identified a set of 28 differentially expressed genes, many of which had cancer and stemness roles. Overexpression of the recently discovered pluripotency gene NR5A2 in malignant EC cells revealed an intriguing indication of how WNT-mediated dysregulation of pluripotency is involved with malignancy. Expression of these 28 genes was further explored within 2 publically available data sets of primary EC tumors and normal testis. At the exon-level, alternative splicing events were detected in ZNF195, DNMT3B, and PMF1, and alternative promoters were detected for ASH2L and ETV5. These events were validated by reverse transcriptase-polymerase chain reaction-based methods in EC and ES lines, where the alternative splicing event in the de novo DNA methyltransferase DNMT3B may have functional consequences. In conclusion, we have identified malignancy-specific gene expression differences within a rigorous pluripotent stem cell context. These findings are of particular interest for both GCT and ES cell biology, and, in general, to the concept of CSCs.

  11. Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

    Science.gov (United States)

    Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

    2017-02-01

    Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

  12. Research of the serum level of neuron-specific enolase in children with various types of seizure

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    WANG Chun

    2012-10-01

    Full Text Available Objective To explore the relevance between the level changes of serum neuron-specific enolase (NSE and neuronal damage in various seizure types of children with epilepsy. Methods According to the classification criteria of seizure types formulated by International League Against Epilepsy (ILAE in 1981, 190 children with epilepsy were enrolled including tonic-clonic seizure group (41 cases, tonic seizure group (34 cases, clonic seizure group (22 cases, myoclonic seizure group (12 cases, atonic seizure group (17 cases, absence seizure group (22 cases, simple partial seizure group (21 cases and complex partial seizure group (21 cases, and 64 healthy children were enrolled as control group. The long-range vedio-electroencephalogram (VEEG was operated and the blood samples were collected from these cases within 72 h after their seizures. Results The serum NSE levels of epileptic children were significantly higher than control group (P = 0.000. Among these seizure groups, serum NSE in myoclonic seizure group [(32.42 ± 6.62 ng/ml] was significantly higher than the other types, except for tonic-clonic seizure group (P = 0.062. There was no significant difference among the other types (P > 0.05, for all. According to rank correlation analysis, there was positive corrlation between serum NSE levels and VEEG abnormal intensity (rs = 0.613, P = 0.000. Conclusion The serum NSE were markedly increased in children with epilepsy after seizures, suggesting that a certain degree of neuronal damage may result from seizures; the higher NSE levels were, the more serious neuronal damage caused by epileptiform discharges was. The serum NSE levels in myoclonic seizure group and tonic-clonic seizure group were significantly higher than other seizure types, indicating the two kinds of seizures may result in greater neuronal damage.

  13. The population genetics of Pseudomonas aeruginosa isolates from different patient populations exhibits high-level host specificity.

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    Rosa van Mansfeld

    Full Text Available OBJECTIVE: To determine whether highly prevalent P. aeruginosa sequence types (ST in Dutch cystic fibrosis (CF patients are specifically linked to CF patients we investigated the population structure of P. aeruginosa from different clinical backgrounds. We first selected the optimal genotyping method by comparing pulsed-field gel electrophoresis (PFGE, multilocus sequence typing (MLST and multilocus variable number tandem-repeat analysis (MLVA. METHODS: Selected P. aeruginosa isolates (n = 60 were genotyped with PFGE, MLST and MLVA to determine the diversity index (DI and congruence (adjusted Rand and Wallace coefficients. Subsequently, isolates from patients admitted to two different ICUs (n = 205, from CF patients (n = 100 and from non-ICU, non-CF patients (n = 58, of which 19 were community acquired were genotyped with MLVA to determine distribution of genotypes and genetic diversity. RESULTS: Congruence between the typing methods was >79% and DIs were similar and all >0.963. Based on costs, ease, speed and possibilities to compare results between labs an adapted MLVA scheme called MLVA9-Utrecht was selected as the preferred typing method. In 363 clinical isolates 252 different MLVA types (MTs were identified, indicating a highly diverse population (DI  = 0.995; CI  = 0.993-0.997. DI levels were similarly high in the diverse clinical sources (all >0.981 and only eight genotypes were shared. MTs were highly specific (>80% for the different patient populations, even for similar patient groups (ICU patients in two distinct geographic regions, with only three of 142 ICU genotypes detected in both ICUs. The two major CF clones were unique to CF patients. CONCLUSION: The population structure of P. aeruginosa isolates is highly diverse and population specific without evidence for a core lineage in which major CF, hospital or community clones co-cluster. The two genotypes highly prevalent among Dutch CF patients appeared unique to CF patients

  14. The learning continuum of ecology based on teachers' opinion about student's level of competence and specific pedagogical learning material

    Science.gov (United States)

    Pramesti, Indah Cahaya; Subali, Bambang

    2017-08-01

    This study aims at designing learning continuum for developing a curriculum based on teachers' opinion about student's level of competence and specific pedagogical learning material on ecological aspect targeted for students of Primary and Secondary Education. This research is a descriptive research using survey methods. The researchers conducted a census by distributing questionnaires that had been validated from the aspects of construct validity and experts judgements to 147 natural science teachers at junior high school and 134 Biology teachers at senior high school as a population throughout 4 regencies and 1 city in Yogyakarta Special Region.. Data analysis techniques used descriptive analysis. In conclusion, teacher's opinion is influenced by curriculum that exist today. According to the opinions of Natural Science teachers at Junior High School, most of the ecological aspects such as characteristics of biomes, characteristics of ecosystems, characteristics of communities, characteristics of populations, etc. should be taught in grade VII with the level of competence: to understand (C2), while Biology teachers at Senior High School state that the ecological aspect should be taught in class X with the level of competence: to understand (C2), apply (C3) and analyze (C4). Teachers should be a privy in the formulation of the curriculum, so they're not only accept and apply the existing curriculum but also give opinions to improve the curriculum, especially in terms of ecology.

  15. Are total, intensity- and domain-specific physical activity levels associated with life satisfaction among university students?

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    Željko Pedišić

    Full Text Available Thorough information about the relationship between physical activity (PA and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity, domain-specific PA (work, transport-related, domestic, and leisure-time, and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI, and self-rated health.The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years, using the International Physical Activity Questionnaire-long form and the Satisfaction with Life Scale.Higher life satisfaction was associated with female gender (β = 0.13; p = <0.001, younger age (β = -0.07; p = 0.024, higher disposable income (β = 0.10; p = 0.001, and better self-rated health (β = 0.30; p = <0.001. No significant association was found between life satisfaction and size of community (p = 0.567, smoking status (p = 0.056, alcohol consumption (p = 0.058, or BMI (p = 0.508. Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045.This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the

  16. Overcoming recurrent spontaneous abortions in women suffering from IgG subclass deficiency: high efficiency of low dose intravenous immunoglobulins treatment.

    Science.gov (United States)

    Manfredi, G; Dell'Aera, L; Liguori, R

    2015-05-01

    It's well known that iv. immunoglobulins may be useful to overcome habitual abortions, but the mechanisms at the base of a successful outcome and the likelihoods are still unknown. In one hundred and sixty women with habitual abortions and one hundred and sixty healthy mothers, we evaluated blood IgG subclasses; among the patients, sixteen merely showed IgG subclass deficiency, after leaving out any autoimmunity and/or coagulation disorders. All the patients (100%) showed IgG3, twelve (75%) IgG1, eight (50%) IgG4 and six (37,5%) IgG2 deficiency; healthy control people's IgG subclasses fell in normal range in 156 women, but just four women showed IgG2 and IgG4 deficiency with neither immune deficiency's clinical marks nor increased vulnerability to infections. All the patients were treated with whole immunoglobulins iv. infusion (200 mg/kg/monthly) all over the pregnancy. The successful pregnancy rate is very high (>90%): 100% out of women showing IgG1 (12/12), 87,5% of IgG3 (14/16), 75% of IgG4 (6/8) and 66% of IgG2 deficiency (4/6) had successful pregnancies. The Odd's Ratio between IgG subclass deficiency and recurrent abortions is 4,33 with confidence interval of 95%; chi square value is 7.68 (pIgG subclass deficiency without autoimmunity and/or coagulation disorders, likely restoring idiotype-antiidiotype network; showing evidence of IgG subclasses deficiency (mostly IgG1 and IgG3) may help identify patients who can benefit from iv. immunoglobulin treatment.

  17. Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle.

    Science.gov (United States)

    Junglen, Sandra; Korries, Marvin; Grasse, Wolfgang; Wieseler, Janett; Kopp, Anne; Hermanns, Kyra; León-Juárez, Moises; Drosten, Christian; Kümmerer, Beate Mareike

    2017-01-01

    The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome functions could generate knowledge critical to predicting arbovirus emergence. Here we isolated a novel flavivirus, termed Niénokoué virus (NIEV), from mosquitoes sampled in Côte d'Ivoire. NIEV groups with insect-specific flaviviruses (ISFs) in phylogeny and grows in insect cells but not in vertebrate cells. We generated an infectious NIEV cDNA clone and a NIEV reporter replicon to study growth restrictions of NIEV in comparison to yellow fever virus (YFV), for which the same tools are available. Efficient RNA replication of the NIEV reporter replicon was observed in insect cells but not in vertebrate cells. Initial translation of the input replicon RNA in vertebrate cells was functional, but RNA replication did not occur. Chimeric YFV carrying the envelope proteins of NIEV was recovered via electroporation in C6/36 insect cells but did not infect vertebrate cells, indicating a block at the level of entry. Since the YF/NIEV chimera readily produced infectious particles in insect cells but not in vertebrate cells despite efficient RNA replication, restriction is also determined at the level of assembly/release. Taking the results together, the ability of ISF to infect vertebrates is blocked at several levels, including attachment/entry and RNA replication as well as assembly/release. IMPORTANCE Most viruses of the genus Flavivirus, e.g., YFV and dengue virus, are mosquito borne and transmitted to vertebrates during blood feeding of mosquitoes. Within the last decade, an increasing number

  18. Serum androgens and prostate-specific antigen levels in androgenetic alopecia: is there a difference between frontal and vertex baldness?

    Science.gov (United States)

    Lis-Święty, A; Arasiewicz, H; Ranosz-Janicka, I; Brzezińska-Wcisło, L

    2017-12-13

    Androgenetic alopecia (AGA) seems to be a marker of increased risk of prostate cancer (PCa). We sought to investigate potential pathophysiological differences between frontal and vertex balding that might have the impact on the incidence of PCa. Serum concentrations of testosterone (T), dihydrotestosterone (DHT) and prostate-specific antigen (PSA) were measured in 88 subjects with AGA. We have examined sixty patients with frontal baldness and 28 patients with vertex baldness. The subgroups did not differ significantly in age, BMI and as regards age of AGA onset, duration of AGA and comorbidities. The mean value of DHT in serum of the men with vertex baldness was higher than those in the men with frontal baldness with statistical significance (P baldness may signal higher exposures to circulating DHT. Serum PSA level cannot serve as surrogate diagnostic marker of increased androgenic activity in men with AGA. © 2017 European Academy of Dermatology and Venereology.

  19. Equine insect bite hypersensitivity: immunoblot analysis of IgE and IgG subclass responses to Culicoides nubeculosus salivary gland extract.

    Science.gov (United States)

    Hellberg, W; Wilson, A D; Mellor, P; Doherr, M G; Torsteinsdottir, S; Zurbriggen, A; Jungi, T; Marti, E

    2006-09-15

    Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides and sometimes Simulium spp. The allergens causing IBH are probably salivary gland proteins from these insects, but they have not yet been identified. The aim of our study was to identify the number and molecular weight of salivary gland extract (SGE) proteins derived from Culicoides nubeculosus which are able to bind IgE antibodies (ab) from the sera of IBH-affected horses. Additionally, we sought to investigate the IgG subclass (IgGa, IgGb and IgGT) reactivity to these proteins. Individual IgE and IgG subclass responses to proteins of C. nubeculosus SGE were evaluated by immunoblot in 42 IBH-affected and 26 healthy horses belonging to different groups (Icelandic horses born in Iceland, Icelandic horses and horses from different breeds born in mainland Europe). Additionally, the specific antibody response was studied before exposure to bites of Culicoides spp. and over a period of 3 years in a cohort of 10 Icelandic horses born in Iceland and imported to Switzerland. Ten IgE-binding protein bands with approximate molecular weights of 75, 66, 52, 48, 47, 32, 22/21, 19, 15, 13/12 kDa were found in the SGE. Five of these bands bound IgE from 50% or more of the horse sera. Thirty-nine of the 42 IBH-affected horses but only 2 of the 26 healthy horses showed IgE-binding to the SGE (p<0.000001). Similarly, more IBH-affected than healthy horses had IgGa ab binding to the Culicoides SGE (19/22 and 9/22, respectively, p<0.01). Sera of IBH-affected horses contained IgE, IgGa and IgGT but not IgGb ab against significantly more protein bands than the sera of the healthy horses. The cohort of 10 Icelandic horses confirmed these results and showed that Culicoides SGE specific IgE correlates with onset of IBH. IBH-affected horses that were born in Iceland had IgGa and IgGT ab (p< or =0.01) as well as IgE ab (p=0.06) against a significantly higher number of

  20. Calculating site-specific evolutionary rates at the amino-acid or codon level yields similar rate estimates.

    Science.gov (United States)

    Sydykova, Dariya K; Wilke, Claus O

    2017-01-01

    Site-specific evolutionary rates can be estimated from codon sequences or from amino-acid sequences. For codon sequences, the most popular methods use some variation of the dN∕dS ratio. For amino-acid sequences, one widely-used method is called Rate4Site, and it assigns a relative conservation score to each site in an alignment. How site-wise dN∕dS values relate to Rate4Site scores is not known. Here we elucidate the relationship between these two rate measurements. We simulate sequences with known dN∕dS, using either dN∕dS models or mutation-selection models for simulation. We then infer Rate4Site scores on the simulated alignments, and we compare those scores to either true or inferred dN∕dS values on the same alignments. We find that Rate4Site scores generally correlate well with true dN∕dS, and the correlation strengths increase in alignments with greater sequence divergence and more taxa. Moreover, Rate4Site scores correlate very well with inferred (as opposed to true) dN∕dS values, even for small alignments with little divergence. Finally, we verify this relationship between Rate4Site and dN∕dS in a variety of empirical datasets. We conclude that codon-level and amino-acid-level analysis frameworks are directly comparable and yield very similar inferences.

  1. Analysis of the epidermal growth factor receptor specific transcriptome: effect of receptor expression level and an activating mutation.

    Science.gov (United States)

    Pedersen, Mikkel W; Pedersen, Nina; Damstrup, Lars; Villingshøj, Mette; Sønder, Søren U; Rieneck, Klaus; Bovin, Lone F; Spang-Thomsen, Mogens; Poulsen, Hans S

    2005-10-01

    Overexpression or expression of activating mutations of the epidermal growth factor receptor (EGFR) is common in cancer and correlates with neoplastic progression. The present study employed Affymetrix oligonucleotide arrays to profile genes induced by ligand-activated EGFR with the receptor either moderately expressed or overexpressed at an in-itself transforming level. These changes were compared to those induced by the naturally occurring constitutively active variant EGFRvIII. This study provides novel insight on the activities and mechanisms of EGFRvIII and EGFR mediated transformation, as genes encoding proteins with functions in promoting cell proliferation, invasion, antiapoptosis, and angiogenesis featured prominently in the EGFRvIII- and EGFR-expressing cells. Surprisingly, it was found that ligand-activated EGFR induced the expression of a large group of genes known to be inducible by interferons. Expression of this module was absent in the EGFRvIII-expressing cell line and the parental cell line. Treatment with the specific EGFR inhibitor AG1478 indicated that the regulations were primary, receptor-mediated events. Furthermore, activation of this module correlated with activation of STAT1 and STAT3. The results thus demonstrate that ligand-activated EGFR at different expression levels results in different kinetics of signaling and induction of gene expression. In addition, the constitutively active variant EGFRvIII seems to activate only a subset of signal pathways and induce a subset of genes as compared to the ligand-activated EGFR. Copyright (c) 2005 Wiley-Liss, Inc.

  2. Cognitive Biases for Social Alcohol-Related Pictures and Alcohol Use in Specific Social Settings: An Event-Level Study.

    Science.gov (United States)

    Groefsema, Martine; Engels, Rutger; Kuntsche, Emmanuel; Smit, Koen; Luijten, Maartje

    2016-09-01

    Alcohol use occurs mainly among friends, in social contexts, and for social reasons. Moreover, cognitive biases, such as attentional and approach biases, have repeatedly been associated with alcohol use. This study aimed to test whether nondependent drinkers display cognitive biases for social alcohol-related (SA) pictures and whether these biases are associated with alcohol use in social drinking contexts. The visual dot probe task and stimulus-response compatibility tasks were used to measure attentional and approach biases for alcohol-related pictures at baseline. Event-level alcohol use was measured using Ecological Momentary Assessments via personal smartphones. One hundred and ninety-two young adults (51.6% men; Mage  = 20.73) completed the study, resulting in 11,257 assessments conducted on Thursday, Friday, and Saturday evenings for 5 consecutive weeks. While no overall attentional bias for alcohol-related pictures was found, young adults showed an approach bias for both social and nonsocial alcohol-related pictures. Multilevel models revealed no direct association between cognitive biases for alcohol-related pictures and alcohol use. However, higher levels of attentional bias for SA pictures were associated with more drinking when individuals were surrounded by a greater number of friends of opposite gender. Higher levels of an approach bias for SA pictures were associated with more drinking in women surrounded by a greater number of friends of the same gender. In a nondependent sample, cognitive biases for SA pictures could not be associated with drinking directly. However, a cognitive bias for SA pictures moderated the association between alcohol use and number of friends present. As most observed effects were gender and situation specific, replication of these effects is warranted. Copyright © 2016 by the Research Society on Alcoholism.

  3. Increasing level of prostate-specific antigen and prostate cancer risk factors among 193 men examined in screening procedure.

    Science.gov (United States)

    Opalińska, Edyta; Michalak, Anna; Stoma, Filip; Latalski, Maciej; Goniewicz, Mariusz

    2003-01-01

    Prostate cancer is one of the most common cancers in men, therefore has become recently an essential problem of public health. The factors influencing cancer include: androgens metabolism disorders, diabetes mellitus, overweight and obesity, smoking, alcohol and black coffee intake, diet rich in saturated fats and poor in unsaturated, lack of physical activity, geographical zone, race, such carcinogenic substances as: cadmium, materials used in rubber, painting, printing, ship industry etc., contagious factors and also older age and a positive family history of the disease. To diagnose prostate cancer in its early stage such screening procedures as physical examination--digital rectal exam (DRE) and determination of prostate-specific antigen (PSA) level in blood serum are used. The aim of the study was to assess prostate cancer risk factors occurrence in the examined 193 men, aged 50-70 years, who reported to urology outpatient department at Clinical Hospital in Lublin, measure the PSA level in blood serum and examine the correlation between them. Respondents filled in a questionnaire about the presence of prostate cancer risk factors and urogenital symptoms. The questionnaire was completed with DRE and PSA measurement. The results led us to the following conclusions: 1/ in the studied population elevated PSA level is determined in 3.1% of 193 examined men, 2/ increased PSA occurs mainly in men from rural areas, with elementary education, divorced, older (>60 years), using fat-rich diet, smokers, black coffee drinkers, with overweight or obesity and non diabetic, 3/ a combination of PSA test with DRE seems to be useful and rather cheap for the detection of prostate cancer in the early stage of its development.

  4. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    DEFF Research Database (Denmark)

    Van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel crea...

  5. Prevalence of Bronchiectasis in Asthma according to Oral Steroid Requirement: Influence of Immunoglobulin Levels

    Directory of Open Access Journals (Sweden)

    Manel Luján

    2013-01-01

    Full Text Available Purpose. To establish the prevalence of bronchiectasis in asthma in relation to patients’ oral corticosteroid requirements and to explore whether the increased risk is due to blood immunoglobulin (Ig concentration. Methods. Case-control cross-sectional study, including 100 sex- and age-matched patients, 50 with non-steroid-dependent asthma (NSDA and 50 with steroid-dependent asthma (SDA. Study protocol: (a measurement of Ig and gG subclass concentration; (b forced spirometry; and (c high-resolution thoracic computed tomography. When bronchiectasis was detected, a specific etiological protocol was applied to establish its etiology. Results. The overall prevalence of bronchiectasis was 12/50 in the SDA group and 6/50 in the NSDA group (p=ns. The etiology was documented in six patients (four NSDA and two SDA. After excluding these patients, the prevalence of bronchiectasis was 20% (10/50 in the SDA group and 2/50 (4% in the NSDA group (P<0.05. Patients with asthma-associated bronchiectasis presented lower FEV1 values than patients without bronchiectasis, but the levels of Ig and subclasses of IgG did not present differences. Conclusions. Steroid-dependent asthma seems to be associated with a greater risk of developing bronchiectasis than non-steroid-dependent asthma. This is probably due to the disease itself rather than to other influencing factors such as immunoglobulin levels.

  6. DMD transcripts in CRL-2061 rhabdomyosarcoma cells show high levels of intron retention by intron-specific PCR amplification.

    Science.gov (United States)

    Niba, Emma Tabe Eko; Yamanaka, Ryo; Rani, Abdul Qawee Mahyoob; Awano, Hiroyuki; Matsumoto, Masaaki; Nishio, Hisahide; Matsuo, Masafumi

    2017-01-01

    The DMD gene encoding dystrophin is mutated in Duchenne muscular dystrophy, a fatal progressive muscle wasting disease. DMD has also been shown to act as a tumor suppressor gene. Rhabdomyosarcoma (RMS) is a mesodermal sarcoma that shares characteristics of skeletal muscle precursors. Products of the DMD gene in RMS have not yet been fully clarified. Here, DMD products were analyzed in CRL-2061 cells established from alveolar RMS. The 14-kb long DMD cDNA was PCR amplified as 20 separated fragments, as were nine short intron regions. Dystrophin was analyzed by Western blotting using an antibody against the C-terminal region of dystrophin. Sixteen of the 20 DMD cDNA fragments could be amplified from CRL-2061 cells as muscle cDNA. Three fragments included aberrant gene products, including one in which exon 71 was omitted and one each with retention of introns 40 and 58. In one fragment, extending from exon 70 to 79, no normally spliced product was obtained. Rather, six alternatively spliced products were identified, including a new product deleting exon 73, with the most abundant product showing deletion of exon 78. Although dystrophin expression was expected in CRL-2061 cells, western blotting of cell lysates showed no evidence of dystrophin, suggesting that translation of full-length DMD mRNA was inhibited by intron retention that generated a premature stop codon. Intron specific PCR amplification of nine short introns, showed retention of introns 40, 58, and 70, which constituted about 60, 25 and 9%, respectively, of the total PCR amplified products. The most abundant DMD transcript contained two abnormalities, intron 40 retention and exon 78 skipping. Intron-specific PCR amplification showed that DMD transcripts contained high levels of introns 40, 58 and 70. Retention of these introns may have been responsible for the lack of dystrophin expression by CRL-2061 cells, thereby abolishing the tumor suppressor activity of dystrophin.

  7. Allocation Mechanism Of Equalization Fund In Indonesia: Current Condition And Alternative Proposals Of Specific Grant In Sub National Level

    OpenAIRE

    Kodrat Wibowo; Bagdja Muljarijadi; Rullan Rinaldi

    2011-01-01

    As one of central government’s tools to equalize fiscal disparities between regions in Indonesia, current allocation mechanism of intergovernmental grant has been a major issue in regional public finance. Specifically, specific grant (DAK) was proven not much more specific than general block grant (DAU). Furthermore, the effectiveness of the specific grant allocation mechanism on poverty alleviation, economic growth, unemployment, and several others specific indicator has not met the desirabl...

  8. Pharmacological levels of Withaferin A (Withania somnifera trigger clinically relevant anticancer effects specific to triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Katarzyna Szarc vel Szic

    Full Text Available Withaferin A (WA isolated from Withania somnifera (Ashwagandha has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8, cell adhesion molecules (integrins, laminins, pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1. In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors

  9. Pharmacological Levels of Withaferin A (Withania somnifera) Trigger Clinically Relevant Anticancer Effects Specific to Triple Negative Breast Cancer Cells

    Science.gov (United States)

    Szarc vel Szic, Katarzyna; Op de Beeck, Ken; Ratman, Dariusz; Wouters, An; Beck, Ilse M.; Declerck, Ken; Heyninck, Karen; Fransen, Erik; Bracke, Marc; De Bosscher, Karolien; Lardon, Filip; Van Camp, Guy; Berghe, Wim Vanden

    2014-01-01

    Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy

  10. Quantitative analysis of commensal Escherichia coli populations reveals host-specific enterotypes at the intra-species level.

    Science.gov (United States)

    Smati, Mounira; Clermont, Olivier; Bleibtreu, Alexandre; Fourreau, Frédéric; David, Anthony; Daubié, Anne-Sophie; Hignard, Cécile; Loison, Odile; Picard, Bertrand; Denamur, Erick

    2015-08-01

    The primary habitat of the Escherichia coli species is the gut of warm-blooded vertebrates. The E. coli species is structured into four main phylogenetic groups A, B1, B2, and D. We estimated the relative proportions of these phylogroups in the feces of 137 wild and domesticated animals with various diets living in the Ile de France (Paris) region by real-time PCR. We distinguished three main clusters characterized by a particular abundance of two or more phylogroups within the E. coli animal commensal populations, which we called "enterocolitypes" by analogy with the enterotypes defined in the human gut microbiota at the genus level. These enterocolitypes were characterized by a dominant (>50%) B2, B1, or A phylogroup and were associated with different host species, diets, and habitats: wild and herbivorous species (wild rabbits and deer), domesticated herbivorous species (domesticated rabbits, horses, sheep, and cows), and omnivorous species (boar, pigs, and chickens), respectively. By analyzing retrospectively the data obtained using the same approach from 98 healthy humans living in Ile de France (Smati et al. 2013, Appl. Environ. Microbiol. 79, 5005-5012), we identified a specific human enterocolitype characterized by the dominant and/or exclusive (>90%) presence of phylogroup B2. We then compared B2 strains isolated from animals and humans, and revealed that human and animal strains differ regarding O-type and B2 subgroup. Moreover, two genes, sfa/foc and clbQ, were associated with the exclusive character of strains, observed only in humans. In conclusion, a complex network of interactions exists at several levels (genus and intra-species) within the intestinal microbiota. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  11. Biochemical Characterization of CPS-1, a Subclass B3 Metallo-β-Lactamase from a Chryseobacterium piscium Soil Isolate

    DEFF Research Database (Denmark)

    Gudeta, Dereje Dadi; Pollini, Simona; Docquier, Jean-Denis

    2016-01-01

    CPS-1 is a subclass B3 metallo-β-lactamase from a Chryseobacterium piscium isolated from soil, showing 68 % amino acid identity to GOB-1 enzyme. CPS-1 was overproduced in Escherichia coli Rosetta (DE3), purified by chromatography and biochemically characterized. This enzyme exhibits a broad...

  12. Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Subclasses

    Directory of Open Access Journals (Sweden)

    Siti Zuraidah Mohamad Zobir

    2016-01-01

    Full Text Available Traditional Chinese medicine (TCM still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs of 45 TCM therapeutic action (subclasses from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (subclass. The MOA of a (subclass was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2 and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR, and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, “the foundation of acquired constitution” that includes spleen and stomach. In short, the TCM (subclasses, in many cases share similar targets/pathways despite having different indications.

  13. Common, low-frequency, and rare genetic variants associated with lipoprotein subclasses and triglyceride measures in Finnish men from the METSIM study.

    Directory of Open Access Journals (Sweden)

    James P Davis

    2017-10-01

    Full Text Available Lipid and lipoprotein subclasses are associated with metabolic and cardiovascular diseases, yet the genetic contributions to variability in subclass traits are not fully understood. We conducted single-variant and gene-based association tests between 15.1M variants from genome-wide and exome array and imputed genotypes and 72 lipid and lipoprotein traits in 8,372 Finns. After accounting for 885 variants at 157 previously identified lipid loci, we identified five novel signals near established loci at HIF3A, ADAMTS3, PLTP, LCAT, and LIPG. Four of the signals were identified with a low-frequency (0.005subclass traits. 30 established lipid-associated loci had a stronger association for a subclass trait than any conventional trait. These novel association signals provide further insight into the molecular basis of dyslipidemia and the etiology of metabolic disorders.

  14. Chronic lymphocytic leukemia patients have a preserved cytomegalovirus-specific antibody response despite progressive hypogammaglobulinemia.

    Directory of Open Access Journals (Sweden)

    Katrina Vanura

    Full Text Available Chronic lymphocytic leukemia (CLL is characterized by progressive hypogammaglobulinemia predisposing affected patients to a variety of infectious diseases but paradoxically not to cytomegalovirus (CMV disease. Moreover, we found reactivity of a panel of CLL recombinant antibodies (CLL-rAbs encoded by a germ-line allele with a single CMV protein, pUL32, despite differing antibody binding motifs. To put these findings into perspective, we studied prospectively relative frequency of viremia, kinetics of total and virus-specific IgG over time, and UL32 genetic variation in a cohort of therapy-naive patients (n=200. CMV-DNA was detected in 3% (6/200 of patients. The decay of total IgG was uniform (mean, 0.03; SD, 0.03 and correlated with that of IgG subclasses 1-4 in the paired samples available (n=64; p<0.001. Total CMV-specific IgG kinetics were more variable (mean, 0,02; SD, 0,06 and mean decay values differed significantly from those of total IgG (p=0.034. Boosts of CMV-specific antibody levels were observed in 49% (22/45 of CMV-seropositive patients. In contrast, VZV- and EBV-specific IgG levels decayed in parallel with total IgG levels (p=0.003 and p=0.001, respectively. VZV-specific IgG even became undetectable in 18% (9/50 of patients whereas CMV-specific ones remained detectable in all seropositive patients. The observed CMV-specific IgG kinetics were predicated upon the highly divergent kinetics of IgG specific for individual antigens - glycoprotein B-specific IgG were boosted in 51% and pUL32-specific IgG in 32% of patients. In conclusion, CLL patients have a preserved CMV-specific antibody response despite progressive decay of total IgG and IgG subclasses. CMV-specific IgG levels are frequently boosted in contrast to that of other herpesviruses indicative of a higher rate of CMV reactivation and antigen-presentation. In contrast to the reactivity of multiple different CLL-rAbs with pUL32, boosts of humoral immunity are triggered

  15. The effect of statins on serum prostate specific antigen levels in a cohort of airline pilots: a preliminary report.

    Science.gov (United States)

    Cyrus-David, Mfon S; Weinberg, Armin; Thompson, Timothy; Kadmon, Dov

    2005-06-01

    Reports of the effect of treatment with statins on prostate cancer risk are inconsistent. We performed a pilot study to assess the effect of statin treatment on a surrogate marker for prostate cancer risk, that is serum prostate specific antigen (PSA), in a cohort of airline pilots from 1992 to 2001. Subject medical records were abstracted for data on age, PSA testing, hyperlipidemia and treatment with statins. The treatment group was composed of 15 men with hypercholesterolemia who received statins and the comparison group of 85 with normal serum lipid levels during the review period. The mean +/- SD and the Wilcoxon rank sum test were used for analyses. Serum PSA was significantly higher in the treatment group at baseline relative to the comparison group (p = 0.05). Interestingly there was no significant difference between the groups on subsequent followup. There was a 41.6% decrease in mean serum PSA in the treated group by visit 4. Simultaneously mean serum PSA increased by 38% in the untreated group. Our results suggest that treatment with statins may lower serum PSA with time. These results must be confirmed in a larger study population while controlling for potential confounders. If validated, our observation provides a rationale for further studies of the role of this class of drugs for prostate cancer chemoprevention.

  16. Elapid snake venom analyses show the specificity of the peptide composition at the level of genera Naja and Notechis.

    Science.gov (United States)

    Munawar, Aisha; Trusch, Maria; Georgieva, Dessislava; Hildebrand, Diana; Kwiatkowski, Marcel; Behnken, Henning; Harder, Sönke; Arni, Raghuvir; Spencer, Patrick; Schlüter, Hartmut; Betzel, Christian

    2014-02-28

    Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms-that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes.

  17. Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice.

    Science.gov (United States)

    Yang, Hua; Zhang, Mengjie; Shi, Jiahao; Zhou, Yunhe; Wan, Zhipeng; Wang, Yicheng; Wan, Yinghan; Li, Jun; Wang, Zhugang; Fei, Jian

    2017-01-01

    Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, could address questions regarding presynaptic alterations that contribute to the etiopathophysiology of SZ and help to consummate the pre- and postsynaptic glutamatergic pathogenesis of the illness.

  18. Low-level neural auditory discrimination dysfunctions in specific language impairment-A review on mismatch negativity findings.

    Science.gov (United States)

    Kujala, Teija; Leminen, Miika

    2017-12-01

    In specific language impairment (SLI), there is a delay in the child's oral language skills when compared with nonverbal cognitive abilities. The problems typically relate to phonological and morphological processing and word learning. This article reviews studies which have used mismatch negativity (MMN) in investigating low-level neural auditory dysfunctions in this disorder. With MMN, it is possible to tap the accuracy of neural sound discrimination and sensory memory functions. These studies have found smaller response amplitudes and longer latencies for speech and non-speech sound changes in children with SLI than in typically developing children, suggesting impaired and slow auditory discrimination in SLI. Furthermore, they suggest shortened sensory memory duration and vulnerability of the sensory memory to masking effects. Importantly, some studies reported associations between MMN parameters and language test measures. In addition, it was found that language intervention can influence the abnormal MMN in children with SLI, enhancing its amplitude. These results suggest that the MMN can shed light on the neural basis of various auditory and memory impairments in SLI, which are likely to influence speech perception. Copyright © 2017. Published by Elsevier Ltd.

  19. Elapid Snake Venom Analyses Show the Specificity of the Peptide Composition at the Level of Genera Naja and Notechis

    Science.gov (United States)

    Munawar, Aisha; Trusch, Maria; Georgieva, Dessislava; Hildebrand, Diana; Kwiatkowski, Marcel; Behnken, Henning; Harder, Sönke; Arni, Raghuvir; Spencer, Patrick; Schlüter, Hartmut; Betzel, Christian

    2014-01-01

    Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms—that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes. PMID:24590383

  20. Sequential Prediction of Literacy Achievement for Specific Learning Disabilities Contrasting in Impaired Levels of Language in Grades 4 to 9.

    Science.gov (United States)

    Sanders, Elizabeth A; Berninger, Virginia W; Abbott, Robert D

    2017-02-01

    Sequential regression was used to evaluate whether language-related working memory components uniquely predict reading and writing achievement beyond cognitive-linguistic translation for students in Grades 4 through 9 ( N = 103) with specific learning disabilities (SLDs) in subword handwriting (dysgraphia, n = 25), word reading and spelling (dyslexia, n = 60), or oral and written language (oral and written language learning disabilities, n = 18). That is, SLDs are defined on the basis of cascading level of language impairment (subword, word, and syntax/text). A five-block regression model sequentially predicted literacy achievement from cognitive-linguistic translation (Block 1); working memory components for word-form coding (Block 2), phonological and orthographic loops (Block 3), and supervisory focused or switching attention (Block 4); and SLD groups (Block 5). Results showed that cognitive-linguistic translation explained an average of 27% and 15% of the variance in reading and writing achievement, respectively, but working memory components explained an additional 39% and 27% of variance. Orthographic word-form coding uniquely predicted nearly every measure, whereas attention switching uniquely predicted only reading. Finally, differences in reading and writing persisted between dyslexia and dysgraphia, with dysgraphia higher, even after controlling for Block 1 to 4 predictors. Differences in literacy achievement between students with dyslexia and oral and written language learning disabilities were largely explained by the Block 1 predictors. Applications to identifying and teaching students with these SLDs are discussed.

  1. Elapid Snake Venom Analyses Show the Specificity of the Peptide Composition at the Level of Genera Naja and Notechis

    Directory of Open Access Journals (Sweden)

    Aisha Munawar

    2014-02-01

    Full Text Available Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms—that of the African cobra, N. m. mossambica (genus Naja, and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis. A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F cytotoxins, bradykinin-potentiating peptides (BPPs and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467 from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes.

  2. Level of job satisfaction amongst nurses in the North-West Province, South Africa: Post occupational specific dispensation

    Directory of Open Access Journals (Sweden)

    Sisinyana H. Khunou

    2016-02-01

    Full Text Available Background: Job satisfaction and burnout have been recurring problems amongst nurses in the Republic of South Africa (RSA. As a result, nurses are still leaving the rural public sector in search of lucrative work at the urban and private sectors and in developed countries. Accordingly, Occupational Specific Dispensation (OSD was introduced as a strategy to ircumvent the problem. However, since the implementation of OSD in 2007, there have been no studies conducted regarding the level of job satisfaction amongst nurses after the implementation of OSD in the North-West Province, especially because each province has its own challenges that are unique to the area.Objectives: The study had two objectives: to describe the level of job satisfaction amongstprofessional and other category nurses (OCNs at a public hospital in the North-West Provinceand describe the perceptions of nurses about OSD and their intention to continue working inthe hospital.Method: A quantitative descriptive cross-sectional design was used. Stratified random sampling was used to select a sample of 92 professional nurses (PNs, 90 enrolled nurses and enrolled nursing assistants (Nursing Act 2005, which made a total of 182 participants. For the purpose of the study, the enrolled nurses and enrolled nursing assistants were referred to as OCNs. Data were collected using the Minnesota Satisfaction Questionnaire–short form and OSD statements and analysed with Statistical Package for Social Science (SPSS, version 18.Results: The majority of PNs (79.3%, n = 73 and OCNs (86.7%, n = 77 were dissatisfied with the working conditions and salary: PNs (80.4%, n = 74 and OCNs (87.8%, n = 79. The nurses mostly discredited the current state of the OSD implementation. Majority of the PNs (84%, n = 77 and OCNs (91%, n = 82 disagreed with the statement that ‘level of job satisfaction has improved after the implementation of OSD’.Conclusions: The National Department of Health should consider a

  3. Use of tactual materials on the achievement of content specific vocabulary and terminology acquisition within an intermediate level science curriculum

    Science.gov (United States)

    Terry, Brian H.

    In this quasi-experimental study, the researcher investigated the effectiveness of three tactual strategies and one non-tactual strategy of content specific vocabulary acquisition. Flash cards, task cards, and learning wheels served as the tactual strategies, and vocabulary review sheets served as a non-tactual strategy. The sample (n=85) consisted of all middle school students in a small high performing middle school located in the northern suburbs of New York City. All of the vocabulary words and terms came from the New York State Intermediate Level Science Core Curriculum. Pre-tests and post-tests were used to collect the data. A repeated measures ANOVA was conducted on the gain scores from each of the treatments. Multiple paired sample t-tests were conducted to analyze the results. Repeated measures ANOVAs were used to determine if there was a variance between the academic achievement levels of the students, gender, and grade level for each of the treatments. All of the treatments significantly improved the science achievement of the students, but significance was found between them. Significance was found between the achievement groups with the above average students attaining a higher mean on the pre-test and post-test for each treatment, whereas the below average students had the lowest mean on both assessments. The sixth grade students showed significant improvement over the seventh grade students while using the flash cards (p=.004) and learning wheel (p=.007). During the learning wheel treatment, the males scored significantly better (p=.021) than the females on the pre-test and post-test. During the worksheet treatment, significance (p=.034) was found between gender and achievement group. The below average male students had the greatest gain from the pre-test to the post-test, but the post-test mean was still the lowest of the groups. Limitations, implications for future research and current practice are discussed. Key words are: flash cards, task cards

  4. Structure determination of a tetrahydro-beta-carboline of arthropod origin: a novel alkaloid-toxin subclass from the web of spider Nephila clavipes.

    Science.gov (United States)

    Marques, Maurício Ribeiro; Mendes, Maria Anita; Tormena, Cláudio Francisco; Souza, Bibiana M; Cesar, Lílian Mari Marcondes; Rittner, Roberto; Palma, Mario S

    2005-04-01

    The orb-web spiders are polyphagous animals in which the web plays a very important role in the capture of preys; oily droplets usually cover the capture-web of the spider Nephila clavipes and seem to be of great importance for prey capture. The knowledge of the chemical composition of these droplets is necessary to understand the function of this adhesive material in web mechanics and prey capture. A novel subclass of spider toxins, tetrahydro-beta-carboline, was identified among the weaponry of compounds present inside of oily droplets. This type of alkaloid is not common among the natural compounds of spider toxins. Apparently, when the prey arthropods get caught by the spider web, their bodies are covered with many adhesive oily droplets, which disrupt delivering the tetrahydro-beta-carboline to the direct contact with the prey integument. Toxicity assays demonstrated a potent lethal effect of the alkaloid toxin to the spider preys; topical applications of the tetrahydro-beta-carboline at first caused clear signs of neurotoxicity, followed by the death of preys. The structure of the major component, a tetrahydro-beta-carboline, among the alkaloid toxins was elucidated by means of UV spectrophotometry, ESI mass spectrometry, 1H-NMR spectroscopy, and high-resolution mass spectrometry. The structure of the natural toxin was determined as 1-(2-guanidinoethyl)-1,2,3,4-tetrahydro-6-hydroxymethyl)-beta-carboline; the investigation of the pharmacological properties and neurotoxic actions of this compound may be used in the future as reference for the development of new drugs to be applied at level of pest control in agriculture.

  5. Correlation of circulating CD133+ progenitor subclasses with a mild phenotype in Duchenne muscular dystrophy patients.

    Directory of Open Access Journals (Sweden)

    Chiara Marchesi

    2008-05-01

    Full Text Available Various prognostic serum and cellular markers have been identified for many diseases, such as cardiovascular diseases and tumor pathologies. Here we assessed whether the levels of certain stem cells may predict the progression of Duchenne muscular dystrophy (DMD.The levels of several subpopulations of circulating stem cells expressing the CD133 antigen were determined by flow cytometry in 70 DMD patients. The correlation between the levels and clinical status was assessed by statistical analysis. The median (+/-SD age of the population was 10.66+/-3.81 (range 3 to 20 years. The levels of CD133+CXCR4+CD34- stem cells were significantly higher in DMD patients compared to healthy controls (mean+/-standard deviation: 17.38+/-1.38 vs. 11.0+/-1.70; P = 0.03 with a tendency towards decreased levels in older patients. Moreover, the levels of this subpopulation of cells correlated with the clinical condition. In a subgroup of 19 DMD patients after 24 months of follow-up, increased levels of CD133+CXCR4+CD34- cells was shown to be associated with a phenotype characterised by slower disease progression. The circulating CD133+CXCR4+CD34- cells in patients from different ages did not exhibit significant differences in their myogenic and endothelial in vitro differentiation capacity.Our results suggest that levels of CD133+CXCR4+CD34- could function as a new prognostic clinical marker for the progression of DMD.

  6. Gestational age-specific reference intervals for serum thyroid hormone levels in a multi-ethnic population.

    Science.gov (United States)

    Ho, Clement K M; Tan, Edward T H; Ng, Mor Jack; Yeo, George S H; Chern, Bernard; Tee, Nancy W S; Kwek, Kenneth Y C; Tan, Kok Hian

    2017-10-26

    Thyroid disorders are common during pregnancy. To date, a limited number of studies have reported differences in serum thyroid hormone concentrations between different ethnic groups. We sought to establish gestational age-specific reference intervals for serum levels of thyroid hormones in a multi-ethnic population and investigate whether separate reference intervals should be used for different ethnic groups. A total of 926 pregnant women from multiple ethnic groups attended four separate study visits spanning the three trimesters. Venous blood samples were taken at 9 to 14 weeks, 18 to 22 weeks, 28 to 32 weeks, and 34 to 39 weeks of gestation. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3), total T4, total T3, thyroid peroxidase antibody and thyroglobulin antibody were measured using Abbott Architect immunoassays. A total of 562 women with singleton pregnancies were found to be negative for both thyroid autoantibodies at all four study visits and thus included in the reference sample group for the establishment of reference intervals (2.5th to 97.5th percentiles). Reference intervals for serum thyroid hormones at 9-14 weeks of gestation derived from the combined group of pregnant women are as follows: TSH, 0.01-2.39 mIU/L; free T4, 11.4-19.5 pmol/L; free T3, 4.23-6.69 pmol/L; total T4, 77.8-182.4 nmol/L; total T3, 1.39-2.97 nmol/L. No differences in the five thyroid parameters' reference intervals are detectable among the ethnic groups except that at study visit 3 (28-32 weeks of gestation), the upper reference limit of total T3 in Malays (3.20 nmol/L; 90% CI, 2.99-3.76 nmol/L) is slightly higher than that in Chinese (2.86 nmol/L; 90% CI, 2.70-2.98 nmol/L). The findings from this study on a multi-ethnic cohort highlight the importance of establishing locally derived and gestational age-specific reference intervals for the five thyroid hormone parameters.

  7. Blueprint for an automated specific decision support system for countering anthelmintic resistance in Haemonchus spp. at farm level.

    Science.gov (United States)

    van Wyk, J A; Reynecke, D P

    2011-05-11

    This article is the first of a series aimed at developing specific decision support software for on-farm optimisation of sustainable integrated management of haemonchosis. It contains a concept framework for such a system for use by farmers and/or their advisors but, as reported in the series, only the first steps have been taken on the road to achieve this goal. Anthelmintic resistance has reached such levels of prevalence and intensity that recently it evoked the comment that for small ruminants the final phase of resistance was being entered, without effective chemotherapeutic agents on some farms with which to control worms at a level commensurate with profitable animal production. In addition, in the case of cattle, a recent survey in New Zealand showed 92% of worm populations to be resistant to at least one anthelmintic group. Ironically, new technology, such as the FAMACHA(©) system which was devised for sustainable management of haemonchosis, is at present being adopted relatively slowly by the majority of farmers and it is suggested that an important reason for this is the complexity of integration of new methods with epidemiological factors. The alternatives to the simple drenching programmes of the past are not only more difficult to manage, but are also more labour-intensive. The problem is further complicated by a progressive global shortage of persons with the necessary experience to train farmers in the new methods. The opinion is advanced that only computerised, automated decision support software can optimise the integration of the range of factors (such as rainfall, temperature, host age and reproductive status, pasture type, history of host and pasture infection, and anthelmintic formulation) for more sustainable worm management than is obtainable with present methods. Other than the conventional method (in which prospective analysis of laboratory and other data is mainly used to suggest when strategic prophylactic drenching of all animals for

  8. Soil Moisture Active Passive (SMAP) Mission Level 4 Surface and Root Zone Soil Moisture (L4_SM) Product Specification Document

    Science.gov (United States)

    Reichle, Rolf H.; Ardizzone, Joseph V.; Kim, Gi-Kong; Lucchesi, Robert A.; Smith, Edmond B.; Weiss, Barry H.

    2015-01-01

    This is the Product Specification Document (PSD) for Level 4 Surface and Root Zone Soil Moisture (L4_SM) data for the Science Data System (SDS) of the Soil Moisture Active Passive (SMAP) project. The L4_SM data product provides estimates of land surface conditions based on the assimilation of SMAP observations into a customized version of the NASA Goddard Earth Observing System, Version 5 (GEOS-5) land data assimilation system (LDAS). This document applies to any standard L4_SM data product generated by the SMAP Project. The Soil Moisture Active Passive (SMAP) mission will enhance the accuracy and the resolution of space-based measurements of terrestrial soil moisture and freeze-thaw state. SMAP data products will have a noteworthy impact on multiple relevant and current Earth Science endeavors. These include: Understanding of the processes that link the terrestrial water, the energy and the carbon cycles, Estimations of global water and energy fluxes over the land surfaces, Quantification of the net carbon flux in boreal landscapes Forecast skill of both weather and climate, Predictions and monitoring of natural disasters including floods, landslides and droughts, and Predictions of agricultural productivity. To provide these data, the SMAP mission will deploy a satellite observatory in a near polar, sun synchronous orbit. The observatory will house an L-band radiometer that operates at 1.40 GHz and an L-band radar that operates at 1.26 GHz. The instruments will share a rotating reflector antenna with a 6 meter aperture that scans over a 1000 km swath.

  9. Dynamic compartment specific changes in glutathione and ascorbate levels in Arabidopsis plants exposed to different light intensities

    Science.gov (United States)

    2013-01-01

    Background Excess light conditions induce the generation of reactive oxygen species (ROS) directly in the chloroplasts but also cause an accumulation and production of ROS in peroxisomes, cytosol and vacuoles. Antioxidants such as ascorbate and glutathione occur in all cell compartments where they detoxify ROS. In this study compartment specific changes in antioxidant levels and related enzymes were monitored among Arabidopsis wildtype plants and ascorbate and glutathione deficient mutants (vtc2-1 and pad2-1, respectively) exposed to different light intensities (50, 150 which was considered as control condition, 300, 700 and 1,500 μmol m-2 s-1) for 4 h and 14 d. Results The results revealed that wildtype plants reacted to short term exposure to excess light conditions with the accumulation of ascorbate and glutathione in chloroplasts, peroxisomes and the cytosol and an increased activity of catalase in the leaves. Long term exposure led to an accumulation of ascorbate and glutathione mainly in chloroplasts. In wildtype plants an accumulation of ascorbate and hydrogen peroxide (H2O2) could be observed in vacuoles when exposed to high light conditions. The pad2-1 mutant reacted to long term excess light exposure with an accumulation of ascorbate in peroxisomes whereas the vtc2-1 mutant reacted with an accumulation of glutathione in the chloroplasts (relative to the wildtype) and nuclei during long term high light conditions indicating an important role of these antioxidants in these cell compartments for the protection of the mutants against high light stress. Conclusion The results obtained in this study demonstrate that the accumulation of ascorbate and glutathione in chloroplasts, peroxisomes and the cytosol is an important reaction of plants to short term high light stress. The accumulation of ascorbate and H2O2 along the tonoplast and in vacuoles during these conditions indicates an important route for H2O2 detoxification under these conditions. PMID

  10. Site-specific evaluation of safety issues for high-level waste disposal in crystalline rocks. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Jobmann, M. (ed.) [DBE Technology GmbH, Peine (Germany)

    2016-03-31

    In the past, German research and development (R and D) activities regarding the disposal of radioactive waste, including spent nuclear fuel, focused mainly on domal rock salt because rock salt was the preferred host rock formation. In addition, generic R and D work regarding alternative host rocks (crystalline rocks and claystones) had been performed as well for a long time but with lower intensity. Around the year 2000, as a consequence of the moratorium on the Gorleben site, the Federal Government decided to have argillaceous rocks and crystalline rocks investigated in more detail. As Germany does not have any underground research and host rock characterization facilities, international cooperation received a high priority in the German R and D programme for high-level waste (HLW) disposal in order to increase the knowledge regarding alternative host rocks. Major cornerstones of the cooperation are joint projects and experiments conducted especially in underground research laboratories (URL) in crystalline rocks at the Grimsel Test Site (Switzerland) and the Hard Rock Laboratory (HRL) Aespoe(Sweden) and in argillaceous rocks at the URL Mont Terri (Switzerland) and Bure (France). In 2001, the topic of radioactive waste disposal was integrated into the agreement between the former Russian Ministry of Atomic Energy (Minatom, now Rosatom) and the German Ministry of Labor (BMWA), now Ministry of Economic Affairs and Energy (BMWi), on cooperation regarding R and D on the peaceful utilization of nuclear power (agreement on ''Wirtschaftlich-Technische Zusammenarbeit'' WTZ). The intention was to have a new and interesting opportunity for international R and D cooperation regarding HLW disposal in crystalline rocks and the unique possibility to perform site-specific work, to test the safety demonstration tools available, and to expand the knowledge to all aspects specific to these host rocks. Another motivation for joining this cooperation was the

  11. A solid dietary fat containing fish oil redistributes lipoprotein subclasses without increasing oxidative stress in men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Hellgren, Lars; Petersen, M.

    2004-01-01

    There is a demand and need for healthy solid dietary fats. However, synthetic fats can be tailored to contain specific physiologic properties. Our goal was to design dietary solid test fats that would be both beneficial to the atherogenic lipid profile and stable against lipid peroxidation. Sixteen...

  12. Serum complexed and free prostate specific antigen levels are lower in female elite athletes in comparison to control women

    OpenAIRE

    Emma Eklund; Diamandis, Eleftherios P.; Carla Muytjens; Sarah Wheeler; Anu Mathew; Martin Stengelin; Eli Glezer; Galina Nikolenko; Brown, Marshall D.; Yingye Zheng; Angelica Lindén Hirschberg

    2017-01-01

    Background: We hypothesize that prostate specific antigen (PSA), a protein that it is under regulation by androgens, may be differentially expressed in female elite athletes in comparison to control women. Methods: We conducted a cross-sectional study of 106 female athletes and 114 sedentary age-matched controls.? Serum from these women was analyzed for complexed prostate specific antigen (cPSA) and free prostate specific antigen (fPSA), by fifth generation assays with limits of detection of ...

  13. SPECIFIC ANTIBODY DEFICIENCY IN CHILDREN SUFFERING RECURRENT INFECTIONS

    Directory of Open Access Journals (Sweden)

    M. Naseri. G.P. Spickett

    1999-08-01

    Full Text Available Specific antibody deficiency lias been recognized as an immunodeficiency. In order to investigate an antipolysaccliaride antibody defect as a cause of rcccttrent infections, 30 children were studied. Patients who had been identified to have a major immunodeficiency or structural abnormality or a disease known to cause infection were excluded."nTliirty patints, aged I to 13.8 years (mean age, 5.8; male; female, 13:17 were chosen; all liad normal IgG and IgGl. Tiic level of IgA, IgG2 and lgG3 were of lower than normal in some cases. All were immunized with Hih conjugate (PRI'-T vaccine, and 26 with pneumococcal vaccine. Antibody responses were measured 4-6 weeks later. Twelve showed a poor response to immunization: 8 to pneumovax 3 to Hib and 1 to both. No correlation was observed between IgG 2 level anil specific antibody responses to polysacciiaridc antigens. Tlie infections were more severe and more frequent in children who responded poorly to polysacciiaridc antigens. Chikircn who had infections in more than one site were most likely to have deficient antibody responses."nThese results show that assessment of specific antibody responses to challenge immunization is an essential part of the investigation of children suffering from recurrent pyogenic infections. The study confirms that measurement of immunoglobulin isotypes and IgG subclasses atone docs not exclude significant hormonal immune deficiency.

  14. Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy

    OpenAIRE

    Decewicz, David J; Neatrour, David M; Burke, Amy; Haberkorn, Mary Jane; Patney, Heather L; Vernalis, Marina N; Ellsworth, Darrell L

    2009-01-01

    Abstract Background Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein ...

  15. Differential effects of calcium antagonist subclasses on markers of nephropathy progression

    National Research Council Canada - National Science Library

    Bakris, George L; Weir, Matthew R; Secic, Michelle; Campbell, Brett; Weis-McNulty, Annette

    2004-01-01

    ... studies have shown that higher levels of proteinuria are associated with increased progression of renal and cardiovascular disease and that reductions in proteinuria are associated with a decrease in the rate of renal function deterioration and cardiovascular events. As a result of this relationship, proteinuria is frequently used as a surrogate end po...

  16. Phylogeny of subclass Scuticociliatia (Protozoa, Ciliophora) using combined data inferred from genetic, morphological, and morphogenetic evidence

    Science.gov (United States)

    Yi, Zhenzhen; Wang, Yangang; Lin, Xiaofeng; Al-Rasheid, Khaled A. S.; Song, Weibo

    2010-07-01

    Gene sequence-based genealogies of scuticociliates are different from those produced by morphological analyses. For this reason, 11 representative scuticociliates and two ambiguously related genera were chosen to test the ability of combined phylogenetic analyses using both gene sequences and morphological/morphogenetic characteristics. Analyses of both the SSrRNA gene sequences and the combined datasets revealed a consistent branching pattern. While the terminal branches and the order level relationships were generally well resolved, the family level relationships remain unresolved. However, two other trees based on ITS1-5.8S-ITS2 region sequences and morphological/morphogenetic characters showed limited information, due to a lack of informative sites in these two datasets. Our data suggest, however, that the combined analysis of morphological/morphogenetic characters and gene sequences did produce some changes to the phylogenetic estimates of this group.

  17. Cancer DNA microarray analysis considering multi-subclass with graph-based clustering method.

    Science.gov (United States)

    Kawamura, Takashi; Mutoh, Hironori; Tomita, Yasuyuki; Kato, Ryuji; Honda, Hiroyuki

    2008-11-01

    It is well known that various genes related to cell cycle, cell-cell adhesion, and transcriptional regulation cause the onset of cancer. Moreover, environmental factors including age, sex, and lifestyle can also contribute to the onset of cancer. Therefore, it is difficult to ascertain which factors influence the onset. Thus, patients suffering from same disease can be divided into several distinct groups. In the present study, we applied graph-based clustering to several DNA microarray datasets before the classification analysis. Several clusters formed by the graph-based clustering were used for the construction of multi-class classification model with the k-nearest neighbor and for finding genes, which are specific to a certain cluster, by One vs. Others classification. Using this approach, the classification model was constructed for four microarray datasets, leukemia, breast cancer, prostate cancer, and colon cancer, and the accuracies of classification with k-nearest neighbor were all more than 80%. And in the breast cancer dataset, we succeeded in finding genes that are specific in a cluster consisting of 38 control group samples. These results indicate the importance of sample clustering before classification model construction.

  18. Using multi-level Bayesian lesion-symptom mapping to probe the body-part-specificity of gesture imitation skills.

    Science.gov (United States)

    Achilles, Elisabeth I S; Weiss, Peter H; Fink, Gereon R; Binder, Ellen; Price, Cathy J; Hope, Thomas M H

    2017-08-16

    Past attempts to identify the neural substrates of hand and finger imitation skills in the left hemisphere of the brain have yielded inconsistent results. Here, we analyse those associations in a large sample of 257 left hemisphere stroke patients. By introducing novel Bayesian methods, we characterise lesion symptom associations at three levels: the voxel-level, the single-region level (using anatomically defined regions), and the region-pair level. The results are inconsistent across those three levels and we argue that each level of analysis makes assumptions which constrain the results it can produce. Regardless of the inconsistencies across levels, and contrary to past studies which implicated differential neural substrates for hand and finger imitation, we find no consistent voxels or regions, where damage affects one imitation skill and not the other, at any of the three analysis levels. Our novel Bayesian approach indicates that any apparent differences appear to be driven by an increased sensitivity of hand imitation skills to lesions that also impair finger imitation. In our analyses, the results of the highest level of analysis (region-pairs) emphasise a role of the primary somatosensory and motor cortices, and the occipital lobe in imitation. We argue that this emphasis supports an account of both imitation tasks based on direct sensor-motor connections, which throws doubt on past accounts which imply the need for an intermediate (e.g. body-part-coding) system of representation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Anti-A/B antibody depletion by semiselective versus ABO blood group-specific immunoadsorption.

    Science.gov (United States)

    Wahrmann, Markus; Schiemann, Martin; Marinova, Lena; Körmöczi, Günther F; Derfler, Kurt; Fehr, Thomas; Stussi, Georg; Böhmig, Georg A

    2012-05-01

    Recipient desensitization using blood group (BG)-specific immunoadsorption (ABO-IA) has proven to enable successful kidney transplantation across major ABO barriers. In this context, the efficiency of non-antigen-specific (semiselective) IA adsorbers has not yet been established. The objective of our study was to quantify anti-A/B antibody depletion by protein A-, peptide ligand- and anti-human immunoglobulin-based semiselective IA in comparison to ABO-IA. Eight ABO-IA-treated transplant candidates and 39 patients subjected to semiselective IA for a variety of different indications outside the context of ABO-incompatible transplantation were included. Antibody patterns (IgG, IgG1-4 subclasses, IgM, C4d-fixing reactivities) were analysed applying conventional agglutination testing and flow cytometry. As assessed by sensitive flow cytometric antibody detection, ABO-IA-based desensitization led to a profound even though often incomplete reduction of anti-A/B reactivities. Persistent complement- or non-complement-fixing reactivities, however, were not associated with transplant rejection or capillary C4d deposition. Single sessions of semiselective IA turned out to be more effective than ABO-IA in decreasing levels of anti-A/B IgG [median reduction to 28 versus 59% (ABO-IA) of baseline values, P tested adsorber types. Analysis of four consecutive IA sessions revealed that inferior efficiency could not be overcome by serial treatment. Our observation of limited adsorption capacities regarding distinct BG-specific Ig (sub)classes suggests caution in applying semiselective IA techniques in ABO-incompatible kidney transplantation.

  20. A livelock control policy for a flexible manufacturing system modeling with a subclass of generalized Petri nets

    Directory of Open Access Journals (Sweden)

    C.Q. Hou

    2014-12-01

    Full Text Available Livelocks, like deadlocks, can result in the serious problems in running process of flexible manufacturing systems (FMSs as well. Current deadlock control policies based on the approaches of siphon detection and control, cannot cope with livelocks in a system of sequential systems with shared resources (S4R, a typical subclass of Petri nets that can model FMSs. On the basis of the mixed integer programming method, this study proposes a livelock control policy (LCP that can not only solve the new smart siphons (NSSs associated with livelocks or deadlocks in an S4R system directly, but also make the solved NSSs max′-controlled by adding the corresponding control places (CPs. As a result, an original S4R system with livelocks or deadlocks can be turned into the live controlled one in which no NSSs can be found. The related theoretical analysis and several examples are given to demonstrate the proposed LCP. Compared with the existing methods in the literature, the proposed one is more general and powerful.

  1. Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    David J. Tischfield

    2017-05-01

    Full Text Available Recent studies indicate that the location of neurogenesis within the medial ganglionic eminence (MGE critically influences the fate determination of cortical interneuron subgroups, with parvalbumin (Pv interneurons originating from subventricular zone divisions and somatostatin (Sst interneurons primarily arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate the transition from apical to basal progenitor and their differentiation into post-mitotic neurons. We find that aPKC inhibition enhances intermediate neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly increased ratio of Pv- to Sst-expressing interneurons. Conversely, inhibition of Notch signaling enriches for Sst subtypes at the expense of Pv fates. These findings confirm that the mode of neurogenesis influences the fate of MGE-derived interneurons and provide a means of further enrichment for the generation of specific interneuron subgroups from pluripotent stem cells.

  2. Specific relationships between psychosocial job conditions and job-related stress : A three-level analytic approach

    NARCIS (Netherlands)

    van Veldhoven, M; de Jonge, J; Broersen, S; Kompier, M; Meijman, T

    2002-01-01

    This cross-sectional questionnaire study presents a multi-level analysis on 2565 workers in 188 departments in 36 organizations in the Netherlands. A three-level model is used in which individual workers are nested within departments, which in turn are nested within organizations. Research questions

  3. Prostate cancer detection rate in patients with fluctuating prostate-specific antigen levels on the repeat prostate biopsy

    Directory of Open Access Journals (Sweden)

    Yong Hyun Park

    2014-03-01

    Conclusions: The current study shows that the risk of prostate cancer at repeat TRUS-Bx was higher in men with a fluctuating PSA level and PSAV=1.0 ng/mL/yr than in those with a fluctuating PSA level and PSAV<1.0 ng/mL/yr.

  4. Plasma fibrinogen level: an independent prognostic factor for disease-free survival and cancer-specific survival in patients with localised renal cell carcinoma.

    Science.gov (United States)

    Obata, Jun; Tanaka, Nobuyuki; Mizuno, Ryuichi; Kanao, Kent; Mikami, Shuji; Matsumoto, Kazuhiro; Kosaka, Takeo; Kikuchi, Eiji; Jinzaki, Masahiro; Oya, Mototsugu

    2016-10-01

    To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma (RCC). We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes. Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan-Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery. Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  5. Multi-element compound specific stable isotope analysis of volatile organic compounds at trace levels in groundwater samples

    Science.gov (United States)

    Herrero-Martín, Sara; Nijenhuis, Ivonne; Schmidt, Marie; Wolfram, Diana; Richnow, Hans. H.; Gehre, Matthias

    2013-04-01

    Groundwater pollution remains one of the major environmental and health concerns. A thorough understanding of sources, sinks and transformation processes of groundwater contaminants is needed to improve risk management evaluation, and to design efficient remediation and water treatment strategies. Isotopic tools provide unique information for an in-depth understanding of the fate of organic chemicals in the environment. During the last decades compound specific isotope analysis (CSIA) of complex mixtures, using gas chromatography-isotope ratio mass spectrometry (GC-IRMS), has gained popularity for the characterization and risk assessment of hazardous waste sites and for isotope forensics of organic contaminants. Multi-element isotope fingerprinting of organic substances provides a more robust framework for interpretation than the isotope analysis of only one element. One major challenge for application of CSIA is the analysis of trace levels of organic compounds in environmental matrices. It is necessary to inject 1 nmol carbon or 8 nmol hydrogen on column, to obtain an accurate and precise measurement of the isotope ratios, which is between two and three orders of magnitude larger than the amount of compound needed for conventional analysis of compound concentrations. Therefore, efficient extraction and pre-concentration techniques have to be integrated with GC-IRMS. Further research is urgently needed in this field, to evaluate the potential of novel and environmental-friendly sample pre-treatment techniques for CSIA to lower the detection limits and extending environmental applications. In this study, the novel coupling of a headspace autosampler (HS) with a programmed temperature vaporizer (PTV), allowing large volume injection of headspace samples, is proposed to improve the sensitivity of CSIA. This automatic, fast and solvent free strategy provides a significant increase on the sensitivity of GC-based methods maintaining the simple headspace instrumentation

  6. A specific database for providing local and national level of integration of clinical data in cystic fibrosis.

    Science.gov (United States)

    Leal, T; Reychler, G; Mailleux, P; Gigi, J; Godding, V; Lebecque, P

    2007-05-01

    It has recently been stated that a database is an essential tool in the management of CF. The purpose of this work is to create a specific database allowing optimal performance of storage, search and retrieval functions on patients with CF. A specific database was developed using a Windev licence, for application via Microsoft supported platforms or Intranet system. The database allows real-time point of care data management of medical, investigational and administrative data. It is currently being used in the 6 Belgian reference centres. It represents a useful tool for gathering information on routine clinical and lab data, bacteriology, treatments, complications and specific outcomes for clinical and research purposes. The ongoing evolution of the database includes enhancements toward research data orientation including comparison of patient data between different centres and completeness of the National CF registry questionnaire. A complimentary copy of the software can be provided to multidisciplinary accredited CF centres worldwide upon request.

  7. Specific serum IgE levels and FcepsilonRIbeta genetic polymorphism in patients with penicillins allergy.

    Science.gov (United States)

    Qiao, H-L; Yang, J; Zhang, Y-W

    2004-12-01

    Numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. The objective of this investigation is to elucidate the underlying mechanism of penicillins allergy and improve the diagnostic methods. Radioallergosorbent test was used to examine eight kinds of specific IgE antibodies, which included four kinds of major and minor antigenic determinants, respectively, in the sera of 448 patients with penicillins allergy and 101 healthy subjects. A restriction endonuclease fragment length polymorphism of a polymerase chain reaction product was used for analysis of the FcepsilonRIbeta polymorphism. The positive rate of specific IgE in 448 patients was 58.26% (261), in which 37.28% (167) patients had positive IgE to major antigenic determinants and 47.09% (211) patients had positive IgE to minor antigenic determinants. Of the 179 patients with allergic history, 70.83% (17/24) patients had positive antibodies within 30 days, while 45.28% (24/53) had positive antibodies after 5 years. The positive reaction degree of skin test was absolutely correlated with specific IgE (P=0.047). Among patients with positive specific IgE, significant differences of E237G genotype were observed between patients with positive benzylpenicillanyl (BPA)-, phenoxomethylpenicilloyl (PVO)- or ampicilloyl (APO)-IgE and control group (P=0.015, 0.015, and 0.008, respectively). There were significant differences in E237G genotype between positive and negative BPA-, PVO- as well as APO-IgE patients (P = 0.014, 0.02, and 0.011, respectively). The patients with penicillins allergy have positive specific IgE not only to major antigenic determinants but also to minor antigenic determinants. The E237G variant of the FcepsilonRIbeta gene is involved in the development of penicillins allergy through the process for the production of specific IgE antibodies.

  8. Architectural protein subclasses shape 3-D organization of genomes during lineage commitment

    Science.gov (United States)

    Phillips-Cremins, Jennifer E.; Sauria, Michael E. G.; Sanyal, Amartya; Gerasimova, Tatiana I.; Lajoie, Bryan R.; Bell, Joshua S. K.; Ong, Chin-Tong; Hookway, Tracy A.; Guo, Changying; Sun, Yuhua; Bland, Michael J.; Wagstaff, William; Dalton, Stephen; McDevitt, Todd C.; Sen, Ranjan; Dekker, Job; Taylor, James; Corces, Victor G.

    2013-01-01

    Summary Understanding the topological configurations of chromatin may reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in looping interactions at different length scales. CTCF/cohesin anchor long-range constitutive interactions that form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge shortrange enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales. PMID:23706625

  9. Plasmodium falciparum spermidine synthase inhibition results in unique perturbation-specific effects observed on transcript, protein and metabolite levels

    CSIR Research Space (South Africa)

    Becker, JVW

    2010-01-01

    Full Text Available This study details the malaria parasite's response to PfSpdSyn inhibition on the transcriptomic, proteomic and metabolic levels. The results corroborate and significantly expand previous functional genomics studies relating to polyamine depletion...

  10. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins

    NARCIS (Netherlands)

    Hendrikx, Lotte H.; Ozturk, Kemal; de Rond, Lia G. H.; Veenhoven, Reinier H.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2011-01-01

    Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore

  11. Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels

    Directory of Open Access Journals (Sweden)

    Kyo Chul Koo

    2015-03-01

    Conclusions: PSA response to androgen deprivation therapy and serum ALP are reliable predictors of survival in patients with BMPCa presenting with extremely high PSA levels. These patients should not be deterred from active treatment based on baseline PSA values.

  12. Pattern of pre-existing IgG subclass responses to a panel of asexual stage malaria antigens reported during the lengthy dry season in Daraweesh, Sudan

    DEFF Research Database (Denmark)

    Nasr, A; Iriemenam, N C; Troye-Blomberg, M

    2011-01-01

    The anti-malarial IgG immune response during the lengthy and dry season in areas of low malaria transmission as in Eastern Sudan is largely unknown. In this study, ELISA was used for the measurement of pre-existing total IgG and IgG subclasses to a panel of malaria antigens, MSP2-3D7, MSP2-FC27...

  13. Acute HIV-1 infection is associated with increased plasma levels of heme oxygenase-1 and presence of heme oxygenase-1-specific regulatory T cells.

    Science.gov (United States)

    Angin, Mathieu; Fathi, Anahita; King, Melanie; Ledoux, Mary B; Piechocka-Trocha, Alicja; Altfeld, Marcus; Addo, Marylyn M

    2017-03-13

    Heme oxygenase-1 (HO-1) is an inducible stress response protein with potent anti-inflammatory activity and recent data suggest a potentially beneficial role in HIV pathogenesis. We investigated the impact of HO-1 and a novel subset of HO-1-specific CD8 regulatory T cells on virus-specific T-cell immunity in HIV-1-infected individuals. HO-1 protein levels were quantified in plasma from individuals at different stages of HIV-1 disease and longitudinally following primary HIV infection. HO-1-specific CD8 T cells were investigated by flow cytometry using human leukocyte antigen (HLA) class I pentamers. Flow-sorted HO-1-specific CD8 T cells were cultured and tested for suppressive activity on HIV-1-specific cytotoxic T-cell clones clones. HO-1 gene expression was determined in sorted peripheral blood mononuclear cell (PBMC) subsets from individuals with acute HIV-1 infection. HO-1 plasma levels were significantly increased in HIV-1 infection, with the highest levels in individuals with acute HIV-1 infection, and gradually declined over time. The frequency of CD8 T cells specific for HO-1 was elevated in study participants with primary HIV-1 infection and flow-sorted HO-1-specific CD8 T cells were capable of suppressing HIV-1-specific lysis of cytotoxic T-cell clones clones. HO-1 gene expression was upregulated in multiple immune cell subsets during acute HIV-1 infection and HO-1 overexpression modulated anti-HIV immunity in vitro. Our data suggest that HO-1 is induced during acute HIV-1 infection, likely mediating anti-inflammatory effects and driving expansion of HO-1-specific CD8 regulatory T cells capable of suppressing HIV-1-specific immune responses in vitro. The investigation of HO-1 and the novel CD8 regulatory cell type described here provide further insight into immune regulation in HIV-1 infection and may hold potential for future immunotherapeutic intervention.

  14. Sequential Prediction of Literacy Achievement for Specific Learning Disabilities Contrasting in Impaired Levels of Language in Grades 4 to 9

    Science.gov (United States)

    Sanders, Elizabeth A.; Berninger, Virginia W.; Abbott, Robert D.

    2018-01-01

    Sequential regression was used to evaluate whether language-related working memory components uniquely predict reading and writing achievement beyond cognitive-linguistic translation for students in Grades 4 through 9 (N = 103) with specific learning disabilities (SLDs) in subword handwriting (dysgraphia, n = 25), word reading and spelling…

  15. Educational gains in cause-specific mortality: Accounting for cognitive ability and family-level confounders using propensity score weighting

    NARCIS (Netherlands)

    Bijwaard, G.E.; Myrskylä, M.; Tynelius, P.; Rasmussen, F.

    2017-01-01

    A negative educational gradient has been found for many causes of death. This association may be partly explained by confounding factors that affect both educational attainment and mortality. We correct the cause-specific educational gradient for observed individual background and unobserved family

  16. Executive Functions and Prader-Willi Syndrome: Global Deficit Linked with Intellectual Level and Syndrome-Specific Associations

    Science.gov (United States)

    Chevalère, Johann; Postal, Virginie; Jauregui, Joseba; Copet, Pierre; Laurier, Virginie; Thuilleaux, Denise

    2015-01-01

    The aim of this study was to support the growing evidence suggesting that Prader-Willi Syndrome (PWS) might present with an impairment of executive functions (EFs) and to investigate whether this impairment is specific to patients with PWS or due to their intellectual disability (ID). Six tasks were administered to assess EFs (inhibition,…

  17. Elevated levels of total and dengue virus-specific immunoglobulin E in patients with varying disease severity

    NARCIS (Netherlands)

    Koraka, Penelopie; Murgue, Bernadette; Deparis, Xavier; Setiati, Tatty E.; Suharti, Catarina; van Gorp, Eric C. M.; Hack, C. E.; Osterhaus, Albert D. M. E.; Groen, Jan

    2003-01-01

    The kinetics of total and dengue virus-specific immunoglobulin E (IgE) were studied in serial serum samples obtained from 168 patients, 41 of whom suffered from primary dengue virus infection and 127 suffered from secondary dengue virus infection. Seventy-one patients were classified as dengue

  18. Analysis of the epidermal growth factor receptor specific transcriptome: effect of receptor expression level and an activating mutation

    DEFF Research Database (Denmark)

    Pedersen, Mikkel W; Pedersen, Nina; Damstrup, Lars

    2005-01-01

    by interferons. Expression of this module was absent in the EGFRvIII-expressing cell line and the parental cell line. Treatment with the specific EGFR inhibitor AG1478 indicated that the regulations were primary, receptor-mediated events. Furthermore, activation of this module correlated with activation of STAT1...

  19. Use of Tactual Materials on the Achievement of Content Specific Vocabulary and Terminology Acquisition within an Intermediate Level Science Curriculum

    Science.gov (United States)

    Terry, Brian H.

    2012-01-01

    In this quasi-experimental study, the researcher investigated the effectiveness of three tactual strategies and one non-tactual strategy of content specific vocabulary acquisition. Flash cards, task cards, and learning wheels served as the tactual strategies, and vocabulary review sheets served as a non-tactual strategy. The sample (n = 85)…

  20. Predicting Homophobic Behavior among Heterosexual Youth: Domain General and Sexual Orientation-Specific Factors at the Individual and Contextual Level

    Science.gov (United States)

    Poteat, V. Paul; DiGiovanni, Craig D.; Scheer, Jillian R.

    2013-01-01

    As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual…

  1. Gender and Spatial Ability and the Use of Specific Labels and Diagrammatic Arrows in a Micro-Level Chemistry Animation

    Science.gov (United States)

    Falvo, David A.; Suits, Jerry P.

    2009-01-01

    This study investigates the effects of using both specific labels and diagrammatic arrows in the animation of salt dissolution. Four different versions of the animation served as treatments that were developed based upon principles of educational technology and cognitive psychology. The researchers studied the effects of spatial ability (high or…

  2. Malassezia spp.-specific immunoglobulin E level is a marker for severity of atopic dermatitis in adults.

    Science.gov (United States)

    Glatz, Martin; Buchner, Matthias; von Bartenwerffer, Wibke; Schmid-Grendelmeier, Peter; Worm, Margitta; Hedderich, Jürgen; Fölster-Holst, Regina

    2015-02-01

    The significance of allergen-specific IgE as marker for severity of atopic dermatitis is controversial. The aim of this study was to determine the frequency of IgE-mediated sensitisation to food and environmental allergens in 132 children and 67 adults with atopic dermatitis, and its correlation to severity of atopic dermatitis (SCORAD). Total IgE was elevated (> 100 kU/l) in 79.7% of adults and 46.8% of children. Sensitisation frequencies to allergens, particularly microbial allergens, were up to 10-fold higher in adults compared to children. Severity of atopic dermatitis correlated with elevated total IgE in adults (r = 0.549, p children (r = 0.344, p = 0.005) and with Malassezia spp.-specific IgE in adults (r = 0.429, p = 0.007). Total IgE is a marker for severe atopic dermatitis in both age groups. Malassezia spp.-specific IgE is an important allergen-specific marker for severity of atopic dermatitis in adults.

  3. Level of functional capacities following soccer-specific warm-up methods among elite collegiate soccer players.

    Science.gov (United States)

    Vazini Taher, Amir; Parnow, Abdolhossein

    2017-05-01

    Different methods of warm-up may have implications in improving various aspects of soccer performance. The present study aimed to investigate acute effects of soccer specific warm-up protocols on functional performance tests. This study using randomized within-subject design, investigated the performance of 22 collegiate elite soccer player following soccer specific warm-ups using dynamic stretching, static stretching, and FIFA 11+ program. Post warm-up examinations consisted: 1) Illinois Agility Test; 2) vertical jump; 3) 30 meter sprint; 4) consecutive turns; 5) flexibility of knee. Vertical jump performance was significantly lower following static stretching, as compared to dynamic stretching (P=0.005). Sprint performance declined significantly following static stretching as compared to FIFA 11+ (P=0.023). Agility time was significantly faster following dynamic stretching as compared to FIFA 11+ (P=0.001) and static stretching (P=0.001). Knee flexibility scores were significantly improved following the static stretching as compared to dynamic stretching (P=016). No significant difference was observed for consecutive turns between three warm-up protocol. The present finding showed that a soccer specific warm-up protocol relied on dynamic stretching is preferable in enhancing performance as compared to protocols relying on static stretches and FIFA 11+ program. Investigators suggest that while different soccer specific warm-up protocols have varied types of effects on performance, acute effects of dynamic stretching on performance in elite soccer players are assured, however application of static stretching in reducing muscle stiffness is demonstrated.

  4. On the relationship between the dual specificity of the bovine brain phosphatidylinositol transfer protein and membrane phosphatidylinositol levels

    NARCIS (Netherlands)

    Paridon, P.A. van; Gadella, T.W.J.; Somerharju, P.J.; Wirtz, K.W.A.

    1987-01-01

    The phosphatidylinositol transfer protein from bovine brain has a remarkable specificity pattern with a distinct preference for phosphatidylinositol (PI) and a low affinity for phosphatidylcholine (PC). In this study we have determined the affinity of PI-transfer protein for PI relative to that for

  5. National patent applications in biotechnology, subclass C12N, in Brazil from 1998 to 2000

    Directory of Open Access Journals (Sweden)

    Celso Luiz Salgueiro Lage

    2006-03-01

    Full Text Available Only 11% of the activities of research and development in Brazil are carried out in private institutions. In the biotechnological field, an area of knowledge significantly closer to the basic sciences, there is a higher participation of public sectors, as might be expected. Among the public institutions, the universities were responsible for the highest number of applications in the evaluated time period, 56%. The national participation in the number of biotechnological patent applications in Brazil was 2.6% from 1998 to 2000. Among the countries with the highest number of biotechnological patent applications in Brazil, there is an obvious domination of the United States of America, representing 51.5% of all countries in 1999 and 42.3% of the 1057 C12N patent applications. Applications in the C12N 15 classification with 31.5% were the most frequent in comparison with the other C12N applications. This fact shows the fast increase of the number of applications in genetic engineering and fields of recombinant DNA technology. This result is a possible consequence of the genome race that is occurring at world level.

  6. Transitions between subclasses of bullying and victimization when entering middle school.

    Science.gov (United States)

    Williford, Anne; Boulton, Aaron J; Jenson, Jeffrey M

    2014-01-01

    We examined the effects of depressive symptoms, antisocial attitudes, and perspective-taking empathy on patterns of bullying and victimization during the transition from late elementary (4th grade to 5th grade) to middle school (6th grade) among 1,077 students who participated in the Youth Matters (YM) bullying prevention trial. Latent transition analysis was used to establish classes of bullying, victimization, bully-victimization, and uninvolvement. The intervention had a positive impact on children as they moved from elementary to middle school. More students in the YM group transitioned from the involved statuses to the uninvolved status than students in the control group during the move to middle school. Elementary school bullies with higher levels of depressive symptoms were less likely than other students to move to an uninvolved status in the first year of middle school. Students who held greater antisocial attitudes were more likely to be a member of the bully-victim status than the uninvolved status during the move to middle school. Perspective-taking empathy, however, was not a significant predictor of status change during the transition to middle school. Implications for school-based prevention programs during the move to middle school are noted. © 2013 Wiley Periodicals, Inc.

  7. The exon-level biomarker SLC39A14 has organ-confined cancer-specificity in colorectal cancer.

    Science.gov (United States)

    Sveen, Anita; Bakken, Anne Cathrine; Ågesen, Trude H; Lind, Guro E; Nesbakken, Arild; Nordgård, Oddmund; Brackmann, Stephan; Rognum, Torleiv O; Lothe, Ragnhild A; Skotheim, Rolf I

    2012-09-15

    An alternative transcript variant of SLC39A14, caused by pre-mRNA splicing, was recently suggested as a biomarker for colorectal cancer (CRC). In our study, we have validated the cancer-specific splicing pattern of the mutually exclusive exons 4A and 4B in altogether 244 colorectal tissue samples. Exon-specific quantitative RT-PCR analyses across 136 Stage I-IV CRC samples and 44 normal colonic mucosa samples showed complete cancer-specificity, as well as 94% sensitivity of SLC39A14-exon4B relative to SLC39A14-exon4A expression. However, across 20 samples from a range of healthy tissues, 18 expressed the CRC variant. This was true also for ten benign lymph nodes, demonstrating that the cancer-specificity is mainly confined to the colon and rectum. Hence, clinical use of SLC39A14-exon4B as a detection marker for CRC other than in samples taken from the bowel wall is diminished. Prognostic value by detection of metastasis to lymph nodes is also abated, elucidating an important pitfall to biomarker discovery. However, analyses of ten nondysplastic biopsies from patients with active inflammatory bowel disease showed negative results in seven samples and only weakly positive results in three samples, suggesting value of SLC39A14-exon4B as a marker to distinguish CRC from other pathologic conditions of the colon. In conclusion, the SLC39A14-exon4B transcript variant is a CRC biomarker with high sensitivity and organ-confined specificity. Further use of the transcript and its encoded protein isoform should be explored in an organ-confined context. Copyright © 2011 UICC.

  8. The catabolism of human γG immunoglobulins of different heavy chain subclasses. III. The catabolism of heavy chain disease proteins and of Fc fragments of myeloma proteins

    Science.gov (United States)

    Spiegelberg, H. L.; Fishkin, B. G.

    1972-01-01

    The catabolism of 131I and 125I paired labelled Fc fragments of myeloma proteins and of H chain disease proteins of different heavy chain subclasses was studied in men and monkeys. In contrast to the previously demonstrated catabolic heterogeneity of intact γG immunoglobulins, the Fc fragments and H chain disease proteins of all subclasses tested were catabolized at a similar rate. These data suggest that structures not present on the Fc fragments are responsible for the faster turnover rate of γG3 immunoglobulins and for the differences in half-lives of myeloma proteins within a given subclass. The catabolic features of the H chain disease proteins differed from those of intact γG. Although the whole body half-lives of the two proteins were similar, the fractional turnover rate of the H chain disease proteins was higher than that of γG, on the average 8% of the intravascular pool/day as compared to 4% for γG. One-half to 1% of the intravascular pool of the H chain disease protein and less than 0·1% of the γG was excreted into the urine. An average of 24% of the H chain disease proteins and 44% of the γG equilibrated into the intravascular compartment. PMID:4624553

  9. The complete mitochondrial genome of the black coral Chrysopathes formosa (Cnidaria:Anthozoa:Antipatharia) supports classification of antipatharians within the subclass Hexacorallia.

    Science.gov (United States)

    Brugler, Mercer R; France, Scott C

    2007-03-01

    Black corals comprise a globally distributed shallow- and deep-water taxon whose phylogenetic position within the Anthozoa has been debated. We sequenced the complete mitochondrial genome of the antipatharian Chrysopathes formosa to further evaluate its phylogenetic relationships. The circular mitochondrial genome (18,398 bp) consists of 13 energy pathway protein-coding genes and two ribosomal RNAs, but only two transfer RNA genes (trnM and trnW), as well as a group I intron within the nad5 gene that contains the only copies of nad1 and nad3. No novel genes were found in the antipatharian mitochondrial genome. Gene order and genome content are most similar to those of the sea anemone Metridium senile (subclass Hexacorallia), with differences being the relative location of three contiguous genes (cox2-nad4-nad6) and absence (from the antipatharian) of a group I intron within the cox1 gene. Phylogenetic analyses of multiple protein-coding genes support classifying the Antipatharia within the subclass Hexacorallia and not the subclass Ceriantipatharia; however, the sister-taxon relationships of black corals within Hexacorallia remain inconclusive.

  10. Settings for Physical Activity – Developing a Site-specific Physical Activity Behavior Model based on Multi-level Intervention Studies

    DEFF Research Database (Denmark)

    Troelsen, Jens; Klinker, Charlotte Demant; Breum, Lars

    of the facilities. Despite the conceptual and contextual differences PA behavior is also affected by cultural and social values related to the specific site which not alone can be explained by intrapersonal, interpersonal or organizational factors. Discussion: The Ecological Model of Four Domains of Active Living......Settings for Physical Activity – Developing a Site-specific Physical Activity Behavior Model based on Multi-level Intervention Studies Introduction: Ecological models of health behavior have potential as theoretical framework to comprehend the multiple levels of factors influencing physical...... activity (PA). The potential is shown by the fact that there has been a dramatic increase in application of ecological models in research and practice. One proposed core principle is that an ecological model is most powerful if the model is behavior-specific. However, based on multi-level interventions...

  11. Asynchronous presentation of global and local information reveals effects of attention on brain electrical activity specific to each level

    Directory of Open Access Journals (Sweden)

    Jorge eIglesias-Fuster

    2015-01-01

    Full Text Available The neural basis of selective attention within hierarchically organized Navon figures has been extensively studied with event related potentials (ERPs, by contrasting responses obtained when attending the global and the local echelons. The findings are inherently ambiguous because both levels are always presented together. Thus only a mixture of the brain responses to two levels can be observed. Here, we use a method that allows unveiling of global and local letters at distinct times, enabling estimation of separate ERPs related to each level. Two interspersed oddball streams were presented, each using letters from one level and comprised of frequent distracters and rare targets. Previous work and our Experiment 1 show that it is difficult to divide attention between two such streams of stimuli. ERP recording in Experiment 2 evinced an early selection negativity (SN, with latencies to the 50% area of about 266 ms for global distracters and 276 ms for local distracters that was larger for attended relative to unattended distracters. The SN was larger over right posterior occipito-temporal derivations for global stimuli and over left posterior occipito-temporal derivations for local stimuli (although the latter was less strongly lateralized. A discrimination negativity (DN, accompanied by a P3b was larger for attended targets relative to attended distracters, with latencies to the 50% area of about 316 ms for global stimuli and 301 ms for local stimuli, which presented a similar distribution for both levels over left temporo-parietal electrodes. The two negativities apparently index successive stages in the processing of a selected level within a compound figure. By resolving the ambiguity of traditional designs, our method allowed us to observe the effects of attention for each hierarchical level on its own.

  12. Mechanical properties of the equine superficial digital flexor tendon relate to specific collagen cross-link levels.

    Science.gov (United States)

    Thorpe, C T; Stark, R J F; Goodship, A E; Birch, H L

    2010-11-01

    Damage to the flexor tendons, particularly the superficial digital flexor tendon (SDFT), is one of the most common musculoskeletal injuries sustained by horses competing in all disciplines. Our previous work has shown that SDFTs from different individuals show a wide variation in mechanical strengths; this is important clinically as it may relate to predisposition to injury. The high mechanical strength of tendon relies on the correct orientation of collagen molecules within fibrils and stabilisation by the formation of chemical cross-links between collagen molecules. It is not known whether the variation in SDFT mechanical properties between individuals relates to differences in collagen cross-link levels. Enzyme-derived, intermolecular cross-linking of tendon collagen correlates with mechanical properties of the SDFT. SDFTs were collected from 38 horses and mechanically tested to failure. Structural and material properties were calculated from the load/deformation plot and cross-sectional area for each tendon. Following mechanical testing, pyrrolic cross-link levels were measured using a spectrophotometric assay for Ehrlich's reactivity and pyridinoline levels were quantified by HPLC. Cross-link levels were correlated with mechanical properties and statistical significance tested using a Pearson's correlation test. Pyrrole cross-link levels showed a significant positive correlation with ultimate stress (P = 0.004), yield stress (P = 0.003) and elastic modulus (P = 0.018) of the tendons, despite being a minor cross-link in these tendons. There was no significant correlation of mechanical properties with either hydroxylysyl- or lysyl-pyridinoline levels. Given the low absolute levels of pyrrole, we suggest that the correlation with high mechanical strength is through an indirect mechanism. Understanding the nature of the relationships between pyrrole cross-links, other matrix characteristics and tendon material properties may allow development of strategies to

  13. Spectrum of Disorders Associated with Elevated Serum IgG4 Levels Encountered in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Jay H. Ryu

    2012-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4 and manifests a wide spectrum of clinical presentations. Although serum IgG4 level has been described to be the most sensitive and specific laboratory test for the diagnosis of IgG4-RD, it is recognized that an elevated serum IgG4 level can be encountered in other diseases. In this study, we sought to identify the frequency of IgG4-RD and other disease associations in patients with elevated serum IgG4 levels seen in clinical practice. Among 3,300 patients who underwent IgG subclass testing over a 2-year period from January 2009 to December 2010, 158 (4.8% had an elevated serum IgG4 level (>140 mg/dL. IgG4 subclass testing was performed for evaluation of suspected IgG4-RD or immunodeficiency. Twenty-nine patients (18.4% had definite or possible IgG4-RD. Among those patients without IgG4-RD, a broad spectrum of biliary tract, pancreatic, liver, and lung diseases, as well as systemic vasculitis, was diagnosed. We conclude that patients with elevated serum IgG4 levels encountered in clinical practice manifest a wide array of disorders, and only a small minority of them has IgG4-RD.

  14. Motor neuron disease mortality and lifetime petrol lead exposure: Evidence from national age-specific and state-level age-standardized death rates in Australia.

    Science.gov (United States)

    Zahran, Sammy; Laidlaw, Mark A S; Rowe, Dominic B; Ball, Andrew S; Mielke, Howard W

    2017-02-01

    The age standardized death rate from motor neuron disease (MND) for persons 40-84 years of age in the Australian States of New South Wales, Victoria, and Queensland increased dramatically from 1958 to 2013. Nationally, age-specific MND death rates also increased over this time period, but the rate of the rise varied considerably by age-group. The historic use of lead (Pb) additives in Australian petrol is a candidate explanation for these trends in MND mortality (International Classification of Disease (ICD)-10 G12.2). Leveraging temporal and spatial variation in petrol lead exposure risk resulting from the slow rise and rapid phase-out of lead as a constituent in gasoline in Australia, we analyze relationships between (1) national age-specific MND death rates in Australia and age-specific lifetime petrol lead exposure, (2) annual between-age dispersions in age-specific MND death rates and age-specific lifetime petrol lead exposure; and (3) state-level age-standardized MND death rates as a function of age-weighted lifetime petrol lead exposure. Other things held equal, we find that a one percent increase in lifetime petrol lead exposure increases the MND death rate by about one-third of one percent in both national age-specific and state-level age-standardized models of MND mortality. Lending support to the supposition that lead exposure is a driver of MND mortality risk, we find that the annual between-age group standard deviation in age-specific MND death rates is strongly correlated with the between-age standard deviation in age-specific lifetime petrol lead exposure. Legacy petrol lead emissions are associated with age-specific MND death rates as well as state-level age-standardized MND death rates in Australia. Results indicate that we are approaching peak lead exposure-attributable MND mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Host Range Restriction of Insect-Specific Flaviviruses Occurs at Several Levels of the Viral Life Cycle

    OpenAIRE

    Sandra Junglen; Marvin Korries; Wolfgang Grasse; Janett Wieseler; Anne Kopp; Kyra Hermanns; Moises León-Juóárez; Christian Drosten; Beate Mareike Kummerer; Glenn Randall

    2017-01-01

    ABSTRACT The genus Flavivirus contains emerging arthropod-borne viruses (arboviruses) infecting vertebrates, as well as insect-specific viruses (ISVs) (i.e., viruses whose host range is restricted to insects). ISVs are evolutionary precursors to arboviruses. Knowledge of the nature of the ISV infection block in vertebrates could identify functions necessary for the expansion of the host range toward vertebrates. Mapping of host restrictions by complementation of ISV and arbovirus genome funct...

  16. DNA barcodes reveal species-specific mercury levels in tuna sushi that pose a health risk to consumers

    Science.gov (United States)

    Lowenstein, Jacob H.; Burger, Joanna; Jeitner, Christian W.; Amato, George; Kolokotronis, Sergios-Orestis; Gochfeld, Michael

    2010-01-01

    Excessive ingestion of mercury—a health hazard associated with consuming predatory fishes—damages neurological, sensory-motor and cardiovascular functioning. The mercury levels found in Bigeye Tuna (Thunnus obesus) and bluefin tuna species (Thunnus maccoyii, Thunnus orientalis, and Thunnus thynnus), exceed or approach levels permissible by Canada, the European Union, Japan, the US, and the World Health Organization. We used DNA barcodes to identify tuna sushi samples analysed for mercury and demonstrate that the ability to identify cryptic samples in the market place allows regulatory agencies to more accurately measure the risk faced by fish consumers and enact policies that better safeguard their health. PMID:20410032

  17. A Review on Level of Specific Absorption Rate Due to High Power Transmission Lines: Analysis toward Human Position Posture

    Directory of Open Access Journals (Sweden)

    Ghazali Z.

    2016-01-01

    Full Text Available The main contribution of this project is the development of a homogeneous model of a man to presents the specific absorption rate (SAR due to high power transmission line. As a low frequency application under high power transmission line of 50 Hz in electrical engineering, to studies the influence of human’s posture on specific absorption rate. This project designs two types of human body which one design uses most cylinder block and another design use brick block where both blocks have a different value of mesh cells. For each design has four types of posture are standing, sitting, arms up and arms out by using Computer Simulation Technology (CST Studio Software. This analysis does toward for four types of the human position postures because each posture has different value of specific absorption rate (SAR based on the size of the mesh cells of the design. Based on two designs of the human body, the lowest of the mesh cells value will reduce time to simulate SAR. For each posture has different value of SAR for each part of the human body because the whole human body has different types of tissues. Therefore, the CST studio software uses extremely to simulate the SAR value toward human position posture due to high power transmission line.

  18. Levels of circulating immune complexes containing Mycobacterium Tuberculosis-specific antigens in pulmonary tuberculosis and sarcoidosis patients

    Directory of Open Access Journals (Sweden)

    B Goyal

    2017-01-01

    Full Text Available The present study was conducted to understand the aetiological link between tuberculosis (TB and sarcoidosis. Sera from smear-positive TB subjects (n = 24, smear-negative TB subjects (n = 24, sarcoidosis patients (n = 24 and healthy controls (n = 24 were collected and circulating immune complexes were isolated. Sandwich ELISA was performed for detecting four highly specific mycobacterial regions of difference (RD proteins (early secretory antigenic target 6 [ESAT6], 10 KDa culture filtrate protein [CFP10], 21 KDa CFP [CFP21] and mycobacterial protein from species TB [MPT 64]. Sensitivity and specificity was calculated, and receiver operating characteristic plots were plotted. Non-parametric Mann–Whitney U-test was used to calculate statistical significance. Seventy per cent of sarcoidosis patients showed the presence of immune complexes of mycobacterial RD proteins similar to that observed in the sera of smear-negative TB patients as opposed to antibody-based detection assay based on these RD proteins. Thus, immunoassays based on specific mycobacterial RD proteins also need to be developed and validated carefully to differentiate TB and sarcoidosis, a close mimic of smear-negative tuberculosis.

  19. Rhinovirus-induced VP1-specific Antibodies are Group-specific and Associated With Severity of Respiratory Symptoms.

    Science.gov (United States)

    Niespodziana, Katarzyna; Cabauatan, Clarissa R; Jackson, David J; Gallerano, Daniela; Trujillo-Torralbo, Belen; Del Rosario, Ajerico; Mallia, Patrick; Valenta, Rudolf; Johnston, Sebastian L

    2015-01-01

    Rhinoviruses (RVs) are a major cause of common colds and induce exacerbations of asthma and chronic inflammatory lung diseases. We expressed and purified recombinant RV coat proteins VP1-4, non-structural proteins as well as N-terminal fragments of VP1 from four RV strains (RV14, 16, 89, C) covering the three known RV groups (RV-A, RV-B and RV-C) and measured specific IgG-subclass-, IgA- and IgM-responses by ELISA in subjects with different severities of asthma or without asthma before and after experimental infection with RV16. Before infection subjects showed IgG1 > IgA > IgM > IgG3 cross-reactivity with N-terminal fragments from the representative VP1 proteins of the three RV groups. Antibody levels were higher in the asthmatic group as compared to the non-asthmatic subjects. Six weeks after infection with RV16, IgG1 antibodies showed a group-specific increase towards the N-terminal VP1 fragment, but not towards other capsid and non-structural proteins, which was highest in subjects with severe upper and lower respiratory symptoms. Our results demonstrate that increases of antibodies towards the VP1 N-terminus are group-specific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups.

  20. Conceptual waste package interim product specifications and data requirements for disposal of borosilicate glass defense high-level waste forms in salt geologic repositories

    Energy Technology Data Exchange (ETDEWEB)

    1983-06-01

    The conceptual waste package interim product specifications and data requirements presented are applicable specifically to the normal borosilicate glass product of the Defense Waste Processing Facility (DWPF). They provide preliminary numerical values for the defense high-level waste form parameters and properties identified in the waste form performance specification for geologic isolation in salt repositories. Subject areas treated include containment and isolation, operational period safety, criticality control, waste form/production canister identification, and waste package performance testing requirements. This document was generated for use in the development of conceptual waste package designs in salt. It will be revised as additional data, analyses, and regulatory requirements become available.

  1. Gender- and Sport-Specific Associations Between Religiousness and Doping Behavior in High-Level Team Sports.

    Science.gov (United States)

    Zvan, Milan; Zenic, Natasa; Sekulic, Damir; Cubela, Mladen; Lesnik, Blaz

    2017-08-01

    Religiousness is known to be specifically associated with substance abuse, but there is an evident lack of studies investigating the association between religiousness and doping behavior as a specific type of substance abuse in athletes. This study aimed to provide evidence for possible gender- and sport-specific associations between religiousness and doping behavior among team-sport athletes of both genders. The participants were 886 athletes (21.9 ± 3.8 years of age; 352 females) involved in four sports: volleyball (n = 154; 78 females), handball (n = 206; 68 females), soccer (n = 316; 110 females) and basketball (n = 230; 96 females) from Croatia and Slovenia (all traditionally Roman Catholics). The data were collected using a previously validated structured questionnaire that examined sociodemographic, sport- and doping-related factors. In addition, religiousness was captured by the Santa Clara Strength of Religious Faith questionnaire (SCSRF). Gender-stratified simple logistic regressions were applied to determine associations between covariates and doping behavior (criterion). There was no significant difference in potential doping behavior between males and females (OR 1.06, 95 % CI 0.76-1.46), while females reported higher religiousness (SCSRF: 23.11 ± 3.23 and 25.46 ± 7.2 for males and females, respectively; t test = 1.82, p sport and age, the SCSRF remained a significant predictor of potential doping behavior (OR 0.95, 95 % CI 0.91-0.99). For males, the belief that doping was present in sport was strongly associated with a higher likelihood of doping. Our results suggest that highly religious females involved in three of the studies sports (i.e., volleyball, handball and basketball) show a weaker tendency toward doping. Meanwhile, there is no evidence that religiousness influences doping behavior among male team-sport athletes. Therefore, sport-specific and gender-specific approach in studying possible relationships that exist

  2. Co-suppression of synthesis of major x-kafirin sub-class together with y-kafirin-1 and y-kafirin-2 required for substantially improved protein digestibility in transgenic sorghum

    CSIR Research Space (South Africa)

    Grootboom, AW

    2014-01-01

    Full Text Available Co-suppressing major kafirin sub-classes is fundamental to improved protein digestibility and nutritional value of sorghum. The improvement is linked to an irregularly invaginated phenotype of protein bodies....

  3. Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer

    DEFF Research Database (Denmark)

    Holten-Andersen, Mads N; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2002-01-01

    levels between healthy donors and IBD or breast cancer patients, whereas patients with CC or RC had significantly elevated TIMP-1 levels. Total TIMP-1 levels identified patients with CC with a sensitivity of 63% at 98% specificity, patients with early CC (Dukes' A+B) with a sensitivity of 56% at 98......: Total TIMP-1 plasma levels were measured by ELISA in blood samples from two different blood donor populations from IBD patients, and preoperative samples from patients with primary colon cancer (CC), rectal cancer (RC), or breast cancer. RESULTS: There were no significant differences in plasma TIMP-1......, including those with early-stage disease. Sensitivity and specificity were both sufficiently high to consider TIMP-1 as a marker for the early identification of CC patients, in particular, those with right-sided CC....

  4. Specific IgG(4) responses during chronic and transient antigen exposure in aspergillosis

    NARCIS (Netherlands)

    Tomee, JFC; Dubois, AEJ; Koeter, GH; Beaumont, F; vanderWerf, TS; Kauffman, HF

    The factors that lead to increased production of specific IgG subclasses are still largely unknown. Recent studies suggest that increased IgG(4) responses may be related to prolonged antigen exposure. We present data showing that increased IgG(4) responses are found under conditions of chronic

  5. Specific immunoglobulin measurements related to exposure and resistance to Schistosoma mansoni infection in Sudanese canal cleaners

    DEFF Research Database (Denmark)

    Satti, M.Z.; Lind, Peter; Vennervald, B.J.

    1996-01-01

    was used to detect specific IgE and IgG subclasses in response to whole worm antigen (WWH) and soluble egg antigen (SEA) before and 3 months after praziquantel treatment in the groups of canal cleaners and before and 1 year after treatment in normally exposed adults. When intensity of infection...

  6. The Relationship between Listening Comprehension of Text and Sentences in Preschoolers: Specific or Mediated by Lower and Higher Level Components?

    Science.gov (United States)

    Florit, Elena; Roch, Maja; Levorato, M. Chiara

    2013-01-01

    Two studies explored the relation between listening comprehension of text and listening comprehension of sentences in preschoolers aged 4 to 5 years, 11 months. The first study analyzed this relationship taking into account the role of lower level components, namely, word knowledge and verbal working memory, as possible mediators. These components…

  7. Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1

    OpenAIRE

    Orthwein, Alexandre; Zahn, Astrid; Methot, Stephen P; Godin, David; Conticello, Silvestro G; Terada, Kazutoyo; Di Noia, Javier M

    2011-01-01

    AID deaminates deoxycytidine at immunoglobulin genes to generate an antibody response. AID misregulation can contribute to cancer and autoimmune disease. Here, the chaperone DnaJa1 is shown to determine AID protein levels and biological activity during the murine immune response.

  8. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    Directory of Open Access Journals (Sweden)

    Kristensen Vessela N

    2011-08-01

    Full Text Available Abstract Background High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. Methods We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Results Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1 were found differentially expressed according to serum estradiol levels (FDR = 0. Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1 and TLN2 were up-regulated and PTGS1 (COX1 was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. Conclusions We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2 production which

  9. Differential suppression of intracellular reactive oxygen species-mediated signaling pathway in vascular endothelial cells by several subclasses of flavonoids.

    Science.gov (United States)

    Yi, Long; Chen, Chun-ye; Jin, Xin; Zhang, Ting; Zhou, Yong; Zhang, Qian-yong; Zhu, Jun-dong; Mi, Man-tian

    2012-09-01

    Increased intracellular reactive oxygen species (ROS) is crucial for vascular endothelial dysfunction, a key step in the initiating of atherosclerosis (AS). The antioxidant activity of flavonoids has been suggested to contribute to AS prevention. However, The association of the structure characteristics to antioxidant capacities in relation to the inhibitory effects on endothelial dysfunction has not been well established. In this study, four subclasses of flavonoids with similar structures, including two anthocyanins (delphinidin and cyanidin), two flavonols (myricetin and quercetin), two flavones (luteolin and apigenin) and two isoflavones (genistein and daidzein) were examined for their inhibitory effects on intracellular ROS-mediated signaling pathway in the human umbilical vein endothelial cell EA.hy926. Cells were pretreated with different flavonoids for 2 h and then exposed to oxLDL of 100 μg/ml for another 24 h. It was found that treatment with different flavonoids alone had no notable effects on cell viability. However, the oxLDL-induced decrease of cell viability, generation of O(2)(·-) and ROS, p38MAPK activation, NF-κB nuclear translocation, NF-κB-modulated transcriptional activity as well as the mRNA expression of genes including ICAM-1, VCAM-1, E-selectin, MMP-1, MMP-2 and MMP-9 were notably inhibited by the pretreatment of different flavonoids through blunting ROS-triggered signaling pathway, in spite of apparent differences. And the number of hydroxyl groups in total, 3',4'-ortho-dihydroxyl in B-ring and 3-hydroxyl group in C-ring of flavonoids were important structure characteristics for the inhibitory effects. Thus, anthocyanins and flavonols such as delphinidin and myricetin exert higher ROS scavenging activities and more significant endothelium-protective effects compared to the other compounds. Our results provide evidence for AS prevention and a basis for designing the potent anti-atherosclerotic agents. Copyright © 2012 Elsevier

  10. 50/50 F-76/DSH-76 Specification and Fit-for-Purpose Level I Test Results

    Science.gov (United States)

    2013-09-27

    single molecule fuel produced from direct fermentation of renewable sugars. This test report summarizes chemical, physical and fit for purpose (FFP) test results of a 70/30 and 50/50 blend of petroleum F-76 and DSH-76. The 70/30 and 50/50 F76/DSH-76 met all specification properties as set forth by MIL-DTL-16884L and FFP criteria as set forth by NAVSEA technical warrant holders, engine OEMs and subject matter experts1. Chemical profiling showed the chemical composition of neat DSH-76 to consist of a C15 iso-paraffinic molecule with very little side products. These test

  11. Serious diabetes-specific emotional problems in patients with type 2 diabetes who have different levels of comorbid depression

    DEFF Research Database (Denmark)

    Kokoszka, A; Pouwer, F; Jodko, A

    2009-01-01

    (MINI), the Beck Depression Inventory, the Hamilton Depression Rating Scale as well as the Problem Areas in Diabetes (PAID) scale (a 20-item measure, with an overall scale measuring diabetes-related emotional distress and four subscales [negative emotions, treatment-related problems, food......-related problems, lack of social support]). RESULTS: A depression diagnosis was made in 35% (n = 35) of the participants, 24% (n = 24) had a subclinical form of depression, 42% (n = 42) were not diagnosed with any kind of depressive disorder. Diabetes-specific emotional problems were most common in DM2 patients...

  12. Prostate-specific antigen levels in relation to background factors: are there links to endocrine disrupting chemicals and AhR expression?

    Science.gov (United States)

    Bidgoli, Sepideh Arbabi; Jabari, Nasim; Zavarhei, Mansour Djamali

    2014-01-01

    Prostate-specific antigen (PSA) is a potential biomarker for early detection of prostate cancer (PCa) but its level is known to be affected by many background factors and roles of ubiquitous toxicants have not been determined. Endocrine disrupting chemicals (EDCs) are ubiquitous reproductive toxicants used in consumer products, which promote tumor formation in some reproductive model systems by binding to AhR, but human data on its expression in prostate cancer as well as its association with PSA levels are not clear. This study aimed to evaluate the expression levels of AhR and its association with serological levels of PSA and to detect possible effects of background factors and EDC exposure history on PSA levels in PCa cases. A cross-sectional study was conducted on the tissue levels of AhR and serum levels of PSA in 53 PCa cases from 2008-2011 and associations between each and background and lifestyle related factors were determined. Although the AhR was overexpressed in PCa and correlated with the age of patients, it did not correlate with PSA levels.Of nutritional factors, increased intake of polysaturated fats and fish in the routine regimen of PCa cases increased the PSA levels significantly. AhR overexpression in PCa pontws to roles of EDCs in PCa but without any direct association with PSA levels. However, PSA levels are affected by exposure to possible toxicants in foods whichneed to be assessed as possible risk factors of PCa in future studies.

  13. Doping Attitudes and Covariates of Potential Doping Behaviour in High-Level Team-Sport Athletes; Gender Specific Analysis

    Directory of Open Access Journals (Sweden)

    Damir Sekulic, Enver Tahiraj, Milan Zvan, Natasa Zenic, Ognjen Uljevic, Blaz Lesnik

    2016-12-01

    Full Text Available Team sports are rarely studied with regard to doping behaviour and doping-related factors regardless of their global popularity. This study aimed to investigate doping factors and covariates of potential doping behaviour in high-level team-sport athletes. The subjects were 457 high-performing, national- and international-level athletes (21.9 ± 3.4 years of age; 179 females involved in volleyball (n = 77, soccer (n = 163, basketball (n = 114 and handball (n = 103. Previously validated self-administered questionnaires aimed at evidencing sport factors, doping-related factors, knowledge on sport nutrition and doping, and attitudes to performance enhancement were used. The results indicated a higher doping likelihood in male athletes, with a significant gender difference for basketball and handball. In males, a higher doping likelihood is found for athletes who had achieved better results at junior-age level, those who regularly consume dietary supplements, and who perceive their sport as being contaminated by doping. A higher sport achievement at senior-age level is protective against potential doping behaviour in males. In females, a higher likelihood of doping is evidenced in those athletes involved in binge drinking, while a lower tendency for doping is evidenced in female athletes who possess better knowledge on sport nutrition. Knowledge about doping is very low and thus education about doping is urgently needed. An improvement of knowledge on sport nutrition might be a potentially effective method for reducing the tendency for doping in females. Future studies should consider other approaches and theories, such as theory of planned behaviour and/or social-cognitive theory, in studying the problem of doping behaviour in team-sports.

  14. Sex-specific effects of serum sulfate level and SLC13A1 nonsense variants on DHEA homeostasis

    Directory of Open Access Journals (Sweden)

    Christina G. Tise

    2017-03-01

    Conclusions: Our results demonstrate an inverse relationship between serum sulfate, and DHEA-S and DHEA-S/DHEA ratio in men, while also suggesting that the sulfate-lowering variants, SLC13A1 R12X and W48X, decrease DHEA and testosterone levels, and increase DHEA-S/DHEA ratio in women. While paradoxical, these results illustrate the complexity of the mechanisms involved in DHEA homeostasis and warrant additional studies to better understand sulfate's role in hormone physiology.

  15. Tachykinin expression levels correlate with caste-specific aggression in workers of the leaf-cutting ant Acromyrmex echinatior

    Directory of Open Access Journals (Sweden)

    Jack eHowe

    2016-05-01

    Full Text Available The tachykinins are a family of neuropeptides that influence a range of behavioral phenotypes in both vertebrates and invertebrates; they appear to have a conserved role in the processing of stimuli, and in the control of aggression in a wide range of animals. Expression of tachykinin in a cluster of neurons was recently shown to determine the stimulus response threshold for aggressive behavior in Drosophila (1. Varying response thresholds are often implicated in division of labor within social insect colonies, so we hypothesized that Tachykinin could play a role in the organization of colony defense by affecting individual response thresholds to non-nestmate stimuli. We used quantitative-PCR in combination with behavioral assays to test for associations between the expression of Tachykinin and its receptor, and the aggressive division of labor among the castes of the leaf-cutting ant Acromyrmex echinatior, a species with multiple worker castes. After correction for differences in brain size among castes, we found that the most aggressive large worker caste had the highest Tachykinin expression levels, but that no such effect was apparent for breeding and virgin queens. To further evaluate these deviating results for the reproductive caste, we manipulated the aggression threshold of virgin-queens by removing their wings, which is known to make them express a soldier-like behavioral phenotype. Despite heightened aggression, expression levels of Tachykinin remained unaffected, suggesting that aggression levels in reproductive caste phenotypes are controlled by differential expression of other genes.

  16. Gender specific effect of LIPC C-514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children.

    Science.gov (United States)

    Wang, Hao; Zhang, Dandan; Ling, Jie; Lu, Wenhui; Zhang, Shuai; Zhu, Yimin; Lai, Maode

    2015-09-01

    Hepatic lipase (LIPC) is a key rate-limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C-514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case-controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C-514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta-analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL-C) in obese boys, and triglyceride (TG), TC and LDL-C in non-obese girls (all P obesity in Chinese boys. The meta-analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  17. Disposable magnetic DNA sensors for the determination at the attomolar level of a specific enterobacteriaceae family gene.

    Science.gov (United States)

    Loaiza, Oscar A; Campuzano, Susana; Pedrero, María; Pividori, M Isabel; García, Pedro; Pingarrón, José M

    2008-11-01

    Disposable magnetic DNA sensors using an enzyme-amplified strategy for the specific detection of a gene related to the Enterobacteriaceae bacterial family, based on the coupling of streptavidin-peroxidase to biotinylated lacZ gene target sequences, has been developed. A biotinylated 25-mer capture probe was attached to streptavidin-modified magnetic beads and hybridization with the biotinylated target was allowed to proceed. Then, a streptavidin-peroxidase polymer was attached to the biotinylated target, and the resulting modified magnetic beads were captured by a magnetic field on the surface of tetrathiafulvalene (TTF) modified gold screen-printed electrodes (Au/SPEs). The amperometric response obtained at -0.15 V after the addition of hydrogen peroxide was used to detect the hybridization process. In order to improve the sensitivity of the determination and reduce the assay time, different variables of the assay protocol were optimized. A low detection limit (5.7 fmol) with good stability (RSD = 7.1%, n = 10) was obtained. The DNA nonspecific adsorption at the magnetic beads was negligible, the obtained results thus demonstrating the possibility to detect the hybridization event with great specificity and sensitivity. The developed method was used for the analysis of Escherichia coli DNA fragments (326 bases) in polymerase chain reaction (PCR) amplicons extracted from a cell culture. As low as 2.5 aM asymmetric PCR product could be detected with the developed methodology.

  18. Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin levels and obesity in the Jackson Heart Study cohort.

    Science.gov (United States)

    Riestra, Pia; Gebreab, Samson Y; Xu, Ruihua; Khan, Rumana J; Bidulescu, Aurelian; Correa, Adolfo; Tekola-Ayele, Fasil; Davis, Sharon K

    2015-08-20

    Despite the important role of adiponectin in regulating general metabolic homeostasis, analysis of genetic determinants of adiponectin and the related cardio-metabolic traits in African American population has been limited and inconsistent. Considering the high genetic admixture of African Americans and thus the important population stratification that may confound the genetic-trait associations, the objective of this work was to perform a comprehensive analysis of the associations between ADIPOQ variants and adiponectin levels and obesity phenotypes in a large African American population from the Jackson Heart Study (JHS) cohort. Genotype data was available for 2968 JHS participants (1131men; 1837women). Single Nucleotide Polymorphisms (SNPs) were selected by a Tag-SNP Approach and literature review. The genotype imputation was performed using IMPUTE2 software and reference phased data from the 1000G project. PLINK software was used for the genetic analysis. Plasma specimens were analyzed by ELISA for adiponectin levels. All analyses were controlled for population stratification assessed by Individual Proportions of European Ancestry (PEA) estimates calculated in HAPMIX using ancestry informative markers (AIMs). We found a gender-dependent association of some ADIPOQ variants and adiponectin levels. In women four of the studied polymorphisms (rs6444174, rs16861205, rs1403697, rs7641507) were associated with adiponectin levels after Bonferroni correction and controlling for the percentage of PEA, age, annual household income and smoking. These results were consistent with the haplotype analysis. The association between the rs12495941 variant and obesity is modulated by the PEA, so that the relationship between the G allele and a higher incidence of obesity was present in those individuals within the lower PEA group. In addition we found an effect modification of obesity on the association between the ADIPOQ rs6444174 SNP and BMI so that the presence of the T allele

  19. Sleep-Dependent Synaptic Down-Selection (II): Single-Neuron Level Benefits for Matching, Selectivity, and Specificity.

    Science.gov (United States)

    Hashmi, Atif; Nere, Andrew; Tononi, Giulio

    2013-01-01

    In a companion paper (1), we used computer simulations to show that a strategy of activity-dependent, on-line net synaptic potentiation during wake, followed by off-line synaptic depression during sleep, can provide a parsimonious account for several memory benefits of sleep at the systems level, including the consolidation of procedural and declarative memories, gist extraction, and integration of new with old memories. In this paper, we consider the theoretical benefits of this two-step process at the single-neuron level and employ the theoretical notion of Matching between brain and environment to measure how this process increases the ability of the neuron to capture regularities in the environment and model them internally. We show that down-selection during sleep is beneficial for increasing or restoring Matching after learning, after integrating new with old memories, and after forgetting irrelevant material. By contrast, alternative schemes, such as additional potentiation in wake, potentiation in sleep, or synaptic renormalization in wake, decrease Matching. We also argue that, by selecting appropriate loops through the brain that tie feedforward synapses with feedback ones in the same dendritic domain, different subsets of neurons can learn to specialize for different contingencies and form sequences of nested perception-action loops. By potentiating such loops when interacting with the environment in wake, and depressing them when disconnected from the environment in sleep, neurons can learn to match the long-term statistical structure of the environment while avoiding spurious modes of functioning and catastrophic interference. Finally, such a two-step process has the additional benefit of desaturating the neuron's ability to learn and of maintaining cellular homeostasis. Thus, sleep-dependent synaptic renormalization offers a parsimonious account for both cellular and systems level effects of sleep on learning and memory.

  20. Systems level approach reveals the correlation of endoderm differentiation of mouse embryonic stem cells with specific microstructural cues of fibrin gels

    Science.gov (United States)

    Task, Keith; D'Amore, Antonio; Singh, Satish; Candiello, Joe; Jaramillo, Maria; Wagner, William R.; Kumta, Prashant; Banerjee, Ipsita

    2014-01-01

    Stem cells receive numerous cues from their associated substrate that help to govern their behaviour. However, identification of influential substrate characteristics poses difficulties because of their complex nature. In this study, we developed an integrated experimental and systems level modelling approach to investigate and identify specific substrate features influencing differentiation of mouse embryonic stem cells (mESCs) on a model fibrous substrate, fibrin. We synthesized a range of fibrin gels by varying fibrinogen and thrombin concentrations, which led to a range of substrate stiffness and microstructure. mESCs were cultured on each of these gels, and characterization of the differentiated cells revealed a strong influence of substrate modulation on gene expression patterning. To identify specific substrate features influencing differentiation, the substrate microstructure was quantified by image analysis and correlated with stem cell gene expression patterns using a statistical model. Significant correlations were observed between differentiation and microstructure features, specifically fibre alignment. Furthermore, this relationship occurred in a lineage-specific manner towards endoderm. This systems level approach allows for identification of specific substrate features from a complex material which are influential to cellular behaviour. Such analysis may be effective in guiding the design of scaffolds with specific properties for tissue engineering applications. PMID:24718448

  1. Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities.

    Directory of Open Access Journals (Sweden)

    Amandine Bemmo

    2010-08-01

    Full Text Available Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases.To identify alternative splicing events (ASEs that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07 and highly metastatic (4T1 mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4% exons and in 1725 out of 189,460 (1% intronic regions, which affect 2623 out of 16,654 (16% genes. These changes correspond to putative alternative isoforms-several of which are novel-that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1. These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers.Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis-specific isoforms may contribute to the

  2. Levels and patterns of nucleotide variation in domestication QTL regions on rice chromosome 3 suggest lineage-specific selection.

    Directory of Open Access Journals (Sweden)

    Xianfa Xie

    Full Text Available Oryza sativa or Asian cultivated rice is one of the major cereal grass species domesticated for human food use during the Neolithic. Domestication of this species from the wild grass Oryza rufipogon was accompanied by changes in several traits, including seed shattering, percent seed set, tillering, grain weight, and flowering time. Quantitative trait locus (QTL mapping has identified three genomic regions in chromosome 3 that appear to be associated with these traits. We would like to study whether these regions show signatures of selection and whether the same genetic basis underlies the domestication of different rice varieties. Fragments of 88 genes spanning these three genomic regions were sequenced from multiple accessions of two major varietal groups in O. sativa--indica and tropical japonica--as well as the ancestral wild rice species O. rufipogon. In tropical japonica, the levels of nucleotide variation in these three QTL regions are significantly lower compared to genome-wide levels, and coalescent simulations based on a complex demographic model of rice domestication indicate that these patterns are consistent with selection. In contrast, there is no significant reduction in nucleotide diversity in the homologous regions in indica rice. These results suggest that there are differences in the genetic and selective basis for domestication between these two Asian rice varietal groups.

  3. Self-Concept Predicts Academic Achievement Across Levels of the Achievement Distribution: Domain Specificity for Math and Reading.

    Science.gov (United States)

    Susperreguy, Maria Ines; Davis-Kean, Pamela E; Duckworth, Kathryn; Chen, Meichu

    2017-09-18

    This study examines whether self-concept of ability in math and reading predicts later math and reading attainment across different levels of achievement. Data from three large-scale longitudinal data sets, the Avon Longitudinal Study of Parents and Children, National Institute of Child Health and Human Development-Study of Early Child Care and Youth Development, and Panel Study of Income Dynamics-Child Development Supplement, were used to answer this question by employing quantile regression analyses. After controlling for demographic variables, child characteristics, and early ability, the findings indicate that self-concept of ability in math and reading predicts later achievement in each respective domain across all quantile levels of achievement. These results were replicated across the three data sets representing different populations and provide robust evidence for the role of self-concept of ability in understanding achievement from early childhood to adolescence across the spectrum of performance (low to high). © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  4. The level of neuron-specific enolase and S-100 protein in the cerebrospinal fluid of patients with acute bacterial meningitis

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    A. V. Sokhan

    2016-08-01

    Full Text Available Aim. To evaluate the diagnostic and prognostic role of neuron-specific enolase (NSE and S-100 protein levels in cerebrospinal fluid (CSF of patients with acute bacterial meningitis in the course of the disease. Materials and Methods. 54 cases of acute bacterial meningitis were analyzed, among them – 26 with pneumococcal and 28 with meningococcal etiology. Patients were divided into groups depending on the severity and etiology of disease. In addition to routine laboratory methods, we analyzed the CSF levels of S-100 protein and NSE at admission and after 10 – 12 days of treatment. 12 patients with acute respiratory infections and meningism were examined as a comparison group. Results. In all patients with acute bacterial meningitis CSF NSE and protein S-100 levels were significantly higher than in the control group (P <0,05. CSF neuro specific proteins level was in direct dependence on severity of the disease, and in patients with severe disease was significantly higher than in patients with moderate severity and in the control group (P <0,01. After 10 – 12 days of treatment, the level of the NSE and S-100 protein decreased, but in severe cases was still higher than in the control group (P <0,05. Conclusions. Increased cerebrospinal fluid NSE and S – 100 protein levels shows the presence and value of neurons and glial cells damage in patients with acute bacterial meningitis. CSF S-100 protein and neuron-specific enolase levels help to determine the severity of neurons destruction and glial cells in patients with acute bacterial meningitis. Level of neurospecific protein is in direct proportion to the severity of the disease and is the highest in patients with severe cases (P<0,05. It confirms the diagnostic and prognostic value of CSF neurospecific protein determination in patients with bacterial meningitis.

  5. Tree specific traits vs. stand level characteristics - assessing the source depths of plant water uptake in a mixed forest stand

    Science.gov (United States)

    Seeger, Stefan; Brinkmann, Nadine; Kahmen, Ansgar; Weiler, Markus

    2017-04-01

    Due to differences in fine root distributions, physiological root characteristics and plant plasticity, the spatial and temporal characteristics of plant water uptake are expected to vary between different tree species. This has implications on the overall water budget of a forest stand as well as on the drought sensitivity of particular trees. A four-year time series of climate data, soil moisture, and stable water isotopes in soil and tree xylem was used to investigate plant water uptake dynamics of four tree species (beech - Fagus sylvatica, spruce - Picea abies, ash - Fraxinus excelsior and maple - Acer pseudoplatanus) in a mixed forest stand. Modeling with a modified version of the soil hydrological model Hydrus-1D allowed us to simulate continuous time series of stable water isotopes in plant water uptake, which were compared to the measured values in tree xylem water and soil water. We found that different estimated species specific fine root distributions and root water uptake parameters lead to very similar simulated water balances and soil water isotope depth profiles for all four species. According to our simulations, differences in evaporative demand (i.e. LAI) had the biggest influence on water uptake and soil water distributions. Comparing the isotopic signatures of simulated root water uptake and measured xylem water, the simulations for beech were most suited to predict the observed signatures of all four species. This indicates that isolated, tree specific parametrized 1-D simulations are not suited to predict actual water uptake of different trees in a mixed stand. Due to overlapping root spaces dominant trees (in our case beeches with an LAI of around 5.5) may influence the soil water storage below accompanying trees (spruces, ashes and maples with LAIs between 1.8 and 3.1) in a degree that their actual water uptake cannot be predicted with 1-D simulations based on their smaller LAI values. Consequently, for a mixed forest stand the interplay of

  6. Specific inspiratory muscle training does not improve performance or VO2max levels in well trained rowers.

    Science.gov (United States)

    Riganas, C S; Vrabas, I S; Christoulas, K; Mandroukas, K

    2008-09-01

    The purpose of this study was to examine the effects of specific inspiratory muscle training (IMT) on inspiratory muscle strength, maximal oxygen uptake (VO2max), maximal lactate accumulation (Lmax), dyspnea sensation and rowing performance in rowers. Ninteen well-trained rowers were divided into two groups: IMT (T) and control (C). The T group, in addition to their daily rowing practice, performed IMT by means of a threshold inspiratory muscle trainer for approximately 0.5h.d(-1), 5 times a week for 6 weeks. The C group participated only in their regular daily rowing training. Prior to the initiation and at the completion of the 6-week IMT program, both groups underwent an incremental treadmill run test to determine VO2max. Maximum inspiratory mouth pressure (PImax) was measured at rest and following the VO2max test. On a separate occasion, rowing performance was evaluated by a 2000 m all-out effort on a rowing ergometer. Dyspnea sensation was assessed by a modified Borg scale and Lmax was measured by an enzymatic method. Six weeks of IMT significantly (P VO2max test in the T group. In contrast, no changes in PImax were observed in the C group during the 6-week period. No significant differences were observed between pre- and post-test values in VO2max, dyspnea sensation, Lmax, and 2000 m race time in both groups. In conclusion, six weeks of IMT increases inspiratory muscle strength by approximately 28% in highly trained rowers. However, this increase in inspiratory muscle strength does not appear to improve VO2max, dyspnea sensation during exercise, or rowing performance in well-trained rowers.

  7. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    Science.gov (United States)

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  8. Annual variation in the levels of transcripts of sex-specific genes in the mantle of the common mussel, Mytilus edulis.

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    Sandhya Anantharaman

    Full Text Available Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL and female-specific vitelline envelope receptor for lysin (VERL could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July - August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5 but a very different pattern was observed for oestrogen receptor 2 (ER2. ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July-August but during gametogenesis (August to January and spawning (March to June VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release.

  9. Innate immune signaling induces high levels of TC-specific deaminase activity in primary monocyte-derived cells through expression of APOBEC3A isoforms.

    Science.gov (United States)

    Thielen, Beth K; McNevin, John P; McElrath, M Juliana; Hunt, Brook Vander Stoep; Klein, Kevin C; Lingappa, Jaisri R

    2010-09-03

    In HIV-1-infected individuals, G-to-A hypermutation is found in HIV-1 DNA isolated from peripheral blood mononuclear cells (PBMCs). These mutations are thought to result from editing by one or more host enzymes in the APOBEC3 (A3) family of cytidine deaminases, which act on CC (APOBEC3G) and TC (other A3 proteins) dinucleotide motifs in DNA (edited cytidine underlined). Although many A3 proteins display high levels of deaminase activity in model systems, only low levels of A3 deaminase activity have been found in primary cells examined to date. In contrast, here we report high levels of deaminase activity at TC motifs when whole PBMCs or isolated primary monocyte-derived cells were treated with interferon-alpha (IFNalpha) or IFNalpha-inducing toll-like receptor ligands. Induction of TC-specific deaminase activity required new transcription and translation and correlated with the appearance of two APOBEC3A (A3A) isoforms. Knockdown of A3A in monocytes with siRNA abolished TC-specific deaminase activity, confirming that A3A isoforms are responsible for all TC-specific deaminase activity observed. Both A3A isoforms appear to be enzymatically active; moreover, our mutational studies raise the possibility that the smaller isoform results from internal translational initiation. In contrast to the high levels of TC-specific activity observed in IFNalpha-treated monocytes, CC-specific activity remained low in PBMCs, suggesting that A3G deaminase activity is relatively inhibited, unlike that of A3A. Together, these findings suggest that deaminase activity of A3A isoforms in monocytes and macrophages may play an important role in host defense against viruses.

  10. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells.

    Science.gov (United States)

    Bauer, Georg

    2015-12-01

    NO metabolism and direct catalase inhibitors. The latter aspect is explicitely studied for the interaction between catalase inhibiting acetylsalicylic acid and an NO donor. It is also shown that hybrid molecules like NO-aspirin utilize this synergistic potential. Our data open novel approaches for rational tumor therapy based on specific ROS signaling and its control in tumor cells. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Species and gamete-specific fertilization success of two sea urchins under near future levels of pCO2

    Science.gov (United States)

    Sung, Chan-Gyung; Kim, Tae Won; Park, Young-Gyu; Kang, Seong-Gil; Inaba, Kazuo; Shiba, Kogiku; Choi, Tae Seob; Moon, Seong-Dae; Litvin, Steve; Lee, Kyu-Tae; Lee, Jung-Suk

    2014-09-01

    Since the Industrial Revolution, rising atmospheric CO2 concentration has driven an increase in the partial pressure of CO2 in seawater (pCO2), thus lowering ocean pH. We examined the separate effects of exposure of gametes to elevated pCO2 and low pH on fertilization success of the sea urchin Strongylocentrotus nudus. Sperm and eggs were independently exposed to seawater with pCO2 levels ranging from 380 (pH 7.96-8.3) to 6000 ppmv (pH 7.15-7.20). When sperm were exposed, fertilization rate decreased drastically with increased pCO2, even at a concentration of 450 ppmv (pH range: 7.94 to 7.96). Conversely, fertilization of Hemicentrotus pulcherrimus was not significantly changed even when sperm was exposed to pCO2 concentrations as high as 750 ppmv. Exposure of S. nudus eggs to seawater with high pCO2 did not affect fertilization success, suggesting that the effect of increased pCO2 on sperm is responsible for reduced fertilization success. Surprisingly, this result was not related to sperm motility, which was insensitive to pCO2. When seawater was acidified using HCl, leaving pCO2 constant, fertilization success in S. nudus remained high (> 80%) until pH decreased to 7.3. While further studies are required to elucidate the physiological mechanism by which elevated pCO2 impairs sperm and reduces S. nudus fertilization, this study suggests that in the foreseeable future, sea urchin survival may be threatened due to lower fertilization success driven by elevated pCO2 rather than by decreased pH in seawater.

  12. Relationship of Endothelial Cell-Specific Molecule 1 Level in Stress Hyperglycemia Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pilot Study.

    Science.gov (United States)

    Qiu, Chongrong; Sui, Jian; Zhang, Qian; Wei, Peng; Wang, Peng; Fu, Qiang

    2016-10-01

    Endothelial cell-specific molecule 1 ([ESM-1], endocan) is a new biomarker of endothelial dysfunction, which may be involved in the pathogenesis of atherosclerosis and stress hyperglycemia in patients with acute ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated serum ESM-1 levels in patients with stress hyperglycemia having STEMI; 105 patients with STEMI and 33 individuals as a control group were included in the study. The patients were followed up for 3 months and major adverse cardiac events (MACEs) were recorded. Serum ESM-1 level was significantly higher in patients with stress hyperglycemia patients having STEMI (P levels correlated positively with glucose levels (r = .21, P levels >1.01 ng/mL (odds ratio 3.01, 95% confidence interval 1.05-8.64, P stress hyperglycemia having STEMI, admission glucose levels are associated with ESM-1 levels, and ESM-1 is an independent predictor of MACEs. An ESM-1 level >1.01 ng/mL is likely to predict a greater risk of MACEs. © The Author(s) 2015.

  13. Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2010-01-01

    The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained...... from a cohort of 136 donors from Daraweesh in Sudan. The cohort was followed for malaria infection for 9 years. After an initial analysis, the immune response to Pf332-C231 antigen was the only one found associated with protection, thus taken for further analysis. The number of previous clinical...... malaria episodes experienced by the donors was used as an index for relative protection. The number of these episodes was found to be negatively correlated with the levels of pre-existing total IgG, IgG2 and IgG3 to Pf332-C231 (correlation coefficient, CC - 0.215, p=0.012; CC - 0.195, p=0.023 and CC - 0...

  14. Antiviral Functions of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific IgG Antibodies: Effects of Antiretroviral Therapy and Implications for Therapeutic HIV-1 Vaccine Design.

    Science.gov (United States)

    French, Martyn A; Tjiam, M Christian; Abudulai, Laila N; Fernandez, Sonia

    2017-01-01

    . As HIV-1 infects cells in GCs and induces GC dysfunction, which may persist during ART, strategies for boosting HIV-1-specific IgG antibody responses should include early commencement of ART and possibly the use of particular antiretroviral drugs to optimize drug levels in lymphoid follicles. Finally, enhancing particular functions of HIV-1-specific IgG antibody responses by using adjuvants or cytokines to modulate the IgG subclass content of the antibody response might be investigated in NHP models of HIV-1 infection and during trials of therapeutic vaccines in HIV patients.

  15. Blood Lead Levels and Cause-Specific Mortality of Inorganic Lead-Exposed Workers in South Korea.

    Directory of Open Access Journals (Sweden)

    Min-Gi Kim

    Full Text Available The objective of this study was to identify the association of blood lead level (BLL with mortality in inorganic lead-exposed workers of South Korea. A cohort was compiled comprising 81,067 inorganic lead exposed workers working between January 1, 2000, and December 31, 2004. This cohort was merged with the Korean National Statistical Office to follow-up for mortality between 2000 and 2008. After adjusting for age and other carcinogenic metal exposure, all-cause mortality (Relative risk [RR] 1.36, 95% confidence interval [CI] 1.03-1.79, digestive disease (RR 3.23, 95% CI 1.33-7.86, and intentional self-harm (RR 2.92, 95% CI 1.07-7.81 were statistically significantly higher in males with BLL >20 μg/dl than of those with BLL ≤10μg/dl. The RR of males with BLL of 10-20 μg/dl was statistically higher than of those with BLL ≤10μg/dl in infection (RR 3.73. 95% CI, 1.06-13.06. The RRs of females with 10-20 μg/dl BLL was statistically significantly greater than those with BLL <10μg/dl in all-cause mortality (RR 1.93, 95% CI 1.16-3.20 and colon and rectal cancer (RR 13.42, 95% CI 1.21-149.4. The RRs of females with BLL 10-20 μg/dl (RR 10.45, 95% CI 1.74-62.93 and BLL ≥20 μg/dl (RR 12.68, 95% CI 1.69-147.86 was statistically significantly increased in bronchus and lung cancer. The increased suicide of males with ≥20 μg/dl BLLs, which might be caused by major depression, might be associated with higher lead exposure. Also, increased bronchus and lung cancer mortality in female workers with higher BLL might be related to lead exposure considering low smoking rate in females. The kinds of BLL-associated mortality differed by gender.

  16. Scaling up health knowledge at European level requires sharing integrated data: an approach for collection of database specification

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    Menditto E

    2016-06-01

    with the aim of improving data sharing on a European level. A total of six databases belonging to three different European countries (Spain, Republic of Ireland, and Italy were included in the analysis. Preliminary results suggest that there are some similarities. However, these results should be applied in different contexts and European countries, supporting the idea that large European studies should be designed in order to get the most of already available databases. Keywords: health care databases, adherence, electronic health records, outcome research

  17. Quantification of Chitinase mRNA Levels in Human and Mouse Tissues by Real-Time PCR: Species-Specific Expression of Acidic Mammalian Chitinase in Stomach Tissues.

    Science.gov (United States)

    Ohno, Misa; Togashi, Yuto; Tsuda, Kyoko; Okawa, Kazuaki; Kamaya, Minori; Sakaguchi, Masayoshi; Sugahara, Yasusato; Oyama, Fumitaka

    2013-01-01

    Chitinase hydrolyzes chitin, which is an N-acetyl-D-glucosamine polymer that is present in a wide range of organisms, including insects, parasites and fungi. Although mammals do not contain any endogenous chitin, humans and mice express two active chitinases, chitotriosidase (Chit1) and acidic mammalian chitinase (AMCase). Because the level of expression of these chitinases is increased in many inflammatory conditions, including Gaucher disease and mouse models of asthma, both chitinases may play important roles in the pathophysiologies of these and other diseases. We recently established a quantitative PCR system using a single standard DNA and showed that AMCase mRNA is synthesized at extraordinarily high levels in mouse stomach tissues. In this study, we applied this methodology to the quantification of chitinase mRNAs in human tissues and found that both chitinase mRNAs were widely expressed in normal human tissues. Chit1 mRNA was highly expressed in the human lung, whereas AMCase mRNA was not overexpressed in normal human stomach tissues. The levels of these mRNAs in human tissues were significantly lower than the levels of housekeeping genes. Because the AMCase expression levels were quite different between the human and mouse stomach tissues, we developed a quantitative PCR system to compare the mRNA levels between human and mouse tissues using a human-mouse hybrid standard DNA. Our analysis showed that Chit1 mRNA is expressed at similar levels in normal human and mouse lung. In contrast, the AMCase expression level in human stomach was significantly lower than that expression level observed in mouse stomach. These mRNA differences between human and mouse stomach tissues were reflecting differences in the chitinolytic activities and levels of protein expression. Thus, the expression level of the AMCase in the stomach is species-specific.

  18. Stimulus-response bindings code both abstract and specific representations of stimuli: evidence from a classification priming design that reverses multiple levels of response representation.

    Science.gov (United States)

    Horner, A J; Henson, R N

    2011-11-01

    Repetition priming can be caused by the rapid retrieval of previously encoded stimulus-response (S-R) bindings. S-R bindings have recently been shown to simultaneously code multiple levels of response representation, from specific Motor-actions to more abstract Decisions ("yes"/"no") and Classifications (e.g., "man-made"/"natural"). Using an experimental design that reverses responses at all of these levels, we assessed whether S-R bindings also code multiple levels of stimulus representation. Across two experiments, we found effects of response reversal on priming when switching between object pictures and object names, consistent with S-R bindings that code stimuli at an abstract level. Nonetheless, the size of this reversal effect was smaller for such across-format (e.g., word-picture) repetition than for within-format (e.g., picture-picture) repetition, suggesting additional coding of format-specific stimulus representations. We conclude that S-R bindings simultaneously represent both stimuli and responses at multiple levels of abstraction.

  19. The Relationship Between Population-Level Exposure to Alcohol Advertising on Television and Brand-Specific Consumption Among Underage Youth in the US

    Science.gov (United States)

    Ross, Craig S.; Maple, Emily; Siegel, Michael; DeJong, William; Naimi, Timothy S.; Padon, Alisa A.; Borzekowski, Dina L.G.; Jernigan, David H.

    2015-01-01

    Aims: We investigated the population-level relationship between exposure to brand-specific advertising and brand-specific alcohol use among US youth. Methods: We conducted an internet survey of a national sample of 1031 youth, ages 13–20, who had consumed alcohol in the past 30 days. We ascertained all of the alcohol brands respondents consumed in the past 30 days, as well as which of 20 popular television shows they had viewed during that time period. Using a negative binomial regression model, we examined the relationship between aggregated brand-specific exposure to alcohol advertising on the 20 television shows [ad stock, measured in gross rating points (GRPs)] and youth brand-consumption prevalence, while controlling for the average price and overall market share of each brand. Results: Brands with advertising exposure on the 20 television shows had a consumption prevalence about four times higher than brands not advertising on those shows. Brand-level advertising elasticity of demand varied by exposure level, with higher elasticity in the lower exposure range. The estimated advertising elasticity of 0.63 in the lower exposure range indicates that for each 1% increase in advertising exposure, a brand's youth consumption prevalence increases by 0.63%. Conclusions: At the population level, underage youths' exposure to brand-specific advertising was a significant predictor of the consumption prevalence of that brand, independent of each brand's price and overall market share. The non-linearity of the observed relationship suggests that youth advertising exposure may need to be lowered substantially in order to decrease consumption of the most heavily advertised brands. PMID:25754127

  20. Micro-organismos da subclasse Coccidia: resistência e implicações para o processamento de materiais de assistência à saúde

    OpenAIRE

    Rafael Queiroz de Souza; Lilian Machado Torres; Kazuko Uchikawa Graziano; Ruth Natália Teresa Turrini

    2012-01-01

    Este estudo teórico propõe uma reflexão sobre a resistência intrínseca da subclasse Coccidia, particularmente o gênero Cryptosporidium, considerado como um agente potencialmente patogênico para pacientes imunocomprometidos, e suas repercussões na prática assistencial. Atualmente, as diretrizes internacionais e nacionais aprovam como procedimento seguro a desinfecção química de alto nível de endoscópios digestivos, após sua limpeza. No entanto, estudos evidenciaram que micro-organismos da subc...

  1. Specific glucosinolate analysis reveals variable levels of epimeric glucobarbarins, dietary precursors of 5-phenyloxazolidine-2-thiones, in watercress types with contrasting chromosome numbers.

    Science.gov (United States)

    Agerbirk, Niels; Olsen, Carl Erik; Cipollini, Don; Ørgaard, Marian; Linde-Laursen, Ib; Chew, Frances S

    2014-10-01

    Watercress obtained in food stores in the United States contained significant levels of epiglucobarbarin [(R)-2-hydroxy-2-phenylethylglucosinolate] and low levels of the 2S-epimer glucobarbarin identified by an HPLC+NMR+MS/MS approach. Typical combined levels were 4-7 μmol/g dry wt. The hydrolysis product, 5-phenyloxazolidine-2-thione (barbarin), was detected at similar levels as the precursor glucosinolates after autolysis of fresh watercress in water. Fragmentation patterns in MS(2) of reference desulfoglucosinolates were side chain specific and suitable for routine identification. Watercress was of two main glucosinolate chemotypes: Material from U.S. food stores had a complex profile including glucobarbarins, gluconasturtiin, indole glucosinolates and high levels (6-28 μmol/g dry wt.) of long-chain methylsulfinylalkyl and methylthioalkyl glucosinolates. Material from European food stores had a simple profile dominated by gluconasturtiin, with low levels of epiglucobarbarin and moderate levels of indole glucosinolates. Some wild U.S. material was similar to the U.S. food store type. Both types were found to be Nasturtium officinale by floral parts morphology. Cytological analysis of one U.S. food store accession indicated that it represented a chromosome-doubled variant within N. officinale. The nutritional consequences and invasive potential of the U.S. food store chemotype are discussed.

  2. The impact of hypoxemia on serum total and free prostate-specific antigen levels in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Ozge, Cengiz; Bozlu, Murat; Ozgur, Eylem Sercan; Tek, Mesut; Tunckiran, Ahmet; Muslu, Necati; Ilvan, Ahmet

    2015-05-01

    Prostate-specific antigen (PSA) is the most important biochemical marker in the diagnosis and follow-up of patients with prostate cancer. In recent years, a relationship between PSA levels and hypoxic conditions has been described. However, no study has investigated the PSA levels in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the impact of hypoxemia on serum total (tPSA) and free PSA (fPSA) levels in patients with COPD. Between January 2010 and January 2014, 95 male patients who hospitalized for acute exacerbations of COPD and 80 control subjects were enrolled in the study. Serum tPSA and fPSA levels and f/tPSA ratios were determined in all patients on the first day of hospitalization (exacerbation) and 7 days after the treatment (stable state). Statistical analysis included paired t test and Mann-Whitney U test. No statistically significant differences were found between COPD and control groups with regard to the baseline characteristics, except for smoking status. The levels of serum tPSA and fPSA during exacerbation of COPD were significantly higher than the levels of the stable period (p 0.05). Hypoxemia during acute exacerbation of COPD can cause a rise in serum tPSA and fPSA levels, but f/tPSA ratio is not affected. Acute exacerbation of COPD may be added to list of the events in which PSA measurements must be interpreted with caution.

  3. Sensitivity and specificity of optical coherence tomography angiography (OCT-A) for detection of choroidal neovascularization in real-life practice and varying retinal expertise level.

    Science.gov (United States)

    Souedan, Vaël; Souied, Eric H; Caillaux, Violaine; Miere, Alexandra; Ameen, Ala El; Blanco-Garavito, Rocio

    2017-05-25

    To evaluate the diagnostic accuracy of OCT angiography (OCT-A) detecting or predicting choroidal neovascularization (CNV), by ophthalmologists of disparate degrees of skills in retinal diseases, using spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) as a standard reference. Retrospective observational case series. Patient presenting maculopathy and complete imaging were included. FA, SD-OCT, OCT-A and FA coupled to SD-OCT images were graded independently for presence or absence of CNV by ophthalmologists with varying expertise levels. Overall sensitivity of OCT-A was 85.62% (95% CI 79.04-90.76%) and specificity was 81.51% (95% CI 73.36-88.03). Sensitivity of FA was 74.51% (95% CI 66.84-81.20), and specificity was 82.35% (95% CI 74.30-88.73). Sensitivity of FA + SD-OCT was 92.72% (95% CI 87.34-96.30), and specificity was 90.91% (95% CI 84.31-95.37). OCT-A has good sensitivity and specificity for the detection of CNV in all expertise level groups. OCT-A may soon become a routine tool for CNV diagnosis and follow-up.

  4. [Correlation between the magnitude of skin prick test reactivity and pollen-specific serum IgE levels in patients with respiratory allergy].

    Science.gov (United States)

    Tlachi-Corona, Laura; Caballero-López, Chrystopherson Gengyny; López-García, Aída Inés; Papaqui-Tapia, Sergio; Arana-Muñoz, Oswaldo; Carcaño-Pérez, María Socorro Yolanda; Marín-Marín, Araceli; Garrido-Priego, Fabiola

    2014-01-01

    For the etiological diagnosis of allergic respiratory diseases skin tests or specific serum IgE determination are used. To determine the correlation between the extent of reactivity to cutaneous prick tests and the levels of pollen specific serum IgE in patients with respiratory allergy. A prolective, descriptive and transversal study was done with patients of both genders, aged 2 to 60 years, who attended for the first time at the service of Allergy and Clinical Immunology of University Hospital of Puebla, Mexico, with presumptive diagnosis of respiratory allergy. All patients underwent clinical history, skin prick tests with standardized allergenic extracts and quantification of pollen specific serum IgE by chemiluminescence method. We estimated the correlation index r using the statistical method Pearson product-moment correlation coefficient; a value r equal to or higher than 0.70 was considered a significant relationship or a high correlation. Nine-one patients were included, of whom 58.2% were female. The diagnoses were: allergic rhinitis (79.1%), asthma and allergic rhinitis (16.5%) and only asthma (4.4%). Only significant correlation was found in patients with allergic rhinitis for Rumex crispus (r = 0.702) and in patients with asthma and rhinitis for Ambrosia trifida (r = 1). Only for Rumex crispus and Ambrosia trifida, the skin prick tests or the determination of specific serum IgE levels are comparable diagnostic methods of allergic respiratory diseases.

  5. Evaluation of Radiation Doses Due to Consumption of Contaminated Food Items and Calculation of Food Class-Specific Derived Intervention Levels

    Energy Technology Data Exchange (ETDEWEB)

    Heinzelman, K M; Mansfield, W G

    2010-04-27

    This document evaluates the expected radiation dose due to the consumption of several specific food classes (dairy, meat, produce, etc.) contaminated with specific radionuclides, and relates concentration levels in food to the detection abilities of typical aboratory analysis/measurement methods. The attached charts present the limiting organ dose as a function of the radionuclide concentration in a particular food class, and allow the user to compare these concentrations and doses to typical analytical detection apabilities. The expected radiation dose depends on several factors: the age of the individual; the radionuclide present in the food; the concentration of the radionuclide in the food; and the amount of food consumed. Food consumption rates for individuals of various ges were taken from the 1998 United States Food and Drug Administration (FDA) document, Accidental Radioactive Contamination of HUman Food and Animal Feeds: Recommendations for State and Local Agencies. In that document, the FDA defines the erived Intervention Level (DIL), which is the concentration of a particular radionuclide in food that if consumed could result in an individual receiving a radiation dose exceeding the Protection Action Guide (PAG) thresholds for intervention. This document also resents odified, food class specific DIL, which is calculated using a somewhat modified version of the FDA's procedure. This document begins with an overview of the FDA's DIL calculation, followed by a description of the food class specific DIL calculations, and finally charts of the radiation dose per radioactivity concentration for several food class/radionuclide combinations.

  6. Level of tissue differentiation influences the activation of a heat-inducible flower-specific system for genetic containment in poplar (Populus tremula L.).

    Science.gov (United States)

    Hoenicka, Hans; Lehnhardt, Denise; Nunna, Suneetha; Reinhardt, Richard; Jeltsch, Albert; Briones, Valentina; Fladung, Matthias

    2016-02-01

    Differentiation level but not transgene copy number influenced activation of a gene containment system in poplar. Heat treatments promoted CRE gene body methylation. The flower-specific transgene deletion