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Sample records for scale immune profiling

  1. Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging

    PubMed Central

    Whiting, Chan C.; Siebert, Janet; Newman, Aaron M.; Du, Hong-wu; Alizadeh, Ash A.; Goronzy, Jorg; Weyand, Cornelia M.; Krishnan, Eswar; Fathman, C. Garrison; Maecker, Holden T.

    2015-01-01

    While many age-associated immune changes have been reported, a comprehensive set of metrics of immune aging is lacking. Here we report data from 243 healthy adults aged 40–97, for whom we measured clinical and functional parameters, serum cytokines, cytokines and gene expression in stimulated and unstimulated PBMC, PBMC phenotypes, and cytokine-stimulated pSTAT signaling in whole blood. Although highly heterogeneous across individuals, many of these assays revealed trends by age, sex, and CMV status, to greater or lesser degrees. Age, then sex and CMV status, showed the greatest impact on the immune system, as measured by the percentage of assay readouts with significant differences. An elastic net regression model could optimally predict age with 14 analytes from different assays. This reinforces the importance of multivariate analysis for defining a healthy immune system. These data provide a reference for others measuring immune parameters in older people. PMID:26197454

  2. Large-scale microarray profiling reveals four stages of immune escape in non-Hodgkin lymphomas.

    PubMed

    Tosolini, Marie; Algans, Christelle; Pont, Frédéric; Ycart, Bernard; Fournié, Jean-Jacques

    2016-07-01

    Non-Hodgkin B-cell lymphoma (B-NHL) are aggressive lymphoid malignancies that develop in patients due to oncogenic activation, chemo-resistance, and immune evasion. Tumor biopsies show that B-NHL frequently uses several immune escape strategies, which has hindered the development of checkpoint blockade immunotherapies in these diseases. To gain a better understanding of B-NHL immune editing, we hypothesized that the transcriptional hallmarks of immune escape associated with these diseases could be identified from the meta-analysis of large series of microarrays from B-NHL biopsies. Thus, 1446 transcriptome microarrays from seven types of B-NHL were downloaded and assembled from 33 public Gene Expression Omnibus (GEO) datasets, and a method for scoring the transcriptional hallmarks in single samples was developed. This approach was validated by matching scores to phenotypic hallmarks of B-NHL such as proliferation, signaling, metabolic activity, and leucocyte infiltration. Through this method, we observed a significant enrichment of 33 immune escape genes in most diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) samples, with fewer in mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) samples. Comparing these gene expression patterns with overall survival data evidenced four stages of cancer immune editing in B-NHL: non-immunogenic tumors (stage 1), immunogenic tumors without immune escape (stage 2), immunogenic tumors with immune escape (stage 3), and fully immuno-edited tumors (stage 4). This model complements the standard international prognostic indices for B-NHL and proposes that immune escape stages 3 and 4 (76% of the FL and DLBCL samples in this data set) identify patients relevant for checkpoint blockade immunotherapies. PMID:27622044

  3. Immune profile alterations in thalassaemic patients.

    PubMed

    Quintiliani, L; Mastromonaco, A; Giuliani, E; Buzzonetti, A; Sisti, P; Guglielmetti, M; Iudicone, P; Greca, E; Damiano, A M; Ciancamerla, A M

    1983-01-01

    Aspects of the humoral and cellular immune response have been studied in polytransfused patients with beta-thalassaemia major. Serum immunoglobulins (G, A, M) levels were significantly higher than in controls; reduced C4 serum level and high incidence of circulating immune complexes and anti-nuclear autoantibodies were found in the majority of patients. Marked increases were also observed in absolute and relative numbers of lymphocytes and their subpopulations. Such results suggested that the allogenic stimulation, by frequent transfusion, is the mainly responsible of the immunological alterations observed in these patients. PMID:6677264

  4. Epigenetic and immune function profiles associated with posttraumatic stress disorder

    PubMed Central

    Uddin, Monica; Aiello, Allison E.; Wildman, Derek E.; Koenen, Karestan C.; Pawelec, Graham; de los Santos, Regina; Goldmann, Emily; Galea, Sandro

    2010-01-01

    The biologic underpinnings of posttraumatic stress disorder (PTSD) have not been fully elucidated. Previous work suggests that alterations in the immune system are characteristic of the disorder. Identifying the biologic mechanisms by which such alterations occur could provide fundamental insights into the etiology and treatment of PTSD. Here we identify specific epigenetic profiles underlying immune system changes associated with PTSD. Using blood samples (n = 100) obtained from an ongoing, prospective epidemiologic study in Detroit, the Detroit Neighborhood Health Study, we applied methylation microarrays to assay CpG sites from more than 14,000 genes among 23 PTSD-affected and 77 PTSD-unaffected individuals. We show that immune system functions are significantly overrepresented among the annotations associated with genes uniquely unmethylated among those with PTSD. We further demonstrate that genes whose methylation levels are significantly and negatively correlated with traumatic burden show a similar strong signal of immune function among the PTSD affected. The observed epigenetic variability in immune function by PTSD is corroborated using an independent biologic marker of immune response to infection, CMV—a typically latent herpesvirus whose activity was significantly higher among those with PTSD. This report of peripheral epigenomic and CMV profiles associated with mental illness suggests a biologic model of PTSD etiology in which an externally experienced traumatic event induces downstream alterations in immune function by reducing methylation levels of immune-related genes. PMID:20439746

  5. Genome-wide analysis of immune system genes by expressed sequence Tag profiling.

    PubMed

    Giallourakis, Cosmas C; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E; Zukerberg, Lawrence R; Daly, Mark J; Rioux, John D; Xavier, Ramnik J

    2013-06-01

    Profiling studies of mRNA and microRNA, particularly microarray-based studies, have been extensively used to create compendia of genes that are preferentially expressed in the immune system. In some instances, functional studies have been subsequently pursued. Recent efforts such as the Encyclopedia of DNA Elements have demonstrated the benefit of coupling RNA sequencing analysis with information from expressed sequence tags (ESTs) for transcriptomic analysis. However, the full characterization and identification of transcripts that function as modulators of human immune responses remains incomplete. In this study, we demonstrate that an integrated analysis of human ESTs provides a robust platform to identify the immune transcriptome. Beyond recovering a reference set of immune-enriched genes and providing large-scale cross-validation of previous microarray studies, we discovered hundreds of novel genes preferentially expressed in the immune system, including noncoding RNAs. As a result, we have established the Immunogene database, representing an integrated EST road map of gene expression in human immune cells, which can be used to further investigate the function of coding and noncoding genes in the immune system. Using this approach, we have uncovered a unique metabolic gene signature of human macrophages and identified PRDM15 as a novel overexpressed gene in human lymphomas. Thus, we demonstrate the utility of EST profiling as a basis for further deconstruction of physiologic and pathologic immune processes. PMID:23616578

  6. Immune cell profiling to guide therapeutic decisions in rheumatic diseases

    PubMed Central

    Ermann, Joerg; Rao, Deepak A.; Teslovich, Nikola C.; Brenner, Michael B.; Raychaudhuri, Soumya

    2016-01-01

    Biomarkers are needed to guide treatment decisions for patients with rheumatic diseases. Although the phenotypic and functional analysis of immune cells is an appealing strategy for understanding immune-mediated disease processes, immune cell profiling currently has no role in clinical rheumatology. New technologies, including mass cytometry, gene expression profiling by RNA sequencing (RNA-seq) and multiplexed functional assays, enable the analysis of immune cell function with unprecedented detail and promise not only a deeper understanding of pathogenesis, but also the discovery of novel biomarkers. The large and complex data sets generated by these technologies—big data—require specialized approaches for analysis and visualization of results. Standardization of assays and definition of the range of normal values are additional challenges when translating these novel approaches into clinical practice. In this Review, we discuss technological advances in the high-dimensional analysis of immune cells and consider how these developments might support the discovery of predictive biomarkers to benefit the practice of rheumatology and improve patient care. PMID:26034835

  7. Profiling the host immune response to tuberculosis vaccines.

    PubMed

    Fletcher, Helen A

    2015-09-29

    There is an urgent need for improved vaccines for protection against tuberculosis (TB) disease and an immune correlate of protection would aid in the design, development and testing of a new TB vaccine candidates. The immune response to TB is likely to be multi-factorial and transcriptional profiling is a potentially useful tool for the simultaneous measurement of multiple immune processes. Although there are 16 candidate TB vaccines in clinical development the only published transcriptomics studies are from the MVA85A trials. With the publication of transcriptional signatures from the South African adolescent cohort study and the GC6 consortium also expected in 2015 the next year could see an increase of interest in the use of transcriptomics in TB vaccine development. PMID:26241949

  8. Mapping immune response profiles: the emerging scenario from helminth immunology.

    PubMed

    Díaz, Alvaro; Allen, Judith E

    2007-12-01

    Metazoan parasites of mammals (helminths) belong to highly divergent animal groups and yet induce a stereotypical host response: Th2-type immunity. It has long been debated whether this response benefits the host or the parasite. We review the current literature and suggest that Th2 immunity is an evolutionarily appropriate response to metazoan invaders both in terms of controlling parasites and repairing the damage they inflict. However, successful parasites induce regulatory responses, which become superimposed with, and control, Th2 responses. Beyond helminth infection, this superimposition of response profiles may be the norm: both Th1 and Th2 responses coexist with regulatory responses or, on the contrary, with the inflammatory Th17 responses. Thus, typical responses to helminth infections may differ from Th2-dominated allergic reactions in featuring not only a stronger regulatory component but also a weaker Th17 component. The similarity of immune response profiles to phylogenetically distinct helminths probably arises from mammalian evolution having hard-wired diverse worm molecules, plus tissue-damage signals, to the beneficial Th2 response, and from the convergent evolution of different helminths to elicit regulatory responses. We speculate that initiation of both Th2 and regulatory responses involves combinatorial signaling, whereby TLR-mediated signals are modulated by signals from other innate receptors, including lectins. PMID:18000958

  9. Estimating Cognitive Profiles Using Profile Analysis via Multidimensional Scaling (PAMS)

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Frisby, Craig L.; Davison, Mark L.

    2004-01-01

    Two of the most popular methods of profile analysis, cluster analysis and modal profile analysis, have limitations. First, neither technique is adequate when the sample size is large. Second, neither method will necessarily provide profile information in terms of both level and pattern. A new method of profile analysis, called Profile Analysis via…

  10. The Ocular Conjunctiva as a Mucosal Immunization Route: A Profile of the Immune Response to the Model Antigen Tetanus Toxoid

    PubMed Central

    Belij, Sandra; Marinkovic, Emilija; Stojicevic, Ivana; Montanaro, Jacqueline; Stein, Elisabeth; Bintner, Nora; Stojanovic, Marijana

    2013-01-01

    Background In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen. Materials and methods BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 × LD50) of tetanus toxin. Results The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFNγ and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p<0.05). Conclusion Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively. PMID

  11. Multi-scale modeling of the CD8 immune response

    NASA Astrophysics Data System (ADS)

    Barbarroux, Loic; Michel, Philippe; Adimy, Mostafa; Crauste, Fabien

    2016-06-01

    During the primary CD8 T-Cell immune response to an intracellular pathogen, CD8 T-Cells undergo exponential proliferation and continuous differentiation, acquiring cytotoxic capabilities to address the infection and memorize the corresponding antigen. After cleaning the organism, the only CD8 T-Cells left are antigen-specific memory cells whose role is to respond stronger and faster in case they are presented this very same antigen again. That is how vaccines work: a small quantity of a weakened pathogen is introduced in the organism to trigger the primary response, generating corresponding memory cells in the process, giving the organism a way to defend himself in case it encounters the same pathogen again. To investigate this process, we propose a non linear, multi-scale mathematical model of the CD8 T-Cells immune response due to vaccination using a maturity structured partial differential equation. At the intracellular scale, the level of expression of key proteins is modeled by a delay differential equation system, which gives the speeds of maturation for each cell. The population of cells is modeled by a maturity structured equation whose speeds are given by the intracellular model. We focus here on building the model, as well as its asymptotic study. Finally, we display numerical simulations showing the model can reproduce the biological dynamics of the cell population for both the primary response and the secondary responses.

  12. Transcriptional Profiling of the Immune Response to Marburg Virus Infection

    PubMed Central

    Yen, Judy; Caballero, Ignacio S.; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J.

    2015-01-01

    ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the

  13. Understanding immune protection against tuberculosis using RNA expression profiling.

    PubMed

    von Both, Ulrich; Kaforou, Myrsini; Levin, Michael; Newton, Sandra M

    2015-09-29

    A major limitation in the development and testing of new tuberculosis (TB) vaccines is the current inadequate understanding of the nature of the immune response required for protection against either infection with Mycobacterium tuberculosis (MTB) or progression to disease. Genome wide RNA expression analysis has provided a new tool with which to study the inflammatory and immunological response to mycobacteria. To explore how currently available transcriptomic data might be used to understand the basis of protective immunity to MTB, we analysed and reviewed published RNA expression studies to (1) identify a "susceptible" immune response in patients with acquired defects in the interferon gamma pathway; (2) identify the "failing" transcriptomic response in patients with TB as compared with latent TB infection (LTBI); and (3) identify elements of the "protective" response in healthy latently infected and healthy uninfected individuals. PMID:26006085

  14. Understanding immune protection against tuberculosis using RNA expression profiling

    PubMed Central

    von Both, Ulrich; Kaforou, Myrsini; Levin, Michael; Newton, Sandra M.

    2015-01-01

    A major limitation in the development and testing of new tuberculosis (TB) vaccines is the current inadequate understanding of the nature of the immune response required for protection against either infection with Mycobacterium tuberculosis (MTB) or progression to disease. Genome wide RNA expression analysis has provided a new tool with which to study the inflammatory and immunological response to mycobacteria. To explore how currently available transcriptomic data might be used to understand the basis of protective immunity to MTB, we analysed and reviewed published RNA expression studies to (1) identify a “susceptible” immune response in patients with acquired defects in the interferon gamma pathway; (2) identify the “failing” transcriptomic response in patients with TB as compared with latent TB infection (LTBI); and (3) identify elements of the “protective” response in healthy latently infected and healthy uninfected individuals. PMID:26006085

  15. Dissemination strategy for immunizing scale-free networks

    NASA Astrophysics Data System (ADS)

    Stauffer, Alexandre O.; Barbosa, Valmir C.

    2006-11-01

    We consider the problem of distributing a vaccine for immunizing a scale-free network against a given virus or worm. We introduce a method, based on vaccine dissemination, that seems to reflect more accurately what is expected to occur in real-world networks. Also, since the dissemination is performed using only local information, the method can be easily employed in practice. Using a random-graph framework, we analyze our method both mathematically and by means of simulations. We demonstrate its efficacy regarding the trade-off between the expected number of nodes that receive the vaccine and the network’s resulting vulnerability to develop an epidemic as the virus or worm attempts to infect one of its nodes. For some scenarios, the method is seen to render the network practically invulnerable to attacks while requiring only a small fraction of the nodes to receive the vaccine.

  16. Determining the significance of scale values from multidimensional scaling profile analysis using a resampling method.

    PubMed

    Ding, Cody S

    2005-02-01

    Although multidimensional scaling (MDS) profile analysis is widely used to study individual differences, there is no objective way to evaluate the statistical significance of the estimated scale values. In the present study, a resampling technique (bootstrapping) was used to construct confidence limits for scale values estimated from MDS profile analysis. These bootstrap confidence limits were used, in turn, to evaluate the significance of marker variables of the profiles. The results from analyses of both simulation data and real data suggest that the bootstrap method may be valid and may be used to evaluate hypotheses about the statistical significance of marker variables of MDS profiles. PMID:16097342

  17. The Theoretical Orientation Profile Scale-Revised: A Validation Study.

    ERIC Educational Resources Information Center

    Worthington, Roger L.; Dillon, Frank R.

    2003-01-01

    This study supported evidence of reliability and validity of the Theoretical Orientation Profile Scale-Revised (TOPS-R) scores. The TOPS-R was designed to measure theoretical orientation among counselors and trainees. Factor analysis yielded a 6-factor solution accounting for 87.5% of the total variance in the scale. The 6 factors corresponded to…

  18. Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology

    PubMed Central

    Michael, Benedict D.; Griffiths, Michael J.; Granerod, Julia; Brown, David; Davies, Nicholas W. S.; Borrow, Ray; Solomon, Tom

    2016-01-01

    Background Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15–60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. Methods We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Results Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Conclusions Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation. PMID:26808276

  19. Expression profiling analysis of immune-related genes in channel catfish (Ictalurus punctatus) skin mucus following Flavobacterium columnare challenge.

    PubMed

    Ren, Yichao; Zhao, Honggang; Su, Baofeng; Peatman, Eric; Li, Chao

    2015-10-01

    Fish are covered by a watery gel-mucus, mainly secreted by the goblet cells, serving as the physical and biochemical barrier between the external environment and the interior milieu, playing more important roles in fish that without scale. Despite the important roles of mucus in fish immunity, the knowledge of detailed molecular events happened during infection process is still limited. While most studies were focused on characterizing the protein and enzyme activities in the mucus following challenge, no studies have examined the gene expression profiles in fish mucus. In this regard, herein we carried out the first gene profiling analysis in catfish mucus using real-time PCR. Ten important immune-related genes were selected according to our previous studies. Their expression levels were examined in the early timepoints (namely, 1 h, 2 h, 4 h, 8 h, and 24 h) following Flavobacterium columnare challenge. Notably, expression levels of most of the selected genes were rapidly altered by the challenge. Seven genes were down-regulated, while only three genes were up-regulated. In addition, the gene expression patterns in mucus were very different from the mucosal surfaces (skin, gill and intestine) and the classical immune organs (liver, spleen and kidney). The unique expression patterns obtained here may be resulted from the great advantage of the large amount of attached bacteria in the mucus than the internal tissues, and resulted from the bacteria virulent actors to suppress the host immune response. Taken together, our results can expand our knowledge of fish mucosal immunity, and the un-lethal mucus sampling can provide early insight for developing the strategies for selection of disease resistant families and strains in catfish as well as other fish species. PMID:26220643

  20. Developmental Profiles of Mucosal Immunity in Pre-school Children

    PubMed Central

    Ewing, Patricia; Otczyk, Diana C.; Occhipinti, Stefano; Kyd, Jennelle M.; Gleeson, Maree; Cripps, Allan W.

    2010-01-01

    This study investigated the effect of attending pre-school on mucosal immunity. Children 3.5 to 5 years of age who attended pre-school were observed for a 10 month period. Demographic information was collected on previous childcare experiences, the home environment and clinical information relating to the child and the family. A daily illness log was kept for each child. A multivariate longitudinal analysis of the relation between immunoglobulins in saliva and age, gender, childcare experience, pre-school exposure, number of siblings, environmental tobacco smoke (ETS), atopy and hospitalisation was conducted. There was a positive association of higher IgA levels with the winter season and with children being older than 4 years (P < .001), having attended childcare prior to commencing pre-school (P < .05), and having been exposed to ETS at home (P < .05). Lower IgA levels were associated with being atopic (P < .05). Higher IgG levels were associated with exposure to ETS (P < .001), while lower levels were associated to having atopy. Higher IgM levels were associated with previous childcare experience (P < .01) whilst having been hospitalised was associated with having low salivary IgM levels (P < .01). Lagged analyses demonstrated that immunological parameters were affected by the number of respiratory infections in the preceding 2 months. PMID:21234378

  1. Immune response profiles after caterpillar exposure: a case report

    PubMed Central

    Smith-Norowitz, Tamar A; Norowitz, Kevin B; Kohlhoff, Stephan; Kalra, Kaushal; Chice, Seto; Bluth, Martin H

    2010-01-01

    Rationale The role of the immune response to caterpillar exposure is not well described. This case study is the first to report a patient who presented with an allergic reaction after exposure to the larvae of the sycamore tussock moth, Halysidota harrisii Walsh, 1864. Methods Blood was collected from an allergic asthmatic adult (m/42 y/o) at 2 hrs – 2 wks after contact urticaria with associated dyspnea after exposure to the larvae of the sycamore tussock moth, Halysidota harrisii Walsh, 1864. Distributions of blood lymphocytes (CD4+, CD8+, CD8+CD60+, CD19+, CD23+, CD16/56+, CD25, CD45RA+, CD45RO+), monocytes (CD1d+), levels of serum immunoglobulins (IgM, IgG, IgA, IgE), and cytokines (IFN-γ, IL-4, TNF-α) were studied (flow cytometry, nephelometry, UniCAP Total IgE Fluoroenzymeimmunoassay, cytokine ELISA, clinical toxicology). Results Numbers of CD4+ T cells, CD25+ cells, CD19+ B cells, and CD1d+ monocytes decreased (22, 27, 33, 20%, respectively) one week post reaction, CD45RA+ naïve T cells decreased at 36 hours (21%),while CD8+CD60+ T cells and CD23+ cells decreased 48 hrs (33, 74%, respectively) post reaction. In contrast, numbers of CD16/56+ NK precursor cells increased (60%) 12 hrs, then decreased (65%) 48 hrs post reaction; other lymphocyte subsets were unaffected. Serum IgM, IgG and IgA were within normal range; however, serum IgE demonstrated a bimodal elevation at 2 hrs (15%) and one week post reaction. Levels of IFN-γ, IL-4, and TNF-α were not detected in serum pre-exposure (<1.0–4.0 pg/mL). However, high levels of IFN-γ (187–319 pg/mL) and TNF-α (549–749 pg/mL) were detected in serum 24–36 hrs and 3.5–24 hrs post reaction, respectively. In contrast, levels of IL-4 were undetected (<1.0 pg/mL) in serum at all time points. Conclusions Exposure to the larvae of the sycamore tussock moth, Halysidota harrisii Walsh, 1864 may result in increased cytokine levels and blood CD16/56+ NK precursor cells. PMID:22096356

  2. DNA methylation profiling reveals a predominant immune component in breast cancers

    PubMed Central

    Dedeurwaerder, Sarah; Desmedt, Christine; Calonne, Emilie; Singhal, Sandeep K; Haibe-Kains, Benjamin; Defrance, Matthieu; Michiels, Stefan; Volkmar, Michael; Deplus, Rachel; Luciani, Judith; Lallemand, Françoise; Larsimont, Denis; Toussaint, Jérôme; Haussy, Sandy; Rothé, Françoise; Rouas, Ghizlane; Metzger, Otto; Majjaj, Samira; Saini, Kamal; Putmans, Pascale; Hames, Gérald; van Baren, Nicolas; Coulie, Pierre G; Piccart, Martine; Sotiriou, Christos; Fuks, François

    2011-01-01

    Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease are still poorly understood. By means of DNA methylation profiling of 248 breast tissues, we have highlighted the existence of previously unrecognized breast cancer groups that go beyond the currently known ‘expression subtypes’. Interestingly, we showed that DNA methylation profiling can reflect the cell type composition of the tumour microenvironment, and in particular a T lymphocyte infiltration of the tumours. Further, we highlighted a set of immune genes having high prognostic value in specific tumour categories. The immune component uncovered here by DNA methylation profiles provides a new perspective for the importance of the microenvironment in breast cancer, holding implications for better management of breast cancer patients. PMID:21910250

  3. Evaluating the Invariance of Cognitive Profile Patterns Derived from Profile Analysis via Multidimensional Scaling (PAMS): A Bootstrapping Approach

    ERIC Educational Resources Information Center

    Kim, Se-Kang

    2010-01-01

    The aim of the current study is to validate the invariance of major profile patterns derived from multidimensional scaling (MDS) by bootstrapping. Profile Analysis via Multidimensional Scaling (PAMS) was employed to obtain profiles and bootstrapping was used to construct the sampling distributions of the profile coordinates and the empirical…

  4. Immune Neuroendocrine Phenotypes in Coturnix coturnix: Do Avian Species Show LEWIS/FISCHER-Like Profiles?

    PubMed Central

    Nazar, F. Nicolas; Barrios, Bibiana E.; Kaiser, Pete; Marin, Raul H.; Correa, Silvia G.

    2015-01-01

    Immunoneuroendocrinology studies have identified conserved communicational paths in birds and mammals, e.g. the Hypothalamus-Pituitary-Adrenal axis with anti-inflammatory activity mediated by glucocorticoids. Immune neuroendocrine phenotypes (INPs) have been proposed for mammals implying the categorization of a population in subgroups underlying divergent immune-neuroendocrine interactions. These phenotypes were studied in the context of the LEWIS/FISCHER paradigm (rats expressing high or low pro-inflammatory profiles, respectively). Although avian species have some common immunological mechanisms with mammals, they have also evolved some distinct strategies and, until now, it has not been studied whether birds may also share with mammals similar INPs. Based on corticosterone levels we determined the existence of two divergent groups in Coturnix coturnix that also differed in other immune-neuroendocrine responses. Quail with lowest corticosterone showed higher lymphoproliferative and antibody responses, interferon-γ and interleukin-1β mRNA expression levels and lower frequencies of leukocyte subpopulations distribution and interleukin-13 levels, than their higher corticosterone counterparts. Results suggest the existence of INPs in birds, comparable to mammalian LEWIS/FISCHER profiles, where basal corticosterone also underlies responses of comparable variables associated to the phenotypes. Concluding, INP may not be a mammalian distinct feature, leading to discuss whether these profiles represent a parallel phenomenon evolved in birds and mammals, or a common feature inherited from a reptilian ancestor millions of years ago. PMID:25793369

  5. Structures, profile consistency, and transport scaling in electrostatic convection

    SciTech Connect

    Bian, N.H.; Garcia, O.E.

    2005-04-15

    Two mechanisms at the origin of profile consistency in models of electrostatic turbulence in magnetized plasmas are considered. One involves turbulent diffusion in collisionless plasmas and the subsequent turbulent equipartition of Lagrangian invariants. By the very nature of its definition, this state can only be reached in the absence of imposed fluxes of the transported quantities. As such, the concept of turbulent equipartition cannot be used to interpret profiles in numerical simulations of interchange modes, as it has nevertheless been done in the past. It is shown in this article that for interchange modes, profile consistency is in fact due to mixing by persistent large-scale convective cells. This mechanism is not a turbulent diffusion, cannot occur in collisionless systems, and is the analog of the well-known laminar 'magnetic flux expulsion' in magnetohydrodynamics. This expulsion process involves a 'pinch' across closed streamlines and further results in the formation of pressure fingers along the separatrix of the convective cells. By nature, these coherent structures are dissipative because the mixing process that leads to their formation relies on a finite amount of collisional diffusion. Numerical simulations of two-dimensional interchange modes confirm the role of laminar expulsion by convective cells for profile consistency and structure formation. They also show that the fingerlike pressure structures ultimately control the rate of heat transport across the plasma layer and thus the transport scaling at large Rayleigh numbers. This contradicts mixing-length arguments which do not account for collisional processes. For interchange modes, the problem of coherent structure formation, profile consistency, and transport scaling are thus intimately linked.

  6. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  7. Immunizations

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en español Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  8. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  9. Systemic Immune Activation Profiles of HIV-1 Subtype C-Infected Children and Their Mothers

    PubMed Central

    Makhubele, Tinyiko G.; Steel, Helen C.; Anderson, Ronald; van Dyk, Gisela; Theron, Annette J.; Rossouw, Theresa M.

    2016-01-01

    Little is known about immune activation profiles of children infected with HIV-1 subtype C. The current study compared levels of selected circulating biomarkers of immune activation in HIV-1 subtype C-infected untreated mothers and their children with those of healthy controls. Multiplex bead array, ELISA, and immunonephelometric procedures were used to measure soluble CD14 (sCD14), beta-2 microglobulin (β2M), CRP, MIG, IP-10, and transforming growth factor beta 1 (TGF-β1). Levels of all 6 biomarkers were significantly elevated in the HIV-infected mothers and, with the exception of MIG, in their children (P < 0.01–P < 0.0001). The effects of antiretroviral therapy (ART) and maternal smoking on these biomarkers were also assessed. With the exception of TGF-β1, which was unchanged in the children 12 months after therapy, initiation of ART was accompanied by decreases in the other biomarkers. Regression analysis revealed that although most biomarkers were apparently unaffected by smoking, exposure of children to maternal smoking was associated with a significant increase in IP-10. These findings demonstrate that biomarkers of immune activation are elevated in HIV-infected children pre-ART and decline, with the exception of TGF-β1, after therapy. Although preliminary, elevation of IP-10 in smoke-exposed infants is consistent with a higher level of immune activation in this group. PMID:27019552

  10. New perspectives for large-scale repertoire analysis of immune receptors.

    PubMed

    Boudinot, Pierre; Marriotti-Ferrandiz, Maria Encarnita; Pasquier, Louis Du; Benmansour, Abdenour; Cazenave, Pierre-André; Six, Adrien

    2008-05-01

    In vertebrates, the world of antigenic motifs is matched to large populations of lymphocytes through specific recognition of an epitope by a given receptor unique to a lymphocyte clone. The concept of immune repertoire was proposed to describe this diversity of lymphocyte receptors - Ig and TCR - required by the network of interactions. The immune repertoires became useful tools to describe lymphocyte and receptor populations through the development of the immune system and in pathological situations. Recently, the development of mass technologies made possible a comprehensive survey of immune repertoires at the genome, transcript and protein levels, and some of these techniques have been already adapted to TCR and Ig repertoire analyses. Such approaches generate very big datasets, which necessitates complex and multi-parametric annotations in dedicated databases. They also require new analysis methods, leading to the integration of structure and dynamics of the immune repertoires, at different time scales (immune response, development of the individual, evolution of the species). Such methods may be extended to the analysis of new classes of adaptive-like receptors, which were recently discovered in different invertebrates and in agnathans. Ultimately, they may allow a parallel monitoring of pathogen and immune repertoires addressing the reciprocal influences that decide for the host survival or death. In this review, we first study the characteristics of Ig and TCR repertoires, and we examine several systematic approaches developed for the analysis of these "classical" immune repertoires at different levels. We then consider examples of the recent developments of modeling and statistical analysis, and we discuss their relevance and their importance for the study of the immune diversity. An extended view of immune repertoires is proposed, integrating the diversity of other receptors involved in immune recognition. Also, we discuss how repertoire studies could link

  11. Transcriptional profiling of vaccine‐induced immune responses in humans and non‐human primates

    PubMed Central

    Wang, I‐Ming; Bett, Andrew J.; Cristescu, Razvan; Loboda, Andrey; ter Meulen, Jan

    2012-01-01

    Summary There is an urgent need for pre‐clinical and clinical biomarkers predictive of vaccine immunogenicity, efficacy and safety to reduce the risks and costs associated with vaccine development. Results emerging from immunoprofiling studies in non‐human primates and humans demonstrate clearly that (i) type and duration of immune memory are largely determined by the magnitude and complexity of the innate immune signals and (ii) genetic signatures highly predictive of B‐cell and T‐cell responses can be identified for specific vaccines. For vaccines with similar composition, e.g. live attenuated viral vaccines, these signatures share common patterns. Signatures predictive of vaccine efficacy have been identified in a few experimental challenge studies. This review aims to give an overview of the current literature on immunoprofiling studies in humans and also presents some of our own data on profiling of licensed and experimental vaccines in non‐human primates. PMID:22103427

  12. Expression profiling of constitutive mast cells reveals a unique identity within the immune system.

    PubMed

    Dwyer, Daniel F; Barrett, Nora A; Austen, K Frank

    2016-07-01

    Mast cells are evolutionarily ancient sentinel cells. Like basophils, mast cells express the high-affinity receptor for immunoglobulin E (IgE) and have been linked to host defense and diverse immune-system-mediated diseases. To better characterize the function of these cells, we assessed the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood. We found that mast cells were transcriptionally distinct, clustering independently from all other profiled cells, and that mast cells demonstrated considerably greater heterogeneity across tissues than previously appreciated. We observed minimal homology between mast cells and basophils, which shared more overlap with other circulating granulocytes than with mast cells. The derivation of mast-cell and basophil transcriptional signatures underscores their differential capacities to detect environmental signals and influence the inflammatory milieu. PMID:27135604

  13. Multi-analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection.

    PubMed

    Huckans, Marilyn; Fuller, Bret E; Olavarria, Hannah; Sasaki, Anna W; Chang, Michael; Flora, Kenneth D; Kolessar, Michael; Kriz, Daniel; Anderson, Jeanne R; Vandenbark, Arthur A; Loftis, Jennifer M

    2014-03-01

    BackgroundThe purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms-depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. MethodsBlood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV-, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. ResultsCompared with HCV- controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV- group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4-10 plasma immune factors; protein signatures significantly accounted for 19-40% of the variance in depression, anxiety, fatigue, and pain. ConclusionsOverall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in

  14. Multi-analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection

    PubMed Central

    Huckans, Marilyn; Fuller, Bret E; Olavarria, Hannah; Sasaki, Anna W; Chang, Michael; Flora, Kenneth D; Kolessar, Michael; Kriz, Daniel; Anderson, Jeanne R; Vandenbark, Arthur A; Loftis, Jennifer M

    2014-01-01

    Background The purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms—depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. Methods Blood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV−, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. Results Compared with HCV− controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV− group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4–10 plasma immune factors; protein signatures significantly accounted for 19–40% of the variance in depression, anxiety, fatigue, and pain. Conclusions Overall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric

  15. Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis.

    PubMed

    Negm, Ola H; Hamed, Mohamed R; Dilnot, Elizabeth M; Shone, Clifford C; Marszalowska, Izabela; Lynch, Mark; Loscher, Christine E; Edwards, Laura J; Tighe, Patrick J; Wilcox, Mark H; Monaghan, Tanya M

    2015-09-01

    Clostridium difficile is an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course of C. difficile infection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purified C. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid and Candida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses to C. difficile protein antigens and may have potential advantages in throughput, convenience, and cost. PMID:26178385

  16. Comprehensive molecular profiling of the B7 family of immune-regulatory ligands in breast cancer.

    PubMed

    Xu, Zhenyu; Shen, Jing; Wang, Maggie Haitian; Yi, Tao; Yu, Yangyang; Zhu, Yinxin; Chen, Bo; Chen, Jianping; Li, Longfei; Li, Minxing; Zuo, Jian; Jiang, Hui; Zhou, Dexi; Luan, Jiajie; Xiao, Zhangang

    2016-08-01

    The B7 gene family has crucial roles in the regulation of adaptive cellular immunity. In cancer, deregulation of co-inhibitory B7 molecules is associated with reduced antitumor immunity and cancer immune evasion. FDA approval of cancer immunotherapy antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1)-both ligands of the B7 family-demonstrate the impact of these checkpoint regulators in cancer. Using data from cBioPortal, we performed comprehensive molecular profiling of the 10 currently known B7 family proteins in 105 different cancers. B7 family members were amplified in breast cancer: with B7 mRNA levels upregulated in a cohort of 1,098 patients with all types of breast cancer and in 82 patients with triple-negative breast cancer. Promoter methylation analysis indicated an epigenetic basis for deregulation of certain B7 family genes in breast cancer. Moreover, patients with B7-H6 genomic alterations had significantly worse overall survival, and certain clinical attributes were associated with B7-H6 expression, which indicates that B7-H6 may be a potential target for breast cancer immunotherapy. Finally, using network analysis (based on data from cBioportal), we identified BTLA, MARCH8, PLSCR1 and SMAD3 as potentially involved in T cell signaling under regulation of B7 family proteins. PMID:27622076

  17. Transcriptome profiling of immune tissues reveals habitat-specific gene expression between lake and river sticklebacks.

    PubMed

    Huang, Yun; Chain, Frédéric J J; Panchal, Mahesh; Eizaguirre, Christophe; Kalbe, Martin; Lenz, Tobias L; Samonte, Irene E; Stoll, Monika; Bornberg-Bauer, Erich; Reusch, Thorsten B H; Milinski, Manfred; Feulner, Philine G D

    2016-02-01

    The observation of habitat-specific phenotypes suggests the action of natural selection. The three-spined stickleback (Gasterosteus aculeatus) has repeatedly colonized and adapted to diverse freshwater habitats across the northern hemisphere since the last glaciation, while giving rise to recurring phenotypes associated with specific habitats. Parapatric lake and river populations of sticklebacks harbour distinct parasite communities, a factor proposed to contribute to adaptive differentiation between these ecotypes. However, little is known about the transcriptional response to the distinct parasite pressure of those fish in a natural setting. Here, we sampled wild-caught sticklebacks across four geographical locations from lake and river habitats differing in their parasite load. We compared gene expression profiles between lake and river populations using 77 whole-transcriptome libraries from two immune-relevant tissues, the head kidney and the spleen. Differential expression analyses revealed 139 genes with habitat-specific expression patterns across the sampled population pairs. Among the 139 differentially expressed genes, eight are annotated with an immune function and 42 have been identified as differentially expressed in previous experimental studies in which fish have been immune challenged. Together, these findings reinforce the hypothesis that parasites contribute to adaptation of sticklebacks in lake and river habitats. PMID:26749022

  18. Seamustard (Undaria pinnatifida) Improves Growth, Immunity, Fatty Acid Profile and Reduces Cholesterol in Hanwoo Steers.

    PubMed

    Hwang, J A; Islam, M M; Ahmed, S T; Mun, H S; Kim, G M; Kim, Y J; Yang, C J

    2014-08-01

    The study was designed to evaluate the effect of 2% seamustard (Undaria pinnatifida) by-product (SW) on growth performance, immunity, carcass characteristics, cholesterol content and fatty acid profile in Hanwoo steers. A total of 20 Hanwoo steers (ave. 22 months old; 619 kg body weight) were randomly assigned to control (basal diet) and 2% SW supplemented diet. Dietary SW supplementation significantly (p<0.05) improved average daily gain and gain:feed ratio as well as serum immunoglobulin G concentration. Chemical composition and quality grade of meat and carcass yield grades evaluated at the end of the trial were found to be unaffected by SW supplementation. Dietary SW significantly reduced meat cholesterol concentration (p<0.05). Dietary SW supplementation significantly reduced the myristic acid (C14:0) and palmitoleic acid (C16:ln-7) concentration, while SW increased the concentration of stearic acid (C18:0) and linolenic acid (C18:3n-3) compared to control (p<0.05). Dietary SW supplementation had no effect on saturated fatty acids (SFA), unsaturated fatty acids, poly unsaturated fatty acid (PUFA) or mono unsaturated fatty acid content in muscles. A reduced ratio of PUFA/SFA and n-6/n-3 were found in SW supplemented group (p<0.05). In conclusion, 2% SW supplementation was found to improve growth, immunity and fatty acid profile with significantly reduced cholesterol of beef. PMID:25083105

  19. Seamustard (Undaria pinnatifida) Improves Growth, Immunity, Fatty Acid Profile and Reduces Cholesterol in Hanwoo Steers

    PubMed Central

    Hwang, J. A.; Islam, M. M.; Ahmed, S. T.; Mun, H. S.; Kim, G. M.; Kim, Y. J.; Yang, C. J.

    2014-01-01

    The study was designed to evaluate the effect of 2% seamustard (Undaria pinnatifida) by-product (SW) on growth performance, immunity, carcass characteristics, cholesterol content and fatty acid profile in Hanwoo steers. A total of 20 Hanwoo steers (ave. 22 months old; 619 kg body weight) were randomly assigned to control (basal diet) and 2% SW supplemented diet. Dietary SW supplementation significantly (p<0.05) improved average daily gain and gain:feed ratio as well as serum immunoglobulin G concentration. Chemical composition and quality grade of meat and carcass yield grades evaluated at the end of the trial were found to be unaffected by SW supplementation. Dietary SW significantly reduced meat cholesterol concentration (p<0.05). Dietary SW supplementation significantly reduced the myristic acid (C14:0) and palmitoleic acid (C16:ln-7) concentration, while SW increased the concentration of stearic acid (C18:0) and linolenic acid (C18:3n-3) compared to control (p<0.05). Dietary SW supplementation had no effect on saturated fatty acids (SFA), unsaturated fatty acids, poly unsaturated fatty acid (PUFA) or mono unsaturated fatty acid content in muscles. A reduced ratio of PUFA/SFA and n-6/n-3 were found in SW supplemented group (p<0.05). In conclusion, 2% SW supplementation was found to improve growth, immunity and fatty acid profile with significantly reduced cholesterol of beef. PMID:25083105

  20. Sparse detector sensor: profiling experiments for broad-scale classification

    NASA Astrophysics Data System (ADS)

    Russomanno, D. J.; Yeasin, M.; Jacobs, E.; Smith, M.; Sorower, S.

    2008-04-01

    This paper presents a simple prototype sparse detector imaging sensor built using sixteen off-the-shelf, retro-reflective, infrared-sensing elements placed at five-inch intervals in a vertical configuration. Profiling experiments for broad-scale classification of objects, such as humans, humans wearing large backpacks, and humans wearing small backpacks were conducted from data acquired from the sensor. Empirical analysis on models developed using fusion of various classifiers based on a diversity measure shows over ninety percent (90.07%) accuracy (using 10-fold cross validation) in categorizing sensed data into specific classes of interest, such as, humans wearing a large backpack. The results demonstrate that shadow images of sufficient resolution can be captured by the sensor such that broad-scale classification of objects is feasible. The sensor appears to be a low-cost alternative to traditional, high-resolution imaging sensors, and, after industrial packaging, it may be a good candidate for deployment in vast geographic regions in which low-cost, unattended ground sensors with highly accurate classification algorithms are needed.

  1. Predicting and comparing long-term measles antibody profiles of different immunization policies.

    PubMed Central

    Lee, M. S.; Nokes, D. J.

    2001-01-01

    OBJECTIVE: Measles outbreaks are infrequent and localized in areas with high coverage of measles vaccine. The need is to assess long-term effectiveness of coverage. Since 1991, no measles epidemic affecting the whole island has occurred in Taiwan, China. Epidemiological models are developed to predict the long-term measles antibody profiles and compare the merits of different immunization policies on the island. METHODS: The current measles immunization policy in Taiwan, China, is 1 dose of measles vaccine at 9 months of age and 1 dose of measles, mumps and rubella (MMR) vaccine at 15 months of age, plus a 'mop-up' of MMR-unvaccinated schoolchildren at 6 years of age. Refinements involve a change to a two-dose strategy. Five scenarios based on different vaccination strategies are compared. The models are analysed using Microsoft Excel. FINDINGS: First, making the assumption that measles vaccine-induced immunity will not wane, the predicted measles IgG seroprevalences in preschool children range from 81% (lower bound) to 94% (upper bound) and in schoolchildren reach 97-98% in all strategy scenarios. Results are dependent on the association of vaccine coverage between the first and second dose of vaccine. Second, if it is assumed that vaccine-induced antibody titres decay, the long-term measles seroprevalence will depend on the initial titres post vaccination, decay rates of antibody titres and cut-off of seropositivity. CONCLUSION: If MMR coverage at 12 months of age can reach > 90%, it would be worth changing the current policy to 2 doses at 12 months and 6 years of age to induce higher antibody titres. These epidemiological models could be applied wherever a similar stage of measles elimination has been reached. PMID:11477964

  2. Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling.

    PubMed

    Bal, Gürkan; Futschik, Matthias E; Hartl, Daniela; Ringel, Frauke; Kamhieh-Milz, Julian; Sterzer, Viktor; Hoheisel, Jörg D; Alhamdani, Mohamed S S; Salama, Abdulgabar

    2016-02-01

    The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration. PMID:26628061

  3. Mechanisms of HO-1 mediated attenuation of renal immune injury: a gene profiling study.

    PubMed

    Duann, Pu; Lianos, Elias A

    2011-10-01

    Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targeted to glomerular epithelial cells (GECs) using a GEC-specific murine nephrin promoter. Injury by administration of antibody against the glomerular basement membrane (anti-GBM) to transgenic (TG) mice with GEC-targeted hHO-1 was attenuated compared with wild-type (WT) controls. To explore changes in the expression of genes that could mediate this salutary effect, we performed gene expression profiling using a microarray analysis of RNA isolated from the renal cortex of WT or TG mice with or without anti-GBM antibody-induced injury. Significant increases in expression were detected in 9 major histocompatibility complex (MHC)-class II genes, 2 interferon-γ (IFN-γ)-inducible guanosine triphosphate (GTP)ases, and 3 genes of the ubiquitin-proteasome system. The increase in MHC-class II and proteasome gene expression in TG mice with injury was validated by real-time polymerase chain reaction (PCR) or Western blot analysis. The observations point to novel mechanisms underlying the cytoprotective effect of HO-1 in renal immune injury. PMID:21925121

  4. Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates

    PubMed Central

    Yabu, Julie M.; Siebert, Janet C.; Maecker, Holden T.

    2016-01-01

    Background Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Methods and Findings Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Conclusions Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to

  5. Immunizations.

    PubMed

    Sanford, Christopher A; Jong, Elaine C

    2016-03-01

    Vaccinations are a cornerstone of the pretravel consultation. The pretravel provider should assess a traveler's past medical history, planned itinerary, activities, mode of travel, and duration of stay and make appropriate vaccine recommendations. Given that domestic vaccine-preventable illnesses are more common in international travelers than are exotic or low-income nation-associated vaccine-preventable illnesses, clinicians should first ensure that travelers are current regarding routine immunizations. Additional immunizations may be indicated in some travelers. Familiarity with geographic distribution and seasonality of infectious diseases is essential. Clinicians should be cognizant of which vaccines are live, as there exist contraindications for live vaccines. PMID:26900111

  6. Transcriptome profiling of immune responses to cardiomyopathy syndrome (CMS) in Atlantic salmon

    PubMed Central

    2011-01-01

    Background Cardiomyopathy syndrome (CMS) is a disease associated with severe myocarditis primarily in adult farmed Atlantic salmon (Salmo salar L.), caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV) with structural similarities to the Totiviridae family. Here we present the first characterisation of host immune responses to CMS assessed by microarray transcriptome profiling. Results Unvaccinated farmed Atlantic salmon post-smolts were infected by intraperitoneal injection of PMCV and developed cardiac pathology consistent with CMS. From analysis of heart samples at several time points and different tissues at early and clinical stages by oligonucleotide microarrays (SIQ2.0 chip), six gene sets representing a broad range of immune responses were identified, showing significant temporal and spatial regulation. Histopathological examination of cardiac tissue showed myocardial lesions from 6 weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery. Viral RNA was detected in all organs from 4 wpi suggesting a broad tissue tropism. High correlation between viral load and cardiac histopathology score suggested that cytopathic effect of infection was a major determinant of the myocardial changes. Strong and systemic induction of antiviral and IFN-dependent genes from 2 wpi that levelled off during infection, was followed by a biphasic activation of pathways for B cells and MHC antigen presentation, both peaking at clinical pathology. This was preceded by a distinct cardiac activation of complement at 6 wpi, suggesting a complement-dependent activation of humoral Ab-responses. Peak of cardiac pathology and viral load coincided with cardiac-specific upregulation of T cell response genes and splenic induction of complement genes. Preceding the reduction in viral load and pathology, these responses were probably important for viral clearance and recovery. Conclusions By comparative analysis of gene expression, histology and

  7. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  8. Moderate alcohol consumption alters both leucocyte gene expression profiles and circulating proteins related to immune response and lipid metabolism in men.

    PubMed

    Joosten, Michel M; van Erk, Marjan J; Pellis, Linette; Witkamp, Renger F; Hendriks, Henk F J

    2012-08-01

    Moderate alcohol consumption has various effects on immune and inflammatory processes, which could accumulatively modulate chronic disease risk. So far, no comprehensive, integrative profiling has been performed to investigate the effects of longer-term alcohol consumption. Therefore, we studied the effects of alcohol consumption on gene expression patterns using large-scale profiling of whole-genome transcriptomics in blood cells and on a number of proteins in blood. In a randomised, open-label, cross-over trial, twenty-four young, normal-weight men consumed 100 ml vodka (30 g alcohol) with 200 ml orange juice or only orange juice daily during dinner for 4 weeks. After each period, blood was sampled for measuring gene expression and selected proteins. Pathway analysis of 345 down-regulated and 455 up-regulated genes revealed effects of alcohol consumption on various signalling responses, immune processes and lipid metabolism. Among the signalling processes, the most prominently changed was glucocorticoid receptor signalling. A network on immune response showed a down-regulated NF-κB gene expression together with increased plasma adiponectin and decreased pro-inflammatory IL-1 receptor antagonist and IL-18, and acute-phase proteins ferritin and α1-antitrypsin concentrations (all P < 0.05) after alcohol consumption. Furthermore, a network of gene expression changes related to lipid metabolism was observed, with a central role for PPARα which was supported by increased HDL-cholesterol and several apo concentrations (all P < 0.05) after alcohol consumption. In conclusion, an integrated approach of profiling both genes and proteins in blood showed that 4 weeks of moderate alcohol consumption altered immune responses and lipid metabolism. PMID:22142458

  9. Genome-wide characterization and expression profiling of immune genes in the diamondback moth, Plutella xylostella (L.)

    PubMed Central

    Xia, Xiaofeng; Yu, Liying; Xue, Minqian; Yu, Xiaoqiang; Vasseur, Liette; Gurr, Geoff M.; Baxter, Simon W.; Lin, Hailan; Lin, Junhan; You, Minsheng

    2015-01-01

    The diamondback moth, Plutella xylostella (L.), is a destructive pest that attacks cruciferous crops worldwide. Immune responses are important for interactions between insects and pathogens and information on these underpins the development of strategies for biocontrol-based pest management. Little, however, is known about immune genes and their regulation patterns in P. xylostella. A total of 149 immune-related genes in 20 gene families were identified through comparison of P. xylostella genome with the genomes of other insects. Complete and conserved Toll, IMD and JAK-STAT signaling pathways were found in P. xylostella. Genes involved in pathogen recognition were expanded and more diversified than genes associated with intracellular signal transduction. Gene expression profiles showed that the IMD pathway may regulate expression of antimicrobial peptide (AMP) genes in the midgut, and be related to an observed down-regulation of AMPs in experimental lines of insecticide-resistant P. xylostella. A bacterial feeding study demonstrated that P. xylostella could activate different AMPs in response to bacterial infection. This study has established a framework of comprehensive expression profiles that highlight cues for immune regulation in a major pest. Our work provides a foundation for further studies on the functions of P. xylostella immune genes and mechanisms of innate immunity. PMID:25943446

  10. Plasma metabolomic profiles and immune responses of piglets after weaning and challenge with E. coli

    PubMed Central

    2014-01-01

    Background The processes of weaning and exposure to pathogenic bacteria induce stress responses, which may alter the metabolism. In this study, we investigated the changes in plasma metabolites and immune responses in piglets in response to the stress induced by weaning and Escherichia coli challenge. Results Fecal dry matter decreased (P = 0.003) and nearly half (44.4%) the piglets developed diarrhea on day 2 and 3 postweaning. The concentration of plasma immunoglobulin A was higher (P < 0.001) on day 11 postweaning than on day 0 or 4 postweaning. The levels of white blood cells increased continuously (P < 0.001) from day 0 to day 11 postweaning. Differences in the percentages of neutrophils (P = 0.029) and lymphocytes (P = 0.022) were seen, but the neutrophil/lymphocyte ratio did not differ in the period after weaning. A clear separation of the metabolomic profile data for day 0 and day 4 postweaning was observed with a principal components analysis (PCA) scores plot, and the data for day 11 were located between those for day 0 and day 4 postweaning. The plasma levels of proline, taurine, and carnitine were higher, whereas those of betaine, creatine, L-arginine and acetylcarnitine were lower on day 4 postweaning than on day 0. Levels of lysophosphatidylcholine and phosphatidylcholine were either higher or lower after weaning, depending on the chain lengths or characters of these metabolites. Conclusions Our results show a clear separation in the plasma metabolomic profiles of piglets that corresponded to the fecal responses to stress on the piglets induced by weaning or exposure to a pathogen (E. coli). These plasma metabolite profiles suggest that the challenges induced proinflammatory responses in the piglets, resulting in postweaning diarrhea, which was associated with higher concentrations of IgA in the plasma. PMID:24624922

  11. Linking environmental variability to village-scale malaria transmission using a simple immunity model

    PubMed Central

    2013-01-01

    constituting a mechanistic link between spatial and temporal environmental variability and village-scale malaria transmission. Incorporating acquired immunity into the model has allowed simulation of prevalence in the two villages, and isolation of the effects of acquired immunity in dampening the difference in prevalence between the two villages. Without these effects, the difference in prevalence between the two villages would have been significantly larger in response to the large differences in mosquito populations and the associated biting rates. PMID:23919581

  12. Large-scale and Convective-scale Updraft Profiles from Satellite Observations

    NASA Astrophysics Data System (ADS)

    Masunaga, H.; Luo, Z. J.

    2015-12-01

    Among the crucial problems involved in the tropical energy budget are the thermodynamic effects of an ensemble of convective clouds on their environment and the large-scale influence imposed back on the convective-scale dynamics. Efforts to seek observational evidence for this problem, however, are challenged by limitations in the capability of measuring vertical motion across different horizontal scales. We have recently been exploring new analysis strategies in hopes to make this seemingly impossible possible, exploiting a suite of satellite instruments including the CloudSat and TRMM radars and Aqua AIRS. Since a complete vertical structure of in-cloud vertical velocity, wc, is unable to be reconstructed from satellite measurements alone, a single-column plume model is run with the environmental soundings from AIRS to obtain a set of synthetic wc profiles under a range of entrainment rates. The solutions are then narrowed down in a Bayesian manner so as to match the cloud-top vertical velocity and buoyancy estimates from A-Train infrared and radar measurements. The vertical profile of large-scale mean vertical motion, ω, is also evaluated from satellite observations in its own approach: ω as a function of pressure is determined so that it satisfies the horizontal divergence terms in the tropospheric water and thermal budget equations in which the remaining terms are constrained by satellite measurements. In this talk, the methodology is briefly outlined and the results are presented and discussed in light of outstanding issues in tropical dynamics. The wc and ω estimates above, although subject to intrinsic uncertainties yet to be verified, do not involve any closure assumption as required for cumulus parameterizations and would offer a useful test bed for climate models and reanalysis data as well as a unique opportunity to study the mechanism of tropical convection.

  13. Global transcriptomic profiling of bovine endometrial immune response in vitro. I. Effect of lipopolysaccharide on innate immunity.

    PubMed

    Oguejiofor, Chike F; Cheng, Zhangrui; Abudureyimu, Ayimuguli; Fouladi-Nashta, Ali A; Wathes, D Claire

    2015-10-01

    The dysregulation of endometrial immune response to bacterial lipopolysaccharide (LPS) has been implicated in uterine disease and infertility in the postpartum dairy cow, although the mechanisms are not clear. Here, we investigated whole-transcriptomic gene expression in primary cultures of mixed bovine epithelial and stromal endometrial cells. Cultures were exposed to LPS for 6 h, and cellular response was measured by bovine microarray. Approximately 30% of the 1006 genes altered by LPS were classified as being involved in immune response. Cytokines and chemokines (IL1A, CX3CL1, CXCL2, and CCL5), interferon (IFN)-stimulated genes (RSAD2, MX2, OAS1, ISG15, and BST2), and the acute phase molecule SAA3 were the most up-regulated genes. Ingenuity Pathway Analysis identified up-regulation of many inflammatory cytokines and chemokines, which function to attract immune cells to the endometrium, together with vascular adhesion molecules and matrix metalloproteinases, which can facilitate immune cell migration from the tissue toward the uterine lumen. Increased expression of many IFN-signaling genes, immunoproteasomes, guanylate-binding proteins, and genes involved in the intracellular recognition of pathogens suggests important roles for these molecules in the innate defense against bacterial infections. Our findings confirmed the important role of endometrial cells in uterine innate immunity, whereas the global approach used identified several novel immune response pathways triggered by LPS in the endometrium. Additionally, many genes involved in endometrial response to the conceptus in early pregnancy were also altered by LPS, suggesting one mechanism whereby an ongoing response to infection may interfere with the establishment of pregnancy. PMID:26353891

  14. Neisseria gonorrhoeae Modulates Immunity by Polarizing Human Macrophages to a M2 Profile.

    PubMed

    Ortiz, María Carolina; Lefimil, Claudia; Rodas, Paula I; Vernal, Rolando; Lopez, Mercedes; Acuña-Castillo, Claudio; Imarai, Mónica; Escobar, Alejandro

    2015-01-01

    Current data suggest that Neisseria gonorrhoeae is able to suppress the protective immune response at different levels, such as B and T lymphocytes and antigen-presenting cells. The present report is focused on gonococcus evasion mechanism on macrophages (MФ) and its impact in the subsequent immune response. In response to various signals MФ may undergo classical-M1 (M1-MФ) or alternative-M2 (M2-MФ) activation. Until now there are no reports of the gonococcus effects on human MФ polarization. We assessed the phagocytic ability of monocyte-derived MФ (MDM) upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on MФ challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-MФ phenotype in which some of the M2b and none of the M1-MФ-associated markers are induced. Interestingly, N. gonorrhoeae exposure leads to upregulation of a Programmed Death Ligand 1 (PD-L1), widely known as an immunosuppressive molecule. Moreover, functional results showed that N. gonorrhoeae-treated MФ are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype. Taken together, our data show that N. gonorroheae interferes with MФ polarization. This study has important implications for understanding the mechanisms of clearance versus long-term persistence of N. gonorroheae infection and might be applicable for the development of new therapeutic strategies. PMID:26125939

  15. Neisseria gonorrhoeae Modulates Immunity by Polarizing Human Macrophages to a M2 Profile

    PubMed Central

    Ortiz, María Carolina; Lefimil, Claudia; Rodas, Paula I.; Vernal, Rolando; Lopez, Mercedes; Acuña-Castillo, Claudio; Imarai, Mónica; Escobar, Alejandro

    2015-01-01

    Current data suggest that Neisseria gonorrhoeae is able to suppress the protective immune response at different levels, such as B and T lymphocytes and antigen-presenting cells. The present report is focused on gonococcus evasion mechanism on macrophages (MФ) and its impact in the subsequent immune response. In response to various signals MФ may undergo classical-M1 (M1-MФ) or alternative-M2 (M2-MФ) activation. Until now there are no reports of the gonococcus effects on human MФ polarization. We assessed the phagocytic ability of monocyte-derived MФ (MDM) upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on MФ challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-MФ phenotype in which some of the M2b and none of the M1-MФ-associated markers are induced. Interestingly, N. gonorrhoeae exposure leads to upregulation of a Programmed Death Ligand 1 (PD-L1), widely known as an immunosuppressive molecule. Moreover, functional results showed that N. gonorrhoeae-treated MФ are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype. Taken together, our data show that N. gonorroheae interferes with MФ polarization. This study has important implications for understanding the mechanisms of clearance versus long-term persistence of N. gonorroheae infection and might be applicable for the development of new therapeutic strategies. PMID:26125939

  16. The substance use risk profile scale: a scale measuring traits linked to reinforcement-specific substance use profiles.

    SciTech Connect

    Woicik, P.A.; Stewart, S.H.; Pihl, R.O.; Conrod, P.J.

    2009-12-01

    The Substance Use Risk Profile Scale (SURPS) is based on a model of personality risk for substance abuse in which four personality dimensions (hopelessness, anxiety sensitivity, impulsivity, and sensation seeking) are hypothesized to differentially relate to specific patterns of substance use. The current series of studies is a preliminary exploration of the psychometric properties of the SURPS in two populations (undergraduate and high school students). In study 1, an analysis of the internal structure of two versions of the SURPS shows that the abbreviated version best reflects the 4-factor structure. Concurrent, discriminant, and incremental validity of the SURPS is supported by convergent/divergent relationships between the SURPS subscales and other theoretically relevant personality and drug use criterion measures. In Study 2, the factorial structure of the SURPS is confirmed and evidence is provided for its test-retest reliability and validity with respect to measuring personality vulnerability to reinforcement-specific substance use patterns. In Study 3, the SURPS was administered in a more youthful population to test its sensitivity in identifying younger problematic drinkers. The results from the current series of studies demonstrate support for the reliability and construct validity of the SURPS, and suggest that four personality dimensions may be linked to substance-related behavior through different reinforcement processes. This brief assessment tool may have important implications for clinicians and future research.

  17. Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows

    PubMed Central

    2012-01-01

    Background All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP) which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR). Results mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P < 0.1) included the T cell receptor signalling pathway, graft-versus-host disease and cytokine-cytokine receptor interaction pathways. However 30 DPP, where the majority of genes were differentially expressed, the enrichment (adjusted P < 0.1) of tissue repair and proliferative activity pathways was observed. Nineteen candidate genes selected from mRNA-Seq results, were independently assessed by qRT-PCR in additional postpartum cows (5 animals) at both time points. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum. Conclusions The results of this study reveal an early activation of the immune

  18. Large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection.

    PubMed

    Li, Ze-Yuan; Xia, Jing; Chen, Zheng; Yu, Yang; Li, Quan-Feng; Zhang, Yu-Chan; Zhang, Jin-Ping; Wang, Cong-Ying; Zhu, Xiao-Yuan; Zhang, Weixiong; Chen, Yue-Qin

    2016-01-01

    Rice blast is a recurrent fungal disease, and resistance to fungal infection is a complex trait. Therefore, a comprehensive examination of rice transcriptome and its variation during fungal infection is necessary to understand the complex gene regulatory networks. In this study, adopting Next-Generation Sequencing we profiled the transcriptomes and microRNAomes of rice varieties, one susceptible and the other resistant to M. oryzae, at multiple time points during the fungal infection. Our results revealed a substantial variation in the plant transcriptome and microRNAome as well as change to rice innate immunity during fungal infection. A number of putative R gene candidates were identified from a perturbed rice transcriptome analysis. The expression of genes and non-coding RNA molecules changed in both fungal resistant and susceptible plants during M. oryzae invasion discovered distinct pathways triggered in the susceptible and resistant plants. In addition, a number of fungus genes in the susceptible and resistant plants were constantly expressed at different time points, suggesting that they were likely to be the potential AVR genes. Our results revealed large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection, which would help to develop more robust blast-resistant rice plants. PMID:27150822

  19. Large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection

    PubMed Central

    Li, Ze-Yuan; Xia, Jing; Chen, Zheng; Yu, Yang; Li, Quan-Feng; Zhang, Yu-Chan; Zhang, Jin-Ping; Wang, Cong-Ying; Zhu, Xiao-Yuan; Zhang, Weixiong; Chen, Yue-Qin

    2016-01-01

    Rice blast is a recurrent fungal disease, and resistance to fungal infection is a complex trait. Therefore, a comprehensive examination of rice transcriptome and its variation during fungal infection is necessary to understand the complex gene regulatory networks. In this study, adopting Next-Generation Sequencing we profiled the transcriptomes and microRNAomes of rice varieties, one susceptible and the other resistant to M. oryzae, at multiple time points during the fungal infection. Our results revealed a substantial variation in the plant transcriptome and microRNAome as well as change to rice innate immunity during fungal infection. A number of putative R gene candidates were identified from a perturbed rice transcriptome analysis. The expression of genes and non-coding RNA molecules changed in both fungal resistant and susceptible plants during M. oryzae invasion discovered distinct pathways triggered in the susceptible and resistant plants. In addition, a number of fungus genes in the susceptible and resistant plants were constantly expressed at different time points, suggesting that they were likely to be the potential AVR genes. Our results revealed large-scale rewiring of innate immunity circuitry and microRNA regulation during initial rice blast infection, which would help to develop more robust blast-resistant rice plants. PMID:27150822

  20. Profiling of miRNA expression in immune thrombocytopenia patients before and after Qishunbaolier (QSBLE) treatment.

    PubMed

    Burenbatu; Borjigin, Mandula; Eerdunduleng; Huo, Wenyan; Gong, Cuiqin; Hasengaowa; Zhang, Guiping; Longmei; Li, Ming; Zhang, Xuemei; Sun, Xiaohui; Yang, Jie; Wang, Shuanglian; Narisu, Narisu; Liu, Yangjian; Bai, Haihua

    2015-10-01

    Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura, is an autoimmune disease characterized by low platelet count and increased bleeding tendency. Currently, glucocorticoid and splenectomy are the main therapies for ITP but with obvious side effects including tendency of relapse and risk of internal bleeding. In this study, we report the Mongolian medicine Qishunbaolier (QSBLE) can significantly and efficiently increase platelet count with a low recurrent rate and unnoticeable side effect. We profiled the microRNA (miRNA) expression in the blood sample of ITP patients and identified 44 miRNAs that are differentially expressed in ITP patients before and after QSBLE treatment. Out of these 44 miRNAs, 25 are expressed in control subjects and are downregulated in ITP patients, whereas the treatment with QSBLE restores their expressions to the level of control subjects. This result suggests that abnormal expression of these 25 miRNAs might be connected to the pathogenesis of ITP. Interestingly, 14 of those 44 miNRAs are predicted to target at least once on 31 known IPT associated genes, indicating the possible mechanism of QSBLE on ITP therapy. PMID:26297543

  1. Immune Response Gene Profiles in the Term Placenta Depend Upon Maternal Muscle Mass

    PubMed Central

    O’Tierney, P. F.; Lewis, R. M.; McWeeney, S. K.; Hanson, M. A.; Inskip, H. M.; Morgan, T. K.; Barker, D. J.; Bagby, G.; Cooper, C.; Godfrey, K. M.

    2012-01-01

    Maternal thinness leads to metabolic challenges in the offspring, but it is unclear whether reduced maternal fat mass or muscle mass drives these metabolic changes. Recently, it has been shown that low maternal muscle mass—as measured by arm muscle area (AMA)—is associated with depressed nutrient transport to the fetus. To determine the role of maternal muscle mass on placental function, we analyzed the gene expression profiles of 30 human placentas over the range of AMA (25.2-90.8 cm2) from uncomplicated term pregnancies from the Southampton Women’s Survey cohort. Eighteen percent of the ∼60 genes that were highly expressed in less muscular women were related to immune system processes and the interferon-γ (IFNG) signaling pathway in particular. Those transcripts related to the IFNG pathway included IRF1, IFI27, IFI30, and GBP6. Placentas from women with low muscularity are, perhaps, more sensitive to the effects of inflammatory cytokines than those from more muscular women. PMID:22534332

  2. Transcription Profiling of Malaria-Naïve and Semi-immune Colombian Volunteers in a Plasmodium vivax Sporozoite Challenge

    PubMed Central

    Rojas-Peña, Monica L.; Vallejo, Andres; Herrera, Sócrates; Gibson, Greg; Arévalo-Herrera, Myriam

    2015-01-01

    Background Continued exposure to malaria-causing parasites in endemic regions of malaria induces significant levels of acquired immunity in adult individuals. A better understanding of the transcriptional basis for this acquired immunological response may provide insight into how the immune system can be boosted during vaccination, and into why infected individuals differ in symptomology. Methodology/Principal Findings Peripheral blood gene expression profiles of 9 semi-immune volunteers from a Plasmodium vivax malaria prevalent region (Buenaventura, Colombia) were compared to those of 7 naïve individuals from a region with no reported transmission of malaria (Cali, Colombia) after a controlled infection mosquito bite challenge with P. vivax. A Fluidigm nanoscale quantitative RT-PCR array was used to survey altered expression of 96 blood informative transcripts at 7 timepoints after controlled infection, and RNASeq was used to contrast pre-infection and early parasitemia timepoints. There was no evidence for transcriptional changes prior to the appearance of blood stage parasites at day 12 or 13, at which time there was a strong interferon response and, unexpectedly, down-regulation of transcripts related to inflammation and innate immunity. This differential expression was confirmed with RNASeq, which also suggested perturbations of aspects of T cell function and erythropoiesis. Despite differences in clinical symptoms between the semi-immune and malaria naïve individuals, only subtle differences in their transcriptomes were observed, although 175 genes showed significantly greater induction or repression in the naïve volunteers from Cali. Conclusion/Significance Gene expression profiling of whole blood reveals the type and duration of the immune response to P. vivax infection, and highlights a subset of genes that may mediate adaptive immunity. PMID:26244760

  3. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.

    PubMed

    Jarvis, Joseph N; Meintjes, Graeme; Bicanic, Tihana; Buffa, Viviana; Hogan, Louise; Mo, Stephanie; Tomlinson, Gillian; Kropf, Pascale; Noursadeghi, Mahdad; Harrison, Thomas S

    2015-04-01

    Understanding the host immune response during cryptococcal meningitis (CM) is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF) immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA). PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL)-6 and interferon-γ, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α). High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS). In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS), more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and IRIS

  4. Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes.

    PubMed

    Sridharan, Vishwajith; Gjini, Evisa; Liao, Xiaoyun; Chau, Nicole G; Haddad, Robert I; Severgnini, Mariano; Hammerman, Peter; El-Naggar, Adel; Freeman, Gordon J; Hodi, F Stephen; Rodig, Scott J; Dranoff, Glenn; Schoenfeld, Jonathan D

    2016-08-01

    Adenoid cystic carcinoma (ACC) is among the most lethal salivary gland tumors, with no treatments for metastatic disease that prolong survival. We examined tissue from 28 primary and metastatic ACC deposits obtained from 21 patients for infiltrating immune cells and PD-L1/PD-L2 expression and determined mRNA profiles of over 1,400 oncogenic and immune-related genes. We also assessed the effect of chemoradiation on immune mediators in a patient who had serial biopsies available. Most tumors expressed PD-L2 but had few infiltrating immune cells. Lack of immune-cell infiltrate was associated with expression of genes in the β-catenin/Wnt and PI3K pathways. Additionally, certain transcripts linked to growth and invasion were differentially expressed among primary and metastatic deposits. Chemoradiation appeared to increase CD8(+) effector T cells, decrease regulatory T cells, and promote a systemic humoral response. These data suggest a potential role for PD-L2 inhibition and immune modulation as treatment for patients with ACC. Cancer Immunol Res; 4(8); 679-87. ©2016 AACR. PMID:27312343

  5. Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy.

    PubMed

    Takahashi, Hideyuki; Sakakura, Koichi; Mito, Ikko; Ida, Shota; Chikamatsu, Kazuaki

    2016-08-01

    Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been revealed in peripheral blood as well as within tumors. In the present study, we first investigated the proportion and activation status of peripheral immune regulatory cells and CD8(+) T-cell subsets in patients with head and neck squamous cell carcinoma (HNSCC) using a multicolor flow cytometer, and then evaluated how therapy with docetaxel, cisplatin, and 5-fluorouracil modulated the immune cell profile in peripheral blood. The proportion of naïve T cells was lower and that of effector memory T cells (TEM ) was higher in HNSCC patients than in healthy donors. Moreover, the proportions of activated TEM cells and effector T cells (TEFF ) were dramatically increased in patients with advanced stage disease. The proportion of regulatory T cells and CD14(+) HLA-DR(-) myeloid-derived suppressor cells was elevated in HNSCC patients. Of note, after therapy, in addition to the transient reduction in immune regulatory cells, decreases in central memory T cells and increases in TEFF cells were observed among CD8(+) T-cell subsets, suggesting differentiation from central memory T cells into TEFF cells. Our results suggested that, despite the immunosuppressive status in HNSCC patients, tumor-specific immune responses mediated by CD8(+) T cells might be induced and maintained. Moreover, chemotherapy can trigger not only a transient reduction in immune regulatory cells but also further activation of CD8(+) T cells. PMID:27228557

  6. Short communication: Cytokine profiles from blood mononuclear cells of dairy cows classified with divergent immune response phenotypes.

    PubMed

    Martin, C E; Paibomesai, M A; Emam, S M; Gallienne, J; Hine, B C; Thompson-Crispi, K A; Mallard, B A

    2016-03-01

    Genetic selection for enhanced immune response has been shown to decrease disease occurrence in dairy cattle. Cows can be classified as high (H), average, or low responders based on antibody-mediated immune response (AMIR), predominated by type-2 cytokine production, and cell-mediated immune response (CMIR) through estimated breeding values for these traits. The purpose of this study was to identify in vitro tests that correlate with in vivo immune response phenotyping in dairy cattle. Blood mononuclear cells (BMC) isolated from cows classified as H-AMIR and H-CMIR through estimated breeding values for immune response traits were stimulated with concanavalin A (ConA; Sigma Aldrich, St. Louis, MO) and gene expression, cytokine production, and cell proliferation was determined at multiple time points. A repeated measures model, which included the effects of immune response group, parity, and stage of lactation, was used to compare differences between immune response phenotype groups. The H-AMIR cows produced more IL-4 protein than H-CMIR cows at 48 h; however, no difference in gene expression of type-2 transcription factor GATA3 or IL4 was noted. The BMC from H-CMIR cows had increased production of IFN-γ protein at 48, 72, and 96 h compared with H-AMIR animals. Further, H-CMIR cows had increased expression of the IFNG gene at 16, 24, and 48 h post-treatment with ConA, although expression of the type-1 transcription factor gene TBX21 did not differ between immune response groups. Although proliferation of BMC increased from 24 to 72 h after ConA stimulation, no differences were found between the immune response groups. Overall, stimulation of H-AMIR and H-CMIR bovine BMC with ConA resulted in distinct cytokine production profiles according to genetically defined groups. These distinct cytokine profiles could be used to define disease resistance phenotypes in dairy cows according to stimulation in vitro; however, other immune response phenotypes should be assessed

  7. The Systemic Profile of Soluble Immune Mediators in Patients with Myelodysplastic Syndromes

    PubMed Central

    Kittang, Astrid Olsnes; Sand, Kristoffer; Brenner, Annette Katharina; Rye, Kristin Paulsen; Bruserud, Øystein

    2016-01-01

    Introduction: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure due to disturbed bone marrow maturation. MDS is associated with increased risk of transformation to acute myeloid leukemia (AML) and features of immunological dysregulation. Materials and methods: Serum levels of 47 soluble immune mediators were examined in samples derived from 49 MDS patients (35 low-risk and 14 high-risk) and 23 healthy adults. Our patients represent an unselected population-based cohort. The mediators included cytokines, soluble adhesion proteins, matrix metalloproteases, and tissue inhibitors of proteases. Levels were determined using Luminex assays. Patients were classified as low- and high-risk based on the international prognostic scoring system (IPSS) score. Results: When comparing the serum levels of single mediators the MDS patients showed a relatively wide variation range for several mediators compared with healthy adults, especially interleukin 6 (IL-6), IL-8/CXCL8, CCL3, and CCL4. The high-risk patients had lower levels of epidermal growth factor (EGF), cluster of differentiation 40 ligand (CD40L), CCL5, CCL11, CXCL5, matrix metalloproteinase 1 (MMP-1), MMP-9, and tissue inhibitor of metalloproteinases 2 (TIMP-2) compared with low-risk patients. Unsupervised hierarchical cluster analysis visualized marked serum mediator profile differences between MDS patients; based on this analysis three patient subsets could be identified. The healthy adults were also included in this analysis and, as expected, they formed their own separate cluster, except for one outlier. Both low- and high-risk patients showed considerable heterogeneity with regard to serum profile, and this heterogeneity seems stable over time (one year follow-up). Finally, very few mediators differed between low- and high-risk patients, but hierarchical clustering based both on all mediators, as well as five selected mediators (EGF, CCL11, TIMP-2, MMP-1, and MMP-9) identified subsets of

  8. 77 FR 68104 - Proposed Information Collection; Comment Request; Socio-Economic Profile of Small-Scale...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-15

    ...-Economic Profile of Small-Scale Commercial Fisheries in the U.S. Caribbean AGENCY: National Oceanic and... socio-economic data about small scale fishermen and seafood dealers operating in the U.S. Caribbean. The...-economic performance of small- scale fleets, and evaluate the socio-economic impacts of Federal...

  9. Resiliency Scales for Children and Adolescents: Profiles of Juvenile Offenders

    ERIC Educational Resources Information Center

    Mowder, Melissa H.; Cummings, Jack A.; McKinney, Robert

    2010-01-01

    An exploratory study of resiliency profiles of male and female juvenile offenders committed to a juvenile correctional facility was conducted. The goal of the present study was to examine juvenile offenders' positive characteristics (e.g., adaptability, optimism, self-efficacy, tolerance of differences). To assess positive characteristics and…

  10. Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles

    PubMed Central

    Varn, Frederick S.; Andrews, Erik H.; Mullins, David W.; Cheng, Chao

    2016-01-01

    Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these results allow for a detailed and personalized assessment of the patient immune response to a tumour. When combined with routinely collected patient biopsy genomic data, this method can enable a richer understanding of the complex interplay between the host immune system and cancer. PMID:26725977

  11. Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles.

    PubMed

    Varn, Frederick S; Andrews, Erik H; Mullins, David W; Cheng, Chao

    2016-01-01

    Transcriptional programmes active in haematopoietic cells enable a variety of functions including dedifferentiation, innate immunity and adaptive immunity. Understanding how these programmes function in the context of cancer can provide valuable insights into host immune response, cancer severity and potential therapy response. Here we present a method that uses the transcriptomes of over 200 murine haematopoietic cells, to infer the lineage-specific haematopoietic activity present in human breast tumours. Correlating this activity with patient survival and tumour purity reveals that the transcriptional programmes of many cell types influence patient prognosis and are found in environments of high lymphocytic infiltration. Collectively, these results allow for a detailed and personalized assessment of the patient immune response to a tumour. When combined with routinely collected patient biopsy genomic data, this method can enable a richer understanding of the complex interplay between the host immune system and cancer. PMID:26725977

  12. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients.

    PubMed

    Paiva, Bruno; Cedena, Maria-Teresa; Puig, Noemi; Arana, Paula; Vidriales, Maria-Belen; Cordon, Lourdes; Flores-Montero, Juan; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Martinez-Lopez, Joaquin; Ocio, Enrique M; Hernandez, Miguel T; Teruel, Ana-Isabel; Rosiñol, Laura; Echeveste, María-Asunción; Martinez, Rafael; Gironella, Mercedes; Oriol, Albert; Cabrera, Carmen; Martin, Jesus; Bargay, Joan; Encinas, Cristina; Gonzalez, Yolanda; Van Dongen, Jacques J M; Orfao, Alberto; Bladé, Joan; Mateos, Maria-Victoria; Lahuerta, Juan José; San Miguel, Jesús F

    2016-06-23

    The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first- to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (<10(-5); n = 54, 34%), MRD positive (between <10(-4) and ≥10(-5); n = 20, 12%), and MRD positive (≥10(-4); n = 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P = .007) and overall survival (OS) (HR, 3.1; P = .04), with significant benefit for MRD-negative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10(-4) and ≥10(-5) vs ≥10(-4) (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P = .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P = .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials.gov as #NCT01237249

  13. Immune gene expression profiles in swine inguinal lymph nodes with different viral loads of porcine circovirus type 2.

    PubMed

    Lin, Chun-Ming; Jeng, Chian-Ren; Liu, Jen-Pei; Lin, En-Chung; Chang, Chih-Cheng; Huang, Yu-Liang; Tsai, Yi-Chieh; Chia, Mi-Yuan; Wan, Cho-Hua; Pang, Victor Fei

    2013-03-23

    Porcine circovirus type 2 (PCV2) infection has been suggested as an acquired immunodeficiency disorder. However, the immunopathogenesis of PCV2 infection is still not fully clarified. In the present study, 35 inguinal lymph nodes (LNs) with different levels of PCV2 load obtained from postwaening multisystemic wasting syndrome (PMWS)-affected pigs and 7 from healthy subclinically PCV2-infected pigs were selected. The LNs were subsequently ranked by their PCV2 loads to mimic the progression of PCV2 infection-associated lesion development. The expressions of 96 selected immune genes in these LNs were assessed by the integration of several reverse transcription quantitative real-time polymerase chain reaction experiments. Hierarchical cluster analysis of the gene expression profiles resulted in 5 major clusters (A, B, C, D, and E). Different clusters of immune gene expression profiles were compatible with the divergent functions of various immune cell subpopulations. 61 out of 96 selected genes belonged to cluster C and were mainly involved in the activation of dendritic cells and B and T lymphocytes. The expression levels of these genes were generally up-regulated in the LNs obtained from PMWS-affected pigs with relatively lower PCV2 loads. However, the up-regulated level tended to reduce or turned into down-regulation as the PCV2 load increased. Genes belonging to cluster B, involved in T cell receptor signaling, became silenced as the PCV2 load increased. The expression profiles of macrophage-associated genes were either independent from or positively correlated with the PCV2 load, such as those in clusters A and E and in cluster D, respectively. In addition, the principle component analysis of the expression of the 96 selected genes in the 42 inguinal LNs revealed that 53.10% and 72.29% of the total data variants could be explained by the top-3 and top-7 principle components, respectively, suggesting that the disease development of PCV2 infection may be associated

  14. Transcriptome Profiling Reveals Th17-Like Immune Responses Induced in Zebrafish Bath-Vaccinated with a Live Attenuated Vibrio anguillarum

    PubMed Central

    Wu, Haizhen; Yang, Minjun; Liu, Qin; Wang, Qiyao; Zhang, Yuanxing

    2013-01-01

    Background A candidate vaccine, live attenuated Vibrio anguillarum developed in our laboratory could prevent vibriosis of fish resulted from V. anguillarum and V. alginolyticus. To elucidate the molecular mechanisms underlying the vaccine protection, we used microarray technology to compare the spleen transcriptomes of bath-vaccinated and unvaccinated zebrafish at 28 days post vaccination. Principal Findings A total of 2164 genes and transcripts were differentially expressed, accounting for 4.9% of all genes represented on the chip. In addition to iron metabolism related to the innate immunity and the signaling pathways, these differentially expressed genes also involved in the adaptive immunity, mainly including the genes associated with B and T cells activation, proliferation and expansion. Transcription profiles of Th17-related transcription factors, cytokines and cytokine receptors during 35 days post-vaccination implied that Th17 cells be activated in bath-vaccinated zebrafish. Conclusion/Significance The transcriptome profiling with microarray revealed the Th17-like immune response to bath-vaccination with the live attenuated V. anguillarum in zebrafish. PMID:24023910

  15. Profiling DNA Methylomes from Microarray to Genome-Scale Sequencing

    PubMed Central

    Huang, Yi-Wen; Huang, Tim H.-M.; Wang, Li-Shu

    2010-01-01

    DNA cytosine methylation is a central epigenetic modification which plays critical roles in cellular processes including genome regulation, development and disease. Here, we review current and emerging microarray and next-generation sequencing based technologies that enhance our knowledge of DNA methylation profiling. Each methodology has limitations and their unique applications, and combinations of several modalities may help build the entire methylome. With advances on next-generation sequencing technologies, it is now possible to globally map the DNA cytosine methylation at single-base resolution, providing new insights into the regulation and dynamics of DNA methylation in genomes. PMID:20218736

  16. Profiling DNA methylomes from microarray to genome-scale sequencing.

    PubMed

    Huang, Yi-Wei; Huang, Tim H-M; Wang, Li-Shu

    2010-04-01

    DNA cytosine methylation is a central epigenetic modification which plays critical roles in cellular processes including genome regulation, development and disease. Here, we review current and emerging microarray and next-generation sequencing based technologies that enhance our knowledge of DNA methylation profiling. Each methodology has limitations and their unique applications, and combinations of several modalities may help build the entire methylome. With advances on next-generation sequencing technologies, it is now possible to globally map the DNA cytosine methylation at single-base resolution, providing new insights into the regulation and dynamics of DNA methylation in genomes. PMID:20218736

  17. Expression Profiling of Innate Immune Genes in Milk Somatic Cells During Subclinical Mastitis in Crossbred Dairy Cows.

    PubMed

    Karthikeyan, A; Radhika, G; Aravindhakshan, T V; Anilkumar, K

    2016-10-01

    Innate immune mechanism plays a key role in mammary defense, from recognition of pathogens to activation of nonspecific and specific immunity involved in elimination of pathogens. Expression profiles of innate immune response genes namely Toll like receptor 2 (TLR-2), Peptidoglycan recognition protein 1 (PGLYRP-1), Interleukin 8 receptor (IL-8 R), L-Selectin (SELL), and Osteopontin (OPN) in milk somatic cells of subclinical mastitis (SCM) affected crossbred cows were investigated under this study at transcript level using quantitative real time polymerase chain reaction (qRT-PCR). Dairy cows in mid lactation were screened for SCM using California Mastitis Test (CMT), Somatic Cell Count (SCC) and Electrical Conductivity test (EC). Based on results of SCM screening tests, crossbred cows were clustered into two groups with four Staphylococcus aureus infected SCM cows and four apparently healthy cows. The expressions levels of TLR-2, PGLYRP-1, IL-8 R, SELL, and OPN in milk somatic cells of SCM affected cows were significantly higher (p < 0.05) than healthy cows. These genes could be considered as candidate genes for innate immune response against S. aureus SCM infection. PMID:27565875

  18. Biochemical, Histopathological and Morphological Profiling of a Rat Model of Early Immune Stimulation: Relation to Psychopathology

    PubMed Central

    Kubesova, Anna; Tejkalova, Hana; Syslova, Kamila; Kacer, Petr; Vondrousova, Jana; Tyls, Filip; Fujakova, Michaela; Palenicek, Tomas; Horacek, Jiri

    2015-01-01

    Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson’s disease and Alzheimer’s disease). The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin), their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases - glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders. PMID:25602957

  19. Quantitative RT-PCR profiling of the Rabbit Immune Response: Assessment of Acute Shigella flexneri Infection

    PubMed Central

    Schnupf, Pamela; Sansonetti, Philippe J.

    2012-01-01

    Quantitative reverse transcription PCR analysis is an important tool to monitor changes in gene expression in animal models. The rabbit is a widely accepted and commonly used animal model in the study of human diseases and infections by viral, fungal, bacterial and protozoan pathogens. Only a limited number of rabbit genes have, however, been analyzed by this method as the rabbit genome sequence remains unfinished. Recently, increasing coverage of the genome has permitted the prediction of a growing number of genes that are relevant in the context of the immune response. We hereby report the design of twenty-four quantitative PCR primer pairs covering common cytokines, chemoattractants, antimicrobials and enzymes for a rapid, sensitive and quantitative analysis of the rabbit immune response. Importantly, all primer pairs were designed to be used under identical experimental conditions, thereby enabling the simultaneous analysis of all genes in a high-throughput format. This tool was used to analyze the rabbit innate immune response to infection with the human gastrointestinal pathogen Shigella flexneri. Beyond the known inflammatory mediators, we identified IL-22, IL-17A and IL-17F as highly upregulated cytokines and as first responders to infection during the innate phase of the host immune response. This set of qPCR primers also provides a convenient tool for monitoring the rabbit immune response during infection with other pathogens and other inflammatory conditions. PMID:22675469

  20. Immune response profile elicited by the model antigen ovalbumin expressed in fusion with the bacterial OprI lipoprotein.

    PubMed

    Basto, Afonso P; Badenes, Marina; Almeida, Sílvia C P; Martins, Carlos; Duarte, António; Santos, Dulce M; Leitão, Alexandre

    2015-03-01

    The use of immunogenic formulations targeting pattern recognition receptors towards modulation of immune responses is a promising strategy to develop better vaccines against infectious and malignant diseases. Molecules targeting TLR2 offer interesting properties that are relevant for vaccine development, including the possibility to covalently attach the lipidic ligands to the antigens. However, the type of immune response elicited by these formulations is still controversial. In this work, we used the model antigen ovalbumin (OVA) expressed in fusion with the bacterial lipoprotein OprI in order to characterize the immunomodulatory properties of this TLR ligand. Murine bone marrow-derived dendritic cells stimulated with OprI-OVA fusion lipoprotein produced high levels of the pro-inflammatory cytokines TNF-α and IL-6 and also IL-10, IL-12(p70) and IL-27, while TGF-β and IL-23 were not detected. Using OT-II and OT-I mice, an enhancement of MHC class II and class I antigen presentation was observed for the OVA antigen in fusion with OprI. Mice immunized by intraperitoneal route with this fusion lipoprotein in prime-boost protocols developed strong specific antibody responses including IgG1, IgG2c, IgG2b, IgG3 and IgE. These results, together with data obtained by restimulation of splenocytes from the immunized mice, point to an immune response profile that does not correspond to a strict Th1 or Th2 polarization. Finally, in a challenge experiment using a melanoma syngeneic mouse model (B16-OVA), prophylactic inoculation with OprI fused with the unrelated antigen eGFP increased the tumor growth, while the fusion with the tumor-associated antigen OVA delayed the tumor growth and increased mice survival. PMID:25467796

  1. RNA-seq Profiles of Immune Related Genes in the Staghorn Coral Acropora cervicornis Infected with White Band Disease

    PubMed Central

    Libro, Silvia; Kaluziak, Stefan T.; Vollmer, Steven V.

    2013-01-01

    Coral diseases are among the most serious threats to coral reefs worldwide, yet most coral diseases remain poorly understood. How the coral host responds to pathogen infection is an area where very little is known. Here we used next-generation RNA-sequencing (RNA-seq) to produce a transcriptome-wide profile of the immune response of the Staghorn coral Acropora cervicornis to White Band Disease (WBD) by comparing infected versus healthy (asymptomatic) coral tissues. The transcriptome of A. cervicornis was assembled de novo from A-tail selected Illumina mRNA-seq data from whole coral tissues, and parsed bioinformatically into coral and non-coral transcripts using existing Acropora genomes in order to identify putative coral transcripts. Differentially expressed transcripts were identified in the coral and non-coral datasets to identify genes that were up- and down-regulated due to disease infection. RNA-seq analyses indicate that infected corals exhibited significant changes in gene expression across 4% (1,805 out of 47,748 transcripts) of the coral transcriptome. The primary response to infection included transcripts involved in macrophage-mediated pathogen recognition and ROS production, two hallmarks of phagocytosis, as well as key mediators of apoptosis and calcium homeostasis. The strong up-regulation of the enzyme allene oxide synthase-lipoxygenase suggests a key role of the allene oxide pathway in coral immunity. Interestingly, none of the three primary innate immune pathways - Toll-like receptors (TLR), Complement, and prophenoloxydase pathways, were strongly associated with the response of A. cervicornis to infection. Five-hundred and fifty differentially expressed non-coral transcripts were classified as metazoan (n = 84), algal or plant (n = 52), fungi (n = 24) and protozoans (n = 13). None of the 52 putative Symbiodinium or algal transcript had any clear immune functions indicating that the immune response is driven by the coral host, and not its algal

  2. Marek's Disease Virus-Induced Immunosuppression: Array Analysis of Chicken Immune Response Gene Expression Profiling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens induced by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latency infection within CD4+ T cells. Host-virus interaction, immune responses to...

  3. A dual challenge of corticotropin releasing hormone and vasopressin alters immune cell profiles in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The duration and magnitude of cortisol release can have different effects on the immune response. Over the last decade, studies have suggested that acute stress, when cortisol is elevated for a short duration of time, can be immuno-stimulatory rather than immuno-suppressive. This study was designed ...

  4. Implementing Broad Scale Childhood Immunization Decision Support as a Web Service

    PubMed Central

    Zhu, Vivienne J.; Grannis, Shaun J.; Rosenman, Marc B.; Downs, Stephen M.

    2009-01-01

    Timely vaccinations decrease a child’s risk of contracting vaccine-preventable disease and prevent disease outbreaks. Childhood immunization schedules may represent the only clinical guideline for which there is official national consensus. So an immunization clinical decision support system (CDSS) is a natural application. However, immunization schedules are complex and change frequently. Maintaining multiple CDSS’s is expensive and error prone. Therefore, a practical strategy would be an immunization CDSS as a centralized web service that can be easily accessed by various electronic medical record (EMR) systems. This allows centralized maintenance of immunization guidelines. We have developed a web service, based on Miller’s tabular model with modifications, which implements routine childhood immunization guidelines. This immunization web service is currently operating in the Regenstrief Institute intranet and system evaluations are ongoing. We will make this web service available on the Internet. In this paper, we describe this web service -based immunization decision support tool. PMID:20351952

  5. Chance and risk of controlling rabies in large-scale and long-term immunized fox populations.

    PubMed

    Tischendorf, L; Thulke, H H; Staubach, C; Müller, M S; Jeltsch, F; Goretzki, J; Selhorst, T; Müller, T; Schlüter, H; Wissel, C

    1998-05-22

    The large-scale immunization of European fox populations against rabies is currently under the microscope for reducing the considerable expenditure without putting public health at risk. Empirical knowledge is inadequate to interpret the lasting sporadic incidences and, therefore, to verify the final success of the immunization campaigns. By using a proven simulation model we show that rabies can persist on a very low level in the form of spatio-temporal moving infection clusters within a highly immunized fox population. We found further: (i) the existence of a threshold after which the chance of eradicating the disease by vaccination increases clearly, and (ii) that at least six years of 70% mean immunization rate are required to guarantee a likely success. PMID:9633109

  6. Genome-wide multi-omics profiling of colorectal cancer identifies immune determinants strongly associated with relapse

    PubMed Central

    Madhavan, Subha; Gusev, Yuriy; Natarajan, Thanemozhi G.; Song, Lei; Bhuvaneshwar, Krithika; Gauba, Robinder; Pandey, Abhishek; Haddad, Bassem R.; Goerlitz, David; Cheema, Amrita K.; Juhl, Hartmut; Kallakury, Bhaskar; Marshall, John L.; Byers, Stephen W.; Weiner, Louis M.

    2013-01-01

    The use and benefit of adjuvant chemotherapy to treat stage II colorectal cancer (CRC) patients is not well understood since the majority of these patients are cured by surgery alone. Identification of biological markers of relapse is a critical challenge to effectively target treatments to the ~20% of patients destined to relapse. We have integrated molecular profiling results of several “omics” data types to determine the most reliable prognostic biomarkers for relapse in CRC using data from 40 stage I and II CRC patients. We identified 31 multi-omics features that highly correlate with relapse. The data types were integrated using multi-step analytical approach with consecutive elimination of redundant molecular features. For each data type a systems biology analysis was performed to identify pathways biological processes and disease categories most affected in relapse. The biomarkers detected in tumors urine and blood of patients indicated a strong association with immune processes including aberrant regulation of T-cell and B-cell activation that could lead to overall differences in lymphocyte recruitment for tumor infiltration and markers indicating likelihood of future relapse. The immune response was the biologically most coherent signature that emerged from our analyses among several other biological processes and corroborates other studies showing a strong immune response in patients less likely to relapse. PMID:24312117

  7. Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection.

    PubMed

    Francis, Suzanna C; Hou, Yanwen; Baisley, Kathy; van de Wijgert, Janneke; Watson-Jones, Deborah; Ao, Trong T; Herrera, Carolina; Maganja, Kaballa; Andreasen, Aura; Kapiga, Saidi; Coulton, Gary R; Hayes, Richard J; Shattock, Robin J

    2016-01-01

    Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1α, IL-1β, IL-2, MIP-1β, IP-10, IL-8, TGF-β, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre-ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL-6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies. PMID:26814891

  8. Host Immune Transcriptional Profiles Reflect the Variability in Clinical Disease Manifestations in Patients with Staphylococcus aureus Infections

    PubMed Central

    Banchereau, Romain; Jordan-Villegas, Alejandro; Ardura, Monica; Mejias, Asuncion; Baldwin, Nicole; Xu, Hui; Saye, Elizabeth; Rossello-Urgell, Jose; Nguyen, Phuong; Blankenship, Derek; Creech, Clarence B.; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; Ramilo, Octavio

    2012-01-01

    Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations. PMID:22496797

  9. Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection

    PubMed Central

    Francis, Suzanna C.; Hou, Yanwen; Baisley, Kathy; van de Wijgert, Janneke; Watson-Jones, Deborah; Ao, Trong T.; Herrera, Carolina; Maganja, Kaballa; Andreasen, Aura; Kapiga, Saidi; Coulton, Gary R.; Hayes, Richard J.; Shattock, Robin J.

    2016-01-01

    Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1α, IL-1β, IL-2, MIP-1β, IP-10, IL-8, TGF-β, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre-ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL-6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies. PMID:26814891

  10. Profiling of Human Acquired Immunity Against the Salivary Proteins of Phlebotomus papatasi Reveals Clusters of Differential Immunoreactivity

    PubMed Central

    Geraci, Nicholas S.; Mukbel, Rami M.; Kemp, Michael T.; Wadsworth, Mariha N.; Lesho, Emil; Stayback, Gwen M.; Champion, Matthew M.; Bernard, Megan A.; Abo-Shehada, Mahmoud; Coutinho-Abreu, Iliano V.; Ramalho-Ortigão, Marcelo; Hanafi, Hanafi A.; Fawaz, Emadeldin Y.; El-Hossary, Shabaan S.; Wortmann, Glenn; Hoel, David F.; McDowell, Mary Ann

    2014-01-01

    Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents. PMID:24615125

  11. Profile of microRNA in Giant Panda Blood: A Resource for Immune-Related and Novel microRNAs.

    PubMed

    Yang, Mingyu; Du, Lianming; Li, Wujiao; Shen, Fujun; Fan, Zhenxin; Jian, Zuoyi; Hou, Rong; Shen, Yongmei; Yue, Bisong; Zhang, Xiuyue

    2015-01-01

    The giant panda (Ailuropoda melanoleuca) is one of the world's most beloved endangered mammals. Although the draft genome of this species had been assembled, little was known about the composition of its microRNAs (miRNAs) or their functional profiles. Recent studies demonstrated that changes in the expression of miRNAs are associated with immunity. In this study, miRNAs were extracted from the blood of four healthy giant pandas and sequenced by Illumina next generation sequencing technology. As determined by miRNA screening, a total of 276 conserved miRNAs and 51 novel putative miRNAs candidates were detected. After differential expression analysis, we noticed that the expressions of 7 miRNAs were significantly up-regulated in young giant pandas compared with that of adults. Moreover, 2 miRNAs were up-regulated in female giant pandas and 1 in the male individuals. Target gene prediction suggested that the miRNAs of giant panda might be relevant to the expressions of 4,602 downstream genes. Subseuqently, the predicted target genes were conducted to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and we found that these genes were mainly involved in host immunity, including the Ras signaling pathway, the PI3K-Akt signaling pathway, and the MAPK signaling pathway. In conclusion, our results provide the first miRNA profiles of giant panda blood, and the predicted functional analyses may open an avenue for further study of giant panda immunity. PMID:26599861

  12. Profile of microRNA in Giant Panda Blood: A Resource for Immune-Related and Novel microRNAs

    PubMed Central

    Yang, Mingyu; Du, Lianming; Li, Wujiao; Shen, Fujun; Fan, Zhenxin; Jian, Zuoyi; Hou, Rong; Shen, Yongmei; Yue, Bisong; Zhang, Xiuyue

    2015-01-01

    The giant panda (Ailuropoda melanoleuca) is one of the world’s most beloved endangered mammals. Although the draft genome of this species had been assembled, little was known about the composition of its microRNAs (miRNAs) or their functional profiles. Recent studies demonstrated that changes in the expression of miRNAs are associated with immunity. In this study, miRNAs were extracted from the blood of four healthy giant pandas and sequenced by Illumina next generation sequencing technology. As determined by miRNA screening, a total of 276 conserved miRNAs and 51 novel putative miRNAs candidates were detected. After differential expression analysis, we noticed that the expressions of 7 miRNAs were significantly up-regulated in young giant pandas compared with that of adults. Moreover, 2 miRNAs were up-regulated in female giant pandas and 1 in the male individuals. Target gene prediction suggested that the miRNAs of giant panda might be relevant to the expressions of 4,602 downstream genes. Subseuqently, the predicted target genes were conducted to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and we found that these genes were mainly involved in host immunity, including the Ras signaling pathway, the PI3K-Akt signaling pathway, and the MAPK signaling pathway. In conclusion, our results provide the first miRNA profiles of giant panda blood, and the predicted functional analyses may open an avenue for further study of giant panda immunity. PMID:26599861

  13. Altered Immune Profiles of Natural Killer Cells in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, Qiong-Fang; Shao, Jian-Ying; Yin, Wen-Wei; Xia, Yang; Chen, Ling; Wang, Xing; Hu, Huai-Dong; Hu, Peng; Ren, Hong; Zhang, Da-Zhi

    2016-01-01

    Background Natural killer (NK) cells are the main effective component of the innate immune system that responds to chronic hepatitis B (CHB) infection. Although numerous studies have reported the immune profiles of NK cells in CHB patients, they are limited by inconsistent results. Thus, we performed a meta-analysis to characterize reliably the immune profiles of NK cells after CHB infection, specifically frequency, phenotype, and function. Methods A literature search of the computer databases MEDLINE, PUBMED, EMBASE, and Cochrane Center Register of Controlled Trails was performed and 19 studies were selected. The standard mean difference (SMD) and 95% confidence interval (CI) of each continuous variable was estimated with a fixed effects model when I2 < 50% for the test for heterogeneity, or the random effects model otherwise. Publication bias was evaluated using Begg’s and Egger’s tests. Results The meta-analysis of publications that reported frequency of peripheral NK cells showed that NK cell levels in CHB patients were significantly lower compared with that of healthy controls. A higher frequency of CD56bright NK subsets was found in CHB patients, but the CD56dim NK subsets of CHB patients and healthy controls were similar. CHB patients before and after antiviral therapy with nucleotide analogues (NUCs) showed no statistical difference in NK frequency. The activating receptors were upregulated, whereas inhibitory receptors were comparable in the peripheral NK cells of CHB individuals and healthy controls. NK cells of CHB patients displayed higher cytotoxic potency as evidenced by CD107a protein levels and conserved potency to produce interferon-gamma (IFNγ), compared with their healthy counterparts. Conclusion Our results revealed that CHB patients had a lower frequency of NK cells compared with healthy individuals not treatable with antiviral NUC therapy. With an activating phenotype, NK cells in CHB patients showed better cytotoxic potency and conserved

  14. Immune response profiling of malignant pleural mesothelioma for diagnostic and prognostic biomarkers.

    PubMed

    Creaney, Jenette; Dick, Ian M; Musk, A W Bill; Olsen, Nola J; Robinson, Bruce W S

    2016-09-01

    The asbestos induced cancer malignant mesothelioma (MM) is difficult to diagnose and has a poor prognosis. MM is an immunological cancer, therefore autoantibodies may be suitable biomarkers and associated with prognosis. We used Protoarray(®) microarrays to determine immune responses to 8798 antigens in 10 MM and 10 asbestos exposed controls and developed diagnostic panels using 17 antigens from this. The AUC of these panels were independently tested in these 10 MM patients and controls and in a validation group of 36 controls and 35 MM patients using luminex assays; none of the antigens identified were validated. Immune responses to RAB38 were associated with a better prognosis. PMID:27009350

  15. Toxicogenomic Profiles in Relation to Maternal Immunotoxic Exposure and Immune Functionality in Newborns

    PubMed Central

    Hochstenbach, Kevin

    2012-01-01

    A crucial period for the development of the immune system occurs in utero. This results in a high fetal vulnerability to immunotoxic exposure, and indeed, immunotoxic effects have been reported, demonstrating negative effects on immune-related health outcomes and immune functionality. Within the NewGeneris cohort BraMat, a subcohort of the Norwegian Mother and Child Cohort Study (MoBa), immunotoxicity was demonstrated for polychlorinated biphenyls and dioxins, showing associations between estimated maternal intake levels and reduced measles vaccination responses in the offspring at the age of 3. The present study aimed to investigate this link at the transcriptomic level within the same BraMat cohort. To this end, whole-genome gene expression in cord blood was investigated and found to be associated with maternal Food Frequency Questionnaires–derived exposure estimates and with vaccination responses in children at 3 years of age. Because the literature reports gender specificity in the innate, humoral, and cell-mediated responses to viral vaccines, separate analysis for males and females was conducted. Separate gene sets for male and female neonates were identified, comprising genes significantly correlating with both 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and polychlorinated biphenyls (PCB) exposure and with measles vaccination response. Noteworthy, genes correlating negatively with exposure in general show positive correlations with antibody levels and vice versa. For both sexes, these included immune-related genes, suggesting immunosuppressive effects of maternal exposure to TCDD and PCB at the transcriptomic level in neonates in relation to measles vaccination response 3 years later. PMID:22738990

  16. Expression Profiles of Circulating Cytokines, Chemokines and Immune Cells in Patients With Hepatitis B Virus Infection

    PubMed Central

    Lian, Jian-Qi; Yang, Xiao-Fei; Zhao, Rong-Rong; Zhao, Yan-Yan; Li, Yu; Zhang, Ye; Huang, Chang-Xing

    2014-01-01

    Background: Immune cells and molecules play a vital role in initiating, maintaining, regulating immunological homeostasis and inflammation in many pathological and physiological processes; however, the changes on expressions and functions of these cells and molecules in hepatitis B virus (HBV) infection have not been elucidated well. Objectives: The current study aimed to determine the expression pattern of different cytokines, chemokines, immune cells in HBV infection and their association with disease progression. Patients and Methods: Sixty-nine patients with chronic HBV infection were enrolled. Five immune cell subsets and 46 cytokines and chemokines were analyzed by flow cytometry and Luminex 200. Results: In comparison to healthy individuals and asymptomatic HBV carriers, expression of CXCL9, CXCL10, CXCL11, and IL-10 were elevated in patients with chronic active HBV and had positive correlation with ALT levels. In contrast, G-CSF, MCP-3, and IFN-γ levels were significantly decreased in patients with chronic active HBV infection in contrast to carriers and healthy individuals; however, these down regulations did not show any correlation with either virological findings or liver inflammation. Although the proportion of CD4+ CD25 high regulatory T cells (Tregs) was higher in patients with HBV infection than in healthy controls, no correlations were found between Tregs and other cytokines or chemokines. Conclusions: CXCR3-associated chemokines might contribute to liver inflammation in chronic hepatitis B, while MCP-3 and G-CSF were inhibited by HBV infection. Host immune response was suppressed as manifested by an increase in CD4+ CD25high Tregs and IL-10 as well as a decrease in IFN-γ. Exploiting the expression pattern of cytokine and chemokine may help to develop a better understanding of chronic HBV infection pathogenesis. PMID:24976843

  17. 1H NMR-Based Profiling Reveals Differential Immune-Metabolic Networks during Influenza Virus Infection in Obese Mice

    PubMed Central

    Milner, J. Justin; Wang, Jue; Sheridan, Patricia A.; Ebbels, Tim; Beck, Melinda A.; Saric, Jasmina

    2014-01-01

    Obese individuals are at greater risk for death from influenza virus infection. Paralleling human evidence, obese mice are also more susceptible to influenza infection mortality. However, the underlying mechanisms driving greater influenza severity in the obese remain unclear. Metabolic profiling has been utilized in infectious disease models to enhance prognostic or diagnostic methods, and to gain insight into disease pathogenesis by providing a more global picture of dynamic infection responses. Herein, metabolic profiling was used to develop a deeper understanding of the complex processes contributing to impaired influenza protection in obese mice and to facilitate generation of new explanatory hypotheses. Diet-induced obese and lean mice were infected with influenza A/Puerto Rico/8/34. 1H nuclear magnetic resonance-based metabolic profiling of urine, feces, lung, liver, mesenteric white adipose tissue, bronchoalveolar lavage fluid and serum revealed distinct metabolic signatures in infected obese mice, including perturbations in nucleotide, vitamin, ketone body, amino acid, carbohydrate, choline and lipid metabolic pathways. Further, metabolic data was integrated with immune analyses to obtain a more comprehensive understanding of potential immune-metabolic interactions. Of interest, uncovered metabolic signatures in urine and feces allowed for discrimination of infection status in both lean and obese mice at an early influenza time point, which holds prognostic and diagnostic implications for this methodology. These results confirm that obesity causes distinct metabolic perturbations during influenza infection and provide a basis for generation of new hypotheses and use of this methodology in detection of putative biomarkers and metabolic patterns to predict influenza infection outcome. PMID:24844920

  18. Decreased antigenicity profiles of immune-escaped and drug-resistant hepatitis B surface antigen (HBsAg) double mutants

    PubMed Central

    2013-01-01

    Background Selective pressure from either the immune response or the use of nucleoside analogs in antiviral therapy could be driving the emergence of HBV mutants. Because of the overlap of the open reading frame (ORF) S for the HBsAg and ORF P for viral polymerase, rtM204I and rtM204V mutations in the polymerase would produce sI195M and sW196S in the HBsAg. The combined effects of immune-escaped mutations (sT118M, sG145K, sG145R) and drug-resistant mutations (rtM204I, rtM204V) on the antigenicity profiles of HBsAg has not been widely explored. Methods To determine the combined effects of immune-escaped and drug-resistant mutants on the antigenicity profiles of HBsAg, recombinant plasmids encoding HBsAg double mutants were constructed using site-directed mutagenesis. The supernatant from each plasmid transfection was analyzed for HBsAg in the western-blotting and five of the most commonly used commercial ELISA kits in China. Results Western-blotting assay showed the successful expression of each HBsAg mutant. All five ELISA kits manifested similar avidity, which were demonstrated by the slope of the curves, for the sT118M mutant, and sT118M-rtM204I (sT118M-sI195M) and sT118M-rtM204V (sT118M-sW196S) double mutants, suggesting that drug-resistant YMDD mutants caused negligible losses in the antigenicity of immune-escaped sT118M HBsAg. In contrast, the presence of the rtM204I (sI195M) mutation, but not rtM204V (sW196S) in combination with the sG145K mutation significantly reduced the avidity of sG145K HBsAg. The rtM204I (sI195M) mutation also decreased the antigenicity profiles for sG145R HBsAg. Conclusions Drug-resistant mutations rtM204I (sI195M) and rtM204V (sW196S) caused significant reduction in antigenicity for the immune-escaped HBsAg mutants sG145K and sG145R, which may hamper HBV diagnosis and disease control from HBV blood-transfusion transmissions in China. The development of ELISA kits with a greater sensitivity for drug-resistant and immune-escaped HBs

  19. Immunological evaluation of four arc welders exposed to fumes from ignited polyurethane (isocyanate) foam: antibodies and immune profiles

    SciTech Connect

    Broughton, A.; Thrasher, J.D.; Gard, Z.

    1988-01-01

    Four arc welders having a flu-like illness with multiple health complaints following an exposure to high concentrations of isocyanate fumes from ignited polyurethane foam underwent immunological tests as follows: ELISA antibody assays, activated lymphocyte profiles, and lymphocyte blastogenesis. ELISA procedures revealed the presence of antibodies to hexamethylene diisocyanate (HDI) and formaldehyde (F) conjugated to human serum albumin (HDI-SA and F-SA). The results from the activated lymphocyte profiles showed deviations from the norm as follows: three welders had elevated helper/suppressor (H/S) ratios; all four had elevated percentages of Tal positive cells; two had decreases in B cells; and one had low total white cell and lymphocyte counts. In contrast, the percentage and absolute numbers of ILS receptor cells were normal in the four subjects. T cell blastogenesis to PHA, Con A and PWM resulted in the following: T-cells from one subject responded normally; in another, a high response (212% of controls) to PHA occurred with normal mitogenesis to Con A and PWM. In the remaining two welders, the T cells responded abnormally low (50 to 75% of controls) to the three mitogens. In conclusion, the existence of IgG antibodies to HDI-SA and F-SA, the altered activated immune profiles, the elevated Tal cells, and the abnormal blastogenesis are interpreted as being linked with the episode of HDI and F exposure and the subsequent flu-like illness of the four welders.

  20. Tomato Aqueous Extract Modulates the Inflammatory Profile of Immune Cells and Endothelial Cells.

    PubMed

    Schwager, Joseph; Richard, Nathalie; Mussler, Bernd; Raederstorff, Daniel

    2016-01-01

    Nutrients transiently or chronically modulate functional and biochemical characteristics of cells and tissues both in vivo and in vitro. The influence of tomato aqueous extract (TAE) on the in vitro inflammatory response of activated human peripheral blood leukocytes (PBLs) and macrophages was investigated. Its effect on endothelial dysfunction (ED) was analyzed in human umbilical vein endothelial cells (HUVECs). Murine macrophages (RAW264.7 cells), PBLs and HUVECs were incubated with TAE. They were activated with LPS or TNF-α in order to induce inflammatory processes and ED, respectively. Inflammatory mediators and adhesion molecules were measured by immune assay-based multiplex analysis. Gene expression was quantified by RT-PCR. TAE altered the production of interleukins (IL-1β, IL-6, IL-10, IL-12) and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CXCL8/IL-8, CXCL10/IP-10) in PBLs. TAE reduced ED-associated expression of adhesion molecules (ICAM-1, VCAM-1) in endothelial cell. In macrophages, the production of nitric oxide, PGE2, cytokines and ILs (TNF-α, IL-1β, IL-6, IL-12), which reflects chronic inflammatory processes, was reduced. Adenosine was identified as the main bioactive of TAE. Thus, TAE had cell-specific and context-dependent effects. We infer from these in vitro data, that during acute inflammation TAE enhances cellular alertness and therefore the sensing of disturbed immune homeostasis in the vascular-endothelial compartment. Conversely, it blunts inflammatory mediators in macrophages during chronic inflammation. A novel concept of immune regulation by this extract is proposed. PMID:26840280

  1. Transcriptome Profiling Reveals Disruption of Innate Immunity in Chronic Heavy Ethanol Consuming Female Rhesus Macaques

    PubMed Central

    Sureshchandra, Suhas; Rais, Maham; Stull, Cara; Grant, Kathleen; Messaoudi, Ilhem

    2016-01-01

    It is well established that heavy ethanol consumption interferes with the immune system and inflammatory processes, resulting in increased risk for infectious and chronic diseases. However, these processes have yet to be systematically studied in a dose and sex-dependent manner. In this study, we investigated the impact of chronic heavy ethanol consumption on gene expression using RNA-seq in peripheral blood mononuclear cells isolated from female rhesus macaques with daily consumption of 4% ethanol available 22hr/day for 12 months resulting in average ethanol consumption of 4.3 g/kg/day (considered heavy drinking). Differential gene expression analysis was performed using edgeR and gene enrichment analysis using MetaCore™. We identified 1106 differentially expressed genes, meeting the criterion of ≥ two-fold change and p-value ≤ 0.05 in expression (445 up- and 661 down-regulated). Pathway analysis of the 879 genes with characterized identifiers showed that the most enriched gene ontology processes were “response to wounding”, “blood coagulation”, “immune system process”, and “regulation of signaling”. Changes in gene expression were seen despite the lack of differences in the frequency of any major immune cell subtype between ethanol and controls, suggesting that heavy ethanol consumption modulates gene expression at the cellular level rather than altering the distribution of peripheral blood mononuclear cells. Collectively, these observations provide mechanisms to explain the higher incidence of infection, delay in wound healing, and increase in cardiovascular disease seen in subjects with Alcohol use disorder. PMID:27427759

  2. Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure

    PubMed Central

    Honko, Anna N.; Garamszegi, Sara; Caballero, Ignacio S.; Johnson, Joshua C.; Mucker, Eric M.; Trefry, John C.; Hensley, Lisa E.; Connor, John H.

    2013-01-01

    Lassa virus (LASV) is a significant human pathogen that is endemic to several countries in West Africa. Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases, and it is estimated that thousands die each year from the disease. Little is known about the complex immune mechanisms governing the response to LASV or the genetic determinants of susceptibility and resistance to infection. In the study presented here, we have used a whole-genome, microarray-based approach to determine the temporal host response in the peripheral blood mononuclear cells (PBMCs) of non-human primates (NHP) following aerosol exposure to LASV. Sequential sampling over the entire disease course showed that there are strong transcriptional changes of the immune response to LASV exposure, including the early induction of interferon-responsive genes and Toll-like receptor signaling pathways. However, this increase in early innate responses was coupled with a lack of pro-inflammatory cytokine response in LASV exposed NHPs. There was a distinct lack of cytokines such as IL1β and IL23α, while immunosuppressive cytokines such as IL27 and IL6 were upregulated. Comparison of IRF/STAT1-stimulated gene expression with the viral load in LASV exposed NHPs suggests that mRNA expression significantly precedes viremia, and thus might be used for early diagnostics of the disease. Our results provide a transcriptomic survey of the circulating immune response to hemorrhagic LASV exposure and provide a foundation for biomarker identification to allow clinical diagnosis of LASV infection through analysis of the host response. PMID:23638192

  3. Scaling laws and vortex profiles in two-dimensional decaying turbulence

    NASA Astrophysics Data System (ADS)

    Laval, Jean-Philippe; Chavanis, Pierre-Henri; Dubrulle, Bérengère; Sire, Clément

    2001-06-01

    We use high resolution numerical simulations over several hundred of turnover times to study the influence of small scale dissipation onto vortex statistics in 2D decaying turbulence. A scaling regime is detected when the scaling laws are expressed in units of mean vorticity and integral scale, like predicted in Carnevale et al., Phys. Rev. Lett. 66, 2735 (1991), and it is observed that viscous effects spoil this scaling regime. The exponent controlling the decay of the number of vortices shows some trends toward ξ=1, in agreement with a recent theory based on the Kirchhoff model [C. Sire and P. H. Chavanis, Phys. Rev. E 61, 6644 (2000)]. In terms of scaled variables, the vortices have a similar profile with a functional form related to the Fermi-Dirac distribution.

  4. Validation of the Substance Use Risk Profile Scale for Adolescents in Hong Kong

    ERIC Educational Resources Information Center

    Siu, Angela F. Y.

    2011-01-01

    This study examines the reliability and validity of a Chinese-translated version of the Substance Use Risk Profile Scale (SURPS) and explores the effect of gender and age on each of the subscales. The sensitivity of SURPS in differentiating substance users and nonusers using the SURPS is also investigated. Data were collected from a convenience…

  5. Immune profile of squamous metaplasia development in autoimmune regulator-deficient dry eye

    PubMed Central

    Chen, Ying-Ting; Li, Shimin; Nikulina, Karina; Porco, Travis; Gallup, Marianne

    2009-01-01

    Purpose Squamous metaplasia of the ocular surface epithelium in severe Sjögren syndrome (SS) dry eye has been implicated to be associated with chronic engagement of immune-mediated inflammation. While the detailed immunopathological mechanism underlying keratinization of the ocular muco-epithelium in this setting remains unclear, mice deficient in the autoimmune regulator gene (Aire) demonstrate SS-like pathological changes in the exocrine organs and ocular surface including squamous metaplasia. Using this murine model, we sought to determine the specific immune events that predict squamous metaplasia of the cornea in Aire deficiency. Methods Lissamine green staining, goblet cell density, and corneal small proline-rich protein 1B (SPRR1B) were compared in Aire-sufficient and -deficient mice at 4, 8, and 16 weeks of age. Corneal, limbal and conjunctival infiltration of CD4+ and CD8+ T cells as well as CD11c+ and MHC class II (I-Ad+) dendritic cells (DCs) were examined at the same time points. Ordinary least squares regression was used to model SPRR1B’s relationship with lissamine green staining, goblet cell density, and immune cell infiltration. Results Lissamine green staining was present in Aire-deficient mice by four weeks of age and increased over time. Compared to Aire-sufficient controls, conjunctival goblet cell density (GCD) decreased and corneal SPRR1B increased in Aire-deficient mice with significant differences noted at both 8 and 16 weeks. Immune-mediated CD4+ T cell infiltration of the conjunctiva and limbus peaked at eight weeks and then decreased. In contrast, corneal T cell infiltration continued to increase over time, reaching a maximum cell number at 16 weeks. CD11c+ myeloid-derived DCs were found in the conjunctiva and limbus at all time points. As the mice aged, there was a notable increase in corneal CD11c+ cell counts. Interestingly, the dynamic of activated MHC class II+ DCs was nearly identical to that of CD4+ T cells, peaking first in the

  6. Continuously distributed magnetization profile for millimeter-scale elastomeric undulatory swimming

    NASA Astrophysics Data System (ADS)

    Diller, Eric; Zhuang, Jiang; Zhan Lum, Guo; Edwards, Matthew R.; Sitti, Metin

    2014-04-01

    We have developed a millimeter-scale magnetically driven swimming robot for untethered motion at mid to low Reynolds numbers. The robot is propelled by continuous undulatory deformation, which is enabled by the distributed magnetization profile of a flexible sheet. We demonstrate control of a prototype device and measure deformation and speed as a function of magnetic field strength and frequency. Experimental results are compared with simple magnetoelastic and fluid propulsion models. The presented mechanism provides an efficient remote actuation method at the millimeter scale that may be suitable for further scaling down in size for micro-robotics applications in biotechnology and healthcare.

  7. Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma.

    PubMed

    Hung, Noelyn A; Eiholzer, Ramona A; Kirs, Stenar; Zhou, Jean; Ward-Hartstonge, Kirsten; Wiles, Anna K; Frampton, Chris M; Taha, Ahmad; Royds, Janice A; Slatter, Tania L

    2016-03-01

    Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumor-associated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P=0.0004, and telomerase with and without macrophages P=0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs >76% for all other subtypes

  8. Suppressor of cytokine signaling 2 modulates the immune response profile and development of experimental cerebral malaria.

    PubMed

    Brant, Fatima; Miranda, Aline S; Esper, Lisia; Gualdrón-López, Melisa; Cisalpino, Daniel; de Souza, Danielle da Gloria; Rachid, Milene Alvarenga; Tanowitz, Herbert B; Teixeira, Mauro Martins; Teixeira, Antônio Lucio; Machado, Fabiana Simão

    2016-05-01

    Plasmodium falciparum infection results in severe malaria in humans, affecting various organs, including the liver, spleen and brain, and resulting in high morbidity and mortality. The Plasmodium berghei ANKA (PbA) infection in mice closely recapitulates many aspects of human cerebral malaria (CM); thus, this model has been used to investigate the pathogenesis of CM. Suppressor of cytokine signaling 2 (SOCS2), an intracellular protein induced by cytokines and hormones, modulates the immune response, neural development, neurogenesis and neurotrophic pathways. However, the role of SOCS2 during CM remains unknown. SOCS2 knockout (SOCS2(-/-)) mice infected with PbA show an initial resistance to infection with reduced parasitemia and production of TNF, TGF-β, IL-12 and IL-17 in the brain. Interestingly, in the late phase of infection, SOCS2(-/-) mice display increased parasitemia and reduced Treg cell infiltration, associated with enhanced levels of Th1 and Th17 cells and related cytokines IL-17, IL-6, and TGF-β in the brain. A significant reduction in protective neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), was also observed. Moreover, the molecular alterations in the brain of infected SOCS2(-/-) mice were associated with anxiety-related behaviors and cognition impairment. Mechanistically, these results revealed enhanced nitric oxide (NO) production in PbA-infected SOCS2(-/-) mice, and the inhibition of NO synthesis through l-NAME led to a marked decrease in survival, the disruption of parasitemia control and more pronounced anxiety-like behavior. Treatment with l-NAME also shifted the levels of Th1, Th7 and Treg cells in the brains of infected SOCS2(-/-) mice to the background levels observed in infected WT, with remarkable exception of increased CD8(+)IFN(+) T cells and inflammatory monocytes. These results indicate that SOCS2 plays a dual role during PbA infection, being detrimental

  9. Pollen Lipidomics: Lipid Profiling Exposes a Notable Diversity in 22 Allergenic Pollen and Potential Biomarkers of the Allergic Immune Response

    PubMed Central

    Bashir, Mohamed Elfatih H.; Lui, Jan Hsi; Palnivelu, Ravishankar; Naclerio, Robert M.; Preuss, Daphne

    2013-01-01

    Background/Aim Pollen grains are the male gametophytes that deliver sperm cells to female gametophytes during sexual reproduction of higher plants. Pollen is a major source of aeroallergens and environmental antigens. The pollen coat harbors a plethora of lipids that are required for pollen hydration, germination, and penetration of the stigma by pollen tubes. In addition to proteins, pollen displays a wide array of lipids that interact with the human immune system. Prior searches for pollen allergens have focused on the identification of intracellular allergenic proteins, but have largely overlooked much of the extracellular pollen matrix, a region where the majority of lipid molecules reside. Lipid antigens have attracted attention for their potent immunoregulatory effects. By being in close proximity to allergenic proteins on the pollen surface when they interact with host cells, lipids could modify the antigenic properties of proteins. Methodology/Principal Findings We performed a comparative pollen lipid profiling of 22 commonly allergenic plant species by the use of gas chromatography-mass spectroscopy, followed by detailed data mining and statistical analysis. Three experiments compared pollen lipid profiles. We built a database library of the pollen lipids by matching acquired pollen-lipid mass spectra and retention times with the NIST/EPA/NIH mass-spectral library. We detected, identified, and relatively quantified more than 106 lipid molecular species including fatty acids, n-alkanes, fatty alcohols, and sterols. Pollen-derived lipids stimulation up-regulate cytokines expression of dendritic and natural killer T cells co-culture. Conclusions/Significance Here we report on a lipidomic analysis of pollen lipids that can serve as a database for identifying potential lipid antigens and/or novel candidate molecules involved in allergy. The database provides a resource that facilitates studies on the role of lipids in the immunopathogenesis of allergy. Pollen

  10. Transcriptional profiling in alopecia areata defines immune and cell cycle control related genes within disease-specific signatures.

    PubMed

    Subramanya, Raghunandan Dudda; Coda, Alvin B; Sinha, Animesh A

    2010-09-01

    Alopecia areata (AA) is a non-scarring inflammatory hair loss disease with a complex autoimmune etiopathogenesis that is poorly understood. In order to investigate the pathogenesis of AA at the molecular level, we examined the gene expression profiles in skin samples from lesional (n=10) and non-lesional sites (n=10) of AA patients using Affymetrix Hu95A-v2 arrays. 363 genes were found to be differentially expressed in AA skin compared to non-lesional skin; 97 were up-regulated and 266 were down-regulated. Functional classification of the differentially expressed genes (DEGs) provides evidence for T-cell mediated immune response (CCL5, CXCL10, CD27, ICAM2, ICAM3, IL7R, and CX3CL1), and a possible humoral mechanism (IGHG3, IGHM, and CXCR5) in AA. We also find modulation in gene expression favoring cellular proliferation arrest at various levels (FGF5, FGF18, EREG, and FOXC2) with apoptotic dysregulation (LCK, TNF, TRAF2, and SFN) and decreased expression of hair follicle structural proteins. Further analysis of patients with AAT (<1 year duration, n=4) and AAP (>1 year duration, n=6) of disease revealed 262 DEGs distinctly separating the 2 groups, indicating the existence of gene profiles unique to the initial and later stages of disease. PMID:20546884

  11. Impact of Persistent Cytomegalovirus Infection on Dynamic Changes in Human Immune System Profile

    PubMed Central

    Vescovini, Rosanna; Telera, Anna Rita; Pedrazzoni, Mario; Abbate, Barbara; Rossetti, Pietro; Verzicco, Ignazio; Arcangeletti, Maria Cristina; Medici, Maria Cristina; Calderaro, Adriana; Volpi, Riccardo; Sansoni, Paolo; Fagnoni, Francesco Fausto

    2016-01-01

    Human cytomegalovirus (HCMV) imprints the immune system after primary infection, however its effect during chronic infection still needs to be deciphered. In this study we report the variation of blood cell count along with anti-HCMV IgG and T cell responses to pp-65 and IE-1 antigens, that occurred after an interval of five years in a cohort of 25 seropositive healthy adults. We found increased anti-viral IgG antibody responses and intracellular interferon-gamma secreting CD8+ T cell responses to pp-65: a result consistent with memory inflation. With the only exception of shortage in naive CD8+ T cells most memory T cell subsets as well as total CD8+ T cells, T cells, lymphocytes, monocytes and leukocytes had increased. By contrast, none of the cell types tested were found to have increased in 14 subjects stably seronegative. Rather, in addition to a shortage in naive CD8+ T cells, also memory T cell subsets and most other cell types decreased, either in a statistically significant or non-significant manner. The trend of T cell pool representation with regard to CD4/CD8 ratio was in the opposing directions depending on HCMV serology. Globally, this study demonstrates different dynamic changes of most blood cell types depending on presence or absence of HCMV infection. Therefore, HCMV plays a continual role in modulating homeostasis of blood T cells and a broader expanding effect on other cell populations of lymphoid and myeloid origin. PMID:26990192

  12. Profile of differentially expressed intratumoral cytokines to predict the immune-polarizing side effects of tamoxifen in breast cancer treatment

    PubMed Central

    Li, Bailiang; Li, Yang; Wang, Xiao-Yu; Yan, Zi-Qiao; Liu, Huidi; Liu, Gui-Rong; Liu, Shu-Lin

    2015-01-01

    Factors within the tissue of breast cancer (BC) may shift the polarization of CD4+ T cells towards Th2 direction. This tendency can promote tumor development and be enhanced by the use of tamoxifen during the treatment. Thus, the patients with low levels of tumor-induced Th2 polarization prior to tamoxifen treatment may better endure the immune-polarizing side effects (IPSE) of tamoxifen and have better prognoses. Estimation of Th2 polarization status should help predict the IPSE among tamoxifen-treated patients and guide the use of tamoxifen among all BC patients before the tamoxifen therapy. Here, we report profiling of differentially expressed (DE) intratumoral cytokines as a signature to evaluate the IPSE of tamoxifen. The DE genes of intratumoral CD4+ T cells (CD4 DEGs) were identified by gene expression profiles of purified CD4+ T cells from BC patients and validated by profiling of cultured intratumoral CD4+ T cells. Functional enrichment analyses showed a directed Th2 polarization of intratumoral CD4+ T cells. To find the factors inducing the Th2 polarization of CD4+ T cells, we identified 995 common DE genes of bulk BC tissues (BC DEGs) by integrating five independent datasets. Five DE cytokines observed in bulk BC tissues with dysregulated receptors in the intratumoral CD4+ T cells were selected as the predictor of the IPSE of tamoxifen. The patients predicted to suffer low IPSE (low Th2 polarization) had a significantly lower distant relapse risk than the patients predicted to suffer high IPSE in independent datasets (n = 608; HR = 4.326, P = 0.000897; HR = 2.014, P = 0.0173; HR = 2.72, P = 0.04077). Patients predicted to suffer low IPSE would benefit from tamoxifen treatment (HR = 2.908, P = 0.03905). The DE intratumoral cytokines identified in this study may help predict the IPSE of tamoxifen and justify the use of tamoxifen in BC treatment. PMID:25973310

  13. Profiling pro-inflammatory cytokine and chemokine mRNA expression levels as a novel method for selection of increased innate immune responsiveness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies using F1 reciprocal crosses and two parental lines of broilers show the sire is instrumental in determining the in vitro leukocyte function and cytokine/chemokine profile. Since the innate immune response is the primary means a young chicken has to protect themselves, we hypothesiz...

  14. Profiles of the National Institutes of Health Stroke Scale Items as a Predictor of Patient Outcome

    PubMed Central

    Sucharew, Heidi; Khoury, Jane; Moomaw, Charles J; Alwell, Kathleen; Kissela, Brett M; Belagaje, Samir; Adeoye, Opeolu; Khatri, Pooja; Woo, Daniel; Flaherty, Matthew L; Ferioli, Simona; Heitsch, Laura; Broderick, Joseph P; Kleindorfer, Dawn

    2013-01-01

    Background and Purpose Initial National Institutes of Health Stroke Scale (NIHSS) score is highly predictive of outcome after ischemic stroke. We examined if grouping strokes by presence of individual NIHSS symptoms could provide prognostic information additional or alternative to the NIHSS total score. Methods Ischemic strokes from the Greater Cincinnati Northern Kentucky Stroke Study in 2005 were used to develop the model. Latent Class Analysis (LCA) was implemented to form groups of patients with similar retrospective NIHSS (rNIHSS) item responses. Profile group was then used as an independent predictor of discharge modified Rankin and mortality using logistic regression and Cox proportional hazards model. Results A total of 2,112 stroke patients were identified in 2005. Six distinct profiles were characterized. Consistent with the profile patterns, the median rNIHSS total score decreased from profile A “most severe” [median(IQR): 20(15,25)] to profile F “mild” [1(1,2)]. Two profiles falling between these extremes, C and D, both had median rNIHSS total score of 5, but different survival rates. Compared with A, C was associated with 59% risk reduction for death, whereas D with 70%. C patients were more likely to have decreased level of consciousness and abnormal language, whereas D patients were more likely to have abnormal right arm and right leg motor function. Conclusions Six rNIHSS profiles were identifiable using LCA. In particular, two symptom profiles with identical median rNIHSSS were observed with widely disparate outcomes, which may prove useful both clinically and for research studies as an enhancement to the overall NIHSS score. PMID:23704102

  15. Identification of systemic immune response markers through metabolomic profiling of plasma from calves given an intra-nasally delivered respiratory vaccine.

    PubMed

    Gray, Darren W; Welsh, Michael D; Doherty, Simon; Mansoor, Fawad; Chevallier, Olivier P; Elliott, Christopher T; Mooney, Mark H

    2015-01-01

    Vaccination procedures within the cattle industry are important disease control tools to minimize economic and welfare burdens associated with respiratory pathogens. However, new vaccine, antigen and carrier technologies are required to combat emerging viral strains and enhance the efficacy of respiratory vaccines, particularly at the point of pathogen entry. New technologies, specifically metabolomic profiling, could be applied to identify metabolite immune-correlates representative of immune protection following vaccination aiding in the design and screening of vaccine candidates. This study for the first time demonstrates the ability of untargeted UPLC-MS metabolomic profiling to identify metabolite immune correlates characteristic of immune responses following mucosal vaccination in calves. Male Holstein Friesian calves were vaccinated with Pfizer Rispoval® PI3 + RSV intranasal vaccine and metabolomic profiling of post-vaccination plasma revealed 12 metabolites whose peak intensities differed significantly from controls. Plasma levels of glycocholic acid, N-[(3α,5β,12α)-3,12-Dihydroxy-7,24-dioxocholan-24-yl]glycine, uric acid and biliverdin were found to be significantly elevated in vaccinated animals following secondary vaccine administration, whereas hippuric acid significantly decreased. In contrast, significant upregulation of taurodeoxycholic acid and propionylcarnitine levels were confined to primary vaccine administration. Assessment of such metabolite markers may provide greater information on the immune pathways stimulated from vaccine formulations and benchmarking early metabolomic responses to highly immunogenic vaccine formulations could provide a means for rapidly assessing new vaccine formulations. Furthermore, the identification of metabolic systemic immune response markers which relate to specific cell signaling pathways of the immune system could allow for targeted vaccine design to stimulate key pathways which can be assessed at the

  16. Assessment of Error in Synoptic-Scale Diagnostics Derived from Wind Profiler and Radiosonde Network Data

    NASA Technical Reports Server (NTRS)

    Mace, Gerald G.; Ackerman, Thomas P.

    1996-01-01

    A topic of current practical interest is the accurate characterization of the synoptic-scale atmospheric state from wind profiler and radiosonde network observations. We have examined several related and commonly applied objective analysis techniques for performing this characterization and considered their associated level of uncertainty both from a theoretical and a practical standpoint. A case study is presented where two wind profiler triangles with nearly identical centroids and no common vertices produced strikingly different results during a 43-h period. We conclude that the uncertainty in objectively analyzed quantities can easily be as large as the expected synoptic-scale signal. In order to quantify the statistical precision of the algorithms, we conducted a realistic observing system simulation experiment using output from a mesoscale model. A simple parameterization for estimating the uncertainty in horizontal gradient quantities in terms of known errors in the objectively analyzed wind components and temperature is developed from these results.

  17. Scaling Behavior and Segment Concentration Profile of Densely Grafted Polymer Brushes Swollen in Vapor.

    PubMed

    Sun, Liang; Akgun, Bulent; Hu, Renfeng; Browning, James F; Wu, David T; Foster, Mark D

    2016-06-01

    The scaling of the thickness, hs, of a densely grafted polymer brush of chain length N and grafting density σ swollen in vapor agrees quantitatively with the scaling reported by Kuhl et al. for densely grafted brushes swollen in liquid. Deep in the brush, next to the substrate, the shape of the segment concentration profile is the same whether the brush is swollen by liquid or by vapor. Differences in the segment concentration profile are manifested primarily in the swollen brush interface with the surrounding fluid. The interface of the polymer brush swollen in vapor is much more abrupt than that of the same brush swollen in liquid. This has implications for the compressibility of the swollen brush surface and for fluctuations at that surface. PMID:27172089

  18. Scale profile as feature for quick satellite image object-based classification

    NASA Astrophysics Data System (ADS)

    Dubois, David; Lepage, Richard

    2013-05-01

    With the increasing precision of recent spaceborne sensors, remotely sensed images have become exceedingly large. These images are being used more and more often in the preparation of emergency maps when a disaster occurs. Visual interpretation of these images is long and automatic pixel-based methods require a lot of memory, processing power and time. In this paper, we propose to use a fast level-set image transformation in order to obtain a hierarchical representation of image's objects. A scale profile is then extracted and included as a relevant feature for land-use classification in urban areas. The main contribution of this paper is the analysis of the scale profile for remote sensing applications. The data set from the earthquake that occurred on 12 January 2012 in Haiti is used.

  19. Turbulence length scales in stably stratified free shear flow analyzed from slant aircraft profiles

    SciTech Connect

    Tjernstroem, M. )

    1993-05-01

    The vertical turbulence structure in the marine atmosphere close to a coastline is investigated using airborne measurements. The measurements are from a field experiment close to the coast in the southeast of Sweden, in the Baltic Sea. The Baltic Sea has two main properties that make it particularly interesting to study: significant annual lag in sea surface temperature compared to inland surface temperatures and the fact that it is surrounded by land in all directions within advection distances of from a few hours up to 10-15 hours in normal meteorological conditions. The present results are mostly from spring or early summer with mainly cool water: with a stable or neutral marine boundary layer but with substantial heating of the land area during daytime. When the daytime inland convective boundary layer is advected out over the cool sea, there is a frictional decoupling in space analogous to the same nocturnal process in time. This sometimes creates a residual layer, a remnant of the inland convective boundary layer, that can be advected for considerable distances over the sea. At the top of this layer, wind shear gives rise to a local increase in turbulent kinetic energy. These layers are used for an analysis of turbulent scales for free shear flow in stable stratification. The analysis is based on different length scales used in numerical model closures for turbulence processes and reveals the asymptotic behavior of different scales in the neutral limit and their functional form, and illustrates the nonlinear relationship between scales for different properties. The profiles from the aircraft are taken from 25 slant soundings performed in connection to low-level boundary-layer flights. The results are calculated from turbulence data extracted through filtering techniques on instantaneous time series (individual profiles). The calculated turbulence parameters from all profiles are grouped and averaged compositely over all profiles. 48 refs., 12 figs., 1 tab.

  20. Mammary gene expression profiles during an intramammary challenge reveal potential mechanisms linking negative energy balance with impaired immune response

    PubMed Central

    Moyes, Kasey M.; Drackley, James K.; Morin, Dawn E.; Rodriguez-Zas, Sandra L.; Everts, Robin E.; Lewin, Harris A.

    2010-01-01

    Our objective was to compare mammary tissue gene expression profiles during a Streptococcus uberis (S. uberis) mastitis challenge between lactating cows subjected to dietary-induced negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive energy balance (PEB; n = 5) to better understand the mechanisms associated with NEB and risk of mastitis during the transition period. The NEB cows were feed-restricted to 60% of calculated net energy for lactation requirements for 7 days, and cows assigned to PEB were fed the same diet for ad libitum intake. Five days after feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis (O140J). At 20 h postinoculation, S. uberis-infected mammary quarters from all cows were biopsied for RNA extraction. Negative energy balance resulted in 287 differentially expressed genes (DEG; false discovery rate ≤ 0.05), with 86 DEG upregulated and 201 DEG downregulated in NEB vs. PEB. Canonical pathways most affected by NEB were IL-8 signaling (10 genes), glucocorticoid receptor signaling (13), and NRF2-mediated oxidative stress response (10). Among the genes differentially expressed by NEB, cell growth and proliferation (48) and cellular development (36) were the most enriched functions. Regarding immune response, HLA-A was upregulated due to NEB, whereas the majority of genes involved in immune response were downregulated (e.g., AKT1, IRAK1, MAPK9, and TRAF6). This study provided new avenues for investigation into the mechanisms relating NEB and susceptibility to mastitis in lactating dairy cows. PMID:20103698

  1. Echinoderm immunity.

    PubMed

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats. PMID:21528703

  2. A Pathway Proteomic Profile of Ischemic Stroke Survivors Reveals Innate Immune Dysfunction in Association with Mild Symptoms of Depression – A Pilot Study

    PubMed Central

    Nguyen, Vinh A.; Carey, Leeanne M.; Giummarra, Loretta; Faou, Pierre; Cooke, Ira; Howells, David W.; Tse, Tamara; Macaulay, S. Lance; Ma, Henry; Davis, Stephen M.; Donnan, Geoffrey A.; Crewther, Sheila G.

    2016-01-01

    Depression after stroke is a common occurrence, raising questions as to whether depression could be a long-term biological and immunological sequela of stroke. Early explanations for post-stroke depression (PSD) focused on the neuropsychological/psychosocial effects of stroke on mobility and quality of life. However, recent investigations have revealed imbalances of inflammatory cytokine levels in association with PSD, though to date, there is only one published proteomic pathway analysis testing this hypothesis. Thus, we examined the serum proteome of stroke patients (n = 44, mean age = 63.62 years) and correlated these with the Montgomery–Åsberg Depression Rating Scale (MADRS) scores at 3 months post-stroke. Overall, the patients presented with mild depression symptoms on the MADRS, M = 6.40 (SD = 7.42). A discovery approach utilizing label-free relative quantification was employed utilizing an LC-ESI–MS/MS coupled to a LTQ-Orbitrap Elite (Thermo-Scientific). Identified peptides were analyzed using the gene set enrichment approach on several different genomic databases that all indicated significant downregulation of the complement and coagulation systems with increasing MADRS scores. Complement and coagulation systems are traditionally thought to play a key role in the innate immune system and are established precursors to the adaptive immune system through pro-inflammatory cytokine signaling. Both systems are known to be globally affected after ischemic or hemorrhagic stroke. Thus, our results suggest that lowered complement expression in the periphery in conjunction with depressive symptoms post-stroke may be a biomarker for incomplete recovery of brain metabolic needs, homeostasis, and inflammation following ischemic stroke damage. Further proteomic investigations are now required to construct the temporal profile, leading from acute lesion damage to manifestation of depressive symptoms. Overall, the findings provide support for the

  3. Transcriptome profiling of the antiviral immune response in Atlantic cod macrophages.

    PubMed

    Eslamloo, Khalil; Xue, Xi; Booman, Marije; Smith, Nicole C; Rise, Matthew L

    2016-10-01

    A study was conducted to determine the transcriptome response of Atlantic cod (Gadus morhua) macrophages to the viral mimic, polyriboinosinic polyribocytidylic acid (pIC), using a 20K Atlantic cod microarray platform and qPCR. We identified 285 significantly up-regulated and 161 significantly down-regulated probes in cod macrophages 24 h after pIC stimulation. A subset of 26 microarray-identified transcripts was subjected to qPCR validation using samples treated with pIC or phosphate-buffered saline (control) over time (3, 6, 12, 24, 48 h), and 77% of them showed a significant response to pIC. The microarray and qPCR analyses in this study showed that pIC induced the expression of cod macrophage transcripts involved in RLR- and TLR-dependent pathogen recognition (e.g. tlr3, tlr7, mda5 and lgp2), as well as signal transducers (e.g. stat1 and nfkbia) and transcription activators (e.g. irf7 and irf10) in the MyD88-independent and dependent signalling pathways. Several immune effectors (e.g. isg15s, viperin, herc4, mip2 and ccl13) were significantly up-regulated in pIC-stimulated cod macrophages. The expression of some transcripts (e.g. irf7, irf10, viperin) was significantly up-regulated by pIC as early as 12 h. All pIC-induced transcripts had peak expression at either 24 h (e.g. tlr7, irf7, mip2) or 48 h (e.g. tlr3, lgp2, stat1). This study suggests possible roles of both vertebrate-conserved (e.g. tlr3 as an up-regulated gene) and fish-specific (tlr22g as a down-regulated gene) receptors in dsRNA recognition, and the importance of conserved and potentially fish-specific interferon stimulated genes in cod macrophages. PMID:27255218

  4. Natural Experiments in Outcrop- vs. Landscape-scale Controls on Longitudinal Profile Form, Finger Lakes, NY

    NASA Astrophysics Data System (ADS)

    Safran, E. B.; Hauser, D.; Hoke, G. D.; Knuepfer, P. L.

    2012-12-01

    Longitudinal stream profiles are commonly used to extract information about the geologic histories of transient landscapes. Correct interpretation of these histories requires understanding the impacts on profile morphology of outcrop-scale controls relative to those imposed by landscape-scale processes driving incision. Previous researchers have suggested that joint-perpendicular channel reaches form waterfalls while joint-oblique channel reaches form cascades. The Finger Lakes region of central New York offers a natural laboratory in which to test this hypothesis. The region is underpinned primarily by relatively flat-lying, well-jointed Devonian shales of the Hamilton Group. Ice retreated from the region and pro-glacial lake levels fell episodically some 14 ka ago, triggering post-glacial incision through plucking and abrasion that has sculpted gorges and waterfalls. All post-glacial streams draining to a given lake have essentially a common lithology and base level history. Using GIS, we analyzed the orientation of 50 m long channel segments relative to mapped patterns of joint orientation. All moderately sized (<20 km2) streams exhibit convex profiles which mimic the overall form of the valley slopes. For streams draining to southern Cayuga Lake, joint perpendicular reaches had an average slope of 4.2 degrees, while joint oblique reaches had an average slope of 3.6 degrees (p = 3e-19). However, the spatial location of major knickpoints do not appear to be controlled by joint orientation patterns, whose alignment with channel orientation varies over wavelengths shorter than knickpoint spacing (order 10-100 m vs. order 100-1000 m). On the other hand, knickpoint location and spacing along streams draining to southern Seneca Lake do not appear to differ systematically from those of the Cayuga profiles. Since Seneca's lake level was more stable than Cayuga's during glacial retreat, this suggests that base level history alone is also not controlling profile

  5. Hematological, oxidative stress, and immune status profiling in elite combat sport athletes.

    PubMed

    Dopsaj, Violeta; Martinovic, Jelena; Dopsaj, Milivoj; Kasum, Goran; Kotur-Stevuljevic, Jelena; Koropanovski, Nenad

    2013-12-01

    The aim of this study was to profile hematological, oxidative stress, and immunological parameters in male athletes who practiced combat sports and to determine whether the type of combat sport influenced the measured parameters. Eighteen karate professionals, 15 wrestlers, and 14 kickboxers participated in the study. Hematological, iron-related, oxidative stress, and immunological parameters were measured at the beginning of a precompetitive period. The general linear model showed significant differences between the karate professionals, wrestlers, and kickboxers with respect to their hematological and iron status parameters (Wilks' Lambda = 0.270, F = 2.186, p < 0.05) and oxidative stress status (Wilks' Lambda = 0.529, F = 1.940, p < 0.05). The immature reticulocyte fraction was significantly higher in wrestlers (0.30 ± 0.03) compared with kickboxers (0.24 ± 0.04; p < 0.05) and karate professionals (0.26 ± 0.04; p < 0.05). Low hemoglobin density was significantly lower in wrestlers and kickboxers (p < 0.05) compared with karate professionals (karate: 3.51 ± 1.19, wrestlers: 1.95 ± 1.10, and kickboxers: 1.77 ± 0.76). Significant differences were observed between the karate professionals and wrestlers with respect to their pro-oxidant-antioxidant balance (437 ± 103 vs. 323 ± 148, p < 0.05) and superoxide-dismutase activity (SOD) (73 ± 37 vs. 103 ± 30, p < 0.05). All the measured parameters (with the exception of SOD activity) fell within their physiological ranges, indicating that the study participants represented a young and healthy male population. Hematological parameters differed between kickboxers and karate professionals. The low pro-oxidant-antioxidant balance and high SOD activity in wrestlers could be associated with the long-term impact of wrestling as a type of strenuous exercise. PMID:24270459

  6. Epidemiology, clinical, immune, and molecular profiles of microsporidiosis and cryptosporidiosis among HIV/AIDS patients

    PubMed Central

    Wumba, Roger; Longo-Mbenza, Benjamin; Menotti, Jean; Mandina, Madone; Kintoki, Fabien; Situakibanza, Nani Hippolyte; Kakicha, Marie Kapepela; Zanga, Josue; Mbanzulu-Makola, Kennedy; Nseka, Tommy; Mukendi, Jean Pierre; Kendjo, Eric; Sala, Jean; Thellier, Marc

    2012-01-01

    parasites. Rural areas, public toilets, and exposure to farm pigs were the univariate risk factors present in the 28 cases with opportunistic intestinal parasites. In logistic regression analysis, a CD4 count of <100 cells/mm3 (OR = 4.60; 95% CI 1.70–12.20; P = 0.002), no ART (OR = 5.00; 95% CI 1.90–13.20; P < 0.001), and exposure to surface water (OR = 2.90; 95% CI 1.01–8.40; P = 0.048) were identified as the significant and independent determinants for the presence of opportunistic intestinal parasites. Conclusion E. bieneusi and Cryptosporidium are becoming more prevalent in Kinshasa, Congo. Based on the findings, we recommend epidemiology surveillance and prevention by means of hygiene, the emphasis of sensitive PCR methods, and treating opportunistic intestinal parasites that may be acquired through fecal–oral transmission, surface water, normal immunity, rural area-based person–person and animal–human infection, and transmission of HIV. Therapy, including ART and treatment with fumagillin, is needed. PMID:22924007

  7. Multi-granularity immunization strategy based on SIRS model in scale-free network

    NASA Astrophysics Data System (ADS)

    Nian, Fuzhong; Wang, Ke

    2015-04-01

    In this paper, a new immunization strategy was established to prevent the epidemic spreading based on the principle of "Multi-granularity" and "Pre-warning Mechanism", which send different pre-warning signal with the risk rank of the susceptible node to be infected. The pre-warning means there is a higher risk that the susceptible node is more likely to be infected. The multi-granularity means the susceptible node is linked with multi-infected nodes. In our model, the effect of the different situation of the multi-granularity immunizations is compared and different spreading rates are adopted to describe the epidemic behavior of nodes. In addition the threshold value of epidemic outbreak is investigated, which makes the result more convincing. The theoretical analysis and the simulations indicate that the proposed immunization strategy is effective and it is also economic and feasible.

  8. Characterising the immune profile of the kidney biopsy at lupus nephritis flare differentiates early treatment responders from non-responders

    PubMed Central

    Parikh, Samir V; Malvar, Ana; Song, Huijuan; Alberton, Valeria; Lococo, Bruno; Vance, Jay; Zhang, Jianying; Yu, Lianbo; Rovin, Brad H

    2015-01-01

    Introduction The kidney biopsy is used to diagnose and guide initial therapy in patients with lupus nephritis (LN). Kidney histology does not correlate well with clinical measurements of kidney injury or predict how patients will respond to standard-of-care immunosuppression. We postulated that the gene expression profile of kidney tissue at the time of biopsy may differentiate patients who will from those who will not respond to treatment. Methods The expression of 511 immune-response genes was measured in kidney biopsies from 19 patients with proliferative LN and 4 normal controls. RNA was extracted from formalin-fixed, paraffin-embedded kidney biopsies done at flare. After induction therapy, 5 patients achieved a complete clinical response (CR), 10 had a partial response (PR) and 4 patients were non-responders (NRs). Transcript expression was compared with normal controls and between renal response groups. Results A principal component analysis showed that intrarenal transcript expression from normal kidney, CR biopsies and NR biopsies segregated from each other. The top genes responsible for CR clustering included several interferon pathway genes (STAT1, IRF1, IRF7, MX1, STAT2, JAK2), while complement genes (C1R, C1QB, C6, C9, C5, MASP2) were mainly responsible for NR clustering. Overall, 35 genes were uniquely expressed in NR compared with CR. Pathway analysis revealed that interferon signalling and complement activation pathways were upregulated in both groups, while BAFF, APRIL, nuclear factor-κB and interleukin-6 signalling were increased in CR but suppressed in NR. Conclusions These data suggest that molecular profiling of the kidney biopsy at LN flare may be useful in predicting treatment response to induction therapy. PMID:26629350

  9. In Silico Modeling of the Immune System: Cellular and Molecular Scale Approaches

    PubMed Central

    Belfiore, Mariagrazia; Aricò, Giuseppina; Ronsisvalle, Simone

    2014-01-01

    The revolutions in biotechnology and information technology have produced clinical data, which complement biological data. These data enable detailed descriptions of various healthy and diseased states and responses to therapies. For the investigation of the physiology and pathology of the immune responses, computer and mathematical models have been used in the last decades, enabling the representation of biological processes. In this modeling effort, a major issue is represented by the communication between models that work at cellular and molecular level, that is, multiscale representation. Here we sketch some attempts to model immune system dynamics at both levels. PMID:24804217

  10. A high-frequency sonar for profiling small-scale subaqueous bedforms

    USGS Publications Warehouse

    Dingler, J.R.; Boylls, J.C.; Lowe, R.L.

    1977-01-01

    A high-resolution ultrasonic profiler has been developed which permits both laboratory and field studies of small-scale subaqueous bedforms. The device uses a 2.5-cm diameter piezoelectric ceramic crystal pulsed at a frequency of 4.5 MHz to obtain vertical accuracy and resolution of at least 1 mm. Compared to other small-scale profiling methods, this ultrasonic technique profiles the bottom more accurately and more rapidly without disturbing the bedforms. These characteristics are vital in wave-dominated nearshore zones where oscillatory flow and low visibility for the most part have stymied detailed bedform studies. In the laboratory the transducer is mounted directly to an instrument carriage. For field work the transducer housing is mounted in a 2 m long aluminum frame which is situated and operated by scuba divers. Observations using the device include ripple geometry and migration, the suspension height of sand during sheet flow, and long-term erosion/deposition at a point. ?? 1977.

  11. Exploring the immune signalling pathway-related genes of the cattle tick Rhipicephalus microplus: From molecular characterization to transcriptional profile upon microbial challenge.

    PubMed

    Rosa, Rafael D; Capelli-Peixoto, Janaína; Mesquita, Rafael D; Kalil, Sandra P; Pohl, Paula C; Braz, Glória R; Fogaça, Andrea C; Daffre, Sirlei

    2016-06-01

    In dipteran insects, invading pathogens are selectively recognized by four major pathways, namely Toll, IMD, JNK, and JAK/STAT, and trigger the activation of several immune effectors. Although substantial advances have been made in understanding the immunity of model insects such as Drosophila melanogaster, knowledge on the activation of immune responses in other arthropods such as ticks remains limited. Herein, we have deepened our understanding of the intracellular signalling pathways likely to be involved in tick immunity by combining a large-scale in silico approach with high-throughput gene expression analysis. Data from in silico analysis revealed that although both the Toll and JAK/STAT signalling pathways are evolutionarily conserved across arthropods, ticks lack central components of the D. melanogaster IMD pathway. Moreover, we show that tick immune signalling-associated genes are constitutively transcribed in BME26 cells (a cell lineage derived from embryos of the cattle tick Rhipicephalus microplus) and exhibit different transcriptional patterns in response to microbial challenge. Interestingly, Anaplasma marginale, a pathogen that is naturally transmitted by R. microplus, causes downregulation of immune-related genes, suggesting that this pathogen may manipulate the tick immune system, favouring its survival and vector colonization. PMID:26724380

  12. Calibrating system errors of large scale three-dimensional profile measurement instruments by subaperture stitching method.

    PubMed

    Dong, Zhichao; Cheng, Haobo; Feng, Yunpeng; Su, Jingshi; Wu, Hengyu; Tam, Hon-Yuen

    2015-07-01

    This study presents a subaperture stitching method to calibrate system errors of several ∼2  m large scale 3D profile measurement instruments (PMIs). The calibration process was carried out by measuring a Φ460  mm standard flat sample multiple times at different sites of the PMI with a length gauge; then the subaperture data were stitched together using a sequential or simultaneous stitching algorithm that minimizes the inconsistency (i.e., difference) of the discrete data in the overlapped areas. The system error can be used to compensate the measurement results of not only large flats, but also spheres and aspheres. The feasibility of the calibration was validated by measuring a Φ1070  mm aspheric mirror, which can raise the measurement accuracy of PMIs and provide more reliable 3D surface profiles for guiding grinding, lapping, and even initial polishing processes. PMID:26193139

  13. SEU immunity: The effects of scaling on the peripheral circuits of SRAMs

    SciTech Connect

    Jacunski, L.; Doyle, S.; Jallice, D.; Haddad, N.; Scott, T. )

    1994-12-01

    Heavy ion testing on a scaled 256K SRAM has shown that SEU analysis of the peripheral circuits as well as the memory cell must be performed as circuits are scaled to smaller and smaller dimensions. This paper describes the SEU induce phenomena experienced by the scaled version of a previous 256K radiation hardened SRAM design, affected by circuits in the periphery.

  14. Canine zona pellucida glycoprotein-3: up-scaled production, immunization strategy and its outcome on fertility.

    PubMed

    Shrestha, Abhinav; Srichandan, Sudeepa; Minhas, Vidisha; Panda, Amulya Kumar; Gupta, Satish Kumar

    2015-01-01

    Zona pellucida (ZP) glycoproteins based contraceptive vaccines have been proposed for the management of wildlife population. In the present study, a fusion protein encompassing promiscuous T cell epitope of tetanus toxoid [TT; amino acid (aa) residues 830-844] followed by a dilysine linker and an ectodomain of dog ZP3 (ZP3; aa residues 23-348) without any affinity tag (TT-KK-ZP3) has been expressed in Escherichia coli. The recombinant protein was successfully produced in fed-batch fermentor and purified. The average yield of purified refolded protein was 12.20 ± 0.61 mg/2g wet cell pellet. Female FvB/J mice immunized with the varying doses of recombinant TT-KK-ZP3 supplemented with alum/PetGel A as adjuvants following a three injection schedule, showed dose dependent increase in serum IgG titer. Antibodies against TT-KK-ZP3 recognized native mouse/dog ZP and significantly inhibited mouse in-vitro fertilization (p=0.012). Immunized mice showed significant reduction in fertility (p<0.05). Higher antibody titers were associated with a decrease in the number of pups born to the immunized female mice. To reduce the number of injections, two injection schedule using various dose combinations of TT-KK-ZP3 supplemented with alum revealed lower immunogenicity and contraceptive efficacy as compared to the three injection schedule. To overcome this, CpG motif was included in addition to alum and both intraperitoneal and intranasal route of immunization following the two injection schedule was investigated. Inclusion of CpG significantly enhanced the antibody titer and improved contraceptive efficacy. In the mice immunized following intraperitoneal route, serum/vaginal IgG and in the mice immunized through intranasal route, vaginal IgA seemed to be important for curtailment in fertility. To conclude, the recombinant protein described herein may be a good candidate for developing contraceptive vaccine for the wildlife population management, in particular street dogs. PMID

  15. Gene expression profiling of coelomic cells and discovery of immune-related genes in the earthworm, Eisenia andrei, using expressed sequence tags.

    PubMed

    Tak, Eun Sik; Cho, Sung-Jin; Park, Soon Cheol

    2015-01-01

    The coelomic cells of the earthworm consist of leukocytes, chlorogocytes, and coelomocytes, which play an important role in innate immunity reactions. To gain insight into the expression profiles of coelomic cells of the earthworm, Eisenia andrei, we analyzed 1151 expressed sequence tags (ESTs) derived from the cDNA library of the coelomic cells. Among the 1151 ESTs analyzed, 493 ESTs (42.8%) showed a significant similarity to known genes and represented 164 unique genes, of which 93 ESTs were singletons and 71 ESTs manifested as two or more ESTs. From the 164 unique genes sequenced, we found 24 immune-related and cell defense genes. Furthermore, real-time PCR analysis showed that levels of lysenin-related proteins mRNA in coelomic cells of E. andrei were upregulated after the injection of Bacillus subtilis bacteria. This EST data-set would provide a valuable resource for future researches of earthworm immune system. PMID:25496401

  16. Evaluating the Stability of RNA-Seq Transcriptome Profiles and Drug-Induced Immune-Related Expression Changes in Whole Blood.

    PubMed

    Bowyer, John F; Tranter, Karen M; Hanig, Joseph P; Crabtree, Nathaniel M; Schleimer, Robert P; George, Nysia I

    2015-01-01

    Methods were developed to evaluate the stability of rat whole blood expression obtained from RNA sequencing (RNA-seq) and assess changes in whole blood transcriptome profiles in experiments replicated over time. Expression was measured in globin-depleted RNA extracted from the whole blood of Sprague-Dawley rats, given either saline (control) or neurotoxic doses of amphetamine (AMPH). The experiment was repeated four times (paired control and AMPH groups) over a 2-year span. The transcriptome of the control and AMPH-treated groups was evaluated on: 1) transcript levels for ribosomal protein subunits; 2) relative expression of immune-related genes; 3) stability of the control transcriptome over 2 years; and 4) stability of the effects of AMPH on immune-related genes over 2 years. All, except one, of the 70 genes that encode the 80s ribosome had levels that ranked in the top 5% of all mean expression levels. Deviations in sequencing performance led to significant changes in the ribosomal transcripts. The overall expression profile of immune-related genes and genes specific to monocytes, T-cells or B-cells were well represented and consistent within treatment groups. There were no differences between the levels of ribosomal transcripts in time-matched control and AMPH groups but significant differences in the expression of immune-related genes between control and AMPH groups. AMPH significantly increased expression of some genes related to monocytes but down-regulated those specific to T-cells. These changes were partially due to changes in the two types of leukocytes present in blood, which indicate an activation of the innate immune system by AMPH. Thus, the stability of RNA-seq whole blood transcriptome can be verified by assessing ribosomal protein subunits and immune-related gene expression. Such stability enables the pooling of samples from replicate experiments to carry out differential expression analysis with acceptable power. PMID:26177368

  17. Evaluating the Stability of RNA-Seq Transcriptome Profiles and Drug-Induced Immune-Related Expression Changes in Whole Blood

    PubMed Central

    Bowyer, John F.; Tranter, Karen M.; Hanig, Joseph P.; Crabtree, Nathaniel M.; Schleimer, Robert P.; George, Nysia I.

    2015-01-01

    Methods were developed to evaluate the stability of rat whole blood expression obtained from RNA sequencing (RNA-seq) and assess changes in whole blood transcriptome profiles in experiments replicated over time. Expression was measured in globin-depleted RNA extracted from the whole blood of Sprague-Dawley rats, given either saline (control) or neurotoxic doses of amphetamine (AMPH). The experiment was repeated four times (paired control and AMPH groups) over a 2-year span. The transcriptome of the control and AMPH-treated groups was evaluated on: 1) transcript levels for ribosomal protein subunits; 2) relative expression of immune-related genes; 3) stability of the control transcriptome over 2 years; and 4) stability of the effects of AMPH on immune-related genes over 2 years. All, except one, of the 70 genes that encode the 80s ribosome had levels that ranked in the top 5% of all mean expression levels. Deviations in sequencing performance led to significant changes in the ribosomal transcripts. The overall expression profile of immune-related genes and genes specific to monocytes, T-cells or B-cells were well represented and consistent within treatment groups. There were no differences between the levels of ribosomal transcripts in time-matched control and AMPH groups but significant differences in the expression of immune-related genes between control and AMPH groups. AMPH significantly increased expression of some genes related to monocytes but down-regulated those specific to T-cells. These changes were partially due to changes in the two types of leukocytes present in blood, which indicate an activation of the innate immune system by AMPH. Thus, the stability of RNA-seq whole blood transcriptome can be verified by assessing ribosomal protein subunits and immune-related gene expression. Such stability enables the pooling of samples from replicate experiments to carry out differential expression analysis with acceptable power. PMID:26177368

  18. Protein array profiling of tic patient sera reveals a broad range and enhanced immune response against Group A Streptococcus antigens.

    PubMed

    Bombaci, Mauro; Grifantini, Renata; Mora, Marirosa; Reguzzi, Valerio; Petracca, Roberto; Meoni, Eva; Balloni, Sergio; Zingaretti, Chiara; Falugi, Fabiana; Manetti, Andrea G O; Margarit, Immaculada; Musser, James M; Cardona, Francesco; Orefici, Graziella; Grandi, Guido; Bensi, Giuliano

    2009-01-01

    The human pathogen Group A Streptococcus (Streptococcus pyogenes, GAS) is widely recognized as a major cause of common pharyngitis as well as of severe invasive diseases and non-suppurative sequelae associated with the existence of GAS antigens eliciting host autoantibodies. It has been proposed that a subset of paediatric disorders characterized by tics and obsessive-compulsive symptoms would exacerbate in association with relapses of GAS-associated pharyngitis. This hypothesis is however still controversial. In the attempt to shed light on the contribution of GAS infections to the onset of neuropsychiatric or behavioral disorders affecting as many as 3% of children and adolescents, we tested the antibody response of tic patient sera to a representative panel of GAS antigens. In particular, 102 recombinant proteins were spotted on nitrocellulose-coated glass slides and probed against 61 sera collected from young patients with typical tic neuropsychiatric symptoms but with no overt GAS infection. Sera from 35 children with neither tic disorder nor overt GAS infection were also analyzed. The protein recognition patterns of these two sera groups were compared with those obtained using 239 sera from children with GAS-associated pharyngitis. This comparative analysis identified 25 antigens recognized by sera of the three patient groups and 21 antigens recognized by tic and pharyngitis sera, but poorly or not recognized by sera from children without tic. Interestingly, these antigens appeared to be, in quantitative terms, more immunogenic in tic than in pharyngitis patients. Additionally, a third group of antigens appeared to be preferentially and specifically recognized by tic sera. These findings provide the first evidence that tic patient sera exhibit immunological profiles typical of individuals who elicited a broad, specific and strong immune response against GAS. This may be relevant in the context of one of the hypothesis proposing that GAS antigen

  19. Gene Expression Profiling of Immune-Competent Human Cells Exposed to Engineered Zinc Oxide or Titanium Dioxide Nanoparticles

    PubMed Central

    Tuomela, Soile; Autio, Reija; Buerki-Thurnherr, Tina; Arslan, Osman; Kunzmann, Andrea; Andersson-Willman, Britta; Wick, Peter; Mathur, Sanjay; Scheynius, Annika; Krug, Harald F.; Fadeel, Bengt; Lahesmaa, Riitta

    2013-01-01

    A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and Jurkat T cell leukemia-derived cell line. TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify transcriptional response underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses 1 µg/ml and 10 µg/ml after 6 and 24 h of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10 µg/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that only the gene expression of metallothioneins was upregulated in all the three cell types and a notable proportion of the genes were regulated in a cell type-specific manner. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Using a panel of modified ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is largely dependent on particle dissolution and show that the ligand used to modify ZnO nanoparticles modulates Zn2+ leaching. Overall, the study provides an extensive resource of transcriptional markers for mediating ZnO nanoparticle-induced toxicity for further mechanistic studies, and demonstrates the value of assessing nanoparticle responses through a combined transcriptomics and bioinformatics approach. PMID:23894303

  20. Immune gene expression profile of Penaeus monodon in response to marine yeast glucan application and white spot syndrome virus challenge.

    PubMed

    Wilson, Wilsy; Lowman, Douglas; Antony, Swapna P; Puthumana, Jayesh; Bright Singh, I S; Philip, Rosamma

    2015-04-01

    Immunostimulant potential of eight marine yeast glucans (YG) from Candida parapsilosis R20, Hortaea werneckii R23, Candida spencermartinsiae R28, Candida haemulonii R63, Candida oceani R89, Debaryomyces fabryi R100, Debaryomyces nepalensis R305 and Meyerozyma guilliermondii R340 were tested against WSSV challenge in Penaeus monodon post larvae (PL). Structural characterization of these marine yeast glucans by proton nuclear magnetic resonance (NMR) indicated structures containing (1-6)-branched (1-3)-β-D-glucan. PL were fed 0.2% glucan incorporated diet once in seven days for a period of 45 days and the animals were challenged with white spot syndrome virus (WSSV). The immunostimulatory activity of yeast glucans were assessed pre- and post-challenge WSSV by analysing the expression profile of six antimicrobial peptide (AMP) genes viz., anti-lipopolysaccharide factor (ALF), crustin-1, crustin-2, crustin-3, penaeidin-3 and penaeidin-5 and 13 immune genes viz., alpha-2-macroglobulin (α-2-M), astakine, caspase, catalase, glutathione peroxidase, glutathione-s-transferase, haemocyanin, peroxinectin, pmCathepsinC, prophenol oxidase (proPO), Rab-7, superoxide dismutase and transglutaminase. Expression of seven WSSV genes viz., DNA polymerase, endonuclease, protein kinase, immediate early gene, latency related gene, thymidine kinase and VP28 were also analysed to detect the presence and intensity of viral infection in the experimental animals post-challenge. The study revealed that yeast glucans (YG) do possess immunostimulatory activity against WSSV and also supported higher survival (40-70 %) post-challenge WSSV. Among the various glucans tested, YG23 showed maximum survival (70.27%), followed by YG20 (66.66%), YG28 (60.97%), YG89 (58.53%), YG100 (54.05%), YG63 (48.64%), YG305 (45.7%) and YG340 (43.24%). PMID:25555812

  1. SCALING LAWS AND TEMPERATURE PROFILES FOR SOLAR AND STELLAR CORONAL LOOPS WITH NON-UNIFORM HEATING

    SciTech Connect

    Martens, P. C. H.

    2010-05-10

    The bulk of solar coronal radiative loss consists of soft X-ray emission from quasi-static loops at the cores of active regions. In order to develop diagnostics for determining the heating mechanism of these loops from observations by coronal imaging instruments, I have developed analytical solutions for the temperature structure and scaling laws of loop strands for a set of temperature- and pressure-dependent heating functions that encompass heating concentrated at the footpoints, uniform heating, and heating concentrated at the loop apex. Key results are that the temperature profile depends only weakly on the heating distribution-not sufficiently to be of significant diagnostic value-and that the scaling laws survive for this wide range of heating distributions, but with the constant of proportionality in the Rosner-Tucker-Vaiana scaling law (P{sub 0} L {approx} T {sup 3}{sub max}) depending on the specific heating function. Furthermore, quasi-static solutions do not exist for an excessive concentration of heating near the loop footpoints, a result in agreement with recent numerical simulations. It is demonstrated that a generalization of the results to a set of solutions for strands with a functionally prescribed variable diameter leads to only relatively small correction factors in the scaling laws and temperature profiles for constant diameter loop strands. A quintet of leading theoretical coronal heating mechanisms is shown to be captured by the formalism of this paper, and the differences in thermal structure between them may be verified through observations. Preliminary results from full numerical simulations demonstrate that, despite the simplifying assumptions, the analytical solutions from this paper are accurate and stable.

  2. Field trial of graded care profile (GCP) scale: a new measure of care

    PubMed Central

    Srivastava, O; Polnay, L

    1997-01-01

    Accepted 20 December 1996
 AIM—The graded care profile (GCP) scale was developed as a practical tool in response to the Children Act 1989 to provide a measure of care in four areas: physical, safety, love, and esteem, on a bipolar continuum. This field trial was to assess its user friendliness and inter-rater agreement.
METHODS—43 nursery children and 11 registered for neglect were each scored on this scale independently by two different raters (health visitor and nursery teacher or social worker). Their inter-rater agreement was assessed by weighted κ and user friendliness by time taken for and completeness of scoring.
RESULTS—An almost perfect level of agreement was achieved in physical care (κ = 0.899; confidence interval (CI) = 0.850 to 0.948), safety (κ = 0.894; CI = 0.854 to 0.933), esteem (κ = 0.877; CI= 0.808 to 0.946), and a substantial level in love (κ = 0.785; CI = 0.720 to 0.849). Mean time taken for scoring was 20 minutes (range 10 to 30); of 54 paired scales, area of safety was not scored only in three by one of the raters.
CONCLUSIONS—This scale appeared user friendly and provided grading of care with high inter-rater agreement. Its use in practice could provide an opportunity for useful comparison with other means of assessment of care, studying outcomes of different care profiles, targeting intervention, and monitoring change.

 PMID:9166027

  3. Extracting tumor tissue immune status from expression profiles: correlating renal cancer prognosis with tumor-associated immunome

    PubMed Central

    Teltsh, Omri

    2015-01-01

    Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation. It is based on reducing the variation which biopsy preparation adds to the apparent expression levels of immune genes. We employed immFocus to normalize gene expression with an immune index using data obtained from renal clear cell carcinoma biopsies. Genes that became less variable due to normalization were found to be preferentially immune-related. Moreover, immune-related genes tended to become more prognostic due to the normalization. These results demonstrate, for the first time, that whole transcriptome sequencing can be used for interrogation of a cancer immunome and for advancing immune-based prognosis. PMID:26384298

  4. Extracting tumor tissue immune status from expression profiles: correlating renal cancer prognosis with tumor-associated immunome.

    PubMed

    Teltsh, Omri; Porgador, Angel; Rubin, Eitan

    2015-10-20

    Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation. It is based on reducing the variation which biopsy preparation adds to the apparent expression levels of immune genes. We employed immFocus to normalize gene expression with an immune index using data obtained from renal clear cell carcinoma biopsies. Genes that became less variable due to normalization were found to be preferentially immune-related. Moreover, immune-related genes tended to become more prognostic due to the normalization. These results demonstrate, for the first time, that whole transcriptome sequencing can be used for interrogation of a cancer immunome and for advancing immune-based prognosis. PMID:26384298

  5. Multi-scale roughness measurement of cementitious materials using different optical profilers and window resizing analysis

    NASA Astrophysics Data System (ADS)

    Montgomery, Paul C.; Salzenstein, Fabien; Gianto, Gianto; Apedo, Komla L.; Serres, Nicolas; Fond, Christophe; Feugeas, Françoise

    2015-05-01

    In the development of new eco-cements for ecologically friendly construction, the porosity, surface structure and chemical nature of the material can influence the bioreceptivity of the surface and the aptitude or not of environmental micro-organisms to form biofilms. Such films are the source of biocontamination that can lead to a degradation in the structural properties over time. Accurate measurement of surface roughness and topography are important to help in the understanding of this interaction. Optical profilers are well adapted to the quantifying of large surface roughness typical of cementitious materials, being more rapid and better able to cope with high roughness compared with stylus and near field probe techniques. But any given surface profiler typically has specific range limits in terms of axial and lateral resolution and field of view, resulting in different roughness values according to the type of optical profiler used. In the present work, unpolished and polished cement paste samples have been measured with two different systems, one using interference microscopy and the other, chromatic confocal sensing. Comparison of the results from both techniques using the method of window re-sizing, more commonly used in tribology, has been used for calculating the average roughness parameters at different scales. The initial results obtained show a successful overlap of the results for the unpolished samples and a slight separation for the polished samples. The validation of the measurements is demonstrated together with a revealing of differences in the measurements on different types of surfaces due to variations in instrument performance.

  6. Immune response-associated gene analysis of 1,000 cancer patients using whole-exome sequencing and gene expression profiling-Project HOPE.

    PubMed

    Akiyama, Yasuto; Kondou, Ryota; Iizuka, Akira; Ohshima, Keiichi; Urakami, Kenichi; Nagashima, Takeshi; Shimoda, Yuji; Tanabe, Tomoe; Ohnami, Sumiko; Ohnami, Shumpei; Kusuhara, Masatoshi; Mochizuki, Tohru; Yamaguchi, Ken

    2016-01-01

    Project HOPE (High-tech Omics-based Patient Evaluation) has been progressing since its implementation in 2014 using whole-exome sequencing (WES) and gene expression profiling (GEP). With the aim of evaluating immune status in cancer patients, a gene panel consisting of 164 immune response-associated genes (56 antigen-presenting cell and T-cell-associated genes, 34 cytokine- and metabolism-associated genes, 47 TNF and TNF receptor superfamily genes, and 27 regulatory T-cell-associated genes) was established, and its expression and mutation status were investigated using 1,000 cancer patient-derived tumors. Regarding WES, sequencing and variant calling were performed using the Ion Proton system. The average number of single-nucleotide variants (SNVs) detected per sample was 183 ± 507, and the number of hypermutators with more than 500 total SNVs was 51 cases. Regarding GEP, seven immune response-associated genes (VTCN1, IL2RA, ULBP2, TREM1, MSR1, TNFSF9 and TNFRSF12A) were more than 2-fold overexpressed compared with normal tissues in more than 2 organs. Specifically, the positive rate of PD-L1 expression in all patients was 25.8%, and PD-L1 expression was significantly upregulated in hypermutators. The simultaneous analyses of WES and GEP based on immune response-associated genes are very intriguing tools to screen cancer patients suitable for immune checkpoint antibody therapy. PMID:27544999

  7. Spatial Scaling of the Profile of Selective Attention in the Visual Field.

    PubMed

    Gannon, Matthew A; Knapp, Ashley A; Adams, Thomas G; Long, Stephanie M; Parks, Nathan A

    2016-01-01

    Neural mechanisms of selective attention must be capable of adapting to variation in the absolute size of an attended stimulus in the ever-changing visual environment. To date, little is known regarding how attentional selection interacts with fluctuations in the spatial expanse of an attended object. Here, we use event-related potentials (ERPs) to investigate the scaling of attentional enhancement and suppression across the visual field. We measured ERPs while participants performed a task at fixation that varied in its attentional demands (attentional load) and visual angle (1.0° or 2.5°). Observers were presented with a stream of task-relevant stimuli while foveal, parafoveal, and peripheral visual locations were probed by irrelevant distractor stimuli. We found two important effects in the N1 component of visual ERPs. First, N1 modulations to task-relevant stimuli indexed attentional selection of stimuli during the load task and further correlated with task performance. Second, with increased task size, attentional modulation of the N1 to distractor stimuli showed a differential pattern that was consistent with a scaling of attentional selection. Together, these results demonstrate that the size of an attended stimulus scales the profile of attentional selection across the visual field and provides insights into the attentional mechanisms associated with such spatial scaling. PMID:27606426

  8. Assessment of error in synoptic-scale diagnostics derived from wind profiler and radiosonde network data

    SciTech Connect

    Mace, G.G.; Ackerman, T.P.

    1996-07-01

    A topic of current practical interest is the accurate characterization of the synoptic-scale atmospheric state from wind profiler and radiosonde network observations. The authors have examined several related and commonly applied objective analysis techniques for performing this characterization and considered their associated level of uncertainty both from a theoretical and a practical standpoint. A case study is presented where two wind profiler triangles with nearly identical centroids and no common vertices produced strikingly different results during a 43-h period. It is concluded that the uncertainty in objectively analyzed quantities can easily be as large as the expected synoptic-scale signal. In order to quantify the statistical precision of the algorithms, the authors conducted a realistic observing system simulation experiment using output from a mesoscale model. A simple parameterization for estimating the uncertainty in horizontal gradient quantities in terms of known errors in the objectively analyzed wind components and temperature is developed from these results. 18 refs., 9 figs., 6 tabs.

  9. Observed large-scale structures and diabatic heating and drying profiles during TWP-ICE

    SciTech Connect

    Xie, Shaocheng; Hume, Timothy; Jakob, Christian; Klein, Stephen A.; McCoy, Renata B.; Zhang, Minghua

    2010-01-01

    This study documents the characteristics of the large-scale structures and diabatic heating and drying profiles observed during the Tropical Warm Pool–International Cloud Experiment (TWP-ICE), which was conducted in January–February 2006 in Darwin during the northern Australian monsoon season. The examined profiles exhibit significant variations between four distinct synoptic regimes that were observed during the experiment. The active monsoon period is characterized by strong upward motion and large advective cooling and moistening throughout the entire troposphere, while the suppressed and clear periods are dominated by moderate midlevel subsidence and significant low- to midlevel drying through horizontal advection. The midlevel subsidence and horizontal dry advection are largely responsible for the dry midtroposphere observed during the suppressed period and limit the growth of clouds to low levels. During the break period, upward motion and advective cooling and moistening located primarily at midlevels dominate together with weak advective warming and drying (mainly from horizontal advection) at low levels. The variations of the diabatic heating and drying profiles with the different regimes are closely associated with differences in the large-scale structures, cloud types, and rainfall rates between the regimes. Strong diabatic heating and drying are seen throughout the troposphere during the active monsoon period while they are moderate and only occur above 700 hPa during the break period. The diabatic heating and drying tend to have their maxima at low levels during the suppressed periods. Furthermore, the diurnal variations of these structures between monsoon systems, continental/coastal, and tropical inland-initiated convective systems are also examined.

  10. Observed large-scale structures and diabatic heating and drying profiles during TWP-ICE

    DOE PAGESBeta

    Xie, Shaocheng; Hume, Timothy; Jakob, Christian; Klein, Stephen A.; McCoy, Renata B.; Zhang, Minghua

    2010-01-01

    This study documents the characteristics of the large-scale structures and diabatic heating and drying profiles observed during the Tropical Warm Pool–International Cloud Experiment (TWP-ICE), which was conducted in January–February 2006 in Darwin during the northern Australian monsoon season. The examined profiles exhibit significant variations between four distinct synoptic regimes that were observed during the experiment. The active monsoon period is characterized by strong upward motion and large advective cooling and moistening throughout the entire troposphere, while the suppressed and clear periods are dominated by moderate midlevel subsidence and significant low- to midlevel drying through horizontal advection. The midlevel subsidence andmore » horizontal dry advection are largely responsible for the dry midtroposphere observed during the suppressed period and limit the growth of clouds to low levels. During the break period, upward motion and advective cooling and moistening located primarily at midlevels dominate together with weak advective warming and drying (mainly from horizontal advection) at low levels. The variations of the diabatic heating and drying profiles with the different regimes are closely associated with differences in the large-scale structures, cloud types, and rainfall rates between the regimes. Strong diabatic heating and drying are seen throughout the troposphere during the active monsoon period while they are moderate and only occur above 700 hPa during the break period. The diabatic heating and drying tend to have their maxima at low levels during the suppressed periods. Furthermore, the diurnal variations of these structures between monsoon systems, continental/coastal, and tropical inland-initiated convective systems are also examined.« less

  11. Cosmology and astrophysics from relaxed galaxy clusters - III. Thermodynamic profiles and scaling relations

    NASA Astrophysics Data System (ADS)

    Mantz, A. B.; Allen, S. W.; Morris, R. G.; Schmidt, R. W.

    2016-03-01

    This is the third in a series of papers studying the astrophysics and cosmology of massive, dynamically relaxed galaxy clusters. Our sample comprises 40 clusters identified as being dynamically relaxed and hot (i.e. massive) in Papers I and II of this series. Here we consider the thermodynamics of the intracluster medium, in particular the profiles of density, temperature and related quantities, as well as integrated measurements of gas mass, average temperature, total luminosity and centre-excluded luminosity. We fit power-law scaling relations of each of these quantities as a function of redshift and cluster mass, which can be measured precisely and with minimal bias for these relaxed clusters using hydrostatic arguments. For the thermodynamic profiles, we jointly model the density and temperature and their intrinsic scatter as a function of radius, thus also capturing the behaviour of the gas pressure and entropy. For the integrated quantities, we also jointly fit a multidimensional intrinsic covariance. Our results reinforce the view that simple hydrodynamical models provide a good description of relaxed clusters outside their centres, but that additional heating and cooling processes are important in the inner regions (radii r ≲ 0.5 r2500 ≈ 0.15 r500). The thermodynamic profiles remain regular, with small intrinsic scatter, down to the smallest radii where deprojection is straightforward (˜20 kpc); within this radius, even the most relaxed systems show clear departures from spherical symmetry. Our results suggest that heating and cooling are continuously regulated in a tight feedback loop, allowing the cluster atmosphere to remain stratified on these scales.

  12. On the use of Cloud Profiling Radar to detect solid precipitation over Antarctica at different scales

    NASA Astrophysics Data System (ADS)

    Milani, Lisa; Kulie, Mark S.; Casella, Daniele; D'Adderio, Leo Pio; Dietrich, Stefano; L'Ecuyer, Tristan S.; Panegrossi, Giulia; Porcù, Federico; Sanò, Paolo; Wood, Norman B.

    2016-04-01

    Precipitation is a key geophysical parameter in understanding the Antarctic climate. However, the particular environmental conditions of the Continent make it difficult to measure directly solid precipitation rate and accumulation from either ground based instruments or passive space-borne sensors. A significant improvement in the study of solid precipitation over Antarctica is possible by using active space-borne instruments: the Cloud Profiling Radar (CPR), a nadir-pointing 94 GHz radar, on board the low earth orbit CloudSat satellite. Five years (2006-2011) of CPR data and products over Antarctica are analyzed to investigate the characteristics of solid precipitation. The aim of this work is twofold: 1) to compare a global snowfall rate retrieval algorithm (Kulie and Bennartz, 2009) with the official CloudSat product (2C-SNOW-PROFILE) over the Antarctic environment, evaluating the sensitivity of the estimated snow fields to: ground clutter, choice of reflectivity-snowfall rate relationship (Z-S), presence of melting snow/liquid precipitation; 2) to provide snow fall rates and accumulation at different scales over Antarctica, evaluating the impact of background physiography and seasonal cycle on the precipitation distribution. Further comparisons are also performed with ERA-Interim snowfall fields and point-like snow stack height measurements by acoustic depth gauges. Results show that the difference between the Kulie and Bennartz (2009) algorithm and the 2C-SNOW-PROFILE product is mainly due to the choice of the Z-S relationship. Furthermore, despite the CPR limited temporal and spatial sampling capabilities, CPR is able to evidence precipitation characteristics difficult to study from conventional ground-based instruments, at spatial and temporal scales of interest for the study of the hydrological cycle over Antarctica. This is of particular relevance given that the CPR follow-on mission on EarthCare will ensure a long-term coverage.

  13. Multifractal analysis of vertical profiles of soil penetration resistance at the field scale

    NASA Astrophysics Data System (ADS)

    Siqueira, G. M.; Silva, E. F. F.; Montenegro, A. A. A.; Vidal Vázquez, E.; Paz-Ferreiro, J.

    2013-07-01

    Soil penetration resistance (PR) is widely used as an indirect indicator of soil strength. Soil PR is linked to basic soil properties and correlated to root growth and plant production, and as such it is extensively used as a practical tool for assessing soil compaction and to evaluate the effects of soil management. This study investigates how results from multifractal analysis can quantify key elements of depth-dependent soil PR profiles and how this information can be used at the field scale. We analysed multifractality of 50 PR vertical profiles, measured from 0 to 60 cm depth and randomly located on a 6.5 ha sugar cane field in northeastern Brazil. The scaling property of each profile was typified by singularity, and Rényi spectra estimated by the method of moments. The Hurst exponent was used to parameterize the autocorrelation of the vertical PR data sets. The singularity and Rènyi spectra showed that the vertical PR data sets exhibited a well-defined multifractal structure. Hurst exponent values were close to 1, ranging from 0.944 to 0.988, indicating strong persistence in PR variation with soil depth. Also, the Hurst exponent was negatively and significantly correlated to coefficient of variation (CV), skewness and maximum values of the depth-dependent PR. Multifractal analysis added valuable information to describe the spatial arrangement of depth-dependent penetrometer data sets, which was not taken into account by classical statistical indices. Multifractal parameters were mapped over the experimental field and compared with mean and maximum values of PR. Combination of spatial variability survey and multifractal analysis appear to be useful to manage soil compaction.

  14. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  15. Construct Validation of Analytic Rating Scales in a Speaking Assessment: Reporting a Score Profile and a Composite

    ERIC Educational Resources Information Center

    Sawaki, Yasuyo

    2007-01-01

    This is a construct validation study of a second language speaking assessment that reported a language profile based on analytic rating scales and a composite score. The study addressed three key issues: score dependability, convergent/discriminant validity of analytic rating scales and the weighting of analytic ratings in the composite score.…

  16. Deep sequencing-based transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus reveals insight into the immune-relevant genes in marine fish

    PubMed Central

    2010-01-01

    Background Systematic research on fish immunogenetics is indispensable in understanding the origin and evolution of immune systems. This has long been a challenging task because of the limited number of deep sequencing technologies and genome backgrounds of non-model fish available. The newly developed Solexa/Illumina RNA-seq and Digital gene expression (DGE) are high-throughput sequencing approaches and are powerful tools for genomic studies at the transcriptome level. This study reports the transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus using RNA-seq and DGE in an attempt to gain insights into the immunogenetics of marine fish. Results RNA-seq analysis generated 169,950 non-redundant consensus sequences, among which 48,987 functional transcripts with complete or various length encoding regions were identified. More than 52% of these transcripts are possibly involved in approximately 219 known metabolic or signalling pathways, while 2,673 transcripts were associated with immune-relevant genes. In addition, approximately 8% of the transcripts appeared to be fish-specific genes that have never been described before. DGE analysis revealed that the host transcriptome profile of Vibrio harveyi-challenged L. japonicus is considerably altered, as indicated by the significant up- or down-regulation of 1,224 strong infection-responsive transcripts. Results indicated an overall conservation of the components and transcriptome alterations underlying innate and adaptive immunity in fish and other vertebrate models. Analysis suggested the acquisition of numerous fish-specific immune system components during early vertebrate evolution. Conclusion This study provided a global survey of host defence gene activities against bacterial challenge in a non-model marine fish. Results can contribute to the in-depth study of candidate genes in marine fish immunity, and help improve current understanding of host-pathogen interactions and evolutionary history

  17. A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies

    PubMed Central

    2011-01-01

    Introduction The clinical efficacy of trastuzumab and taxanes is at least partly related to their ability to mediate or promote antitumor immune responses. On these grounds, a careful analysis of basal immune profile may be capital to dissect the heterogeneity of clinical responses to these drugs in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. Methods Blood samples were collected from 61 locally advanced breast cancers (36 HER2- and 25 HER2+) at diagnosis and from 23 healthy women. Immunophenotypic profiling of circulating and intratumor immune cells, including regulatory T (Treg) cells, was assessed by flow cytometry and immunohistochemistry, respectively. Serum levels of 10 different cytokines were assessed by multiplex immunoassays. CD8+ T cell responses to multiple tumor-associated antigens (TAA) were evaluated by IFN-γ-enzyme-linked immunosorbent spot (ELISPOT). The Student's t test for two tailed distributions and the Wilcoxon two-sample test were used for the statistical analysis of the data. Results The proportion of circulating immune effectors was similar in HER2+ patients and healthy donors, whereas higher percentages of natural killer and Treg cells and a lower CD4+/CD8+ T cell ratio (with a prevalence of naïve and central memory CD8+ T cells) were observed in HER2- cases. Higher numbers of circulating CD8+ T cells specific for several HLA-A*0201-restricted TAA-derived peptides were observed in HER2+ cases, together with a higher prevalence of intratumor CD8+ T cells. Serum cytokine profile of HER2+ patients was similar to that of controls, whereas HER2- cases showed significantly lower cytokine amounts compared to healthy women (IL-2, IL-8, IL-6) and HER2+ cases (IL-2, IL-1β, IL-8, IL-6, IL-10). Conclusions Compared to HER2- cases, patients with HER2-overexpressing locally advanced breast cancer show a more limited tumor-related immune suppression. This may account for the clinical benefit achieved in this subset

  18. Nutrient content in sludge profiles from a full-scale stabilization pond in a temperate location.

    PubMed

    Faleschini, Mauricio; Esteves, José L

    2014-09-01

    The inorganic nutrient concentrations in sludge profiles from a full-scale municipal facultative pond in Puerto Madryn City (Argentina) were measured. Sludge samples were collected with cores during autumn, winter, and summer at three sites: inlet, intermediate, and outlet. In general, the sludge accumulates NH4+ and PO4(3-), increasing their concentrations with depth. However, NH4+ presented a different behavior at the outlet station during the summer, when the lower concentrations were recorded. This finding reflects a nutrient release, originating in their greater demand from the water column. In the sludge, the NO3- followed the spatial and seasonal pattern recorded in the surface water: detectable concentrations in the warmer months at the outlet. The vertical reduction of NO3- could be an indication of denitrification. The study supported the hypothesis that the sludge can act as a nutrient trap or source, depending on factors such as the temperature, nutrients/oxygen concentration, mixing processes, and location. PMID:25327021

  19. Translatome profiling: methods for genome-scale analysis of mRNA translation.

    PubMed

    King, Helen A; Gerber, André P

    2016-01-01

    During the past decade, there has been a rapidly increased appreciation of the role of translation as a key regulatory node in gene expression. Thereby, the development of methods to infer the translatome, which refers to the entirety of mRNAs associated with ribosomes for protein synthesis, has facilitated the discovery of new principles and mechanisms of translation and expanded our view of the underlying logic of protein synthesis. Here, we review the three main methodologies for translatome analysis, and we highlight some of the recent discoveries made using each technique. We first discuss polysomal profiling, a classical technique that involves the separation of mRNAs depending on the number of bound ribosomes using a sucrose gradient, and which has been combined with global analysis tools such as DNA microarrays or high-throughput RNA sequencing to identify the RNAs in polysomal fractions. We then introduce ribosomal profiling, a recently established technique that enables the mapping of ribosomes along mRNAs at near-nucleotide resolution on a global scale. We finally refer to ribosome affinity purification techniques that are based on the cell-type-specific expression of tagged ribosomal proteins, allowing the capture of translatomes from specialized cells in organisms. We discuss the advantages and disadvantages of these three main techniques in the pursuit of defining the translatome, and we speculate about future developments. PMID:25380596

  20. Protein-based profiling of the immune response to uropathogenic Escherichia coli in adult patients immediately following hospital admission for acute cystitis.

    PubMed

    Sundac, Lana; Dando, Samantha J; Sullivan, Matthew J; Derrington, Petra; Gerrard, John; Ulett, Glen C

    2016-08-01

    Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are common infections in humans. Despite the substantial healthcare cost represented by these infections, the human immune response associated with the infection immediately following the onset of symptoms in patients remains largely undefined. We performed a prospective study aimed at defining the milieu of urinary cytokines in adult inpatients in the 24-48 h period immediately following hospital admission for acute cystitis due to UPEC. Urine samples, analyzed using 27-target multiplex protein assays, were used to generate immune profiles for patients and compared to age- and gender-matched healthy controls. The levels of multiple pro-inflammatory cytokines were significantly elevated in urine as a result of infection, an observation consistent with prior findings in murine models and clinical literature. We also identified significant responses for several novel factors not previously associated with the human response to UTI, including Interleukin (IL)-4, IL-7, IL-9, IL-17A, eotaxin, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and several growth factors. These data establish crucial parallels between the human immune response to UPEC and murine model UTI studies, and emphasize the complex but poorly defined nature of the human immune response to UPEC, particularly in the immediate period following the onset of symptoms for acute cystitis. PMID:27354295

  1. Transcriptional Profiles of Host-Pathogen Responses to Necrotic Enteritis and Differential Regulation of Immune Genes in Two Inbreed Chicken Lines Showing Disparate Disease Susceptibility

    PubMed Central

    Kim, Duk Kyung; Lillehoj, Hyun S.; Jang, Seung I.; Lee, Sung Hyen; Hong, Yeong Ho; Cheng, Hans H.

    2014-01-01

    Necrotic enteritis (NE) is an important intestinal infectious disease of commercial poultry flocks caused by Clostridium perfringens. Using an experimental model of NE involving co-infection with C. perfringens and Eimeria maxima, transcriptome profiling and functional genomics approaches were applied to identify the genetic mechanisms that might regulate the host response to this disease. Microarray hybridization identified 1,049 transcripts whose levels were altered (601 increased, 448 decreased) in intestinal lymphocytes from C. perfringens/E. maxima co-infected Ross chickens compared with uninfected controls. Five biological functions, all related to host immunity and inflammation, and 11 pathways were identified from this dataset. To further elucidate the role of host genetics in NE susceptibility, two inbred chicken lines, ADOL line 6 and line 7 which share an identical B2 major histocompatibility complex haplotype but differ in their susceptibility to virus infection, were compared for clinical symptoms and the expression levels of a panel of immune-related genes during experimental NE. Line 6 chickens were more susceptible to development of experimental NE compared with line 7, as revealed by decreased body weight gain and increased E. maxima oocyst shedding. Of 21 immune-related genes examined, 15 were increased in C. perfringens/E. maxima co-infected line 6 vs. line 7 chickens. These results suggest that immune pathways are activated in response to experimental NE infection and that genetic determinants outside of the chicken B complex influence resistance to this disease. PMID:25504150

  2. Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia

    PubMed Central

    Hwang, Y; Kim, J; Shin, J-Y; Kim, J-II; Seo, J-S; Webster, M J; Lee, D; Kim, S

    2013-01-01

    Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease. PMID:24169640

  3. Antibody Profiling in Naïve and Semi-immune Individuals Experimentally Challenged with Plasmodium vivax Sporozoites

    PubMed Central

    Arévalo-Herrera, Myriam; Lopez-Perez, Mary; Dotsey, Emmanuel; Jain, Aarti; Rubiano, Kelly; Felgner, Philip L.; Davies, D. Huw; Herrera, Sócrates

    2016-01-01

    Background Acquisition of malaria immunity in low transmission areas usually occurs after relatively few exposures to the parasite. A recent Plasmodium vivax experimental challenge trial in malaria naïve and semi-immune volunteers from Colombia showed that all naïve individuals developed malaria symptoms, whereas semi-immune subjects were asymptomatic or displayed attenuated symptoms. Sera from these individuals were analyzed by protein microarray to identify antibodies associated with clinical protection. Methodology/Principal Findings Serum samples from naïve (n = 7) and semi-immune (n = 9) volunteers exposed to P. vivax sporozoite-infected mosquito bites were probed against a custom protein microarray displaying 515 P. vivax antigens. The array revealed higher serological responses in semi-immune individuals before the challenge, although malaria naïve individuals also had pre-existing antibodies, which were higher in Colombians than US adults (control group). In both experimental groups the response to the P. vivax challenge peaked at day 45 and returned to near baseline at day 145. Additional analysis indicated that semi-immune volunteers without fever displayed a lower response to the challenge, but recognized new antigens afterwards. Conclusion Clinical protection against experimental challenge in volunteers with previous P. vivax exposure was associated with elevated pre-existing antibodies, an attenuated serological response to the challenge and reactivity to new antigens. PMID:27014875

  4. On the computation of a retina resistivity profile for applications in multi-scale modeling of electrical stimulation and absorption

    NASA Astrophysics Data System (ADS)

    Loizos, Kyle; RamRakhyani, Anil Kumar; Anderson, James; Marc, Robert; Lazzi, Gianluca

    2016-06-01

    This study proposes a methodology for computationally estimating resistive properties of tissue in multi-scale computational models, used for studying the interaction of electromagnetic fields with neural tissue, with applications to both dosimetry and neuroprosthetics. Traditionally, models at bulk tissue- and cellular-level scales are solved independently, linking resulting voltage from existing resistive tissue-scale models as extracellular sources to cellular models. This allows for solving the effects that external electric fields have on cellular activity. There are two major limitations to this approach: first, the resistive properties of the tissue need to be chosen, of which there are contradicting measurements in literature; second, the measurements of resistivity themselves may be inaccurate, leading to the mentioned contradicting results found across different studies. Our proposed methodology allows for constructing computed resistivity profiles using knowledge of only the neural morphology within the multi-scale model, resulting in a practical implementation of the effective medium theory; this bypasses concerns regarding the choice of resistive properties and accuracy of measurement setups. A multi-scale model of retina is constructed with an external electrode to serve as a test bench for analyzing existing and resulting resistivity profiles, and validation is presented through the reconstruction of a published resistivity profile of retina tissue. Results include a computed resistivity profile of retina tissue for use with a retina multi-scale model used to analyze effects of external electric fields on neural activity.

  5. On the computation of a retina resistivity profile for applications in multi-scale modeling of electrical stimulation and absorption.

    PubMed

    Loizos, Kyle; RamRakhyani, Anil Kumar; Anderson, James; Marc, Robert; Lazzi, Gianluca

    2016-06-21

    This study proposes a methodology for computationally estimating resistive properties of tissue in multi-scale computational models, used for studying the interaction of electromagnetic fields with neural tissue, with applications to both dosimetry and neuroprosthetics. Traditionally, models at bulk tissue- and cellular-level scales are solved independently, linking resulting voltage from existing resistive tissue-scale models as extracellular sources to cellular models. This allows for solving the effects that external electric fields have on cellular activity. There are two major limitations to this approach: first, the resistive properties of the tissue need to be chosen, of which there are contradicting measurements in literature; second, the measurements of resistivity themselves may be inaccurate, leading to the mentioned contradicting results found across different studies. Our proposed methodology allows for constructing computed resistivity profiles using knowledge of only the neural morphology within the multi-scale model, resulting in a practical implementation of the effective medium theory; this bypasses concerns regarding the choice of resistive properties and accuracy of measurement setups. A multi-scale model of retina is constructed with an external electrode to serve as a test bench for analyzing existing and resulting resistivity profiles, and validation is presented through the reconstruction of a published resistivity profile of retina tissue. Results include a computed resistivity profile of retina tissue for use with a retina multi-scale model used to analyze effects of external electric fields on neural activity. PMID:27223656

  6. On the computation of a retina resistivity profile for applications in multi-scale modeling of electrical stimulation and absorption

    PubMed Central

    Loizos, Kyle; RamRakhyani, Anil Kumar; Anderson, James; Marc, Robert; Lazzi, Gianluca

    2016-01-01

    This study proposes a methodology for computationally estimating resistive properties of tissue in multi-scale computational models, used for studying the interaction of electromagnetic fields with neural tissue, with applications to both dosimetry and neuroprosthetics. Traditionally, models at bulk tissue- and cellular-level scales are solved independently, linking resulting voltage from existing resistive tissue-scale models as extracellular sources to cellular models. This allows for solving the effects that external electric fields have on cellular activity. There are two major limitations to this approach: first, the resistive properties of the tissue need to be chosen, of which there are contradicting measurements in literature; second, the measurements of resistivity themselves may be inaccurate, leading to the mentioned contradicting results found across different studies. Our proposed methodology allows for constructing computed resistivity profiles using knowledge of only the neural morphology within the multi-scale model, resulting in a practical implementation of the effective medium theory; this bypasses concerns regarding the choice of resistive properties and accuracy of measurement setups. A multi-scale model of retina is constructed with an external electrode to serve as a test bench for analyzing existing and resulting resistivity profiles, and validation is presented through the reconstruction of a published resistivity profile of retina tissue. Results include a computed resistivity profile of retina tissue for use with a retina multi-scale model used to analyze effects of external electric fields on neural activity. PMID:27223656

  7. Transcriptome and Expression Profiling Analysis of the Hemocytes Reveals a Large Number of Immune-Related Genes in Mud Crab Scylla paramamosain during Vibrio parahaemolyticus Infection

    PubMed Central

    Xie, Chuping; Chen, Yaping; Sun, Wanwei; Ding, Jun; Zhou, Lizhen; Wang, Shasha; Wang, Shuqi; Zhang, Yueling; Zhu, Dashi; Wen, Xiaobo; Hu, Songnian; Li, Shengkang

    2014-01-01

    Background Mud crab Scylla paramamosain is an economically important marine species in China. However, frequent outbreaks of infectious diseases caused by marine bacteria, such as Vibrio parahaemolyticus, result in great economic losses. Methodology/Principal Findings Comparative de novo transcriptome analysis of S. paramamosain infected with V. parahaemolyticus was carried out to investigate the molecular mechanisms underlying the immune response to pathogenic bacteria by using the Illumina paired-end sequencing platform. A total of 52,934,042 clean reads from the hemocytes of V. parahaemolyticus-infected mud crabs and controls were obtained and assembled into 186,193 contigs. 59,120 unigenes were identified from 81,709 consensus sequences of mud crabs and 48,934 unigenes were matched proteins in the Nr or Swissprot databases. Among these, 10,566 unigenes belong to 3 categories of Gene Ontology, 25,349 to 30 categories of KEGG, and 15,191 to 25 categories of COG database, covering almost all functional categories. By using the Solexa/Illumina's DGE platform, 1213 differentially expressed genes (P<0.05), including 538 significantly up-regulated and 675 down-regulated, were detected in V. parahaemolyticus-infected crabs as compared to that in the controls. Transcript levels of randomly-chosen genes were further measured by quantitative real-time PCR to confirm the expression profiles. Many differentially expressed genes are involved in various immune processes, including stimulation of the Toll pathway, Immune Deficiency (IMD) pathway, Ras-regulated endocytosis, and proPO-activating system. Conclusions/Significance Analysis of the expression profile of crabs under infection provides invaluable new data for biological research in S. paramamosain, such as the identification of novel genes in the hemocytes during V. parahaemolyticus infection. These results will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial

  8. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response.

    PubMed

    Jayawardena, Uthpala A; Ratnasooriya, Wanigasekara D; Wickramasinghe, Deepthi D; Udagama, Preethi V

    2016-10-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~5ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~9360pg/mL) of all cytokines tested. Significantly elevated IFNγ production (P<0.05) was evident in heavy metal exposed frogs. Th1/Th2 cytokine ratio in both serum and liver tissue homogenates was Th1 skewed due to significantly higher production of pro-inflammatory cytokines, IFNγ in serum and TNFα in the liver (P<0.01).Metal mediated aggregations of melanomacrophages in the liver were positively and significantly (P<0.05) correlated with the hepatic expression of TNFα, IL6 and IL10 activity. Overall, Th1 skewed response may well be due to oxidative stress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco

  9. Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

    PubMed

    Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

    2015-09-01

    The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed. PMID:25996520

  10. Transcriptome Profiling of the Virus-Induced Innate Immune Response in Pteropus vampyrus and Its Attenuation by Nipah Virus Interferon Antagonist Functions

    PubMed Central

    Glennon, Nicole B.; Jabado, Omar; Lo, Michael K.

    2015-01-01

    ABSTRACT Bats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. As the innate immune response is critical for controlling viruses, the nature of this response in bats and how it may differ from that in other mammals are of great interest. Using next-generation transcriptome sequencing (mRNA-seq), we profiled the transcriptional response of Pteropus vampyrus bat kidney (PVK) cells to Newcastle disease virus (NDV), an avian paramyxovirus known to elicit a strong innate immune response in mammalian cells. The Pteropus genus is a known reservoir of Nipah virus (NiV) and Hendra virus (HeV). Analysis of the 200 to 300 regulated genes showed that genes for interferon (IFN) and antiviral pathways are highly upregulated in NDV-infected PVK cells, including genes for beta IFN, RIG-I, MDA5, ISG15, and IRF1. NDV-infected cells also upregulated several genes not previously characterized to be antiviral, such as RND1, SERTAD1, CHAC1, and MORC3. In fact, we show that MORC3 is induced by both IFN and NDV infection in PVK cells but is not induced by either stimulus in human A549 cells. In contrast to NDV infection, HeV and NiV infection of PVK cells failed to induce these innate immune response genes. Likewise, an attenuated response was observed in PVK cells infected with recombinant NDVs expressing the NiV IFN antagonist proteins V and W. This study provides the first global profile of a robust virus-induced innate immune response in bats and indicates that henipavirus IFN antagonist mechanisms are likely active in bat cells. IMPORTANCE Bats are the reservoir host for many highly pathogenic human viruses, including henipaviruses, lyssaviruses, severe acute respiratory syndrome coronavirus, and filoviruses, and many other viruses have also been isolated from bats. Viral infections are reportedly asymptomatic or heavily attenuated in bat populations. Despite their ecological importance to viral

  11. Immune gene expression profiling of PBMC isolated from horses vaccinated with attenuated African horsesickness virus serotype 4.

    PubMed

    Pretorius, A; Faber, F E; van Kleef, M

    2016-02-01

    Development of African horsesickness (AHS) subunit vaccines will have to include a rational approach that uses knowledge of how the virus interacts with the host immune system. The global in vivo immune response induced by attenuated AHSV serotype 4 in horses was characterised using transcriptome sequencing. PBMC were collected with 24h intervals for four days after inoculation and four days after a second boost, 21 days later. Transcriptome data were normalised to the day 0 naïve transcriptome and up- or down-regulated immune genes identified using the CLC workbench. Peak expression was observed 24h after each inoculation. Innate immunity was up-regulated after both inoculations and was characterised by type-1 interferon activation via the RIG-1/MDA5 pathway and the up-regulation of complement cascade components. After the second boost an adaptive immune response could be identified that included the production of cytokines indicative of T helper (Th)1, Th2 and Th17 responses. PMID:26382058

  12. Genomic and Immunological Tumor Profiling Identifies Targetable Pathways and Extensive CD8+/PDL1+ Immune Infiltration in Inflammatory Breast Cancer Tumors.

    PubMed

    Hamm, Christopher A; Moran, Diarmuid; Rao, Kakuturu; Trusk, Patricia B; Pry, Karen; Sausen, Mark; Jones, Siân; Velculescu, Victor E; Cristofanilli, Massimo; Bacus, Sarah

    2016-07-01

    Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that remains poorly understood at the molecular level. Comprehensive tumor profiling was performed to understand clinically actionable alterations in IBC. Targeted next-generation sequencing (NGS) and IHC were performed to identify activated pathways in IBC tumor tissues. siRNA studies examined the impact of IBC genomic variants in cellular models. IBC tumor tissues were further characterized for immune infiltration and immune checkpoint expression by IHC. Genomic analysis identified recurrent alterations in core biologic pathways, including activating and targetable variants in HER/PI3K/mTOR signaling. High rates of activating HER3 point mutations were discovered in IBC tumors. Cell line studies confirmed a role for mutant HER3 in IBC cell proliferation. Immunologic analysis revealed a subset of IBC tumors associated with high CD8(+)/PD-L1(+) lymphocyte infiltration. Immune infiltration positively correlated with an NGS-based estimate of neoantigen exposure derived from the somatic mutation rate and mutant allele frequency, iScore. Additionally, DNA mismatch repair alterations, which may contribute to higher iScores, occurred at greater frequency in tumors with higher immune infiltration. Our study identifies genomic alterations that mechanistically contribute to oncogenic signaling in IBC and provides a genetic basis for the selection of clinically relevant targeted and combination therapeutic strategies. Furthermore, an NGS-based estimate of neoantigen exposure developed in this study (iScore) may be a useful biomarker to predict immune infiltration in IBC and other cancers. The iScore may be associated with greater levels of response to immunotherapies, such as PD-L1/PD-1-targeted therapies. Mol Cancer Ther; 15(7); 1746-56. ©2016 AACR. PMID:27196778

  13. Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn "On" Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model.

    PubMed

    VanderVeen, Nathan; Raja, Nicholas; Yi, Elizabeth; Appelman, Henry; Ng, Philip; Palmer, Donna; Zamler, Daniel; Dzaman, Marta; Lowenstein, Pedro R; Castro, Maria G

    2016-06-01

    Glioblastoma multiforme (GBM) is the most commonly occurring primary brain cancer in adults, in whom its highly infiltrative cells prevent total surgical resection, often leading to tumor recurrence and patient death. Our group has discovered a gene therapy approach for GBM that utilizes high-capacity "gutless" adenoviral vectors encoding regulatable therapeutic transgenes. The herpes simplex type 1-thymidine kinase (TK) actively kills dividing tumor cells in the brain when in the presence of the prodrug, ganciclovir (GCV), whereas the FMS-like tyrosine kinase 3 ligand (Flt3L) is an immune-stimulatory molecule under tight regulation by a tetracycline-inducible "Tet-On" activation system that induces anti-GBM immunity. As a prelude to a phase I clinical trial, we evaluated the safety and efficacy of Food and Drug Administration (FDA)-approved doses of the tetracycline doxycycline (DOX) allometrically scaled for rats. DOX initiates the expression of Flt3L, which has been shown to recruit dendritic cells to the brain tumor microenvironment-an integral first step in the development of antitumor immunity. The data revealed a highly safe profile surrounding these human-equivalent doses of DOX under an identical therapeutic window as proposed in the clinical trial. This was confirmed through a neuropathological analysis, liver and kidney histopathology, detection of neutralizing antibodies, and systemic toxicities in the blood. Interestingly, we observed a significant survival advantage in rats with GBM receiving the 300 mg/day equivalent dosage of DOX versus the 200 mg/day equivalent. Additionally, rats rejected "recurrent" brain tumor threats implanted 90 days after their primary brain tumors. We also show that DOX detection within the plasma can be an indicator of optimal dosing of DOX to attain therapeutic levels. This work has significant clinical relevance for an ongoing phase I clinical trial in humans with primary GBM and for other therapeutic approaches using

  14. Gene expression profile analysis of Manila clam (Ruditapes philippinarum) hemocytes after a Vibrio alginolyticus challenge using an immune-enriched oligo-microarray

    PubMed Central

    2014-01-01

    Background The Manila clam (Ruditapes philippinarum) is a cultured bivalve with worldwide commercial importance, and diseases cause high economic losses. For this reason, interest in the immune genes in this species has recently increased. The present work describes the construction of the first R. philippinarum microarray containing immune-related hemocyte sequences and its application to study the gene transcription profiles of hemocytes from clams infected with V. alginolyticus through a time course. Results The complete set of sequences from R. philippinarum available in the public databases and the hemocyte sequences enriched in immune transcripts were assembled successfully. A total of 12,156 annotated sequences were used to construct the 8 ×15 k oligo-microarray. The microarray experiments yielded a total of 579 differentially expressed transcripts. Using the gene expression results, the associated Gene Ontology terms and the enrichment analysis, we found different response mechanisms throughout the experiment. Genes related to signaling, transcription and apoptosis, such as IL-17D, NF-κB or calmodulin, were typically expressed as early as 3 hours post-challenge (hpc), while characteristic immune genes, such as PGRPs, FREPs and defense proteins appeared later at 8 hpc. This immune-triggering response could have affected a high number of processes that seemed to be activated 24 hpc to overcome the Vibrio challenge, including the expression of many cytoskeleton molecules, which is indicative of the active movement of hemocytes. In fact functional studies showed an increment in apoptosis, necrosis or cell migration after the infection. Finally, 72 hpc, activity returned to normal levels, and more than 50% of the genes were downregulated in a negative feedback of all of the previously active processes. Conclusions Using a new version of the R. philippinarum oligo-microarray, a putative timing for the response against a Vibrio infection was established. The key

  15. Projected profile similarity in gyrokinetic simulations of Bohm and gyro-Bohm scaled DIII-D L and H modes

    SciTech Connect

    Waltz, R. E.; Candy, J.; Petty, C. C.

    2006-07-15

    Global gyrokinetic simulations of DIII-D [M. A. Mahdavi and J. L. Luxon, in 'DIII-D Tokamak Special Issue', Fusion Sci. Technol. 48, 2 (2005)] L- and H-mode dimensionally similar discharge pairs are treated in detail. The simulations confirm the Bohm scaling of the well-matched L-mode pair. The paradoxical but experimentally apparent gyro-Bohm scaling of the H-mode pair at larger relative gyroradius (rho-star) and lower transport levels is due to poor profile similarity. Simulations of projected experimental plasma profiles with perfect similarity show both the L- and H-mode pairs to have Bohm scaling. A {rho}{sub *} stabilization rule for predicting the breakdown of gyro-Bohm scaling from simulations of a single discharge is presented.

  16. Consanguinity profile in the Gaza Strip of Palestine: large-scale community-based study.

    PubMed

    Sirdah, Mahmoud M

    2014-02-01

    Consanguineous marriages which have been practiced throughout history continue to be practiced within different ethnic, religious and social groups to varying degrees with highest prevalences in North Africa, Middle East and central and south Asia. In the Gaza Strip of Palestine, little is known about the consanguinity profile, so the present large-scale study aims to explore the consanguinity profile of two generations using data from the β-thalassemia premarital screening program. Sociodemographic data analysis included 156,635 (141,200 males and 15,435 females) persons and their parents, representing 141,200 couples who were referred to the Thalassemia and Hemophilia Center for premarital testing. In addition, the consanguinity characteristics of parents of 217 transfusion-dependent β-thalassemic non-sibling patients were analyzed. Results revealed a significant decrease in the overall prevalence of consanguineous (first- and second-cousin) marriages between the previous (fathers') generation (45.2%) and the current (groom/bride) generation (39.9%). Among the five governorates of the Gaza Strip, records of Gaza Governorate revealed the lowest occurrence (36.9% current generation and 42.1% previous generation) of consanguineous marriages, as compared to all others. Consanguineous marriages are significantly higher in semi-urban areas (41.6%) than in urban areas (39.1%) in the current generation (previous generation, 46.4% vs 44.7%, respectively). Compound consanguinity (two generation) and a single level of consanguinity were seen in 20.7% and 43.7%, respectively, of the cases. The average age of those with first-cousin marriages is significantly lower (22.4±4.4 years) than those with second-cousin marriages (24.3±6.1 years) and the non-consanguineous (26.5±8.2 years). The rate of consanguineous marriages among never married people (42.2%) is significantly much higher than the rate of people with multiple marriages (18.1%). About 74.7% of the non

  17. Metabolic Profiling of Geobacter sulfurreducens during Industrial Bioprocess Scale-Up

    PubMed Central

    Muhamadali, Howbeer; Xu, Yun; Ellis, David I.; Allwood, J. William; Rattray, Nicholas J. W.; Correa, Elon; Alrabiah, Haitham

    2015-01-01

    During the industrial scale-up of bioprocesses it is important to establish that the biological system has not changed significantly when moving from small laboratory-scale shake flasks or culturing bottles to an industrially relevant production level. Therefore, during upscaling of biomass production for a range of metal transformations, including the production of biogenic magnetite nanoparticles by Geobacter sulfurreducens, from 100-ml bench-scale to 5-liter fermentors, we applied Fourier transform infrared (FTIR) spectroscopy as a metabolic fingerprinting approach followed by the analysis of bacterial cell extracts by gas chromatography-mass spectrometry (GC-MS) for metabolic profiling. FTIR results clearly differentiated between the phenotypic changes associated with different growth phases as well as the two culturing conditions. Furthermore, the clustering patterns displayed by multivariate analysis were in agreement with the turbidimetric measurements, which displayed an extended lag phase for cells grown in a 5-liter bioreactor (24 h) compared to those grown in 100-ml serum bottles (6 h). GC-MS analysis of the cell extracts demonstrated an overall accumulation of fumarate during the lag phase under both culturing conditions, coinciding with the detected concentrations of oxaloacetate, pyruvate, nicotinamide, and glycerol-3-phosphate being at their lowest levels compared to other growth phases. These metabolites were overlaid onto a metabolic network of G. sulfurreducens, and taking into account the levels of these metabolites throughout the fermentation process, the limited availability of oxaloacetate and nicotinamide would seem to be the main metabolic bottleneck resulting from this scale-up process. Additional metabolite-feeding experiments were carried out to validate the above hypothesis. Nicotinamide supplementation (1 mM) did not display any significant effects on the lag phase of G. sulfurreducens cells grown in the 100-ml serum bottles. However

  18. Metabolic Profiling of Geobacter sulfurreducens during Industrial Bioprocess Scale-Up.

    PubMed

    Muhamadali, Howbeer; Xu, Yun; Ellis, David I; Allwood, J William; Rattray, Nicholas J W; Correa, Elon; Alrabiah, Haitham; Lloyd, Jonathan R; Goodacre, Royston

    2015-05-15

    During the industrial scale-up of bioprocesses it is important to establish that the biological system has not changed significantly when moving from small laboratory-scale shake flasks or culturing bottles to an industrially relevant production level. Therefore, during upscaling of biomass production for a range of metal transformations, including the production of biogenic magnetite nanoparticles by Geobacter sulfurreducens, from 100-ml bench-scale to 5-liter fermentors, we applied Fourier transform infrared (FTIR) spectroscopy as a metabolic fingerprinting approach followed by the analysis of bacterial cell extracts by gas chromatography-mass spectrometry (GC-MS) for metabolic profiling. FTIR results clearly differentiated between the phenotypic changes associated with different growth phases as well as the two culturing conditions. Furthermore, the clustering patterns displayed by multivariate analysis were in agreement with the turbidimetric measurements, which displayed an extended lag phase for cells grown in a 5-liter bioreactor (24 h) compared to those grown in 100-ml serum bottles (6 h). GC-MS analysis of the cell extracts demonstrated an overall accumulation of fumarate during the lag phase under both culturing conditions, coinciding with the detected concentrations of oxaloacetate, pyruvate, nicotinamide, and glycerol-3-phosphate being at their lowest levels compared to other growth phases. These metabolites were overlaid onto a metabolic network of G. sulfurreducens, and taking into account the levels of these metabolites throughout the fermentation process, the limited availability of oxaloacetate and nicotinamide would seem to be the main metabolic bottleneck resulting from this scale-up process. Additional metabolite-feeding experiments were carried out to validate the above hypothesis. Nicotinamide supplementation (1 mM) did not display any significant effects on the lag phase of G. sulfurreducens cells grown in the 100-ml serum bottles. However

  19. Spreading analysis and finite-size scaling study of the critical behavior of a forest fire model with immune trees

    NASA Astrophysics Data System (ADS)

    Albano, Ezequiel V.

    1995-02-01

    In a forest fire model with immune trees (FFMIT) recently proposed by Drossel and Schwabl (Physica A 199 (1993) 183), the sites of the lattice are either empty, a tree or a burning tree, and at each time step the system is updated in parallel according to the following rules: (i) A burning tree becomes an empty site, (ii) trees grow with probability p from empty sites, and (iii) a green tree becomes a burning tree with probability (1- g) if at least one next neighbor is burning. Fixing an arbitrary grow probability ( p) and starting with a small immunity ( g), increments of g causes the fire density of the steady state to decrease until the fire becomes irreversibly extinguished at a certain critical point of coordinates { pc, gc}. The set of critical points defines a critical curve gc ( p) which, in the L = ∞ limit, divides the { p, g}-plane in two regions: a steady state with fire fronts for g < gc( p) and an unique absorbing state with all sites occupied by green trees for g ≥ gc( p). It is shown, by means of an epidemic spreading analysis that the continuous irreversible phase transition between the stationary regime and the absorbing state belongs to the same universality class as Reggeon field theory. It is found that within the absorbing state time correlations are short-ranged and that the fire density decrease exponentially. Within the stationary regime the irreversible transition is studied in terms of the finite-size scaling theory that was already developed to describe reversible transitions. The results reported in this work show that problems emerging from (apparently) unrelated branches of science such as particle physics, catalysis, directed percolation, and epidemic spreading can be understood by means of a unified description.

  20. Modified live virus vaccine induces a distinct immune response profile compared to inactivated influenza A virus vaccines in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic and antigenic diversity within H1 influenza A virus (IAV) subtypes circulating in swine is increasing. The need for cross-protective influenza vaccines in swine is necessary as the virus becomes more diverse. This study compared the humoral and cell-mediated immune response of modified live ...

  1. Transcriptome profiling analysis of naked carp (Gymnocypris przewalskii) provides insights into the immune-related genes in highland fish.

    PubMed

    Tong, Chao; Zhang, Cunfang; Zhang, Renyi; Zhao, Kai

    2015-10-01

    The naked carp, Gymnocypris przewalskii, is one of the dominant aquaculture fish species in Qinghai Province, China. Its wild stocks have severely suffered from overfishing, and the farming species are vulnerable to various pathogens infections. Here we report the first immune-related tissues transcriptome of a wild naked carp using a deep sequencing approach. A total of 158,087 unigenes are generated, 2687 gill-specific gene and 3215 kidney-specific genes are identified, respectively. Gene ontology analysis shows that 51,671 unigenes are involved in three major functional categories: biological process, cellular component, and molecular function. Further analysis shows that numerous consensus sequences are homologous to known immune-related genes. Pathways mapping annotate 56,270 unigenes and identify a large number of immune-related pathways. In addition, we focus on the immune-related genes and gene family in Toll-like receptor signaling pathway involved in innate immunity, including toll-like receptors (TLRs), interferon regulatory factors (IRFs), interleukins (ILs) and tumor necrosis factors (TNFs). Eventually, we identify 5 TLRs, 4 IRFs, 3 ILs and 2 TNFs with a completed coding sequence though mining the transcriptome data. Phylogeny analysis shows these genes of naked carp are mostly close to zebrafish. Protein domain and selection pressure analyses together show that all these genes are highly conserved in gene sequence and protein domain structure with other species, and purifying selection underwent in these genes, implied functionally important features are conserved in the genes above. Intriguingly, we detect positive selection signals in naked carp TLR4, and significant divergence occurred among tested species TLR4, suggested that naked carp TLR4 function may be affected. Finally, we identify 23,867 simple sequence repeat (SSR) marks in this transcriptome. Taken together, this study not only contributes a large number of candidate genes in naked carp

  2. Immune response

    MedlinePlus

    Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense system ...

  3. Profiling and Improving I/O Performance of a Large-Scale Climate Scientific Application

    NASA Technical Reports Server (NTRS)

    Liu, Zhuo; Wang, Bin; Wang, Teng; Tian, Yuan; Xu, Cong; Wang, Yandong; Yu, Weikuan; Cruz, Carlos A.; Zhou, Shujia; Clune, Tom; Klasky, Scott

    2013-01-01

    Exascale computing systems are soon to emerge, which will pose great challenges on the huge gap between computing and I/O performance. Many large-scale scientific applications play an important role in our daily life. The huge amounts of data generated by such applications require highly parallel and efficient I/O management policies. In this paper, we adopt a mission-critical scientific application, GEOS-5, as a case to profile and analyze the communication and I/O issues that are preventing applications from fully utilizing the underlying parallel storage systems. Through in-detail architectural and experimental characterization, we observe that current legacy I/O schemes incur significant network communication overheads and are unable to fully parallelize the data access, thus degrading applications' I/O performance and scalability. To address these inefficiencies, we redesign its I/O framework along with a set of parallel I/O techniques to achieve high scalability and performance. Evaluation results on the NASA discover cluster show that our optimization of GEOS-5 with ADIOS has led to significant performance improvements compared to the original GEOS-5 implementation.

  4. Molecular profiling of thyroid cancer subtypes using large-scale text mining

    PubMed Central

    2014-01-01

    Background Thyroid cancer is the most common endocrine tumor with a steady increase in incidence. It is classified into multiple histopathological subtypes with potentially distinct molecular mechanisms. Identifying the most relevant genes and biological pathways reported in the thyroid cancer literature is vital for understanding of the disease and developing targeted therapeutics. Results We developed a large-scale text mining system to generate a molecular profiling of thyroid cancer subtypes. The system first uses a subtype classification method for the thyroid cancer literature, which employs a scoring scheme to assign different subtypes to articles. We evaluated the classification method on a gold standard derived from the PubMed Supplementary Concept annotations, achieving a micro-average F1-score of 85.9% for primary subtypes. We then used the subtype classification results to extract genes and pathways associated with different thyroid cancer subtypes and successfully unveiled important genes and pathways, including some instances that are missing from current manually annotated databases or most recent review articles. Conclusions Identification of key genes and pathways plays a central role in understanding the molecular biology of thyroid cancer. An integration of subtype context can allow prioritized screening for diagnostic biomarkers and novel molecular targeted therapeutics. Source code used for this study is made freely available online at https://github.com/chengkun-wu/GenesThyCan. PMID:25521965

  5. The Rosenberg Self-Esteem Scale and Harter's Self-Perception Profile for Adolescents: A Concurrent Validity Study.

    ERIC Educational Resources Information Center

    Hagborg, Winston J.

    1993-01-01

    Administered Rosenberg Self-Esteem Scale (RSE) and Harter's Self-Perception Profile for Adolescents to 150 adolescents in grades 8 through 12. Correlational and cross-validation multiple regression analyses found that RSE total score and both its factor scores were strongly related to Global Self-Worth. Females reported significantly lower RSE…

  6. The Feasibility of Constructing Profiles of Native Americans from the People of Color Racial Identity Attitude Scale: A Brief Report.

    ERIC Educational Resources Information Center

    Bryant, Alfred, Jr.; Baker, Stanley B.

    2003-01-01

    One hundred and fifty Lumbee Native American college students participated in an investigation of the feasibility of constructing profiles of Native Americans from the People of Color Racial Identity Attitude Scale. Findings suggest that Helms's instrument may be feasible for constructing racial identity attitudes of Native Americans. (Contains 26…

  7. Measuring Child Poverty in South Africa: Sensitivity to the Choice of Equivalence Scale and an Updated Profile

    ERIC Educational Resources Information Center

    Streak, Judith Christine; Yu, Derek; Van der Berg, Servaas

    2009-01-01

    This paper offers evidence on the sensitivity of child poverty in South Africa to changes in the adult equivalence scale (AES) and updates the child poverty profile based on the Income and Expenditure Survey 2005/06. Setting the poverty line at the 40th percentile of households calculated with different AESs the scope and composition of child…

  8. Measuring the Interactive Skills of Caregivers in Child Care Centers: Development and Validation of the Caregiver Interaction Profile Scales

    ERIC Educational Resources Information Center

    Helmerhorst, Katrien O. W.; Riksen-Walraven, J. Marianne; Vermeer, Harriet J.; Fukkink, Ruben G.; Tavecchio, Louis W. C.

    2014-01-01

    Research Findings: High-quality caregiver-child interactions constitute the core of high-quality child care for young children. This article describes the background and development of the Caregiver Interaction Profile (CIP) scales to rate 6 key skills of caregivers for interacting with 0-to 4-year-old children in child care centers: sensitive…

  9. Factor Structure and Reliability of the Dutch Version of Seven Scales of the Communication Profile for the Hearing Impaired (CPHI)

    ERIC Educational Resources Information Center

    Mokkink, Lidwine B.; Knol, Dirk L.; Zekveld, Adriana A.; Goverts, S. Theo; Kramer, Sophia E.

    2009-01-01

    Purpose: Seven scales of the Communication Profile for the Hearing Impaired (CPHI; M. E. Demorest & S. A. Erdman, 1987) were translated into Dutch: Maladaptive Behavior, Verbal Strategies, and Nonverbal Strategies (within the area of Communication Strategies) and Self-Acceptance, Acceptance of Loss, Stress, and Withdrawal (within the area of…

  10. Differential profiles of immune mediators and in vitro HIV infectivity between endocervical and vaginal secretions from women with Chlamydia trachomatis infection: A pilot study☆

    PubMed Central

    Sperling, Rhoda; Kraus, Thomas A.; Ding, Jian; Veretennikova, Alina; Lorde-Rollins, Elizabeth; Singh, Tricia; Lo, Yungtai; Quayle, Alison J.; Chang, Theresa L.

    2013-01-01

    Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection. PMID:23993451

  11. Community Immunity (Herd Immunity)

    MedlinePlus

    ... Content Marketing Share this: Main Content Area ​Community Immunity ("Herd" Immunity) Vaccines can prevent outbreaks of disease and save ... disease is contained. This is known as "community immunity." In the illustration below, the top box depicts ...

  12. Cross Racial Identity Scale (CRIS) scores and profiles in African American adolescents involved with the juvenile justice system.

    PubMed

    Worrell, Frank C; Andretta, James R; Woodland, Malcolm H

    2014-10-01

    In this study, we examined the internal consistency and structural validity of Cross Racial Identity Scale (CRIS) scores in a sample of 477 African American adolescents who had been arrested in a city in the mid-Atlantic. Using cluster analysis, we also identified profiles of CRIS scores and compared adolescents with different profiles on Major Depressive Episode, Manic Episode, Generalized Anxiety Disorder, and Obsessive-Compulsive Disorder scores. Results indicated that CRIS subscale scores were reliable, and the 6-factor structure of the CRIS was supported. Five nigrescence profiles were identified: Miseducation-Pro-Black, Conflicted-Self-Hatred, Multiculturalist, Low Race Salience, and Conflicted-Anti-White. Individuals with Conflicted-Self-Hatred profiles reported significantly and meaningfully higher scores on the 4 syndromes than did their peers, and individuals with the Multiculturalist and Low Race Salience profiles reported the lowest scores. A greater percentage of individuals with Conflicted racial identity profiles had syndrome scores in the clinically significant range. The results of this study demonstrate that some of the nigrescence profiles found in college-age students generalize to adolescents. The implications of the findings for theory, research, and practice are discussed. PMID:25151117

  13. The fight-or-flight response is associated with PBMC expression profiles related to immune defence and recovery in swine.

    PubMed

    Oster, Michael; Scheel, Mathias; Muráni, Eduard; Ponsuksili, Siriluck; Zebunke, Manuela; Puppe, Birger; Wimmers, Klaus

    2015-01-01

    Defining phenotypes according to molecular features would promote the knowledge of functional traits like behaviour in both human and animal research. Beside physiological states or environmental factors, an innate predisposition of individual coping strategies was discussed, including the proactive and reactive pattern. According to backtest reactivity, animals assigned as high-resisting (proactive) and low-resisting (reactive) were immune challenged with tetanus toxoid in a time course experiment. Using the Affymetrix platform and qPCR, individual coping characteristics were reflected as gene expression signatures in porcine peripheral blood mononuclear cells (PBMC) at naïve state (day 0) and in response to the model antigen (day 14, day 28, and day 140). Further, the blood cell count was analysed at all stages. On the transcriptional level, processes acting on cell communication, vasculogenesis, and blood coagulation were highlighted in high-resisting animals at naïve state (day 0), temporarily blurred due to immune challenge (day 14) but subsequently restored and intensified (day 28). Notably, similar amounts of white and red blood cells, platelets and haematocrit between high-resisting and low-resisting samples suggest coping-specific expression patterns rather than alterations in blood cell distribution. Taken together, the gene expression patterns indicate that proactive pigs might favour molecular pathways enabling an effective strategy for defence and recovery. This corroborates the previously suggested belief, that proactive animals are prone to an increased number of injuries as an evolutionary inherited mechanism. In contrast to previous assumptions, coping-specific immunity in pigs lacks inherited shifts between cellular and humoral immune responses. PMID:25793368

  14. The impacts of invaders: basal and acute stress glucocorticoid profiles and immune function in native lizards threatened by invasive ants.

    PubMed

    Graham, Sean P; Freidenfelds, Nicole A; McCormick, Gail L; Langkilde, Tracy

    2012-05-01

    As anthropogenic stressors increase exponentially in the coming decades, native vertebrates will likely face increasing threats from these novel challenges. The success or failure of the primary physiological mediator of these stressors--the HPA axis--will likely involve numerous and chaotic outcomes. Among the most challenging of these new threats are invasive species. These have the capacity to simultaneously challenge the HPA axis and the immune system as they are often associated with, or the cause of, emerging infectious diseases, and energetic tradeoffs with the HPA response can have immunosuppressive effects. To determine the effects of invasive species on the vertebrate GC response to a novel stressor, and on immunity, we examined the effects of invasive fire ants on native lizards, comparing lizards from sites with long histories with fire ants to those outside the invasion zone. We demonstrated higher baseline and acute stress (captive restraint) CORT levels in lizards from within fire ant invaded areas; females are more strongly affected than males, suggesting context-specific effects of invasion. We found no effect of fire ant invasion on the immune parameters we measured (complement bacterial lysis and antibody hemagglutination) with the exception of ectoparasite infestation. Mites were far less prevalent on lizards within fire ant invaded sites, suggesting fire ants may actually benefit lizards in this regard. This study suggests that invasive species may impose physiological stress on native vertebrates, but that the consequences of this stress may be complicated and unpredictable. PMID:22226759

  15. Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes.

    PubMed

    Boggaram, Vijay; Loose, David S; Gottipati, Koteswara R; Natarajan, Kartiga; Mitchell, Courtney T

    2016-04-01

    The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1β, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells. PMID:26884459

  16. Population-scale three-dimensional reconstruction and quantitative profiling of microglia arbors

    PubMed Central

    Rey-Villamizar, Nicolas; Merouane, Amine; Lu, Yanbin; Mukherjee, Amit; Trett, Kristen; Chong, Peter; Harris, Carolyn; Shain, William; Roysam, Badrinath

    2015-01-01

    Motivation: The arbor morphologies of brain microglia are important indicators of cell activation. This article fills the need for accurate, robust, adaptive and scalable methods for reconstructing 3-D microglial arbors and quantitatively mapping microglia activation states over extended brain tissue regions. Results: Thick rat brain sections (100–300 µm) were multiplex immunolabeled for IBA1 and Hoechst, and imaged by step-and-image confocal microscopy with automated 3-D image mosaicing, producing seamless images of extended brain regions (e.g. 5903 × 9874 × 229 voxels). An over-complete dictionary-based model was learned for the image-specific local structure of microglial processes. The microglial arbors were reconstructed seamlessly using an automated and scalable algorithm that exploits microglia-specific constraints. This method detected 80.1 and 92.8% more centered arbor points, and 53.5 and 55.5% fewer spurious points than existing vesselness and LoG-based methods, respectively, and the traces were 13.1 and 15.5% more accurate based on the DIADEM metric. The arbor morphologies were quantified using Scorcioni’s L-measure. Coifman’s harmonic co-clustering revealed four morphologically distinct classes that concord with known microglia activation patterns. This enabled us to map spatial distributions of microglial activation and cell abundances. Availability and implementation: Experimental protocols, sample datasets, scalable open-source multi-threaded software implementation (C++, MATLAB) in the electronic supplement, and website (www.farsight-toolkit.org). http://www.farsight-toolkit.org/wiki/Population-scale_Three-dimensional_Reconstruction_and_Quanti-tative_Profiling_of_Microglia_Arbors Contact: broysam@central.uh.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701570

  17. MicroRNA Profile in CD8+ T-Lymphocytes from HIV-Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression

    PubMed Central

    Bargalló, Manel E.; Planet, Evarist; Vilaplana, Elisenda; Escribà, Tuixent; Pérez, Iñaki; Gatell, Josep Maria; García, Felipe; Arnedo, Mireia; Plana M, Montserrat

    2016-01-01

    Background The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response. Methods miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms. Results A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response. Conclusions Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non

  18. Administration of Lactobacillus evokes coordinated changes in the intestinal expression profile of genes regulating energy homeostasis and immune phenotype in mice.

    PubMed

    Nerstedt, Annika; Nilsson, Elisabeth C; Ohlson, Kajsa; Håkansson, Janet; Thomas Svensson, L; Löwenadler, Björn; Svensson, Ulla K; Mahlapuu, Margit

    2007-06-01

    Lactic acid bacteria are probiotics widely used in functional food products, with a variety of beneficial effects reported. Recently, intense research has been carried out to provide insight into the mechanism of the action of probiotic bacteria. We have used gene array technology to map the pattern of changes in the global gene expression profile of the host caused by Lactobacillus administration. Affymetrix microarrays were applied to comparatively characterize differences in gene transcription in the distal ileum of normal microflora (NMF) and germ-free (GF) mice evoked by oral administration of two Lactobacillus strains used in fermented dairy products today - Lactobacillus paracasei ssp. paracasei F19 (L. F19) or Lactobacillus acidophilus NCFB 1748. We show that feeding either of the two strains caused very similar effects on the transcriptional profile of the host. Both L. F19 and L. acidophilus NCFB 1748 evoked a complex response in the gut, reflected by differential regulation of a number of genes involved in essential physiological functions such as immune response, regulation of energy homeostasis and host defence. Notably, the changes in intestinal gene expression caused by Lactobacillus were different in the mice raised under GF v. NMF conditions, underlying the complex and dynamic nature of the host-commensal relationship. Differential expression of an array of genes described in this report evokes novel hypothesis of possible interactions between the probiotic bacteria and the host organism and warrants further studies to evaluate the functional significance of these transcriptional changes on the metabolic profile of the host. PMID:17433125

  19. Yeast-containing feed additive alters gene expression profiles associated with innate immunity in whole blood of a rodent model.

    PubMed

    Branson, Jennifer A; McLean, Derek J; Forsberg, Neil E; Bobe, Gerd

    2016-05-01

    Feeding a yeast-containing additive (YCA; OmniGen-AF) improves immune responses in ruminant livestock and reduces subsequent production losses. The objective was to identify molecular pathways by which dietary YCA may modify immune responses using a rodent model. Thirty-seven healthy, unchallenged CD rats received a diet containing 0 (control; n = 5, only 28 d), 0.5% (n = 15) or 1% (n = 17) YCA for 7 (n = 4/group), 14 (n = 3 or 4/group), 21 (n = 3 or 4/group) or 28 (n = 5/group) d. At the end of the feeding periods, whole blood was collected and the isolated RNA was analyzed for the expression of 84 genes involved in innate and cell-mediated adaptive immune responses. Three bacterial pattern recognition receptors TLR1 (0.5%: + 2.01; 1%: + 2.38), TLR6 (0.5%: + 2.11; 1%: + 2.34) and NOD2 (0.5%: + 2.32; 1%: + 2.23), two APC surface receptors CD1D1 (0.5%: + 1.75; 1%: + 2.33) and CD80 (0.5%: +2.45; 1%: +3.00), and the cell signaling molecule MAPK8 (0.5%: +1.87; 1%: +2.35) were significantly up-regulated by YCA at both inclusion rates. In conclusion, feeding YCA may potentially increase recognition and responses to bacterial pathogens and T-cell activation and differentiation and thereby maintain health and prevent production losses. PMID:27033362

  20. Global Gene Expression Profiling of Myeloid Immune Cell Subsets in Response to In Vitro Challenge with Porcine Circovirus 2b

    PubMed Central

    Mavrommatis, Bettina; Offord, Victoria; Patterson, Robert; Watson, Mick; Kanellos, Theo; Steinbach, Falko; Grierson, Sylvia; Werling, Dirk

    2014-01-01

    Compelling evidence suggests that the early interaction between porcine circovirus 2 (PCV-2) and the innate immune system is the key event in the pathogenesis of Post-Weaning Multisystemic Wasting Syndrome (PMWS). Furthermore, PCV2 has been detected in bone-marrow samples, potentially enabling an easy spread and reservoir for the virus. To assess the gene-expression differences induced by an in-vitro PCV2b infection in different three different myeloid innate immune cell subsets generated from the same animal, we used the Agilent Porcine Gene Expression Microarray (V2). Alveolar macrophages (AMØs), monocyte-derived dendritic cells (MoDCs) and bone-marrow cells (BMCs) were generated from each animal, and challenged with a UK-isolate of a PCV2 genotype b-strain at a MOI of 0.5. Remarkably, analysis showed a highly distinct and cell-type dependent response to PCV2b challenge. Overall, MoDCs showed the most marked response to PCV2b challenge in vitro and revealed a key role for TNF in the interaction with PCV2b, whereas only few genes were affected in BMCs and AMØs. These observations were further supported by an enrichment of genes in the downstream NF-κB Signalling pathway as well as an up regulation of genes with pro-apoptotic functions post-challenge. PCV2b challenge increases the expression of a large number of immune-related and pro-apoptotic genes mainly in MoDC, which possibly explain the increased inflammation, granulomatous inflammation and lymphocyte depletion seen in PMWS-affected pigs. PMID:24618842

  1. Behavioral coping strategies in response to social stress are associated with distinct neuroendocrine, monoaminergic and immune response profiles in mice.

    PubMed

    De Miguel, Zurine; Vegas, Oscar; Garmendia, Larraitz; Arregi, Amaia; Beitia, Garikoitz; Azpiroz, Arantza

    2011-12-01

    Individual variation in behavioral coping strategies to stress implies that animals may have a distinct physiological adaptation to stress; these differences may underlie differences in vulnerability to stress-related diseases. This study was designed to test the hypothesis that different behavioral coping strategies (active vs. passive) are stable over time and that they would be associated with differences in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adreno-medular (SAM) axes, and monoaminergic and immune activity. Male mice were subjected to social stress. Twelve days after the first social interaction, mice were subjected to a second identical social stress interaction. Behavior was videotaped and assessed during both sessions. One hour after the final social interaction, serum was collected for corticosterone and adrenaline concentrations and brains were collected for hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression. Monoaminergic system activity was determined by mRNA expression of serotonin, dopamine and noradrenaline synthetic enzymes in the brain stem. Immune system activity was determined by mRNA expression of hypothalamic interleukin-1β (IL-1β) and splenic IL-1β and interleukin-2 (IL-2). Mice engaging in a passive strategy had higher serum corticosterone and lower serum adrenaline concentrations than the active group. The passive group showed lower hypothalamic mRNA expression of IL-1β and CRH and lower splenic mRNA expression of IL-2 and IL-1β relative to mice in the active group. An active strategy was associated with higher expression of the dopaminergic synthetic enzyme, while a passive strategy was associated with decreased expression of the serotonergic synthetic enzyme. These findings indicate that individual coping strategies are stable over time and are related to differences in the physiological stress response and immune activity. PMID:21864582

  2. West Nile Virus Challenge Alters the Transcription Profiles of Innate Immune Genes in Rabbit Peripheral Blood Mononuclear Cells

    PubMed Central

    Uddin, Muhammad J.; Suen, Willy W.; Prow, Natalie A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

    2015-01-01

    The peripheral innate immune response to West Nile virus (WNV) is crucial for control of virus spread to the central nervous system. Therefore, transcriptomes encoding the innate immune response proteins against WNV were investigated in peripheral blood mononuclear cells (PBMCs) of New Zealand White rabbits, a recently established novel rabbit model for WNV pathogenesis studies. PBMCs were challenged with an Australian WNV strain, WNVNSW2011, in vitro, and mRNA expression of selected immune response genes were quantified at 2-, 6-, 12-, and 24-h post-infection (pi) using qRT-PCR. Compared to mock-inoculated PBMCs, WNV-stimulated PBMCs expressed high levels of interferon (IFN) alpha (IFNA), gamma (IFNG), IL6, IL12, IL22, CXCL10, and pentraxin 3 (PTX3) mRNA. Likewise, TLR1, 2, 3, 4, 6, and 10 mRNA became up-regulated with the highest expression seen for TLR3, 4, and 6. TLRs-signaling downstream genes (MyD88, STAT1, TRAF3, IRF7, and IRF9) subsequently became up-regulated. The high expression of IFNs, TLR3, TLR4, TRAF3, STAT1, IRF7, and IRF9 are in accordance with antiviral activities, while expression of TNFA, HO1, iNOS, caspase 3, and caspase 9 transcripts suggests the involvement of oxidative stress and apoptosis in WNV-stimulated rabbit PBMCs, respectively. The level of WNVNSW2011 RNA increased at 24-h pi in PBMCs challenged with virus in vitro compared to input virus. The expression dynamics of selected genes were validated in PBMCs from rabbits experimentally infected with WNV in vivo. Higher expression of IFNA, IFN beta (IFNB), IFNG, TNFA, IL6, IL22, PTX3, TLR3 and TLR4, IRF7, IRF9, STST1, TRAF3, caspase 3, and caspase 9 were seen in PBMCs from WNV-infected rabbits on day 3 post-intradermal virus inoculation compared to PBMCs from uninfected control rabbits. This study highlights the array of cytokines and TLRs involved in the host innate immune response to WNV in the rabbit leukocytes and suggests that these cells may be a useful in vitro model for WNV

  3. Mesenchymal Stem Cells Derived from Human Exfoliated Deciduous Teeth (SHEDs) Induce Immune Modulatory Profile in Monocyte-Derived Dendritic Cells

    PubMed Central

    Silva, Fernando de Sá; Ramos, Rodrigo Nalio; de Almeida, Danilo Candido; Bassi, Enio Jose; Gonzales, Roberto Pereira; Miyagi, Sueli Patricia Harumi; Maranduba, Claudinéia Pereira; Sant'Anna, Osvaldo Augusto Brazil Esteves; Marques, Márcia Martins; Barbuto, José Alexandre Marzagão; Câmara, Niels Olsen Saraiva; da Costa Maranduba, Carlos Magno

    2014-01-01

    Background Mesenchymal stem cells have prominent immune modulatory properties, which may have clinical applications; however their major source, bone marrow, is of limited availability. On the other hand, mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs) are readily accessible, but their immune regulatory properties have not been completely investigated. This study was designed, therefore, to evaluate the SHEDs influence on DCs differentiation, maturation, ability to activate T cells and to expand CD4+Foxp3+ T cells. Methodology/Principal Findings The experiments were based in cellular co-culture during differentiation and maturation of monocyte derived-DCs (moDCs), with, or not, presence of SHEDs. After co-culture with SHEDs, (moDCs) presented lower expression of BDCA-1 and CD11c, in comparison to DC cultivated without SHEDs. CD40, CD80, CD83 and CD86 levels were also decreased in mature DCs (mDCs) after co-cultivation with SHEDs. To assess the ability of SHEDs-exposed moDCs to modulate T cell responses, the former were separated from SHEDs, and co-cultured with peripheral blood lymphocytes. After 5 days, the proliferation of CD4+ and CD8+ T cells was evaluated and found to be lower than that induced by moDCs cultivated without SHEDs. In addition, an increase in the proportion of CD4+Foxp3+IL-10+ T cells was observed among cells stimulated by mature moDCs that were previously cultivated with SHEDs. Soluble factors released during co-cultures also showed a reduction in the pro-inflammatory cytokines (IL-2, TNF-α and IFN-γ), and an increase in the anti-inflammatory molecule IL-10. Conclusion/Significance This study shows that SHEDs induce an immune regulatory phenotype in moDCs cells, evidenced by changes in maturation and differentiation rates, inhibition of lymphocyte stimulation and ability to expand CD4+Foxp3+ T cells. Further characterization and validation of this phenomenon could support the use of SHEDs, directly or indirectly

  4. Profiles of Personal Resiliency for Normative and Clinical Samples of Youth Assessed by the Resiliency Scales for Children and Adolescents[TM

    ERIC Educational Resources Information Center

    Prince-Embury, Sandra; Steer, Robert A.

    2010-01-01

    Cluster analyses with the three global scores of the Resiliency Scales for Children and Adolescents[TM] (RSCA) were used to determine personal resiliency profiles within normative (641) and outpatient clinical (285) samples of youth aged 9 to 18 years. Normative and clinical profiles were compared with each other and the clinical profiles were…

  5. Molecular aspects, genomic arrangement and immune responsive mRNA expression profiles of two CXC chemokine receptor homologs (CXCR1 and CXCR2) from rock bream, Oplegnathus fasciatus.

    PubMed

    Umasuthan, Navaneethaiyer; Wan, Qiang; Revathy, Kasthuri Saranya; Whang, Ilson; Noh, Jae Koo; Kim, Seokryel; Park, Myoung-Ae; Lee, Jehee

    2014-09-01

    The CXCR1 and CXCR2 are the prototypical receptors and are the only known receptors for mammalian ELR+ (Glu-Leu-Arg) CXC chemokines, including CXCL8 (interleukin 8). These receptors transduce the ELR+ chemokine signals and operate the downstream signaling pathways in inflammation and innate immunity. In this study, we report the identification and characterization of CXCR1 and CXCR2 genes from rock bream fish (OfCXCR1 and OfCXCR2) at the molecular level. The cDNA and genomic DNA sequences of the OfCXCR1 and OfCXCR2 were identified from a transcriptome library and a custom-constructed BAC library, respectively. Both OfCXCR genes consisted of two exons, separated by an intron. The 5'-flanking regions of OfCXCR genes possessed multiple putative transcription factor binding sites related to immune response. The coding sequences of OfCXCR1 and OfCXCR2 encoded putative peptides of 355 and 360 amino acids (aa), respectively. The deduced aa sequences of OfCXCR1 and OfCXCR2 comprised of a G-protein coupled receptors (GPCR) family 1 profile with a GPCR signature and a DRY motif. In addition, seven conserved transmembrane regions were predicted in both OfCXCRs. While our multiple alignment study revealed the functionally significant conserved elements of the OfCXCR1 and OfCXCR2, phylogeny analyses further confirmed their position in teleost sub clade, in which they manifested an evolutionary relatedness with other fish counterparts. Based on comparative analyses, teleost CXC chemokine receptors appear to be distinct from their non-fish orthologs in terms of evolution (both CXCR1 and CXCR2) and genomic organization (CXCR2). Quantitative real-time PCR (qPCR) detected the transcripts of OfCXCR1 and OfCXCR2 in eleven examined tissues, with higher levels in head kidney, kidney and spleen highlighting their crucial importance in immunity. In vitro stimulation of peripheral blood leukocytes (PBLs) with concanavalin A (Con A) resulted in modulation of OfCXCR2 transcription, but not

  6. Luminous and Dark Matter Profiles from Galaxies to Clusters: Bridging the Gap with Group-scale Lenses

    NASA Astrophysics Data System (ADS)

    Newman, Andrew B.; Ellis, Richard S.; Treu, Tommaso

    2015-11-01

    Observations of strong gravitational lensing, stellar kinematics, and larger-scale tracers enable accurate measures of the distribution of dark matter (DM) and baryons in massive early-type galaxies (ETGs). While such techniques have been applied to galaxy-scale and cluster-scale lenses, the paucity of intermediate-mass systems with high-quality data has precluded a uniform analysis of mass-dependent trends. With the aim of bridging this gap, we present new observations and analyses of 10 group-scale lenses at < z> =0.36, characterized by Einstein radii {θ }{{Ein}}=2\\buildrel{\\prime\\prime}\\over{.} 5-5\\buildrel{\\prime\\prime}\\over{.} 1 and a mean halo mass of {M}200={10}14.0 {M}ȯ . We measure a mean concentration c200 = 5.0 ± 0.8 consistent with unmodified cold dark matter halos. By combining our data with other lens samples, we analyze the mass structure of ETGs in 1013 {M}ȯ –1015 {M}ȯ halos using homogeneous techniques. We show that the slope of the total density profile γtot within the effective radius depends on the stellar surface density, as demonstrated previously, but also on the halo mass. We analyze these trends using halo occupation models and resolved stellar kinematics with the goal of testing the universality of the DM profile. Whereas the central galaxies of clusters require a shallow inner DM density profile, group-scale lenses are consistent with a Navarro–Frenk–White profile or one that is slightly contracted. The largest uncertainties arise from the sample size and likely radial gradients in stellar populations. We conclude that the net effect of baryons on the DM distribution may not be universal, but more likely varies with halo mass due to underlying trends in star formation efficiency and assembly history.

  7. Prince-Embury, S. (2007, 2006). "Resiliency Scales for Children and Adolescents: A Profile of Personal Strengths". San Antonio, TX: Harcourt Assessment, Inc.

    ERIC Educational Resources Information Center

    Thorne, Keoma J.; Kohut, Candace S.

    2007-01-01

    The "Resiliency Scales for Children and Adolescents: A Profile of Personal Strengths" (Resiliency Scales; Prince-Embury, 2007) provides a quick and easy individually or group administered self-report of personal strengths and vulnerabilities in children and adolescents. The Resiliency Scales comprise the following three scales: (a) Sense of…

  8. An Exercise on Magnetic-Anomaly Profiles and the Geomagnetic Polar-Reversal Time Scale.

    ERIC Educational Resources Information Center

    Shea, James Herbert

    1988-01-01

    Develops an exercise in which students use magnetic-profile data gathered in the South Pacific to test the Vine-Matthews-Morley hypothesis. Uses the Eltanin 19N and 20N profiles. Relates the exercise to 20 current geology texts. (MVL)

  9. Biomarker Analysis Revealed Distinct Profiles of Innate and Adaptive Immunity in Infants with Ocular Lesions of Congenital Toxoplasmosis

    PubMed Central

    Machado, Anderson Silva; Carneiro, Ana Carolina Aguiar Vasconcelos; Béla, Samantha Ribeiro; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-dos-Reis, Jordana G.; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis; —UFMG-CTBG, UFMG Congenital Toxoplasmosis Brazilian Group

    2014-01-01

    Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14+CD16+HLA-DRhigh monocytes and CD56dim cytotoxic NK-cells in ARL. Moreover, augmented TCRγδ+ and CD8+ T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8+ T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis. PMID:25328286

  10. Biomarker analysis revealed distinct profiles of innate and adaptive immunity in infants with ocular lesions of congenital toxoplasmosis.

    PubMed

    Machado, Anderson Silva; Carneiro, Ana Carolina Aguiar Vasconcelos; Béla, Samantha Ribeiro; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-dos-Reis, Jordana G; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis

    2014-01-01

    Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14(+)CD16(+)HLA-DR(high) monocytes and CD56(dim) cytotoxic NK-cells in ARL. Moreover, augmented TCRγ δ (+) and CD8(+) T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8(+) T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis. PMID:25328286

  11. Immune Suppression and Immune Activation in Depression

    PubMed Central

    Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities

  12. The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

    PubMed Central

    Lo, Chien-Chi; Bonner, Carol A.

    2012-01-01

    Summary: One form of immune evasion is a developmental state called “persistence” whereby chlamydial pathogens respond to the host-mediated withdrawal of l-tryptophan (Trp). A sophisticated survival mode of reversible quiescence is implemented. A mechanism has evolved which suppresses gene products necessary for rapid pathogen proliferation but allows expression of gene products that underlie the morphological and developmental characteristics of persistence. This switch from one translational profile to an alternative translational profile of newly synthesized proteins is proposed to be accomplished by maximizing the Trp content of some proteins needed for rapid proliferation (e.g., ADP/ATP translocase, hexose-phosphate transporter, phosphoenolpyruvate [PEP] carboxykinase, the Trp transporter, the Pmp protein superfamily for cell adhesion and antigenic variation, and components of the cell division pathway) while minimizing the Trp content of other proteins supporting the state of persistence. The Trp starvation mechanism is best understood in the human-Chlamydia trachomatis relationship, but the similarity of up-Trp and down-Trp proteomic profiles in all of the pathogenic Chlamydiaceae suggests that Trp availability is an underlying cue relied upon by this family of pathogens to trigger developmental transitions. The biochemically expensive pathogen strategy of selectively increased Trp usage to guide the translational profile can be leveraged significantly with minimal overall Trp usage by (i) regional concentration of Trp residue placements, (ii) amplified Trp content of a single protein that is required for expression or maturation of multiple proteins with low Trp content, and (iii) Achilles'-heel vulnerabilities of complex pathways to high Trp content of one or a few enzymes. PMID:22688818

  13. A Curative Immune Profile One Week after Treatment of Indian Kala-Azar Patients Predicts Success with a Short-Course Liposomal Amphotericin B Therapy

    PubMed Central

    Mondal, Smriti; Bhattacharya, Pradyot; Rahaman, Mehebubar; Ali, Nahid; Goswami, Rama Prosad

    2010-01-01

    Background The present pilot study investigating the minimum dose for short-course single and double-dose treatment of kala-azar with an apparently new liposomal formulation of amphotericin B, Fungisome, led to identification of immunological components for early detection of success and/or failure to cure. Methods Patients were treated with 5, 7.5 (single-dose) and 10 mg/kg body weight (5 mg/kg double-dose) of Fungisome. Immunological investigations involving plasma cytokines and antigen-specific lymphoproliferation and cytokine responses from PBMCs were carried out before, 1 week after Fungisome treatment, at the time of relapse, and again after conventional amphotericin B treatment. Results At 1-month follow-up all the patients showed 100% initial cure. However, total doses of 5, 7.5 and 10 mg/kg Fungisome showed 60%, 50% and 90% cure, respectively, at 6-months posttreatment. Patients successfully cured demonstrated downregulation of IL-12 and IL-10 in plasma, and two-fold or more elevation of IFN-γ, IL-12 and TNF, and significant down-regulation of IL-10 and TGF-β in culture supernatants 1-week posttreatment irrespective of drug-dose. A differential immune profile, involving insignificant decline in IL-10 and IL-12 in plasma and negligible elevation of IFN-γ, IL-12 and TNF, and persistence of IL-10, despite decline in TGF-β in culture supernatants, in apparently cured individuals, corresponded with relapse within 6-months of treatment. Conclusion Immunological investigations revealed significant curative and non-curative immunomodulation 1-week posttreatment, correlating with successful cure and relapse, respectively. Although immune-correlation was dose-independent, almost consistent curative response in patients treated with the highest dose 10 mg/kg reflected a definitive impact of the higher-dose on the immune response. Trial registration name and number Clinical Trials Registry - India (CTRI) CTRI/2009/091/000764 PMID:20668544

  14. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function.

    PubMed

    Reddy, Manjula; Eirikis, Edward; Davis, Cuc; Davis, Hugh M; Prabhakar, Uma

    2004-10-01

    Activation of lymphocytes is a complex, yet finely regulated cascade of events that results in the expression of cytokine receptors, production and secretion of cytokines and expression of several cell surface molecules that eventually lead to divergent immune responses. Assessing the qualitative and quantitative nature of lymphocyte function following immunotherapy provides valuable information about the immune responses mediated by a therapeutic agent. To facilitate evaluation of the immunomodulatory activity of therapeutic agents, we have established a platform of in vitro immunoassays with normal human peripheral blood mononuclear cells (PBMCs) treated with several polyclonal activators that are known to exhibit different modes of action. We evaluated the kinetics of cell surface marker expression and cytokine release from PBMCs stimulated in parallel with various activating agents over a time course. These stimulating agents induced early (CD69 and CD71) and late (CD25 and HLA-DR) activation markers to varying antigen densities, indicated different cytokine profiles, and showed differential inhibition with dexamethasone (DEX), an inhibitor of early signaling events. Based on the association or correlation of the kinetics of activation marker expression and secreted cytokines, the results of our study indicate the appropriate time points for the simultaneous measurement of both these activation products. This study defines the kinetics for both measures of T cell activation and provides a comprehensive review with various polyclonal activators that can serve as a reference for monitoring lymphocyte function in clinical study samples. PMID:15541283

  15. The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer.

    PubMed

    Wichmann, Gunnar; Rosolowski, Maciej; Krohn, Knut; Kreuz, Markus; Boehm, Andreas; Reiche, Anett; Scharrer, Ulrike; Halama, Dirk; Bertolini, Julia; Bauer, Ulrike; Holzinger, Dana; Pawlita, Michael; Hess, Jochen; Engel, Christoph; Hasenclever, Dirk; Scholz, Markus; Ahnert, Peter; Kirsten, Holger; Hemprich, Alexander; Wittekind, Christian; Herbarth, Olf; Horn, Friedemann; Dietz, Andreas; Loeffler, Markus

    2015-12-15

    Stratification of head and neck squamous cell carcinomas (HNSCC) based on HPV16 DNA and RNA status, gene expression patterns, and mutated candidate genes may facilitate patient treatment decision. We characterize head and neck squamous cell carcinomas (HNSCC) with different HPV16 DNA and RNA (E6*I) status from 290 consecutively recruited patients by gene expression profiling and targeted sequencing of 50 genes. We show that tumors with transcriptionally inactive HPV16 (DNA+ RNA-) are similar to HPV-negative (DNA-) tumors regarding gene expression and frequency of TP53 mutations (47%, 8/17 and 43%, 72/167, respectively). We also find that an immune response-related gene expression cluster is associated with lymph node metastasis, independent of HPV16 status and that disruptive TP53 mutations are associated with lymph node metastasis in HPV16 DNA- tumors. We validate each of these associations in another large data set. Four gene expression clusters which we identify differ moderately but significantly in overall survival. Our findings underscore the importance of measuring the HPV16 RNA (E6*I) and TP53-mutation status for patient stratification and identify associations of an immune response-related gene expression cluster and TP53 mutations with lymph node metastasis in HNSCC. PMID:26095926

  16. Effects of dietary n-3 highly unsaturated fatty acids (HUFAs) on growth, fatty acid profiles, antioxidant capacity and immunity of sea cucumber Apostichopus japonicus (Selenka).

    PubMed

    Yu, Haibo; Gao, Qinfeng; Dong, Shuanglin; Zhou, Jishu; Ye, Zhi; Lan, Ying

    2016-07-01

    The present study was conducted to understand the effects of dietary n-3 highly unsaturated fatty acids (HUFAs) on growth, fatty acid profiles, antioxidant capacity and the immunity of sea cucumber Apostichopus japonicus (Selenka). Five experimental diets were prepared, containing graded levels of n-3 HUFAs (0.46%, 0.85%, 1.25%, 1.61% and 1.95%, respectively), and the 0.46% group was used as control group. The specific growth rates, fatty acid profiles, activities and gene expression of antioxidative enzymes and lysozyme of the sea cucumbers that were fed with the 5 experimental diets were determined. The results showed that the specific growth rate of sea cucumbers in all the treatment groups significantly increased compared to the control group (P < 0.05), indicating the positive effects of n-3 HUFAs on the growth of sea cucumbers. The contents of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in the body wall of the sea cucumbers gradually increased with the increasing levels of n-3 HUFAs in the diets. The suitable supplement of n-3 HUFAs in diets improved the activities of superoxide dismutase (SOD) and catalase (CAT) of sea cucumbers by up-regulating the expression of SOD and CAT mRNA in sea cucumbers. However, excess n-3 HUFAs in diets caused lipid peroxidation, inhibited the expression of lysozyme (LSZ) mRNA and decreased the activities of LSZ in sea cucumbers. In summary, the suitable supplement levels of n-3 HUFAs in diets of sea cucumbers A. japonicus were estimated between 0.85% and 1.25% considering the growth performance, cost and the indicators of antioxidant capacity and immunity. PMID:27079426

  17. Characterization of photoresist and simulation of a developed resist profile for the fabrication of gray-scale diffractive optic elements

    NASA Astrophysics Data System (ADS)

    Park, Jong Rak; Sierchio, Justin; Zaverton, Melissa; Kim, Youngsik; Milster, Tom D.

    2012-02-01

    We have characterized a photoresist used for the fabrication of gray-scale diffractive optic elements in terms of Dill's and Mack's model parameters. The resist model parameters were employed for the simulations of developed resist profiles for sawtooth patterns executed by solving the Eikonal equation with the fast-marching method. The simulated results were shown to be in good agreement with empirical data.

  18. RNA-seq Profiles of Immune Related Genes in the Spleen of Necrotic Enteritis-afflicted Chicken Lines.

    PubMed

    Truong, Anh Duc; Hong, Yeong Ho; Lillehoj, Hyun S

    2015-10-01

    The study aimed to compare the necrotic enteritis (NE)-induced transcriptome differences between the spleens of Marek's disease resistant chicken line 6.3 and susceptible line 7.2 co-infected with Eimeria maxima/Clostridium perfringens using RNA-Seq. Total RNA from the spleens of two chicken lines were used to make libraries, generating 42,736,296 and 42,617,720 usable reads, which were assembled into groups of 29,897 and 29,833 mRNA genes, respectively. The transcriptome changes were investigated using the differentially expressed genes (DEGs) package, which indicated 3,255, 2,468 and 2,234 DEGs of line 6.3, line 7.2, and comparison between two lines, respectively (fold change ≥2, p<0.01). The transcription levels of 14 genes identified were further examined using qRT-PCR. The results of qRT-PCR were consistent with the RNA-seq data. All of the DEGs were analysed using gene ontology terms, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the DEGs in each term were found to be more highly expressed in line 6.3 than in line 7.2. RNA-seq analysis indicated 139 immune related genes, 44 CD molecular genes and 150 cytokines genes which were differentially expressed among chicken lines 6.3 and 7.2 (fold change ≥2, p<0.01). Novel mRNA analysis indicated 15,518 novel genes, for which the expression was shown to be higher in line 6.3 than in line 7.2 including some immune-related targets. These findings will help to understand host-pathogen interaction in the spleen and elucidate the mechanism of host genetic control of NE, and provide basis for future studies that can lead to the development of marker-based selection of highly disease-resistant chickens. PMID:26323406

  19. Immunohistochemical study and mRNA cytokine profile of the local immune response in cattle naturally infected with Calicophoron daubneyi.

    PubMed

    Fuertes, Miguel; Manga-González, Yolanda; Benavides, Julio; González-Lanza, M Camino; Giráldez, Francisco Javier; Mezo, Mercedes; González-Warleta, Marta; Fernández, Miguel; Regidor-Cerrillo, Javier; Castaño, Pablo; Royo, Marcos; Ortega-Mora, Luis M; Pérez, Valentín; Ferreras, M Carmen

    2015-11-30

    In order to recognize the local immune response of the definitive host to Calicophoron daubneyi natural infection, an immunohistochemical study was carried out in the reticulum and rumen in 49 naturally infected cattle. The role of cytokines (IL-4 and IL-10 interleukins and IFN-γ) in the activation of specific defence mechanisms was evaluated by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays to study cytokine mRNA expression. In all infected animals, CD3+ T lymphocytes seemed to be the main element of the inflammatory infiltrate in the reticular and ruminal lamina propria at the point of the parasite adhesion. Intraepithelial globule leukocytes also showed immunolabelling for CD3. Most CD3+ cells also expressed CD4 (T cell helper) antigen although sporadic CD8+-cytotoxic lymphocytes were observed. Local expression of IFN-γ was observed in damaged papillae at the site of parasite attachment and in scattered cells in the lamina propria. B cells (CD79αcy+, CD45+ and IgG+) were found constantly in relation to lymphoid aggregates. MAC387 was expressed in squamous epithelium and in macrophages of the lamina propria of affected papillae. Macrophages in this location also stained positively for CD163 and CD68. Intraepithelial Langerhans cells and macrophages located in the lamina propria showed immunopositivity for MHCII in the affected areas. RT-qPCR analysis confirmed a statistical significant increase of IFN-γ, and IL-10 expression (p<0.01) in the rumen associated with the presence of flukes. These findings suggest a predominant Th1 polarized local immune response with the probable involvement of Th regulatory cells in cattle C. daubneyi natural infection. PMID:26508417

  20. The Profile of Immune Modulation by Cannabidiol (CBD) Involves Deregulation of Nuclear Factor of Activated T Cells (NFAT)

    PubMed Central

    Kaplan, Barbara L. F.; Springs, Alison E. B.; Kaminski, Norbert E.

    2009-01-01

    Cannabidiol (CBD) is a cannabinoid compound derived from Cannabis Sativa that does not possess high affinity for either the CB1 or CB2 cannabinoid receptors. Similar to other cannabinoids, we demonstrated previously that CBD suppressed interleukin-2 (IL-2) production from phorbol ester plus calcium ionophore (PMA/Io)-activated murine splenocytes. Thus, the focus of the present studies was to further characterize the effect of CBD on immune function. CBD also suppressed IL-2 and interferon-γ (IFN-γ) mRNA expression, proliferation, and cell surface expression of the IL-2 receptor alpha chain, CD25. While all of these observations support the fact that CBD suppresses T cell function, we now demonstrate that CBD suppressed IL-2 and IFN-γ production in purified splenic T cells. CBD also suppressed activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) transcriptional activity, which are critical regulators of IL-2 and IFN-γ. Furthermore, CBD suppressed the T cell-dependent anti-sheep red blood cell immunoglobulin M antibody forming cell (anti-sRBC IgM AFC) response. Finally, using splenocytes derived from CB1-/-/CB2-/- mice, it was determined that suppression of IL-2 and IFN-γ and suppression of the in vitro anti-sRBC IgM AFC response occurred independently of both CB1 and CB2. However, the magnitude of the immune response to sRBC was significantly depressed in CB1-/-/CB2-/- mice. Taken together, these data suggest that CBD suppresses T cell function and that CB1 and/or CB2 play a critical role in the magnitude of the in vitro anti-sRBC IgM AFC response. PMID:18656454

  1. Immune profile of asplenic patients following single or double vaccine administration: A longitudinal cross-sectional study

    PubMed Central

    Doğan, Sait Murat; Aykas, Ahmet; Yücel, Evrim Şefika; Okut, Gökalp; Şimşek, Cenk; Çayhan, Kürşat; Zengel, Baha; Uslu, Adam

    2015-01-01

    Objective: Splenectomy poses a lifelong threat for the development of uncontrolled sepsis despite vaccination. As it is impractical to measure the levels of each antibody against 23 most frequent bacterial serotypes, different surrogate markers of immune response should be identified. Material and Methods: Forty-eight patients with benign disorders were vaccinated with Pneumo-23 and Act-HIB before or at the day of surgery. The immunological response and opsonization capacity of the patients after splenectomy was analyzed through the quantitative measurement of IgG, IgM, C3, and C4 titers; flow-cytometric analysis of (CD3+) T-lymphocytes and (CD19+) B-lymphocytes; and isolation of CD27+ B cells by immunomagnetic positive selection. Blood samples were drawn at the sixth month and 5 and 7 years after surgery. Results: The mean follow-up period was 98.4 months. All the patients in this series had normal IgG, C3, C4 levels and a normal distribution of CD19+ B-cells and CD8+ T-cells in three follow-up periods. Moreover, C3 levels markedly improved to 133.5±37.3 mg/dL at 5 years and remained stable thereafter. CD19+ B-lymphocyte values have progressively improved to the normal range in 98% patients at 7 years. Further, low levels of CD27+ B-cell population (memory cells) was observed in only 12.5% patients at the last follow-up. Adequate seroconversion of IgG, IgM with normal C3, C4, and CD19+ B-cell levels were accomplished in almost all patients. Early postoperative death and late overwhelming infections did not occur. Conclusion: Our results are indicative of the resumption of the immune function following Pneumo-23 and Act-HIB administrations, instigated by the probable activation of B cells and adequate production of C3, C4, IgG, and IgM antibodies in remote lymphoid tissues. PMID:26504413

  2. RNA-seq Profiles of Immune Related Genes in the Spleen of Necrotic Enteritis-afflicted Chicken Lines

    PubMed Central

    Truong, Anh Duc; Hong, Yeong Ho; Lillehoj, Hyun S.

    2015-01-01

    The study aimed to compare the necrotic enteritis (NE)-induced transcriptome differences between the spleens of Marek’s disease resistant chicken line 6.3 and susceptible line 7.2 co-infected with Eimeria maxima/Clostridium perfringens using RNA-Seq. Total RNA from the spleens of two chicken lines were used to make libraries, generating 42,736,296 and 42,617,720 usable reads, which were assembled into groups of 29,897 and 29,833 mRNA genes, respectively. The transcriptome changes were investigated using the differentially expressed genes (DEGs) package, which indicated 3,255, 2,468 and 2,234 DEGs of line 6.3, line 7.2, and comparison between two lines, respectively (fold change ≥2, p<0.01). The transcription levels of 14 genes identified were further examined using qRT-PCR. The results of qRT-PCR were consistent with the RNA-seq data. All of the DEGs were analysed using gene ontology terms, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the DEGs in each term were found to be more highly expressed in line 6.3 than in line 7.2. RNA-seq analysis indicated 139 immune related genes, 44 CD molecular genes and 150 cytokines genes which were differentially expressed among chicken lines 6.3 and 7.2 (fold change ≥2, p<0.01). Novel mRNA analysis indicated 15,518 novel genes, for which the expression was shown to be higher in line 6.3 than in line 7.2 including some immune-related targets. These findings will help to understand host-pathogen interaction in the spleen and elucidate the mechanism of host genetic control of NE, and provide basis for future studies that can lead to the development of marker-based selection of highly disease-resistant chickens. PMID:26323406

  3. Immune-spaying as an alternative to surgical spaying in Iberian × Duroc females: Effect on the VOC profile of dry-cured shoulders and dry-cured loins as detected by PTR-ToF-MS.

    PubMed

    Gamero-Negrón, Rafael; Sánchez del Pulgar, José; Cappellin, Luca; García, Carmen; Gasperi, Flavia; Biasioli, Franco

    2015-12-01

    Immunocastration in pigs has been proposed as a cruelty-free alternative to surgical castration. In this work the effect of immune-spaying of female pigs on the volatile compound profile of Iberian dry-cured products was evaluated. The head-space volatile compound of dry-cured shoulders and loins from surgically spayed, immune-spayed and entire Iberian × Duroc females was characterized by proton transfer reaction-time of flight-mass spectrometry. It was not possible to identify a significant effect of the castration modality on dry-cured shoulders, probably because of the heterogeneity of samples. Contrarily, Principal Component Analysis of dry-cured loins indicates a better homogeneity of samples and the separation of loins from surgically spayed and immune-spayed females. Some mass peaks tentatively identified as important flavor compounds in dry-cured products, 3-methylbutanal, 2,3-butanedione and 3-methylbutanoic acid, were significantly higher in the immune-spayed females. Therefore, immune-spaying seems to have a negligible effect on the volatile compound profile of dry-cured shoulders, whereas it could affect the VOC profile in the case of dry-cured loins. PMID:26233671

  4. High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry

    PubMed Central

    Nair, Nitya; Newell, Evan W.; Vollmers, Christopher; Quake, Stephen R.; Morton, John M.; Davis, Mark M.; He, Xiao-Song; Greenberg, Harry B.

    2015-01-01

    In-depth phenotyping of human intestinal antibody secreting cells (ASCs) and their precursors is important for developing improved mucosal vaccines. We used single-cell mass cytometry to simultaneously analyze 34 differentiation and trafficking markers on intestinal and circulating B cells. In addition, we labeled rotavirus double-layered particles with a metal isotope and characterized B cells specific to the rotavirus VP6 major structural protein. We describe the heterogeneity of the intestinal B cell compartment, dominated by ASCs with some phenotypic and transcriptional characteristics of long-lived plasma cells. Using principal component analysis, we visualized the phenotypic relationships between major B cell subsets in the intestine and blood, and revealed that IgM+ memory B cells (MBCs) and naïve B cells were phenotypically related as were CD27− MBCs and switched MBCs. ASCs in the intestine and blood were highly clonally related, but associated with distinct trajectories of phenotypic development. VP6-specific B cells were present among diverse B cell subsets in immune donors, including naïve B cells, with phenotypes representative of the overall B cell pool. These data provide a high dimensional view of intestinal B cells and the determinants regulating humoral memory to a ubiquitous, mucosal pathogen at steady-state. PMID:25899688

  5. Immune cell-specific transcriptional profiling highlights distinct molecular pathways controlled by Tob1 upon experimental autoimmune encephalomyelitis.

    PubMed

    Didonna, Alessandro; Cekanaviciute, Egle; Oksenberg, Jorge R; Baranzini, Sergio E

    2016-01-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by focal lymphocytic infiltration, demyelination and neurodegeneration. Despite the recent advances in understanding MS molecular basis, no reliable biomarkers have been identified yet to monitor disease progression. Our group has previously reported that low levels of TOB1 in CD4(+) T cells are strongly associated with a higher risk of MS conversion in individuals experiencing an initial demyelinating event. Consistently, Tob1 ablation in mice exacerbates the clinical phenotype of the MS model experimental autoimmune encephalomyelitis (EAE). To shed light on Tob1 molecular functions in the immune system, we have conducted the first cell-based transcriptomic analysis in Tob1(-/-) and wildtype mice upon EAE. Next-generation sequencing was employed to characterize the changes in gene expression in T and B cells at pre- and post-symptomatic EAE stages. Remarkably, we found only modest overlap among the different genetic signatures, suggesting that Tob1 may control distinct genetic programs in the different cytotypes. This hypothesis was corroborated by gene ontology and global interactome analyses, which highlighted specific cellular pathways in each cellular subset before and after EAE induction. In summary, our work pinpoints a multifaceted activity of Tob1 in both homeostasis and disease progression. PMID:27546286

  6. Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia.

    PubMed

    Mitchell, William Beau; Pinheiro, Mariana P; Boulad, Nayla; Kaplan, David; Edison, Michele N; Psaila, Bethan; Karpoff, Marissa; White, Michael J; Josefsson, Emma C; Kile, Benjamin T; Bussel, James B

    2014-12-01

    Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak, which are regulated by thrombopoietin (TPO)-mediated AKT signaling. Thrombopoietin receptor (TPO-R) signaling might decrease platelet and/or megakaryocyte apoptosis and increase the platelet count. This study therefore explored anti-apoptotic effects of TPO-R-agonists in vivo on platelets of patients with immune thrombocytopenia. Patients received eltrombopag or romiplostim for two weeks. Total, immature, and large platelet counts were assessed as were Bcl-xL inhibitor assay; Bcl-xL Western blot; and flow cytometric (FACS) analysis of the AKT-signaling pathway. Eight/ten patients had platelet responses to eltrombopag and all three to romiplostim. Platelet sensitivity to apoptosis by Bcl-xL inhibition was greater in pretreatment patients than controls. This sensitivity normalized after one week of therapy, but surprisingly returned to pretreatment levels at week two. FACS analysis revealed increased AKT-pathway signaling after one week, followed by a decrease at week two. Platelet counts correlated with the Bcl-xL /Bak ratio. Platelet survival may be enhanced by TPO-R-agonists as a transient decrease in platelet sensitivity to apoptosis was accompanied by transient activation of AKT. However, this mechanism has only a short-lived effect. Megakaryocytes and platelets already present at the start of TPO-R-agonist treatment appear to respond differently than those generated de novo. PMID:25132654

  7. Immune cell-specific transcriptional profiling highlights distinct molecular pathways controlled by Tob1 upon experimental autoimmune encephalomyelitis

    PubMed Central

    Didonna, Alessandro; Cekanaviciute, Egle; Oksenberg, Jorge R.; Baranzini, Sergio E.

    2016-01-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by focal lymphocytic infiltration, demyelination and neurodegeneration. Despite the recent advances in understanding MS molecular basis, no reliable biomarkers have been identified yet to monitor disease progression. Our group has previously reported that low levels of TOB1 in CD4+ T cells are strongly associated with a higher risk of MS conversion in individuals experiencing an initial demyelinating event. Consistently, Tob1 ablation in mice exacerbates the clinical phenotype of the MS model experimental autoimmune encephalomyelitis (EAE). To shed light on Tob1 molecular functions in the immune system, we have conducted the first cell-based transcriptomic analysis in Tob1−/− and wildtype mice upon EAE. Next-generation sequencing was employed to characterize the changes in gene expression in T and B cells at pre- and post-symptomatic EAE stages. Remarkably, we found only modest overlap among the different genetic signatures, suggesting that Tob1 may control distinct genetic programs in the different cytotypes. This hypothesis was corroborated by gene ontology and global interactome analyses, which highlighted specific cellular pathways in each cellular subset before and after EAE induction. In summary, our work pinpoints a multifaceted activity of Tob1 in both homeostasis and disease progression. PMID:27546286

  8. Large-scale profiling of archival lymph nodes reveals pervasive remodeling of the follicular lymphoma methylome.

    PubMed

    Killian, J Keith; Bilke, Sven; Davis, Sean; Walker, Robert L; Killian, M Scott; Jaeger, Erich B; Chen, Yidong; Hipp, Jason; Pittaluga, Stefania; Raffeld, Mark; Cornelison, Robert; Smith, William I; Bibikova, Marina; Fan, Jian-Bing; Emmert-Buck, Michael R; Jaffe, Elaine S; Meltzer, Paul S

    2009-02-01

    Emerging technologies allow broad profiling of the cancer genome for differential DNA methylation relative to benign cells. Herein, bisulfite-modified DNA from lymph nodes with either reactive hyperplasia or follicular lymphoma (FL) were analyzed using a commercial C/UpG genotyping assay. Two hundred fifty-nine differentially methylated targets (DMT) distributed among 183 unique genes were identified in FL. Comparison of matched formalin-fixed, paraffin-embedded and frozen surgical pathology replicates showed the complete preservation of the cancer methylome among differently archived tissue specimens. Analysis of the DMT profile is consistent with a pervasive epigenomic remodeling process in FL that affects predominantly nonlymphoid genes. PMID:19155300

  9. Saturation Profiles from Lab-scale Permittivity Measurements and 2-Phase Flow Models.

    NASA Astrophysics Data System (ADS)

    Gorriti, A. G.

    2005-05-01

    Laboratory fluid-flow experiments through soils are important to study the different fluid-flow processes that occur in the subsurface of the Earth. Most of them, measure the flow conditions at the entry and exit points of the sample, while, the saturation profile in the sample, and its change with time, is unknown. Until now, only very expensive and time-consuming techniques, such as CT or MRI scans, could provide information about the flow in the sample. Now, for the first time, we have developed a technique to measure the saturation profile of soil samples that is cheap and easy. With this technique, we obtain the saturation profiles from the inversion of permittivity measurements. The experimental set-up consists of a coaxial transmission line with a large sample holder (3 cm of diameter and 10 cm long) that allows for fluid-flow through the sample. The complex electric permittivity is reconstructed, per frequency, from the electromagnetic reflection and transmission responses of the line. Relative changes in the permittivity in the order of 1% can be detected over a wide frequency band up to 3 GHz, while the lowest usable frequency depends on the permittivity of the material filling the sample holder. The accurate measurements of permittivity performed with the described tool assume that the measured quantity is an effective property. The assumption then is that the sample is homogeneous. Under non-flowing conditions this can be a reasonable assumption, but during a flow experiment it cannot. This is clear from the fact that the reconstruction of the permittivity of these samples is not successful. The model of the sample must be modified to include the resulting heterogeneity. This is done by assuming a multilayered sample, each layer considered to be homogeneous with a constant permittivity and a known frequency dependence. Minimizing a cost function involving the measured reflection and transmission coefficients and the modelled response of the multilayered

  10. Profiling medical school learning environments in Malaysia: a validation study of the Johns Hopkins Learning Environment Scale

    PubMed Central

    Tackett, Sean; Bakar, Hamidah Abu; Shilkofski, Nicole A.; Coady, Niamh; Rampal, Krishna; Wright, Scott

    2015-01-01

    Purpose: While a strong learning environment is critical to medical student education, the assessment of medical school learning environments has confounded researchers. Our goal was to assess the validity and utility of the Johns Hopkins Learning Environment Scale (JHLES) for preclinical students at three Malaysian medical schools with distinct educational and institutional models. Two schools were new international partnerships, and the third was school leaver program established without international partnership. Methods: First- and second-year students responded anonymously to surveys at the end of the academic year. The surveys included the JHLES, a 28-item survey using five-point Likert scale response options, the Dundee Ready Educational Environment Measure (DREEM), the most widely used method to assess learning environments internationally, a personal growth scale, and single-item global learning environment assessment variables. Results: The overall response rate was 369/429 (86%). After adjusting for the medical school year, gender, and ethnicity of the respondents, the JHLES detected differences across institutions in four out of seven domains (57%), with each school having a unique domain profile. The DREEM detected differences in one out of five categories (20%). The JHLES was more strongly correlated than the DREEM to two thirds of the single-item variables and the personal growth scale. The JHLES showed high internal reliability for the total score (α=0.92) and the seven domains (α, 0.56-0.85). Conclusion: The JHLES detected variation between learning environment domains across three educational settings, thereby creating unique learning environment profiles. Interpretation of these profiles may allow schools to understand how they are currently supporting trainees and identify areas needing attention. PMID:26165949

  11. Immunological profiling of tuberculosis-associated immune reconstitution inflammatory syndrome and non-immune reconstitution inflammatory syndrome death in HIV-infected adults with pulmonary tuberculosis starting antiretroviral therapy: a prospective observational cohort study

    PubMed Central

    Ravimohan, Shruthi; Tamuhla, Neo; Steenhoff, Andrew P.; Letlhogile, Rona; Nfanyana, Kebatshabile; Bellamy, Scarlett L.; MacGregor, Rob Roy; Gross, Robert; Weissman, Drew; Bisson, Gregory P.

    2015-01-01

    Summary Background Patients co-infected with advanced HIV and tuberculosis are at risk of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) and death soon after initiation of antiretroviral therapy (ART). Tuberculosis-associated IRIS has been associated with quicker recovery of cellular immune responses after ART initiation and early mortality with slower recovery of these responses. We aimed to assess whether patients who have these outcomes have distinct immunological profiles before and after ART initiation. Methods We undertook this prospective cohort study at 22 public clinics and the main public hospital in Gaborone, Botswana, in ART-naive adults (aged ≥21 years) with advanced HIV (CD4 cell counts ≤125 cells per μL) and pulmonary tuberculosis. We obtained data for clinical variables and for levels of 29 plasma biomarkers, quantified by Luminex assay. We classified patients as having tuberculosis-associated IRIS, early mortality, or survival without a diagnosis of tuberculosis-associated IRIS (controls), on the basis of outcomes recorded in the 6 months after ART initiation. We used rank-sum or χ² tests, and logistic regression with odds ratios (OR) and 95% CIs, to assess the association between variables measured before and 4 weeks after ART initiation with death and tuberculosis-associated IRIS, compared with controls. Findings Between Nov 12, 2009, and July 3, 2013, we enrolled 201 participants. 31 (15%) patients left the study before ART initiation, leaving 170 (85%) patients for analysis. Patients with tuberculosis-associated IRIS had reduced pre-ART concentrations of several pro-inflammatory biomarkers, including interleukin (IL)-6 (adjusted OR per 1 log10 increase 0·40 [95% CI 0·18–0·89]). However, patients with early death had increased pre-ART concentrations of inflammatory biomarkers, including monocyte chemoattractant protein-1 (adjusted OR 9·0 [95% CI 1·0–80·0]) and tumour necrosis factor (TNF)-α (7·8 [1

  12. Adolescent Risk Behaviors: Studying Typical and Atypical Individuals via Multidimensional Scaling Profile Analysis

    ERIC Educational Resources Information Center

    Dong, Yang; Ding, Cody

    2012-01-01

    Within the framework of problem behavior theory, the purpose of this study was to examine risk behavior profiles of typical and atypical adolescents and the differential outcomes of well-beings for these individuals in the United States. Based on the data from the survey of Health Behavior of School-Aged Children by World Health Organization,…

  13. Dysarthria Impact Profile: Development of a Scale to Measure Psychosocial Effects

    ERIC Educational Resources Information Center

    Walshe, Margaret; Peach, Richard K.; Miller, Nick

    2009-01-01

    Background: The psychosocial impact of acquired dysarthria on the speaker is well recognized. To date, speech-and-language therapists have no instrument available to measure this construct. This has implications for outcome measurement and for planning intervention. This paper describes the Dysarthria Impact Profile (DIP), an instrument that has…

  14. Vineland Adaptive Behavior Scales: II Profile of Young Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Yang, Sabrina; Paynter, Jessica M.; Gilmore, Linda

    2016-01-01

    Adaptive behaviour is a crucial area of assessment for individuals with Autism Spectrum Disorder (ASD). This study examined the adaptive behaviour profile of 77 young children with ASD using the Vineland-II, and analysed factors associated with adaptive functioning. Consistent with previous research with the original Vineland a distinct autism…

  15. Long-term aerosol study on continental scale through EARLINET vertical profiles

    NASA Astrophysics Data System (ADS)

    Mona, Lucia; Pappalardo, Gelsomina; Linne, Holger; Wandinger, Ulla

    2015-04-01

    Lidar techniques offer the opportunity for investigating the aerosol vertical profiles, which is an important information for climatological, meteorological and air quality issues. EARLINET (European Aerosol Research Lidar Network) has been providing aerosol optical properties vertical profiles over Europe since May 2000. Long-term aerosol observations performed within EARLINET allows a climatological study of aerosol properties over Europe. All EARLINET stations perform almost simultaneously measurements three times per week following a scheduling established in 2000. Besides these climatological measurements, additional measurements are performed in order to monitor special events (as volcanic eruptions and desert dust intrusion), for satellite data evaluation and integrated studies and during intensive measurements campaigns. Aerosol optical properties vertical profiles are freely available at www.earlinet.org and through ACRIS data center http://www.actris.net/. This data are currently published on the CERA database with an associated doi number. Based mainly on Raman technique, EARLINET stations typically provide direct measurement of extinction profiles, and therefore of the aerosol optical depth (AOD), a key parameter for understanding the aerosol role on radiation budget. The free troposphere contribution to AOD and altitude of lofted layers are provided thanks to the vertical profiling capability of lidar technique. The representativeness of EARLINET regular scheduling for climatological studies is investigating through the comparison with AERONET and MODIS measurements. We find that the regular measurements schedule is typically sufficient for climatological studies. In addition lidar punctual measurements are representative for a larger area (1°x1°) in a climatological sense. Long term analysis of EARLINET profiles shows that the AOD in generally decreasing over Europe in agreement with both passive-sensors and in situ measurements. Mean vertical

  16. The influence of physical activity on the profile of immune response cells and cytokine synthesis in mice with experimental breast tumors induced by 7,12-dimethylbenzanthracene.

    PubMed

    Abdalla, Douglas R; Murta, Eddie F C; Michelin, Márcia A

    2013-05-01

    This study aims to investigate cytokine synthesis by lymphocytes in the presence of mammary tumors and the interaction with physical activity. For this study, we used 56 female Balb/c, 8-week-old, virgin mice with a body mass between 20 and 30 g. The mice were divided into four groups: a no tumor/nontrained control group; a no tumor/trained group subjected to physical training of swimming in water (30 ± 4°C) for 45 min, five times per week for 8 weeks; a tumor/nontrained (sedentary) group in which the animals received 7,12-dimethylbenzanthracene [(DMBA) 1 mg/ml weekly for 6 weeks)]; and a tumor/trained group in which animals were subjected to the aforementioned DMBA tumor induction and swim training protocols. After the experimental period, immune cells were collected from spleen cell specimens, placed in culture, and stimulated with lipopolysaccharide. The presence of cluster of differentiation (CD)3, CD4, and CD8 markers and the expression of interferon-γ, interleukin (IL)-2, IL-4, IL-10, IL-12, transforming growth factor β, and tumor necrosis factor α cytokines were assessed by flow cytometry and enzyme-linked immunosorbent assay. Physical activity increased the quantities of lymphocytes producing interferon γ, IL-2, IL-12, and tumor necrosis factor α and decreased the quantities of lymphocytes and macrophages expressing IL-4, IL-10, and transforming growth factor β. In contrast, tumor induction, in the absence of swim training, reduced Th1 cytokine levels while increasing the presence of Th2 cytokines and Treg cells. Physical activity promoted reductions in the incidence of tumor development and promoted immune system polarization toward an antitumor Th1 response pattern profile. PMID:22976388

  17. Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components

    PubMed Central

    Chen, Liang; Hu, Peizhen; Li, Zengshan; Chen, Jun; Song, Chaojun; Chen, Lihua; Ting, Jenny Pan-Yun

    2015-01-01

    NLRs (nucleotide-binding domain leucine-rich repeat proteins or NOD-like receptors) are regulators of inflammation and immunity. A subgroup of NLRs and the innate immune receptor, AIM2 (absent-in-melanoma 2), can induce the assembly of a large caspase-1 activating complex called the inflammasome. Other NLRs regulate key signaling pathways such as NF-kB and MAPK. Since inflammation is a central component of colorectal cancer (CRC), this work was undertaken to analyze NLR and AIM2 expression in human CRC by combining bioinformatics analysis and experimental verification using clinical tissue samples. Additional experiments analyzed the association of (i) gene expression and cancer staging, and (ii) gene expression among inflammasome components. Ten public CRC datasets from the Oncomine® Platform were analyzed. Genes analyzed include NLRP1, NLRP3, NLRP6, NLRP12, NLRC3, NLRC4, NLRC5, NOD1, NOD2 and AIM2. Additionally, forty case-matched cancer samples and adjacent healthy control tissues isolated from a cohort of Chinese CRC patients were profiled. Three patterns of gene expression in CRC are shown. The expression of NLRC3, a checkpoint of inflammation, and the inflammasome components NLRP1, NLRP3, NLRC4 and AIM2 were reduced in CRC. NOD1 and NOD2 expression was increased in CRC, while NLRC5, NLRP6 and NLRP12 showed little difference compared to controls. Reduced expression of NLRC3 in CRC was verified in all available databases analyzed and confirmed with our patient cohort. Furthermore, the extent of NLRC3 and AIM2 gene reduction was correlated with cancer progression. This report reveals the potential value of NLR and AIM2 genes as biomarkers of CRC and cancer progression. PMID:26378020

  18. Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components.

    PubMed

    Liu, Rongrong; Truax, Agnieszka D; Chen, Liang; Hu, Peizhen; Li, Zengshan; Chen, Jun; Song, Chaojun; Chen, Lihua; Ting, Jenny Pan-Yun

    2015-10-20

    NLRs (nucleotide-binding domain leucine-rich repeat proteins or NOD-like receptors) are regulators of inflammation and immunity. A subgroup of NLRs and the innate immune receptor, AIM2 (absent-in-melanoma 2), can induce the assembly of a large caspase-1 activating complex called the inflammasome. Other NLRs regulate key signaling pathways such as NF-kB and MAPK. Since inflammation is a central component of colorectal cancer (CRC), this work was undertaken to analyze NLR and AIM2 expression in human CRC by combining bioinformatics analysis and experimental verification using clinical tissue samples. Additional experiments analyzed the association of (i) gene expression and cancer staging, and (ii) gene expression among inflammasome components.Ten public CRC datasets from the Oncomine® Platform were analyzed. Genes analyzed include NLRP1, NLRP3, NLRP6, NLRP12, NLRC3, NLRC4, NLRC5, NOD1, NOD2 and AIM2. Additionally, forty case-matched cancer samples and adjacent healthy control tissues isolated from a cohort of Chinese CRC patients were profiled.Three patterns of gene expression in CRC are shown. The expression of NLRC3, a checkpoint of inflammation, and the inflammasome components NLRP1, NLRP3, NLRC4 and AIM2 were reduced in CRC. NOD1 and NOD2 expression was increased in CRC, while NLRC5, NLRP6 and NLRP12 showed little difference compared to controls. Reduced expression of NLRC3 in CRC was verified in all available databases analyzed and confirmed with our patient cohort. Furthermore, the extent of NLRC3 and AIM2 gene reduction was correlated with cancer progression. This report reveals the potential value of NLR and AIM2 genes as biomarkers of CRC and cancer progression. PMID:26378020

  19. Changes in selected biochemical indices, leukocyte profile, and pterins as biomarkers of immune system activity due to antipecking measures in pheasants.

    PubMed

    Voslarova, E; Bedanova, I; Pistekova, V; Marsalek, P; Chloupek, J

    2013-07-01

    The physiological changes in response to beak trimming and spectacle usage as antipecking measures were monitored in 10-mo-old common pheasants (Phasianus colchicus). Short-term analysis conducted before the beginning of the laying period showed immediate increases of plasma corticosterone (P < 0.05) and lactate dehydrogenase (P < 0.001) concentrations and decrease of plasma triglycerides (P < 0.01) levels in response to both beak trimming and the application of spectacles. Beak-trimmed pheasants exhibited higher plasma corticosterone concentrations than pheasants fitted with spectacles (P < 0.001). To assess long-term changes, blood samples for biochemical (neopterin and biopterin determination) and hematological (leukocyte profile determination) examinations were taken from beak-trimmed, spectacles-fitted, and control pheasant hens housed in cages during their laying period. At the end of the laying period, hens fitted with spectacles exhibited lower concentrations of plasma neopterin (P = 0.005) and biopterin (P = 0.005) than beak-trimmed pheasant hens. Our findings suggest that the immune system was suppressed in spectacles-fitted pheasant hens as a result of chronic stress, as also indicated by the higher heterophil-to-lymphocyte ratio (P = 0.001) compared with beak-trimmed hens. Our study found a negative correlation (r = -0.31, P = 0.019) between the heterophil-to-lymphocyte ratio and plasma neopterin concentration. This study demonstrated that both beak trimming and use of spectacles are not only stressful procedures for pheasants, but long-term effects may also include a negative impact on the immune system. PMID:23776255

  20. Large-scale gene expression profiling of discrete brain regions: potential, limitations, and application in genetics of aggressive behavior.

    PubMed

    Feldker, Dorine E M; de Kloet, E Ronald; Kruk, Menno R; Datson, Nicole A

    2003-09-01

    Many behavioral geneticists are interested in unraveling the molecular mechanisms underlying aggressive behavior. So far, most scientists have based their search for aggression-related genes on a preliminary functional hypothesis. Large-scale gene expression profiling techniques, such as serial analysis of gene expression (SAGE) and DNA microarrays, now enable the screening of expression levels of thousands of genes simultaneously, allowing the identification of new candidate aggression-related genes expressed in brain and thus the generation of new hypotheses. However, expression profiling in the brain is challenging, as brain is a complex heterogeneous tissue where large numbers of genes are expressed and relatively small changes in gene expression occur. In this special issue, we focus on the principles of SAGE and DNA microarrays, as well as their advantages and disadvantages and application to analysis in brain tissue in order to identify aggression-related genes. PMID:14574131

  1. GHEP-ISFG collaborative simulated exercise for DVI/MPI: Lessons learned about large-scale profile database comparisons.

    PubMed

    Vullo, Carlos M; Romero, Magdalena; Catelli, Laura; Šakić, Mustafa; Saragoni, Victor G; Jimenez Pleguezuelos, María Jose; Romanini, Carola; Anjos Porto, Maria João; Puente Prieto, Jorge; Bofarull Castro, Alicia; Hernandez, Alexis; Farfán, María José; Prieto, Victoria; Alvarez, David; Penacino, Gustavo; Zabalza, Santiago; Hernández Bolaños, Alejandro; Miguel Manterola, Irati; Prieto, Lourdes; Parsons, Thomas

    2016-03-01

    The GHEP-ISFG Working Group has recognized the importance of assisting DNA laboratories to gain expertise in handling DVI or missing persons identification (MPI) projects which involve the need for large-scale genetic profile comparisons. Eleven laboratories participated in a DNA matching exercise to identify victims from a hypothetical conflict with 193 missing persons. The post mortem database was comprised of 87 skeletal remain profiles from a secondary mass grave displaying a minimal number of 58 individuals with evidence of commingling. The reference database was represented by 286 family reference profiles with diverse pedigrees. The goal of the exercise was to correctly discover re-associations and family matches. The results of direct matching for commingled remains re-associations were correct and fully concordant among all laboratories. However, the kinship analysis for missing persons identifications showed variable results among the participants. There was a group of laboratories with correct, concordant results but nearly half of the others showed discrepant results exhibiting likelihood ratio differences of several degrees of magnitude in some cases. Three main errors were detected: (a) some laboratories did not use the complete reference family genetic data to report the match with the remains, (b) the identity and/or non-identity hypotheses were sometimes wrongly expressed in the likelihood ratio calculations, and (c) many laboratories did not properly evaluate the prior odds for the event. The results suggest that large-scale profile comparisons for DVI or MPI is a challenge for forensic genetics laboratories and the statistical treatment of DNA matching and the Bayesian framework should be better standardized among laboratories. PMID:26716885

  2. Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events

    PubMed Central

    2013-01-01

    Background Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. Methods To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. Results In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. Conclusions Gene expression profiling of peripheral blood, sampled before or early in the course of

  3. Effect of tanniferous leaf meal based multi-nutrient blocks on feed intake, hematological profile, immune response, and body weight changes in Haemonchus contortus infected goats

    PubMed Central

    Singh, Surender; Pathak, A. K.; Sharma, R. K.; Khan, Muzaffer

    2015-01-01

    Aim: The aim was to assess the effect of multi nutrient block (MNB) supplementation with and without tanniferous leaf meal mixture on feed intake, hematological profile, immune response, and body weight changes of goats that were experimentally infected with Haemonchus contortus. Materials and Methods: Total 12 adult male goats of similar age and body weight (26.49±0.87) were allocated in 3 groups in completely randomized design. MNB supplemented in first two groups i.e. in T1 (no infection) and T2 (H. contortus infection @ 1500 L3/goat) group, while, MNB-condensed tannin (CT) supplemented in T3 (H. contortus infection @ 1500 L3/goat + CT source). All goats were fed concentrate mixture @ 100 g/day/goat, ad lib wheat straw and MNB or MNB-CT to meet their requirement for maintenance. Body weights were recorded and blood and fecal samples were collected at 0 day and thereafter at 15 days intervals for a period of 75 days for the assessment of body weight changes, hematological profile and H. contortus loads. Both humoral and cell-mediated immune (CMI) response were assessed at the end of feeding trial. Results: Mean hemoglobin and packed cell volume (PCV) levels were found to be highest (p<0.001, p<0.05) in T1 group followed by T3 group and lowest values were observed in T2 group. However, The PCV values between T1 and T3 groups were found to be statistically non-significant (p<0.05). The humoral and CMI response were significantly (p<0.036) higher in T3 group as compared to T2 group. MNB-CT supplementation significantly (p<0.001) reduced fecal egg counts in T3 group as compared to MNB supplemented T2 group. Conclusion: Supplementation of MNB-CT could be used as an alternative sustainable method to control H. contortus and maintained health status and performance of goats in face of parasitic challenge. PMID:27047137

  4. Millimeter scale profiles of chlorophyll fluorescence: Deciphering the microscale spatial structure of phytoplankton

    NASA Astrophysics Data System (ADS)

    Doubell, Mark J.; Prairie, Jennifer C.; Yamazaki, Hidekatsu

    2014-03-01

    Marine food webs and biogeochemical cycles are driven by interactions between individual phytoplankton and other micro-organisms embedded within turbulent flows. Understanding the causes and ecological consequences of these interactions requires measurement of the spatial distribution of organisms across sub-meter scales relevant to their activities. However, estimates of many microscale processes (e.g., encounter rates, competition) are implicitly based on a random distribution of plankton despite increasing evidence of patchy distributions of turbulence and phytoplankton at the oceans microscale. Further complicating our understanding of microscale phytoplankton ecology, recent studies have suggested that the high levels of fluorescence variability measured at sub-centimeter scales may be due to the detection of separate, large phytoplankton particles (i.e. large cells, chains and aggregates) rather than 'patches' of increased cell abundances. By comparing coincident fluorescence estimates measured with millimeter (μL) and centimeter (mL) scale resolution, we show that estimates of phytoplankton biomass made at centimeter scales are consistent with averaging discrete variations in fluorescence measured at millimeter scales and that a critical scale exists where measures of fluorescence variability transitions from representing an individual to a patch. Application of nearest neighbor analysis to the discrete fluorescence patterns showed deviations from complete spatial randomness towards clustering across scales of millimeters to tens of centimeters. The strength of the deviation from random increased significantly in regions of elevated phytoplankton concentrations. No relationship was observed between fluorescent particle concentrations or nearest neighbor distances with the rate of dissipation of turbulent kinetic energy. Our results provide empirical evidence that the scale at which phytoplankton distributions are estimated by chlorophyll fluorescence may be

  5. Quantitative expression profiling of immune response genes in rainbow trout following infectious haematopoietic necrosis virus (IHNV) infection or DNA vaccination

    USGS Publications Warehouse

    Purcell, Maureen K.; Kurath, Gael; Garver, Kyle A.; Herwig, Russell P.; Winton, James R.

    2004-01-01

    Infectious haematopoietic necrosis virus (IHNV) is a well-studied virus of salmonid fishes. A highly efficacious DNA vaccine has been developed against this virus and studies have demonstrated that this vaccine induces both an early and transient non-specific anti-viral phase as well as long-term specific protection. The mechanisms of the early anti-viral phase are not known, but previous studies noted changes in Mx gene expression, suggesting a role for type I interferon. This study used quantitative real-time reverse transcriptase PCR methodology to compare expression changes over time of a number of cytokine or cytokine-related genes in the spleen of rainbow trout following injection with poly I:C, live IHNV, the IHNV DNA vaccine or a control plasmid encoding the non-antigenic luciferase gene. The target genes included Mx-1, viral haemorrhagic septicaemia virus induced gene 8 (Vig-8), TNF-α1, TNF-α2, IL-1β1, IL-8, TGF-β1 and Hsp70. Poly I:C stimulation induced several genes but the strongest and significant response was observed in the Mx-1 and Vig-8 genes. The live IHN virus induced a significant response in all genes examined except TGF-β1. The control plasmid construct and the IHNV DNA vaccine marginally induced a number of genes, but the main difference between these two groups was a statistically significant induction of the Mx-1 and Vig-8 genes by the IHNV vaccine only. The gene expression profiles elicited by the live virus and the IHNV DNA vaccine differed in a number of aspects but this study confirms the clear role for a type I interferon-like response in early anti-viral defence.

  6. Dryline on 22 May 2002 During IHOP: Convective Scale Measurements at the Profiling Site

    NASA Technical Reports Server (NTRS)

    Demoz, Belay; Flamant, Cyrille; Miller, David; Evans, Keith; Fabry, Federic; DiGirolamo, Paolo; Whiteman, David; Geerts, Bart; Weckwerth, Tammy; Brown, William

    2004-01-01

    A unique set of measurements of wind, water vapor mixing ratio and boundary layer height variability was observed during the first MOP dryline mission of 22 May 2002. Water vapor mixing ratio from the Scanning Raman Lidar (SRL), high-resolution profiles of aerosol backscatter from the HARLIE and wind profiles from the GLOW are combined with the vertical velocity derived from the NCAR/ISS/MAPR and the high-resolution FMCW radar to reveal the convective variability of the cumulus cloud-topped boundary layer. A combined analysis of the in-situ and remote sensing data from aircraft, radiosonde, lidars, and radars reveals moisture variability within boundary layer updraft and downdraft regions as well as characterizes the boundary layer height variability in the dry and moist sides of the dryline. The profiler site measurements will be tied to aircraft data to reveal the relative intensity and location of these updrafts to the dry line. This study provides unprecedented high temporal and spatial resolution measurements of wind, moisture and backscatter within a dryline and the associated convective boundary layer.

  7. Watershed Scale Shear Stress From Tethersonde Wind Profile Measurements Under Near Neutral and Unstable Atmospheric Stability

    NASA Astrophysics Data System (ADS)

    Parlange, M. B.; Katul, G. G.

    1995-04-01

    Mean wind speed profiles were measured in the atmospheric surface layer, using a tethersonde system, above the Ojai Valley Watershed in southern California. The valley is mainly planted with mature avocado and orange trees. The surface shear stress and latent and sensible heat fluxes were measured above the trees which are up to 9 m in height. Near-neutral wind speed profile measurements allowed the determination of the watershed surface roughness (z0 = 1.4 m) and the momentum displacement height (d0 = 7.0 m). The wind speed measurements obtained under unstable atmospheric stability were analyzed using Monin-Obukhov similarity theory. New stability correction functions proposed based on theory and experiments of Kader-Yaglom as well as the now classic Businger-Dyer type functions were tested. The watershed shear stress values calculated using the surface layer wind speed profiles with the new Monin-Obukhov stability functions were found to be improved in comparison with the values obtained with the Businger-Dyer functions under strongly unstable stability conditions. The Monin-Obukhov model with the Businger-Dyer stability correction function underpredicted the momentum flux by 25% under strongly unstable stability conditions, while the new Kader-Yaglom formulation compared well on average (R2 = 0.77) with the surface eddy correlation measurements for all atmospheric stability conditions. The unstable 100-m drag coefficient was found to be u*2/V1002 = 0.0182.

  8. Difference in microRNA expression and editing profile of lung tissues from different pig breeds related to immune responses to HP-PRRSV.

    PubMed

    Li, Jia; Chen, Zhisheng; Zhao, Junlong; Fang, Liurong; Fang, Rui; Xiao, Jiang; Chen, Xing; Zhou, Ao; Zhang, Yingyin; Ren, Liming; Hu, Xiaoxiang; Zhao, Yaofeng; Zhang, Shujun; Li, Ning

    2015-01-01

    Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating diseases for the pig industry. Our goal was to identify microRNAs involved in the host immune response to PRRS. We generated microRNA expression profiles of lung tissues from Tongcheng or Landrace pigs infected with a highly pathogenic PRRS virus (PRRSV) at 3, 5, 7 dpi (day post infection) and control individuals from these two breeds. Our data showed that 278 known and 294 novel microRNAs were expressed in these combined microRNA transcriptomes. Compared with control individuals, almost half of the known microRNAs (116 in Tongcheng and 153 in Landrace) showed significantly differential expression (DEmiRNAs) at least once. The numbers of down-regulated DEmiRNAs were larger than the corresponding number of up-regulated DEmiRNAs in both breeds. Interestingly, miR-2320-5p, which was predicted to bind to conserved sequences of the PRRSV genome, was down-regulated significantly at 3 dpi after PRRSV infection in both breeds. In addition, PRRSV infection induced a significant increase of microRNA editing level in both breeds. Our results provide novel insight into the role of microRNA in response to PRRSV infection in vivo, which will aid the research for developing novel therapies against PRRSV. PMID:25856272

  9. Increased miR-155 expression in peripheral blood mononuclear cells of primary immune thrombocytopenia patients was correlated with serum cytokine profiles.

    PubMed

    Qian, Bao-Hua; Ye, Xin; Zhang, Lei; Sun, Yi; Zhang, Jian-Rong; Gu, Ming-Li; Qin, Qin; Chen, Jie; Deng, An-Mei

    2015-01-01

    We investigated the possible pathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β1 levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β1, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1. PMID:25413124

  10. Immunization of complex networks

    NASA Astrophysics Data System (ADS)

    Pastor-Satorras, Romualdo; Vespignani, Alessandro

    2002-03-01

    Complex networks such as the sexual partnership web or the Internet often show a high degree of redundancy and heterogeneity in their connectivity properties. This peculiar connectivity provides an ideal environment for the spreading of infective agents. Here we show that the random uniform immunization of individuals does not lead to the eradication of infections in all complex networks. Namely, networks with scale-free properties do not acquire global immunity from major epidemic outbreaks even in the presence of unrealistically high densities of randomly immunized individuals. The absence of any critical immunization threshold is due to the unbounded connectivity fluctuations of scale-free networks. Successful immunization strategies can be developed only by taking into account the inhomogeneous connectivity properties of scale-free networks. In particular, targeted immunization schemes, based on the nodes' connectivity hierarchy, sharply lower the network's vulnerability to epidemic attacks.

  11. Large-Scale, Virtual Seismic Profiles: New Technique and Results from Tibet and Northern China (Invited)

    NASA Astrophysics Data System (ADS)

    Chen, W.; Yu, C.; Ning, J.; Tseng, T.

    2010-12-01

    We developed a new approach of constructing deep-penetrating seismic profiles using earthquake-sources and successfully applied this technique over distances of up to 1,000 km in two geologically important regions. Along a north-south trending profile across southern and central Tibet, there are significant, regional variations in crustal thickness under near-constant elevation (~ 5 km above sea-level) over a distance of 550 km. The crust is as thick as 75 km in southern Tibet but shoals to just over 60 km under the Qiangtang terrane in central Tibet where the deviation from Airy isostasy is equivalent to a thickness of over 10 km in missing crust. Northward thinning of crust occurs gradually over a distance of about 200 km where mechanical deformation, instead of pervasive magmatism, also seems to have disrupted the crust-mantle interface. Over a distance of nearly 1,000 km, an east-west trending profile, extending over the North China craton, across the active Shanxi rift, and over the Ordos plateau, also reveals intriguing changes in crustal thickness, almost by a factor of two over a distance of only about 100 km, which do not correlate well with topography. These examples demonstrate the power of this new approach which has some unique advantages: 1) Deep-penetration is virtually certain given the broadband nature and great power of earthquake-sources, and very large amplitude of wide-angle reflections, 2) low cost of operations, 3) negligible impact on the environment during field deployment, and 4) the same dataset is valuable for many other applications for basic research.

  12. Large-scale profiling of diterpenoid glycosides from Stevia rebaudiana using ultrahigh performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Shafii, Behnaz; Vismeh, Ramin; Beaudry, Randy; Warner, Ryan; Jones, A Daniel

    2012-07-01

    The plant Stevia rebaudiana accumulates a suite of diterpenoid metabolites that are natural sweeteners finding increased use as sugar substitutes. To guide breeding of stevia plants that accumulate substances with desirable flavor in high yield, rapid and accurate methods are needed to profile these substances in plant populations. This report describes an 8-min ultrahigh performance liquid chromatography-tandem mass spectrometry method for separation and quantification of seven stevia glycosides including steviolbioside; stevioside; rebaudiosides A, B, and C; rubusoside; and dulcoside as well as aglycones steviol and isosteviol. This negative mode electrospray ionization/multiple reaction monitoring method yielded low limits of detection <1 ng/mL for steviol, 6 ng/mL for isosteviol, and <15 ng/mL for all stevia glycosides. Stevioside and Reb A, B, and C were quantified in more than 1,100 extracts from stevia leaves as part of a large-scale profiling exercise. Leaf tissue levels in this population spanned about two orders of magnitude for stevioside (2-125 mg/g dry weight), Reb A (2.5-164 mg/g), Reb B (0.5-50 mg/g), and Reb C (1.5-125 mg/g), but levels of individual metabolites exhibited independent variation. The wide spread of metabolite levels highlights the utility and importance of performing targeted metabolic profiling for large plant populations. PMID:22580424

  13. Neighborhood-Scale Spatial Models of Diesel Exhaust Concentration Profile Using 1-Nitropyrene and Other Nitroarenes.

    PubMed

    Schulte, Jill K; Fox, Julie R; Oron, Assaf P; Larson, Timothy V; Simpson, Christopher D; Paulsen, Michael; Beaudet, Nancy; Kaufman, Joel D; Magzamen, Sheryl

    2015-11-17

    With emerging evidence that diesel exhaust exposure poses distinct risks to human health, the need for fine-scale models of diesel exhaust pollutants is growing. We modeled the spatial distribution of several nitrated polycyclic aromatic hydrocarbons (NPAHs) to identify fine-scale gradients in diesel exhaust pollution in two Seattle, WA neighborhoods. Our modeling approach fused land-use regression, meteorological dispersion modeling, and pollutant monitoring from both fixed and mobile platforms. We applied these modeling techniques to concentrations of 1-nitropyrene (1-NP), a highly specific diesel exhaust marker, at the neighborhood scale. We developed models of two additional nitroarenes present in secondary organic aerosol: 2-nitropyrene and 2-nitrofluoranthene. Summer predictors of 1-NP, including distance to railroad, truck emissions, and mobile black carbon measurements, showed a greater specificity to diesel sources than predictors of other NPAHs. Winter sampling results did not yield stable models, likely due to regional mixing of pollutants in turbulent weather conditions. The model of summer 1-NP had an R(2) of 0.87 and cross-validated R(2) of 0.73. The synthesis of high-density sampling and hybrid modeling was successful in predicting diesel exhaust pollution at a very fine scale and identifying clear gradients in NPAH concentrations within urban neighborhoods. PMID:26501773

  14. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions.

    PubMed

    Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

    2015-01-01

    Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA. PMID:26479481

  15. Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines.

    PubMed

    Campbell, James; Ryan, Colm J; Brough, Rachel; Bajrami, Ilirjana; Pemberton, Helen N; Chong, Irene Y; Costa-Cabral, Sara; Frankum, Jessica; Gulati, Aditi; Holme, Harriet; Miller, Rowan; Postel-Vinay, Sophie; Rafiq, Rumana; Wei, Wenbin; Williamson, Chris T; Quigley, David A; Tym, Joe; Al-Lazikani, Bissan; Fenton, Timothy; Natrajan, Rachael; Strauss, Sandra J; Ashworth, Alan; Lord, Christopher J

    2016-03-15

    One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors. PMID:26947069

  16. Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines

    PubMed Central

    Campbell, James; Ryan, Colm J.; Brough, Rachel; Bajrami, Ilirjana; Pemberton, Helen N.; Chong, Irene Y.; Costa-Cabral, Sara; Frankum, Jessica; Gulati, Aditi; Holme, Harriet; Miller, Rowan; Postel-Vinay, Sophie; Rafiq, Rumana; Wei, Wenbin; Williamson, Chris T.; Quigley, David A.; Tym, Joe; Al-Lazikani, Bissan; Fenton, Timothy; Natrajan, Rachael; Strauss, Sandra J.; Ashworth, Alan; Lord, Christopher J.

    2016-01-01

    Summary One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors. PMID:26947069

  17. Profiling motives behind hedonic eating. Preliminary validation of the Palatable Eating Motives Scale.

    PubMed

    Burgess, E E; Turan, B; Lokken, K L; Morse, A; Boggiano, M M

    2014-01-01

    The purpose of this study was to validate a new scale designed to measure individual motives for eating tasty foods and determine if any specific motive(s) are associated with obesity. The "Palatable Eating Motives Scale" (PEMS) is a self-report measure adapted from the Drinking Motives Questionnaire Revised (DMQ-R). N=150 racially-diverse college students (mean age: 24.4, BMI: 16-51kg/m(2)) were administered the PEMS along with the Binge-Eating Scale (BES) and the Yale Food Addiction Scale (YFAS) to test for convergent and incremental validity and the Sensitivity to Punishment and Reward Questionnaire (SPSRQ) for discriminant validity. The PEMS identified four motives for eating tasty food, the same ones found with the DMQ-R for alcohol intake: Social, Conformity, Enhancement, and Coping motives. The scales had good convergent validity with BES and YFAS scores but discriminated from the broader motivational constructs of inhibition and activation measured by the SPSRQ. Of the PEMS motives, Coping (eating tasty food to deal with problems and negative feelings) accounted for unique variance in BMI, and added to variance in BMI contributed by BES scores, showing incremental validity. YFAS scores did not contribute to BMI after controlling for binge-eating. Coping subscale scores were also significantly higher (p<0.001) among the severely obese (BMI>40). Motives behind palatable food intake are not homogenous and should be considered in personalized weight-loss strategies in future studies. In normal weight individuals, knowing one's dominant motive for eating tasty foods may help promote healthier food choices in times and places where they are most vulnerable to do otherwise. PMID:24076018

  18. Transcriptional Profiles of Cytokine/Chemokine Factors of Immune Cell-Homing to the Parasitic Lesions: A Comprehensive One-Year Course Study in the Liver of E. multilocularis-Infected Mice

    PubMed Central

    Zhang, Wenbao; Li, Liang; Gottstein, Bruno; Blagosklonov, Oleg; Lü, Guodong; Zhang, Chuangshan; Lu, Xiaomei; Vuitton, Dominique A.; Wen, Hao

    2014-01-01

    Pathogenesis of chronically developing alveolar echinococcosis (AE) is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis) in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to complement the only

  19. Immune-spaying as an alternative to surgical spaying in Iberian×Duroc females: effect on quality characteristics and fatty acid profile in dry-cured shoulders and loins.

    PubMed

    Gamero-Negrón, Rafael; Sánchez Del Pulgar, José; García, Carmen

    2015-06-01

    The aim of this study was to assess the effect of immune-spaying on meat quality characteristics and fatty acid profile of dry-cured shoulders and loins by comparing Iberian×Duroc surgically spayed females, immune-spayed females and entire females. There were no significant differences on the physicochemical composition of dry-cured shoulders; however the intramuscular fat content of dry-cured loins was higher in immune-spayed females than entire ones, but not significantly different from spayed females. Immune-spayed females showed the highest values, which could improve the sensory quality of Iberian dry-cured loins, since it is considered an index of high quality. On the other hand, the PUFA content of both dry-cured shoulders and loins proved to be lower in immune-spayed than spayed females, which could prevent excessive fat oxidation responsible for rancidity. Therefore, immune-spaying could be a viable alternative to surgical spaying from the meat quality point of view. PMID:25697853

  20. Immune System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  1. V S Profiles from Noise Cross Correlation at Local and Small Scale

    NASA Astrophysics Data System (ADS)

    de Nisco, G.; Nunziata, C.

    2011-03-01

    Ambient noise measurements have been performed at local and small scales in the Neapolitan and surrounding areas (Campania, southern Italy) by employing two broad-band Kinemetrics Q330 stations, equipped with Episensor ES-T three component accelerometers. In both experiments frequency time analysis (FTAN method) has been performed on the vertical and radial components of noise cross correlations to retrieve the Rayleigh wave dispersion (Green's function). At local scale, over an interstation distance of about 26 km, the group velocity dispersion values have been compared with those obtained from FTAN analysis on recordings of two earthquakes with similar path. At small scale, measurements have been carried out over an interstation distance of about 440 m in the public gardens of Scampia, the northernmost quarter of Naples. The Rayleigh wave group velocity dispersion data obtained from noise cross correlation, have been combined with those from active seismic experiment along the same alignment, but shorter (120 m offset). The non linear inversion of such a dispersion curve has allowed the definition of V S models to depths of 100 m, in agreement with nearby stratigraphy. Moreover, a good agreement has resulted for the resonance frequency among the H/V ratio, the ellipticity of the fundamental mode computed for the chosen V S model, and the average two-dimensional (2D) spectral amplification computed along a cross section representative of the Scampia quarter.

  2. Small scale temporal distribution of radiocesium in undisturbed coniferous forest soil: Radiocesium depth distribution profiles.

    PubMed

    Teramage, Mengistu T; Onda, Yuichi; Kato, Hiroaki

    2016-04-01

    The depth distribution of pre-Fukushima and Fukushima-derived (137)Cs in undisturbed coniferous forest soil was investigated at four sampling dates from nine months to 18 months after the Fukushima nuclear power plant accident. The migration rate and short-term temporal variability among the sampling profiles were evaluated. Taking the time elapsed since the peak deposition of pre-Fukushima (137)Cs and the median depth of the peaks, its downward displacement rates ranged from 0.15 to 0.67 mm yr(-1) with a mean of 0.46 ± 0.25 mm yr(-1). On the other hand, in each examined profile considerable amount of the Fukushima-derived (137)Cs was found in the organic layer (51%-92%). At this moment, the effect of time-distance on the downward distribution of Fukushima-derived (137)Cs seems invisible as its large portion is still found in layers where organic matter is maximal. This indicates that organic matter seems the primary and preferential sorbent of radiocesium that could be associated with the physical blockage of the exchanging sites by organic-rich dusts that act as a buffer against downward propagation of radiocesium, implying radiocesium to be remained in the root zone for considerable time period. As a result, this soil section can be a potential source of radiation dose largely due to high radiocesium concentration coupled with its low density. Generally, such kind of information will be useful to establish a dynamic safety-focused decision support system to ease and assist management actions. PMID:26803260

  3. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

    PubMed Central

    Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

    2015-01-01

    Simple Summary This research established an association between lactation number and milk production and metabolic and inflammatory responses in high-producing dairy cows affected by left abomasal displacement in small-scaled dairy farms. The study showed metabolic alterations, liver damage, and inflammation in the sick cows, which were further exacerbated with increasing lactation number and milk yield of the cows. Abstract Left displaced abomasum (LDA) is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1) evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2) establish an association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca), but greater concentrations of non-esterified fatty acids (NEFA) and beta-hydroxy-butyrate (BHBA), in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA), regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA. PMID:26479481

  4. Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam.

    PubMed

    Bi, Xiuqiong; Ishizaki, Azumi; Nguyen, Lam Van; Matsuda, Kazunori; Pham, Hung Viet; Phan, Chung Thi Thu; Ogata, Kiyohito; Giang, Thuy Thi Thanh; Phung, Thuy Thi Bich; Nguyen, Tuyen Thi; Tokoro, Masaharu; Pham, An Nhat; Khu, Dung Thi Khanh; Ichimura, Hiroshi

    2016-01-01

    CD4⁺ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(-)) aged 2-12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4⁺-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38⁺HLA (human leukocyte antigen)-DR⁺CD8⁺- (activated CD8⁺) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(-) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8⁺-cell activation status. Among the ART(+) children, the total CD4⁺-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8-8.3 years, whereas Th1 counts and the CD8⁺-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8⁺ cells and monocytes, and ART induced rapid Th1 recovery and early CD8⁺-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring. PMID:27490536

  5. Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam

    PubMed Central

    Bi, Xiuqiong; Ishizaki, Azumi; Nguyen, Lam Van; Matsuda, Kazunori; Pham, Hung Viet; Phan, Chung Thi Thu; Ogata, Kiyohito; Giang, Thuy Thi Thanh; Phung, Thuy Thi Bich; Nguyen, Tuyen Thi; Tokoro, Masaharu; Pham, An Nhat; Khu, Dung Thi Khanh; Ichimura, Hiroshi

    2016-01-01

    CD4+ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(−)) aged 2–12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4+-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38+HLA (human leukocyte antigen)-DR+CD8+- (activated CD8+) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(−) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8+-cell activation status. Among the ART(+) children, the total CD4+-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8–8.3 years, whereas Th1 counts and the CD8+-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8+ cells and monocytes, and ART induced rapid Th1 recovery and early CD8+-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring. PMID:27490536

  6. Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.

    PubMed

    Nield, Lynne E; von Both, Ingo; Popel, Najla; Strachan, Kate; Manlhiot, Cedric; Shannon, Patrick; McCrindle, Brian W; Atkinson, Adelle; Miner, Steven E S; Jaeggi, Edgar T; Taylor, Glenn P

    2016-02-01

    The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium. Of 60 fetal autopsy cases identified from institutional databases, 10 had aDCM (18-38 weeks), 12 iDCM (19-37 weeks) and 38 had normal hearts (11-40 weeks). Paraffin-embedded myocardium sections were stained for all lymphocyte (CD45), B cells (CD20, CD79a), T cells (CD3, CD4, CD7, CD8) and monocyte (CD68) surface markers. Two independent, blinded cell counts were performed. Normal hearts expressed all B and T cell markers in a bimodal fashion, with peaks at 22 and 37 weeks of gestation. The aDCM cohort was most distinct from normal hearts, with less overall T cell markers [EST -9.1 (2.6) cells/mm(2), p = 0.001], CD4 [EST -2.0 (0.6), p = 0.001], CD3 [EST -3.9 (1.0), p < 0.001], CD7 [EST -3.0 (1.1), p = 0.01] overall B cell markers [EST -4.9 (1.8), p = 0.01] and CD79a counts [EST -2.3 (0.9), p = 0.01]. The iDCM group had less overall B cell markers [EST -4.0 (1.8), p = 0.03] and CD79a [EST -1.7 (0.9), p = 0.05], but no difference in T cell markers. Autoimmune-mediated DCM fetuses have less B and T cell markers, whereas iDCM fetuses have less B cell markers compared with normal fetal hearts. The fetal immune system may play a role in the normal development of the heart and evolution of dilated cardiomyopathy. PMID:26481221

  7. A direct dynamical measurement of the Milky Way's disk surface density profile, disk scale length, and dark matter profile at 4 kpc ≲ R ≲ 9 kpc

    SciTech Connect

    Bovy, Jo; Rix, Hans-Walter

    2013-12-20

    We present and apply rigorous dynamical modeling with which we infer unprecedented constraints on the stellar and dark matter mass distribution within our Milky Way (MW), based on large sets of phase-space data on individual stars. Specifically, we model the dynamics of 16,269 G-type dwarfs from SEGUE, which sample 5 kpc < R{sub GC} < 12 kpc and 0.3 kpc ≲ |Z| ≲ 3 kpc. We independently fit a parameterized MW potential and a three-integral, action-based distribution function (DF) to the phase-space data of 43 separate abundance-selected sub-populations (MAPs), accounting for the complex selection effects affecting the data. We robustly measure the total surface density within 1.1 kpc of the mid-plane to 5% over 4.5 kpc < R{sub GC} < 9 kpc. Using metal-poor MAPs with small radial scale lengths as dynamical tracers probes 4.5 kpc ≲ R{sub GC} ≲ 7 kpc, while MAPs with longer radial scale lengths sample 7 kpc ≲ R{sub GC} ≲ 9 kpc. We measure the mass-weighted Galactic disk scale length to be R{sub d} = 2.15 ± 0.14 kpc, in agreement with the photometrically inferred spatial distribution of stellar mass. We thereby measure dynamically the mass of the Galactic stellar disk to unprecedented accuracy: M {sub *} = 4.6 ± 0.3 + 3.0 (R {sub 0}/ kpc – 8) × 10{sup 10} M {sub ☉} and a total local surface density of Σ{sub R{sub 0}}(Z=1.1 kpc)=68 ± 4 M{sub ⊙} pc{sup −2} of which 38 ± 4 M {sub ☉} pc{sup –2} is contributed by stars and stellar remnants. By combining our surface density measurements with the terminal velocity curve, we find that the MW's disk is maximal in the sense that V {sub c,} {sub disk}/V {sub c,} {sub total} = 0.83 ± 0.04 at R = 2.2 R{sub d} . We also constrain for the first time the radial profile of the dark halo at such small Galactocentric radii, finding that ρ{sub DM}(r; ≈R {sub 0})∝1/r {sup α} with α < 1.53 at 95% confidence. Our results show that action-based DF modeling of complex stellar data sets is now a feasible

  8. Advanced Enzymology, Expression Profile and Immune Response of Clonorchis sinensis Hexokinase Show Its Application Potential for Prevention and Control of Clonorchiasis

    PubMed Central

    Tang, Zeli; Xie, Zhizhi; Lin, Zhipeng; Sun, Hengchang; Wan, Shuo; Li, Xuerong; Huang, Yan; Yu, Xinbing; Xu, Jin

    2015-01-01

    Background Approximately 35 million people are infected with Clonorchis sinensis (C. sinensis) globally, of whom 15 million are in China. Glycolytic enzymes are recognized as crucial molecules for trematode survival and have been targeted for vaccine and drug development. Hexokinase of C. sinensis (CsHK), as the first key regulatory enzyme of the glycolytic pathway, was investigated in the current study. Principal Findings There were differences in spatial structure and affinities for hexoses and phosphate donors between CsHK and HKs from humans or rats, the definitive hosts of C. sinensis. Effectors (AMP, PEP, and citrate) and a small molecular inhibitor regulated the enzymatic activity of rCsHK, and various allosteric systems were detected. CsHK was distributed in the worm extensively as well as in liver tissue and serum from C. sinensis infected rats. Furthermore, high-level specific IgG1 and IgG2a were induced in rats by immunization with rCsHK. The enzymatic activity of CsHK was suppressed by the antibody in vitro. Additionally, the survival of C. sinensis was inhibited by the antibody in vivo and in vitro. Conclusions/Significance Due to differences in putative spatial structure and enzymology between CsHK and HK from the host, its extensive distribution in adult worms, and its expression profile as a component of excretory/secretory products, together with its good immunogenicity and immunoreactivity, as a key glycolytic enzyme, CsHK shows potential as a vaccine and as a promising drug target for Clonorchiasis. PMID:25799453

  9. Large-scale profiling of microRNAs for The Cancer Genome Atlas

    PubMed Central

    Chu, Andy; Robertson, Gordon; Brooks, Denise; Mungall, Andrew J.; Birol, Inanc; Coope, Robin; Ma, Yussanne; Jones, Steven; Marra, Marco A.

    2016-01-01

    The comprehensive multiplatform genomics data generated by The Cancer Genome Atlas (TCGA) Research Network is an enabling resource for cancer research. It includes an unprecedented amount of microRNA sequence data: ∼11 000 libraries across 33 cancer types. Combined with initiatives like the National Cancer Institute Genomics Cloud Pilots, such data resources will make intensive analysis of large-scale cancer genomics data widely accessible. To support such initiatives, and to enable comparison of TCGA microRNA data to data from other projects, we describe the process that we developed and used to generate the microRNA sequence data, from library construction through to submission of data to repositories. In the context of this process, we describe the computational pipeline that we used to characterize microRNA expression across large patient cohorts. PMID:26271990

  10. The Carroll rating scale for depression. II. Factor analyses of the feature profiles.

    PubMed

    Smouse, P E; Feinberg, M; Carroll, B J; Park, M H; Rawson, S G

    1981-03-01

    Factor analyses were conducted for the Hamilton depression rating scale (HRS) and the self administered Carroll counterpart (CRS). The factor loadings for the respective first factors were similar; those for the respective second factors showed strict sign consistency but only moderate consistency of magnitude; the loadings for the respective third factors showed no particular consistency. The first three CRS and first three HRS factor scores were computed for each individual and correlations were computed from these factor scores. The first and second factors were highly correlated but the third factors were negatively correlated indicating that they were not measuring the same thing. The first factors of the CRS and HRS correlated highly with their respective raw total scores and were indices of the severity of illness. The self-administered CRS (with matching weights) is a credible alternative to the HRS for routine clinical assessment of the severity of depression. PMID:7272610

  11. Bacterial profiling of soil using genus-specific markers and multidimensional scaling.

    PubMed

    Lenz, Erin J; Foran, David R

    2010-11-01

    Forensic identification of soil based on microbial DNA fingerprinting has met with mixed success, with research efforts rarely considering temporal variability or local heterogeneity in soil's microbial makeup. In the research presented, the nitrogen fixing bacteria rhizobia were specifically examined. Soils were collected monthly from five habitats for 1 year, and quarterly in each cardinal direction from the main collection site. When all habitats were compared simultaneously using Terminal Restriction Fragment Length Polymorphism analysis of the rhizobial recA gene and multidimensional scaling, only two were differentiated over a year's time, however pairwise comparisons allowed four of five soils to be effectively differentiated. Adding in 10-foot distant soils as "questioned" samples correctly grouped them in 40-70% of cases, depending on restriction enzyme used. The results indicate that the technique has potential for forensic soil identification, although extensive anthropogenic manipulation of a soil makes such identification much more tentative. PMID:20533986

  12. Large-scale profiling of microRNAs for The Cancer Genome Atlas.

    PubMed

    Chu, Andy; Robertson, Gordon; Brooks, Denise; Mungall, Andrew J; Birol, Inanc; Coope, Robin; Ma, Yussanne; Jones, Steven; Marra, Marco A

    2016-01-01

    The comprehensive multiplatform genomics data generated by The Cancer Genome Atlas (TCGA) Research Network is an enabling resource for cancer research. It includes an unprecedented amount of microRNA sequence data: ~11 000 libraries across 33 cancer types. Combined with initiatives like the National Cancer Institute Genomics Cloud Pilots, such data resources will make intensive analysis of large-scale cancer genomics data widely accessible. To support such initiatives, and to enable comparison of TCGA microRNA data to data from other projects, we describe the process that we developed and used to generate the microRNA sequence data, from library construction through to submission of data to repositories. In the context of this process, we describe the computational pipeline that we used to characterize microRNA expression across large patient cohorts. PMID:26271990

  13. Translating aboveground cosmic-ray neutron intensity to high-frequency soil moisture profiles at sub-kilometer scale

    NASA Astrophysics Data System (ADS)

    Rosolem, R.; Hoar, T.; Arellano, A.; Anderson, J. L.; Shuttleworth, W. J.; Zeng, X.; Franz, T. E.

    2014-11-01

    Above-ground cosmic-ray neutron measurements provide an opportunity to infer soil moisture at the sub-kilometer scale. Initial efforts to assimilate those measurements have shown promise. This study expands such analysis by investigating (1) how the information from aboveground cosmic-ray neutrons can constrain the soil moisture at distinct depths simulated by a land surface model, and (2) how changes in data availability (in terms of retrieval frequency) impact the dynamics of simulated soil moisture profiles. We employ ensemble data assimilation techniques in a "nearly-identical twin" experiment applied at semi-arid shrubland, rainfed agricultural field, and mixed forest biomes in the USA. The performance of the Noah land surface model is compared with and without assimilation of observations at hourly intervals, as well as every 2 days. Synthetic observations of aboveground cosmic-ray neutrons better constrain the soil moisture simulated by Noah in root-zone soil layers (0-100cm), despite the limited measurement depth of the sensor (estimated to be 12-20cm). The ability of Noah to reproduce a "true" soil moisture profile is remarkably good, regardless of the frequency of observations at the semi-arid site. However, soil moisture profiles are better constrained when assimilating synthetic cosmic-ray neutron observations hourly rather than every 2 days at the cropland and mixed forest sites. This indicates potential benefits for hydrometeorological modeling when soil moisture measurements are available at a relatively high frequency. Moreover, differences in summertime meteorological forcing between the semi-arid site and the other two sites may indicate a possible controlling factor to soil moisture dynamics in addition to differences in soil and vegetation properties.

  14. Injury Profiles Associated with Artisanal and Small-Scale Gold Mining in Tarkwa, Ghana

    PubMed Central

    Calys-Tagoe, Benedict N. L.; Ovadje, Lauretta; Clarke, Edith; Basu, Niladri; Robins, Thomas

    2015-01-01

    Artisanal and small-scale gold mining (ASGM) is inherently risky, but little is known about mining-associated hazards and injuries despite the tremendous growth worldwide of ASGM and the benefits it offers. The current study aimed to characterize the physical injuries associated with ASGM in Ghana to guide policy formulation. A cross-sectional survey was carried out in the Tarkwa mining district of the Western Region of Ghana in 2014. A total of 404 small-scale miners were recruited and interviewed regarding their occupational injury experiences over the preceding 10 years using a paper-based structured questionnaire. Nearly one-quarter (23.5%) of the miners interviewed reported getting injured over the previous 10 years, and the overall injury rate was calculated to be 5.39 per 100 person years. The rate was significantly higher for women (11.93 per 100 person years) and those with little mining experience (e.g., 25.31 per 100 person years for those with less than one year of work experience). The most injury-prone mining activities were excavation (58.7%) and crushing (23.1%), and over 70% of the injuries were reported to be due to miners being hit by an object. The majority of the injuries (57%) were lacerations, and nearly 70% of the injuries were to the upper or lower limbs. Approximately one-third (34.7%) of the injuries resulted in miners missing more than two weeks of work. One-quarter of the injured workers believed that abnormal work pressure played a role in their injuries, and nearly two-fifths believed that their injuries could have been prevented, with many citing personal protective equipment as a solution. About one-quarter of the employees reported that their employers never seemed to be interested in the welfare or safety of their employees. These findings greatly advance our understanding of occupational hazards and injuries amongst ASGM workers and help identify several intervention points. PMID:26184264

  15. Millennial-scale hard rock erosion rates deduced from luminescence-depth profiles

    NASA Astrophysics Data System (ADS)

    Sohbati, R.; Liu, J.; Murray, A. S.; Jain, M.; Pederson, J. L.; Guralnik, B.; Egholm, D. L.; Gupta, S.

    2015-12-01

    Optically stimulated luminescence (OSL) is a well-established Quaternary dating method that is conventionally used to determine the time when sedimentary grains were last exposed to daylight. Recently, a very different approach to this concept has helped develop a new technique to estimate the length of time a rock surface was exposed to daylight. When a rock surface is first exposed to daylight the charge population (and so the latent luminescence signal) trapped in its constituent minerals (e.g. quartz and feldspar) starts to decrease. This charge had accumulated due to previous exposure to natural ionizing radiation. As the surface is exposed to light for longer periods, the latent luminescence signal is reduced farther into the rock. In a rock surface which has been exposed to light for a prolonged period (decades to millennia), the remaining luminescence will be zero (fully bleached) at the surface and then increase, initially exponentially, before approaching saturation at a depth where charge detrapping due to light penetration is negligible compared to the rate of charge trapping due to the environmental dose rate. By modelling the characteristic shape of luminescence resetting with depth into rock surfaces, Sohbati et al. (2012) proposed a new surface-exposure dating technique based on OSL. Here we further develop the current model to include the effect of erosion rate on luminescence-depth profiles. By fitting the model to local known-age calibration samples, we first determine the site-specific resetting rates of the luminescence signal at rock surfaces. We then use the calibration values in a numerical model to derive the steady-state erosion rate for rocks of different mineralogy and different geological settings. The preliminary erosion rates obtained from glacial and landslide granite boulders from the Chinese Pamir Plateau are ~1 mm.ka-1, whereas active streambeds of Permian sandstone in the Grabens district of Canyonlands National Park, Utah, are

  16. Genome-scale RNAi profiling of cell division in human tissue culture cells.

    PubMed

    Kittler, Ralf; Pelletier, Laurence; Heninger, Anne-Kristine; Slabicki, Mikolaj; Theis, Mirko; Miroslaw, Lukasz; Poser, Ina; Lawo, Steffen; Grabner, Hannes; Kozak, Karol; Wagner, Jan; Surendranath, Vineeth; Richter, Constance; Bowen, Wayne; Jackson, Aimee L; Habermann, Bianca; Hyman, Anthony A; Buchholz, Frank

    2007-12-01

    Cell division is fundamental for all organisms. Here we report a genome-scale RNA-mediated interference screen in HeLa cells designed to identify human genes that are important for cell division. We have used a library of endoribonuclease-prepared short interfering RNAs for gene silencing and have used DNA content analysis to identify genes that induced cell cycle arrest or altered ploidy on silencing. Validation and secondary assays were performed to generate a nine-parameter loss-of-function phenoprint for each of the genes. These phenotypic signatures allowed the assignment of genes to specific functional classes by combining hierarchical clustering, cross-species analysis and proteomic data mining. We highlight the richness of our dataset by ascribing novel functions to genes in mitosis and cytokinesis. In particular, we identify two evolutionarily conserved transcriptional regulatory networks that govern cytokinesis. Our work provides an experimental framework from which the systematic analysis of novel genes necessary for cell division in human cells can begin. PMID:17994010

  17. Measurement profiles of nano-scale ion beam for optimized radiation energy losses

    NASA Astrophysics Data System (ADS)

    Woo, T. H.; Cho, H. S.

    2011-10-01

    The behavior of charged particles is investigated for nano-scale ion beam therapy using a medical accelerator. Computational work is performed for the Bragg-peak simulation, which is focused on human organ material of pancreas and thyroid. The Results show that the trends of the dose have several different kinds of distributions. Before constructing a heavy ion collider, this study can give us the reliability of the therapeutic effect. Realistic treatment using human organs is calculated in a simple and cost effective manner using the computational code, the Stopping and Range of Ions in Matter 2008 (SRIM 2008). Considering the safety of the therapy, it is suggested to give a patient orient planning of the cancer therapy. The energy losses in ionization and phonon are analyzed, which are the behaviors in the molecular level nano-scopic investigation. The different fluctuations are shown at 150 MeV, where the lowest temperature is found in proton and pancreas case. Finally, the protocol for the radiation therapy is constructed by the simulation in which the procedure for a better therapy is selected. An experimental measurement incorporated with the simulations could be programmed by this protocol.

  18. Differentiation of F4 receptor profiles in pigs based on their mucin 4 polymorphism, responsiveness to oral F4 immunization and in vitro binding of F4 to villi.

    PubMed

    Nguyen, V U; Goetstouwers, T; Coddens, A; Van Poucke, M; Peelman, L; Deforce, D; Melkebeek, V; Cox, E

    2013-03-15

    F4(+) enterotoxigenic Escherichia coli (F4(+) ETEC) are an important cause of diarrhoea and mortality in piglets. F4(+) ETEC use their F4 fimbriae to adhere to specific receptors (F4Rs) on small intestinal brush borders, resulting in colonization of the small intestine. To prevent pigs from post-weaning diarrhoea, pigs should be vaccinated during the suckling period. Previously, we demonstrated that F4acR(+), but not F4acR(-) piglets could be orally immunized with purified F4 fimbriae resulting in a protective immunity against F4(+) ETEC infections, indicating that this immune response was F4R dependent. Recently, aminopeptidase N has been identified as a glycoprotein receptor important for this oral immune response. However, in some oral immunization experiments, a few F4acR(+) piglets did not show an antibody response upon oral immunization, suggesting additional receptors. Therefore, the binding profile of F4 to brush border membrane (glyco)proteins was determined for pigs differing in F4-specific antibody response upon oral immunization, in in vitro adhesion of F4(+)E. coli to small intestinal villi, and in Muc4 genotype. Six groups of pigs could be identified. Only two groups positive in all three assays showed two high molecular weight (MW) glycoprotein bands (>250kDa) suggesting that these high MW bands are linked to the MUC4 susceptible genotype. The fact that these bands were absent in the MUC4 resistant group which showed a positive immune response against F4 and was positive in the adhesion test confirm that at least one or perhaps more other F4Rs exist. Interestingly, two pigs that were positive in the villous adhesion assay did not show an immune response against F4 fimbriae. This suggests that a third receptor category might exist which allows the bacteria to adhere but does not allow effective immunization with soluble F4 fimbriae. Future research will be necessary to confirm or reveal the identity of these receptors. PMID:23084626

  19. Microbial Forensics: Predicting Phenotypic Characteristics and Environmental Conditions from Large-Scale Gene Expression Profiles

    PubMed Central

    Kim, Minseung; Zorraquino, Violeta; Tagkopoulos, Ilias

    2015-01-01

    A tantalizing question in cellular physiology is whether the cellular state and environmental conditions can be inferred by the expression signature of an organism. To investigate this relationship, we created an extensive normalized gene expression compendium for the bacterium Escherichia coli that was further enriched with meta-information through an iterative learning procedure. We then constructed an ensemble method to predict environmental and cellular state, including strain, growth phase, medium, oxygen level, antibiotic and carbon source presence. Results show that gene expression is an excellent predictor of environmental structure, with multi-class ensemble models achieving balanced accuracy between 70.0% (±3.5%) to 98.3% (±2.3%) for the various characteristics. Interestingly, this performance can be significantly boosted when environmental and strain characteristics are simultaneously considered, as a composite classifier that captures the inter-dependencies of three characteristics (medium, phase and strain) achieved 10.6% (±1.0%) higher performance than any individual models. Contrary to expectations, only 59% of the top informative genes were also identified as differentially expressed under the respective conditions. Functional analysis of the respective genetic signatures implicates a wide spectrum of Gene Ontology terms and KEGG pathways with condition-specific information content, including iron transport, transferases, and enterobactin synthesis. Further experimental phenotypic-to-genotypic mapping that we conducted for knock-out mutants argues for the information content of top-ranked genes. This work demonstrates the degree at which genome-scale transcriptional information can be predictive of latent, heterogeneous and seemingly disparate phenotypic and environmental characteristics, with far-reaching applications. PMID:25774498

  20. Effects of levan-type fructan supplementation on growth performance, digestibility, blood profile, fecal microbiota, and immune responses after lipopolysaccharide challenge in growing pigs.

    PubMed

    Li, J; Kim, I H

    2013-11-01

    In Exp. 1, 80 growing pigs (27.1±0.7 kg) were used in a 42-d experiment to evaluate the effect of levan-type fructan on growth performance, digestibility, blood profile, and fecal microbiota. Pigs were randomly allocated to 1 of 4 treatments, according to initial BW and gender, with 5 replicate pens per treatment and 2 barrows and 2 gilts per pen. Treatments were corn-soybean meal-based diets supplemented with 0%, 0.05%, 0.10%, or 0.20% levan-type fructan. Average daily gain and G:F increased (quadratic, P<0.05), as dietary levan-type fructan increased from 0 to 0.2%. Similarly, the apparent total tract digestibility of N and GE increased (quadratic, P<0.05), as dietary supplementation of levan-type fructan increased. Dietary levan-type fructan supplementation increased fecal Lactobacillus counts linearly (P<0.05). In Exp. 2, 20 individually housed barrows (26.2±0.6 kg) were used to evaluate immune responses after an Escherichia coli lipopolysaccharide (LPS) challenge. Pigs were fed corn-soybean meal-based diets supplemented with 0% or 0.10% levan-type fructan for 42 d. At d 42, 5 pigs from each treatment were injected with E. coli LPS (0.01% of BW) and the other 5 pigs with sterile saline solution, resulting in a 2×2 factorial arrangement of treatments. Blood was taken 0, 2, 4, 6, and 8 h after challenge. Challenge with LPS decreased blood lymphocyte percentage and had an interactive effect with levan-type fructan inclusion at 4, 6, and 8 h (P<0.01). Levan-type fructan supplementation increased (P<0.05) white blood cells at 6 and 8 h, and increased (P<0.05) lymphocyte percentage at 8 h after the challenge. Lipopolysaccharide injection increased (P<0.05) rectal temperature at 2 and 4 h, and had an interactive effect (P<0.05) with levan-type fructan supplementation at 4 h after the challenge. At 2, 4, 6, and 8 h, serum cortisol, tumor necrosis factor-α, and IL-6 concentration increased (P<0.05) by LPS challenge, and there was an interactive effect between LPS

  1. Scales

    MedlinePlus

    Scales are a visible peeling or flaking of outer skin layers. These layers are called the stratum ... Scales may be caused by dry skin, certain inflammatory skin conditions, or infections. Eczema , ringworm , and psoriasis ...

  2. Improving immunization strategies

    NASA Astrophysics Data System (ADS)

    Gallos, Lazaros K.; Liljeros, Fredrik; Argyrakis, Panos; Bunde, Armin; Havlin, Shlomo

    2007-04-01

    We introduce an immunization method where the percentage of required vaccinations for immunity are close to the optimal value of a targeted immunization scheme of highest degree nodes. Our strategy retains the advantage of being purely local, without the need for knowledge on the global network structure or identification of the highest degree nodes. The method consists of selecting a random node and asking for a neighbor that has more links than himself or more than a given threshold and immunizing him. We compare this method to other efficient strategies on three real social networks and on a scale-free network model and find it to be significantly more effective.

  3. Immune Restoration

    MedlinePlus

    ... marrow cells immune to HIV infection. Letting the immune system repair itself: CD4 counts have increased for many ... have taken ART. Some scientists believe that the immune system might be able to heal and repair itself ...

  4. Immune response

    MedlinePlus Videos and Cool Tools

    ... cells. T cells are responsible for cell-mediated immunity. This type of immunity becomes deficient in persons with HIV, the virus ... blood. B lymphocytes provide the body with humoral immunity as they circulate in the fluids in search ...

  5. Gene expression profiling of Gram-negative bacteria-induced inflammation in human whole blood: The role of complement and CD14-mediated innate immune response.

    PubMed

    Lau, Corinna; Olstad, Ole Kristoffer; Holden, Marit; Nygård, Ståle; Fure, Hilde; Lappegård, Knut Tore; Brekke, Ole-Lars; Espevik, Terje; Hovig, Eivind; Mollnes, Tom Eirik

    2015-09-01

    Non-sterile pathogen-induced sepsis and sterile inflammation like in trauma or ischemia-reperfusion injury may both coincide with the life threatening systemic inflammatory response syndrome and multi-organ failure. Consequently, there is an urgent need for specific biomarkers in order to distinguish sepsis from sterile conditions. The overall aim of this study was to uncover putative sepsis biomarkers and biomarker pathways, as well as to test the efficacy of combined inhibition of innate immunity key players complement and Toll-like receptor co-receptor CD14 as a possible therapeutic regimen for sepsis. We performed whole blood gene expression analyses using microarray in order to profile Gram-negative bacteria-induced inflammatory responses in an ex vivo human whole blood model. The experiments were performed in the presence or absence of inhibitors of complement proteins (C3 and CD88 (C5a receptor 1)) and CD14, alone or in combination. In addition, we used blood from a C5-deficient donor. Anti-coagulated whole blood was challenged with heat-inactivated Escherichia coli for 2 h, total RNA was isolated and microarray analyses were performed on the Affymetrix GeneChip Gene 1.0 ST Array platform. The initial experiments were performed in duplicates using blood from two healthy donors. C5-deficiency is very rare, and only one donor could be recruited. In order to increase statistical power, a technical replicate of the C5-deficient samples was run. Subsequently, log2-transformed intensities were processed by robust multichip analysis and filtered using a threshold of four. In total, 73 microarray chips were run and analyzed. The normalized and filtered raw data have been deposited in NCBI's Gene Expression Omnibus (GEO) and are accessible with GEO Series accession number GSE55537. Linear models for microarray data were applied to estimate fold changes between data sets and the respective multiple testing adjusted p-values (FDR q-values). The interpretation of the

  6. Immunizations and Asians and Pacific Islanders

    MedlinePlus

    ... Profiles > Asian American > Immunizations Immunizations and Asians and Pacific Islanders Asian/Pacific Islander adults are 10% less likely to ever ... to non-Hispanic white adults. In 2014, Asian/Pacific Islander adults aged 65 years and older were ...

  7. National-Scale Changes in Soil Profile C and N in New Zealand Pastures are Determined by Land Use

    NASA Astrophysics Data System (ADS)

    Schipper, L. A.; Parfitt, R.; Ross, C.; Baisden, W. T.; Claydon, J.; Fraser, S.

    2010-12-01

    Grazed pasture is New Zealand’s predominant agricultural land-use and has been relatively recently developed from forest and native grasslands/shrub communities. From the 1850s onwards, land was cleared and exotic pastures established. Phosphorus fertilizer was increasingly used after 1950 which accelerated N fixation by clover. In the last two decades N fertilizers have been used, and grazing intensity has increased, thus affecting soil C and N. Re-sampling of 31 New Zealand soil profiles under grazed pasture measured surprisingly large losses of C and N over the last 2-3 decades (Schipper et al., 2007 Global Change Biology 13:1138-1144). These profiles were predominantly on the most intensively grazed flat land. We extended this re-sampling to 83 profiles (to 90 cm depth), to investigate whether changes in soil C and N stocks also occurred in less intensively managed pasture. Archived soils samples were analysed for total soil C and N alongside the newly collected samples. Intact cores were collected to determine bulk density through the profile. Over an average of 27 years, soils (0-30 cm) in flat dairy pastures significantly lost 0.73±0.16 Mg C ha-1y-1 and 57±16 kg N ha-1y-1 while we observed no change in soil C or N in flat pasture grazed by “dry stock” (e.g., sheep, beef), or in grazed tussock grasslands. Grazed hill country soils (0-30 cm) gained 0.52±0.18 Mg C ha-1y-1 and 66±18 kg N ha-1y-1. The losses of C and N were strongly correlated and C:N ratio has generally declined suggesting soils are becoming N saturated. Losses and gains also occurred in soil layers below 30 cm demonstrating that organic matter throughout the profile was responding to land use. The losses under dairying may be due to greater grazing pressure, fertilizer inputs and exports of C and N. There is evidence that grazing pressure reduces inputs of C below ground, reduces soil microbial C, and that dairy cow urine can mobilise C and N. Gains in hill country pastures may be due

  8. Source profiles of particulate matter emissions from a pilot-scale boiler burning North American coal blends.

    PubMed

    Lee, S W

    2001-11-01

    Recent awareness of suspected adverse health effects from ambient particulate matter (PM) emission has prompted publication of new standards for fine PM with aerodynamic diameter less than 2.5 microm (PM2.5). However, scientific data on fine PM emissions from various point sources and their characteristics are very limited. Source apportionment methods are applied to identify contributions of individual regional sources to tropospheric particulate concentrations. The existing industrial database developed using traditional source measurement techniques provides total emission rates only, with no details on chemical nature or size characteristics of particulates. This database is inadequate, in current form, to address source-receptor relationships. A source dilution system was developed for sampling and characterization of total PM, PM2.5, and PM10 (i.e., PM with aerodynamic diameter less than 10 pm) from residual oil and coal combustion. This new system has automatic control capabilities for key parameters, such as relative humidity (RH), temperature, and sample dilution. During optimization of the prototype equipment, three North American coal blends were burned using a 0.7-megawatt thermal (MWt) pulverized coal-fired, pilot-scale boiler. Characteristic emission profiles, including PM2.5 and total PM soluble acids, and elemental and carbon concentrations for three coal blends are presented. Preliminary results indicate that volatile trace elements such as Pb, Zn, Ti, and Se are preferentially enriched in PM2.5. PM2.5 is also more concentrated in soluble sulfates relative to total PM. Coal fly ash collected at the outlet of the electrostatic precipitator (ESP) contains about 85-90% PM10 and 30-50% PM2.5. Particles contain the highest elemental concentrations of Si and Al while Ca, Fe, Na, Ba, and K also exist as major elements. Approximately 4-12% of the materials exists as soluble sulfates in fly ash generated by coal blends containing 0.2-0.8% sulfur by mass

  9. The Dryline on 22 May 2002 during IHOP_2002: Convective-Scale Measurements at the Profiling Site

    NASA Technical Reports Server (NTRS)

    Demoz, Belay; Flamant, Cyrille; Weckwerth, Tammy; Whiteman, David; Evans, Keith; Fabry, Frederic; DiGirolamo, Paolo; Miller, David; Geerts, Bart; Brown, William; Schwemmer, Geary; Gentry, Bruce; Feltz, Wayne; Wang, Zhien

    2006-01-01

    A detailed analysis of the structure of a double dryline observed over the Oklahoma panhandle during the first International H2O Project (IHOP_2002) convective initiation (CI) mission on 22 May 2002 is presented. A unique and unprecedented set of high temporal and spatial resolution measurements of water vapor mixing ratio, wind, and boundary layer structure parameters were acquired using the National Aeronautics and Space Administration (NASA) scanning Raman lidar (SRL), the Goddard Lidar Observatory for Winds (GLOW), and the Holographic Airborne Rotating Lidar Instrument Experiment (HARLIE), respectively. These measurements are combined with the vertical velocity measurements derived from the National Center for Atmospheric Research (NCAR) Multiple Antenna Profiler Radar (MAPR) and radar structure function from the high-resolution University of Massachusetts frequency-modulated continuous-wave (FMCW) radar to reveal the evolution and structure of the late afternoon double-dryline boundary layer. The eastern dryline advanced and then retreated over the Homestead profiling site in the Oklahoma panhandle, providing conditions ripe for a detailed observation of the small-scale variability within the boundary layer and the dryline. In situ aircraft data, dropsonde and radiosonde data, along with NCAR S-band dual-polarization Doppler radar (S-Pol) measurements, are also used to provide the larger-scale picture of the double-dryline environment. Moisture and temperature jumps of about 3 g kg(sup -1) and 1 -2 K, respectively, were observed across the eastern radar fine line (dryline), more than the moisture jumps (1-2 g kg(sup -1)) observed across the western radar fine line (secondary dryline). Most updraft plumes observed were located on the moist side of the eastern dryline with vertical velocities exceeding 3 m s(sup -1) and variable horizontal widths of 2-5 km, although some were as wide as 7-8 km. These updrafts were up to 1.5 g kg(sup -1) moister than the

  10. Expression profile of immune-associated genes in the kidney of cultured large yellow croaker Larimichthys crocea in the East China Sea area

    NASA Astrophysics Data System (ADS)

    Zhao, Shujiang; Zhao, Qian; Chen, Yinghua; Lv, Baoqiang; Wu, Xiongfei; Liu, Huihui; Zhu, Aiyi; Wu, Changwen

    2016-08-01

    To explore the effect of environment conditions on immune activity of fish, eight immune-associated genes responsible for innate immunity were selected from the GenBank, i.e. Pgrn-a, Ifit2, P-hepcidin, Lect2, β2m, Irf1, Il25 and Hsp96, and the mRNA expressions of them in the kidney of cultured large yellow croaker Larimichthys crocea in different sea areas in the East China Sea were examined with qPCR techniques. In the contrasts of immune-associated gene expression between areas and populations, significant differences were found, expression levels of these immune-associated genes were lower in the clear water area than in the poor water quantity area, and lower in May than in October. MY was more sensitive to environmental factors than DQ, which was coincident with the water quality in the culturing areas. Differential analyses of the expression levels of these immune-associated genes showed that significant up-regulation could be triggered by poor environmental factors. The expression patterns indicated that the expression levels of these genes were sensitive to ecological changes, thereby the immune-associated genes, especially Pgrn-a, Ifit2, β2m, Il25 and Hsp96, might serve as immediate and sensitive indicators of population immunologic vigor and ecosystem health. But the expression of immunity-associated genes at the level of gene transcription is highly influenced by multiple factors, and the exact causes or influencing factors of the up-regulation or down-regulation of these genes still need further thorough investigation.

  11. Inferring ice formation processes from global-scale black carbon profiles observed in the remote atmosphere and model simulations

    NASA Astrophysics Data System (ADS)

    Fan, S.-M.; Schwarz, J. P.; Liu, J.; Fahey, D. W.; Ginoux, P.; Horowitz, L. W.; Levy, H., II; Ming, Y.; Spackman, J. R.

    2012-12-01

    Black carbon (BC) aerosol absorbs solar radiation and can act as cloud condensation nucleus and ice formation nucleus. The current generation of climate models have difficulty in accurately predicting global-scale BC concentrations. Previously, an ensemble of such models was compared to measurements, revealing model biases in the tropical troposphere and in the polar troposphere. Here global aerosol distributions are simulated using different parameterizations of wet removal, and model results are compared to BC profiles observed in the remote atmosphere to explore the possible sources of these biases. The model-data comparison suggests a slow removal of BC aerosol during transport to the Arctic in winter and spring, because ice crystal growth causes evaporation of liquid cloud via the Bergeron process and, hence, release of BC aerosol back to ambient air. By contrast, more efficient model wet removal is needed in the cold upper troposphere over the tropical Pacific. Parcel model simulations with detailed droplet and ice nucleation and growth processes suggest that ice formation in this region may be suppressed due to a lack of ice nuclei (mainly insoluble dust particles) in the remote atmosphere, allowing liquid and mixed-phase clouds to persist under freezing temperatures, and forming liquid precipitation capable of removing aerosol incorporated in cloud water. Falling ice crystals can scavenge droplets in lower clouds, which also results in efficient removal of cloud condensation nuclei. The combination of models with global-scale BC measurements in this study has provided new, latitude-dependent information on ice formation processes in the atmosphere, and highlights the importance of a consistent treatment of aerosol and moist physics in climate models.

  12. Carrier separation and transport in perovskite solar cells studied by nanometre-scale profiling of electrical potential

    PubMed Central

    Jiang, Chun-Sheng; Yang, Mengjin; Zhou, Yuanyuan; To, Bobby; Nanayakkara, Sanjini U.; Luther, Joseph M.; Zhou, Weilie; Berry, Joseph J.; van de Lagemaat, Jao; Padture, Nitin P.; Zhu, Kai; Al-Jassim, Mowafak M.

    2015-01-01

    Organometal–halide perovskite solar cells have greatly improved in just a few years to a power conversion efficiency exceeding 20%. This technology shows unprecedented promise for terawatt-scale deployment of solar energy because of its low-cost, solution-based processing and earth-abundant materials. We have studied charge separation and transport in perovskite solar cells—which are the fundamental mechanisms of device operation and critical factors for power output—by determining the junction structure across the device using the nanoelectrical characterization technique of Kelvin probe force microscopy. The distribution of electrical potential across both planar and porous devices demonstrates p–n junction structure at the TiO2/perovskite interfaces and minority-carrier diffusion/drift operation of the devices, rather than the operation mechanism of either an excitonic cell or a p-i-n structure. Combining the potential profiling results with solar cell performance parameters measured on optimized and thickened devices, we find that carrier mobility is a main factor that needs to be improved for further gains in efficiency of the perovskite solar cells. PMID:26411597

  13. Carrier separation and transport in perovskite solar cells studied by nanometre-scale profiling of electrical potential.

    PubMed

    Jiang, Chun-Sheng; Yang, Mengjin; Zhou, Yuanyuan; To, Bobby; Nanayakkara, Sanjini U; Luther, Joseph M; Zhou, Weilie; Berry, Joseph J; van de Lagemaat, Jao; Padture, Nitin P; Zhu, Kai; Al-Jassim, Mowafak M

    2015-01-01

    Organometal-halide perovskite solar cells have greatly improved in just a few years to a power conversion efficiency exceeding 20%. This technology shows unprecedented promise for terawatt-scale deployment of solar energy because of its low-cost, solution-based processing and earth-abundant materials. We have studied charge separation and transport in perovskite solar cells-which are the fundamental mechanisms of device operation and critical factors for power output-by determining the junction structure across the device using the nanoelectrical characterization technique of Kelvin probe force microscopy. The distribution of electrical potential across both planar and porous devices demonstrates p-n junction structure at the TiO2/perovskite interfaces and minority-carrier diffusion/drift operation of the devices, rather than the operation mechanism of either an excitonic cell or a p-i-n structure. Combining the potential profiling results with solar cell performance parameters measured on optimized and thickened devices, we find that carrier mobility is a main factor that needs to be improved for further gains in efficiency of the perovskite solar cells. PMID:26411597

  14. Carrier separation and transport in perovskite solar cells studied by nanometre-scale profiling of electrical potential

    NASA Astrophysics Data System (ADS)

    Jiang, Chun-Sheng; Yang, Mengjin; Zhou, Yuanyuan; To, Bobby; Nanayakkara, Sanjini U.; Luther, Joseph M.; Zhou, Weilie; Berry, Joseph J.; van de Lagemaat, Jao; Padture, Nitin P.; Zhu, Kai; Al-Jassim, Mowafak M.

    2015-09-01

    Organometal-halide perovskite solar cells have greatly improved in just a few years to a power conversion efficiency exceeding 20%. This technology shows unprecedented promise for terawatt-scale deployment of solar energy because of its low-cost, solution-based processing and earth-abundant materials. We have studied charge separation and transport in perovskite solar cells--which are the fundamental mechanisms of device operation and critical factors for power output--by determining the junction structure across the device using the nanoelectrical characterization technique of Kelvin probe force microscopy. The distribution of electrical potential across both planar and porous devices demonstrates p-n junction structure at the TiO2/perovskite interfaces and minority-carrier diffusion/drift operation of the devices, rather than the operation mechanism of either an excitonic cell or a p-i-n structure. Combining the potential profiling results with solar cell performance parameters measured on optimized and thickened devices, we find that carrier mobility is a main factor that needs to be improved for further gains in efficiency of the perovskite solar cells.

  15. Carrier Separation and Transport in Perovskite Solar Cells Studied by Nanometre-Scale Profiling of Electrical Potential

    DOE PAGESBeta

    Jiang, Chun-Sheng; Yang, Mengjin; Zhou, Yuanyuan; To, Bobby; Nanayakkara, Sanjini U.; Luther, Joseph M.; Zhou, Weilie; Berry, Joseph J.; van de Lagemaat, Jao; Padture, Nitin P.; et al

    2015-09-28

    Organometal–halide perovskite solar cells have greatly improved in just a few years to a power conversion efficiency exceeding 20%. This technology shows unprecedented promise for terawatt-scale deployment of solar energy because of its low-cost, solution-based processing and earth-abundant materials. We have studied charge separation and transport in perovskite solar cells—which are the fundamental mechanisms of device operation and critical factors for power output—by determining the junction structure across the device using the nanoelectrical characterization technique of Kelvin probe force microscopy. Moreover, the distribution of electrical potential across both planar and porous devices demonstrates p–n junction structure at the TiO2/perovskite interfacesmore » and minority-carrier diffusion/drift operation of the devices, rather than the operation mechanism of either an excitonic cell or a p-i-n structure. When we combined the potential profiling results with solar cell performance parameters measured on optimized and thickened devices, we find that carrier mobility is a main factor that needs to be improved for further gains in efficiency of the perovskite solar cells.« less

  16. Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens

    PubMed Central

    Lo, Yu-Chen; Senese, Silvia; Li, Chien-Ming; Hu, Qiyang; Huang, Yong; Damoiseaux, Robert; Torres, Jorge Z.

    2015-01-01

    Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (60–70%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/). PMID:25826798

  17. Carrier Separation and Transport in Perovskite Solar Cells Studied by Nanometre-Scale Profiling of Electrical Potential

    SciTech Connect

    Jiang, Chun-Sheng; Yang, Mengjin; Zhou, Yuanyuan; To, Bobby; Nanayakkara, Sanjini U.; Luther, Joseph M.; Zhou, Weilie; Berry, Joseph J.; van de Lagemaat, Jao; Padture, Nitin P.; Zhu, Kai; Al-Jassim, Mowafak M.

    2015-09-28

    Organometal–halide perovskite solar cells have greatly improved in just a few years to a power conversion efficiency exceeding 20%. This technology shows unprecedented promise for terawatt-scale deployment of solar energy because of its low-cost, solution-based processing and earth-abundant materials. We have studied charge separation and transport in perovskite solar cells—which are the fundamental mechanisms of device operation and critical factors for power output—by determining the junction structure across the device using the nanoelectrical characterization technique of Kelvin probe force microscopy. Moreover, the distribution of electrical potential across both planar and porous devices demonstrates p–n junction structure at the TiO2/perovskite interfaces and minority-carrier diffusion/drift operation of the devices, rather than the operation mechanism of either an excitonic cell or a p-i-n structure. When we combined the potential profiling results with solar cell performance parameters measured on optimized and thickened devices, we find that carrier mobility is a main factor that needs to be improved for further gains in efficiency of the perovskite solar cells.

  18. Mesozoic(?) lithosphere-scale buckling of the East European Craton in southern Ukraine: DOBRE-4 deep seismic profile

    NASA Astrophysics Data System (ADS)

    Starostenko, Vitaly; Janik, Tomasz; Lysynchuk, Dmytro; Środa, Piotr; Czuba, Wojciech; Kolomiyets, Katherina; Aleksandrowski, Paweł; Gintov, Oleg; Omelchenko, Victor; Komminaho, Kari; Guterch, Aleksander; Tiira, Timo; Gryn, Dmytro; Legostaeva, Olga; Thybo, Hans; Tolkunov, Anatoliy

    2013-04-01

    In order to study the lithospheric structure in southern Ukraine, a seismic wide-angle reflection/refraction project DOBRE-4 was conducted. The 500 km-long profile starts in the SW from the Alpine/Variscan North Dobrudja fold-thrust belt, being part of the Trans-European Suture Zone. It runs to the NE, mostly along the NW Black Sea coastal plain, towards the center of the Precambrian Ukrainian Shield. The field acquisition in October 2009 included 13 chemical shot points with charge sizes 600-1000 kg every 35-50 km and 230 recording stations, every ~2.5 km. The high data quality allows modelling of the P- and S-wave velocity structure along the profile. Two methods were used for the modelling of the seismic data. At first, ray-tracing trial-and-error modelling was developed using arrivals of major refracted and reflected P- and S-wave phases. Next, the amplitudes of the recorded phases were analysed using finite-difference full waveform method. The resulting velocity model shows fairly homogeneous structure of the middle to lower crust both vertically and laterally. The situation is different in the upper crust, with Vp velocities decreasing upwards from c. 6.35 at 15-20 km to 5.9-5.8 km/s at the top of the crystalline basement and to c. 5.15 to 3.80 km/s in Neoproterozoic and Palaeozoic and to 2.70 to 2.30 km/s in Mesozoic strata. Below the upper crust the Vp smoothly increases downward, from c. 6.5 to 6.7-6.8 km/s near the crustal base, making it difficult to differentiate between the middle and lower crust. No Vp velocities exceeding 6.80 km/s have been recorded even in the lowermost part of the crust, unlike in similar profiles on the East European Craton. There is no clear change in the velocity field when moving laterally from the Precambrian platform into the younger tectonic units to the SW. Therefore, on purely seismic grounds it is not possible to distinguish major tectonic units known from the surface. The Moho is, however, clearly delineated by a

  19. Mesozoic(?) lithosphere-scale buckling of the East European Craton in southern Ukraine: DOBRE-4 deep seismic profile

    NASA Astrophysics Data System (ADS)

    Starostenko, V.; Janik, T.; Lysynchuk, D.; Środa, P.; Czuba, W.; Kolomiyets, K.; Aleksandrowski, P.; Gintov, O.; Omelchenko, V.; Komminaho, K.; Guterch, A.; Tiira, T.; Gryn, D.; Legostaeva, O.; Thybo, H.; Tolkunov, A.

    2013-11-01

    In order to study the lithospheric structure in southern Ukraine, a seismic wide-angle reflection/refraction project DOBRE-4 was conducted. The 500-km-long profile starts in the SW from the Alpine/Variscan North Dobrudja Fold-Thrust Belt, being part of the Trans-European Suture Zone. It runs to the NE, mostly along the NW Black Sea coastal plain, towards the centre of the Precambrian Ukrainian Shield. The field acquisition in October 2009 included 13 chemical shot points with charge sizes 600-1000 kg every 35-50 km and 230 recording stations, every ˜2.5 km. The high data quality allows modelling of the P- and S-wave velocity structure along the profile. Two methods were used for the modelling of the seismic data. At first, ray tracing trial-and-error modelling was developed using arrivals of major refracted and reflected P- and S-wave phases. Next, the amplitudes of the recorded phases were analysed using finite-difference full waveform method. The resulting velocity model shows fairly homogeneous structure of the middle to lower crust both vertically and laterally. The situation is different in the upper crust, with Vp velocities decreasing upwards from ca. 6.35 at 15-20 km to 5.9-5.8 km s-1 at the top of the crystalline basement and to ca. 5.15-3.80 km s-1 in Neoproterozoic and Palaeozoic and to 2.70-2.30 km s-1 in Mesozoic strata. Below the upper crust the Vp smoothly increases downward, from ca. 6.50 to 6.7-6.8 km s-1 near the crustal base, making it difficult to differentiate between the middle and lower crust. No Vp velocities exceeding 6.80 km s-1 have been recorded even in the lowermost part of the crust, unlike in similar profiles on the East European Craton. There is no clear change in the velocity field when moving laterally from the Precambrian platform into the younger tectonic units to the SW. Therefore, on purely seismic grounds it is not possible to distinguish major tectonic units known from the surface. The Moho is, however, clearly delineated by

  20. Performance assessment and calibration of a profiling lab-scale acoustic Doppler velocimeter for application over mixed sand-gravel beds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acoustic Doppler velocimetry has made high-resolution turbulence measurements in sediment-laden flows possible. Recent developments have resulted in a commercially available lab-scale acoustic Doppler profiling device, a Nortek Vectrino II, that allows for three-dimensional velocity data to be colle...

  1. Improving the Quality and Applicability of the Dutch Scales of the Communication Profile for the Hearing Impaired Using Item Response Theory

    ERIC Educational Resources Information Center

    Mokkink, Lidwine B.; Knol, Dirk L.; van Nispen, Ruth M. A.; Kramer, Sophia E.

    2010-01-01

    Purpose: The aim of this study was to improve the quality and applicability of the 6 Dutch scales of the Communication Profile for the Hearing Impaired (CPHI; Demorest & Erdman, 1986, 1987, 1988) using item response theory (IRT). IRT modeling can produce precise, valid, and relatively brief instruments, resulting in minimal response burden (Edelen…

  2. Integrated Immune

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

    2010-01-01

    This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  3. Possibilities of LA-ICP-MS technique for the spatial elemental analysis of the recent fish scales: Line scan vs. depth profiling

    NASA Astrophysics Data System (ADS)

    Holá, Markéta; Kalvoda, Jiří; Nováková, Hana; Škoda, Radek; Kanický, Viktor

    2011-01-01

    LA-ICP-MS and solution based ICP-MS in combination with electron microprobe are presented as a method for the determination of the elemental spatial distribution in fish scales which represent an example of a heterogeneous layered bone structure. Two different LA-ICP-MS techniques were tested on recent common carp ( Cyprinus carpio) scales: A line scan through the whole fish scale perpendicular to the growth rings. The ablation crater of 55 μm width and 50 μm depth allowed analysis of the elemental distribution in the external layer. Suitable ablation conditions providing a deeper ablation crater gave average values from the external HAP layer and the collagen basal plate. Depth profiling using spot analysis was tested in fish scales for the first time. Spot analysis allows information to be obtained about the depth profile of the elements at the selected position on the sample. The combination of all mentioned laser ablation techniques provides complete information about the elemental distribution in the fish scale samples. The results were compared with the solution based ICP-MS and EMP analyses. The fact that the results of depth profiling are in a good agreement both with EMP and PIXE results and, with the assumed ways of incorporation of the studied elements in the HAP structure, suggests a very good potential for this method.

  4. Expression profile of key immune-related genes in Penaeus monodon juveniles after oral administration of recombinant envelope protein VP28 of white spot syndrome virus.

    PubMed

    Thomas, Ancy; Sudheer, Naduvilamuriparampu Saidumuhammed; Kiron, Viswanath; Bright Singh, Issac S; Narayanan, Rangarajan Badri

    2016-07-01

    White spot syndrome virus (WSSV) is the most catastrophic pathogen the shrimp industry has ever encountered. VP28, the abundant envelope protein of WSSV was expressed in bacteria, the purified protein administered orally to Penaeus monodon juveniles and its immune modulatory effects examined. The results indicated significant up-regulation of caspase, penaeidin, crustin, astakine, syntenin, PmRACK, Rab7, STAT and C-type lectin in animals orally administered with this antigen. This revealed the immune modulations in shrimps followed by oral administration of rVP28P which resulted in the reduced transcription of viral gene vp28 and delay in mortality after WSSV challenge. The study suggests the potential of rVP28P to elicit a non-specific immune stimulation in shrimps. PMID:27154537

  5. Broad-Scale Phosphoprotein Profiling of Beta Adrenergic Receptor (β-AR) Signaling Reveals Novel Phosphorylation and Dephosphorylation Events

    PubMed Central

    Chruscinski, Andrzej J.; Singh, Harvir; Chan, Steven M.; Utz, Paul J.

    2013-01-01

    β-adrenergic receptors (β-ARs) are model G-protein coupled receptors that mediate signal transduction in the sympathetic nervous system. Despite the widespread clinical use of agents that target β-ARs, the signaling pathways that operate downstream of β-AR stimulation have not yet been completely elucidated. Here, we utilized a lysate microarray approach to obtain a broad-scale perspective of phosphoprotein signaling downstream of β-AR. We monitored the time course of phosphorylation states of 54 proteins after β-AR activation mouse embryonic fibroblast (MEF) cells. In response to stimulation with the non-selective β-AR agonist isoproterenol, we observed previously described phosphorylation events such as ERK1/2(T202/Y204) and CREB(S133), but also novel phosphorylation events such as Cdc2(Y15) and Pyk2(Y402). All of these events were mediated through cAMP and PKA as they were reproduced by stimulation with the adenylyl cyclase activator forskolin and were blocked by treatment with H89, a PKA inhibitor. In addition, we also observed a number of novel isoproterenol-induced protein dephosphorylation events in target substrates of the PI3K/AKT pathway: GSK3β(S9), 4E-BP1(S65), and p70s6k(T389). These dephosphorylations were dependent on cAMP, but were independent of PKA and correlated with reduced PI3K/AKT activity. Isoproterenol stimulation also led to a cAMP-dependent dephosphorylation of PP1α(T320), a modification known to correlate with enhanced activity of this phosphatase. Dephosphorylation of PP1α coincided with the secondary decline in phosphorylation of some PKA-phosphorylated substrates, suggesting that PP1α may act in a feedback loop to return these phosphorylations to baseline. In summary, lysate microarrays are a powerful tool to profile phosphoprotein signaling and have provided a broad-scale perspective of how β-AR signaling can regulate key pathways involved in cell growth and metabolism. PMID:24340001

  6. Integrated analysis of miRNAs and transcriptomes in Aedes albopictus midgut reveals the differential expression profiles of immune-related genes during dengue virus serotype-2 infection.

    PubMed

    Liu, Yan-Xia; Li, Fen-Xiang; Liu, Zhuan-Zhuan; Jia, Zhi-Rong; Zhou, Yan-He; Zhang, Hao; Yan, Hui; Zhou, Xian-Qiang; Chen, Xiao-Guang

    2016-06-01

    Mosquito microRNAs (miRNAs) are involved in host-virus interaction, and have been reported to be altered by dengue virus (DENV) infection in Aedes albopictus (Diptera: Culicidae). However, little is known about the molecular mechanisms of Aedes albopictus midgut-the first organ to interact with DENV-involved in its resistance to DENV. Here we used high-throughput sequencing to characterize miRNA and messenger RNA (mRNA) expression patterns in Aedes albopictus midgut in response to dengue virus serotype 2. A total of three miRNAs and 777 mRNAs were identified to be differentially expressed upon DENV infection. For the mRNAs, we identified 198 immune-related genes and 31 of them were differentially expressed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses also showed that the differentially expressed immune-related genes were involved in immune response. Then the differential expression patterns of six immune-related genes and three miRNAs were confirmed by real-time reverse transcription polymerase chain reaction. Furthermore, seven known miRNA-mRNA interaction pairs were identified by aligning our two datasets. These analyses of miRNA and mRNA transcriptomes provide valuable information for uncovering the DENV response genes and provide a basis for future study of the resistance mechanisms in Aedes albopictus midgut. PMID:27029517

  7. Immune Repertoire Profiling Reveals that Clonally Expanded B and T Cells Infiltrating Diseased Human Kidneys Can Also Be Tracked in Blood

    PubMed Central

    Schaller, Susanne; Suessner, Susanne; Sunzenauer, Judith; Reindl-Schwaighofer, Roman; Weiss, Richard; Winkler, Stephan; Gabriel, Christian; Danzer, Martin; Oberbauer, Rainer

    2015-01-01

    Recent advances in high-throughput sequencing allow for the competitive analysis of the human B and T cell immune repertoire. In this study we compared Immunoglobulin and T cell receptor repertoires of lymphocytes found in kidney and blood samples of 10 patients with various renal diseases based on next-generation sequencing data. We used Biomed-2 primer panels and ImmunExplorer software to sequence, analyze and compare complementarity determining regions and V-(D)-J elements. While generally an individual’s renal receptor repertoire is different from the repertoire present in blood, 94% (30/32) of the lymphocytes with clonal expansion in kidney can also be traced in blood however, not all of these clonotypes are equally abundant. Summarizing the data of all analyzed patients, 68% of highly expanded T cell clonotypes and 30% of the highly expanded B cell clonotypes that have infiltrated the kidney can be found amongst the five most abundant clonotypes in blood. In addition, complementarity determining region 3 sequences of the immunoglobulin heavy chains are on average more diverse than T cell receptor beta chains. Immune repertoire analysis of tissue infiltrating B and T cells adds new approaches to the assessment of adaptive immune response in kidney diseases. Our data suggest that expanded clonotypes in the tissues might be traceable in blood samples in the course of treatment or the natural history of the disease. PMID:26600245

  8. Differential immune gene expression profiles in susceptible and resistant full-sibling families of Atlantic salmon (Salmo salar) challenged with infectious pancreatic necrosis virus (IPNV).

    PubMed

    Reyes-López, Felipe E; Romeo, Jose S; Vallejos-Vidal, Eva; Reyes-Cerpa, Sebastián; Sandino, Ana M; Tort, Lluis; Mackenzie, Simon; Imarai, Mónica

    2015-11-01

    This study aims to identify at the expression level the immune-related genes associated with IPN-susceptible and resistant phenotypes in Atlantic salmon full-sibling families. We have analyzed thirty full-sibling families infected by immersion with IPNV and then classified as resistant or susceptible using a multivariate survival analysis based on a gamma-Cox frailty model and the Kaplan-Meier mortality curves. In four families within each group head kidneys were pooled for real-time PCR and one-color salmon-specific oligonucleotide microarray (21K) analysis at day 1 and 5 post-infection. Transcripts involved in innate response (IL-6, IFN-α), antigen presentation (HSP-70, HSP-90, MHC-I), TH1 response (IL-12, IFN-γ, CRFB6), immunosuppression (IL-10, TGF-β1) and leukocyte activation and migration (CCL-19, CD18) showed a differential expression pattern between both phenotypes, except in IL-6. In susceptible families, except for IFN-γ, the expressions dropped to basal values at day 5 post-infection. In resistant families, unlike susceptible families, levels remained high or increased (except for IL-6) at day 5. Transcriptomic analysis showed that both families have a clear differential expression pattern, resulting in a marked down-regulation in immune related genes involved in innate response, complement system, antigen recognition and activation of immune response in IPN-resistant. Down-regulation of genes, mainly related to tissue differentiation and protein degradation metabolism, was also observed in resistant families. We have identified an immune-related gene patterns associated with susceptibility and resistance to IPNV infection of Atlantic salmon. This suggests that a limited immune response is associated with resistant fish phenotype to IPNV challenge while a highly inflammatory but short response is associated with susceptibility. PMID:26123889

  9. Immune Profile Predicts Survival and Reflects Senescence in a Small, Long-Lived Mammal, the Greater Sac-Winged Bat (Saccopteryx bilineata)

    PubMed Central

    Schneeberger, Karin; Courtiol, Alexandre; Czirják, Gábor Á.; Voigt, Christian C.

    2014-01-01

    The immune system imposes costs that may have to be traded against investment of resources in other costly life-history traits. Yet, it is unknown if a trade-off between immunity and longevity occurs in free-ranging mammals. Here, we tested if age and survival, two aspects associated with longevity, are linked to immune parameters in an 8 g bat species. Using a combination of cross-sectional and longitudinal data, we assessed whether total white blood cell (WBC) counts, bacterial killing ability of the plasma (BKA) and immunoglobulin G (IgG) concentration change with age. Furthermore, we asked if these immune parameters impose costs resulting in decreased survival probabilities. We found that WBC counts decreased with age both within and among individuals. IgG concentrations were higher in older individuals, but did not change with age within individuals. Furthermore, individuals with above average WBC counts or IgG concentration had lower probabilities to survive the next six months. High WBC counts and IgG concentrations may reflect infections with parasites and pathogens, however, individuals that were infected with trypanosomes or nematodes showed neither higher WBC counts or IgG concentrations, nor was infection connected with survival rates. BKA was higher in infected compared with uninfected bats, but not related to age or survival. In conclusion, cellular (WBC) and humoral (IgG) parts of the immune system were both connected to age and survival, but not to parasite infections, which supports the hypothesis that energetically costly immunological defences are traded against other costly life-history traits, leading to a reduced lifespan in this free-ranging mammal. PMID:25254988

  10. Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407.

    PubMed

    Chakraborty, Subhra; Harro, Clayton; DeNearing, Barbara; Ram, Malathi; Feller, Andrea; Cage, Alicia; Bauers, Nicole; Bourgeois, A Louis; Walker, Richard; Sack, David A

    2016-01-01

    Enterotoxigenic Escherichia coli (ETEC) bacteria are the most common bacterial cause of diarrhea in children in resource-poor settings as well as in travelers. Although there are several approaches to develop an effective vaccine for ETEC, no licensed vaccines are currently available. A significant challenge to successful vaccine development is our poor understanding of the immune responses that correlate best with protection against ETEC illness. In this study, ETEC-specific mucosal immune responses were characterized and compared in subjects challenged with ETEC strain H10407 and in subjects rechallenged with the homologous organism. IgA responses to lipopolysaccharide (LPS), heat-labile toxin B subunit (LTB), and colonization factor antigen I (CFA/I) in antibody in lymphocyte supernatant (ALS), feces, lavage fluid, and saliva samples were evaluated. In all assay comparisons, ALS was the most sensitive indicator of a local immune response, but serum IgA was also a useful indirect marker of immune response to oral antigens. Volunteers challenged and then rechallenged with strain H10407 were protected from illness following rechallenge. Comparing mucosal antibody responses after primary and homologous rechallenge, protection against disease was reflected in reduced antibody responses to key ETEC antigens and in reduced fecal shedding of the H10407 challenge strain. Subjects challenged with strain H10407 mounted stronger antibody responses to LPS and LTB than subjects in the rechallenge group, while responses to CFA/I in the rechallenge group were higher than in the challenge group. We anticipate that this study will help provide an immunological benchmark for the evaluation of ETEC vaccines and immunization regimens in the future. PMID:26581889

  11. Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407

    PubMed Central

    Harro, Clayton; DeNearing, Barbara; Ram, Malathi; Feller, Andrea; Cage, Alicia; Bauers, Nicole; Bourgeois, A. Louis; Walker, Richard; Sack, David A.

    2015-01-01

    Enterotoxigenic Escherichia coli (ETEC) bacteria are the most common bacterial cause of diarrhea in children in resource-poor settings as well as in travelers. Although there are several approaches to develop an effective vaccine for ETEC, no licensed vaccines are currently available. A significant challenge to successful vaccine development is our poor understanding of the immune responses that correlate best with protection against ETEC illness. In this study, ETEC-specific mucosal immune responses were characterized and compared in subjects challenged with ETEC strain H10407 and in subjects rechallenged with the homologous organism. IgA responses to lipopolysaccharide (LPS), heat-labile toxin B subunit (LTB), and colonization factor antigen I (CFA/I) in antibody in lymphocyte supernatant (ALS), feces, lavage fluid, and saliva samples were evaluated. In all assay comparisons, ALS was the most sensitive indicator of a local immune response, but serum IgA was also a useful indirect marker of immune response to oral antigens. Volunteers challenged and then rechallenged with strain H10407 were protected from illness following rechallenge. Comparing mucosal antibody responses after primary and homologous rechallenge, protection against disease was reflected in reduced antibody responses to key ETEC antigens and in reduced fecal shedding of the H10407 challenge strain. Subjects challenged with strain H10407 mounted stronger antibody responses to LPS and LTB than subjects in the rechallenge group, while responses to CFA/I in the rechallenge group were higher than in the challenge group. We anticipate that this study will help provide an immunological benchmark for the evaluation of ETEC vaccines and immunization regimens in the future. PMID:26581889

  12. De novo assembly and analysis of tissue-specific transcriptomes revealed the tissue-specific genes and profile of immunity from Strongylocentrotus intermedius.

    PubMed

    Chen, Yadong; Chang, Yaqing; Wang, Xiuli; Qiu, Xuemei; Liu, Yang

    2015-10-01

    Strongylocentrotus intermedius is an important marine species in north China and Japan. Recent years, diseases are threating the sea urchin aquaculture industry seriously. To provide a genetic resource for S. intermedius as well as overview the immune-related genes of S. intermedius, we performed transcriptome sequencing of three cDNA libraries representing three tissues, coelomocytes, gut and peristomial membrane respectively. In total 138,421 contigs were assembled from all sequencing data. 96,764 contigs were annotated according to bioinformatics databases, including NT, nr, Swiss-Prot, KEGG, COG. 49,336 Contigs were annotated as CDS. In this study, we obtained 24,778 gene families from S. intermedius transcriptome. The gene expression analysis revealed that more genes were expressed in gut, more high expression level genes in coelomocytes when compared with other tissues. Specific expressed contigs in coelomocytes, gut, and peristomial membrane were 546, 1136, and 1012 respectively. Pathway analysis suggested 25, 17 and 36 potential specifically pathways may specific progressed in peristomial membrane, gut and coelomocytes respectively. Similarities and differences between S. intermedius and other echinoderms were analyzed. S. intermedius was more homology to Strongylocentrotus purpuratus than others sea urchin. Of 24,778 genes, 1074 genes are immune-related, immune genes were expressed with a higher level in coelomocytes than other tissues. Complement system may be the most important immune system in sea urchin. We also identified 2438 SSRs and 16,236 SNPs for S. intermedius. These results provide a transcriptome resource and foundation to study molecular mechanisms of sea urchin immune system. PMID:26253994

  13. Moving toward finer scales in oceanography: Predictive linear functional model of Chlorophyll a profile from light data

    NASA Astrophysics Data System (ADS)

    Bayle, Séverine; Monestiez, Pascal; Guinet, Christophe; Nerini, David

    2015-05-01

    The Southern Ocean plays a key role in ocean-atmosphere carbon dioxide fluxes. Estimation of carbon exchanges between ocean and atmosphere must rely on accurate estimations of primary productivity which require measurements of phytoplankton concentration within the water column. In this paper, we are interested in relationships between primary productivity and light in the Antarctic ocean. The originality of this work is twofold. Starting from physical hypothesis, a statistical model is constructed for the prediction of Chlorophyll a (Chl a) profiles where light profiles are used as a covariate. Taking into account of the functional nature of the data, solutions are proposed to estimate continuous vertical profiles from discrete data sampled by elephant seals equipped with a new generation of oceanographic tags. Bootstrapped prediction intervals show a good quality of prediction of Chl a profiles, giving access to the shape of the profiles along depth and to the submesoscale structure of phytoplankton within the euphotic layer of the Southern Ocean.

  14. Childhood Immunization

    MedlinePlus

    ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ... child provide protection for many years, adults need immunizations too. Centers for Disease Control and Prevention

  15. Immunizations - diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  16. Scale

    ERIC Educational Resources Information Center

    Schaffhauser, Dian

    2009-01-01

    The common approach to scaling, according to Christopher Dede, a professor of learning technologies at the Harvard Graduate School of Education, is to jump in and say, "Let's go out and find more money, recruit more participants, hire more people. Let's just keep doing the same thing, bigger and bigger." That, he observes, "tends to fail, and fail…

  17. Immunity to Francisella

    PubMed Central

    Cowley, Siobhán C.; Elkins, Karen L.

    2011-01-01

    In recent years, studies on the intracellular pathogen Francisella tularensis have greatly intensified, generating a wealth of new information on the interaction of this organism with the immune system. Here we review the basic elements of the innate and adaptive immune responses that contribute to protective immunity against Francisella species, with special emphasis on new data that has emerged in the last 5 years. Most studies have utilized the mouse model of infection, although there has been an expansion of work on human cells and other new animal models. In mice, basic immune parameters that operate in defense against other intracellular pathogen infections, such as interferon gamma, TNF-α, and reactive nitrogen intermediates, are central for control of Francisella infection. However, new important immune mediators have been revealed, including IL-17A, Toll-like receptor 2, and the inflammasome. Further, a variety of cell types in addition to macrophages are now recognized to support Francisella growth, including epithelial cells and dendritic cells. CD4+ and CD8+ T cells are clearly important for control of primary infection and vaccine-induced protection, but new T cell subpopulations and the mechanisms employed by T cells are only beginning to be defined. A significant role for B cells and specific antibodies has been established, although their contribution varies greatly between bacterial strains of lower and higher virulence. Overall, recent data profile a pathogen that is adept at subverting host immune responses, but susceptible to many elements of the immune system's antimicrobial arsenal. PMID:21687418

  18. Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

    SciTech Connect

    Battaglia, Alessandra; Buzzonetti, Alexia; Martinelli, Enrica; Fanelli, Mara; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Fattorossi, Andrea

    2010-04-15

    Purpose: To assess how neoadjuvant chemoradiation regimens modulate the immune system state in tumor-draining lymph nodes (TDLN), in the setting of advanced cervical cancer. Methods and Materials: Tumor-draining lymph nodes of patients undergoing chemotherapy only (nonirradiated, NI-TDLN) and chemoradiation with lower-dose (39.6 Gy, LD-TDLN) and higher-dose radiation (50 Gy, HD-TDLN) were analyzed by multicolor flow cytometry. Results: Enlarging our previous data, LD-TDLN showed features overall indicative of an enhanced antitumor response as compared with NI-TDLN, namely a significant Th1 and Tc1 polarization and a lower amount of the potent CD4{sup +}Foxp3{sup +}CD25{sup high} regulatory T cell (Treg) subset identified by neuropilin-1 expression. Conversely, compared with NI-TDLN, HD-TDLN showed features overall indicative of an impaired antitumor response, namely a significantly inverted CD4/CD8 cell ratio, a higher Nrp1{sup +}Treg frequency, and a higher frequency of CCR4{sup +}Treg, a Treg subset facilitated in migrating out from TDLN to suppress the immune response against distant cancer cells. Moreover, the Th1 and Tc1 polarization induced by LD radiation was lost, and there was an unfavorable tolerogenic/immunogenic dendritic cell ratio compared with LD-TDLN. Conclusions: Even minor differences in radiation dose in neoadjuvant regimens for locally advanced cervical cancer are crucial for determining the balance between a tolerogenic and an efficacious antitumor immune response in TDLN. Because most of the anticancer immune response takes place in TDLN, the present findings also emphasize the importance of chemoradiation protocols in the context of immunotherapeutic trials.

  19. Global transcriptomic profiling of bovine endometrial immune response in vitro. II. Effect of bovine viral diarrhea virus on the endometrial response to lipopolysaccharide.

    PubMed

    Oguejiofor, Chike F; Cheng, Zhangrui; Abudureyimu, Ayimuguli; Anstaett, Olivia L; Brownlie, Joe; Fouladi-Nashta, Ali A; Wathes, D Claire

    2015-10-01

    Infection with noncytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS). Primary cultures of mixed epithelial and stromal cells were divided into four treatment groups (control [CONT], BVDV, CONT+LPS, and BVDV+LPS) and infected with ncpBVDV for 4 days followed by treatment with LPS for 6 h. Whole-transcriptomic gene expression was measured followed by Ingenuity Pathway Analysis. Differential expression of 184 genes was found between CONT and BVDV treatments, showing interplay between induction and inhibition of responses. Up-regulation of TLR3, complement, and chemotactic and TRIM factors by ncpBVDV all suggested an ongoing immune response to viral infection. Down-regulation of inflammatory cytokines, chemokines, CXCR4, and serine proteinase inhibitors suggested mechanisms by which ncpBVDV may simultaneously counter the host response. Comparison between BVDV+LPS and CONT+LPS treatments showed 218 differentially expressed genes. Canonical pathway analysis identified the key importance of interferon signaling. Top down-regulated genes were RSAD2, ISG15, BST2, MX2, OAS1, USP18, IFIT3, IFI27, SAMD9, IFIT1, and DDX58, whereas TRIM56, C3, and OLFML1 were most up-regulated. Many of these genes are also regulated by IFNT during maternal recognition of pregnancy. Many innate immune genes that typically respond to LPS were inhibited by ncpBVDV, including those involved in pathogen recognition, inflammation, interferon response, chemokines, tissue remodeling, cell migration, and cell death/survival. Infection with ncpBVDV can thus compromise immune function and pregnancy recognition, thereby potentially predisposing infected cows to postpartum bacterial endometritis and reduced fertility. PMID:26353892

  20. Regional immune responses with stage-specific antigen recognition profiles develop in lymph nodes of pigs following Ascaris suum larval migration.

    PubMed

    Jungersen, G; Eriksen, L; Nansen, P; Lind, P; Rasmussen, T; Meeusen, E N

    2001-04-01

    The early life-cycle of the pig round worm, Ascaris suum, involves well-defined larval development in the liver, lungs and finally the small intestine. Distinct regional immune responses to larval antigens of A. suum were observed in the draining lymph nodes of immunized and challenged pigs during larval migration. This was reflected in a transient enlargement of the stimulated lymph nodes, due to increases in numbers of B cells and CD4 T cells, and the production of A. suum-specific antibody by antibody secreting cell (ASC) cultures. Larval antigen recognition pattern of antibodies in serum, bile and draining lymph node ASC culture supernatant (ASC-probes) was examined by immunoblotting. This revealed distinct organ-specific recognition patterns of larval-specific antigens by the draining lymph nodes at different times after challenge. In particular, an early larval 42 kDa antigen was recognized specifically by ASC-probes of the liver lymph nodes at 7 but not 14 days postchallenge (pc) which was not detected in other lymph nodes, serum or bile of the same pig. Similarly, a late larval antigen of 34 kDa was uniquely detected by lung and jejunal ASC-probes at 14 days pc. These observations demonstrate how development of distinct regional immune responses in tissues with different antigen stimulation can be monitored with ASC-probes and flow cytometry. PMID:11298295

  1. Altered HLA Class I Profile Associated with Type A/D Nucleophosmin Mutation Points to Possible Anti-Nucleophosmin Immune Response in Acute Myeloid Leukemia

    PubMed Central

    Kuželová, Kateřina; Brodská, Barbora; Fuchs, Ota; Dobrovolná, Marie; Soukup, Petr; Cetkovský, Petr

    2015-01-01

    Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute myeloid leukemia (AML) and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal individuals (large datasets available from Allele Frequency Net Database). Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B*07, B*18, and B*40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein. PMID:25992555

  2. Toxoplasma gondii Is Dependent on Glutamine and Alters Migratory Profile of Infected Host Bone Marrow Derived Immune Cells through SNAT2 and CXCR4 Pathways

    PubMed Central

    Lee, I-Ping; Works, Melissa G.; Kumar, Vineet; De Miguel, Zurine; Manley, Nathan C.; Sapolsky, Robert M.

    2014-01-01

    The obligate intracellular parasite, Toxoplasma gondii, disseminates through its host inside infected immune cells. We hypothesize that parasite nutrient requirements lead to manipulation of migratory properties of the immune cell. We demonstrate that 1) T. gondii relies on glutamine for optimal infection, replication and viability, and 2) T. gondii-infected bone marrow-derived dendritic cells (DCs) display both “hypermotility” and “enhanced migration” to an elevated glutamine gradient in vitro. We show that glutamine uptake by the sodium-dependent neutral amino acid transporter 2 (SNAT2) is required for this enhanced migration. SNAT2 transport of glutamine is also a significant factor in the induction of migration by the small cytokine stromal cell-derived factor-1 (SDF-1) in uninfected DCs. Blocking both SNAT2 and C-X-C chemokine receptor 4 (CXCR4; the unique receptor for SDF-1) blocks hypermotility and the enhanced migration in T. gondii-infected DCs. Changes in host cell protein expression following T. gondii infection may explain the altered migratory phenotype; we observed an increase of CD80 and unchanged protein level of CXCR4 in both T. gondii-infected and lipopolysaccharide (LPS)-stimulated DCs. However, unlike activated DCs, SNAT2 expression in the cytosol of infected cells was also unchanged. Thus, our results suggest an important role of glutamine transport via SNAT2 in immune cell migration and a possible interaction between SNAT2 and CXCR4, by which T. gondii manipulates host cell motility. PMID:25299045

  3. Altered HLA Class I Profile Associated with Type A/D Nucleophosmin Mutation Points to Possible Anti-Nucleophosmin Immune Response in Acute Myeloid Leukemia.

    PubMed

    Kuželová, Kateřina; Brodská, Barbora; Fuchs, Ota; Dobrovolná, Marie; Soukup, Petr; Cetkovský, Petr

    2015-01-01

    Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute myeloid leukemia (AML) and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal individuals (large datasets available from Allele Frequency Net Database). Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B(*)07, B(*)18, and B(*)40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein. PMID:25992555

  4. Scales

    ScienceCinema

    Murray Gibson

    2010-01-08

    Musical scales involve notes that, sounded simultaneously (chords), sound good together. The result is the left brain meeting the right brain ? a Pythagorean interval of overlapping notes. This synergy would suggest less difference between the working of the right brain and the left brain than common wisdom would dictate. The pleasing sound of harmony comes when two notes share a common harmonic, meaning that their frequencies are in simple integer ratios, such as 3/2 (G/C) or 5/4 (E/C).

  5. Scales

    SciTech Connect

    Murray Gibson

    2007-04-27

    Musical scales involve notes that, sounded simultaneously (chords), sound good together. The result is the left brain meeting the right brain — a Pythagorean interval of overlapping notes. This synergy would suggest less difference between the working of the right brain and the left brain than common wisdom would dictate. The pleasing sound of harmony comes when two notes share a common harmonic, meaning that their frequencies are in simple integer ratios, such as 3/2 (G/C) or 5/4 (E/C).

  6. Transcriptional profiling of the ovine abomasal lymph node reveals a role for timing of the immune response in gastrointestinal nematode resistance.

    PubMed

    McRae, Kathryn M; Good, Barbara; Hanrahan, James P; McCabe, Matthew S; Cormican, Paul; Sweeney, Torres; O'Connell, Mary J; Keane, Orla M

    2016-07-15

    Gastrointestinal nematodes are a serious cause of morbidity and mortality in grazing ruminants. The major ovine defence mechanism is acquired immunity, with protective immunity developing over time in response to infection. Nematode resistance varies both within and between breeds and is moderately heritable. A detailed understanding of the genes and mechanisms involved in protective immunity, and the factors that regulate this response, is required to aid both future breeding strategies and the development of effective and sustainable nematode control methods. The aim of this study was to compare the abomasal lymph node transcriptome of resistant and susceptible lambs in order to determine biological processes differentially expressed between resistant and susceptible individuals. Scottish Blackface lambs, with divergent phenotypes for resistance, were challenged with 30,000 Teladorsagia circumcincta larvae (L3), and abomasal lymph nodes recovered at 7 and 14days post-infection (dpi). High-throughput sequencing of cDNA from the abomasal lymph node was used to quantitatively sample the transcriptome with an average of 32 million reads per sample. A total of 194 and 144 genes were differentially expressed between resistant and susceptible lambs at 7 and 14 dpi respectively. Differentially expressed networks and biological processes were identified using Ingenuity Pathway Analysis. Genes involved in the inflammatory response, attraction of T lymphocytes and binding of leukocytes were more highly expressed in resistant animals at 7 dpi and in susceptible animals at 14 dpi indicating that resistant animals respond to infection earlier than susceptible animals. Twenty-four Single Nucleotide Polymorphisms (SNP) within 11 differentially expressed genes, were tested for association with gastrointestinal nematode resistance in the Scottish Blackface lambs. Four SNP, in 2 genes (SLC30A2 and ALB), were suggestively associated with faecal egg count. In conclusion, a large

  7. Co-occurring genomic alterations define major subsets of KRAS - mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities

    PubMed Central

    Skoulidis, Ferdinandos; Byers, Lauren A.; Diao, Lixia; Papadimitrakopoulou, Vassiliki A.; Tong, Pan; Izzo, Julie; Behrens, Carmen; Kadara, Humam; Parra, Edwin R.; Canales, Jaime Rodriguez; Zhang, Jianjun; Giri, Uma; Gudikote, Jayanthi; Cortez, Maria A.; Yang, Chao; Fan, You Hong; Peyton, Michael; Girard, Luc; Coombes, Kevin R.; Toniatti, Carlo; Heffernan, Timothy P.; Choi, Murim; Frampton, Garrett M.; Miller, Vincent; Weinstein, John N.; Herbst, Roy S.; Wong, Kwok-Kin; Zhang, Jianhua; Sharma, Padmanee; Mills, Gordon B.; Hong, Waun K.; Minna, John D.; Allison, James P.; Futreal, Andrew; Wang, Jing; Wistuba, Ignacio I.; Heymach, John V.

    2015-01-01

    The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC) are poorly characterized. We performed an integrative analysis of genomic, transcriptomic and proteomic data from early-stage and chemo-refractory LUAC and identified three robust subsets of KRAS-mutant LUAC dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP) and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further reveal biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant LUAC with distinct biology and therapeutic vulnerabilities. PMID:26069186

  8. RNA-seq Analysis of δ9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation.

    PubMed

    Yang, Xiaoming; Bam, Marpe; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2016-07-22

    Marijuana has drawn significant public attention and concern both for its medicinal and recreational use. Δ9-Tetrahydrocannabinol (THC), which is the main bioactive component in marijuana, has also been shown to possess potent anti-inflammatory properties by virtue of its ability to activate cannabinoid receptor-2 (CB-2) expressed on immune cells. In this study, we used RNA-seq to quantify the transcriptomes and transcript variants that are differentially regulated by THC in super antigen-activated lymph node cells and CD4(+) T cells. We found that the expressions of many transcripts were altered by THC in both total lymph node cells and CD4(+) T cells. Furthermore, the abundance of many miRNA precursors and long non-coding RNAs was dramatically altered in THC-treated mice. For example, the expression of miR-17/92 cluster and miR-374b/421 cluster was down-regulated by THC. On the other hand miR-146a, which has been shown to induce apoptosis, was up-regulated by THC. Long non-coding RNAs that are expressed from the opposite strand of CD27 and Appbp2 were induced by THC. In addition, THC treatment also caused alternative promoter usage and splicing. The functions of those altered transcripts were mainly related to immune response and cell proliferation. PMID:27268054

  9. DNA Immunization

    PubMed Central

    Wang, Shixia; Lu, Shan

    2013-01-01

    DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed. PMID:24510291

  10. EFFECTS OF LEAF AREA PROFILES AND CANOPY STRATIFICATION ON SIMULATED ENERGY FLUXES: THE PROBLEM OF VERTICAL SPATIAL SCALE. (R827676)

    EPA Science Inventory

    We investigated the effects of the shape of leaf area profiles and the number of canopy layers on simulated sensible and latent heat fluxes using a gradient diffusion-based biometeorological model. Three research questions were addressed through simulation experiments: (1) Given ...

  11. A Comparison of Physical Self-Perception Profile Questionnaire Formats: Structured Alternative and Ordered Response Scale Formats

    ERIC Educational Resources Information Center

    Kalmet, Natalie; Fouladi, Rachel T.

    2008-01-01

    This study assessed the performance of the original version of the Physical Self-Perception Profile (PSPP; Fox & Corbin, 1989) as compared to a revised version. University students (N = 259) participated in the study, each answering and comparing the clarity of the original and a revised PSPP. While participants found the revised version to be…

  12. Global gene expression profiling reveals a suppressed immune response pathway associated with 3q amplification in squamous carcinoma of the lung

    PubMed Central

    Qian, Jun; Zou, Yong; Wang, Jing; Zhang, Bing; Massion, Pierre P.

    2015-01-01

    Chromosome 3q26–28 is a critical region of genomic amplification in non-small cell lung cancer (NSCLC), particularly lung squamous cell carcinomas (SCCs). No molecular therapeutic target has shown clinical utility for SCC, in contrast with adenocarcinomas of the lung. To identify novel candidate drivers in this region, we performed both Array Comparative Genomic Hybridization (array CGH, Agilent Human Genome CGH 244A oligo-microarrays) and Gene Expression Microarray (Agilent Human Gene Expression 4 × 44 K microarray) on 24 untreated lung SCC specimens. Using our previously published integrative genomics approach, we identified 12 top amplified driver genes within this region that are highly correlated and overexpressed in lung SCC. We further demonstrated one of the 12 top amplified driver Fragile X mental retardation-related protein 1 (FXR1) as a novel cancer gene in NSCLC and FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota ( PRKCI) and epithelial cell transforming 2 (ECT2) within the same amplicon in lung cancer cell. Here we report that immune response pathways are significantly suppressed in lung SCC and negatively associated with 3q driver gene expression, implying a potential role of 3q drivers in cancer immune-surveillance. In light of the attractive immunotherapy strategy using blockade of negative regulators of T cell function for multiple human cancer including lung SCC, our findings may provide a rationale for targeting 3q drivers in combination of immunotherapies for human tumors harboring the 3q amplicon. The data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE40089. PMID:26484266

  13. Asian Citrus Psyllid Expression Profiles Suggest Candidatus Liberibacter Asiaticus-Mediated Alteration of Adult Nutrition and Metabolism, and of Nymphal Development and Immunity.

    PubMed

    Vyas, Meenal; Fisher, Tonja W; He, Ruifeng; Nelson, William; Yin, Guohua; Cicero, Joseph M; Willer, Mark; Kim, Ryan; Kramer, Robin; May, Greg A; Crow, John A; Soderlund, Carol A; Gang, David R; Brown, Judith K

    2015-01-01

    The Asian citrus psyllid (ACP) Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is the insect vector of the fastidious bacterium Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening disease, or Huanglongbing (HLB). The widespread invasiveness of the psyllid vector and HLB in citrus trees worldwide has underscored the need for non-traditional approaches to manage the disease. One tenable solution is through the deployment of RNA interference technology to silence protein-protein interactions essential for ACP-mediated CLas invasion and transmission. To identify psyllid interactor-bacterial effector combinations associated with psyllid-CLas interactions, cDNA libraries were constructed from CLas-infected and CLas-free ACP adults and nymphs, and analyzed for differential expression. Library assemblies comprised 24,039,255 reads and yielded 45,976 consensus contigs. They were annotated (UniProt), classified using Gene Ontology, and subjected to in silico expression analyses using the Transcriptome Computational Workbench (TCW) (http://www.sohomoptera.org/ACPPoP/). Functional-biological pathway interpretations were carried out using the Kyoto Encyclopedia of Genes and Genomes databases. Differentially expressed contigs in adults and/or nymphs represented genes and/or metabolic/pathogenesis pathways involved in adhesion, biofilm formation, development-related, immunity, nutrition, stress, and virulence. Notably, contigs involved in gene silencing and transposon-related responses were documented in a psyllid for the first time. This is the first comparative transcriptomic analysis of ACP adults and nymphs infected and uninfected with CLas. The results provide key initial insights into host-parasite interactions involving CLas effectors that contribute to invasion-virulence, and to host nutritional exploitation and immune-related responses that appear to be essential for successful ACP-mediated circulative, propagative CLas transmission. PMID

  14. Asian Citrus Psyllid Expression Profiles Suggest Candidatus Liberibacter Asiaticus-Mediated Alteration of Adult Nutrition and Metabolism, and of Nymphal Development and Immunity

    PubMed Central

    He, Ruifeng; Nelson, William; Yin, Guohua; Cicero, Joseph M.; Willer, Mark; Kim, Ryan; Kramer, Robin; May, Greg A.; Crow, John A.; Soderlund, Carol A.; Gang, David R.; Brown, Judith K.

    2015-01-01

    The Asian citrus psyllid (ACP) Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is the insect vector of the fastidious bacterium Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening disease, or Huanglongbing (HLB). The widespread invasiveness of the psyllid vector and HLB in citrus trees worldwide has underscored the need for non-traditional approaches to manage the disease. One tenable solution is through the deployment of RNA interference technology to silence protein-protein interactions essential for ACP-mediated CLas invasion and transmission. To identify psyllid interactor-bacterial effector combinations associated with psyllid-CLas interactions, cDNA libraries were constructed from CLas-infected and CLas-free ACP adults and nymphs, and analyzed for differential expression. Library assemblies comprised 24,039,255 reads and yielded 45,976 consensus contigs. They were annotated (UniProt), classified using Gene Ontology, and subjected to in silico expression analyses using the Transcriptome Computational Workbench (TCW) (http://www.sohomoptera.org/ACPPoP/). Functional-biological pathway interpretations were carried out using the Kyoto Encyclopedia of Genes and Genomes databases. Differentially expressed contigs in adults and/or nymphs represented genes and/or metabolic/pathogenesis pathways involved in adhesion, biofilm formation, development-related, immunity, nutrition, stress, and virulence. Notably, contigs involved in gene silencing and transposon-related responses were documented in a psyllid for the first time. This is the first comparative transcriptomic analysis of ACP adults and nymphs infected and uninfected with CLas. The results provide key initial insights into host-parasite interactions involving CLas effectors that contribute to invasion-virulence, and to host nutritional exploitation and immune-related responses that appear to be essential for successful ACP-mediated circulative, propagative CLas transmission. PMID

  15. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  16. SPECIAL TOPIC: A two-time-scale dynamic-model approach for magnetic and kinetic profile control in advanced tokamak scenarios on JET

    NASA Astrophysics Data System (ADS)

    Moreau, D.; Mazon, D.; Ariola, M.; DeTommasi, G.; Laborde, L.; Piccolo, F.; Sartori, F.; Tala, T.; Zabeo, L.; Boboc, A.; Bouvier, E.; Brix, M.; Brzozowski, J.; Challis, C. D.; Cocilovo, V.; Cordoliani, V.; Crisanti, F.; DeLa Luna, E.; Felton, R.; Hawkes, N.; King, R.; Litaudon, X.; Loarer, T.; Mailloux, J.; Mayoral, M.; Nunes, I.; Surrey, E.; Zimmerman, O.; EFDA Contributors, JET

    2008-10-01

    Real-time simultaneous control of several radially distributed magnetic and kinetic plasma parameters is being investigated on JET, in view of developing integrated control of advanced tokamak scenarios. This paper describes the new model-based profile controller which has been implemented during the 2006-2007 experimental campaigns. The controller aims to use the combination of heating and current drive (H&CD) systems—and optionally the poloidal field (PF) system—in an optimal way to regulate the evolution of plasma parameter profiles such as the safety factor, q(x), and gyro-normalized temperature gradient, \\rho _Te^*(x) . In the first part of the paper, a technique for the experimental identification of a minimal dynamic plasma model is described, taking into account the physical structure and couplings of the transport equations, but making no quantitative assumptions on the transport coefficients or on their dependences. To cope with the high dimensionality of the state space and the large ratio between the time scales involved, the model identification procedure and the controller design both make use of the theory of singularly perturbed systems by means of a two-time-scale approximation. The second part of the paper provides the theoretical basis for the controller design. The profile controller is articulated around two composite feedback loops operating on the magnetic and kinetic time scales, respectively, and supplemented by a feedforward compensation of density variations. For any chosen set of target profiles, the closest self-consistent state achievable with the available actuators is uniquely defined. It is reached, with no steady state offset, through a near-optimal proportional-integral control algorithm. Conventional optimal control is recovered in the limiting case where the ratio of the plasma confinement time to the resistive diffusion time tends to zero. Closed-loop simulations of the controller response have been performed in

  17. Characterising the Profile of Everyday Executive Functioning and Relation to IQ in Adults with Williams Syndrome: Is the BRIEF Adult Version a Valid Rating Scale?

    PubMed

    Hocking, Darren R; Reeve, Jessica; Porter, Melanie A

    2015-01-01

    Although there is evidence of a distinct profile of executive dysfunction in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, the utility of informant reports of everyday executive function (EF) impairments and their relation to intelligence is not yet clear. Here we aimed to evaluate the functional impact of executive dysfunction in adults with WS and to establish the validity of child and adult versions of the most commonly used rating scale for EF assessment, the Behaviour Rating Inventory of Executive Function (BRIEF). We were also interested in whether distinct components of everyday EF relate to intelligence in WS. Parent report child (BRIEF-C) and adult (BRIEF-A) ratings were collected on 20 adults with WS (aged 18.5 to 53 years), with a mean IQ of 60.95 (SD = 17.67). Neuropsychological measures of EF included: The Shape School Test (Espy, 2007); select subdomains of EF from the Woodcock-Johnson III Tests of Cognitive Abilities, Australian Adaptation (WJ III COG); and select subdomains from the Vineland Adaptive Behaviour Scales, Second Edition-Parent Survey (Vineland-II). Results showed that the BRIEF-A, but not the BRIEF-C, was the most highly correlated with neuropsychological measures of EF, suggesting that it was a valid measure of the profile of EF impairments in adults with WS. The profile of everyday EF dysfunction revealed relative impairments in monitoring, working memory, planning and organisation in WS. In addition, both neuropsychological and rating scale measures showed an association between the shifting component of EF and intelligence. These findings indicate that the BRIEF-A is a valid measure of the multidimensional nature of real-world impairments in EF, and highlight its utility as a less labor intensive and low-cost screening tool for measuring specific EF impairments that could become the focus of targeted intervention in adults with WS. PMID:26355600

  18. Characterising the Profile of Everyday Executive Functioning and Relation to IQ in Adults with Williams Syndrome: Is the BRIEF Adult Version a Valid Rating Scale?

    PubMed Central

    Porter, Melanie A.

    2015-01-01

    Although there is evidence of a distinct profile of executive dysfunction in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, the utility of informant reports of everyday executive function (EF) impairments and their relation to intelligence is not yet clear. Here we aimed to evaluate the functional impact of executive dysfunction in adults with WS and to establish the validity of child and adult versions of the most commonly used rating scale for EF assessment, the Behaviour Rating Inventory of Executive Function (BRIEF). We were also interested in whether distinct components of everyday EF relate to intelligence in WS. Parent report child (BRIEF-C) and adult (BRIEF-A) ratings were collected on 20 adults with WS (aged 18.5 to 53 years), with a mean IQ of 60.95 (SD = 17.67). Neuropsychological measures of EF included: The Shape School Test (Espy, 2007); select subdomains of EF from the Woodcock-Johnson III Tests of Cognitive Abilities, Australian Adaptation (WJ III COG); and select subdomains from the Vineland Adaptive Behaviour Scales, Second Edition—Parent Survey (Vineland-II). Results showed that the BRIEF-A, but not the BRIEF-C, was the most highly correlated with neuropsychological measures of EF, suggesting that it was a valid measure of the profile of EF impairments in adults with WS. The profile of everyday EF dysfunction revealed relative impairments in monitoring, working memory, planning and organisation in WS. In addition, both neuropsychological and rating scale measures showed an association between the shifting component of EF and intelligence. These findings indicate that the BRIEF-A is a valid measure of the multidimensional nature of real-world impairments in EF, and highlight its utility as a less labor intensive and low-cost screening tool for measuring specific EF impairments that could become the focus of targeted intervention in adults with WS. PMID:26355600

  19. Maternal immunization

    PubMed Central

    Moniz, Michelle H; Beigi, Richard H

    2014-01-01

    Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

  20. Does CD4+CD25+foxp3+ cell (Treg) and IL-10 profile determine susceptibility to immune reconstitution inflammatory syndrome (IRIS) in HIV disease?

    PubMed Central

    Shankar, Esaki Muthu; Vignesh, Ramachandran; Velu, Vijayakumar; Murugavel, Kailapuri G; Sekar, Ramalingam; Balakrishnan, Pachamuthu; Lloyd, Charmaine AC; Saravanan, Shanmugam; Solomon, Suniti; Kumarasamy, Nagalingeswaran

    2008-01-01

    HIV-specific T-lymphocyte responses that underlie IRIS are incomplete and largely remain hypothetical. Of the several mechanisms presented by the host to control host immunological damage, Treg cells are believed to play a critical role. Using the available experimental evidence, it is proposed that enormous synthesis of conventional FoxP3- Th cells (responsive) often renders subjects inherently vulnerable to IRIS, whereas that of natural FoxP3+ Treg cell synthesis predominate among subjects that may not progress to IRIS. We also propose that IRIS non-developers generate precursor T-cells with a high avidity to generate CD4+CD25+FoxP3+ Tregs whereas IRIS developers generate T-cells of intermediate avidity yielding Th0 cells and effector T-cells to mediate the generation of proinflammatory cytokines in response to cell-signaling factors (IL-2, IL-6 etc.). Researchers have shown that IL-10 Tregs (along with TGF-β, a known anti-inflammatory cytokine) limit immune responses against microbial antigens in addition to effectively controlling HIV replication, the prime objective of HAART. Although certain technical limitations are described herein, we advocate measures to test the role of Tregs in IRIS. PMID:18282273

  1. Comparison of the Expression Profiles of Immune Response Gene mRNA in Umbilical and Venous Blood of Newborns of the First Day of Life.

    PubMed

    Nepsha, O S; Nikitina, I V; Donnikov, A E; Bystritsky, A A; Mullabaeva, S M; Pavlovich, S V; Aleksandrova, N V

    2016-04-01

    The expression of immune response gene mRNA in the umbilical and venous blood were compared in newborns of the first day of life with and without signs of infection. The expression of il1b, il6, il8, il10, il12a, il15, il18, tnfa, tgfb1, tbx21, gata3, foxp3, rorc2, cd45, cd68, cd69, tlr2, tlr4, tlr9, and mmp8 mRNA was evaluated in umbilical and venous blood cells of newborns by reverse transcription real time PCR. In full-term newborns without signs of infection, the expression of il8, tlr2, tlr4, and mmp8 in venous blood was higher than in umbilical blood, while in preterm newborns, the levels of mmp8 transcript were elevated while the levels of tlr9, cd45, and gata3 were reduced. The expression of some markers differed in the umbilical and venous blood and in newborns with congenital infectious disease and without signs of infection. PMID:27165068

  2. Profiling the ionome of rice and its use in discriminating geographical origins at the regional scale, China.

    PubMed

    Li, Gang; Nunes, Luis; Wang, Yijie; Williams, Paul N; Zheng, Maozhong; Zhang, Qiufang; Zhu, Yongguan

    2013-01-01

    Element profile was investigated for their use to trace the geographical origin of rice (Oryza sativa L.) samples. The concentrations of 13 elements (calcium (Ca), potassium (K), magnesium (Mg), phosphorus (P), boron (B), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), molybdenum (Mo), and cadmium (Cd)) were determined in the rice samples by inductively coupled plasma optical emission and mass spectrometry. Most of the essential elements for human health in rice were within normal ranges except for Mo and Se. Mo concentrations were twice as high as those in rice from Vietnam and Spain. Meanwhile, Se concentrations were three times lower in the whole province compared to the Chinese average level of 0.088 mg/kg. About 12% of the rice samples failed the Chinese national food safety standard of 0.2 mg/kg for Cd. Combined with the multi-elemental profile in rice, the principal component analysis (PCA), discriminant function analysis (DFA) and Fibonacci index analysis (FIA) were applied to discriminate geographical origins of the samples. Results indicated that the FIA method could achieve a more effective geographical origin classification compared with PCA and DFA, due to its efficiency in making the grouping even when the elemental variability was so high that PCA and DFA showed little discriminatory power. Furthermore, some elements were identified as the most powerful indicators of geographical origin: Ca, Ni, Fe and Cd. This suggests that the newly established methodology of FIA based on the ionome profile can be applied to determine the geographical origin of rice. PMID:23586309

  3. Properties of blends for profiles and semi-rigid films made of PVC nanocomposites produced in pilot scale

    NASA Astrophysics Data System (ADS)

    Obloj-Muzaj, Maria; Abramowicz, Agnieszka; Kumosinski, Marcin; Zielecka, Maria; Kozakiewicz, Janusz; Gorska, Agnieszka

    2016-05-01

    PVC nanocomposites containing 0.5 wt. %/VCM of either nanosilica or hybrid core/shell type nanofiller were produced in-situ in suspension polymerisation. Significant increase in impact strength of PVC composites obtained was observed (higher 25 - 60 % in comparison with PVC). The amount of impact modifier in selected rigid PVC blends (e.g. in window profiles) could be significantly reduced (≥ 50 %). Tensile and flexural properties of nanocomposites were similar to PVC, however, at smaller amount of impact modifier other mechanical properties improve. Tear resistance of rigid films was better.

  4. Maternal Immunization

    PubMed Central

    Chu, Helen Y.; Englund, Janet A.

    2014-01-01

    Maternal immunization has the potential to protect the pregnant woman, fetus, and infant from vaccine-preventable diseases. Maternal immunoglobulin G is actively transported across the placenta, providing passive immunity to the neonate and infant prior to the infant's ability to respond to vaccines. Currently inactivated influenza, tetanus toxoid, and acellular pertussis vaccines are recommended during pregnancy. Several other vaccines have been studied in pregnancy and found to be safe and immunogenic and to provide antibody to infants. These include pneumococcus, group B Streptococcus, Haemophilus influenzae type b, and meningococcus vaccines. Other vaccines in development for potential maternal immunization include respiratory syncytial virus, herpes simplex virus, and cytomegalovirus vaccines. PMID:24799324

  5. Immunity challenge.

    PubMed

    Davenport, R John

    2003-06-11

    As people get older, their immune systems falter. The elderly are more susceptible to infections than youngsters are, and hyperactive inflammatory responses appear to contribute to some age-associated illnesses, including Alzheimer's disease and atherosclerosis. Investigating the effect of aging on the immune system was once a scientific stepchild, but card-carrying immunologists are now tackling the problem head-on. Despite the immune system's complexity, researchers have started to make sense of how its components change with age. As the research progresses, scientists hope to bolster elderly people's response to infectious diseases and quiet the inflammation that can make aging a painful experience. PMID:12844525

  6. Gene Expression Profiles Underlying Selective T-Cell-Mediated Immunity Activity of a Chinese Medicine Granule on Mice Infected with Influenza Virus H1N1

    PubMed Central

    Lu, Na-na; Liu, Qi; Gu, Li-gang; Ge, Shi-jie; Wu, Jun; Ze-ji, Qiu; Qiu, Ze-ji; Zhang, Hong-chun; Chao, En-xiang; Yu, Zhuo-nan

    2014-01-01

    A Chinese medicine granule, Shu-Feng-Xuan-Fei (SFXF), is critical for viral clearance in early phase of influenza virus infection. In this study, 72 ICR mice were randomly divided into six groups: normal control group, virus control group, Oseltamivir group, low-dose SFXF, medium-dose SFXF, and high-dose SFXF. Mice were anesthetized and inoculated with 4LD50 of influenza virus A (H1N1) except normal control group. Oseltamivir group received 11.375 mg·kg−1·d−1 Oseltamivir Phosphate. SFXF 3.76, 1.88 and 0.94 g·kg−1·d−1 were administrated to mice in all SFXF groups. Each group was in equal dose of 0.2ml daily for 4 consecutive days. Mice were sacrificed and then total RNA was extracted in lung tissue. Some genes involved in T-cell-mediated immunity were selected by DNA microarray. These candidate genes were verified by Real-Time PCR and western immunoblotting. Compared with virus control group, in Toll-like receptor signaling pathway, 12 virus-altered genes were significantly reduced following medium-dose SFXF treatment. Eighteen antigen processing presentation-associated genes were upregulated by medium-dose SFXF. In the process of T cell receptor signaling pathway, 19 genes were downregulated by medium-dose SFXF treatment. On exploration into effector T cells activation and cytokines, all of altered genes in virus control group were reversed by medium-dose SFXF. Real-time PCR and western immunoblotting showed that the regulation of medium-dose SFXF in IL-4, IFN-γ, TNF-α, IL-1β, TLR7, MyD88, p38, and JNK was superior to Oseltamivir and high-dose SFXF group. Therefore, SFXF granules could reduce influenza infected cells and activation of T cells. PMID:24527057

  7. The Relationship of MacAndrew Alcoholism Scale Scores to MMPI Profile Type and Degree of Elevation.

    ERIC Educational Resources Information Center

    Pfost, Karen S.; And Others

    1984-01-01

    Investigated the relationship of the MacAndrew Alcoholism Scale (MAC) to personality type and level of emotional distress using Minnesota Multiphasic Personality Inventory scores of 38 alcoholic males. No relationship was found between the MAC and magnitude of psychological distress, as measured by T scores. (JAC)

  8. Cohort Profile of the Goals Study: A Large-Scale Research of Physical Activity in Dutch Students

    ERIC Educational Resources Information Center

    de Groot, Renate H. M.; van Dijk, Martin L.; Kirschner, Paul A.

    2015-01-01

    The GOALS study (Grootschalig Onderzoek naar Activiteiten van Limburgse Scholieren [Large-scale Research of Activities in Dutch Students]) was set up to investigate possible associations between different forms of physical activity and inactivity with cognitive performance, academic achievement and mental well-being. It was conducted at a…

  9. Pilot-scale data provide enhanced estimates of the life cycle energy and emissions profile of algae biofuels produced via hydrothermal liquefaction.

    PubMed

    Liu, Xiaowei; Saydah, Benjamin; Eranki, Pragnya; Colosi, Lisa M; Greg Mitchell, B; Rhodes, James; Clarens, Andres F

    2013-11-01

    Life cycle assessment (LCA) has been used widely to estimate the environmental implications of deploying algae-to-energy systems even though no full-scale facilities have yet to be built. Here, data from a pilot-scale facility using hydrothermal liquefaction (HTL) is used to estimate the life cycle profiles at full scale. Three scenarios (lab-, pilot-, and full-scale) were defined to understand how development in the industry could impact its life cycle burdens. HTL-derived algae fuels were found to have lower greenhouse gas (GHG) emissions than petroleum fuels. Algae-derived gasoline had significantly lower GHG emissions than corn ethanol. Most algae-based fuels have an energy return on investment between 1 and 3, which is lower than petroleum biofuels. Sensitivity analyses reveal several areas in which improvements by algae bioenergy companies (e.g., biocrude yields, nutrient recycle) and by supporting industries (e.g., CO2 supply chains) could reduce the burdens of the industry. PMID:24045203

  10. On the consistency of personality types across adulthood: latent profile analyses in two large-scale panel studies.

    PubMed

    Specht, Jule; Luhmann, Maike; Geiser, Christian

    2014-09-01

    Consistency and change in personality were analyzed by examining personality types across adulthood and old age using data from 2 nationally representative panel studies from Germany (N = 14,718; 16-82 years) and Australia (N = 8,315; 15-79 years). In both samples, the Big Five personality traits were measured twice across a period of 4 years. Latent profile analyses and latent profile transition analyses revealed 4 main findings: First, solutions with 3 (in the German sample) or 4 (in the Australian sample) personality types were found to be most interpretable. Second, measurement invariance tests revealed that these personality types were consistent across all age groups but differed slightly between men and women. Third, age was related to the number of individuals classified within each personality type. Namely, there were more resilients and fewer undercontrollers in older compared with younger age groups. Fourth, there was strong consistency of personality type membership across a period of 4 years in both genders and most age cohorts. Comparatively less consistency across time was found for undercontrollers and individuals in old age. Taken together, these findings show that in the 2 nations studied here, personality types were highly consistent across gender, age, and time. PMID:25133730

  11. Immunization Coverage

    MedlinePlus

    ... underused vaccines is increasing. Immunization currently averts an estimated 2 to 3 million deaths every year. An ... avoided, however, if global vaccination coverage improves. An estimated 19.4 million infants worldwide are still missing ...

  12. Immune response

    MedlinePlus

    ... inflammation and tissue repair. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... and adaptive immune systems. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  13. Childhood Immunization

    MedlinePlus

    Today, children in the United States routinely get vaccines that protect them from more than a dozen ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ...

  14. Immune response

    MedlinePlus Videos and Cool Tools

    The immune system includes specialized white blood cells, called lymphocytes that adapt themselves to fight specific foreign invaders. These cells develop into two groups in the bone marrow. From the bone ...

  15. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile.

    PubMed

    Daniel, Carolin; Sartory, Nico A; Zahn, Nadine; Radeke, Heinfried H; Stein, Jürgen M

    2008-01-01

    A number of recent studies testify that calcitriol alone or in combination with corticosteroids exerts strong immune modulatory activity. As a new approach, we evaluated the protolerogenic potential of calcitriol and dexamethasone in acute T helper (Th)1-mediated colitis in mice. A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg) was applied to BALB/c mice. Calcitriol and/or dexamethasone were administered i.p. from days 0 to 3 or 3 to 5 following the instillation of the haptenating agent. Assessment of colitis severity was performed daily. Colon tissue was analyzed macroscopically and microscopically, and myeloperoxidase activity, as well as cytokine levels [tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-12p70, IL-1beta, IL-10, IL-4] were determined by enzyme-linked immunosorbent assay, T-bet, GATA family of transcription factors 3, a Th2 master regulator (GATA3), Foxp3, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), IL-23p19 and IL-17 expression by immunoblot analysis. The combination of the steroids most effectively reduced the clinical and histopathologic severity of TNBS colitis. Th1-related parameters were down-regulated, whereas Th2 markers like IL-4 and GATA3 were up-regulated. Apart from known steroid effects, calcitriol in particular promoted regulatory T cell profiles as indicated by a marked increase of IL-10, TGFbeta, FoxP3, and CTLA4. Furthermore, analysis of dendritic cell mediators responsible for a proinflammatory differentiation of T cells revealed a significant reduction of IL-12p70 and IL23p19 as well as IL-6 and IL-17. Thus, our data support a rationale for a steroid-sparing, clinical application of calcitriol derivatives in inflammatory bowel disease. Furthermore they suggest that early markers of inflammatory dendritic cell and Th17 differentiation qualify as new target molecules for both calcitriol and highly selective immune-modulating vitamin D analogs. PMID:17911375

  16. The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice.

    PubMed

    Nakamura, Takashi; Takeda, Tomoya; Tokuji, Yoshihiko

    2014-01-01

    The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05% Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p<0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression. PMID:26098482

  17. Gaining insight into the spatial distribution of soil hydraulic properties on the soil profile scale by high resolution TDR and tensiometer measurements

    NASA Astrophysics Data System (ADS)

    Altfelder, S.; Ganz, C.; Noell, U.; Duijnisveld, W. H. M.; Bachmann, J.

    2010-05-01

    different structures visible in the soil profile. For these groups, water characteristic reference functions are calculated and heterogeneity is formulated using different scaling approaches. The resulting heterogeneous distributions are compared and evaluated with regard to their ability to capture the characteristics of the true heterogeneity in the profile. Results of this investigation will eventually be fed into a soil water transport model that will be used for a hindcast model exercise aiming at remodelling the infiltration experiment. Model results will be compared to electrical resistivity tomography measurements carried out parallel to the infiltration experiment.

  18. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response

    PubMed Central

    2015-01-01

    Recurrent airway obstruction (RAO) is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17). We examined global gene expression profiles in mediastinal (pulmonary-draining) lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1) and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health. PMID:26561853

  19. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python.

    PubMed

    Rey-Villamizar, Nicolas; Somasundar, Vinay; Megjhani, Murad; Xu, Yan; Lu, Yanbin; Padmanabhan, Raghav; Trett, Kristen; Shain, William; Roysam, Badri

    2014-01-01

    In this article, we describe the use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes, including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis tasks, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral images of brain tissue surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels. Each channel consists of 6000 × 10,000 × 500 voxels with 16 bits/voxel, implying image sizes exceeding 250 GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analysis for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN) capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment. Our Python script enables efficient data storage and movement between computers and storage servers, logs all the processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries. PMID:24808857

  20. Spatially-explicit risk profiling of Plasmodium falciparum infections at a small scale: a geostatistical modelling approach

    PubMed Central

    Silué, Kigbafori D; Raso, Giovanna; Yapi, Ahoua; Vounatsou, Penelope; Tanner, Marcel; N'Goran, Eliézer K; Utzinger, Jürg

    2008-01-01

    Background There is a renewed political will and financial support to eradicate malaria. Spatially-explicit risk profiling will play an important role in this endeavour. Patterns of Plasmodium falciparum infection prevalence were examined among schoolchildren in a highly malaria-endemic area. Methods A questionnaire was administered and finger prick blood samples collected from 3,962 children, aged six to 16 years, attending 55 schools in a rural part of western Côte d'Ivoire. Information was gathered from the questionnaire on children's socioeconomic status and the use of bed nets for the prevention of malaria. Blood samples were processed with standardized, quality-controlled methods for diagnosis of Plasmodium spp. infections. Environmental data were obtained from satellite images and digitized maps. Bayesian variogram models for spatially-explicit risk modelling of P. falciparum infection prevalence were employed, assuming for stationary and non-stationary spatial processes. Findings The overall prevalence of P. falciparum infection was 64.9%, ranging between 34.0% and 91.9% at the unit of the school. Risk factors for a P. falciparum infection included age, socioeconomic status, not sleeping under a bed net, distance to health care facilities and a number of environmental features (i.e. normalized difference vegetation index, rainfall and distance to rivers). After taking into account spatial correlation only age remained significant. Non-stationary models performed better than stationary models. Conclusion Spatial risk profiling of P. falciparum prevalence data provides a useful tool for targeting malaria control intervention, and hence will play a role in the quest of local elimination and ultimate eradication of the disease. PMID:18570685

  1. Endometrial stromal fibroblasts from women with polycystic ovary syndrome have impaired progesterone-mediated decidualization, aberrant cytokine profiles and promote enhanced immune cell migration in vitro

    PubMed Central

    Piltonen, T.T.; Chen, J.C.; Khatun, M.; Kangasniemi, M.; Liakka, A.; Spitzer, T.; Tran, N.; Huddleston, H.; Irwin, J.C.; Giudice, L.C.

    2015-01-01

    STUDY QUESTION Do endometrial stromal fibroblasts (eSF) in women with polycystic ovary syndrome (PCOS) (eSFpcos) exhibit altered estrogen and/or progesterone (P4) responses, which may explain some of the adverse reproductive outcomes and endometrial pathologies in these women? SUMMARY ANSWER In vitro, eSF from women with PCOS exhibit an aberrant decidualization response and concomitant changes in pro-inflammatory cytokine, chemokine and matrix metalloproteinase (MMP) release and immune cell chemoattraction. In vivo these aberrations may result in suboptimal implantation and predisposition to endometrial cancer. WHAT IS KNOWN ALREADY The endometrium in women with PCOS has several abnormalities including progesterone (P4) resistance at the gene expression level, likely contributing to subfertility, pregnancy complications and increased endometrial cancer risk in PCOS women. STUDY DESIGN, SIZE, DURATION Prospective, university-based, case–control, in vitro study. PARTICIPANTS/MATERIALS, SETTING, METHODS Cultures of eSFPCOS (n = 12, Rotterdam and NIH criteria) and eSFControl (Ctrl) (n = 6, regular cycle length, no signs of hyperandrogenism) were treated with vehicle, estradiol (E2, 10 nM) or E2P4 (10 nM/1 μM) for 14 days. Progesterone receptor (PGR) mRNA was assessed with quantitative real-time PCR (qRT–PCR) and eSF decidualization was confirmed by insulin-like growth factor-binding protein-1 (IGFBP-1) transcript and protein expression. Fractalkine (CX3CL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL) 6, 8 and 11, macrophage chemoattractant protein (MCP) 1 and 3, CCL5 (RANTES) and MMPs (MMP1, 2, 3, 7, 9, 10 and 12) were measured in conditioned media by Luminex multiplex assays, and chemotactic activity of the conditioned media was tested in a migration assay using CD14+ monocyte and CD4+ T-cell migration assay. Effects of IL-6 (0.02, 0.2, 2 or 20 ng/ml) or IL-8 (0.04, 0.4, 4, or 40 ng/ml) or combination (0.2 ng/ml IL-6 and 4.0 ng

  2. Valuing the Child Health Utility 9D: Using profile case best worst scaling methods to develop a new adolescent specific scoring algorithm.

    PubMed

    Ratcliffe, Julie; Huynh, Elisabeth; Chen, Gang; Stevens, Katherine; Swait, Joffre; Brazier, John; Sawyer, Michael; Roberts, Rachel; Flynn, Terry

    2016-05-01

    In contrast to the recent proliferation of studies incorporating ordinal methods to generate health state values from adults, to date relatively few studies have utilised ordinal methods to generate health state values from adolescents. This paper reports upon a study to apply profile case best worst scaling methods to derive a new adolescent specific scoring algorithm for the Child Health Utility 9D (CHU9D), a generic preference based instrument that has been specifically designed for the estimation of quality adjusted life years for the economic evaluation of health care treatment and preventive programs targeted at young people. A survey was developed for administration in an on-line format in which consenting community based Australian adolescents aged 11-17 years (N = 1982) indicated the best and worst features of a series of 10 health states derived from the CHU9D descriptive system. The data were analyzed using latent class conditional logit models to estimate values (part worth utilities) for each level of the nine attributes relating to the CHU9D. A marginal utility matrix was then estimated to generate an adolescent-specific scoring algorithm on the full health = 1 and dead = 0 scale required for the calculation of QALYs. It was evident that different decision processes were being used in the best and worst choices. Whilst respondents appeared readily able to choose 'best' attribute levels for the CHU9D health states, a large amount of random variability and indeed different decision rules were evident for the choice of 'worst' attribute levels, to the extent that the best and worst data should not be pooled from the statistical perspective. The optimal adolescent-specific scoring algorithm was therefore derived using data obtained from the best choices only. The study provides important insights into the use of profile case best worst scaling methods to generate health state values with adolescent populations. PMID:27060541

  3. Organising for immunization.

    PubMed

    Michie, S

    1993-06-01

    In the late 1960s, health workers from a mission hospital in rural Zambia began registering children under 14 years old within 30 miles of the hospital (about 3000 children) by incorporating the cooperation of community leaders. They wanted to give every 0-4 year old child a Road to Health card and every 5-14 year old a vaccine record card and to promote the significance of immunization to parents and community leaders. The mission hospital established mobile health units to conduct regular visits in the center of villages. Staff hugh scales from a tree and borrowed a table to conduct the clinic. They kept a good relationship and communication with the community, leading successful education and communication activities. By 1988, many younger mothers were unfamiliar with a measles or whooping cough epidemic so they tended to not have their infants immunized. Epidemics began killing children nationwide, frightening these mothers so they brought their children for immunizations. The medical mission achieved an 85-90% vaccination coverage rate with immunization clinic attendance climbing quickly. 1 mother even walked 30 miles to have her infant injected with the DPT vaccine, but 10 years earlier, she did not bring her children. Further, measles had not reached her area because the immunization level was so high that it stopped the epidemic. PMID:12318293

  4. Role of synoptic- and meso-scales on the evolution of the boundary-layer wind profile over a coastal region: the near-coast diurnal acceleration

    NASA Astrophysics Data System (ADS)

    Jiménez, Pedro A.; de Arellano, Jordi Vilà-Guerau; Dudhia, Jimy; Bosveld, Fred C.

    2016-02-01

    The contributions of synoptic- and meso-scales to the boundary layer wind profile evolution in a coastal environment are examined. The analysis is based on observations of the wind profile within the first 200 m of the atmosphere continuously recorded during a 10 year period (2001-2010) at the 213-m meteorological tower at the Cabauw Experimental Site for Atmospheric Research (CESAR, The Netherlands). The analysis is supported by a numerical experiment based on the Weather Research and Forecasting (WRF) model performed at high horizontal resolution of 2 km and spanning the complete observational period (10 years). Results indicate that WRF is able to reproduce the inter-annual wind variability but with a tendency to be too geostrophic. At seasonal scales, we find a differentiated behavior between Winter and Summer seasons with the Spring and Autumn transition periods more similar to the Summer and Winter modes, respectively. The winter momentum budget shows a weak intradiurnal variability. The synoptic scale controls the shape of the near surface wind profile that is characterized by weaker and more ageostrophic winds near the surface than at higher altitudes within the planetary boundary layer (PBL) as a result of the frictional turning. In turn, during summer, mesoscale circulations associated with the differential heating of land and sea become important. As a result, the PBL winds show a stronger intradiurnal component that is characterized by an oscillation of the near surface winds around the geostrophic direction with the maximum departure in the afternoon. Although also driven by thermal land-sea differences, this mesoscale component is not associated with the classical concept of a sea-breeze front. It originates from the thermal expansion of the boundary layer over land and primarily differs from the sea-breeze in its propagation speed resulting in a wind rotation far ahead of any coastal front. We refer to it as the near-coast diurnal acceleration (NCDA

  5. MOND implications for spectral line profiles of shell galaxies: shell formation history and mass-velocity scaling relations

    NASA Astrophysics Data System (ADS)

    Bílek, M.; Jungwiert, B.; Ebrová, I.; Bartošková, K.

    2015-03-01

    Context. Many ellipticals are surrounded by round stellar shells probably stemming from minor mergers. A new method for constraining gravitational potential in elliptical galaxies has recently been suggested. It uses the spectral line profiles of these shells to measure the circular velocity at the edge of the shell and the expansion velocity of the shell itself. MOND is an alternative to the dark matter framework aiming to solve the missing mass problem. Aims: We study how the circular and expansion velocities behave in MOND for large shells. Methods: The asymptotic behavior for infinitely large shells is derived analytically. The applicability of the asymptotic results for finitely sized shells is studied numerically on a grid of galaxies modeled with Sérsic spheres. Results: Circular velocity settles asymptotically at a value determined by the baryonic mass of the galaxy forming the baryonic Tully-Fisher relation known for disk galaxies. Shell expansion velocity also becomes asymptotically constant. The expansion velocities of large shells form a multibranched analogy to the baryonic Tully-Fisher relation, together with the galactic baryonic masses. For many - but not all - shell galaxies, the asymptotic values of these two types of velocities are reached under the effective radius. If MOND is assumed to work in ellipticals, then the shell spectra allow many details of the history to be revealed about the formation of the shell system, including its age. The results pertaining to circular velocities apply to all elliptical galaxies, not only those with shells.

  6. Large-scale gene expression profiling reveals physiological response to deletion of chaperone dnaKJ in Escherichia coli.

    PubMed

    Fan, Dongjie; Liu, Chuanpeng; Liu, Lushan; Zhu, Lingxiang; Peng, Fang; Zhou, Qiming

    2016-01-01

    Chaperone DnaK and its co-chaperone DnaJ plays various essential roles such as in assisting in the folding of nascent peptides, preventing protein aggregation and maintaining cellular protein homeostasis. Global transcriptional changes in vivo associated with deletion of dnaKJ were monitored using DNA microarray to elucidate the role of DnaKJ at the transcriptional level. Microarray profiling and bioinformatics analysis revealed that a few chaperone and protease genes, stress-related genes and genes involved in the tricarboxylic acid cycle and oxidative phosphorylation were up-regulated, whereas various transporter genes, pentose phosphate pathway and transcriptional regulation related genes were down-regulated. This study is the first to systematically analyze the alterations at the transcriptional level in vivo in deletion of dnaKJ. Fatty acid methyl esters analysis indicated that the amount of unsaturated fatty acid sharply increased and subcellular location prediction analysis showed a marked decrease in transcription of inner-membrane protein genes, which might have triggered the development of aberrant cell shape and susceptibility for some antibiotics in the ΔdnaKJ strain. PMID:27242140

  7. The Immune Space: A Concept and Template for Rationalizing Vaccine Development

    PubMed Central

    Adams, Elizabeth; Barouch, Dan H.; Fast, Pat; Graham, Barney S.; Kim, Jerome H.; Kublin, James G.; McCluskey, Margaret; Pantaleo, Giuseppe; Robinson, Harriet L.; Russell, Nina; Snow, William; Johnston, Margaret I.

    2014-01-01

    Abstract Empirical testing of candidate vaccines has led to the successful development of a number of lifesaving vaccines. The advent of new tools to manipulate antigens and new methods and vectors for vaccine delivery has led to a veritable explosion of potential vaccine designs. As a result, selection of candidate vaccines suitable for large-scale efficacy testing has become more challenging. This is especially true for diseases such as dengue, HIV, and tuberculosis where there is no validated animal model or correlate of immune protection. Establishing guidelines for the selection of vaccine candidates for advanced testing has become a necessity. A number of factors could be considered in making these decisions, including, for example, safety in animal and human studies, immune profile, protection in animal studies, production processes with product quality and stability, availability of resources, and estimated cost of goods. The “immune space template” proposed here provides a standardized approach by which the quality, level, and durability of immune responses elicited in early human trials by a candidate vaccine can be described. The immune response profile will demonstrate if and how the candidate is unique relative to other candidates, especially those that have preceded it into efficacy testing and, thus, what new information concerning potential immune correlates could be learned from an efficacy trial. A thorough characterization of immune responses should also provide insight into a developer's rationale for the vaccine's proposed mechanism of action. HIV vaccine researchers plan to include this general approach in up-selecting candidates for the next large efficacy trial. This “immune space” approach may also be applicable to other vaccine development endeavors where correlates of vaccine-induced immune protection remain unknown. PMID:24857015

  8. Photodynamic immune modulation (PIM)

    NASA Astrophysics Data System (ADS)

    North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

    1999-09-01

    Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

  9. Discriminating the molecular basis of hepatotoxicity using the large-scale characteristic molecular signatures of toxicants by expression profiling analysis.

    PubMed

    Eun, Jung Woo; Ryu, So Yeon; Noh, Ji Heon; Lee, Min-Jae; Jang, Ja-Jun; Ryu, Jae Chun; Jung, Kwang Hwa; Kim, Jeong Kyu; Bae, Hyun Jin; Xie, Hongjian; Kim, Su Young; Lee, Sug Hyung; Park, Won Sang; Yoo, Nam Jin; Lee, Jung Young; Nam, Suk Woo

    2008-07-30

    Predicting the potential human health risk posed by chemical stressors has long been a major challenge for toxicologists, and the use of microarrays to measure responses to toxicologically relevant genes, and to identify selective, sensitive biomarkers of toxicity is a major application of predictive and discovery toxicology. To investigate this possibility, we investigated whether carcinogens (at doses known to induce liver tumors in chronic exposure bioassays) deregulate characteristic sets of genes in mice. Male C3H/He mice were dosed with two hepatocarcinogens (vinyl chloride (VC, 50-25 mg/kg), aldrin (AD, 0.8-0.4 mg/kg)), or two non-hepatocarcinogens (copper sulfate (CS, 150-60 mg/kg), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T, 150-60 mg/kg)). Large-scale molecular changes elicited by these four hepatotoxicants in liver tissues were analyzed using DNA microarray. Three days after administration, no significant phenotypic changes were induced by these four different hepatotoxicants in terms of histological examination or blood biochemical assay. However, unsupervised hierarchical analysis of gene expressional changes induced by hepatotoxicants resulted in two major gene subclusters on dendrogram, i.e., a carcinogen (VN, AD) and non-carcinogen group (CS, 2,4,5-T), and also revealed that distinct molecular signatures exist. These signatures were founded on well-defined functional gene categories and may differentiate genotoxic and non-genotoxic carcinogens. Furthermore, Venn diagram analysis allowed us to identify carcinogen and non-carcinogen-associated molecular signatures. Using statistical methods, we analyzed outlier genes for four different classes (genotoxic-, non-genotoxic-carcinogen, genotoxic-, non-genotoxic non-carcinogen) in terms of their potential to predict different modes-of-action. In conclusion, the identification of large-scale molecular changes in different hepatocarcinogen exposure models revealed that different types of hepatotoxicants are

  10. Genes versus environment: geography and phylogenetic relationships shape the chemical profiles of stingless bees on a global scale

    PubMed Central

    Leonhardt, Sara D.; Rasmussen, Claus; Schmitt, Thomas

    2013-01-01

    Chemical compounds are highly important in the ecology of animals. In social insects, compounds on the body surface represent a particularly interesting trait, because they comprise different compound classes that are involved in different functions, such as communication, recognition and protection, all of which can be differentially affected by evolutionary processes. Here, we investigate the widely unknown and possibly antagonistic influence of phylogenetic and environmental factors on the composition of the cuticular chemistry of tropical stingless bees. We chose stingless bees because some species are unique in expressing not only self-produced compounds, but also compounds that are taken up from the environment. By relating the cuticular chemistry of 40 bee species from all over the world to their molecular phylogeny and geographical occurrence, we found that distribution patterns of different groups of compounds were differentially affected by genetic relatedness and biogeography. The ability to acquire environmental compounds was, for example, highly correlated with the bees' phylogeny and predominated in evolutionarily derived species. Owing to the presence of environmentally derived compounds, those species further expressed a higher chemical and thus functional diversity. In Old World species, chemical similarity of both environmentally derived and self-produced compounds was particularly high among sympatric species, even when they were less related to each other than to allopatric species, revealing a strong environmental effect even on largely genetically determined compounds. Thus, our findings do not only reveal an unexpectedly strong influence of the environment on the cuticular chemistry of stingless bees, but also demonstrate that even within one morphological trait (an insect's cuticular profile), different components (compound classes) can be differentially affected by different drivers (relatedness and biogeography), depending on the

  11. Cognitive Profiles in Youth with Autism Spectrum Disorder: An Investigation of Base Rate Discrepancies using the Differential Ability Scales--Second Edition.

    PubMed

    Nowell, Kerri P; Schanding, G Thomas; Kanne, Stephen M; Goin-Kochel, Robin P

    2015-07-01

    Extant data suggest that the cognitive profiles of individuals with ASD may be characterized by variability, particularly in terms of verbal intellectual functioning (VIQ) and non-verbal intellectual functioning (NVIQ) discrepancies. The Differential Ability Scales, Second Edition (DAS-II) has limited data available on its use with youth with ASD. The current study examined data from 2,110 youth with ASD in order to characterize performance on the DAS-II and to investigate potential discrepancies between VIQ and NVIQ. A larger proportion of individuals in the ASD sample had significant discrepancies between VIQ and NVIQ when compared to the normative sample [early years sample χ2 (2) = 38.36; p < .001; school age sample χ2 (2) = 13.48; p < .01]. Clinical and research implications are discussed. PMID:25614020

  12. Immune thrombocytopenia.

    PubMed

    Kistangari, Gaurav; McCrae, Keith R

    2013-06-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary or a secondary form. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age-specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Corticosteroids remain the most common first line therapy for ITP. This article summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. PMID:23714309

  13. Plant Immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants are faced with defending themselves against a multitude of pathogens, including bacteria, fungi, viruses, nematodes, etc. Immunity is multi-layered and complex. Plants can induce defenses when they recognize small peptides, proteins or double-stranded RNA associated with pathogens. Recognitio...

  14. Predictive functional profiling using marker gene sequences and community diversity analyses of microbes in full-scale anaerobic sludge digesters.

    PubMed

    Gao, Jing; Liu, Guoji; Li, Hongping; Xu, Li; Du, Lili; Yang, Bo

    2016-07-01

    Anaerobic digestion (AD) is widely used in treating the sewage sludge, as it can reduce the amount of sludge, eliminate pathogens and produce biofuel. To enhance the operational performance and stability of anaerobic bioreactors, operational and conventional chemical data from full-scale sludge anaerobic digesters were collected over a 2-year period and summarized, and the microbial community diversity of the sludge sample was investigated at various stages of the AD process. For the purpose of distinguishing between the functional and community diversity of the microbes, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software was used to impute the prevalence of 16S rDNA marker gene sequences in the difference in various sludge samples. Meanwhile, a taxa analysis was also carried out to investigate the different sludge samples. The microbial community diversity analysis of one AD sludge sample showed that the most dominant bacterial genera were Saccharicrinis, Syntrophus, Anaerotruncus and Thermanaerothrix. Among archaea, acetoclastic Methanosaeta represented 56.0 %, and hydrogenotrophic Methanospirillum, Methanoculleus, Methanothermus and Methanolinea accounted for 41.3 % of all methanogens. The taxa, genetic and functional prediction analyses of the feedstock and AD sludge samples suggested great community diversity differences between them. The taxa of bacteria in two AD sludge samples were considerably different, but the abundances of the functional KEGG pathways took on similar levels. The numbers of identified pathogens were significantly lower in the digested sludge than in the feedstock, but the PICRUSt results showed the difference in "human diseases" abundances in the level-1 pathway between the two sludge samples was small. PMID:27016946

  15. Using river long profiles and geomorphic indices to evaluate the geomorphological signature of continental scale drainage capture, Duero basin (NW Iberia)

    NASA Astrophysics Data System (ADS)

    Antón, Loreto; De Vicente, Gerardo; Muñoz-Martín, Alfonso; Stokes, Martin

    2014-02-01

    Well-constrained case studies of transient landscape responses are needed to improve our understanding of erosion processes associated with drainage captures. The Duero basin is an excellent location for such a study because the landscape is currently undergoing pronounced geomorphological changes resulting from the opening of a former closed drainage. The present-day continental interior basin (> 50,000 km2) drains to the Atlantic Ocean via the Duero River, but during the Cenozoic the basin experienced a long endorheic period marked by the formation of evaporites. Currently, the entire continental interior is an area of relative tectonic quiescence, characterised by a relict low-relief upland topography (Meseta). Systematic variations in lithology and a well-constrained tectonic setting throughout the basin and adjacent areas allow for the comparison of channel morphology between the Cenozoic Duero basin and its western fringe. To explore the signal of transient geomorphic response to capture and opening of the former endorheic basin, the main channel and 24 tributaries were analysed in terms of their longitudinal profiles and the application of geomorphic indices (concavity index [Ci], valley floor width-to-height ratio [Vf], and stream-length gradient index [SL]). The analysis reveals two zones with distinctive morphologies: (1) an upper reach domain consisting of broad flat valleys and low-gradient streams where concave longitudinal profiles dominate and (2) a middle reach domain characterised by steep, deeply incised canyons where a convex long profile dominates marking a major kinckzone. The quantitative information on channel shapes and long profile geometries allows the interpretation of these patterns in terms of driving forces for fluvial landscape development. Large-scale morphometric analysis highlights the transient response of the entire basin to a capture-related base level lowering and illustrates the importance of drainage captures as potential

  16. Immune Infiltration and Prostate Cancer

    PubMed Central

    Strasner, Amy; Karin, Michael

    2015-01-01

    It is becoming increasingly clear that inflammation influences prostate cancer (PCa) development and that immune cells are among the primary drivers of this effect. This information has launched numerous clinical trials testing immunotherapy drugs in PCa patients. The results of these studies are promising but have yet to generate a complete response. Importantly, the precise immune profile that determines clinical outcome remains unresolved. Individual immune cell types are divided into various functional subsets whose effects on tumor development may differ depending on their particular phenotype and functional status, which is often shaped by the tumor microenvironment. Thus, this review aims to examine the current knowledge regarding the role of inflammation and specific immune cell types in mediating PCa progression to assist in directing and optimizing immunotherapy targets, regimens, and responses and to uncover areas in which further research is needed. Finally, a summary of ongoing immunotherapy clinical trials in PCa is provided. PMID:26217583

  17. Convective and large-scale mass flux profiles over tropical oceans determined from synergistic analysis of a suite of satellite observations

    NASA Astrophysics Data System (ADS)

    Masunaga, Hirohiko; Luo, Zhengzhao Johnny

    2016-07-01

    A new, satellite-based methodology is developed to evaluate convective mass flux and large-scale total mass flux. To derive the convective mass flux, candidate profiles of in-cloud vertical velocity are first constructed with a simple plume model under the constraint of ambient sounding and then narrowed down to the solution that matches satellite-derived cloud top buoyancy. Meanwhile, the large-scale total mass flux is provided separately from satellite soundings by a method developed previously. All satellite snapshots are sorted into a composite time series that delineates the evolution of a vigorous and organized convective system. Principal findings are the following. First, convective mass flux is modulated primarily by convective cloud cover, with the intensity of individual convection being less variable over time. Second, convective mass flux dominates the total mass flux only during the early hours of the convective evolution; as convective system matures, a residual mass flux builds up in the mass flux balance that is reminiscent of stratiform dynamics. The method developed in this study is expected to be of unique utility for future observational diagnosis of tropical convective dynamics and for evaluation of global climate model cumulus parameterizations in a global sense.

  18. A concurrent validity study between the Hypnotic Induction Profile (HIP) and the Stanford Hypnotic Clinical Scale for Adults (SHCS:A) in an inpatient sample: a brief report.

    PubMed

    Gritzalis, Nicoletta; Oster, Marc; Frischholz, Edward J

    2009-10-01

    The Hypnotic Induction Profile (HIP) is a brief, standardized assessment of hypnotizability which takes 5-10 minutes to administer. The Stanford Hypnotic Clinical Scale for Adults (SHCS:A) is a different clinical measure of hypnotizability that takes about 20-25 minutes to administer. Although both scales purport to measure the same thing, they were based on different theories of hypnosis and constructed using different psychometric techniques. The present investigation is a concurrent validation study comparing scores on the two instruments in a sample of 24 inpatients. The correlation between the SHCS:A and HIP Induction score was 0.41 (p < .01). However, the Eye Roll Sign (ERS) did not correlate significantly with either the SHCS:A (.04, ns) or the HIP-IND score (-.05, ns). These results indicate that while scores on the HIP and SHCS:A are significantly correlated the inter-correlations are not high enough to consider them as interchangeable measures. Implications of these findings for future research are discussed. PMID:19862895

  19. Epidemic processes with immunization

    NASA Astrophysics Data System (ADS)

    Jiménez-Dalmaroni, Andrea; Hinrichsen, Haye

    2003-09-01

    We study a model of directed percolation (DP) with immunization, i.e., with different probabilities for the first infection and subsequent infections. The immunization effect leads to an additional non-Markovian term in the corresponding field theoretical action. We consider immunization as a small perturbation around the DP fixed point in d<6, where the non-Markovian term is relevant. The immunization causes the system to be driven away from the neighborhood of the DP critical point. In order to investigate the dynamical critical behavior of the model, we consider the limits of low and high first-infection rate, while the second-infection rate remains constant at the DP critical value. Scaling arguments are applied to obtain an expression for the survival probability in both limits. The corresponding exponents are written in terms of the critical exponents for ordinary DP and DP with a wall. We find that the survival probability does not obey a power-law behavior, decaying instead as a stretched exponential in the low first-infection probability limit and to a constant in the high first-infection probability limit. The theoretical predictions are confirmed by optimized numerical simulations in 1+1 dimensions.

  20. A combined analysis of the Frost Multidimensional Perfectionism Scale (FMPS), Child and Adolescent Perfectionism Scale (CAPS), and Almost Perfect Scale-Revised (APS-R): Different perfectionist profiles in adolescent high school students.

    PubMed

    Sironic, Amanda; Reeve, Robert A

    2015-12-01

    To investigate differences and similarities in the dimensional constructs of the Frost Multidimensional Perfectionism Scale (FMPS; Frost, Marten, Lahart, & Rosenblate, 1990), Child and Adolescent Perfectionism Scale (CAPS; Flett, Hewitt, Boucher, Davidson, & Munro, 2000), and Almost Perfect Scale-Revised (APS-R; Slaney, Rice, Mobley, Trippi, & Ashby, 2001), 938 high school students completed the 3 perfectionism questionnaires, as well as the Depression Anxiety Stress Scales (DASS; Lovibond & Lovibond, 1995). Preliminary analyses revealed commonly observed factor structures for each perfectionism questionnaire. Exploratory factor analysis of item responses from the questionnaires (combined) yielded a 4-factor solution (factors were labeled High Personal Standards, Concerns, Doubts and Discrepancy, Externally Motivated Perfectionism, and Organization and Order). A latent class analysis of individuals' mean ratings on each of the 4 factors yielded a 6-class solution. Three of the 6 classes represented perfectionist subgroups (labeled adaptive perfectionist, externally motivated maladaptive perfectionist, and mixed maladaptive perfectionist), and 3 represented nonperfectionist subgroups (labeled nonperfectionist A, nonperfectionist B, and order and organization nonperfectionist). Each of the 6 subgroups was meaningfully associated with the DASS. Findings showed that 3 out of 10 students were classified as maladaptive perfectionists, and maladaptive perfectionists were more prevalent than adaptive perfectionists. In sum, it is evident that combined ratings from the FMPS, CAPS, and APS-R offer a meaningful characterization of perfectionism. PMID:25984636

  1. Immune Thrombocytopenia

    PubMed Central

    Kistanguri, Gaurav; McCrae, Keith R.

    2013-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP, with the risk of bleeding and related morbidity increased in elderly patients. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Thrombocytopenia is caused by antibodies that react with glycoproteins expressed on platelets and megakaryocytes (glycoprotein IIb/IIIa, Ib/IX and others), causing shortened survival of circulating platelets and impairing platelet production. Diminished numbers and function of regulatory T cells, as well as the effects of cytotoxic T cells also contribute to the pathogenesis of ITP. Corticosteroids remain the most common first line therapy for ITP, occasionally in conjunction with intravenous immunoglobulin (IVIg) and anti-Rh(D). However, these agents do not lead to durable remissions in the majority of adults with ITP, and considerable heterogeneity exists in the use of second line approaches, which may include splenectomy, Rituximab, or thrombopoietin receptor agonists (TRAs). This review summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. Remarkable advances in the understanding and management of ITP have been achieved over the last decade, though many questions remain. PMID:23714309

  2. Immunization Schedules for Adults

    MedlinePlus

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedules for Adults in Easy-to-read Formats ... previous immunizations. View or Print a Schedule Recommended Immunizations for Adults (19 Years and Older) by Age ...

  3. Deceptive Imprinting and Immune Refocusing in Vaccine Design

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A large number of the world’s most widespread and problematic pathogens evade host immune responses by inducing strain specific immunity to immunodominant epitopes with high mutation rates capable of altering antigenic profiles. The immune system appears to be decoyed into reacting to these immunod...

  4. Cellular immune response in intraventricular experimental neurocysticercosis.

    PubMed

    Moura, Vania B L; Lima, Sarah B; Matos-Silva, Hidelberto; Vinaud, Marina C; Loyola, Patricia R A N; Lino, Ruy S

    2016-03-01

    Neurocysticercosis (NCC) is considered a neglected parasitic infection of the human central nervous system. Its pathogenesis is due to the host immune response, stage of evolution and location of the parasite. The aim of this study was to evaluate the in situ and systemic immune response through cytokines dosage (IL-4, IL-10, IL-17 and IFN-γ) as well as the local inflammatory response of the experimental NCC with Taenia crassiceps. The in situ and systemic cellular and inflammatory immune response were evaluated through the cytokines quantification at 7, 30, 60 and 90 days after inoculation and histopathological analysis. All cysticerci were found within the cerebral ventricles. There was a discrete intensity of inflammatory cells of mixed immune profile, polymorphonuclear and mononuclear cells, at the beginning of the infection and predominance of mononuclear cells at the end. The systemic immune response showed a significant increase in all the analysed cytokines and predominance of the Th2 immune profile cytokines at the end of the infection. These results indicate that the location of the cysticerci may lead to ventriculomegaly. The acute phase of the infection showed a mixed Th1/Th17 profile accompanied by high levels of IL-10 while the late phase showed a Th2 immune profile. PMID:26626017

  5. Exploring the Effects of Genetic Variants on Clinical Profiles of Parkinson's Disease Assessed by the Unified Parkinson's Disease Rating Scale and the Hoehn-Yahr Stage.

    PubMed

    Shi, Chen; Zheng, Zheng; Wang, Qi; Wang, Chaodong; Zhang, Dabao; Zhang, Min; Chan, Piu; Wang, Xiaomin

    2016-01-01

    Many genetic variants have been linked to familial or sporadic Parkinson's disease (PD), among which those identified in PARK16, BST1, SNCA, LRRK2, GBA and MAPT genes have been demonstrated to be the most common risk factors worldwide. Moreover, complex gene-gene and gene-environment interactions have been highlighted in PD pathogenesis. Compared to studies focusing on the predisposing effects of genes, there is a relative lack of research investigating how these genes and their interactions influence the clinical profiles of PD. In a cohort consisting of 2,011 Chinese Han PD patients, we selected 9 representative variants from the 6 above-mentioned common PD genes to analyze their main and epistatic effects on the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage of PD. With multiple linear regression models adjusting for medication status, disease duration, gender and age at onset, none of the variants displayed significant main effects on UPDRS or the H-Y scores. However, for gene-gene interaction analyses, 7 out of 37 pairs of variants showed significant or marginally significant associations with these scores. Among these, the GBA rs421016 (L444P)×LRRK2 rs33949390 (R1628P) interaction was consistently significant in relation to UPDRS III and UPDRS total (I+II+III), even after controlling for the family-wise error rate using False Discovery Rate (FDR-corrected p values are 0.0481 and 0.0070, respectively). Although the effects of the remaining pairs of variants did not survive the FDR correction, they showed marginally significant associations with either UPDRS or the H-Y stage (raw p<0.05). Our results highlight the importance of epistatic effects of multiple genes on the determination of PD clinical profiles and may have implications for molecular classification and personalized intervention of the disease. PMID:27299523

  6. Examining the relationship between personality and affect-related attributes and adolescents' intentions to try smoking using the Substance Use Risk Profile Scale.

    PubMed

    Memetovic, Jasmina; Ratner, Pamela A; Gotay, Carolyn; Richardson, Christopher G

    2016-05-01

    Assessments of adolescents' smoking intentions indicate that many are susceptible to smoking initiation because they do not have resolute intentions to abstain from trying smoking in the future. Although researchers have developed personality and affect-related risk factor profiles to understand risk for the initiation of substance use and abuse (e.g., alcohol), few have examined the extent to which these risk factors are related to the tobacco use intentions of adolescents who have yet to try tobacco smoking. The objective of this study was to examine the relationships between personality and affect-related risk factors measured by the Substance Use Risk Profile Scale (SURPS) and smoking intentions in a sample of adolescents who have not experimented with tobacco smoking. Data is based on responses from 1352 participants in the British Columbia Adolescent Substance Use Survey (56% female, 76% in Grade 8) who had never tried smoking tobacco. Of these 1352 participants, 29% (n=338) were classified as not having resolute intentions to not try smoking. Generalized estimating equations were used to examine the relationship between each SURPS dimension (Anxiety Sensitivity, Hopelessness, Impulsivity and Sensation Seeking) and the intention to try cigarettes in the future. Hopelessness (AOR 1.06, 95% CI [1.03, 1.10], p<.001), Impulsivity (AOR 1.07 [1.03, 1.11], p<.001) and Sensation Seeking (AOR 1.05 95% CI [1.02, 1.09], p<.01) had independent statistically significant associations with having an intention to try smoking. These findings may be used to inform a prevention-oriented framework to reduce susceptibility to tobacco smoking. PMID:26803399

  7. Factors associated with sinus bradycardia during crizotinib treatment: a retrospective analysis of two large-scale multinational trials (PROFILE 1005 and 1007).

    PubMed

    Ou, Sai-Hong Ignatius; Tang, Yiyun; Polli, Anna; Wilner, Keith D; Schnell, Patrick

    2016-04-01

    Decreases in heart rate (HR) have been described in patients receiving crizotinib. We performed a large retrospective analysis of HR changes during crizotinib therapy. HRs from vital-sign data for patients with anaplastic lymphoma kinase (ALK)-positive nonsmall cell lung cancer enrolled in PROFILE 1005 and the crizotinib arm of PROFILE 1007 were analyzed. Sinus bradycardia (SB) was defined as HR <60 beats per minute (bpm). Magnitude and timing of HR changes were assessed. Potential risk factors for SB were investigated by logistic regression analysis. Progression-free survival (PFS) was evaluated according to HR decrease by <20 versus ≥20 bpm within the first 50 days of starting treatment. For the 1053 patients analyzed, the mean maximum postbaseline HR decrease was 25 bpm (standard deviation 15.8). Overall, 441 patients (41.9%) had at least one episode of postbaseline SB. The mean precrizotinib treatment HR was significantly lower among patients with versus without postbaseline SB (82.2 bpm vs. 92.6 bpm). The likelihood of experiencing SB was statistically significantly higher among patients with a precrizotinib treatment HR <70 bpm. PFS was comparable among patients with or without HR decrease of ≥20 bpm within the first 50 days of starting crizotinib. Decrease in HR is very common among patients on crizotinib. The likelihood of experiencing SB was statistically significantly higher among patients with a precrizotinib treatment HR <70 bpm. This is the first large-scale report investigating the association between treatment with a tyrosine kinase inhibitor and the development of bradycardia. HRs should be closely monitored during crizotinib treatment. PMID:26823131

  8. Development of the first marmoset-specific DNA microarray (EUMAMA): a new genetic tool for large-scale expression profiling in a non-human primate

    PubMed Central

    Datson, Nicole A; Morsink, Maarten C; Atanasova, Srebrena; Armstrong, Victor W; Zischler, Hans; Schlumbohm, Christina; Dutilh, Bas E; Huynen, Martijn A; Waegele, Brigitte; Ruepp, Andreas; de Kloet, E Ronald; Fuchs, Eberhard

    2007-01-01

    Background The common marmoset monkey (Callithrix jacchus), a small non-endangered New World primate native to eastern Brazil, is becoming increasingly used as a non-human primate model in biomedical research, drug development and safety assessment. In contrast to the growing interest for the marmoset as an animal model, the molecular tools for genetic analysis are extremely limited. Results Here we report the development of the first marmoset-specific oligonucleotide microarray (EUMAMA) containing probe sets targeting 1541 different marmoset transcripts expressed in hippocampus. These 1541 transcripts represent a wide variety of different functional gene classes. Hybridisation of the marmoset microarray with labelled RNA from hippocampus, cortex and a panel of 7 different peripheral tissues resulted in high detection rates of 85% in the neuronal tissues and on average 70% in the non-neuronal tissues. The expression profiles of the 2 neuronal tissues, hippocampus and cortex, were highly similar, as indicated by a correlation coefficient of 0.96. Several transcripts with a tissue-specific pattern of expression were identified. Besides the marmoset microarray we have generated 3215 ESTs derived from marmoset hippocampus, which have been annotated and submitted to GenBank [GenBank: EF214838 – EF215447, EH380242 – EH382846]. Conclusion We have generated the first marmoset-specific DNA microarray and demonstrated its use to characterise large-scale gene expression profiles of hippocampus but also of other neuronal and non-neuronal tissues. In addition, we have generated a large collection of ESTs of marmoset origin, which are now available in the public domain. These new tools will facilitate molecular genetic research into this non-human primate animal model. PMID:17592630

  9. Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses*

    PubMed Central

    2016-01-01

    To determine the effectiveness of immunization strategies used in therapeutic antibody or vaccine development, it is critical to assess the quality of immunization-induced polyclonal antibody responses. Here, we developed a workflow that uses sensitive methods to quantitatively and qualitatively assess immune responses against foreign antigens with regard to antibody binding affinity and epitope diversity. The application of such detailed assessments throughout an immunization campaign can significantly reduce the resources required to generate highly specific antibodies. Our workflow consists of the following two steps: 1) the use of surface plasmon resonance to quantify antigen-specific antibodies and evaluate their apparent binding affinities, and 2) the recovery of serum IgGs using an automated small scale purification system, followed by the determination of their epitope diversity using hydrogen deuterium exchange coupled with mass spectrometry. We showed that these methods were sensitive enough to detect antigen-specific IgGs in the nanogram/μl range and that they provided information for differentiating the antibody responses of the various immunized animals that could not be obtained by conventional methods. We also showed that this workflow can guide the selection of an animal that produces high affinity antibodies with a desired epitope coverage profile, resulting in the generation of potential therapeutic monoclonal antibody clones with desirable functional profiles. We postulate that this workflow will be an important tool in the development of effective vaccines to combat the highly sophisticated evasion mechanisms of pathogens. PMID:27288409

  10. Efficient Qualitative and Quantitative Determination of Antigen-induced Immune Responses.

    PubMed

    Yang, Danlin; Frego, Lee; Lasaro, Marcio; Truncali, Kristopher; Kroe-Barrett, Rachel; Singh, Sanjaya

    2016-07-29

    To determine the effectiveness of immunization strategies used in therapeutic antibody or vaccine development, it is critical to assess the quality of immunization-induced polyclonal antibody responses. Here, we developed a workflow that uses sensitive methods to quantitatively and qualitatively assess immune responses against foreign antigens with regard to antibody binding affinity and epitope diversity. The application of such detailed assessments throughout an immunization campaign can significantly reduce the resources required to generate highly specific antibodies. Our workflow consists of the following two steps: 1) the use of surface plasmon resonance to quantify antigen-specific antibodies and evaluate their apparent binding affinities, and 2) the recovery of serum IgGs using an automated small scale purification system, followed by the determination of their epitope diversity using hydrogen deuterium exchange coupled with mass spectrometry. We showed that these methods were sensitive enough to detect antigen-specific IgGs in the nanogram/μl range and that they provided information for differentiating the antibody responses of the various immunized animals that could not be obtained by conventional methods. We also showed that this workflow can guide the selection of an animal that produces high affinity antibodies with a desired epitope coverage profile, resulting in the generation of potential therapeutic monoclonal antibody clones with desirable functional profiles. We postulate that this workflow will be an important tool in the development of effective vaccines to combat the highly sophisticated evasion mechanisms of pathogens. PMID:27288409

  11. Large-Scale microRNA Expression Profiling Identifies Putative Retinal miRNA-mRNA Signaling Pathways Underlying Form-Deprivation Myopia in Mice.

    PubMed

    Tkatchenko, Andrei V; Luo, Xiaoyan; Tkatchenko, Tatiana V; Vaz, Candida; Tanavde, Vivek M; Maurer-Stroh, Sebastian; Zauscher, Stefan; Gonzalez, Pedro; Young, Terri L

    2016-01-01

    Development of myopia is associated with large-scale changes in ocular tissue gene expression. Although differential expression of coding genes underlying development of myopia has been a subject of intense investigation, the role of non-coding genes such as microRNAs in the development of myopia is largely unknown. In this study, we explored myopia-associated miRNA expression profiles in the retina and sclera of C57Bl/6J mice with experimentally induced myopia using microarray technology. We found a total of 53 differentially expressed miRNAs in the retina and no differences in miRNA expression in the sclera of C57BL/6J mice after 10 days of visual form deprivation, which induced -6.93 ± 2.44 D (p < 0.000001, n = 12) of myopia. We also identified their putative mRNA targets among mRNAs found to be differentially expressed in myopic retina and potential signaling pathways involved in the development of form-deprivation myopia using miRNA-mRNA interaction network analysis. Analysis of myopia-associated signaling pathways revealed that myopic response to visual form deprivation in the retina is regulated by a small number of highly integrated signaling pathways. Our findings highlighted that changes in microRNA expression are involved in the regulation of refractive eye development and predicted how they may be involved in the development of myopia by regulating retinal gene expression. PMID:27622715

  12. [Reactions and psychic disorders in Besnier-Boeck-Schaumann disease. Clinical and psychological approach; application of a scale of aggressive behavior to the mental profile].

    PubMed

    Escande, M; Gardes, J P; Gayral, L F

    1980-01-01

    35 cases of sarcoïdosis were studied at the onset of the disease. 25 cases of important or deep anxiety were recorded. None of them was correlated nor with organic lesions or medical seriousness, neither with psychopathic background, previous mental illness or treatment by corticoidic drugs. All patients were submitted to the Rorschach test, the self-assessment test of Catell, the Rosenzweig picture frustration test and the agressiveness rating scale test (L.-F. Gayral). It appears that, by comparison with three control groups: A) without sarcoïdosis but with another pulmonary disease, B) "normal", C) psychopathic personality. There is not a mental type profile for the patients with sarcoïdosis. Anxiety or/and with depression, or agressiveness are more important and frequent in patients not treated by corticoïdes than in patient treated. Another conclusion is the necessity to dispense careful psychotherapy to patients with sarcoïdosis, although the case does not require medical treatment. Quite contrary these last patients peculiarly need psychotherapy. PMID:7458104

  13. Psychometric Evaluation of the Substance Use Risk Profile Scale (SURPS) in an Inpatient Sample of Substance Users Using Cue-Reactivity Methodology

    PubMed Central

    Schlauch, Robert C.; Crane, Cory A.; Houston, Rebecca J.; Molnar, Danielle S.; Schlienz, Nicolas J.; Lang, Alan R.

    2015-01-01

    The current project sought to examine the psychometric properties of a personality based measure (Substance Use Risk Profile Scale; SURPS: introversion-hopelessness, anxiety sensitivity, impulsivity, and sensation seeking) designed to differentially predict substance use preferences and patterns by matching primary personality-based motives for use to the specific effects of various psychoactive substances. Specifically, we sought to validate the SURPS in a clinical sample of substance users using cue reactivity methodology to assess current inclinations to consume a wide range of psychoactive substances. Using confirmatory factor analysis and correlational analyses, the SURPS demonstrated good psychometric properties and construct validity. Further, impulsivity and sensation-seeking were associated with use of multiple substances but could be differentiated by motives for use and susceptibility to the reinforcing effects of stimulants (i.e., impulsivity) and alcohol (i.e. sensation-seeking). In contrast, introversion-hopelessness and anxiety sensitivity demonstrated a pattern of use more focused on reducing negative affect, but were not differentiated based on specific patterns of use. Taken together, results suggests that among those receiving inpatient treatment for substance use disorders, the SURPS is a valid instrument for measuring four distinct personality dimensions that may be sensitive to motivational susceptibilities to specific patterns of alcohol and drug use. PMID:26052180

  14. Large-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases.

    PubMed

    Tajuddin, Salman M; Schick, Ursula M; Eicher, John D; Chami, Nathalie; Giri, Ayush; Brody, Jennifer A; Hill, W David; Kacprowski, Tim; Li, Jin; Lyytikäinen, Leo-Pekka; Manichaikul, Ani; Mihailov, Evelin; O'Donoghue, Michelle L; Pankratz, Nathan; Pazoki, Raha; Polfus, Linda M; Smith, Albert Vernon; Schurmann, Claudia; Vacchi-Suzzi, Caterina; Waterworth, Dawn M; Evangelou, Evangelos; Yanek, Lisa R; Burt, Amber; Chen, Ming-Huei; van Rooij, Frank J A; Floyd, James S; Greinacher, Andreas; Harris, Tamara B; Highland, Heather M; Lange, Leslie A; Liu, Yongmei; Mägi, Reedik; Nalls, Mike A; Mathias, Rasika A; Nickerson, Deborah A; Nikus, Kjell; Starr, John M; Tardif, Jean-Claude; Tzoulaki, Ioanna; Velez Edwards, Digna R; Wallentin, Lars; Bartz, Traci M; Becker, Lewis C; Denny, Joshua C; Raffield, Laura M; Rioux, John D; Friedrich, Nele; Fornage, Myriam; Gao, He; Hirschhorn, Joel N; Liewald, David C M; Rich, Stephen S; Uitterlinden, Andre; Bastarache, Lisa; Becker, Diane M; Boerwinkle, Eric; de Denus, Simon; Bottinger, Erwin P; Hayward, Caroline; Hofman, Albert; Homuth, Georg; Lange, Ethan; Launer, Lenore J; Lehtimäki, Terho; Lu, Yingchang; Metspalu, Andres; O'Donnell, Chris J; Quarells, Rakale C; Richard, Melissa; Torstenson, Eric S; Taylor, Kent D; Vergnaud, Anne-Claire; Zonderman, Alan B; Crosslin, David R; Deary, Ian J; Dörr, Marcus; Elliott, Paul; Evans, Michele K; Gudnason, Vilmundur; Kähönen, Mika; Psaty, Bruce M; Rotter, Jerome I; Slater, Andrew J; Dehghan, Abbas; White, Harvey D; Ganesh, Santhi K; Loos, Ruth J F; Esko, Tõnu; Faraday, Nauder; Wilson, James G; Cushman, Mary; Johnson, Andrew D; Edwards, Todd L; Zakai, Neil A; Lettre, Guillaume; Reiner, Alex P; Auer, Paul L

    2016-07-01

    White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases. PMID:27346689

  15. Integrated Circuit Immunity

    NASA Technical Reports Server (NTRS)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  16. Nanoengineering of Immune Cell Function

    PubMed Central

    Shen, Keyue; Milone, Michael C.; Dustin, Michael L.; Kam, Lance C.

    2010-01-01

    T lymphocytes are a key regulatory component of the adaptive immune system. Understanding how the micro- and nano-scale details of the extracellular environment influence T cell activation may have wide impact on the use of T cells for therapeutic purposes. In this article, we examine how the micro- and nano-scale presentation of ligands to cell surface receptors, including microscale organization and nanoscale mobility, influences the activation of T cells. We extend these studies to include the role of cell-generated forces, and the rigidity of the microenvironment, on T cell activation. These approaches enable delivery of defined signals to T cells, a step toward understanding the cell-cell communication in the immune system, and developing micro/nano- and material- engineered systems for tailoring immune responses for adoptive T cell therapies. PMID:21562611

  17. Clinical Development of Immune Checkpoint Inhibitors.

    PubMed

    Ito, Ayumu; Kondo, Shunsuke; Tada, Kohei; Kitano, Shigehisa

    2015-01-01

    Recent progress in cancer immunotherapy has been remarkable. Most striking are the clinical development and approval of immunomodulators, also known as immune checkpoint inhibitors. These monoclonal antibodies (mAb) are directed to immune checkpoint molecules, which are expressed on immune cells and mediate signals to attenuate excessive immune reactions. Although mAbs targeting tumor associated antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells and induce cell death, immune checkpoint inhibitors restore and augment the antitumor immune activities of cytotoxic T cells by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of immune checkpoint inhibitors in a variety of cancers. The first in class approved immune checkpoint inhibitor is ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) mAb. Two pivotal phase III randomized controlled trials demonstrated a survival benefit in patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved ipilimumab for metastatic melanoma. Several clinical trials have since investigated new agents, alone and in combination, for various cancers. In this review, we discuss the current development status of and future challenges in utilizing immune checkpoint inhibitors. PMID:26161407

  18. Clinical Development of Immune Checkpoint Inhibitors

    PubMed Central

    Ito, Ayumu; Kondo, Shunsuke; Tada, Kohei; Kitano, Shigehisa

    2015-01-01

    Recent progress in cancer immunotherapy has been remarkable. Most striking are the clinical development and approval of immunomodulators, also known as immune checkpoint inhibitors. These monoclonal antibodies (mAb) are directed to immune checkpoint molecules, which are expressed on immune cells and mediate signals to attenuate excessive immune reactions. Although mAbs targeting tumor associated antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells and induce cell death, immune checkpoint inhibitors restore and augment the antitumor immune activities of cytotoxic T cells by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of immune checkpoint inhibitors in a variety of cancers. The first in class approved immune checkpoint inhibitor is ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) mAb. Two pivotal phase III randomized controlled trials demonstrated a survival benefit in patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved ipilimumab for metastatic melanoma. Several clinical trials have since investigated new agents, alone and in combination, for various cancers. In this review, we discuss the current development status of and future challenges in utilizing immune checkpoint inhibitors. PMID:26161407

  19. Immune thrombocytopenia.

    PubMed

    Maher, George M

    2014-10-01

    Immune thrombocytopenia (ITP) in children is a relatively uncommon and generally benign condition presenting as abrupt onset of bruising, petechiae and thrombocytopenia in an otherwise healthy child due to production of anti-platelet autoantibodies. Diagnosis is largely clinical and laboratory investigation should be kept to a minimum. Indications for treatment have not been standardized and include bleeding, parental anxiety and quality of life. Multiple treatments are available that have been proven to increase the platelet count; the most commonly employed include IVIG, steroids and WinRho (anti-D). Intracranial hemorrhage is the most serious potential complication but is extremely rare and splenectomy is reserved for chronically symptomatic patients who have not responded to other modalities. Identification of molecular targets may be a promising avenue for future research. PMID:25423768

  20. Is there a typical germinal center? A large-scale immunohistological study on the cellular composition of germinal centers during the hapten-carrier-driven primary immune response in mice.

    PubMed

    Wittenbrink, Nicole; Klein, Anke; Weiser, Armin A; Schuchhardt, Johannes; Or-Guil, Michal

    2011-12-15

    Germinal centers (GCs) are complex, multicell-type, transient structures that form in secondary lymphatic tissues in response to T cell-dependent stimulation. This process is crucial to the adaptive immune response because it is the source of affinity maturation and long-lived B cell memory. Our previous studies showed that the growth of murine splenic GCs is nonsynchronized, involving broad-volume distributions of individual GCs at any time. This raises the question whether such a thing as a typical GC exists. To address this matter, we acquired large-scale confocal data on GCs throughout the course of the 2-phenyl-5-oxazolone chicken serum albumin-driven primary immune response in BALB/c mice. Semiautomated image analysis of 3457 GC sections revealed that, although there is no typical GC in terms of size, GCs have a typical cellular composition in that the cell ratios of resident T cells, macrophages, proliferating cells, and apoptotic nuclei are maintained during the established phase of the response. Moreover, our data provide evidence that the dark zone (DZ) and light zone (LZ) compartments of GCs are about the same size and led us to estimate that the minimal cell loss rate in GCs is 3% per hour. Furthermore, we found that the population of GC macrophages is larger and more heterogeneous than previously thought, and that despite enrichment of T cells in the LZ, the DZ of murine splenic GCs is not poor in T cells. DZ and LZ differ in the T cell-to-macrophage ratio rather than in the density of T cells. PMID:22102720

  1. Immunization and Pregnancy

    MedlinePlus

    Immunization & Pregnancy Vaccines help keep apregnant woman and her growing family healthy. Vaccine Before pregnancy Hepatitis A ... 232-4636) • English or Spanish National Center for Immunization and Respiratory Diseases Immunization Services Division CS238938B 03/ ...

  2. Immune System Involvement

    MedlinePlus

    ... Tips" to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... swollen and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  3. Childhood Immunization Schedule

    MedlinePlus

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  4. Immune System and Disorders

    MedlinePlus

    ... substances that are usually not harmful Immune deficiency diseases - disorders in which the immune system is missing one or more of its parts Autoimmune diseases - diseases causing your immune system to attack your ...

  5. Large-Scale Glycomics of Livestock: Discovery of Highly Sensitive Serum Biomarkers Indicating an Environmental Stress Affecting Immune Responses and Productivity of Holstein Dairy Cows.

    PubMed

    Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro

    2015-12-01

    Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity. PMID:26595672

  6. Long-Term Stability of Membership in a Wechsler Intelligence Scale for Children--Third Edition (WISC-III) Subtest Core Profile Taxonomy

    ERIC Educational Resources Information Center

    Borsuk, Ellen R.; Watkins, Marley W.; Canivez, Gary L.

    2006-01-01

    Although often applied in practice, clinically based cognitive subtest profile analysis has failed to achieve empirical support. Nonlinear multivariate subtest profile analysis may have benefits over clinically based techniques, but the psychometric properties of these methods must be studied prior to their implementation and interpretation. The…

  7. Co-administration of plasmid expressing IL-12 with 14-kDa Schistosoma mansoni fatty acid-binding protein cDNA alters immune response profiles and fails to enhance protection induced by Sm14 DNA vaccine alone.

    PubMed

    Fonseca, Cristina T; Pacífico, Lucila G G; Barsante, Michele M; Rassi, Tatiana; Cassali, Geovanni D; Oliveira, Sérgio C

    2006-08-01

    Schistosomiasis is an endemic disease that affects 200 million people worldwide. DNA-based vaccine is a promising strategy to induce protective immunity against schistosomiasis, since both humoral and cellular immune responses are involved in parasite elimination. In this study, we evaluated the ability of Sm14 cDNA alone or in association with a plasmid expressing murine interleukin (IL)-12 to induce protection against challenge infection. Mice were immunized with four doses of the DNA vaccine and the levels of protection were determined by worm burden recovery after challenge infection. Specific antibody production to rSm14 was determined by ELISA, and cytokine production was measured in splenocyte culture supernatants stimulated with rSm14 and in bronchoalveolar lavage of vaccinated mice after challenge infection. DNA immunization with pCI/Sm14 alone induced 40.5% of worm reduction. However, the use of pCI/IL-12 as adjuvant to pCI/Sm14 immunization failed to enhance protection against challenge infection. Protection induced by pCI/Sm14 immunization correlates with specific IgG antibody production against Sm14, Th1 type of immune response with high levels of interferon (IFN)-gamma and low levels of IL-4 in splenocyte culture supernatants and in bronchoalveolar lavage after challenge infection. IL-12 co-administration with pCI/Sm14 induced a significant production of nitric oxide in splenocyte culture supernatants and also lymphocyte suppression, with reduced percentage of T cells producing IFN-gamma and tumor necrosis factor-alpha. PMID:16914349

  8. Gut microbiota, metabolites and host immunity.

    PubMed

    Rooks, Michelle G; Garrett, Wendy S

    2016-05-27

    The microbiota - the collection of microorganisms that live within and on all mammals - provides crucial signals for the development and function of the immune system. Increased availability of technologies that profile microbial communities is facilitating the entry of many immunologists into the evolving field of host-microbiota studies. The microbial communities, their metabolites and components are not only necessary for immune homeostasis, they also influence the susceptibility of the host to many immune-mediated diseases and disorders. In this Review, we discuss technological and computational approaches for investigating the microbiome, as well as recent advances in our understanding of host immunity and microbial mutualism with a focus on specific microbial metabolites, bacterial components and the immune system. PMID:27231050

  9. Total magnitudes of Virgo galaxies - III. Scale errors in the Reference Catalogue of Bright Galaxies T system and light-profile distortion by resolution-degrading and differential-distance effects

    NASA Astrophysics Data System (ADS)

    Young, Christopher Ke-shih

    2004-11-01

    We investigate the BT magnitude scales of the Second and Third Reference Catalogues of Bright Galaxies, finding both scales to be reasonably reliable for 11.5 <~Bt<~ 14.0. However, large-scale errors of 0.26 and 0.24mag per unit mag interval respectively are uncovered for early-type galaxies at the bright ends, whilst even larger ones of 0.74 and 0.36mag per unit mag interval are found for galaxies of all morphological types at the faint ends. We attribute this situation to several effects already discussed by Young et al. and Young (Paper I), including the application of relatively inflexible growth-curve models that are only in a few specific cases appropriate to the galaxies concerned. Of particular interest to this study though, we find that the apparent profile shapes of giant galaxies in the Virgo direction of cz < 15000 km s-1 tend to be less centrally concentrated the greater their distance. This demonstrates that even for relatively nearby galaxies, the distortion of the overall shapes of light profiles by resolution-degrading effects such as seeing and data smoothing, as originally predicted and modelled by Young & Currie and Young et al., is a significant effect. It is, therefore, not good practice simply to extrapolate the profiles of galaxies of identical intrinsic size and intrinsic profile shape (i.e. identical morphology) by means of the same growth-curve model, unless the galaxies are known a priori to be at the same distance and unless their photometry is of the same angular resolution. We also investigate the total-magnitude scale of the catalogue of photometric types of Prugniel & Héraudeau, finding it to be much more reliable than the BT one. However, we argue that photometric type is really a measure of apparent profile shape (i.e. intrinsic profile shape after scale reduction on account of distance followed by convolution with a seeing disc and often a smoothing function as well). Strictly, it should therefore only be applicable to

  10. Global analysis of the immune response

    NASA Astrophysics Data System (ADS)

    Ribeiro, Leonardo C.; Dickman, Ronald; Bernardes, Américo T.

    2008-10-01

    The immune system may be seen as a complex system, characterized using tools developed in the study of such systems, for example, surface roughness and its associated Hurst exponent. We analyze densitometric (Panama blot) profiles of immune reactivity, to classify individuals into groups with similar roughness statistics. We focus on a population of individuals living in a region in which malaria endemic, as well as a control group from a disease-free region. Our analysis groups individuals according to the presence, or absence, of malaria symptoms and number of malaria manifestations. Applied to the Panama blot data, our method proves more effective at discriminating between groups than principal-components analysis or super-paramagnetic clustering. Our findings provide evidence that some phenomena observed in the immune system can be only understood from a global point of view. We observe similar tendencies between experimental immune profiles and those of artificial profiles, obtained from an immune network model. The statistical entropy of the experimental profiles is found to exhibit variations similar to those observed in the Hurst exponent.

  11. Mechanisms of Immune Evasion in Leishmaniasis

    PubMed Central

    Gupta, Gaurav; Oghumu, Steve; Satoskar, Abhay R.

    2013-01-01

    Diseases caused by Leishmania present a worldwide problem, and current therapeutic approaches are unable to achieve a sterile cure. Leishmania is able to persist in host cells by evading or exploiting host immune mechanisms. A thorough understanding of these mechanisms could lead to better strategies for effective management of Leishmania infections. Current research has focused on parasite modification of host cell signaling pathways, entry into phagocytic cells, and modulation of cytokine and chemokine profiles that alter immune cell activation and trafficking to sites of infection. Immuno-therapeutic approaches that target these mechanisms of immune evasion by Leishmania offer promising areas for preclinical and clinical research. PMID:23415155

  12. Stress, Nutrition, and Intestinal Immune Responses in Pigs - A Review.

    PubMed

    Lee, In Kyu; Kye, Yoon Chul; Kim, Girak; Kim, Han Wool; Gu, Min Jeong; Umboh, Johnny; Maaruf, Kartini; Kim, Sung Woo; Yun, Cheol-Heui

    2016-08-01

    Modern livestock production became highly intensive and large scaled to increase production efficiency. This production environment could add stressors affecting the health and growth of animals. Major stressors can include environment (air quality and temperature), nutrition, and infection. These stressors can reduce growth performance and alter immune systems at systemic and local levels including the gastrointestinal tract. Heat stress increases the permeability, oxidative stress, and inflammatory responses in the gut. Nutritional stress from fasting, antinutritional compounds, and toxins induces the leakage and destruction of the tight junction proteins in the gut. Fasting is shown to suppress pro-inflammatory cytokines, whereas deoxynivalenol increases the recruitment of intestinal pro-inflammatory cytokines and the level of lymphocytes in the gut. Pathogenic and viral infections such as Enterotoxigenic E. coli (ETEC) and porcine epidemic diarrhea virus can lead to loosening the intestinal epithelial barrier. On the other hand, supplementation of Lactobacillus or Saccharaomyces reduced infectious stress by ETEC. It was noted that major stressors altered the permeability of intestinal barriers and profiles of genes and proteins of pro-inflammatory cytokines and chemokines in mucosal system in pigs. However, it is not sufficient to fully explain the mechanism of the gut immune system in pigs under stress conditions. Correlation and interaction of gut and systemic immune system under major stressors should be better defined to overcome aforementioned obstacles. PMID:27189643

  13. Protective Antigens Against Glanders Identified by Expression Library Immunization

    PubMed Central

    Whitlock, Gregory C.; Robida, Mark D.; Judy, Barbara M.; Qazi, Omar; Brown, Katherine A.; Deeraksa, Arpaporn; Taylor, Katherine; Massey, Shane; Loskutov, Andrey; Borovkov, Alex Y.; Brown, Kevin; Cano, Jose A.; Magee, D. Mitchell; Torres, Alfredo G.; Estes, D. Mark; Sykes, Kathryn F.

    2011-01-01

    Burkholderia are highly evolved Gram-negative bacteria that primarily infect solipeds but are transmitted to humans by ingestion and cutaneous or aerosol exposures. Heightened concern over human infections of Burkholderia mallei and the very closely related species B. pseudomallei is due to the pathogens’ proven effectiveness as bioweapons, and to the increased potential for natural opportunistic infections in the growing diabetic and immuno-compromised populations. These Burkholderia species are nearly impervious to antibiotic treatments and no vaccine exists. In this study, the genome of the highly virulent B. mallei ATCC23344 strain was examined by expression library immunization for gene-encoded protective antigens. This protocol for genomic-scale functional screening was customized to accommodate the unusually large complexity of Burkholderia, and yielded 12 new putative vaccine candidates. Five of the candidates were individually tested as protein immunogens and three were found to confer significant partial protection against a lethal pulmonary infection in a murine model of disease. Determinations of peripheral blood cytokine and chemokine profiles following individual protein immunizations show that interleukin-2 (IL-2) and IL-4 are elicited by the three confirmed candidates, but unexpectedly interferon-γ and tumor necrosis factor-α are not. We suggest that these pathogen components, discovered using genetic immunization and confirmed in a conventional protein format, will be useful toward the development of a safe and effective glanders vaccine. PMID:22125550

  14. Our Immune System

    MedlinePlus

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  15. Immunization for Women

    MedlinePlus

    ... nfid.org/#sthash.eZ72dCSP.dpuf Diseases & Vaccines Overview Immunization Schedules Talk to you doctor about your immunization ... years Immunization Schedule for Children, 7-18 years Immunization News July 8, 2016 HPV-related cancers on ...

  16. Your Child's Immunizations

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Your Child's Immunizations KidsHealth > For Parents > Your Child's Immunizations Print A A A Text Size What's in ... But in both cases, the protection is temporary. Immunization (vaccination) is a way of creating immunity to ...

  17. The modulation of immunity

    SciTech Connect

    Mitchell, M.S.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: Modulation of Immunity by Thymus-Derived Lymphocytes; Modulation of Immunity by Macrophages; Modulation of Immunity by Soluble Mediators; Viruses and the Immune Response; and Methanol Extraction Residue: Effects and Mechanisms of Action.

  18. Epigenetic Control of Immunity

    PubMed Central

    Busslinger, Meinrad; Tarakhovsky, Alexander

    2014-01-01

    Immunity relies on the heterogeneity of immune cells and their ability to respond to pathogen challenges. In the adaptive immune system, lymphocytes display a highly diverse antigen receptor repertoire that matches the vast diversity of pathogens. In the innate immune system, the cell's heterogeneity and phenotypic plasticity enable flexible responses to changes in tissue homeostasis caused by infection or damage. The immune responses are calibrated by the graded activity of immune cells that can vary from yeast-like proliferation to lifetime dormancy. This article describes key epigenetic processes that contribute to the function of immune cells during health and disease. PMID:24890513

  19. Integrated Immune Experiment

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2009-01-01

    This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  20. ACUTE PHASE IMMUNE GENE PROFILING OF SPLEEN AND PEYER’S PATCH IN NAÏVE AND VACCINATED CHICKENS FOLLOWING AVIAN INFLUENZA A (H5N1) VIRUS INFECTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, we applied functional genomics tools to investigate the early immunological response of chickens to highly pathogenic (HP) avian influenza virus (AIV). Infection with HPAIV usually results in the rapid death of poultry. The aim of this study was to identify host immune genes which a...

  1. Immune Responses in Hookworm Infections

    PubMed Central

    Loukas, Alex; Prociv, Paul

    2001-01-01

    Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinoophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections. PMID:11585781

  2. An Item Response Theory Analysis of Harter's Self-Perception Profile for Children or Why Strong Clinical Scales Should Be Distrusted

    ERIC Educational Resources Information Center

    Egberink, Iris J. L.; Meijer, Rob R.

    2011-01-01

    The authors investigated the psychometric properties of the subscales of the Self-Perception Profile for Children with item response theory (IRT) models using a sample of 611 children. Results from a nonparametric Mokken analysis and a parametric IRT approach for boys (n = 268) and girls (n = 343) were compared. The authors found that most scales…

  3. Computational Typologies of Multidimensional End-of-Primary-School Performance Profiles from an Educational Perspective of Large-Scale TIMSS and PIRLS Surveys

    ERIC Educational Resources Information Center

    Unlu, Ali; Schurig, Michael

    2015-01-01

    Recently, performance profiles in reading, mathematics and science were created using the data collectively available in the Trends in International Mathematics and Science Study (TIMSS) and the Progress in International Reading Literacy Study (PIRLS) 2011. In addition, a classification of children to the end of their primary school years was…

  4. Cancer-Associated Immune Resistance and Evasion of Immune Surveillance in Colorectal Cancer.

    PubMed

    Parcesepe, Pietro; Giordano, Guido; Laudanna, Carmelo; Febbraro, Antonio; Pancione, Massimo

    2016-01-01

    Data from molecular profiles of tumors and tumor associated cells provide a model in which cancer cells can acquire the capability of avoiding immune surveillance by expressing an immune-like phenotype. Recent works reveal that expression of immune antigens (PDL1, CD47, CD73, CD14, CD68, MAC387, CD163, DAP12, and CD15) by tumor cells "immune resistance," combined with prometastatic function of nonmalignant infiltrating cells, may represent a strategy to overcome the rate-limiting steps of metastatic cascade through (a) enhanced interactions with protumorigenic myeloid cells and escape from T-dependent immune response mediated by CD8+ and natural killer (NK) cells; (b) production of immune mediators that establish a local and systemic tumor-supportive environment (premetastatic niche); (c) ability to survive either in the peripheral blood as circulating tumor cells (CTCs) or at the metastatic site forming a cooperative prometastatic loop with foreign "myeloid" cells, macrophages, and neutrophils, respectively. The development of cancer-specific "immune resistance" can be orchestrated either by cooperation with tumor microenvironment or by successive rounds of genetic/epigenetic changes. Recognition of the applicability of this model may provide effective therapeutic avenues for complete elimination of immune-resistant metastatic cells and for enhanced antitumor immunity as part of a combinatorial strategy. PMID:27006653

  5. Cancer-Associated Immune Resistance and Evasion of Immune Surveillance in Colorectal Cancer

    PubMed Central

    Laudanna, Carmelo; Febbraro, Antonio

    2016-01-01

    Data from molecular profiles of tumors and tumor associated cells provide a model in which cancer cells can acquire the capability of avoiding immune surveillance by expressing an immune-like phenotype. Recent works reveal that expression of immune antigens (PDL1, CD47, CD73, CD14, CD68, MAC387, CD163, DAP12, and CD15) by tumor cells “immune resistance,” combined with prometastatic function of nonmalignant infiltrating cells, may represent a strategy to overcome the rate-limiting steps of metastatic cascade through (a) enhanced interactions with protumorigenic myeloid cells and escape from T-dependent immune response mediated by CD8+ and natural killer (NK) cells; (b) production of immune mediators that establish a local and systemic tumor-supportive environment (premetastatic niche); (c) ability to survive either in the peripheral blood as circulating tumor cells (CTCs) or at the metastatic site forming a cooperative prometastatic loop with foreign “myeloid” cells, macrophages, and neutrophils, respectively. The development of cancer-specific “immune resistance” can be orchestrated either by cooperation with tumor microenvironment or by successive rounds of genetic/epigenetic changes. Recognition of the applicability of this model may provide effective therapeutic avenues for complete elimination of immune-resistant metastatic cells and for enhanced antitumor immunity as part of a combinatorial strategy. PMID:27006653

  6. Immunizations: Active vs. Passive

    MedlinePlus

    ... they’ve been exposed. For example, the passive rabies immunization (rabies immune globulin) is commonly used after a certain ... of your pediatrician. There may be variations in treatment that your pediatrician may recommend based on individual ...

  7. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  8. Immune system structures (image)

    MedlinePlus

    The immune system protects the body from potentially harmful substances. The inflammatory response (inflammation) is part of innate immunity. It occurs when tissues are injured by bacteria, trauma, toxins, heat or any other cause.

  9. Immune system structures (image)

    MedlinePlus

    The immune system protects the body from potentially harmful substances. The inflammatory response (inflammation) is part of innate immunity. It occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause.

  10. Aging changes in immunity

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. Aging Changes and Their Effects on the Immune System ...

  11. Immune System and Disorders

    MedlinePlus

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  12. Pneumonia - weakened immune system

    MedlinePlus

    ... medlineplus.gov/ency/article/000093.htm Pneumonia - weakened immune system To use the sharing features on this page, ... fighting off infection because of problems with the immune system. This type of disease is called "pneumonia in ...

  13. Immunity to cancer

    SciTech Connect

    Reif, A.E.; Mitchell, M.S.

    1985-01-01

    This book contains five sections, each containing several papers. The section titles are: Identification and Characterization of Tumor Antigens; Immune Responses to Tumor Antigens; Regulation of the Immune Response to Tumor Cells, Immunotherapy and Biomodulators, and Immunotherapy and Immunoprophylaxis.

  14. NATIONAL IMMUNIZATION SURVEY (NIS)

    EPA Science Inventory

    The National Immunization Survey (NIS) is sponsored by the National Immunization Program (NIP) and conducted by the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention.

  15. Exercise and immunity

    MedlinePlus

    ... know exactly if or how exercise increases your immunity to certain illnesses, but there are several theories ( ... not exercise more intensely just to increase their immunity. Heavy, long-term exercise (such as marathon running ...

  16. Receptor signaling clusters in the immune synapse

    PubMed Central

    Dustin, Michael L.; Groves, Jay T.

    2014-01-01

    Signaling processes between various immune cells involve large scale spatial reorganization of receptors and signaling molecules within the cell-cell junction. These structures, now collectively referred to as immune synapses, interleave physical and mechanical processes with the cascades of chemical reactions that constitute signal transduction systems. Molecular level clustering, spatial exclusion, and long range directed transport are all emerging as key regulatory mechanisms. The study of these processes is drawing researchers from physical sciences to join the effort and represents a rapidly growing branch of biophysical chemistry. Recent advances in the physical and quantitative analysis of signaling within the immune synapses will be reviewed here. PMID:22404679

  17. Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system

    PubMed Central

    Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O’Keeffe, Gerard; Gutierrez, Humberto

    2015-01-01

    During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune–related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS. PMID:26379506

  18. Surface forcing of the infrared cooling profile over the Tibetan Plateau. I - Influence of relative longwave radiative heating at high altitude. II - Cooling-rate variation over large-scale plateau domain during summer monsoon transition

    NASA Technical Reports Server (NTRS)

    Smith, Eric A.; Shi, Lei

    1992-01-01

    The role of the Tibetan Plateau on the behavior of the surface longwave radiation budget is investigated, and the behavior of the vertical profile of longwave cooling over the plateau, including its diurnal variation, is quantified. A medium spectral-resolution IR radiative transfer model utilizing a simple modification for applications in idealized complex (valley) terrain is developed for the investigation. An understanding of how surface and elevation biophysical factors, which are highly variable over the large-scale plateau domain, regulate the spatial distribution of clear-sky IR cooling during the transition phase of the summer monsoon, is described.

  19. Immune System Quiz

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A Text Size How much do you know about your immune system? Find out by taking this quiz! View Survey ...

  20. Immune Disorder HSCT Protocol

    ClinicalTrials.gov

    2016-01-09

    Immune Deficiency Disorders:; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorder:; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  1. The Immune System Game

    ERIC Educational Resources Information Center

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  2. Intestinal Parasite Profile in the Stool of HIV Positive Patients in relation to Immune Status and Comparison of Various Diagnostic Techniques with Special Reference to Cryptosporidium at a Tertiary Care Hospital in South India

    PubMed Central

    Moorkoth, Anitha Puduvail; Mathew, Sheela

    2016-01-01

    Acquired immunodeficiency syndrome and related opportunistic infections are a significant cause of morbidity and mortality in susceptible population. This study aims to negate the paucity of data regarding the relation between CD4 levels, prevalence of enteric parasites, and the outcome of treatment with HAART (highly active antiretroviral therapy) and Cotrimoxazole in Kerala, India. Multiple stool samples from 200 patients in a cross-sectional study were subjected to microscopy and Cryptosporidium stool antigen ELISA. Parasites were identified in 18 samples (9%). Cystoisospora and Cryptosporidium spp. were seen in 9 cases (4.5%) and 5 cases (2.5%), respectively. Microsporidium spores and Chilomastix mesnili cysts were identified in 1 case each (0.5% each). Seven cases of Cystoisospora diarrhoea recovered after treatment with Cotrimoxazole. Diarrhoea due to Cryptosporidium spp. in all 5 cases subsided after immune reconstitution with HAART. This study concludes that a positive association was seen between low CD4 count (<200 cells/μL) and overall parasite positivity (P value < 0.01). ELISA is a more sensitive modality for the diagnosis of Cryptosporidium diarrhoea. Chilomastix mesnili, generally considered a nonpathogen, may be a cause of diarrhoeal disease in AIDS. Immune reconstitution and Cotrimoxazole prophylaxis remain to be the best therapeutic approach in AIDS-related diarrhoea. PMID:27493988

  3. Immunity-related genes and gene families in Anopheles gambiae.

    PubMed

    Christophides, George K; Zdobnov, Evgeny; Barillas-Mury, Carolina; Birney, Ewan; Blandin, Stephanie; Blass, Claudia; Brey, Paul T; Collins, Frank H; Danielli, Alberto; Dimopoulos, George; Hetru, Charles; Hoa, Ngo T; Hoffmann, Jules A; Kanzok, Stefan M; Letunic, Ivica; Levashina, Elena A; Loukeris, Thanasis G; Lycett, Gareth; Meister, Stephan; Michel, Kristin; Moita, Luis F; Müller, Hans-Michael; Osta, Mike A; Paskewitz, Susan M; Reichhart, Jean-Marc; Rzhetsky, Andrey; Troxler, Laurent; Vernick, Kenneth D; Vlachou, Dina; Volz, Jennifer; von Mering, Christian; Xu, Jiannong; Zheng, Liangbiao; Bork, Peer; Kafatos, Fotis C

    2002-10-01

    We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire. PMID:12364793

  4. Improved immune response to recombinant influenza nucleoprotein formulated with ISCOMATRIX.

    PubMed

    Cargnelutti, Diego E; Sanchez, Maria V; Alvarez, Paula; Boado, Lorena; Glikmann, Graciela; Mattion, Nora; Scodeller, Eduardo A

    2012-03-01

    Current influenza vaccines elicit antibodies effective against homologous strains, but new strategies are urgently needed for protection against emerging epidemic or pandemic strains. Although influenza vaccine candidates based on the viral nucleoprotein (NP) or matrix protein do not elicit sterilizing immunity, they have the advantage of inducing immunity that may cover a larger number of viral strains. In this study, recombinant NP produced in Escherichia coli was purified and formulated in combination with the adjuvant ISCOMATRIX. This formulation increased a NP-specific immunity in mice, with a Th1 profile, and may constitute a promising low-cost influenza vaccine candidate, with ability to stimulate humoral and cellular immune responses.. PMID:22450799

  5. Chapter 2: Innate Immunity

    PubMed Central

    Turvey, Stuart E.; Broide, David H.

    2009-01-01

    Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

  6. Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation.

    PubMed

    Jones, Charles H; Chen, Mingfu; Ravikrishnan, Anitha; Reddinger, Ryan; Zhang, Guojian; Hakansson, Anders P; Pfeifer, Blaine A

    2015-01-01

    Given the rise of antibiotic resistance and other difficult-to-treat diseases, genetic vaccination is a promising preventative approach that can be tailored and scaled according to the vector chosen for gene delivery. However, most vectors currently utilized rely on ubiquitous delivery mechanisms that ineffectively target important immune effectors such as antigen presenting cells (APCs). As such, APC targeting allows the option for tuning the direction (humoral vs cell-mediated) and strength of the resulting immune responses. In this work, we present the development and assessment of a library of mannosylated poly(beta-amino esters) (PBAEs) that represent a new class of easily synthesized APC-targeting cationic polymers. Polymeric characterization and assessment methodologies were designed to provide a more realistic physiochemical profile prior to in vivo evaluation. Gene delivery assessment in vitro showed significant improvement upon PBAE mannosylation and suggested that mannose-mediated uptake and processing influence the magnitude of gene delivery. Furthermore, mannosylated PBAEs demonstrated a strong, efficient, and safe in vivo humoral immune response without use of adjuvants when compared to genetic and protein control antigens. In summary, the gene delivery effectiveness provided by mannosylated PBAE vectors offers specificity and potency in directing APC activation and subsequent immune responses. PMID:25453962

  7. Minimally Managed Composting of Beef Manure at the Pilot Scale: Effects of Manure Pile Construction on Pile Temperature Profiles and the Fate of Oxytetracycline and Chlorotetracycline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxytetracycline (OTC) and chlorotetracycline (CTC) are broad-spectrum antibiotics used in livestock production. Although laboratory-scale studies have shown that extractable levels of these compounds decrease over time within treated and untreated manures and soils, there is relatively little infor...

  8. WRFv3.2-SPAv2: development and validation of a coupled ecosystem-atmosphere model, scaling from surface fluxes of CO2 and energy to atmospheric profiles

    NASA Astrophysics Data System (ADS)

    Smallman, T. L.; Moncrieff, J. B.; Williams, M.

    2013-03-01

    The Weather Research & Forecasting meteorological (WRF) model has been coupled to the Soil Plant Atmosphere (SPA) terrestrial ecosystem model, to produce WRF-SPA. SPA generates realistic land-atmosphere exchanges through fully coupled hydrological, carbon and energy cycles. The addition of a land surface model (SPA) capable of modelling biospheric CO2 exchange allows WRF-SPA to be used for investigating the feedbacks between biosphere carbon balance, meteorology and land management/land use change. We have extensively validated WRF-SPA using multi-annual observations of air temperature, turbulent fluxes, net radiation and net ecosystem exchange of CO2 at three sites, representing the dominant vegetation types in Scotland (forest, managed grassland and arable agriculture). WRF-SPA generates more realistic seasonal behaviour at the site level compared to an unmodified version of WRF, and produces realistic CO2 exchanges. WRF-SPA is also able to realistically model atmospheric profiles of CO2 over Scotland, spanning a 3 yr period (2004-2006), capturing both profile structure, indicating realistic transport, and magnitude indicating appropriate source sink distribution and CO2 exchange. WRF-SPA makes use of CO2 tracer pools and can therefore identify and quantify land surface contributions to the modelled atmospheric CO2 signal at a specified location.

  9. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus) by qRT-PCR.

    PubMed

    Maher, Iona E; Griffith, Joanna E; Lau, Quintin; Reeves, Thomas; Higgins, Damien P

    2014-01-01

    Investigation of the immune response of the koala (Phascolarctos cinereus) is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV), which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala's susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1) and Th2 lymphocyte responses are important to an individual's susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala's adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNγ) along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A). Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not consistently up-regulated by

  10. Among-lake reciprocal transplants induce convergent expression of immune genes in threespine stickleback.

    PubMed

    Stutz, William E; Schmerer, Matthew; Coates, Jessica L; Bolnick, Daniel I

    2015-09-01

    Geographic variation in parasite communities can drive evolutionary divergence in host immune genes. However, biotic and abiotic environmental variation can also induce plastic differences in immune function among populations. At present, there is little information concerning the relative magnitudes of heritable vs. induced immune divergence in natural populations. We examined immune gene expression profiles of threespine stickleback (Gasterosteus aculeatus) from six lakes on Vancouver Island, British Columbia. Parasite community composition differs between lake types (large or small, containing limnetic- or benthic-like stickleback) and between watersheds. We observed corresponding differences in immune gene expression profiles among wild-caught stickleback, using a set of seven immune genes representing distinct branches of the immune system. To evaluate the role of environmental effects on this differentiation, we experimentally transplanted wild-caught fish into cages in their native lake, or into a nearby foreign lake. Transplanted individuals' immune gene expression converged on patterns typical of their destination lake, deviating from their native expression profile. Transplant individuals' source population had a much smaller effect, suggesting relatively weak genetic underpinning of population differences in immunity, as viewed through gene expression. This strong environmental regulation of immune gene expression provides a counterpoint to the large emerging literature documenting microevolution and genetic diversification of immune function. Our findings illustrate the value of studying immunity in natural environmental settings where the immune system has evolved and actively functions. PMID:26118468

  11. Early-Life Environmental Variation Affects Intestinal Microbiota and Immune Development in New-Born Piglets

    PubMed Central

    Zhang, Ling-li; Vastenhouw, Stéphanie A.; Heilig, Hans G. H. J.; Smidt, Hauke; Rebel, Johanna M. J.; Smits, Mari A.

    2014-01-01

    Background Early-life environmental variation affects gut microbial colonization and immune competence development; however, the timing and additional specifics of these processes are unknown. The impact of early-life environmental variations, as experienced under real life circumstances, on gut microbial colonization and immune development has not been studied extensively so far. We designed a study to investigate environmental variation, experienced early after birth, to gut microbial colonization and intestinal immune development. Methodology/Principal Findings To investigate effects of early-life environmental changes, the piglets of 16 piglet litters were divided into 3 groups per litter and experimentally treated on day 4 after birth. During the course of the experiment, the piglets were kept with their mother sow. Group 1 was not treated, group 2 was treated with an antibiotic, and group 3 was treated with an antibiotic and simultaneously exposed to several routine, but stressful management procedures, including docking, clipping and weighing. Thereafter, treatment effects were measured at day 8 after birth in 16 piglets per treatment group by community-scale analysis of gut microbiota and genome-wide intestinal transcriptome profiling. We observed that the applied antibiotic treatment affected the composition and diversity of gut microbiota and reduced the expression of a large number of immune-related processes. The effect of management procedures on top of the use of an antibiotic was limited. Conclusions/Significance We provide direct evidence that different early-life conditions, specifically focusing on antibiotic treatment and exposure to stress, affect gut microbial colonization and intestinal immune development. This reinforces the notion that the early phase of life is critical for intestinal immune development, also under regular production circumstances. PMID:24941112

  12. Sequential Immune Responses: The Weapons of Immunity

    PubMed Central

    Mills, Charles D.; Ley, Klaus; Buchmann, Kurt; Canton, Johnathan

    2016-01-01

    Sequential immune responses (SIR) is a new model that describes what ‘immunity’ means in higher animals. Existing models, such as self/nonself discrimination or danger, focus on how immune responses are initiated. However, initiation is not protection. SIR describes the actual immune responses that provide protection. SIR resulted from a comprehensive analysis of the evolution of immune systems that revealed that several very different types of host innate responses occur (and at different tempos) which together provide host protection. SIR1 uses rapidly activated enzymes like the NADPH oxidases and is present in all animal cells. SIR2 is mediated by the first ‘immune’ cells: macrophage-like cells. SIR3 evolved in animals like invertebrates and provides enhanced protection through advanced macrophage recognition and killing of pathogens and through other innate immune cells such as neutrophils. Finally, in vertebrates, macrophages developed SIR4: the ability to present antigens to T cells. Though much slower than SIR1–3, adaptive responses provide a unique new protection for higher vertebrates. Importantly, newer SIR responses were added on top of older, evolutionarily conserved functions to provide ‘layers’ of host protection. SIR transcends existing models by elucidating the different weapons of immunity that provide host protection in higher animals. PMID:25871013

  13. Retrieving the vertical distribution of chlorophyll a concentration and phytoplankton community composition from in situ fluorescence profiles: A method based on a neural network with potential for global-scale applications

    NASA Astrophysics Data System (ADS)

    Sauzède, R.; Claustre, H.; Jamet, C.; Uitz, J.; Ras, J.; Mignot, A.; D'Ortenzio, F.

    2015-01-01

    neural network-based method is developed to assess the vertical distribution of (1) chlorophyll a concentration ([Chl]) and (2) phytoplankton community size indices (i.e., microphytoplankton, nanophytoplankton, and picophytoplankton) from in situ vertical profiles of chlorophyll fluorescence. This method (FLAVOR for Fluorescence to Algal communities Vertical distribution in the Oceanic Realm) uses as input only the shape of the fluorescence profile associated with its acquisition date and geo-location. The neural network is trained and validated using a large database including 896 concomitant in situ vertical profiles of High-Performance Liquid Chromatography (HPLC) pigments and fluorescence. These profiles were collected during 22 oceanographic cruises representative of the global ocean in terms of trophic and oceanographic conditions, making our method applicable to most oceanic waters. FLAVOR is validated with respect to the retrieval of both [Chl] and phytoplankton size indices using an independent in situ data set and appears to be relatively robust spatially and temporally. To illustrate the potential of the method, we applied it to in situ measurements of the BATS (Bermuda Atlantic Time Series Study) site and produce monthly climatologies of [Chl] and associated phytoplankton size indices. The resulting climatologies appear very promising compared to climatologies based on available in situ HPLC data. With the increasing availability of spatially and temporally well-resolved data sets of chlorophyll fluorescence, one possible global-scale application of FLAVOR could be to develop 3-D and even 4-D climatologies of [Chl] and associated composition of phytoplankton communities. The Matlab and R codes of the proposed algorithm are provided as supporting information.

  14. Assessing barriers to immunization.

    PubMed

    Niederhauser, Victoria; Ferris, Catherine

    2016-05-01

    Parental barriers to childhood immunizations vary among countries, states and communities. There is a plethora of studies that exist to examine barriers to immunizations including many intervention studies designed to improve immunization rates in children. Often, intervention studies designed to minimize barriers and increase immunization uptake among children lack the inclusion of a standardized instrument to measure accurately parental barriers to childhood immunizations before and after interventions. The Searching for Hardships and Obstacles To Shots (SHOTS) survey is a standardized survey instrument to measure parental barriers to childhood immunizations. In several studies, the SHOTS survey has demonstrated consistent reliability and has been validated in diverse populations. The inclusion of the SHOTS survey instrument in studies to examine barriers to childhood immunization will provide researchers and clinicians with a better understanding of parents' individualized barriers to immunizations. Furthermore, use of the SHOTS survey instrument to collect information about parental barriers to immunizations can lead to targeted interventions to minimize these obstacles at the individual and community level and to help us to achieve our national, state and community childhood immunization goals. PMID:26810618

  15. P- and S-wave velocity model along crustal scale refraction and wide-angle reflection profile in the southern Korean peninsula

    NASA Astrophysics Data System (ADS)

    Cho, Hyun-Moo; Baag, Chang-Eob; Lee, Jung Mo; Moon, Wooil M.; Jung, Heeok; Kim, Ki Young

    2013-01-01

    The onshore seismic experiment, KCRT2004, explored the crustal velocity structure of the southern Korean peninsula. We present an interpretation of seismic data along this 340 km long NNW-SSE trending profile. The crust was found to consist of three layers: the upper, middle, and lower crust with P- and S-wave velocities ranging 5.50 to 6.95 km/s and 2.82 to 3.91 km/s, respectively. The average P-wave velocity (6.26 km/s) and Pn velocity (7.82-7.88 km/s) are lower than the worldwide average of continental crust. Moho depths are 29.0-34.9 km, gradually thickening toward south. The Vp/Vs ratio of crustal material is estimated to be 1.73 (σ = 0.249) for the upper and middle crust and the ratio increases with the depth in the lower crust. The Gyeonggi massif in the north of the profile has a lower Vp/Vs ratio than other tectonic units. The average crustal Vp/Vs ratio of 1.74 (σ = 0.253) is remarkably lower than the average value 1.78 (σ = 0.27) for the bulk continental crust. The low average crustal Vp/Vs ratio is similar to that measured in eastern China. The empirical analysis using both P-wave velocity and Vp/Vs ratio shows that the upper and middle crust is dominantly felsic and the lower crust is intermediate in composition. The absence of the mafic material in the lower crust that is also found in eastern China contrasts with the generally accepted global model of the mafic lower crust.

  16. WRFv3.2-SPAv2: development and validation of a coupled ecosystem-atmosphere model, scaling from surface fluxes of CO2 and energy to atmospheric profiles

    NASA Astrophysics Data System (ADS)

    Smallman, T. L.; Moncrieff, J. B.; Williams, M.

    2013-07-01

    The Weather Research and Forecasting meteorological (WRF) model has been coupled to the Soil-Plant-Atmosphere (SPA) terrestrial ecosystem model, to produce WRF-SPA. SPA generates realistic land-atmosphere exchanges through fully coupled hydrological, carbon and energy cycles. The addition of a~land surface model (SPA) capable of modelling biospheric CO2 exchange allows WRF-SPA to be used for investigating the feedbacks between biosphere carbon balance, meteorology, and land use and land cover change. We have extensively validated WRF-SPA using multi-annual observations of air temperature, turbulent fluxes, net radiation and net ecosystem exchange of CO2 at three sites, representing the dominant vegetation types in Scotland (forest, managed grassland and arable agriculture). For example air temperature is well simulated across all sites (forest R2 = 0.92, RMSE = 1.7 °C, bias = 0.88 °C; managed grassland R2 = 0.73, RMSE = 2.7 °C, bias = -0.30 °C; arable agriculture R2 = 0.82, RMSE = 2.2 °C, bias = 0.46 °C; RMSE, root mean square error). WRF-SPA generates more realistic seasonal behaviour at the site level compared to an unmodified version of WRF, such as improved simulation of seasonal transitions in latent heat flux in arable systems. WRF-SPA also generates realistic seasonal CO2 exchanges across all sites. WRF-SPA is also able to realistically model atmospheric profiles of CO2 over Scotland, spanning a 3 yr period (2004-2006), capturing both profile structure, indicating realistic transport, and magnitude (model-data residual <±4 ppm) indicating appropriate source sink distribution and CO2 exchange. WRF-SPA makes use of CO2 tracer pools and can therefore identify and quantify land surface contributions to the modelled atmospheric CO2 signal at a specified location.

  17. Origins of adaptive immunity.

    PubMed

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity. PMID:21395512

  18. Neural circuitry and immunity.

    PubMed

    Pavlov, Valentin A; Tracey, Kevin J

    2015-12-01

    Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuro-immune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex, are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases define the emerging field of Bioelectronic Medicine. PMID:26512000

  19. Breakthrough of two pesticides into tile drain and shallow groundwater: comparison of tile drain reaction and soil profiles within a field scale irrigation experiment

    NASA Astrophysics Data System (ADS)

    Klaus, Julian; Zehe, Erwin; Elsner, Martin; Palm, Juliane; Schneider, Dorothee; Schröder, Boris; Steinbeiss, Sibylle; West, Stephanie

    2010-05-01

    Preferential flow in macropores is a key process which strongly affects infiltration and may cause rapid transport of pesticides into depths of 80 to 150 cm. At these depths they experience a much slower degradation, may leach into shallow groundwater or enter a tile-drain and are transported into surface water bodies. Therefore, preferential transport might be an environmental problem, if the topsoil is bypassed, which has been originally thought to act as a filter to protect the subsoil and shallow groundwater. To investigate the behaviour of two pesticides with different chemical characteristics and to compare their transport behaviour in soil and into the tile drain an irrigation experiment was performed on a 400 m² field site. The experimental plot is located in the Weiherbach valley, south-west Germany, which basic geology consists of Loess and Keuper layers, the soil at the test site is a gleyic Colluvisol. The distance of the irrigation site to the Weiherbach brook is approximately 12 m, the field is drained with a tile-drain in about 1.2 m depth and shows discharge over the entire year. Three hours before the irrigation started, the farmer applied a pesticide solution consisting of Isoproturon (80 g) and Flufenacet (20 g) (IPU and FLU) according to conventional agricultural practice on the field plot. The irrigation took place in three time blocks (80 min, 60 min, 80 min) with in total 33.6 mm of precipitation. During the first block 1600 g of Bromide were mixed in the irrigation water. The drainage outlet was instrumented with a pressure probe. About 50 water samples ware taken during the experimental day, and several samples more the days after the experiment. They were analysed for the pesticides, bromide and water isotopes. In the two days after the experiment three soil profiles were excavated and soil samples were taken on a 10x10 cm² scheme. One week after the experiment two additional profiles were excavated. The soil was analysed for IPU, FLU

  20. Comparison of the pathogen species-specific immune response in udder derived cell types and their models.

    PubMed

    Günther, Juliane; Koy, Mirja; Berthold, Anne; Schuberth, Hans-Joachim; Seyfert, Hans-Martin

    2016-01-01

    The outcome of an udder infection (mastitis) largely depends on the species of the invading pathogen. Gram-negative pathogens, such as Escherichia coli often elicit acute clinical mastitis while Gram-positive pathogens, such as Staphylococcus aureus tend to cause milder subclinical inflammations. It is unclear which type of the immune competent cells residing in the udder governs the pathogen species-specific physiology of mastitis and which established cell lines might provide suitable models. We therefore profiled the pathogen species-specific immune response of different cell types derived from udder and blood. Primary cultures of bovine mammary epithelial cells (pbMEC), mammary derived fibroblasts (pbMFC), and bovine monocyte-derived macrophages (boMdM) were challenged with heat-killed E. coli, S. aureus and S. uberis mastitis pathogens and their immune response was scaled against the response of established models for MEC (bovine MAC-T) and macrophages (murine RAW 264.7). Only E. coli provoked a full scale immune reaction in pbMEC, fibroblasts and MAC-T cells, as indicated by induced cytokine and chemokine expression and NF-κB activation. Weak reactions were induced by S. aureus and none by S. uberis challenges. In contrast, both models for macrophages (boMdM and RAW 264.7) reacted strongly against all the three pathogens accompanied by strong activation of NF-κB factors. Hence, the established cell models MAC-T and RAW 264.7 properly reflected key aspects of the pathogen species-specific immune response of the respective parental cell type. Our data imply that the pathogen species-specific physiology of mastitis likely relates to the respective response of MEC rather to that of professional immune cells. PMID:26830914

  1. Lipid antigens in immunity

    PubMed Central

    Dowds, C. Marie; Kornell, Sabin-Christin

    2014-01-01

    Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity. PMID:23999493

  2. Triacylglycerol Analysis in Human Milk and Other Mammalian Species: Small-Scale Sample Preparation, Characterization, and Statistical Classification Using HPLC-ELSD Profiles.

    PubMed

    Ten-Doménech, Isabel; Beltrán-Iturat, Eduardo; Herrero-Martínez, José Manuel; Sancho-Llopis, Juan Vicente; Simó-Alfonso, Ernesto Francisco

    2015-06-24

    In this work, a method for the separation of triacylglycerols (TAGs) present in human milk and from other mammalian species by reversed-phase high-performance liquid chromatography using a core-shell particle packed column with UV and evaporative light-scattering detectors is described. Under optimal conditions, a mobile phase containing acetonitrile/n-pentanol at 10 °C gave an excellent resolution among more than 50 TAG peaks. A small-scale method for fat extraction in these milks (particularly of interest for human milk samples) using minimal amounts of sample and reagents was also developed. The proposed extraction protocol and the traditional method were compared, giving similar results, with respect to the total fat and relative TAG contents. Finally, a statistical study based on linear discriminant analysis on the TAG composition of different types of milks (human, cow, sheep, and goat) was carried out to differentiate the samples according to their mammalian origin. PMID:26028153

  3. The scope for using the volatile profiles of Pinus caribaea var. bahamensis as indicators of susceptibility to pine tortoise scale and as predictors of environmental stresses.

    PubMed

    Green, Paul W C; Hamilton, Martin A; Sanchez, Michele D; Corcoran, Marcella R; Manco, Bryan N; Malumphy, Chris P

    2015-04-01

    Climate change, unseasonal fire and urbanization are contributing to the decline of Pinus caribaea var. bahamensis populations in the Turks and Caicos Islands (TCI). Infestation of pines with the invasive pine tortoise scale (PTS, Toumeyella parvicornis) is accelerating this decline. Pine trees in the Bahamas are larger and healthier and are not infested with PTS although they are subject to some of the same environmental pressures as the trees in TCI. Volatile compounds were collected from wild and nursery-reared P. caribaea var. bahamensis from TCI and the Bahamas and characterized using GC/MS analysis, to look for differences between the compounds detected in insect-infested pines of TCI and the healthy pines of the Bahamas. Ten compounds contributing at least 1% of the total detected peak areas in any one of the samples were selected for further study. Eight of these compounds were identified using authentic standards and mass spectral libraries. The main constituents in the samples were α- and β-pinene as well as β-phellandrene, and, together with β-myrcene, their contents varied the most between samples collected at different locations. Principal-component analysis showed that the two structural isomers of pinene, together with β-myrcene and β-phellandrene, contributed 98.4% of the variance between samples. There was a positive relationship between the concentrations of the two structural isomers of pinene and between levels of β-myrcene and β-phellandrene. The results are discussed in relation to the biology and adaptations of invasive scale insects, the importance of monoterpenes in pine as a defense against insect predation, whether these compounds can be used as indicators of tree health, and future directions for research into conserving the Caicos pine. PMID:25879508

  4. Comparing global-scale topographic and climatic metrics to long-term erosion rates using ArcSwath, an efficient new ArcGIS tool for swath profile analysis

    NASA Astrophysics Data System (ADS)

    Blomqvist, Niclas; Whipp, David

    2016-04-01

    The topography of the Earth's surface is the result of the interaction of tectonics, erosion and climate. Thus, topography should contain a record of these processes that can be extracted by topographic analysis. The question considered in this study is whether the spatial variations in erosion that have sculpted the modern topography are representative of the long-term erosion rates in mountainous regions. We compare long-term erosion rates derived from low-temperature thermochronometry to erosional proxies calculated from topographic and climatic data analysis. The study has been performed on a global scale including six orogens: The Himalaya, Andes, Taiwan, Olympic Mountains, Southern Alps in New Zealand and European Alps. The data was analyzed using a new swath profile analysis tool for ArcGIS called ArcSwath (https://github.com/HUGG/ArcSwath) to determine the correlations between the long-term erosion rates and modern elevations, slope angles, relief in 2.5-km- and 5-km-diameter circles, erosion potential, normalized channel steepness index ksn, and annual rainfall. ArcSwath uses a Python script that has been incorporated into an ArcMap 10.2 add-in tool, extracting swath profiles in about ten seconds compared to earlier workflows that could take more than an hour. In ArcMap, UTM-projected point or raster files can be used for creating swath profiles. Point data are projected onto the swath and the statistical parameters (minimum, mean and maximum of the values across the swath) are calculated for the raster data. Both can be immediately plotted using the Python matplotlib library, or plotted externally using the csv-file that is produced by ArcSwath. When raster and point data are plotted together, it is easier to make comparisons and see correlations between the selected data. An unambiguous correlation between the topographic or climatic metrics and long-term erosion rates was not found. Fitting of linear regression lines to the topographic/ climatic metric

  5. Variations in the depth distribution of phosphorus in soil profiles and implications for model-based catchment-scale predictions of phosphorus delivery to surface waters

    NASA Astrophysics Data System (ADS)

    Owens, P. N.; Deeks, L. K.; Wood, G. A.; Betson, M. J.; Lord, E. I.; Davison, P. S.

    2008-02-01

    SummaryThe PSYCHIC process-based model for predicting sediment and phosphorus (P) transfer within catchments uses spatial data on soil-P derived from the National Soil Inventory (NSI) data set. These soil-P values are based on bulked 0-15 cm depth and do not account for variations in soil-P with depth. We describe the depth distribution of soil-P (total and Olsen) in grassland and arable soils for the dominant soil types in the two PSYCHIC study catchments: the Avon and the Wye, UK. There were clear variations in soil-P (particularly Olsen-P) concentrations with depth in untilled grassland soils while concentrations of total-P were broadly constant within the plough layer of arable soils. Concentrations of Olsen-P in arable soils, however, exhibited maximum values near the soil surface reflecting surface applications of fertilisers and manures between consecutive ploughing events. When the soil-P concentrations for the surface soil (0-5 cm average) were compared to both the profile-averaged (0-15 cm) and the NSI (0-15 cm) values, those for the surface soil were considerably greater than those for the average 0-15 cm depth. Modelled estimates of P loss using the depth-weighted average soil-P concentrations for the 0-5 cm depth layer were up to 14% greater than those based on the NSI data set due to the preferential accumulation of P at the soil surface. These findings have important implications for the use of soil-P data (and other data) in models to predict P losses from land to water and the interpretation of these predictions for river basin management.

  6. Differential protein network analysis of the immune cell lineage.

    PubMed

    Clancy, Trevor; Hovig, Eivind

    2014-01-01

    Recently, the Immunological Genome Project (ImmGen) completed the first phase of the goal to understand the molecular circuitry underlying the immune cell lineage in mice. That milestone resulted in the creation of the most comprehensive collection of gene expression profiles in the immune cell lineage in any model organism of human disease. There is now a requisite to examine this resource using bioinformatics integration with other molecular information, with the aim of gaining deeper insights into the underlying processes that characterize this immune cell lineage. We present here a bioinformatics approach to study differential protein interaction mechanisms across the entire immune cell lineage, achieved using affinity propagation applied to a protein interaction network similarity matrix. We demonstrate that the integration of protein interaction networks with the most comprehensive database of gene expression profiles of the immune cells can be used to generate hypotheses into the underlying mechanisms governing the differentiation and the differential functional activity across the immune cell lineage. This approach may not only serve as a hypothesis engine to derive understanding of differentiation and mechanisms across the immune cell lineage, but also help identify possible immune lineage specific and common lineage mechanism in the cells protein networks. PMID:25309909

  7. Immune interventions in stroke

    PubMed Central

    Fu, Ying; Liu, Qiang; Anrather, Josef

    2016-01-01

    Inflammatory and immune responses in the brain can shape the clinical presentation and outcome of stroke. Approaches for effective management of acute stroke are sparse and many measures for brain protection fail, but our ability to modulate the immune system and modify the disease progression of multiple sclerosis is increasing. As a result, immune interventions are currently being explored as therapeutic interventions in acute stroke. In this Review, we compare the immunological features of acute stroke with those of multiple sclerosis, identify unique immunological features of stroke, and consider the evidence for immune interventions. In acute stroke, microglia activation and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the ischaemia or haemorrhage. Immune interventions that restrict brain inflammation, vascular permeability and tissue oedema must be administered rapidly to reduce acute immune-mediated destruction and to avoid subsequent immunosuppression. Preliminary results suggest that the use of drugs that modify disease in multiple sclerosis might accomplish these goals in ischaemic and haemorrhagic stroke. Further elucidation of the immune mechanisms involved in stroke is likely to lead to successful immune interventions. PMID:26303850

  8. Immunizations. Position Statement. Revised

    ERIC Educational Resources Information Center

    Bobo, Nichole; Garrett, Jennifer; Teskey, Carmen; Duncan, Kay; Strasser, Kathy; Burrows-Mezu, Alicia L.

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that immunizations are essential to primary prevention of disease from infancy through adulthood. Promotion of immunizations by the registered professional school nurse (hereinafter referred to as school nurse) is central to the public health focus of school nursing practice…

  9. Chemoimmunotherapy: reengineering tumor immunity

    PubMed Central

    Chen, Gang

    2013-01-01

    Cancer chemotherapy drugs have long been considered immune suppressive. However, more recent data indicate that some cytotoxic drugs effectively treat cancer in part by facilitating an immune response to the tumor when given at the standard dose and schedule. These drugs induce a form of tumor cell death that is immunologically active, thereby inducing an adaptive immune response specific for the tumor. In addition, cancer chemotherapy drugs can promote tumor immunity through ancillary and largely unappreciated immunologic effects on both the malignant and normal host cells present within the tumor microenvironment. These more subtle immunomodulatory effects are dependent on the drug itself, its dose, and its schedule in relation to an immune-based intervention. The recent approvals of two new immune-based therapies for prostate cancer and melanoma herald a new era in cancer treatment and have led to heightened interest in immunotherapy as a valid approach to cancer treatment. A detailed understanding of the cellular and molecular basis of interactions between chemotherapy drugs and the immune system is essential for devising the optimal strategy for integrating new immune-based therapies into the standard of care for various cancers, resulting in the greatest long-term clinical benefit for cancer patients. PMID:23389507

  10. Innate immunity and adjuvants.

    PubMed

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  11. Immunization alters body odor.

    PubMed

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. PMID:24524972

  12. Swine immune system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Probably no area of veterinary medicine has seen a greater explosion in knowledge then the immune system and its implications in disease and vaccination. In this chapter on the Swine Immune System for the 10th Edition of Diseases of Swine we expand on the information provided in past editions by in...

  13. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  14. The Genetics of Immunity

    PubMed Central

    Lazzaro, Brian P.; Schneider, David S.

    2014-01-01

    In this commentary, Brian P. Lazzaro and David S. Schneider examine the topic of the Genetics of Immunity as explored in this month's issues of GENETICS and G3: Genes|Genomes|Genetics. These inaugural articles are part of a joint Genetics of Immunity collection (ongoing) in the GSA journals. PMID:24939182

  15. Immunity and Nutrition.

    ERIC Educational Resources Information Center

    Dupin, Henri; Guerin, Nicole

    1990-01-01

    The three articles in this issue of a periodical focussed on various aspects of the life and health of children in the tropics concern: (1) immune defenses; (2) interactions between nutrition disorders and infection; and (3) immunity and vaccination. The science of immunology has progressed rapidly in recent years. A brief review of present…

  16. Immune Cells and Inflammation in Diabetic Nephropathy

    PubMed Central

    Zheng, Zihan; Zheng, Feng

    2016-01-01

    Diabetic nephropathy (DN) is a serious complication of diabetes. At its core, DN is a metabolic disorder which can also manifest itself in terms of local inflammation in the kidneys. Such inflammation can then drive the classical markers of fibrosis and structural remodeling. As a result, resolution of immune-mediated inflammation is critical towards achieving a cure for DN. Many immune cells play a part in DN, including key members of both the innate and adaptive immune systems. While these cells were classically understood to primarily function against pathogen insult, it has also become increasingly clear that they also serve a major role as internal sensors of damage. In fact, damage sensing may serve as the impetus for much of the inflammation that occurs in DN, in a vicious positive feedback cycle. Although direct targeting of these proinflammatory cells may be difficult, new approaches that focus on their metabolic profiles may be able to alleviate DN significantly, especially since dysregulation of the local metabolic environment may well be responsible for triggering inflammation to begin with. In this review, the authors consider the metabolic profile of several relevant immune types and discuss their respective roles. PMID:26824038

  17. Large-scale variability of wind erosion mass flux rates at Owens Lake 1. Vertical profiles of horizontal mass fluxes of wind-eroded particles with diameter greater than 50 μm

    USGS Publications Warehouse

    Gillette, Dale A.; Fryrear, D.W.; Xiao, Jing Bing; Stockton, Paul; Ono, Duane; Helm, Paula J.; Gill, Thomas E; Ley, Trevor

    1997-01-01

    A field experiment at Owens (dry) Lake, California, tested whether and how the relative profiles of airborne horizontal mass fluxes for >50-μm wind-eroded particles changed with friction velocity. The horizontal mass flux at almost all measured heights increased proportionally to the cube of friction velocity above an apparent threshold friction velocity for all sediment tested and increased with height except at one coarse-sand site where the relative horizontal mass flux profile did not change with friction velocity. Size distributions for long-time-averaged horizontal mass flux samples showed a saltation layer from the surface to a height between 30 and 50 cm, above which suspended particles dominate. Measurements from a large dust source area on a line parallel to the wind showed that even though the saltation flux reached equilibrium ∼650 m downwind of the starting point of erosion, weakly suspended particles were still input into the atmosphere 1567 m downwind of the starting point; thus the saltating fraction of the total mass flux decreased after 650 m. The scale length difference and ratio of 70/30 suspended mass flux to saltation mass flux at the farthest down wind sampling site confirm that suspended particles are very important for mass budgets in large source areas and that saltation mass flux can be a variable fraction of total horizontal mass flux for soils with a substantial