Science.gov

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 Central

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

    2016-01-01

    ABSTRACT 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. Large Scale Immune Profiling of Infected Humans and Goats Reveals Differential Recognition of Brucella melitensis Antigens

    PubMed Central

    Liang, Li; Leng, Diana; Burk, Chad; Nakajima-Sasaki, Rie; Kayala, Matthew A.; Atluri, Vidya L.; Pablo, Jozelyn; Unal, Berkay; Ficht, Thomas A.; Gotuzzo, Eduardo; Saito, Mayuko; Morrow, W. John W.; Liang, Xiaowu; Baldi, Pierre; Gilman, Robert H.; Vinetz, Joseph M.; Tsolis, Renée M.; Felgner, Philip L.

    2010-01-01

    Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host. PMID:20454614

  4. Large scale immune profiling of infected humans and goats reveals differential recognition of Brucella melitensis antigens.

    PubMed

    Liang, Li; Leng, Diana; Burk, Chad; Nakajima-Sasaki, Rie; Kayala, Matthew A; Atluri, Vidya L; Pablo, Jozelyn; Unal, Berkay; Ficht, Thomas A; Gotuzzo, Eduardo; Saito, Mayuko; Morrow, W John W; Liang, Xiaowu; Baldi, Pierre; Gilman, Robert H; Vinetz, Joseph M; Tsolis, Renée M; Felgner, Philip L

    2010-05-04

    Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host.

  5. Profile Analysis: Multidimensional Scaling Approach.

    ERIC Educational Resources Information Center

    Ding, Cody S.

    2001-01-01

    Outlines an exploratory multidimensional scaling-based approach to profile analysis called Profile Analysis via Multidimensional Scaling (PAMS) (M. Davison, 1994). The PAMS model has the advantages of being applied to samples of any size easily, classifying persons on a continuum, and using person profile index for further hypothesis studies, but…

  6. Vineland Social Maturity Scale Profile.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    The Vineland Social Maturity Scale (VSMS), despite its limitations, is an excellent clinical technique and includes psychometric and questionnaire characteristics. It is a good single measure of adaptive behavior. The VSMS Profile in this paper uses content categories different from the original Scale, but based upon the same items. It lends…

  7. Immunity profile in breast cancer patients.

    PubMed

    Hrubisko, M; Sanislo, L; Zuzulova, M; Michalickova, J; Zeleznikova, T; Sedlak, J; Bella, V

    2010-01-01

    Despite the multifactorial pathogenesis of malignant transformation, it is assumed that deficiency in some immune mechanisms plays a considerable role in its development. Chronically activated immune cells exert tumour-promoting effects directly by influencing the proliferation and survival of neoplastic cells, as well as by indirect modulation of neoplastic microenvironments in favour of tumour progression. We refer to results of two separate investigations that aim to monitor the immune functions in patients with breast cancer. In the first investigation, we compare the picture of basic cellular immunity profile of patients in early stage of breast cancer with those suffering from advanced disease; in the second one, we compare the production of Th1-cytokines in patients in different stages of breast cancer and atopic healthy controls. We recognized that the totals of T-lymphocytes and T-helpers were lower and the expression of HLADR on T-lymphocytes were higher in patients with advanced disease; the expression of IL-2 and LFN-gamma by T-lymphocytes was decreased in metastatic breast cancer patients, however IL-2 production was increased in patients in early stage of disease. We conclude that the role of immune system in cancer development is ambivalent as it may be not only protective, but also harmful (Tab. 1, Fig. 3, Ref. 22). Full Text (Free, PDF) www.bmj.sk.

  8. Immune profiling and cancer post transplantation

    PubMed Central

    Hope, Christopher Martin; Coates, Patrick Toby H; Carroll, Robert Peter

    2015-01-01

    Half of all long-term (> 10 year) australian kidney transplant recipients (KTR) will develop squamous cell carcinoma (SCC) or solid organ cancer (SOC), making cancer the leading cause of death with a functioning graft. At least 30% of KTR with a history of SCC or SOC will develop a subsequent SCC or SOC lesion. Pharmacological immunosuppression is a major contributor of the increased risk of cancer for KTR, with the cancer lesions themselves further adding to systemic immunosuppression and could explain, in part, these phenomena. Immune profiling includes; measuring immunosuppressive drug levels and pharmacokinetics, enumerating leucocytes and leucocyte subsets as well as testing leucocyte function in either an antigen specific or non-specific manner. Outputs can vary from assay to assay according to methods used. In this review we define the rationale behind post-transplant immune monitoring assays and focus on assays that associate and/or have the ability to predict cancer and rejection in the KTR. We find that immune monitoring can identify those KTR of developing multiple SCC lesions and provide evidence they may benefit from pharmacological immunosuppressive drug dose reductions. In these KTR risk of rejection needs to be assessed to determine if reduction of immunosuppression will not harm the graft. PMID:25664246

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

    PubMed

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

    2004-10-01

    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 Multidimensional Scaling (PAMS; Davison, 1996), is introduced to meet the challenge. PAMS extends the use of simple multidimensional scaling methods to identify latent profiles in a multi-test battery. Application of PAMS to profile analysis is described. The PAMS model is then used to identify latent profiles from a subgroup (N = 357) within the sample of the Woodcock-Johnson Psychoeducational Battery-Revised (WJ-R; McGrew, Werder, & Woodcock, 1991; Woodcock & Johnson, 1989), followed by a discussion of procedures for interpreting participants' observed score profiles from the latent PAMS profiles. Finally, advantages and limitations of the PAMS technique are discussed.

  10. Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling

    DTIC Science & Technology

    2013-10-01

    Patients By Genetic And Immune Profiling PRINCIPAL INVESTIGATOR: Dr. Jose Montoya ...W81XWH-12-1-0388 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Dr. Jose Montoya , Ian Valencia, Holden Maecker, Michael Mindrinos

  11. Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-12-1-0388 TITLE: Subgrouping Chronic Fatigue Syndrome Patients by Genetic and Immune Profiling...2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Subgrouping Chronic Fatigue Syndrome Patients By Genetic And Immune Profiling 5b. GRANT...at the HLA level that makes you more susceptible to have Chronic Fatigue Syndrome (CFS) or any differences between the cases and controls. In order

  12. The immune profile of contact allergy patients.

    PubMed

    Janecková, V; Znojemská, S; Korcáková, L; Wagnerová, M; Kalenský, J; Svobodová, J

    1989-01-01

    Nonspecific parameters of antibody-related and cellular immune responses were studied in a group of 30 patients treated for manifest contact allergy to metals (chromium, cobalt, nickel) or non-metals (epoxy resin, rubber) confirmed in each of them by specific patch test positivity. In addition, every patient was tested for the pattern of skin reactivity to the Immunoskintest (USOL, Prague) antigens administered intradermally. The group of 20 metal allergy patients had decreased suppressor index values, enhanced formation of immediate active rosettes and an elevation of serum IgM and IgA immunoglobulins. The remaining 10 patients reacted by a reduced ability of neutrophils to exert phagocytic action on HEMA particles and a decrease in levels of alpha-2-macroglobulins in serum. This may help select a series of suitable immune parameters to be used as prediction tests in the secondary prevention of cases of occupational contact dermatitis.

  13. 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

  14. 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

  15. 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.

  16. 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…

  17. 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…

  18. Confirmatory Factor Analysis and Profile Analysis via Multidimensional Scaling

    ERIC Educational Resources Information Center

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

    2007-01-01

    This paper describes the Confirmatory Factor Analysis (CFA) parameterization of the Profile Analysis via Multidimensional Scaling (PAMS) model to demonstrate validation of profile pattern hypotheses derived from multidimensional scaling (MDS). Profile Analysis via Multidimensional Scaling (PAMS) is an exploratory method for identifying major…

  19. Confirmatory Factor Analysis and Profile Analysis via Multidimensional Scaling

    ERIC Educational Resources Information Center

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

    2007-01-01

    This paper describes the Confirmatory Factor Analysis (CFA) parameterization of the Profile Analysis via Multidimensional Scaling (PAMS) model to demonstrate validation of profile pattern hypotheses derived from multidimensional scaling (MDS). Profile Analysis via Multidimensional Scaling (PAMS) is an exploratory method for identifying major…

  20. Using Profile Analysis via Multidimensional Scaling (PAMS) to Identify Core Profiles from the WMS-III

    ERIC Educational Resources Information Center

    Frisby, Craig L.; Kim, Se-Kang

    2008-01-01

    Profile Analysis via Multidimensional Scaling (PAMS) is a procedure for extracting latent core profiles in a multitest data set. The PAMS procedure offers several advantages compared with other profile analysis procedures. Most notably, PAMS estimates individual profile weights that reflect the degree to which an individual's observed profile…

  1. Using Profile Analysis via Multidimensional Scaling (PAMS) to Identify Core Profiles from the WMS-III

    ERIC Educational Resources Information Center

    Frisby, Craig L.; Kim, Se-Kang

    2008-01-01

    Profile Analysis via Multidimensional Scaling (PAMS) is a procedure for extracting latent core profiles in a multitest data set. The PAMS procedure offers several advantages compared with other profile analysis procedures. Most notably, PAMS estimates individual profile weights that reflect the degree to which an individual's observed profile…

  2. Host Immunity via Mutable Virtualized Large-Scale Network Containers

    DTIC Science & Technology

    2016-07-25

    migrate to different IP addresses multiple 6mes. We implement a virtual machine based system prototype and evaluate it using state-of-the-a1t scanning...entire !Pv4 address space within 5 Host Immunity via Mutable Virtualized Large-Scale Network Containers 45 minutes from a single machine . Second, when...that the attacker will be trapped into one decoy instead of the real server. We implement a virtual machine (VM)-based prototype that integrates

  3. Pangolin genomes and the evolution of mammalian scales and immunity

    PubMed Central

    Rayko, Mike; Tan, Tze King; Hari, Ranjeev; Komissarov, Aleksey; Wee, Wei Yee; Yurchenko, Andrey A.; Kliver, Sergey; Tamazian, Gaik; Antunes, Agostinho; Wilson, Richard K.; Warren, Wesley C.; Koepfli, Klaus-Peter; Minx, Patrick; Krasheninnikova, Ksenia; Kotze, Antoinette; Dalton, Desire L.; Vermaak, Elaine; Paterson, Ian C.; Dobrynin, Pavel; Sitam, Frankie Thomas; Rovie-Ryan, Jeffrine J.; Johnson, Warren E.; Yusoff, Aini Mohamed; Luo, Shu-Jin; Karuppannan, Kayal Vizi; Fang, Gang; Zheng, Deyou; Gerstein, Mark B.; Lipovich, Leonard; O'Brien, Stephen J.; Wong, Guat Jah

    2016-01-01

    Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology and evolution, we developed genome assemblies of the Malayan (Manis javanica) and Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon (IFNE), exclusively expressed in epithelial cells and important in skin and mucosal immunity, is pseudogenized in all African and Asian pangolin species that we examined, perhaps impacting resistance to infection. We propose that scale development was an innovation that provided protection against injuries or stress and reduced pangolin vulnerability to infection. Further evidence of specialized adaptations was evident from positively selected genes involving immunity-related pathways, inflammation, energy storage and metabolism, muscular and nervous systems, and scale/hair development. Olfactory receptor gene families are significantly expanded in pangolins, reflecting their well-developed olfaction system. This study provides insights into mammalian adaptation and functional diversification, new research tools and questions, and perhaps a new natural IFNE-deficient animal model for studying mammalian immunity. PMID:27510566

  4. Pangolin genomes and the evolution of mammalian scales and immunity.

    PubMed

    Choo, Siew Woh; Rayko, Mike; Tan, Tze King; Hari, Ranjeev; Komissarov, Aleksey; Wee, Wei Yee; Yurchenko, Andrey A; Kliver, Sergey; Tamazian, Gaik; Antunes, Agostinho; Wilson, Richard K; Warren, Wesley C; Koepfli, Klaus-Peter; Minx, Patrick; Krasheninnikova, Ksenia; Kotze, Antoinette; Dalton, Desire L; Vermaak, Elaine; Paterson, Ian C; Dobrynin, Pavel; Sitam, Frankie Thomas; Rovie-Ryan, Jeffrine J; Johnson, Warren E; Yusoff, Aini Mohamed; Luo, Shu-Jin; Karuppannan, Kayal Vizi; Fang, Gang; Zheng, Deyou; Gerstein, Mark B; Lipovich, Leonard; O'Brien, Stephen J; Wong, Guat Jah

    2016-10-01

    Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology and evolution, we developed genome assemblies of the Malayan (Manis javanica) and Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon (IFNE), exclusively expressed in epithelial cells and important in skin and mucosal immunity, is pseudogenized in all African and Asian pangolin species that we examined, perhaps impacting resistance to infection. We propose that scale development was an innovation that provided protection against injuries or stress and reduced pangolin vulnerability to infection. Further evidence of specialized adaptations was evident from positively selected genes involving immunity-related pathways, inflammation, energy storage and metabolism, muscular and nervous systems, and scale/hair development. Olfactory receptor gene families are significantly expanded in pangolins, reflecting their well-developed olfaction system. This study provides insights into mammalian adaptation and functional diversification, new research tools and questions, and perhaps a new natural IFNE-deficient animal model for studying mammalian immunity.

  5. Molecular Profiling of Phagocytic Immune Cells in Anopheles gambiae Reveals Integral Roles for Hemocytes in Mosquito Innate Immunity.

    PubMed

    Smith, Ryan C; King, Jonas G; Tao, Dingyin; Zeleznik, Oana A; Brando, Clara; Thallinger, Gerhard G; Dinglasan, Rhoel R

    2016-11-01

    The innate immune response is highly conserved across all eukaryotes and has been studied in great detail in several model organisms. Hemocytes, the primary immune cell population in mosquitoes, are important components of the mosquito innate immune response, yet critical aspects of their biology have remained uncharacterized. Using a novel method of enrichment, we isolated phagocytic granulocytes and quantified their proteomes by mass spectrometry. The data demonstrate that phagocytosis, blood-feeding, and Plasmodium falciparum infection promote dramatic shifts in the proteomic profiles of An. gambiae granulocyte populations. Of interest, large numbers of immune proteins were induced in response to blood feeding alone, suggesting that granulocytes have an integral role in priming the mosquito immune system for pathogen challenge. In addition, we identify several granulocyte proteins with putative roles as membrane receptors, cell signaling, or immune components that when silenced, have either positive or negative effects on malaria parasite survival. Integrating existing hemocyte transcriptional profiles, we also compare differences in hemocyte transcript and protein expression to provide new insight into hemocyte gene regulation and discuss the potential that post-transcriptional regulation may be an important component of hemocyte gene expression. These data represent a significant advancement in mosquito hemocyte biology, providing the first comprehensive proteomic profiling of mosquito phagocytic granulocytes during homeostasis blood-feeding, and pathogen challenge. Together, these findings extend current knowledge to further illustrate the importance of hemocytes in shaping mosquito innate immunity and their principal role in defining malaria parasite survival in the mosquito host.

  6. The ocular conjunctiva as a mucosal immunization route: a profile of the immune response to the model antigen tetanus toxoid.

    PubMed

    Barisani-Asenbauer, Talin; Inic-Kanada, Aleksandra; Belij, Sandra; Marinkovic, Emilija; Stojicevic, Ivana; Montanaro, Jacqueline; Stein, Elisabeth; Bintner, Nora; Stojanovic, Marijana

    2013-01-01

    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. 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. 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). 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.

  7. 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

  8. Cross Validated Temperament Scale Validities Computed Using Profile Similarity Metrics

    DTIC Science & Technology

    2017-04-27

    1 Cross Validated Temperament Scale Validities Computed Using Profile Similarity Metrics Peter Legree, Robert N. Kilcullen and...TYPE Final 3. DATES COVERED (From - To) April 2016 – May 2017 4. TITLE AND SUBTITLE Temperament Scale Validities Computed Using...14. ABSTRACT Personality and temperament scales are used in employment settings to predict performance because they are valid and have

  9. Picornavirus-Induced Airway Mucosa Immune Profile in Asymptomatic Neonates

    PubMed Central

    Wolsk, Helene M.; Følsgaard, Nilofar V.; Birch, Sune; Brix, Susanne; Hansel, Trevor T.; Johnston, Sebastian L.; Kebadze, Tatiana; Chawes, Bo L.; Bønnelykke, Klaus; Bisgaard, Hans

    2016-01-01

    Background. Bacterial airway colonization is known to alter the airway mucosa immune response in neonates whereas the impact of viruses is unknown. The objective was therefore to examine the effect of respiratory viruses on the immune signature in the airways of asymptomatic neonates. Methods. Nasal aspirates from 571 asymptomatic 1-month-old neonates from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort were investigated for respiratory viruses. Simultaneously, unstimulated airway mucosal lining fluid was obtained and quantified for levels of 20 immune mediators related to type 1, type 2, type 17, and regulatory immune paths. The association between immune mediator levels and viruses was tested by conventional statistics and partial least square discriminant analysis. Results. Picornaviruses were detected in 58 neonates (10.2%) and other viruses in 10 (1.8%). A general up-regulation of immune mediators was found in the neonates with picornavirus (P < .0001; partial least square discriminant analysis). The association was pronounced for type 1– and type 2–related markers and was unaffected by comprehensive confounder adjustment. Detection of picornavirus and bacteria was associated with an additive general up-regulating effect. Conclusions. Asymptomatic presence of picornavirus in the neonatal airway is a potent activator of the topical immune response. This is relevant to understanding the immune potentiating effect of early life exposure to viruses. PMID:26655299

  10. Using Profile Analysis via Multidimensional Scaling (PAMS) to identify core profiles from the WMS-III.

    PubMed

    Frisby, Craig L; Kim, Se-Kang

    2008-03-01

    Profile Analysis via Multidimensional Scaling (PAMS) is a procedure for extracting latent core profiles in a multitest data set. The PAMS procedure offers several advantages compared with other profile analysis procedures. Most notably, PAMS estimates individual profile weights that reflect the degree to which an individual's observed profile approximates the shape and scatter of latent core profiles. The PAMS procedure was applied to index scores of nonreplicated participants from the standardization sample (N = 1,033) for the Wechsler Memory Scale--Third Edition (D. Tulsky, J. Zhu, & M. F. Ledbetter, 2002). PAMS extracted discrepant visual memory and auditory memory versus working memory core profiles for the complete 16- to 89-year-old sample and discrepant working memory and auditory memory versus working memory core profiles for the 75- to 89-year-old cohort. Implications for use of PAMS in future research are discussed.

  11. Lifewide profile of cytokine production by innate and adaptive immune cells from Brazilian individuals.

    PubMed

    Silveira-Nunes, Gabriela; Speziali, Elaine; Teixeira-Carvalho, Andréa; Vitelli-Avelar, Danielle M; Sathler-Avelar, Renato; Figueiredo-Soares, Taciana; Silva, Maria Luiza; Peruhype-Magalhães, Vanessa; Chaves, Daniel Gonçalves; Brito-Melo, Gustavo Eustáquio; Cardoso, Glenda Meira; Soares, Eric Bassetti; Elói-Santos, Silvana Maria; Teixeira, Rosângela; Queiroz, Dulciene Magalhães; Corrêa-Oliveira, Rodrigo; Faria, Ana Maria Caetano; Martins-Filho, Olindo Assis

    2017-01-01

    Immunosenescence is associated with several changes in adaptive and innate immune cells. Altered cytokine production is among the most prominent of these changes. The impact of age-related alterations on cytokine global profiles produced by distinct populations of leukocytes from healthy Brazilian individuals was studied. We analysed frequencies of cytokine-producing lymphocytes and innate immune cells from individuals at several ages spanning a lifetime period (0-85 years). Healthy adult individuals presented a balanced profile suggestive of a mature immune system with equal contributions of both innate and adaptive immunity and of both categories of cytokines (inflammatory and regulatory). In healthy newborns and elderly, innate immune cells, especially neutrophils and NK-cells, contributed the most to a balanced profile of cytokines. Our results support the hypothesis that ageing is not associated with a progressive pro-inflammatory cytokine production by all leukocytes but rather with distinct fluctuations in the frequency of cytokine-producing cells throughout life.

  12. Multi-scale modeling of the CD8 immune response

    SciTech Connect

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

    2016-06-08

    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.

  13. 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.

  14. Type 1 and type 2 immune response profiles of commercial dairy cows in 4 regions across Canada

    PubMed Central

    Thompson-Crispi, Kathleen A.; Mallard, Bonnie A.

    2012-01-01

    Diseases of dairy cattle have adverse implications for both the dairy industry and animal welfare. Understanding adaptive immune response profiles of cattle on a national scale will provide insight into the potential for improving health and decreasing disease. The objectives of the present study were to evaluate immune response phenotypes of Holstein cows outside the peripartum period and to determine if antibody isotype bias to putative type 1 and type 2 test antigens is maintained. The cows, housed on commercial farms in 4 key dairy regions across Canada, were immunized with test antigens to measure their ability to mount cell-mediated immune responses (CMIR) and antibody-mediated immune responses (AMIR). Delayed-type hypersensitivity (DTH) was used as an indicator of CMIR and primary and secondary serum antibodies of the immunoglobulin (Ig) G1 and IgG2 isotypes were used to determine AMIR to the test antigens. Immune response phenotypes varied significantly among regions, herds, and cows. Cows in Alberta had significantly higher DTH responses and secondary responses to the type 2 test antigen than those in other regions. However, cows in Alberta had significantly lower primary antibody responses. It was found that Alberta had the lowest incidence of mastitis caused by Escherichia coli and Staphylococcus aureus compared with other regions. The IgG1/IgG2 antibody isotype ratio confirmed the nature of the test antigens. This was the first study to evaluate adaptive immune response profiles and disease incidence of dairy cows on a national scale and it therefore provides a glimpse of the current situation in Canada. PMID:23024454

  15. 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

  16. Proteomic profile of circulating immune complexes in chronic Chagas disease.

    PubMed

    Ohyama, K; Huy, N T; Yoshimi, H; Kishikawa, N; Nishizawa, J E; Roca, Y; Revollo Guzmán, R J; Velarde, F U G; Kuroda, N; Hirayama, K

    2016-10-01

    Immune complexes (ICs) are the direct and real-time products of humoral immune responses. The identification of constituent foreign or autoantigens within ICs might bring new insights into the pathology of infectious diseases. We applied immune complexome analysis of plasma to the study of Chagas disease caused by Trypanosoma cruzi. Twenty seropositive plasma samples including cardiac and/or megacolon determinate patients (n = 11) and indeterminate (n = 9) were analysed along with 10 seronegative individuals to characterize the antigens bound to circulating ICs. We identified 39 T. cruzi antigens and 114 human autoantigens specific to patients with Chagas. Among those antigens, two T. cruzi antigens (surface protease GP63, glucose-6-isomerase) and six human autoantigens (CD180 antigen, ceruloplasmin, fibrinogen beta chain, fibrinogen beta chain isoform 2 preprotein, isoform gamma-A of fibrinogen γ-chain, serum paraoxonase) were detected in more than 50% of the patients tested. Human isoform short of complement factor H-related protein 2 and trans-sialidase of T. cruzi were more frequently found in the indeterminate (5/9 for both) compared with in the determinate Chagas (0/11, P = 0·046 for human, 1/11, P = 0·0498 for T. cruzi). The immune complexome could illustrate the difference of immune status between clinical forms of chronic Chagas disease. © 2016 John Wiley & Sons Ltd.

  17. Large-scale field trials of active immunizing agents

    PubMed Central

    Cockburn, W. Charles

    1955-01-01

    In this discussion of the methods to be used in large-scale field trials of active immunizing agents and of the results to be expected from such trials, special emphasis is laid on pertussis vaccine trials in Great Britain. After a review of the criteria for strictly controlled field studies and of the investigation of typhoid vaccines conducted in 1904-08 by the Antityphoid Committee of the British Army, the author describes the pertussis vaccine studies which have been and are now being carried by the Whooping-Cough Immunization Committee of the Medical Research Council of Great Britain. The original strictly controlled trials have been completed and the results published. Studies are now being made of vaccines prepared by different methods and evaluated both in the field and in the laboratory. Each vaccine is given to some 2000-3000 children of 4-6 months to 4 years of age. By the end of the studies 30 000-40 000 children will have been followed up for a period of two years. Since in the current studies all the children are vaccinated and none are left as unvaccinated controls, the relative and not the absolute protective value of the vaccines will be measured. PMID:13270079

  18. Comprehensive immune profiling reveals substantial immune system alterations in a subset of patients with amyotrophic lateral sclerosis

    PubMed Central

    Gustafson, Michael P.; Staff, Nathan P.; Bornschlegl, Svetlana; Butler, Greg W.; Maas, Mary L.; Kazamel, Mohamed; Zubair, Adeel; Gastineau, Dennis A.; Windebank, Anthony J.

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a median lifespan of 2–3 years after diagnosis. There are few meaningful treatments that alter progression in this disease. Preclinical and clinical studies have demonstrated that neuroinflammation may play a key role in the progression rate of ALS. Despite this, there are no validated biomarkers of neuroinflammation for use in clinical practice or clinical trials. Biomarkers of neuroinflammation could improve patient management, provide new therapeutic targets, and possibly help stratify clinical trial selection and monitoring. However, attempts to identify a singular cause of neuroinflammation have not been successful. Here, we performed multi-parameter flow cytometry to comprehensively assess 116 leukocyte populations and phenotypes from lymphocytes, monocytes, and granulocytes in a cohort of 80 ALS patients. We identified 32 leukocyte phenotypes that were altered in ALS patients compared to age and gender matched healthy volunteers (HV) that included phenotypes of both inflammation and immune suppression. Unsupervised hierarchical clustering and principle component analysis of ALS and HV immunophenotypes revealed two distinct immune profiles of ALS patients. ALS patients were clustered into a profile distinct from HVs primarily due to differences in a multiple T cell phenotypes, CD3+CD56+ T cells and HLA-DR on monocytes. Patients clustered into an abnormal immune profile were younger, more likely to have a familial form of the disease, and survived longer than those patients who clustered similarly with healthy volunteers (344 weeks versus 184 weeks; p = 0.012). The data set generated from this study establishes an extensive accounting of immunophenotypic changes readily suitable for biomarker validation studies. The extensive immune system changes measured in this study indicate that normal immune homeostatic mechanisms are disrupted in ALS patients, and that multiple immune states

  19. 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.

  20. Bioinformatic profiling identifies an immune-related risk signature for glioblastoma.

    PubMed

    Cheng, Wen; Ren, Xiufang; Zhang, Chuanbao; Cai, Jinquan; Liu, Yang; Han, Sheng; Wu, Anhua

    2016-06-14

    To investigate the local immune status and its prognostic value in glioma. A cohort of 297 glioma samples with whole genome microarray expression data from the Chinese Glioma Genome Atlas database were included for discovery. The Cancer Genome Atlas (TCGA) database was used for validation. Principal components analysis and gene set enrichment analysis were used to explore the bioinformatic implication. Distinct local immune status was identified according to histologic grade. Glioblastoma (GBM) exhibited an enhanced immune phenotype compared to lower grade glioma. We profiled the immune-related gene set and identified 8 genes (FOXO3, IL6, IL10, ZBTB16, CCL18, AIMP1, FCGR2B, and MMP9) with the greatest prognostic value in GBM. A local immune-related risk signature was developed from the genes to distinguish cases as high or low risk of unfavorable prognosis, which could be validated in TCGA database. High-risk patients conferred an enhanced intensity of local immune response compared to low-risk ones. Additionally, the signature exhibited different distribution based on molecular features. The signature had prognostic significance in the stratified cohorts and was identified as an independent prognostic factor for GBM. We profiled the immune status in glioma and established a local immune signature for GBM, which could independently identify patients with a high risk of reduced survival, indicating the relationship between prognosis and local immune response. © 2016 American Academy of Neurology.

  1. Genetic aspects of auto-immune profiles of healthy chickens.

    PubMed

    Parmentier, Henk K; van der Vaart, Priscilla S; Nieuwland, Mike G B; Savelkoul, Huub F J

    2017-09-01

    Auto-antibody profiles binding liver antigens differed between chicken lines divergently selected for specific antibody responses to SRBC, and were affected by ageing suggesting both genetic and environmental effects. Presence and levels of IgM and IgG antibodies binding chicken liver cell lysate (CLL) fragments in plasma at 5 weeks of age from 10 individual full sibs and their parents from 5 Hsrbc and 5 Lsrbc line families was studied to reveal genetic relations. Non-genetic maternal effects were studied by comparing auto-antibody profiles of 36 weeks old hens from 2 other unrelated lines with the profiles from their chicks at hatch. IgM and IgG antibodies from parents and progeny from both Hsrbc and Lsrbc lines bound CLL fragments. Significant line and generation differences and their interactions were found for both isotypes. Higher staining of CLL fragments was usually found for Hsrbc line birds. Lines were clustered by auto-antibody profiles, but staining by birds of both lines in both generations was very individual for IgG and IgM. The current data with full sibs therefore not supported a genetic basis for auto-antibody profiles. IgG but not IgM auto-antibody profiles of chicks correlated with maternal auto-antibody profiles. The results suggest that the auto-antibody repertoire of healthy chickens is largely stochastically initiated and may be affected by environmental challenges during ageing, but genetic mechanisms may underlie staining intensity of individual bound CLL fragments. The present results suggest that identification of fragments or profiles to be used at early age for genetic selection for health traits is not feasible yet. Secondly, the IgM profile of neonatal chickens seems non-organised independent of the maternal profile, but the neonatal IgG profile is much more related with the maternal profile. Consequences of these findings for disease susceptibility or breeding for optimal health are discussed. Copyright © 2017 Elsevier Ltd. All

  2. A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis.

    PubMed

    Davis, John M; Knutson, Keith L; Skinner, John A; Strausbauch, Michael A; Crowson, Cynthia S; Therneau, Terry M; Wettstein, Peter J; Matteson, Eric L; Gabriel, Sherine E

    2012-01-31

    Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA. The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls. The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-γ, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-γ and IL-13 to CMV/EBV stimulation were associated with greater joint damage. A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV

  3. A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis

    PubMed Central

    2012-01-01

    Introduction Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA. Methods The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls. Results The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-γ, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-γ and IL-13 to CMV/EBV stimulation were associated with greater joint damage. Conclusions A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The

  4. Subgrouping Chronic Fatigue Syndrome Patients By Genetic and Immune Profiling

    DTIC Science & Technology

    2015-12-01

    SUPPLEMENTARY NOTES 14. ABSTRACT We have successfully performed all testing of the approximately 600 samples (200 CFS /ME patients vs 397 healthy...in the pathogenesis of chronic fatigue syndrome ( CFS )/myalgic encephalomyelitis (ME). It is likely that these findings will also result in an...unveil the pathogenesis of ME/ CFS and subsequently of GWI. It appears that we will gain a significant understanding of the immune responses and

  5. Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

    PubMed Central

    2013-01-01

    Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to

  6. Confirmatory Factor Analysis and Profile Analysis via Multidimensional Scaling.

    PubMed

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

    2007-01-01

    This paper describes the Confirmatory Factor Analysis (CFA) parameterization of the Profile Analysis via Multidimensional Scaling (PAMS) model to demonstrate validation of profile pattern hypotheses derived from multidimensional scaling (MDS). Profile Analysis via Multidimensional Scaling (PAMS) is an exploratory method for identifying major profiles in a multi-subtest test battery. Major profile patterns are represented as dimensions extracted from a MDS analysis. PAMS represents an individual observed score as a linear combination of dimensions where the dimensions are the most typical profile patterns present in a population. While the PAMS approach was initially developed for exploratory purposes, its results can later be confirmed in a different sample by CFA. Since CFA is often used to verify results from an exploratory factor analysis, the present paper makes the connection between a factor model and the PAMS model, and then illustrates CFA with a simulated example (that was generated by the PAMS model) and at the same time with a real example. The real example demonstrates confirmation of PAMS exploratory results by using a different sample. Fit indexes can be used to indicate whether the CFA reparameterization as a confirmatory approach works for the PAMS exploratory results.

  7. Relatively scaled ECE temperature profiles of KSTAR plasmas.

    PubMed

    Choi, M J; Yun, G S; Park, H K; Jeon, Y M; Jeong, S H

    2010-10-01

    A scheme to obtain relatively scaled profiles of electron cyclotron emission (ECE) temperature directly from uncalibrated raw radiometer data is proposed and has been tested for the 2009 campaign KSTAR plasmas. The proposed method utilizes a position controlled system to move the plasma adiabatically and compares ECE radiometer channels at the same relative radial positions assuming the profile consistency during the adiabatic change. This scaling method is an alternative solution when an absolute calibration is unreliable or too time consuming. The application to the two dimensional ECE imaging data, wherein calibration is extremely difficult, may also prove to be useful.

  8. Relatively scaled ECE temperature profiles of KSTAR plasmas

    SciTech Connect

    Choi, M. J.; Yun, G. S.; Park, H. K.; Jeon, Y. M.; Jeong, S. H.

    2010-10-15

    A scheme to obtain relatively scaled profiles of electron cyclotron emission (ECE) temperature directly from uncalibrated raw radiometer data is proposed and has been tested for the 2009 campaign KSTAR plasmas. The proposed method utilizes a position controlled system to move the plasma adiabatically and compares ECE radiometer channels at the same relative radial positions assuming the profile consistency during the adiabatic change. This scaling method is an alternative solution when an absolute calibration is unreliable or too time consuming. The application to the two dimensional ECE imaging data, wherein calibration is extremely difficult, may also prove to be useful.

  9. Age and genetic selection affect auto-immune profiles of chickens.

    PubMed

    Parmentier, Henk K; Harms, Elmer; Lammers, Aart; Nieuwland, Mike G B

    2014-12-01

    Specificity, antibody isotype distribution and levels, of natural autoantibodies (NAAb) may be potential informative parameters for immune mediated natural disease resistance, immune modulation, and maintenance of physiological homeostasis. In a previous study we detected IgM and IgG antibodies to liver antigens in plasma from 1 year old chickens. Auto-immune profiles directed towards liver antigens differed between chicken lines divergently selected for specific antibody responses to sheep red blood cells. In the present study we measured the presence and typed levels and antibody isotypes (IgG and IgM) of NAAb binding the 'auto-antigen' complex chicken liver cell lysate (CLL) in plasma samples obtained from chickens at 5 weeks and at 1-year of age, respectively, by quantitative western blotting. Extensive staining patterns of plasma antibodies binding CLL were found for both isotypes and at both ages in all birds. At both ages, IgM and IgG bound similar numbers of CLL antigens, which remained almost constant for IgM, whereas the number of IgG stained bands in time was enhanced. Significant differences of binding patterns of NAAb (stained antigen fragments of CLL and staining intensity) were detected between the three different chicken lines at both ages and between both ages, and lines could be clustered on the basis of their auto-antibody profile. The present results indicate that analysis of the plasma NAAb repertoire of poultry like in mammals could provide a way of distinguishing differences of immune competence (as reflected by the selection criterion of antibody responses) between individuals and lines, and could provide tools to select individual birds for health and other traits. The age-dependency of the auto-immune profile suggest that such profiles may also reflect immune maturation, which should be taken into account when relating an auto-immune profile with other traits.

  10. 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…

  11. Molecular profile of cochlear immunity in the resident cells of the organ of Corti.

    PubMed

    Cai, Qunfeng; Vethanayagam, R Robert; Yang, Shuzhi; Bard, Jonathan; Jamison, Jennifer; Cartwright, Daniel; Dong, Youyi; Hu, Bo Hua

    2014-10-14

    The cochlea is the sensory organ of hearing. In the cochlea, the organ of Corti houses sensory cells that are susceptible to pathological insults. While the organ of Corti lacks immune cells, it does have the capacity for immune activity. We hypothesized that resident cells in the organ of Corti were responsible for the stress-induced immune response of the organ of Corti. This study profiled the molecular composition of the immune system in the organ of Corti and examined the immune response of non-immune epithelial cells to acoustic overstimulation. Using high-throughput RNA-sequencing and qRT-PCR arrays, we identified immune- and inflammation-related genes in both the cochlear sensory epithelium and the organ of Corti. Using bioinformatics analyses, we cataloged the immune genes expressed. We then examined the response of these genes to acoustic overstimulation and determined how changes in immune gene expression were related to sensory cell damage. The RNA-sequencing analysis reveals robust expression of immune-related genes in the cochlear sensory epithelium. The qRT-PCR array analysis confirms that many of these genes are constitutively expressed in the resident cells of the organ of Corti. Bioinformatics analyses reveal that the genes expressed are linked to the Toll-like receptor signaling pathway. We demonstrate that expression of Toll-like receptor signaling genes is predominantly from the supporting cells in the organ of Corti cells. Importantly, our data demonstrate that these Toll-like receptor pathway genes are able to respond to acoustic trauma and that their expression changes are associated with sensory cell damage. The cochlear resident cells in the organ of Corti have immune capacity and participate in the cochlear immune response to acoustic overstimulation.

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

    PubMed

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

    2016-01-01

    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. 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. 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). 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.

  13. 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

  14. 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.

  15. Profiling Humoral Immune Responses to P. falciparum Infection with Protein Microarrays

    PubMed Central

    Doolan, Denise L.; Mu, Yunxiang; Unal, Berkay; Sundaresh, Suman; Hirst, Siddiqua; Valdez, Conrad; Randall, Arlo; Molina, Douglas; Liang, Xiaowu; Freilich, Daniel A.; Oloo, J. Aggrey; Blair, Peter L.; Aguiar, Joao C.; Baldi, Pierre; Davies, D. Huw; Felgner, Philip L.

    2010-01-01

    A complete description of the serological response following exposure of humans to complex pathogens is lacking and approaches suitable for accomplishing this are limited. Here we report, using malaria as a model, a method which elucidates the profile of antibodies that develop after natural or experimental infection or after vaccination with attenuated organisms, and which identifies immunoreactive antigens of interest for vaccine development or other applications. Expression vectors encoding 250 Plasmodium falciparum (Pf) proteins were generated by PCR/recombination cloning; the proteins were individually expressed with >90% efficiency in E. coli cell-free in vitro transcription and translation reactions, and printed directly without purification onto microarray slides. The protein microarrays were probed with human sera from one of four groups which differed in immune status: sterile immunity or no immunity against experimental challenge following vaccination with radiation-attenuated Pf sporozoites, partial immunity acquired by natural exposure, and no previous exposure to Pf. Overall, 72 highly reactive Pf antigens were identified. Proteomic features associated with immunoreactivity were identified. Importantly, antibody profiles were distinct for each donor group. Information obtained from such analyses will facilitate identifying antigens for vaccine development, dissecting the molecular basis of immunity, monitoring the outcome of whole-organism vaccine trials, and identifying immune correlates of protection. PMID:18937256

  16. Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia.

    PubMed

    Jain, Prachi; Klotz, Jeffrey; Dunavin, Neil; Lu, Kit; Koklanaris, Eleftheria; Draper, Debbie; Superata, Jeanine; Chinian, Fariba; Yu, Quan; Keyvanfar, Keyvan; Wong, Susan; Muranski, Pawel; Barrett, A John; Ito, Sawa; Battiwalla, Minoo

    2017-01-01

    Patients with high risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

  17. An improved local immunization strategy for scale-free networks with a high degree of clustering

    NASA Astrophysics Data System (ADS)

    Xia, Lingling; Jiang, Guoping; Song, Yurong; Song, Bo

    2017-01-01

    The design of immunization strategies is an extremely important issue for disease or computer virus control and prevention. In this paper, we propose an improved local immunization strategy based on node's clustering which was seldom considered in the existing immunization strategies. The main aim of the proposed strategy is to iteratively immunize the node which has a high connectivity and a low clustering coefficient. To validate the effectiveness of our strategy, we compare it with two typical local immunization strategies on both real and artificial networks with a high degree of clustering. Simulations on these networks demonstrate that the performance of our strategy is superior to that of two typical strategies. The proposed strategy can be regarded as a compromise between computational complexity and immune effect, which can be widely applied in scale-free networks of high clustering, such as social network, technological networks and so on. In addition, this study provides useful hints for designing optimal immunization strategy for specific network.

  18. Gene Expression Profile of the Hypothalamus in DNP-KLH Immunized Mice Following Electroacupuncture Stimulation

    PubMed Central

    Kim, Sun Kwang; Kim, Jeungshin; Ko, Eunjung; Kim, Hyunseong; Hwang, Deok-Sang; Lee, Sanghoon; Baek, Yonghyeon; Min, Byung-Il; Nam, Sangsoo; Bae, Hyunsu

    2011-01-01

    Clinical evidence indicates that electroacupuncture (EA) is effective for allergic disorder. Recent animal studies have shown that EA treatment reduces levels of IgE and Th2 cytokines in BALB/c mice immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH). The hypothalamus, a brain center of the neural-immune system, is known to be activated by EA stimulation. This study was performed to identify and characterize the differentially expressed genes in the hypothalamus of DNP-KLH immunized mice that were stimulated with EA or only restrained. To this aim, we conducted a microarray analysis to evaluate the global gene expression profiles, using the hypothalamic RNA samples taken from three groups of mice: (i) normal control group (no treatments); (ii) IMH group (DNP-KLH immunization + restraint); and (iii) IMEA group (immunization + EA stimulation). The microarray analysis revealed that total 39 genes were altered in their expression levels by EA treatment. Ten genes, including T-cell receptor alpha variable region family 13 subfamily 1 (Tcra-V13.1), heat shock protein 1B (Hspa1b) and 2′–5′ oligoadenylate synthetase 1F (Oas1f), were up-regulated in the IMEA group when compared with the IMH group. In contrast, 29 genes, including decay accelerating factor 2 (Daf2), NAD(P)H dehydrogenase, quinone 1 (Nqo1) and programmed cell death 1 ligand 2 (Pdcd1lg2) were down-regulated in the IMEA group as compared with the IMH group. These results suggest that EA treatment can modulate immune response in DNP-KLH immunized mice by regulating expression levels of genes that are associated with innate immune, cellular defense and/or other kinds of immune system in the hypothalamus. PMID:21799680

  19. Making the case for chromatin profiling: a new tool to investigate the immune-regulatory landscape.

    PubMed

    Winter, Deborah R; Jung, Steffen; Amit, Ido

    2015-09-15

    Recent technological advances have enabled researchers to accurately and efficiently assay the chromatin dynamics of scarce cell populations. In this Opinion article, we advocate the application of these technologies to central questions in immunology. Unlike changes to other molecular structures in the cell, chromatin features can reveal the past (developmental history), present (current activity) and future (potential response to challenges) of a given immune cell type; chromatin profiling is therefore an important new tool for studying the immune-regulatory networks of health and disease.

  20. Dual Expression Profile of Type VI Secretion System Immunity Genes Protects Pandemic Vibrio cholerae

    PubMed Central

    Miyata, Sarah T.; Unterweger, Daniel; Rudko, Sydney P.; Pukatzki, Stefan

    2013-01-01

    The Vibrio cholerae type VI secretion system (T6SS) assembles as a molecular syringe that injects toxic protein effectors into both eukaryotic and prokaryotic cells. We previously reported that the V. cholerae O37 serogroup strain V52 maintains a constitutively active T6SS to kill other Gram-negative bacteria while being immune to attack by kin bacteria. The pandemic O1 El Tor V. cholerae strain C6706 is T6SS-silent under laboratory conditions as it does not produce T6SS structural components and effectors, and fails to kill Escherichia coli prey. Yet, C6706 exhibits full resistance when approached by T6SS-active V52. These findings suggested that an active T6SS is not required for immunity against T6SS-mediated virulence. Here, we describe a dual expression profile of the T6SS immunity protein-encoding genes tsiV1, tsiV2, and tsiV3 that provides pandemic V. cholerae strains with T6SS immunity and allows T6SS-silent strains to maintain immunity against attacks by T6SS-active bacterial neighbors. The dual expression profile allows transcription of the three genes encoding immunity proteins independently of other T6SS proteins encoded within the same operon. One of these immunity proteins, TsiV2, protects against the T6SS effector VasX which is encoded immediately upstream of tsiV2. VasX is a secreted, lipid-binding protein that we previously characterized with respect to T6SS-mediated virulence towards the social amoeba Dictyostelium discoideum. Our data suggest the presence of an internal promoter in the open reading frame of vasX that drives expression of the downstream gene tsiV2. Furthermore, VasX is shown to act in conjunction with VasW, an accessory protein to VasX, to compromise the inner membrane of prokaryotic target cells. The dual regulatory profile of the T6SS immunity protein-encoding genes tsiV1, tsiV2, and tsiV3 permits V. cholerae to tightly control T6SS gene expression while maintaining immunity to T6SS activity. PMID:24348240

  1. Innate immune response gene expression profiles of N9 microglia are pathogen-type specific.

    PubMed

    McKimmie, Clive S; Roy, Douglas; Forster, Thorsten; Fazakerley, John K

    2006-06-01

    Glial cells, particularly microglia, are thought to play a pivotal role in initiating and guiding innate immune responses to CNS infections and in perpetuating inflammation and pathology in CNS diseases such as multiple sclerosis and Alzheimer's disease. We describe here the development and use of a new microarray designed to specifically profile transcript expression of innate immunity genes. Microarray analysis validated by quantitative PCR demonstrated an extensive range of pattern recognition receptor gene expression in resting N9 microglia, including Toll-like receptors, scavenger receptors and lectins. Stimulation with LPS or infection with virus modulated pattern recognition receptor, cytokine, chemokine and other innate immune transcripts in a distinct and stimulus-specific manner. This study demonstrates that a single glial cell phenotype has an innate capability to detect infection, determine its form and generate specific responses.

  2. Social impairments in autism spectrum disorder are related to maternal immune history profile.

    PubMed

    Patel, S; Masi, A; Dale, R C; Whitehouse, A J O; Pokorski, I; Alvares, G A; Hickie, I B; Breen, E; Guastella, A J

    2017-10-10

    Maternal immune activation has been highlighted as a factor that might increase the risk and severity of autism spectrum disorder (ASD) in children. Preclinical animal evidence shows that immune activation in mothers during pregnancy causes ASD-like behavioural traits in offspring. To this point, there has been no investigation of whether immune system activation in human mothers during pregnancy is associated with more severe symptoms in children with ASD. In this study, data from an existing ASD cohort (N=220) were analysed to investigate whether immune conditions in the mother were associated with greater severity of autism-related symptoms. Results showed that children whose mothers reported a history of immune activation (allergies and asthma) had significantly higher scores on the Social Responsiveness Scale (SRS; P=0.016), suggesting more severe social impairment symptoms in these children. This increasing severity of social impairment symptoms was further shown on the SRS cognition (P=0.007) and mannerisms (P=0.002) subscales. While immune history was associated with an increase in the severity of social impairment symptoms, history of autoimmune conditions in the mother did not have any effect in this cohort. To the best of our knowledge, this study is the first to show an association between immune activation history in the mother and increased ASD symptom severity in children with ASD. These findings support the idea of an immune system-mediated subtype in ASD, where the immune history of the mother may be an important factor.Molecular Psychiatry advance online publication, 10 October 2017; doi:10.1038/mp.2017.201.

  3. Scaling of equilibrium bed profiles in short tidal channels

    NASA Astrophysics Data System (ADS)

    Toffolon, M.; Lanzoni, S.

    2009-04-01

    We study the equilibrium bottom profile in short tidal channels using a simplified erosion/deposition relationship. The proposed approach, developed within the framework of a one-dimensional model and valid for the case of fine sediments, exploits some common assumptions: the inertial terms are neglected in the momentum equation, a purely sinusoidal tidal wave is considered; moreover the channel head is assumed to be always wet. The analytical solution is obtained for weakly dissipative channels in the limit of morphological long-term equilibrium by means of a perturbation analysis and is correct up to the second order of the perturbation of the frictional term. No assumption is made about the scale of the tidal amplitude with respect to the depth. The resulting bed profile is described by a single analytical relationship if expressed in terms of a modified longitudinal coordinate and tends to be flat in the landward part and linearly deepening seaward. The effect of channel convergence is included in the modified coordinate and tends to increase the upward concavity of the profile seaward when rewritten as a function of the physical variable; the possible presence of lateral tidal flats has a similar effect. The adoption of a suitably modified longitudinal coordinate, on the other hand, implies that the mouth of channels with different lengths is simply represented by points moving along the analytical curve describing the equilibrium profile. It is also possible to define a threshold between short flat channels and long linear channels, depending only on the critical velocity for erosion and the convergence length, so that convergent channels or sediment difficult to erode determine the tendency towards an almost horizontal bottom profile.

  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. Soil-based organisms improve immune function: shift cytokine profile from TH2 to TH1.

    PubMed

    1998-01-01

    SRL 172, a protein derived from a soil-based organism, is advertised for being able to restart the immune systems of persons with allergies, lung cancer, and tuberculosis. SRL 172 also appears to shift the cytokine profile in persons with Gulf War Syndrome and Chronic Fatigue Syndrome from TH2 back to the more effective TH1 profile. One patient reports improved DTH skin responses to topical DNCB after using Nature's Biotics Soil-based Organisms (SBOs). There also appeared to be improved immunity response indicating a shift from a weaker TH2 to a TH1 cytokine profile. The patient explains his successful use of SBOs and reveals that all but 1 out of 100 other patients who have used the product for a variety of ailments cite successful outcomes. Among the ailments whose symptoms the SBOs have helped relieve are foot sores from diabetes, Chronic Fatigue Syndrome, insomnia, and genital herpes. Recent use of SBOs by HIV-infected patients has had positive results in energy and weight gain and improvements in some types of chronic conditions indicating an improvement of cell mediated immunity and antibody production.

  6. Early immune responses and development of pathogenesis of avian infectious bronchitis viruses with different virulence profiles

    PubMed Central

    Mores, Marcos Antônio Zanella; Trevisol, Iara Maria; Coldebella, Arlei; Montassier, Hélio José; Brentano, Liana

    2017-01-01

    Avian infectious bronchitis virus (IBV) primarily replicates in epithelial cells of the upper respiratory tract of chickens, inducing both morphological and immune modulatory changes. However, the association between the local immune responses induced by IBV and the mechanisms of pathogenesis has not yet been completely elucidated. This study compared the expression profile of genes related to immune responses in tracheal samples after challenge with two Brazilian field isolates (A and B) of IBV from the same genotype, associating these responses with viral replication and with pathological changes in trachea and kidney. We detected a suppressive effect on the early activation of TLR7 pathway, followed by lower expression levels of inflammatory related genes induced by challenge with the IBV B isolate when compared to the challenge with to the IBV A isolate. Cell-mediated immune (CMI) related genes presented also lower levels of expression in tracheal samples from birds challenged with B isolate at 1dpi. Increased viral load and a higher percentage of birds with relevant lesions were observed in both tracheal and renal samples from chickens exposed to challenge with IBV B isolate. This differential pattern of early immune responses developed after challenge with IBV B isolate, related to the downregulation of TLR7, leading to insufficient pro-inflammatory response and lower CMI responses, seem to have an association with a most severe renal lesion and an enhanced capability of replication of this isolate in chicken. PMID:28199419

  7. Immune adaptive microenvironment profiles in intracerebral and intrasplenic lymphomas share common characteristics

    PubMed Central

    Donnou, S; Galand, C; Daussy, C; Crozet, L; Fridman, W H; Sautès-Fridman, C; Fisson, S

    2011-01-01

    A large body of evidence indicates that the immune microenvironment controls tumour development. Primary central nervous system lymphomas (PCNSL) are aggressive tumours growing in the central nervous system (CNS). To evaluate the role and characteristics of this immune-privileged site in anti-tumour defences, we compared the cellular and molecular immune microenvironments of growing murine lymphoma B cells injected into the brain or the spleen. In the brain, immune cells, including dendritic cells and T lymphocytes with a large proportion of CD4+forkhead box P3 (FoxP3+) regulatory T cells, rapidly infiltrated the tumour microenvironment. These populations also increased in number in the spleen. The T cell cytokine profiles in tumour-bearing mice were similar in the two sites, with predominant T helper type 1 (Th1)/Th17 polarization after polyclonal stimulation, although some interleukin (IL)-4 could also be found. We demonstrated that these T cells have anti-tumour activity in the CNS, although less than in the spleen: nude mice that received lymphoma cells intracerebrally died significantly earlier than immunocompetent animals. These results demonstrate that the brain is able to recruit all the major actors to mount a specific anti-tumour immune response against lymphoma. PMID:21668435

  8. The Impact of Large Scale Environments on Cluster Entropy Profiles

    NASA Astrophysics Data System (ADS)

    Trierweiler, Isabella; Su, Yuanyuan

    2017-01-01

    We perform a systematic analysis of 21 clusters imaged by the Suzaku satellite to determine the relation between the richness of cluster environments and entropy at large radii. Entropy profiles for clusters are expected to follow a power-law, but Suzaku observations show that the entropy profiles of many clusters are significantly flattened beyond 0.3 Rvir. While the entropy at the outskirts of clusters is thought to be highly dependent on the large scale cluster environment, the exact nature of the environment/entropy relation is unclear. Using the Sloan Digital Sky Survey and 6dF Galaxy Survey, we study the 20 Mpc large scale environment for all clusters in our sample. We find no strong relation between the entropy deviations at the virial radius and the total luminosity of the cluster surroundings, indicating that accretion and mergers have a more complex and indirect influence on the properties of the gas at large radii. We see a possible anti-correlation between virial temperature and richness of the cluster environment and find that density excess appears to play a larger role in the entropy flattening than temperature, suggesting that clumps of gas can lower entropy.

  9. Molecular profiling of T-helper immune genes during dengue virus infection

    PubMed Central

    Chen, Jincheng; Ng, Mary Mah Lee; Chu, Justin Jang Hann

    2008-01-01

    In this study, we provide a comprehensive molecular profiling of the involvement of T- helper (Th) genes during dengue virus infection of different cell types. The Th gene profiles of three human cell types (monocytes, T-cells and hepatocytes) were analyzed simultaneously via array-based RT-PCR upon infection with dengue virus. Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability. Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability. Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome. PMID:19117515

  10. Early life allergen and air pollutant exposures alter longitudinal blood immune profiles in infant rhesus monkeys.

    PubMed

    Crowley, Candace M; Fontaine, Justin H; Gerriets, Joan E; Schelegle, Edward S; Hyde, Dallas M; Miller, Lisa A

    2017-08-01

    Early life is a critical period for the progressive establishment of immunity in response to environmental stimuli; the impact of airborne challenges on this process is not well defined. In a longitudinal fashion, we determined the effect of episodic house dust mite (HDM) aerosol and ozone inhalation, both separately and combined, on peripheral blood immune cell phenotypes and cytokine expression from 4 to 25weeks of age in an infant rhesus monkey model of childhood development. Immune profiles in peripheral blood were compared with lung lavage at 25weeks of age. Independent of exposure, peripheral blood cell counts fluctuated with chronologic age of animals, while IFNγ and IL-4 mRNA levels increased over time in a linear fashion. At 12weeks of age, total WBC, lymphocyte numbers, FoxP3 mRNA and IL-12 mRNA were dramatically reduced relative to earlier time points, but increased to a steady state with age. Exposure effects were observed for monocyte numbers, as well as CCR3, FoxP3, and IL-12 mRNA levels in peripheral blood. Significant differences in cell surface marker and cytokine expression were detected following in vitro HDM or PMA/ionomycin stimulation of PBMC isolated from animals exposed to either HDM or ozone. Lavage revealed a mixed immune phenotype of FoxP3, IFNγ and eosinophilia in association with combined HDM plus ozone exposure, which was not observed in blood. Collectively, our findings show that airborne challenges during postnatal development elicit measureable cell and cytokine changes in peripheral blood over time, but exposure-induced immune profiles are not mirrored in the lung. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Profiles.

    ERIC Educational Resources Information Center

    Macintosh, Henry G.

    An introduction to profiles is presented with examples provided to permit an overall appraisal of the potential of profiles, of the principles upon which they might be based, and of the problems that will have to be overcome if their potential is to be realized in practice. The larger scale examples of profiles discussed are the Scottish Pupil…

  12. Large-scale profiling of metabolic dysregulation in ovarian cancer.

    PubMed

    Ke, Chaofu; Hou, Yan; Zhang, Haiyu; Fan, Lijun; Ge, Tingting; Guo, Bing; Zhang, Fan; Yang, Kai; Wang, Jingtao; Lou, Ge; Li, Kang

    2015-02-01

    Ovarian cancer is the leading cause of death in gynecologic malignancies. Profiling of endogenous metabolites has potential to identify changes caused by cancer and provide inspiring insights into cancer metabolism. To systematically investigate ovarian cancer metabolism, we performed metabolic profiling of 448 plasma samples related to epithelial ovarian cancer (EOC) based on ultra-performance liquid chromatography mass spectrometry in both positive and negative modes. These unbiased metabolomic profiles could well distinguish EOC from benign ovarian tumor (BOT) and uterine fibroid (UF). Fifty-three metabolites were identified as specific biomarkers for EOC, and this is the first report of piperine, 3-indolepropionic acid, 5-hydroxyindoleacetaldehyde and hydroxyphenyllactate as metabolic biomarkers of EOC. The AUC values of these metabolites for discriminating EOC from BOT/UF and early-stage EOC from BOT/UF were 0.9100/0.9428 and 0.8385/0.8624, respectively. Meanwhile, our metabolites were able to distinguish early-stage EOC from late-stage EOC with an AUC of 0.8801. Importantly, analysis of dysregulated metabolic pathways extends our current understanding of EOC metabolism. Metabolic pathways in EOC patients are mainly characterized by abnormal phospholipid metabolism, altered l-tryptophan catabolism, aggressive fatty acid β-oxidation and aberrant metabolism of piperidine derivatives. Together, these metabolic pathways provide a foundation to support cancer development and progression. In conclusion, our large-scale plasma metabolomics study yielded fundamental insights into dysregulated metabolism in ovarian cancer, which could facilitate clinical diagnosis, therapy, prognosis and shed new lights on ovarian cancer pathogenesis.

  13. Continuum description of profile scaling in nanostructure decay

    NASA Astrophysics Data System (ADS)

    Margetis, Dionisios; Aziz, Michael J.; Stone, Howard A.

    2003-03-01

    The technological drive toward smaller features in devices has fueled much interest in low-temperature kinetic processes such as growth, etching and morphological relaxation. We consider temperatures below the rougnening transition and report a continuum treatment of surface relaxation using a partial differential equation for axisymmetric crystal surfaces with a single facet. Our model accounts for step energy g1 and step-step interaction energy g_3. For diffusion-limited kinetics and ɛ=g_3/g_1<< 1, we apply boundary-layer theory to describe self-similar shapes close to the growing facet. For long times, (a) a universal equation holds for the profile, (b) the layer thickness varies as ɛ^1/3, and (c) distinct solutions for different ɛ are found since ɛ enters the boundary conditions; we argue that the profile peak scales as ɛ-1/6. Our results for a conical shape compare favorably with kinetic simulations [N. Israeli and D. Kandel, PRB 60, 5946 (1999)].

  14. Immune profiling of plasma and cervical secretions using recycling immunoaffinity chromatography.

    PubMed

    Castle, Philip E; Phillips, Terry M; Hildesheim, Allan; Herrero, Rolando; Bratti, M Concepcion; Rodríguez, Ana Cecilia; Morera, Lidia Ana; Pfeiffer, Ruth; Hutchinson, Martha L; Pinto, Ligia A; Schiffman, Mark

    2003-12-01

    Small volumes of cervical secretions have limited measurements of immunity at the cervix, which may be important to studies of human papillomavirus (HPV). We report the use of recycling immunoaffinity chromatography to efficiently study immune profiles in cervical secretions. Frozen pairs of plasma and cervical secretions (collected on ophthalmic sponges) were selected randomly from women with normal cervical cytology (n = 50) participating in a natural history study of HPV in Guanacaste, Costa Rica. Single 25- micro l aliquots of plasma and (diluted) cervical secretions were assayed for interleukin (IL) -1 beta, -2, -4, -6, -8, -10, -12, -13, -15, IFN-alpha, -beta, -gamma, tumor necrosis factor-alpha, -beta, RANTES (regulated on activation normal T-cell express and secreted), MCP-1 (monocyte chemoattractant protein), -2, -3, macrophage inflammatory protein-1 alpha, -1 beta (regulated on activation normal T-cell express and secreted), macrophage colony-stimulating factor, IgG, IgA, and cyclooxygenase 2. All of the specimens were tested as blind replicates, and refrozen plasma was retested 4 months later. To evaluate the reproducibility of the repeat measurements and to examine the correlation between plasma and cervical secretions, we calculated kappa values with 95% confidence intervals among categorized analyte values and Spearman correlation coefficients (rho) among detectable, continuous analyte values. Measurements of all of the analytes in either plasma or cervical secretions were highly reproducible, with all of the kappa > or = 0.78 (70% above 0.90), and all of the rho > or = 0.88 (96% above 0.90). Only IL-1 beta (kappa = 0.60 and rho = 0.82) and IL-6 (kappa = 0.50 and rho = 0.78) levels were strongly correlated between plasma and cervical secretions. IFN-gamma, tumor necrosis factor-beta, RANTES, MCP-1, MCP -2, macrophage inflammatory protein-1 alpha, and macrophage colony-stimulating factor levels were especially poorly correlated between plasma and

  15. Immunizations

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness 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 ...

  16. 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. ...

  17. Marek's disease virus-induced immunosuppression: array analysis of chicken immune response gene expression profiling.

    PubMed

    Heidari, Mohammad; Sarson, Aimie J; Huebner, Marianne; Sharif, Shayan; Kireev, Dmitry; Zhou, Huaijun

    2010-06-01

    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 infection, and transcriptional profiling of chicken gene expression in MD are poorly understood. In this study we conducted a global host gene expression analysis in the splenocytes of MDV-infected chickens using oligonucleotide-based Affymetrix GeneChip Chicken Genome Arrays. These arrays contain probes for more than 32,000 chicken transcripts and most of the known MDV genes and open reading frames. Two-week-old MD-susceptible chickens were inoculated with an oncogenic strain of MDV, and spleen samples were collected 5 and 15 days post-infection (dpi) for RNA isolation and microarray analysis. Array results displayed a significant differential pattern of immune response transcriptome between the two phases of MDV infection. The expression levels of more than 22 immune-response and related genes were downregulated, while the expression levels of at least 58 genes were increased at 5 dpi (cytolytic infection), compared to age-matched control birds. In comparison, out of 73 immune-response and related genes, 67 genes were downregulated, with only 6 genes having higher expression levels at 15 dpi (latency infection). Cytokines, chemokines, MHC molecules and related receptors, and adhesion molecules were among the many MDV-induced downregulated genes that are critical for an effective antiviral immune response. In addition, several apoptosis-associated genes were decreased in expression during latent infection, suggesting an MDV-induced blocking of initiation or progression of programmed cell death processes. These chicken arrays are valuable tools in understanding the molecular mechanisms behind viral pathogenesis and chicken gene expression patterns, and associated

  18. Unique transcriptional profile of liver-resident memory CD8+ T cells induced by immunization with malaria sporozoites

    PubMed Central

    Tse, Sze-Wah; Cockburn, Ian A.; Zhang, Hao; Scott, Alan L.; Zavala, Fidel

    2013-01-01

    Sterile immunity against live Plasmodium infection can be achieved by immunization with radiation attenuated sporozoites. This protection is known to be mediated in part by antigen-specific memory CD8+ T cells, presumably those residing in the liver. We characterized and compared the transcriptional profile of parasite-specific memory CD8+ T cells residing in the liver and spleen after immunization of mice with irradiated sporozoites. Microarray-based expression analysis of these memory CD8+ T cells indicated that liver resident memory cells display a distinct gene expression profile. We found major differences in the expression of immune function genes as well as genes involved in the cell cycle, cell trafficking, transcription and intracellular signaling. Importantly, the malaria parasite-induced liver resident CD8+ T cells display a transcriptional profile different to that described for CD8+ T cells following other microbial challenges. PMID:23594961

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

    PubMed Central

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

    2016-01-01

    Mast cells are evolutionarily ancient sentinel cells. Like basophils, mast cells express the high-affinity IgE receptor and are implicated in host defense and diverse immune-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 share more overlap with other circulating granulocytes than with mast cells. Derivation of mast cell and basophil transcriptional signatures underscores their differential capacity to detect environmental signals and influence the inflammatory milieu. PMID:27135604

  20. Contrasting expression of immune genes in scaled and scaleless skin of Atlantic salmon infected with young stages of Lepeophtheirus salmonis.

    PubMed

    Holm, H Jodaa; Skugor, S; Bjelland, A K; Radunovic, S; Wadsworth, S; Koppang, E O; Evensen, Ø

    2017-02-01

    Atlantic salmon skin tissues with and without scales were taken from two preferred sites of salmon louse (Lepeophtheirus salmonis) attachment, behind the dorsal fin (scaled) and from the top of the head (scaleless), respectively. Tissues were profiled by qPCR of 32 genes to study responses to copepodids, 4 days post infection (dpi), and during the moult of copepodids to the chalimus stage, at 8 dpi. Basal/constitutive differences were found for many immune-related genes between the two skin sites; e.g., mannose binding protein C was over 100 fold higher expressed in the scaled skin from the back in comparison to the skin without scales from the head. With lice-infection, at 4 dpi most genes in both tissues showed lower values than in the non-infected control. By 8 dpi, the majority of responses increased towards the control levels, including cytokines of Th1, Th17 and Th2 pathways. Immunohistochemistry of three immune factors revealed an even distribution of MHC class II positive cells throughout epidermis, including the top layer of keratinocytes, marked compartmentalization of Mx(+) and CD8α(+) cells close to stratum basale, and an increase in numbers of CD8α(+) cells in response to infection. In conclusion, suppression of immune genes during the copepodid stage likely sets off a beneficial situation for the parasite. At the moult to chalimus stage 8 dpi, only few genes surpassed the non-infected control levels, including CD8α. The gene expression pattern was reflected in the increased number of CD8α expressing cells, thus revealing a relatively minor activation of skin T-cell defenses in Atlantic salmon in response to L. salmonis infection.

  1. 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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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

    PubMed Central

    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.

    2015-01-01

    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

  3. Immune Profile of Honduran Schoolchildren with Intestinal Parasites: The Skewed Response against Geohelminths

    PubMed Central

    Rueda, María Mercedes; Rodríguez, Carol Anahelka; Canales, Maritza

    2016-01-01

    Soil-transmitted helminth infections typically induce a type-2 immune response (Th2), but no immunoepidemiological studies have been undertaken in Honduras, an endemic country where the main control strategy is children's annual deworming. We aimed to characterize the immune profile of Honduran schoolchildren harbouring these parasitoses. Demographic and epidemiological data were obtained through a survey; nutritional status was assessed through anthropometry; intestinal parasites were diagnosed by formol-ether and Kato-Katz; and blood samples were collected to determine immunological markers including Th1/Th2 cytokines, IgE, and eosinophil levels. A total of 225 children participated in the study, all of whom had received deworming during the national campaign five months prior to the study. Trichuriasis and ascariasis prevalence were 22.2% and 20.4%, respectively. Stunting was associated with both age and trichuriasis, whereas ascariasis was associated with sex and household conditions. Helminth infections were strongly associated with eosinophilia and hyper-IgE as well as with a Th2-polarized response (increased levels of IL-13, IL-10, and IL4/IFN-γ ratios and decreased levels of IFN-γ). Pathogenic protozoa infections were associated with a Th1 response characterized by elevated levels of IFN-γ and decreased IL10/IFN-γ ratios. Even at low prevalence levels, STH infections affect children's nutrition and play a polarizing role in their immune system. PMID:27882241

  4. 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

  5. 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.

  6. Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder

    PubMed Central

    Wingo, Aliza P.; Gibson, Greg

    2014-01-01

    Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD. PMID:25300922

  7. Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder.

    PubMed

    Wingo, Aliza P; Gibson, Greg

    2015-01-01

    Prospective epidemiological studies found that generalized anxiety disorder (GAD) can impair immune function and increase risk for cardiovascular disease or events. Mechanisms underlying the physiological reverberations of anxiety, however, are still elusive. Hence, we aimed to investigate molecular processes mediating effects of anxiety on physical health using blood gene expression profiles of 336 community participants (157 anxious and 179 control). We examined genome-wide differential gene expression in anxiety, as well as associations between nine major modules of co-regulated transcripts in blood gene expression and anxiety. No significant differential expression was observed in women, but 631 genes were differentially expressed between anxious and control men at the false discovery rate of 0.1 after controlling for age, body mass index, race, and batch effect. Gene set enrichment analysis (GSEA) revealed that genes with altered expression levels in anxious men were involved in response of various immune cells to vaccination and to acute viral and bacterial infection, and in a metabolic network affecting traits of metabolic syndrome. Further, we found one set of 260 co-regulated genes to be significantly associated with anxiety in men after controlling for the relevant covariates, and demonstrate its equivalence to a component of the stress-related conserved transcriptional response to adversity profile. Taken together, our results suggest potential molecular pathways that can explain negative effects of GAD observed in epidemiological studies. Remarkably, even mild anxiety, which most of our participants had, was associated with observable changes in immune-related gene expression levels. Our findings generate hypotheses and provide incremental insights into molecular mechanisms mediating negative physiological effects of GAD.

  8. Whole genome expression profiling reveals a significant role for immune function in human abdominal aortic aneurysms

    PubMed Central

    Lenk, Guy M; Tromp, Gerard; Weinsheimer, Shantel; Gatalica, Zoran; Berguer, Ramon; Kuivaniemi, Helena

    2007-01-01

    Background Abdominal aortic aneurysms are a common disorder with an incompletely understood etiology. We used Illumina and Affymetrix microarray platforms to generate global gene expression profiles for both aneurysmal (AAA) and non-aneurysmal abdominal aorta, and identified genes that were significantly differentially expressed between cases and controls. Results Affymetrix and Illumina arrays included 18,057 genes in common; 11,542 (64%) of these genes were considered to be expressed in either aneurysmal or normal abdominal aorta. There were 3,274 differentially expressed genes with a false discovery rate (FDR) ≤ 0.05. Many of these genes were not previously known to be involved in AAA, including SOST and RUNX3, which were confirmed using Q-RT-PCR (Pearson correlation coefficient for microarray and Q-RT-PCR data = 0.89; p-values for differences in expression between AAA and controls for SOST: 4.87 × 10-4 and for RUNX3: 4.33 × 10-5). Analysis of biological pathways, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), indicated extreme overrepresentation of immune related categories. The enriched categories included the GO category Immune Response (GO:0006955; FDR = 2.1 × 10-14), and the KEGG pathways natural killer cell mediated cytotoxicity (hsa04650; FDR = 5.9 × 10-6) and leukocyte transendothelial migration (hsa04670; FDR = 1.1 × 10-5). Conclusion Previous studies have provided evidence for the involvement of the immune system in AAA. The current expression analysis extends these findings by demonstrating broad coordinate gene expression in immunological pathways. A large number of genes involved in immune function were differentially expressed in AAA, and the pathway analysis gave these results a biological context. The data provide valuable insight for future studies to dissect the pathogenesis of human AAA. These pathways might also be used as targets for the development of therapeutic agents for AAA. PMID:17634102

  9. 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.

  10. Profiling the Humoral Immune Response of Acute and Chronic Q Fever by Protein Microarray*

    PubMed Central

    Vigil, Adam; Chen, Chen; Jain, Aarti; Nakajima-Sasaki, Rie; Jasinskas, Algimantas; Pablo, Jozelyn; Hendrix, Laura R.; Samuel, James E.; Felgner, Philip L.

    2011-01-01

    Antigen profiling using comprehensive protein microarrays is a powerful tool for characterizing the humoral immune response to infectious pathogens. Coxiella burnetii is a CDC category B bioterrorist infectious agent with worldwide distribution. In order to assess the antibody repertoire of acute and chronic Q fever patients we have constructed a protein microarray containing 93% of the proteome of Coxiella burnetii, the causative agent of Q fever. Here we report the profile of the IgG and IgM seroreactivity in 25 acute Q fever patients in longitudinal samples. We found that both early and late time points of infection have a very consistent repertoire of IgM and IgG response, with a limited number of proteins undergoing increasing or decreasing seroreactivity. We also probed a large collection of acute and chronic Q fever patient samples and identified serological markers that can differentiate between the two disease states. In this comparative analysis we confirmed the identity of numerous IgG biomarkers of acute infection, identified novel IgG biomarkers for acute and chronic infections, and profiled for the first time the IgM antibody repertoire for both acute and chronic Q fever. Using these results we were able to devise a test that can distinguish acute from chronic Q fever. These results also provide a unique perspective on isotype switch and demonstrate the utility of protein microarrays for simultaneously examining the dynamic humoral immune response against thousands of proteins from a large number of patients. The results presented here identify novel seroreactive antigens for the development of recombinant protein-based diagnostics and subunit vaccines, and provide insight into the development of the antibody response. PMID:21817167

  11. 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.

  12. Immunization Strategies against Piscirickettsia salmonis Infections: Review of Vaccination Approaches and Modalities and Their Associated Immune Response Profiles

    PubMed Central

    Evensen, Øystein

    2016-01-01

    Salmonid rickettsial septicemia (SRS) is a serious, infectious disease in Chilean salmon farming caused by Piscirickettsia salmonis, causing heavy losses to the salmonid industry. P. salmonis belongs to the Gammaproteobacteria, order Thiotrichales. SRS was first described in Chile in 1989, and infection with P. salmonis has since been described from a high number of fish species and in several geographic regions globally. P. salmonis infection of salmonids causes multifocal, necrotic areas of internal organs such as liver, kidney, and spleen. Histologically and immunologically, the tissue response is the formation of granulomas, often with central suppuration. The exact sequence of infection is not known, but bacteria likely gain access to internal organs through mucosal surfaces and when infected, fish carry bacteria in macrophages. It has not been fully determined if the bacterium resides in the cytosol or “hide” within vesicular structures intracellularly, although there are indications that in vitro infection results in actin reorganization and formation of actin-coated vesicle within which the bacterium resides. Protection against lethal challenge is well documented in lab scale experiments, but protection from vaccination has proven more difficult to attain long term under field conditions. Current vaccination protocols include whole cell, inactivated and adjuvanted vaccines for injection for primary immunization followed by oral boost where timing of boost delivery is followed by measuring circulating antibody levels against the pathogen. Documentation also exist that there is correlation between antibody titers and protection against mortality. Future vaccination regimes will likely also include live-attenuated vaccines or other technologies such as DNA vaccination. So far, there is no documentation available for live vaccines and, for DNA vaccines, studies have been unsuccessful under laboratory conditions. PMID:27917172

  13. 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

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

    PubMed

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

    2016-01-01

    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. 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. 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 desensitization, select candidates, and personalize

  15. 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

  16. Transcriptional Profiling of Midgut Immunity Response and Degeneration in the Wandering Silkworm, Bombyx mori

    PubMed Central

    Xiao, Guohua; Yang, Bing; Zhang, Jie; Li, Xuquan; Guan, Jingmin; Shao, Qimiao; Beerntsen, Brenda T.; Zhang, Peng; Wang, Chengshu; Ling, Erjun

    2012-01-01

    Background Lepidoptera insects have a novel development process comprising several metamorphic stages during their life cycle compared with vertebrate animals. Unlike most Lepidoptera insects that live on nectar during the adult stage, the Bombyx mori silkworm adults do not eat anything and die after egg-laying. In addition, the midguts of Lepidoptera insects produce antimicrobial proteins during the wandering stage when the larval tissues undergo numerous changes. The exact mechanisms responsible for these phenomena remain unclear. Principal Findings We used the silkworm as a model and performed genome-wide transcriptional profiling of the midgut between the feeding stage and the wandering stage. Many genes concerned with metabolism, digestion, and ion and small molecule transportation were down-regulated during the wandering stage, indicating that the wandering stage midgut loses its normal functions. Microarray profiling, qRT-PCR and western blot proved the production of antimicrobial proteins (peptides) in the midgut during the wandering stage. Different genes of the immune deficiency (Imd) pathway were up-regulated during the wandering stage. However, some key genes belonging to the Toll pathway showed no change in their transcription levels. Unlike butterfly (Pachliopta aristolochiae), the midgut of silkworm moth has a layer of cells, indicating that the development of midgut since the wandering stage is not usual. Cell division in the midgut was observed only for a short time during the wandering stage. However, there was extensive cell apoptosis before pupation. The imbalance of cell division and apoptosis probably drives the continuous degeneration of the midgut in the silkworm since the wandering stage. Conclusions This study provided an insight into the mechanism of the degeneration of the silkworm midgut and the production of innate immunity-related proteins during the wandering stage. The imbalance of cell division and apoptosis induces irreversible

  17. Expression profile of human immune-responsive gene 1 and generation and characterization of polyclonal antiserum.

    PubMed

    Xiao, Wei; Wang, Lan; Xiao, Ruijing; Wu, Mengjun; Tan, Jinquan; He, Yuling

    2011-07-01

    Murine immune-responsive gene 1 (IRG1) plays significant roles in embryonic implantation and neurodegeneration. The expression pattern of the human IRG1 gene, however, has not yet been established, and the predicted gene sequence has been revised several times according to computed expressed sequence tags (ESTs). To determine the human IRG1 gene expression profile, human fetal tissue samples, peripheral blood mononuclear cells (PBMCs) from normal healthy subjects, and the human leukemia cell lines THP-1 and K-562 challenged with lipopolysaccharide (LPS) were subjected to RT-PCR using degenerate primers. The results indicated that the IRG1 gene is differentially expressed in human fetal PBMCs and LPS-stimulated adult PBMCs. The amplified gene fragment was cloned into the pET32a(+) vector and fusion-expressed with a His-tag in a prokaryotic system. After affinity chromatography, human IRG1h fusion proteins were isolated by SDS-PAGE and identified by mass spectrometric analysis for use as an immunogen to immunize rabbits. The titer and specificity of the purified rabbit antiserum were sufficient to measure human IRG1 gene expression in various tissues and cultures. This purified polyclonal antiserum will allow us to initiate studies to elucidate the biological roles of the human IRG1 gene.

  18. Relationship between the clinical heterogeneity of neurocysticercosis and the immune-inflammatory profiles.

    PubMed

    Chavarría, Anahí; Fleury, Agnes; García, Esperanza; Márquez, Carlos; Fragoso, Gladis; Sciutto, Edda

    2005-09-01

    Human neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. Neurocysticercosis may be asymptomatic or manifested by non-specific mild to severe neurological symptoms. Host factors may be involved in this heterogeneous clinical picture. An immune-inflammatory profile that underlies neurocysticercosis presentation was determined in 45 cerebral spinal fluid (CSF), from clinical and radiologically characterized neurocysticercosis patients, measuring specific IgG subclasses and cytokines. Severity related with increased cellularity in the CSF which was characterized by increased levels of IgG subclasses, IL6/IL5/IL10, proteins, and eosinophils. Multiple neurocysticercosis showed higher levels of IL5/IL6 than single neurocysticercosis. Women presented increased IL6/IL5/IL10 levels pointing out immunological differences due to gender. Severe symptomatology was found when cysticerci were located intraventricular or in the subarachnoid space of the base, inducing an exacerbated response in the CSF. These results constitute an integrative insight to understand the immune-inflammatory response that underlies symptomatic neurocysticercosis.

  19. Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies.

    PubMed

    Merkies, I S J; Schmitz, P I M; van der Meché, F G A; Samijn, J P A; van Doorn, P A

    2002-05-01

    To determine the validity, reliability, and responsiveness of a new overall disability sum score in immune mediated polyneuropathies. Three impairment measures (MRC sum score, sensory sum score, grip strength (Vigorimeter)) and three disability scales (an overall disability sum score (ODSS), Hughes' functional scale (f score), Rankin scale) were assessed in a cross sectional group of 113 clinically stable patients (83 with Guillain-Barré syndrome, 22 with chronic inflammatory demyelinating polyneuropathy (CIDP), eight with a gammopathy related polyneuropathy). The ODSS was also used serially in 20 patients with recently diagnosed Guillain-Barré syndrome (n = 7) or CIDP (n = 13) and changing clinical conditions. Multiple regression studies were performed to compare the impact of impairment disturbances (independent variables) on the various disability scales (dependent variable). Moderate to good construct validity (stable group: Spearman's rank test (absolute values), r = 0.41-0.79; longitudinal group: multiple correlation coefficient, R = 0.69-0.89; p < 0.006 for all associations) and reliability (intraclass correlation coefficient, R = 0.90-0.95; p < 0.0001) were demonstrated for the ODSS. Its SRM values were high (> 0.8), indicating good responsiveness. Impairment measures accounted for a higher variance proportion of the ODSS compared with the f score and Rankin (R = 0.64 v 0.56 and 0.45, respectively). All clinimetric requirements were met by the overall (arm and leg) disability sum score in immune mediated polyneuropathies. Its use is therefore suggested in evaluating immune mediated polyneuropathies.

  20. Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling.

    PubMed

    Siska, Peter J; Johnpulle, Romany A N; Zhou, Alice; Bordeaux, Jennifer; Kim, Ju Young; Dabbas, Bashar; Dakappagari, Naveen; Rathmell, Jeffrey C; Rathmell, W Kimryn; Morgans, Alicia K; Balko, Justin M; Johnson, Douglas B

    2017-01-01

    Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel). Publically available data sets were used to validate primary sample analyses. Nearly all samples had some degree of T-cell infiltration and immune checkpoint expression. Seminomas were associated with increased CD3(+) T-cell infiltration, decreased Regulatory T-cells, increased PD-L1, and increased PD-1/PD-L1 spatial interaction compared with non-seminomas using FIHC. Gene expression profiling confirmed these findings and also demonstrated increased expression of T-cell markers (e.g., IFNγ, and LAG3) and cancer/testis antigens (e.g., PRAME) in seminomas, whereas non-seminomas demonstrated high neutrophil and macrophage gene signatures. Irrespective of histology, advanced TGCT stage was associated with decreased T-cell and NK-cell signatures, while Treg, neutrophil, mast cell and macrophage signatures increased with advanced stage. Importantly, cancer/testis antigen, neutrophil, and CD8(+)/regulatory T-cell signatures correlated with recurrence free survival. Thus, deep immune characterization of TGCT using IHC and gene expression profiling identified activated T-cell infiltration which correlated with seminoma histology and good prognosis. These results may provide a rationale for testing of anti-PD-1/PD-L1 agents and suggest prognostic markers.

  1. The Facial Affective Scale as a Predictor for Pain Unpleasantness When Children Undergo Immunizations

    PubMed Central

    Finnström, Berit; Mörelius, Evalotte

    2014-01-01

    Needle fear is a common problem in children undergoing immunization. To ensure that the individual child's needs are met during a painful procedure it would be beneficial to be able to predict whether there is a need for extra support. The self-reporting instrument facial affective scale (FAS) could have potential for this purpose. The aim of this study was to evaluate whether the FAS can predict pain unpleasantness in girls undergoing immunization. Girls, aged 11-12 years, reported their expected pain unpleasantness on the FAS at least two weeks before and then experienced pain unpleasantness immediately before each vaccination. The experienced pain unpleasantness during the vaccination was also reported immediately after each immunization. The level of anxiety was similarly assessed during each vaccination and supplemented with stress measures in relation to the procedure in order to assess and evaluate concurrent validity. The results show that the FAS is valid to predict pain unpleasantness in 11-12-year-old girls who undergo immunizations and that it has the potential to be a feasible instrument to identify children who are in need of extra support to cope with immunization. In conclusion, the FAS measurement can facilitate caring interventions. PMID:24734174

  2. 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

  3. Profile Similarity Metrics Increase Personality Scale Validity (Briefing Charts)

    DTIC Science & Technology

    2016-04-15

    temperament scales are used in employment settings to predict performance because they are generally valid and reduce adverse impact. This research...personality and temperament scales against job continuance outcomes. Analyses documented that: PSMs consistently accounted for over 90% of the variance in...personality and temperament scales computed using conventional metrics; the optimal weighting of PSMs provided incremental validity gains over

  4. Altered miRNAs expression profiles and modulation of immune response genes and proteins during neonatal sepsis.

    PubMed

    Chen, Jiande; Jiang, Siyuan; Cao, Yun; Yang, Yi

    2014-04-01

    The dysregulated expression of miRNAs in the immune system may be critical for immune responses to pathogens and evolve into the inflammation seen in sepsis. The aim of this study is to explore the important role of miRNAs in the regulation of the immune response during neonatal sepsis. Using a microarray we performed the miRNA expression profiling of peripheral blood leukocytes from neonates with sepsis and uninfected neonates. Based on the predicted target genes of these miRNAs we selected 26 immune-related miRNAs out of the differentially expressed miRNAs for further testing by quantitative PCR. We simultaneously detected the immune response genes by PCR array and plasma cytokine levels using a protein chip to investigate the effect of the altered miRNAs on the immune response in neonatal sepsis. There were 10 immune regulatory miRNAs whose expression was significantly changed more than two fold in the neonates with sepsis compared with the uninfected neonates. The expression levels of 11 immune response genes and the plasma levels of 15 cytokines or receptors were significantly up- or down-regulated in the neonates with sepsis compared to the uninfected neonates. This comprehensive analysis suggests that the altered miRNAs modulate the immune response during neonatal sepsis in a way that represses the inflammatory response. Our investigation demonstrated some miRNAs with altered expression levels and their probable association with the regulation of immune response during neonatal sepsis. The characteristics of the neonatal inflammatory response could be attributed to immature immune function of neonates.

  5. 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

  6. Immune diffuse alveolar hemorrhage: a retrospective assessment of a diagnostic scale.

    PubMed

    de Prost, Nicolas; Parrot, Antoine; Cuquemelle, Elise; Picard, Clément; Cadranel, Jacques

    2013-10-01

    Initiating early steroid treatment in patients with immune diffuse alveolar hemorrhage (DAH) is a key aspect of early management. However, steroid initiation is often delayed until the results of immunological markers and/or tissue biopsy have been obtained, which could contribute to poor outcomes. We previously developed a clinical score allowing for the early diagnosis of DAH of immune causes. However, this score has not been validated in an independent cohort of patients. The aim of this study was to assess the validity of this diagnostic score using an independent cohort of patients admitted for DAH of immune and nonimmune causes. We conducted a retrospective cohort study of patients admitted between January 2002 and December 2009 for DAH of immune and nonimmune causes. Forty-six patients were included in the study, with 12 patients having immune DAH and 34 patients with nonimmune DAH. Application of our previously validated clinical scale of immune DAH to this independent population of patients yielded an area under the ROC curve of 0.95 [0.90-1.01]. A score ≥4/10 was associated with the best performances of this scale: sensitivity = 1.00 [0.73-1.00], specificity = 0.88 [0.72-0.97], positive predictive value = 0.75 [0.48-0.93], and negative predictive value = 1.00 [0.88-1.00]. While immunological tests and tissue biopsy results are pending, deciding whether to initiate an immunosuppressive treatment is challenging. The initiation of early corticosteroid treatment is warranted in patients with immune DAH and could improve outcomes. This study confirms that this score allows for a good discrimination between patients with immune and nonimmune DAH. Because this series has several limitations, including its single-center and retrospective nature, the small number of patients included, and the lack of therapeutic intervention, a prospective evaluation of this score is warranted to ascertain whether it can improve the adequacy of early treatment strategies

  7. 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

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

    PubMed

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

    2015-05-06

    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.

  9. Exploiting the diversity of time scales in the immune system: A B-cell antibody model

    SciTech Connect

    Segel, L.A. Los Alamos National Lab., NM ); Perelson, A.S. )

    1991-06-01

    Using the continuous shape-space formalism, the authors develop an immune system model involving both B lymphocytes and antibody molecules. The binding and cross-linking of receptors on B cells stimulates the cells to divide and, with a lag, to secrete antibody. Using the method of multiple scales, it is shown how to correctly formulate long-time-scale equations for the population dynamics of B cells, the total antibody concentration, and rate of antibody secretion. The authors model is compared with previous phenomenological formulations.

  10. Comparison between impairment and disability scales in immune-mediated polyneuropathies.

    PubMed

    Merkies, Ingemar S J; Schmitz, Paul I M; Van Der Meché, Frans G A; Van Doorn, Pieter A

    2003-07-01

    The ability of a scale to detect clinical relevant changes over time, i.e., its "responsiveness," may help clinicians to choose among valid and reliable measures. Therefore, we investigated the responsiveness' rank ordering (best to worse) of six selected valid and reliable scales, namely the Medical Research Council (MRC)-sumscore, sensory-sumscore, grip-strength (Vigorimeter), nine-hole peg, ten-meters walking, and a disability-sumscore, in immune-mediated polyneuropathies. Patients with newly diagnosed Guillain-Barré syndrome (n = 7) or chronic inflammatory demyelinating polyneuropathy (n = 13) were examined over 52 weeks. Responsiveness of each scale was measured using different methods (effect-size, standardized response mean score, Wilcoxon matched-pairs signed-rank, and a newly devised Schmitz's distribution-free responsiveness score), and the obtained scores in each method were plotted against the follow-up period, thus allowing area-under-the-curve calculations (higher area-under-the-curve indicating better responsiveness). Also, longitudinal correlations were performed between the scales' values and patients' own clinical judgments (deteriorated, unchanged, improved) (higher correlation = better responsiveness). A consistent rank ordering was observed in each technique with the disability-sumscore, MRC-sumscore, and Vigorimeter being among the best responsive scales. Hence, the primary use of these measures is suggested in studies of immune-mediated polyneuropathies.

  11. Improving fatigue assessment in immune-mediated neuropathies: the modified Rasch-built fatigue severity scale.

    PubMed

    van Nes, Sonja I; Vanhoutte, Els K; Faber, Catharina G; Garssen, Marcel; van Doorn, Pieter A; Merkies, Ingemar S J

    2009-12-01

    Fatigue is a major disabling complaint in patients with immune-mediated neuropathies (IN). The 9-item fatigue severity scale (FSS) has been used to assess fatigue in these conditions, despite having limitations due to its classic ordinal construct. The aim was to improve fatigue assessment in IN through evaluation of the FSS using a modern clinimetric approach [Rasch unidimensional measurement model (RUMM2020)]. Included were 192 stable patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUSP). The obtained FSS data were exposed to RUMM2020 model to investigate whether this scale would meet its expectations. Also, reliability and validity studies were performed. The original FSS did not meet the Rasch model expectations, primarily based on two misfitting items, one of these also showing bias towards the factor 'walking independent.' After removing these two items and collapsing the original 7-point Likert options to 4-point response categories for the remaining items, we succeeded in constructing a 7-item Rasch-built scale that fulfilled all requirements of unidimensionality, linearity, and rating scale model. Good reliability and validity were also obtained for the modified FSS scale. In conclusion, a 7-item linearly weighted Rasch-built modified FSS is presented for more proper assessment of fatigue in future studies in patients with immune-mediated neuropathies.

  12. 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.

  13. 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

  14. What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

    PubMed Central

    Ruiz, Lorena; Espinosa-Martos, Irene; García-Carral, Cristina; Manzano, Susana; McGuire, Michelle K.; Meehan, Courtney L.; McGuire, Mark A.; Williams, Janet E.; Foster, James; Sellen, Daniel W.; Kamau-Mbuthia, Elizabeth W.; Kamundia, Egidioh W.; Mbugua, Samwel; Moore, Sophie E.; Kvist, Linda J.; Otoo, Gloria E.; Lackey, Kimberly A.; Flores, Katherine; Pareja, Rossina G.; Bode, Lars; Rodríguez, Juan M.

    2017-01-01

    Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the “core” soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02670278. PMID:28713365

  15. What's Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings.

    PubMed

    Ruiz, Lorena; Espinosa-Martos, Irene; García-Carral, Cristina; Manzano, Susana; McGuire, Michelle K; Meehan, Courtney L; McGuire, Mark A; Williams, Janet E; Foster, James; Sellen, Daniel W; Kamau-Mbuthia, Elizabeth W; Kamundia, Egidioh W; Mbugua, Samwel; Moore, Sophie E; Kvist, Linda J; Otoo, Gloria E; Lackey, Kimberly A; Flores, Katherine; Pareja, Rossina G; Bode, Lars; Rodríguez, Juan M

    2017-01-01

    Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the "core" soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02670278.

  16. 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…

  17. 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…

  18. Alterations in immune cell subsets and their cytokine secretion profile in childhood idiopathic thrombocytopenic purpura (ITP).

    PubMed

    Talaat, R M; Elmaghraby, A M; Barakat, S S; El-Shahat, M

    2014-05-01

    Immune thrombocytopenic purpura (ITP) is acquired autoimmune disease in children characterized by the breakdown of immune tolerance. This work is designed to explore the contribution of different lymphocyte subsets in acute and chronic ITP children. Imbalance in the T helper type 1 (Th1)/Th2 cytokine secretion profile was investigated. The frequency of T (CD3(+), CD4(+), CD8(+)) and B (CD19(+)) lymphocytes, natural killer (NK) (CD16(+) 56(+)) and regulatory T (T(reg)) [CD4(+) CD25(+high) forkhead box protein 3 (FoxP3)(+) ] cells was investigated by flow cytometry in 35 ITP children (15 acute and 20 chronic) and 10 healthy controls. Plasma levels of Th1 cytokines [interferon (IFN-γ) and tumour necrosis factor (TNF-α)] and Th2 [interleukin (IL)-4, IL-6 and IL-10)] cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Treg (P < 0·001) and natural killer (NK) (P < 0·001) cells were significantly decreased in ITP patients compared to healthy controls. A negative correlation was reported between the percentage of T(reg) cells and development of acute (r = -0·737; P < 0·01) and chronic (r = -0·515; P < 0·01) disease. All evaluated cytokines (IFN-γ, TNF-α, IL-4, IL-6 and IL-10) were elevated significantly in ITP patients (P < 0·001, P < 0·05, P < 0·05, P < 0·05 and P < 0·001, respectively) compared to controls. In conclusion, our data shed some light on the fundamental role of immune cells and their related cytokines in ITP patients. The loss of tolerance in ITP may contribute to the dysfunction of T(regs). Understanding the role of T cell subsets will permit a better control of autoimmunity through manipulation of their cytokine network. © 2014 British Society for Immunology.

  19. 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

  20. 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…

  1. 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…

  2. [Profile of immune and allergic dermatoses among children at the outpatient dermatology clinic in Cotonou (Benin)].

    PubMed

    Adégbidi, H; Degboé, B; Saka, B; Elégbédé, A; Atadokpèdé, F; Koudoukpo, C; Yédomon, H; do-Ango Padonou, F

    2014-01-01

    The aim of this work was to study the profile of immune and allergic dermatoses (IAD) in children consulting at the outpatient dermatology clinic at the National University Hospital in Cotonou (Benin). This retrospective descriptive study examined records of children consulting with this diagnosis over a 10-year period. IAD (902 cases, 37%) were the most common pediatric dermatosis, followed by infectious dermatosis (24%). The sex ratio of children was 0.78. The age groups most strongly affected were those aged 1-30 months (25.39%) and 150-180 months (19.73%). The main IAD were: eczema (47.9%) and prurigo simplex (40.7%). Other IADs included lichen planus (5.1%), toxicoderma (3.8%), urticaria (1.5%), and erythrodermic eczema (1%). The incidence of eczema increased from 13.5% in 2000 to 21.5% in 2009, an increase of 62.2% over 10 years. IADs are common at the Cotonou hospital clinic and are dominated by eczema, the incidence of which has increased significantly over time.

  3. New insights into autoantibody profiles from immune privileged sites in the eye: a glaucoma study.

    PubMed

    Boehm, Nils; Wolters, Dominik; Thiel, Uta; Lossbrand, Ulrike; Wiegel, Nelli; Pfeiffer, Norbert; Grus, Franz H

    2012-01-01

    Glaucoma is a chronic neurodegenerative disease and one of the leading causes of blindness. Autoantibody based immune processes are assumed to be involved in its pathogenesis. However, it is still unclear to what extent autoantibody patterns found in the eye (aqueous humor) are congruent to systemic autoantibodies (blood). Consistency would underline the specificity of known serum antibody markers for glaucoma. In this study we used antigen microarrays to analyze autoantibody reactivities in sera and corresponding aqueous humor samples of primary open-angle glaucoma patients (N=37) and non-glaucomatous controls (N=31). Compared to control subjects several divergent immunoreactivities were identified for the glaucoma group in both body fluids. Interestingly, 20% of the tested antigens revealed increased immunoreactivities (e.g., against HSP27, MBP, and α-1-antitrypsin) and 7.5% decreased immunoreactivities (e.g., against GFAP and β-L-crystallin), thus demonstrating a significant alteration of the autoantibody profiles in glaucoma patients. Using an artificial neural network in combination with a unique serum autoantibody pattern on prospective sera we were able to detect glaucoma with a specificity and sensitivity of approximately 93%. The intraindividual comparison revealed a strong correlation of detected immunoreactivities in sera and comparative aqueous humor samples in both study groups. These results emphasize the specificity of immunoreactions found in blood samples of glaucoma patients. Furthermore they indicate the necessity of analyzing not only up-regulated but also down-regulated antibody reactivities, which might be likewise relevant for the understanding of other diseases.

  4. 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

  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.

  6. Genomic scale profiling of autoimmune inflammation in the central nervous system: the nervous response to inflammation.

    PubMed

    Carmody, Ruaidhrí J; Hilliard, Brendan; Maguschak, Kimberly; Chodosh, Lewis A; Chen, Youhai H

    2002-12-01

    Using gene microarray technology, we found that inflammation in the central nervous system (CNS) not only induced the expression of many immune-related genes, but also significantly altered the gene expression profile of neural cells. Two unique groups of CNS genes were identified. The first group includes genes encoding ion channels, neural transmitters and growth factors. The second group includes genes that are important for nervous tissue regeneration. Additionally, a distinct pattern of gene expression was also identified in recovering animals. Thus, during autoimmune inflammation, the CNS actively responds to immune attacks by activating its own defense and repair genes.

  7. Nanometer-Scale Electrical Potential Profiling Across Perovskite Solar Cells

    SciTech Connect

    Xiao, Chuanxiao; Jiang, Chun-Sheng; Ke, Weijun; Wang, Changlei; Gorman, Brian; Yan, Yanfa; Al-Jassim, Mowafak

    2016-11-21

    We used Kelvin probe force microscopy to study the potential distribution on cross-section of perovskite solar cells with different types of electron-transporting layers (ETLs). Our results explain the low open-circuit voltage and fill factor in ETL-free cells, and support the fact that intrinsic SnO2 as an alternative ETL material can make high-performance devices. Furthermore, the potential-profiling results indicate a reduction in junction-interface recombination by the optimized SnO2 layer and adding a fullerene layer, which is consistent with the improved device performance and current-voltage hysteresis.

  8. 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.

  9. Systems biology of complex symptom profiles: capturing interactivity across behavior, brain and immune regulation.

    PubMed

    Broderick, Gordon; Craddock, Travis John Adrian

    2013-03-01

    As our thinking about the basic principles of biology and medicine continue to evolve, the importance of context and regulatory interaction is becoming increasingly obvious. Biochemical and physiological components do not exist in isolation but instead are part of a tightly integrated network of interacting elements that ensure robustness and support the emergence of complex behavior. This integration permeates all levels of biology from gene regulation, to immune cell signaling, to coordinated patterns of neuronal activity and the resulting psychosocial interaction. Systems biology is an emerging branch of science that sits as a translational catalyst at the interface of the life and computational sciences. While there is no universally accepted definition of systems biology, we attempt to provide an overview of some the basic unifying concepts and current efforts in the field as they apply to illnesses where brain and subsequent behavior are a chief component, for example autism, schizophrenia, depression, and others. Methods in this field currently constitute a broad mosaic that stretches across multiple scales of biology and physiological compartments. While this work by no means constitutes an exhaustive list of all these methods, this work highlights the principal sub-disciplines presently driving the field as well as future directions of progress. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Protein expression profile of Gasterophilus intestinalis larvae causing horse gastric myiasis and characterization of horse immune reaction

    PubMed Central

    Roelfstra, Liselore; Deeg, Cornelia A; Hauck, Stefanie M; Buse, Christina; Membrez, Mathieu; Betschart, Bruno; Pfister, Kurt

    2009-01-01

    Background Little information is available on the immunological aspect of parasitic Gasterophilus intestinalis (Diptera, Oestridae) larvae causing horse gastric myiasis. The objectives of this research were to analyze the protein content of larval crude extracts of the migrating second and third larvae (L2 and L3) of G. intestinalis in order to characterize the immune response of horses. Results The proteomic profile of L2 and L3, investigated by using one and two dimensional approaches, revealed a migration pattern specific to each larval stage. Furthermore, Western blots were performed with horse sera and with sera of Balb/c mice immunised with the larval crude extracts of L2 or L3, revealing a different immune reaction in naturally infected horses vs. artificially induced immune reaction in mice. The comparisons of the immunoblot profiles demonstrate that the stage L2 is more immunogenic than the stage L3 most likely as an effect of the highest enzymatic production of L2 while migrating through the host tissues. Fifteen proteins were identified by mass spectrometry. Conclusion This work provides further information into the understanding of the interaction between G. intestinalis and their host and by contributing a novel scheme of the proteomic profile of the main larval stages. PMID:19133133

  11. The Oral Health Impact Profile-14: a unidimensional scale?

    PubMed

    Santos, Camila Mello dos; Oliveira, Branca Heloisa de; Nadanovsky, Paulo; Hilgert, Juliana Balbinot; Celeste, Roger Keller; Hugo, Fernando Neves

    2013-04-01

    The aim of this study was to investigate the dimensional structure of the Oral Health Impact Profile-14: (OHIP-14). Data was obtained from studies carried out in Rio de Janeiro (N = 504) and Carlos Barbosa (N = 872), in the State of Rio Grande do Sul, Brazil. Exploratory factor analysis (EFA) was performed to identify the latent dimensions of the OHIP-14. Confirmatory factor analysis (CFA) was carried out of both samples to compare the one-dimensional structure found by the EFA and the proposed three-dimensional structure. This factorial structure was assessed using goodness-of-fit indices. In the Rio de Janeiro study, the eigenvalue was 9.2 and this one factor explained 65.6% of total variance, while in the Carlos Barbosa study the eigenvalue was 7.9 and this one factor explained 56.6% of variance. CFA indicated an adequate fit of the one-factor model for the Rio de Janeiro study (RMSEA = 0.04; CFI = 0.98; TLI = 0.98) and for the Carlos Barbosa study (RMSEA = 0.05; CFI = 0.97; TLI = 0.97). Our findings suggest that the OHIP-14 measures one single construct.

  12. Immune system functional pathway analysis using single cell network profiling (SCNP): a novel tool in cancer immunotherapy.

    PubMed

    Cesano, Alessandra; Spellmeyer, David

    2014-01-01

    The development of cancer immunotherapies has been ongoing for many years and has shown limited success. Novel biomarkers are needed to identify patients most likely to respond to anticancer immune-therapeutic approaches. Moreover, a systems-level approach is required for comprehensive understanding of the interconnected components, pathways, and cell types associated with an immune response. In this chapter, we describe single cell network profiling (SCNP), a novel method for assessing and measuring immune function/dysfunction at a systems level. SCNP is a multiparametric flow-cytometry-based analysis that can simultaneously measure, at the single cell level, both extracellular surface markers and changes in intracellular signaling proteins in response to extracellular modulators. Measuring changes in signaling proteins following the application of an external modulation informs on the functional capacity of the signaling network which cannot be assessed by the measurement of basal signaling alone. In addition, the simultaneous analysis of multiple pathways in multiple cell subsets can provide insight into the connectivity of both cell signaling networks and immune cell subtypes. The experimental steps associated with an SCNP assay are (1) pre-analytical sample preparation; (2) modulation for functional analysis; (3) staining with antibody cocktail; (4) data acquisition on flow cytometer; and (5) data analysis and metrics. Important considerations for each step of the assay will be discussed, and data demonstrating the utility of SCNP for immune monitoring applications will be summarized.

  13. Landscape-scale variation in an anthropogenic factor shapes immune gene variation within a wild population.

    PubMed

    Gonzalez-Quevedo, Catalina; Davies, Richard G; Phillips, Karl P; Spurgin, Lewis G; Richardson, David S

    2016-09-01

    Understanding the spatial scale at which selection acts upon adaptive genetic variation in natural populations is fundamental to our understanding of evolutionary ecology, and has important ramifications for conservation. The environmental factors to which individuals of a population are exposed can vary at fine spatial scales, potentially generating localized patterns of adaptation. Here, we compared patterns of neutral and major histocompatibility complex (MHC) variation within an island population of Berthelot's pipit (Anthus berthelotii) to assess whether landscape-level differences in pathogen-mediated selection generate fine-scale spatial structuring in these immune genes. Specifically, we tested for spatial associations between the distribution of avian malaria, and the factors previously shown to influence that distribution, and MHC variation within resident individuals. Although we found no overall genetic structure across the population for either neutral or MHC loci, we did find localized associations between environmental factors and MHC variation. One MHC class I allele (ANBE48) was directly associated with malaria infection risk, while the presence of the ANBE48 and ANBE38 alleles within individuals correlated (positively and negatively, respectively) with distance to the nearest poultry farm, an anthropogenic factor previously shown to be an important determinant of disease distribution in the study population. Our findings highlight the importance of considering small spatial scales when studying the patterns and processes involved in evolution at adaptive loci.

  14. 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

  15. Tools for Interpreting Large-Scale Protein Profiling in Microbiology

    PubMed Central

    Hendrickson, E. L.; Lamont, R. J.; Hackett, M.

    2009-01-01

    Quantitative proteome analysis of microbial systems generates large datasets that can be difficult and time consuming to interpret. Fortunately, many of the data display and gene clustering tools developed to analyze large transcriptome microarray datasets are also applicable to proteomes. Plots of abundance ratio versus total signal or spectral counts can highlight regions of random error and putative change. Displaying data in the physical order of the genes in the genome sequence can highlight potential operons. At a basic level of transcriptional organization, identifying operons can give insights into regulatory pathways as well as provide corroborating evidence for proteomic results. Classification and clustering algorithms can group proteins together by their abundance changes under different conditions, helping to identify interesting expression patterns, but often work poorly with noisy data like that typically generated in a large-scale proteome analysis. Biological interpretation can be aided more directly by overlaying differential protein abundance data onto metabolic pathways, indicating pathways with altered activities. More broadly, ontology tools detect altered levels of protein abundance for different metabolic pathways, molecular functions and cellular localizations. In practice, pathway analysis and ontology are limited by the level of database curation associated with the organism of interest. PMID:18946006

  16. Autoantibody‐Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity

    PubMed Central

    Slight‐Webb, Samantha; Lu, Rufei; Ritterhouse, Lauren L.; Munroe, Melissa E.; Maecker, Holden T.; Fathman, Charles G.; Utz, Paul J.; Merrill, Joan T.; Guthridge, Joel M.

    2016-01-01

    Objective Antinuclear antibodies (ANAs) are detected in ∼18% of females, yet autoimmune disease develops in only 5–8%. Immunologic differences between ANA‐positive healthy individuals and patients with systemic lupus erythematosus (SLE) may elucidate the regulatory mechanisms by which ANA‐positive individuals avoid transition to clinical autoimmune disease. Methods Healthy individuals (n = 790) were screened for autoantibodies specific for 11 antigens associated with lupus, systemic sclerosis, and Sjögren's syndrome. From this screening, 31 European American ANA‐positive healthy individuals were selected and demographically matched to ANA‐negative controls and SLE patients. Serum cytokine profiles, leukocyte subset frequency, and reactivity were analyzed by multiplex assays, immunophenotyping, and phosphospecific flow cytometry. Results Of 790 individuals screened, 57 (7%) were ANA‐positive. The majority of proinflammatory cytokines, including interferon‐γ (IFNγ), tumor necrosis factor, interleukin‐17 (IL‐17), and granulocyte colony‐stimulating factor, exhibited a stepwise increase in serum levels from ANA‐negative controls to ANA‐positive healthy individuals to SLE patients (P < 0.0001). IFNα, IFNβ, IL‐12p40, and stem cell factor/c‐Kit ligand were increased in SLE patients only (P < 0.05). B lymphocyte stimulator (BlyS) was elevated in SLE patients but decreased in ANA‐positive individuals (P < 0.001). Further, IL‐1 receptor antagonist (IL‐1Ra) was down‐regulated in SLE patients only (P < 0.0001). ANA‐positive individuals had increased frequencies of monocytes, memory B cells, and plasmablasts and increased levels of pSTAT‐1 and pSTAT‐3 following IFNα stimulation compared with ANA‐negative controls (P < 0.05). Conclusion ANA‐positive healthy individuals exhibit dysregulation in multiple immune pathways yet differ from SLE patients by the absence of elevated IFNs, BLyS, IL‐12p40, and stem cell factor

  17. 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.

  18. 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.

  19. Genome-Wide Transcriptional Profiling and Structural Magnetic Resonance Imaging in the Maternal Immune Activation Model of Neurodevelopmental Disorders.

    PubMed

    Richetto, Juliet; Chesters, Robert; Cattaneo, Annamaria; Labouesse, Marie A; Gutierrez, Ana Maria Carrillo; Wood, Tobias C; Luoni, Alessia; Meyer, Urs; Vernon, Anthony; Riva, Marco A

    2017-06-01

    Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation. Genome-wide transcriptional profiling revealed that prenatal immune activation caused a differential expression of 116 and 251 genes in the medial prefrontal cortex and nucleus accumbens, respectively. A large part of genes that were commonly affected in both brain areas were related to myelin functionality and stability. Subsequent epigenetic analyses indicated that altered DNA methylation of promoter regions might contribute to the differential expression of myelin-related genes. Quantitative relaxometry comparing T1, T2, and myelin water fraction revealed sparse increases in T1 relaxation times and consistent reductions in T2 relaxation times. Together, our multi-system approach demonstrates that prenatal viral-like immune activation causes myelin-related transcriptional and epigenetic changes in corticostriatal areas. Even though these abnormalities do not seem to be associated with overt white matter reduction, they may provide a molecular mechanism whereby prenatal infection can impair myelin functionality and stability. © The Author 2017. Published by Oxford University Press.

  20. Obesity alters immune and metabolic profiles: New insight from obese-resistant mice on high-fat diet.

    PubMed

    Boi, Shannon K; Buchta, Claire M; Pearson, Nicole A; Francis, Meghan B; Meyerholz, David K; Grobe, Justin L; Norian, Lyse A

    2016-10-01

    Diet-induced obesity has been shown to alter immune function in mice, but distinguishing the effects of obesity from changes in diet composition is complicated. It was hypothesized that immunological differences would exist between diet-induced obese (DIO) and obese-resistant (OB-Res) mice fed the same high-fat diet (HFD). BALB/c mice were fed either standard chow or HFD to generate lean or DIO and OB-Res mice, respectively. Resulting mice were analyzed for serum immunologic and metabolic profiles and cellular immune parameters. BALB/c mice on HFD were categorized as DIO or OB-Res, based on body weight versus lean controls. DIO mice were physiologically distinct from OB-Res mice, whose serum insulin, leptin, gastric inhibitory polypeptide, and eotaxin concentrations remained similar to lean controls. DIO mice had increased macrophage(+) crown-like structures in white adipose tissue, although macrophage percentages were unchanged from OB-Res and lean mice. DIO mice also had decreased splenic CD4(+) T cells, elevated serum GM-CSF, and increased splenic CD11c(+) dendritic cells, but impaired dendritic cell stimulatory capacity (P < 0.05 vs. lean controls). These parameters were unaltered in OB-Res mice versus lean controls. Diet-induced obesity results in alterations in immune and metabolic profiles that are distinct from effects caused by HFD alone. © 2016 The Obesity Society.

  1. Evolutionary causes and consequences of diversified CRISPR immune profiles in natural populations.

    PubMed

    England, Whitney E; Whitaker, Rachel J

    2013-12-01

    Host-pathogen co-evolution is a significant force which shapes the ecology and evolution of all types of organisms, and such interactions are driven by resistance and immunity mechanisms of the host. Diversity of resistance and immunity can affect the co-evolutionary trajectory of both host and pathogen. The microbial CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system is one host immunity mechanism which offers a tractable model for examining the dynamics of diversity in an immune system. In the present article, we review CRISPR variation observed in a variety of natural populations, examine the forces which can push CRISPRs towards high or low diversity, and investigate the consequences of various levels of diversity on microbial populations.

  2. The profile of cytokines and IgG subclasses in BALB/c mice after immunization with Brucella ribosomal gene.

    PubMed

    Abtahi, H; Salmanian, A H; Rafati, S; Nejad, G B; Saffari, M; Ghazavi, A; Mosayebi, G

    2008-11-01

    This study was evaluated the ability of DNA vaccine encoding L7/L12 protein of Brucella sp. to induce cellular and humoral immune responses in BALB/c mice and the profile of cytokines and IgG sub classes were determined. Intra muscular vaccination of mice using L7/L12 gene. Three vaccinations at 3 week intervals were performed. Cytokines and IgG subclasses were analyzed 3 week after the last DNA vaccination. Splenic lymphocytes from L7/L12pCDNA3-vaccinated mice produced high levels of IFNy (3100 pg mL(-1)) and low levels of IL-5 (300 pg mL(-1)), 3 weeks post-vaccination. The L7/L12pCDNA3 immunizations elicited high IgG2a isotype response in mice immunized. This antigen also induced IgG1 titers which were slightly lower than the IgG2a titers. Immunological analysis shows the appropriate immune response in BALB/c mice model after vaccination with L7/L12 gene. The high level of IFNgamma and low level of IL-5 in combination with high IgG2a/IgG1 ratio show the activation of Th1 cell response. The lower bacterial cfu from vaccinated mice in comparison with control groups show the efficiency of L7/L12 DNA vaccination in mice model.

  3. 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.

  4. Skin immune response in the zebrafish, Danio rerio (Hamilton), to Aeromonas hydrophila infection: a transcriptional profiling approach.

    PubMed

    Lü, A-J; Hu, X-C; Wang, Y; Zhu, A-H; Shen, L-L; Tian, J; Feng, Z-Z; Feng, Z-J

    2015-02-01

    Skin plays an important role in innate immune responses to bacterial infection, but its molecular mechanism remains unclear in fish. The transcriptional profiling of the skin immune response to Aeromonas hydrophila infection of the zebrafish, Danio rerio (Hamilton), was performed by Affymetrix microarray analysis. The results showed that 538 genes were differentially expressed, of which 388 genes were up-regulated and 150 genes were down-regulated. The expression patterns for 106 representative genes were observed to be up-regulated in zebrafish skin at 24 and 36 h post-infection, and gene expression changes were clearly greater at 36 h. Gene Ontology classification indicated that 222 genes were significantly associated with the skin immunity, including complement activation, acute-phase response, stress response, chemotaxis and apoptosis. Further Kyoto Encyclopedia of Genes and Genomes analysis showed that the significant pathways included MAPK, p53, Wnt, TGF-β, Notch, ErbB, JAK-STAT, VEGF, mTOR and Calcium signalling in skin immune responses, and several genes (e.g. akt2l, frap1, nras, rac1, xiap) were found to be involved in signalling networks. Moreover, expression changes in nine selected genes were verified by real-time qPCR analysis. This is the first known report on transcriptome analysis in the skin of zebrafish against the pathogen A. hydrophila. © 2014 John Wiley & Sons Ltd.

  5. Inference of immune cell composition on the expression profiles of mouse tissue

    PubMed Central

    Chen, Ziyi; Huang, Anfei; Sun, Jiya; Jiang, Taijiao; Qin, F. Xiao-Feng; Wu, Aiping

    2017-01-01

    Mice are some of the widely used experimental animal models for studying human diseases. Defining the compositions of immune cell populations in various tissues from experimental mouse models is critical to understanding the involvement of immune responses in various physiological and patho-physiological conditions. However, non-lymphoid tissues are normally composed of vast and diverse cellular components, which make it difficult to quantify the relative proportions of immune cell types. Here we report the development of a computational algorithm, ImmuCC, to infer the relative compositions of 25 immune cell types in mouse tissues using microarray-based mRNA expression data. The ImmuCC algorithm showed good performance and robustness in many simulated datasets. Remarkable concordances were observed when ImmuCC was used on three public datasets, one including enriched immune cells, one with normal single positive T cells, and one with leukemia cell samples. To validate the performance of ImmuCC objectively, thorough cross-comparison of ImmuCC predicted compositions and flow cytometry results was done with in-house generated datasets collected from four distinct mouse lymphoid tissues and three different types of tumor tissues. The good correlation and biologically meaningful results demonstrate the broad utility of ImmuCC for assessing immune cell composition in diverse mouse tissues under various conditions. PMID:28084418

  6. Comprehensive transcriptome profiling and functional analysis of the frog (Bombina maxima) immune system.

    PubMed

    Zhao, Feng; Yan, Chao; Wang, Xuan; Yang, Yang; Wang, Guangyin; Lee, Wenhui; Xiang, Yang; Zhang, Yun

    2014-02-01

    Amphibians occupy a key phylogenetic position in vertebrates and evolution of the immune system. But, the resources of its transcriptome or genome are still little now. Bombina maxima possess strong ability to survival in very harsh environment with a more mature immune system. We obtained a comprehensive transcriptome by RNA-sequencing technology. 14.3% of transcripts were identified to be skin-specific genes, most of which were not isolated from skin secretion in previous works or novel non-coding RNAs. 27.9% of transcripts were mapped into 242 predicted KEGG pathways and 6.16% of transcripts related to human disease and cancer. Of 39 448 transcripts with the coding sequence, at least 1501 transcripts (570 genes) related to the immune system process. The molecules of immune signalling pathway were almost presented, several transcripts with high expression in skin and stomach. Experiments showed that lipopolysaccharide or bacteria challenge stimulated pro-inflammatory cytokine production and activation of pro-inflammatory caspase-1. These frog's data can remarkably expand the existing genome or transcriptome resources of amphibians, especially immunity data. The entity of the data provides a valuable platform for further investigation on more detailed immune response in B. maxima and a comparative study with other amphibians.

  7. Meaning in life for patients with cancer: validation of the Life Attitude Profile-Revised Scale.

    PubMed

    Erci, Behice

    2008-06-01

    This paper is a report of a study to adapt the Life Attitude Profile-Revised Scale for Turkish patients with cancer and to evaluate its psychometric properties. Cancer is a life-threatening illness that can challenge the experience of meaning in life. Meaning in life is a multidimensional concept involving meaning and purpose in life, as well as the motivation to find meaning and purpose in life. As meaning in life may be influenced by culture, a culture-sensitive tool is needed for its measurement. A convenience sample of 199 patients with cancer at a Turkish university hospital completed a structured questionnaire including demographic characteristics and the Life Attitude Profile-Revised Scale for Patients with Cancer in 2006. Item analysis, principal components analysis, internal consistency reliability and Cronbach's alpha were used to measure the psychometric properties of the items of the scale. In the assessment of construct validity, identified four factors with eigenvalues greater than 1 explained 46.91% of the total variance. Internal reliability coefficients of these four factor-based scales were 0.73 and 0.82 respectively. The present study provides evidence of the Life Attitude Profile-Revised Scale's validity, reliability and acceptability. This scale should be further evaluated with a larger sample, in different regions in Turkey and diverse populations of world. The scale has potential applications for use both in research and as a screening tool in clinical settings.

  8. The colitis-associated transcriptional profile of commensal Bacteroides thetaiotaomicron enhances adaptive immune responses to a bacterial antigen.

    PubMed

    Hansen, Jonathan J; Huang, Yong; Peterson, Daniel A; Goeser, Laura; Fan, Ting-Jia; Chang, Eugene B; Sartor, R Balfour

    2012-01-01

    Inflammatory bowel diseases (IBD) may be caused in part by aberrant immune responses to commensal intestinal microbes including the well-characterized anaerobic gut commensal Bacteroides thetaiotaomicron (B. theta). Healthy, germ-free HLA-B27 transgenic (Tg) rats develop chronic colitis when colonized with complex gut commensal bacteria whereas non-transgenic (nTg) rats remain disease-free. However, the role of B. theta in causing disease in Tg rats is unknown nor is much known about how gut microbes respond to host inflammation. Tg and nTg rats were monoassociated with a human isolate of B. theta. Colonic inflammation was assessed by histologic scoring and tissue pro-inflammatory cytokine measurement. Whole genome transcriptional profiling of B. theta recovered from ceca was performed using custom GeneChips and data analyzed using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment Analysis (GSEA) software. Western Blots were used to determine adaptive immune responses to a differentially expressed B. theta gene. B. theta monoassociated Tg rats, but not nTg or germ-free controls, developed chronic colitis. Transcriptional profiles of cecal B. theta were significantly different in Tg vs. nTg rats. GSEA revealed that genes in KEGG canonical pathways involved in bacterial growth and metabolism were downregulated in B. theta from Tg rats with colitis though luminal bacterial concentrations were unaffected. Bacterial genes in the Gene Ontology molecular function "receptor activity", most of which encode nutrient binding proteins, were significantly upregulated in B. theta from Tg rats and include a SusC homolog that induces adaptive immune responses in Tg rats. B. theta induces colitis in HLA-B27 Tg rats, which is associated with regulation of bacterial genes in metabolic and nutrient binding pathways that may affect host immune responses. These studies of the host-microbial dialogue may lead to the identification of novel microbial targets for IBD

  9. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    PubMed

    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.

  10. Effects of tussah immunoreactive substances on growth, immunity, disease resistance against Vibrio splendidus and gut microbiota profile of Apostichopus japonicus.

    PubMed

    Ma, Shuhui; Sun, Yongxin; Wang, Fuqiang; Mi, Rui; Wen, Zhixin; Li, Xuejun; Meng, Nan; Li, Yajie; Du, Xingfan; Li, Shuying

    2017-04-01

    Tussah immunoreactive substance (TIS) comprises a number of active chemicals with various bioactivities. The current study investigated the effects of these substances on the sea cucumber Apostichopus japonicus. The specific growth rate (SGR) of TIS-fed sea cucumbers was significantly enhanced, whereas no significant difference in SGR was observed between those soaked in antibiotics and those fed with basal diet only. TIS also improved the immune response of the animals when given at a dose of 1.0% or 2.0%, as shown by increased phagocytic, lysozyme, superoxide dismutase, alkaline phosphatase, acid phosphatase, and catalase activities following injection with live Vibrio splendidus. At a dose of 1.0% or 2.0%, TIS significantly enhanced the immune ability (P < 0.05) of the sea cucumbers, but except for lysozyme activity, other immune indices were reduced one day after the animals were injected with Vibrio splendidus. However, the values of these immune indexes were still significantly higher compared to those of the control groups (P < 0.05). Intestinal micro flora counts and high-throughput sequencing showed that dietary TIS could improve the amount of probiotic bacteria, yielding a 6-fold increase in Bacillus and 10-fold increase in Lactobacillus for sea cucumbers fed with 2.0% TIS diet compared to the control. Furthermore, TIS-containing diet also greatly reduced the number of harmful bacteria, with the number of Vibrio in sea cucumbers fed with 1%TIS diet decreased by 67% compared to the control. The results thus indicated that TIS increased the growth of sea cucumbers and enhanced their resistance to V. splendidus infection by improving the immunity of the animals. TIS also improved the gut microbiota profiles of the animals by increasing the probiotics and reducing the harmful bacteria within their guts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles.

    PubMed

    Pham, T N Q; Mercer, S E; Michalak, T I

    2009-08-01

    Hepatitis C virus (HCV) replicates in immune cells in both chronic hepatitis C (CHC) and occult HCV infection, but the extent of virus replication in this compartment in these opposing infection forms varies greatly. It was unknown whether this could be linked to HCV genotype or to differences in host gene expression shaping the immune response, and whether HCV replication in immune cells is sensitive to endogenous antiviral cytokines. In this study, we uncovered that significantly greater HCV load in peripheral blood mononuclear cells (PBMC), but not in plasma, coincided with HCV genotypes 2 and 3 in CHC, but with genotype 1 in residual occult infection after clinical resolution of hepatitis C. Moreover, PBMC from individuals with occult infection transcribed significantly greater levels of IFN-alpha, IFN-gamma and TNF-alpha, but less interleukin (IL)-10 than those from CHC. In CHC, PBMC with low HCV load expressed significantly more IFN-gamma but less IL-12 than did cells with high virus content. In occult infection, HCV RNA detection in PBMC was associated with much lower IFN-alpha and IL-12 expression. Further, HCV replication in T lymphocytes could be completely eliminated by activation of endogenous IFN-gamma in CHC, but of IFN-alpha in occult infection. In conclusion, CHC and persistent occult HCV infection are characterized by clearly different profiles of antiviral cytokine response in circulating immune cells which are also different from those of healthy individuals. Higher expression of IL-10, combined with lower transcription of IFN-alpha, IFN-gamma and TNF-alpha, is associated with a more robust HCV replication in immune cells.

  12. 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

  13. RNA-seq profiles of immune related genes in the staghorn coral Acropora cervicornis infected with white band disease.

    PubMed

    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

  14. Allometric scaling and prediction of concentration-time profiles of coagulation factors in humans from animals.

    PubMed

    Mahmood, Iftekhar

    2013-09-01

    Allometric scaling is a useful tool in early drug development and can be used for the prediction of human pharmacokinetic (PK) parameters from animal PK parameters. The main objective of this work was to predict concentration-time profiles of coagulation factors in humans in a multi-compartment system using animal PK parameters. The prediction of concentration-time profiles in humans in a multi-compartment system was based on the predicted values of clearance and volumes of distribution (V(c), V(ss) and V(β)) from animals. Five coagulation factors from the literature were chosen that were described by two-compartment model in both humans and animals. Clearance and volumes of distribution from animals were allometrically scaled to humans and then were used to predict concentration-time profiles in humans. The predicted concentration-time profile for a given coagulation factor was accurate for most of the time points. Percent prediction error range varied across coagulation factors. The prediction error >50% was observed either at 1 or a maximum of two time points for a given drug. The study indicated that the allometric scaling can be useful in the prediction of concentration-time profiles of coagulation factors in humans from animals and may be helpful in designing a first-in-human study.

  15. Implementing broad scale childhood immunization decision support as a web service.

    PubMed

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

    2009-11-14

    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.

  16. 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…

  17. Electron-density profiles from automatically scaled digital ionograms. the artist's valley solution. Technical report

    SciTech Connect

    Gamache, R.R.; Kersey, W.T.; Reinisch, B.W.

    1985-07-01

    Electron-density true-height profiles are calculated from automatically scaled Digisonde ionograms. The profile algorithm uses the modified polynomial fitting method separately for the E- and the F-region profile calculations. A new approach to considering the transition region between the E and F layers allows to determine the F profile with good accuracy from the ordinary echo trace. The total electron content between the peak of the E layer and the bottom of the F layer is estimated to account for the observed retardation as a function of frequency on the F trace. No effort is made to find the valley shape since this is not possible from the O trace alone. The new algorithm is tested on some model ionograms.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  20. Transcriptional profiling of immune-related genes in Pacific white shrimp (Litopenaeus vannamei) during ontogenesis.

    PubMed

    Quispe, Ruth L; Justino, Emily B; Vieira, Felipe N; Jaramillo, Michael L; Rosa, Rafael D; Perazzolo, Luciane M

    2016-11-01

    We have performed here a gene expression analysis to determine the developmental stage at the main genes involved in crustacean immune response begin to be expressed and their changes in mRNA abundance during shrimp development. By using a quantitative PCR-based approach, we have measured the mRNA abundance of 24 immune-related genes from different functional categories in twelve developmental stages ranging from fertilized eggs to larval and postlarval stages and also in juveniles. We showed for the first time that the main genes from the RNAi-based post-transcriptional pathway involved in shrimp antiviral immunity are transcribed in all developmental stages, but exhibit a diverse pattern of gene expression during shrimp ontogenesis. On the other hand, hemocyte-expressed genes mainly involved in antimicrobial defenses appeared to be transcribed in larval stages, indicating that hematopoiesis initiates early in development. Moreover, transcript levels of some genes were early detected in fertilized eggs at 0-4 h post-spawning, suggesting a maternal contribution of immune-related transcripts to shrimp progeny. Altogether, our results provide important clues regarding the ontogenesis of hemocytes as well the establishment of antiviral and antimicrobial defenses in shrimp.

  1. Developmental profile of select immune cells in mice infected with Trichinella spiralis during the intestinal phase

    USDA-ARS?s Scientific Manuscript database

    Trichinella spiralis can cause immunosuppression during the intestinal phase of early infection. However, changes in the peripheral blood during T. spiralis early infection remain unclear. Here, select immune cells in mice infected with 500 muscle larvae (ML) of T. spiralis during the intestinal pha...

  2. An examination of obsessive-compulsive symptoms and dimensions using profile analysis via multidimensional scaling (PAMS).

    PubMed

    McKay, Dean; Kim, Se-Kang; Taylor, Steven; Abramowitz, Jonathan S; Tolin, David; Coles, Meredith; Timpano, Kiara R; Olatunji, Bunmi

    2014-05-01

    Contemporary cognitive models of obsessive-compulsive disorder (OCD) emphasize the importance of various types of dysfunctional beliefs in contributing to OC symptoms, such as beliefs about excessive personal responsibility, perfectionism, and intolerance for uncertainty. The present study seeks to further our understanding of the role of these beliefs by identifying the common profiles of such beliefs, using profile analysis via multidimensional scaling (PAMS). In Study 1, a large student sample (N=4079) completed the 44-item obsessive beliefs questionnaire. One major profile, control of thoughts and perfectionism, was extracted. Study 2 examined profiles of the 87-item obsessive beliefs questionnaire in people with obsessive-compulsive disorder (OCD; n=398), other anxiety disorders (n=104), and a sample of undergraduate students (n=285). Inflated responsibility was a prominent subscale in the profiles of all three groups. Only control over thoughts was a unique subscale in the profile obtained for the OCD group, with this group having lower scores compared to the other groups. The results suggest that while inflated responsibility is a significant subscale in the profile of individuals with OCD, it is not a unique contributor; instead, control over thoughts is unique to OCD. The data, as well as recent research investigating obsessive beliefs, suggest the need to revise the contemporary cognitive model of OCD.

  3. MCF: a tool to find multi-scale community profiles in biological networks.

    PubMed

    Gao, Shang; Chen, Alan; Rahmani, Ali; Jarada, Tamer; Alhajj, Reda; Demetrick, Doug; Zeng, Jia

    2013-12-01

    Recent developments of complex graph clustering methods have implicated the practical applications with biological networks in different settings. Multi-scale Community Finder (MCF) is a tool to profile network communities (i.e., clusters of nodes) with the control of community sizes. The controlling parameter is referred to as the scale of the network community profile. MCF is able to find communities in all major types of networks including directed, signed, bipartite, and multi-slice networks. The fast computation promotes the practicability of the tool for large-scaled analysis (e.g., protein-protein interaction and gene co-expression networks). MCF is distributed as an open-source C++ package for academic use with both command line and user interface options, and can be downloaded at http://bsdxd.cpsc.ucalgary.ca/MCF. Detailed user manual and sample data sets are also available at the project website. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Identification of an infectious bronchitis coronavirus strain exhibiting a classical genotype but altered antigenicity, pathogenicity, and innate immunity profile

    PubMed Central

    Lin, Shu-Yi; Li, Yao-Tsun; Chen, You-Ting; Chen, Ting-Chih; Hu, Che-Ming J.; Chen, Hui-Wen

    2016-01-01

    Avian coronavirus infectious bronchitis virus (IBV) poses economic threat to the poultry industry worldwide. Pathogenic IBV 3575/08 was isolated from broilers vaccinated with the attenuated viral vaccine derived from a Taiwan strain 2575/98. In this study, extensive investigations were conducted on the genome sequences, antigenicity, pathogenicity, and host immune responses of several IBV strains in specific-pathogen-free chickens. Sequence analyses revealed that 3575/08 and 2575/98 shared high homology in their structural genes, but not in non-structural accessory proteins such as 3a, 3b and 5b. Despite a high degree of homology in their spike protein genes, cross neutralization test showed low cross protection between 3575/08 and 2575/98, suggesting distinct antigenicity for the two strains. Animal challenge experiments exhibited strong respiratory and renal pathogenicity for 3575/08. In addition, early and prolonged viral shedding and rapid viral dissemination were observed. Immune gene expression profiling by PCR array showed chickens infected with 3575/08 had delayed expression of a subset of early innate immune genes, whereas chickens infected with the wild-type or attenuated-type 2575/08 revealed quick gene induction and efficient virus control. In summary, this study reveals a new IBV strain, which harbors a known local genotype but displays remarkably altered antigenicity, pathogenicity and host defenses. PMID:27876864

  5. Analysis of the transcriptomic profilings of Mandarin fish (Siniperca chuatsi) infected with Flavobacterium columnare with an emphasis on immune responses.

    PubMed

    Zhou, Weidong; Zhang, Yulei; Wen, Yi; Ji, Wei; Zhou, Yang; Ji, Yachan; Liu, Xiaoling; Wang, Weimin; Asim, Muhammad; Liang, Xufang; Ai, Taoshan; Lin, Li

    2015-03-01

    Flavobacterium columnare (FC) is the causative pathogen of columnaris which has caused great economic loss in fish culture worldwide, including in Mandarin fish (Siniperca chuatsi) culture. In the present study, the transcriptomic profiles of the head kidneys from FC-infected and non-infected Mandarin fish were obtained using HiSeq™ 2000 (Illumina). Totally 31,168 unigenes with high quality were obtained. Genes involved in protein folding, metabolism and energy, immune responses, oxidoreductase activity, cell growth and death were identified as enriched classes. 1019 differently expressed genes between the two groups were identified, including 603 up-regulated and 416 down-regulated genes. 27 differently expressed immune related genes were scrutinized, including 17 up-regulated and 10 down-regulated genes. Six of the differently expressed genes were further validated by qRT-PCR. The roles of the immune related genes were discussed. Identification of the host genes in response to FC infection will shed a new light on the prevention of columnaris.

  6. 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

  7. 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

  8. Effects of Shewanella putrefaciens on innate immunity and cytokine expression profile upon high stocking density of gilthead seabream specimens.

    PubMed

    Cordero, Héctor; Morcillo, Patricia; Meseguer, José; Cuesta, Alberto; Esteban, M Ángeles

    2016-04-01

    High stocking density increases the number of emerging diseases triggering economic losses worldwide. Probiotics provide an effective and natural solution for preventing some diseases through an improvement of innate immune system among others. In the present work dietary administration of the probiotic Shewanella putrefaciens (known as Pdp11) was evaluated under stress by high stocking density after 2 and 4 weeks of administration to gilthead seabream (Sparus aurata) specimens. Results showed an increase in cellular peroxidase and respiratory burst activity as well as a modulation of cytokine profile when Pdp11 was administered to fish reared at high stocking density. Overall, our results showed how Pdp11 is not only able to improve to some extent the cellular and humoral immunity but also to increase the gene expression profile of pro-inflammatory cytokines such as il1b or il6 in response to high stocking density in gilthead seabream. These findings may support the potential use of this probiotic as functional feed against stress in fish farms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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

  10. 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

  11. Scaling of confinement and profiles in the EXTRAP T2 reversed-field pinch

    NASA Astrophysics Data System (ADS)

    Welander, A.

    1999-01-01

    In the EXTRAP T2 reversed-field pinch the diagnostic techniques for the measurement of electron density and temperature include; Thomson scattering which gives values at three radial positions in the core (r/a = 0, 0.28, 0.56), Langmuir probes which give values at the edge (r/a > 0.9) and interferometry which gives a line-averaged density. The empirical scaling of electron density and temperature including profile information with global plasma parameters has been studied. The density profile is subject to large variations, with an average parabolic shape when the density is low and flatter shapes when the density is increased. The change in the profile shape can be attributed to a shift in the penetration length of neutrals from the vicinity of the wall. The temperature scales roughly as I/n1/2 where I is the plasma current and n is the density. The temperature profile is always quite flat with lower variations and there is a tendency for a flatter profile at higher temperatures.

  12. Unmasking targets of T cell-mediated antitumor immunity through high-throughput antigen profiling

    PubMed Central

    Battaglia, Sebastiano; Muhitch, Jason B

    2017-01-01

    More than three decades of evidence has established that antitumor immune responses, initially shown with IL-2 treatment, can result in complete, durable eradication of malignant disease in metastatic patients. Recent studies have demonstrated that immune checkpoint blockade as well as cellular therapies, including dendritic cell activation of T cells and adoptive T cell transfer, can induce long-lasting responses. To elicit cytolysis of tumor cells, effector T cells rely on tumor expression of target antigens. However, the antigens targeted during antitumor responses are largely unknown. Technological advancements and availability of sequencing data have paved the way for more efficient screening and validation of tumor-associated antigens and neoantigens derived from non-synonymous mutations targeted by T cells under baseline conditions and in the context of immunotherapy. PMID:27010105

  13. Antioxidant status, metabolic profile and immune response of lambs supplemented with tannin rich Ficus infectoria leaf meal.

    PubMed

    Dey, Avijit; Dutta, Narayan; Pattanaik, Ashok Kumar; Sharma, Kusumakar

    2015-02-01

    To study the effect of supplementation of tanniferous tree leaves Ficus infectoria on antioxidant status and immune response, twenty four lambs were randomly divided into four groups of six each in a completely randomized design and fed either a conventional supplement (CON) or experimental supplements (FILM-I, FILM-II and FILM-III) containing 1.0, 1.5 and 2.0% condensed tannins (CT), respectively by replacement of wheat bran of supplement CON with Ficus infectoria leaf meal (FILM). Blood biochemical profile was monitored in all lambs at 0, 45, 90, 135, 180 days of feeding. Although haemato-biochemical parameters remained similar, there was significant (p < 0.05) improvement in catalase activity, total thiol and protein thiol groups with reduction in lipid peroxidation (LPO) in lambs fed FILM diet irrespective of levels. However, intracellular status of reduced glutathione, and superoxide dismutase activity was improved (p < 0.05) only in FILM-II and FILM-III supplemented lambs. The cell-mediated immune response was significantly (p < 0.05) improved in all the lambs fed FILM supplemented diets. Improved antioxidant status and immunity in FILM supplemented lambs increased voluntary feed intake irrespective of level. However, the average daily gain for a period of 180 d showed a significant (p < 0.05) increase by the supplementation of FILM-II diet containing 1.5% CT. The present study reveals that the supplementation of Ficus infectoria leaf meal up to 21.2% in the concentrate mixture could improve the antioxidant status and immunity in lambs. However, as feed efficiency was reduced at higher levels due to presence of CT, 15.9% supplementation containing 1.5% condensed tannins in concentrate mixture is suggested to improve the health and production performance of lambs.

  14. Transcription profiling of immune genes during parasite infection in susceptible and resistant strains of the flour beetles (Tribolium castaneum).

    PubMed

    Zhong, Daibin; Wang, Mei-Hui; Pai, Aditi; Yan, Guiyun

    2013-05-01

    The flour beetle, Tribolium castaneum, is an intermediate host for the tapeworm Hymenolepis diminuta and has become an important genetic model to explore immune responses to parasite infection in insect hosts. The present study examined the immune responses to tapeworm infection in resistant (TIW1) and susceptible (cSM) strains of the red flour beetle, T. castaneum, using real-time quantitative reverse transcription PCR on 29 immunity-related genes that exhibit antimicrobial properties. Thirteen of the 29 genes showed constitutive differences in expression between the two strains. Fourteen to fifteen of the 29 genes exhibited significant differences in transcription levels when beetles were challenged with tapeworm parasite in the resistant and susceptible strains. Nine genes (GNBP3, cSPH2, lysozyme4, defensin1, PGRP-SA, defensin2, coleoptericin1, attacin2 and serpin29) in cSM and 13 genes (lysozyme2, proPO1, GNBP3, cSPH2, lysozyme4, defensin1, PGRP-SA, defensin2, coleoptericin1, attacin2, proPO2/3, PGRP-LE and PGRP-SB) in TIW1 were up-regulated by infections or showed parasite infection-induced expression. Seven genes (attacin2, coleoptericin1, defensin1, defensin2, lysozyme2, PGRP-SA and PGRP-SB) were more than 10 folds higher in the resistant TIW1 strain than in the susceptible cSM strain after exposure to tapeworm parasites. This study demonstrated the effects of genetic background, the transcription profile to parasite infection, and identified the immunity-related genes that were significantly regulated by the infection of tapeworms in Tribolium beetles.

  15. Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross.

    PubMed

    Green, Richard; Wilkins, Courtney; Thomas, Sunil; Sekine, Aimee; Hendrick, Duncan M; Voss, Kathleen; Ireton, Renee C; Mooney, Michael; Go, Jennifer T; Choonoo, Gabrielle; Jeng, Sophia; de Villena, Fernando Pardo-Manuel; Ferris, Martin T; McWeeney, Shannon; Gale, Michael

    2017-06-07

    The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes. Copyright © 2017 Green et al.

  16. Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross

    PubMed Central

    Green, Richard; Wilkins, Courtney; Thomas, Sunil; Sekine, Aimee; Hendrick, Duncan M.; Voss, Kathleen; Ireton, Renee C.; Mooney, Michael; Go, Jennifer T.; Choonoo, Gabrielle; Jeng, Sophia; de Villena, Fernando Pardo-Manuel; Ferris, Martin T.; McWeeney, Shannon; Gale, Michael

    2017-01-01

    The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes. PMID:28592649

  17. Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.

    PubMed

    Imam, Shahnawaz; Paparodis, Rodis; Sharma, Deepak; Jaume, Juan Carlos

    2014-06-01

    Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (<5%) DN T cells associated with thyroid autoimmunity increased in numbers (>20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity.

  18. Transcriptome profiling indicating canine parvovirus type 2a as a potential immune activator.

    PubMed

    Fan, Xu-Xu; Gao, Yuan; Shu, Long; Wei, Yan-Quan; Yao, Xue-Ping; Cao, Sui-Zhong; Peng, Guang-Neng; Liu, Xiang-Tao; Sun, Shi-Qi

    2016-12-01

    Canine parvovirus type 2a (CPV-2a) is a variant of CPV-2, which is a highly contagious pathogen causing severe gastroenteritis and death in young dogs. However, how CPV-2 participates in cell regulation and immune response remains unknown. In this study, persistently infected MDCK cells were generated through culture passage of the CPV-2a-infected cells for ten generations. Our study showed that CPV-2a induces cell proliferation arrest and cell morphology alternation before the fourth generation, whereas, the cell morphology returns to normal after five times of passages. PCR detection of viral VP2 gene demonstrated that CPV-2a proliferate with cell passage. An immunofluorescence assay revealed that CPV-2a particles were mainly located in the cell nuclei of MDCK cell. Then transcriptome microarray revealed that gene expression pattern of MDCK with CPV-2a persistent infection is distinct compared with normal cells. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genome pathway analysis demonstrated that CPV-2a infection induces a series of membrane-associated genes expression, including many MHC protein or MHC-related complexes. These genes are closely related to signaling pathways of virus-host interaction, including antigen processing and presentation pathway, intestinal immune network, graft-versus-host disease, and RIG-I-like helicases signaling pathway. In contrast, the suppressed genes mediated by CPV-2a showed low enrichment in any category, and were only involved in pathways linking to synthesis and metabolism of amino acids, which was confirmed by qPCR analysis. Our studies indicated that CPV-2a is a natural immune activator and has the capacity to activate host immune responses, which could be used for the development of antiviral strategy and biomaterial for medicine.

  19. 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

  20. Immune response of Staphylococcus aureus strains in a mouse mastitis model is linked to adaptive capacity and genotypic profiles.

    PubMed

    Pereyra, Elizabet A L; Sacco, Sofía C; Duré, Andrea; Baravalle, Celina; Renna, María S; Andreotti, Carolina S; Monecke, Stefan; Calvinho, Luis F; Dallard, Bibiana E

    2017-05-01

    Staphylococcus aureus is one of the most frequently isolated major pathogens from intramammary infections (IMI) worldwide. The mechanisms by which S. aureus IMI are established and maintained in dairy cows involve both bacterial escape strategies and modulation of the host immune response. Moreover, it was shown that different S. aureus strains have varying effects on the immune response. The aim of this study was to investigate the immune response in a mouse mastitis model of two S. aureus strains isolated from bovine IMI with different clinical manifestation (persistent-P or non-persistent-NP), phenotypic and genotypic profile. Both strains were capable of establishing an IMI after 264h post inoculation (pi). Strain A (NP) showed a more aggressive behaviour than strain B (P) at early stages of IMI, while strain B multiplied initially at a lower rate but increased its replication capacity from 120h pi to the end of the study (264h pi). Strain A triggered a stronger initial inflammatory response compared with strain B inducing higher gene and protein expression of TLR2, NF-κB activation and higher gene expression of IL-1α at initial stage of IMI (6-12h pi) but inducing extensive mammary tissue damage. Immune cells response was different for each S. aureus strain throughout the course of infection, showing mammary glands inoculated with strain A greater initial immune cells stimulation compared with strain B and then a second immune cells stimulation (from 120 to 264h pi) represented by monocytes-macrophages, T and B lymphocytes, mainly stimulated by strain B, consistent with inflammatory process becoming chronic. Strain-specific pathogenicity observed underscores the importance of pathogen factors in the progression of the infectious process. These results contribute to increase the available information on host-pathogen interaction and point out for the need of further research to expand the knowledge about these interactions for developing new strategies to

  1. Transcriptome Profile of the Chicken Thrombocyte: New Implications as an Advanced Immune Effector Cell

    PubMed Central

    Ferdous, Farzana; Saski, Christopher; Bridges, William; Burns, Matthew; Dunn, Heather; Elliott, Kathryn; Scott, Thomas R.

    2016-01-01

    Thrombocytes are nucleated platelets involved in immune functions such as pathogen recognition and release of pro-inflammatory bioactive compounds when exposed to bacterial and viral molecules. However, the complete role of these cells in innate and adaptive immune responses is not understood, and little is known about their biology at the molecular-genetic level. Highly sensitive RNA-sequencing technologies were used to analyze the complete transcriptome of thrombocytes for the first time with analytical resolution focused on cell-based components of the immune system/response. Amongst all the genes listed in the current chicken genome assembly, 10,041 gene transcripts were found in the chicken thrombocyte. After 1-hour in vitro stimulation with lipopolysaccharide (LPS, Salmonella minnesota), 490 genes were upregulated and 359 genes were downregulated, respectively, with at least a 1-fold change relative to unexposed thrombocytes. Additionally, by constructing a de novo assembly, we were able to identify a total of 3,030 novel genes in the thrombocyte transcriptome. The information generated here is useful in development of novel solutions to lower the economic burden and zoonotic threat that accompanies infectious diseases for birds and fish. In addition, the resources created here have translational utility as a model system to find orthologous genes and genes related to its enucleated counterpart, the platelet. PMID:27711235

  2. Innate immune performance and steroid hormone profiles of pregnant versus nonpregnant cottonmouth snakes (Agkistrodon piscivorus).

    PubMed

    Graham, Sean P; Earley, Ryan L; Guyer, Craig; Mendonça, Mary T

    2011-12-01

    Squamates (lizards and snakes) have independently evolved viviparity over 100 times, and exhibit a wide range of maternal investment in developing embryos from the extremes of lecithotrophic oviparity to matrotrophic viviparity. This group therefore provides excellent comparative opportunities for studying endocrine and immune involvement during pregnancy, and their possible interactions. We studied the cottonmouth (Agkistrodon piscivorus), since they exhibit limited placentation (e.g., ovoviviparity), allowing comparison with squamate species hypothesized to require considerable maternal immune modulation due to the presence of a more extensive placental connection. Furthermore, the cottonmouth's biennial reproductive cycle provides an opportunity for simultaneously comparing pregnant and non-pregnant females in the wild. We document significantly elevated concentrations of progesterone (P4) and significantly lower concentrations of estradiol (E2) in pregnant females relative to non-pregnant females. Pregnant females had lower plasma bacteria lysis capacity relative to non-pregnant females. This functional measure of innate immunity is a proxy for complement performance, and we also determined significant correlations between P4 and decreased complement performance in pregnant females. These findings are consistent with studies that have determined P4's role in complement modulation during pregnancy in mammals, and thus this study joins a growing number of studies that have demonstrated convergent and/or conserved physiological mechanisms regulating viviparous reproduction in vertebrates.

  3. Analysis of dysregulation of immune system in pancreatic cancer based on gene expression profile.

    PubMed

    Wang, Baosheng; Sun, Shaolong; Liu, Zhen

    2014-07-01

    The aim of this study was to explore the dysregulated expression of the immune system in pancreatic cancer and clarify the pathogenesis of pancreatic cancer. The Dataset GSE15471 was downloaded from GEO database, Student's t test was used to screen differentially expressed genes (DEGs) between the pancreatic cancer group and the normal control group. Kyoto Encyclopedia of Genes and Genomes (KEGG) provides functional annotation was employed to explore the significant DEGs involved in biological functions. We got 988 significantly DEGs, including 832 up-regulated genes and 156 down-regulated genes. The ratio of up-regulated genes and down-regulated genes was 5.3. Total 13 biological pathways which were significant enriched with DEGs by KEGG pathway enrichment analysis. Finally, we constructed a overall network of the immune system in pancreatic cancer with these biological pathways information. Our study reveals that dysregulated pathways in pancreatic cancer associated with the immune system. Besides, we also identify some important molecular biomarkers of the pancreatic cancer, including CXCR4 and CD4. Dysfunctional pathways and important molecular biomarkers of pancreatic cancer will provide useful information for potential treatment of pancreatic cancer.

  4. Leveraging large-scale behavioral profiling in zebrafish to explore neuroactive polypharmacology

    PubMed Central

    McCarroll, Matthew N; Gendelev, Leo; Keiser, Michael J; Kokel, David

    2016-01-01

    Many psychiatric drugs modulate the nervous system through multi-target mechanisms. However, systematic identification of multi-target compounds has been difficult using traditional in vitro screening assays. New approaches to phenotypic profiling in zebrafish can help researchers identify novel compounds with complex polypharmacology. For example, large-scale behavior-based chemical screens can rapidly identify large numbers of structurally diverse and phenotype-related compounds. Once these compounds have been identified, a systems-level analysis of their structures may help to identify statistically enriched target pathways. Together, systematic behavioral profiling and multi-target predictions may help researchers identify new behavior-modifying pathways and CNS therapeutics. PMID:26845413

  5. 1H NMR-based profiling reveals differential immune-metabolic networks during influenza virus infection in obese mice.

    PubMed

    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.

  6. 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.

  7. Profiles of the National Institutes of Health Stroke Scale items as a predictor of patient outcome.

    PubMed

    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

    2013-08-01

    Initial National Institutes of Health Stroke Scale (NIHSS) score is highly predictive of outcome after ischemic stroke. We examined whether grouping strokes by presence of individual NIHSS symptoms could provide prognostic information additional or alternative to the NIHSS total score. Ischemic strokes from the Greater Cincinnati Northern Kentucky Stroke Study in 2005 were used to develop the model. Latent class analysis 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. A total of 2112 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 [interquartile range], 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. Six rNIHSS profiles were identifiable using latent class analysis. In particular, 2 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.

  8. 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

  9. 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

  10. Transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure.

    PubMed

    Malhotra, Shikha; Yen, Judy Y; 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.

  11. Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis.

    PubMed

    Hendrickx, Wouter; Simeone, Ines; Anjum, Samreen; Mokrab, Younes; Bertucci, François; Finetti, Pascal; Curigliano, Giuseppe; Seliger, Barbara; Cerulo, Luigi; Tomei, Sara; Delogu, Lucia Gemma; Maccalli, Cristina; Wang, Ena; Miller, Lance D; Marincola, Francesco M; Ceccarelli, Michele; Bedognetti, Davide

    2017-01-01

    Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection. The T helper 1 (Th-1) phenotype (ICR4), which also displays upregulation of immune-regulatory transcripts such as PDL1, PD1, FOXP3, IDO1, and CTLA4, was associated with prolonged patients' survival. We validated these findings in an independent meta-cohort of 1,954 breast cancer gene expression data. Chromosome segment 4q21, which includes genes encoding for the Th-1 chemokines CXCL9-11, was significantly amplified only in the immune favorable phenotype (ICR4). The mutation and neoantigen load progressively decreased from ICR4 to ICR1 but could not fully explain immune phenotypic differences. Mutations of TP53 were enriched in the immune favorable phenotype (ICR4). Conversely, the presence of MAP3K1 and MAP2K4 mutations were tightly associated with an immune-unfavorable phenotype (ICR1). Using both the TCGA and the validation dataset, the degree of MAPK deregulation segregates breast tumors according to their immune disposition. These findings suggest that mutation-driven perturbations of MAPK pathways are linked to the negative regulation of intratumoral immune response in breast cancer. Modulations of MAPK pathways could be experimentally tested to enhance breast cancer immune sensitivity.

  12. Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis

    PubMed Central

    Simeone, Ines; Anjum, Samreen; Mokrab, Younes; Bertucci, François; Finetti, Pascal; Curigliano, Giuseppe; Cerulo, Luigi; Tomei, Sara; Delogu, Lucia Gemma; Maccalli, Cristina; Miller, Lance D.; Ceccarelli, Michele

    2017-01-01

    ABSTRACT Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection. The T helper 1 (Th-1) phenotype (ICR4), which also displays upregulation of immune-regulatory transcripts such as PDL1, PD1, FOXP3, IDO1, and CTLA4, was associated with prolonged patients' survival. We validated these findings in an independent meta-cohort of 1,954 breast cancer gene expression data. Chromosome segment 4q21, which includes genes encoding for the Th-1 chemokines CXCL9-11, was significantly amplified only in the immune favorable phenotype (ICR4). The mutation and neoantigen load progressively decreased from ICR4 to ICR1 but could not fully explain immune phenotypic differences. Mutations of TP53 were enriched in the immune favorable phenotype (ICR4). Conversely, the presence of MAP3K1 and MAP2K4 mutations were tightly associated with an immune-unfavorable phenotype (ICR1). Using both the TCGA and the validation dataset, the degree of MAPK deregulation segregates breast tumors according to their immune disposition. These findings suggest that mutation-driven perturbations of MAPK pathways are linked to the negative regulation of intratumoral immune response in breast cancer. Modulations of MAPK pathways could be experimentally tested to enhance breast cancer immune sensitivity. PMID:28344865

  13. 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.

  14. 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.

  15. Adaptation to the Spanish population of the Substance Use Risk Profile Scale (SURPS) and psychometric properties.

    PubMed

    Fernández-Calderón, Fermín; Díaz-Batanero, Carmen; Rojas-Tejada, Antonio J; Castellanos-Ryan, Natalie; Lozano-Rojas, Óscar M

    2017-07-14

    The identification of different personality risk profiles for substance misuse is useful in preventing substance-related problems. This study aims to test the psychometric properties of a new version of the Substance Use Risk Profile Scale (SURPS) for Spanish college students. Cross-sectional study with 455 undergraduate students from four Spanish universities. A new version of the SURPS, adapted to the Spanish population, was administered with the Beck Hopelessness Scale, the UPPS-P Impulsive Behavior Scale, the State-Trait Anxiety Inventory (STAI) and the Alcohol Use Disorders Identification Test (AUDIT). Internal consistency reliability ranged between 0.652 and 0.806 for the four SURPS subscales, while reliability estimated by split-half coefficients varied from 0.686 to 0.829. The estimated test-retest reliability ranged between 0.733 and 0.868. The expected four-factor structure of the original scale was replicated. As evidence of convergent validity, we found that the SURPS subscales were significantly associated with other conceptually-relevant personality scales and significantly associated with alcohol use measures in theoretically-expected ways. This SURPS version may be a useful instrument for measuring personality traits related to vulnerability to substance use and misuse when targeting personality with preventive interventions.

  16. Mechanistic Feature-Scale Profile Simulation of SiO2LPCVD by TEOS Pyrolysis

    SciTech Connect

    CALE, TIMOTHY S.; LABUN, ANDREW H.; MOFFAT, HARRY K.

    1999-09-13

    Simulation of chemical vapor deposition (CVD) in submicron features typical of semiconductor devices has been facilitated by extending the EVOLVE thin film etch and deposition simulation code to use thermal reaction mechanisms expressed in the Chemkin format. This allows consistent coupling between EVOLVE and reactor simulation codes that use Chemkin. In an application of a reactor-scale simulation code providing surface fluxes to a feature-scale simulation code, a proposed reaction mechanism for TEOS pyrolysis to deposit SiO{sub 2}, which had been applied successfully to reactor-scale simulation, is seen not to predict the low step coverage over trenches observed under short reactor residence time conditions. An apparent discrepancy between the mechanism and profile-evolution observations is a reduced degree of sensitivity of the deposition rate to the presence of reaction products, i.e., the byproduct inhibition effect is underpredicted. The cause of the proposed mechanism's insensitivity to byproduct inhibition is investigated with the combined reactor and topography simulators first by manipulating the surface to volume ratio of a simulated reactor and second by calibrating parameters in the proposed mechanism such as the calculated free energies of surface molecules. The conclusion is that the byproduct inhibition can not be enhanced to fit profile evolution data without comprising agreement with reactor scale data by simply adjusting mechanism parameters. Thus, additional surface reaction channels seem to be required to reproduce simultaneously experimental reactor-scale growth rates and experimental step coverages.

  17. Understanding and Predicting Profile Structure and Parametric Scaling of Intrinsic Rotation

    NASA Astrophysics Data System (ADS)

    Wang, Weixing

    2016-10-01

    It is shown for the first time that turbulence-driven residual Reynolds stress can account for both the shape and magnitude of the observed intrinsic toroidal rotation profile. Nonlinear, global gyrokinetic simulations using GTS of DIII-D ECH plasmas indicate a substantial ITG fluctuation-induced non-diffusive momentum flux generated around a mid-radius-peaked intrinsic toroidal rotation profile. The non-diffusive momentum flux is dominated by the residual stress with a negligible contribution from the momentum pinch. The residual stress profile shows a robust anti-gradient, dipole structure in a set of ECH discharges with varying ECH power. Such interesting features of non-diffusive momentum fluxes, in connection with edge momentum sources and sinks, are found to be critical to drive the non-monotonic core rotation profiles in the experiments. Both turbulence intensity gradient and zonal flow ExB shear are identified as major contributors to the generation of the k∥-asymmetry needed for the residual stress generation. By balancing the residual stress and the momentum diffusion, a self-organized, steady-state rotation profile is calculated. The predicted core rotation profiles agree well with the experimentally measured main-ion toroidal rotation. The validated model is further used to investigate the characteristic dependence of global rotation profile structure in the multi-dimensional parametric space covering turbulence type, q-profile structure and collisionality with the goal of developing physics understanding needed for rotation profile control and optimization. Interesting results obtained include intrinsic rotation reversal induced by ITG-TEM transition in flat-q profile regime and by change in q-profile from weak to normal shear.. Fluctuation-generated poloidal Reynolds stress is also shown to significantly modify the neoclassical poloidal rotation in a way consistent with experimental observations. Finally, the first-principles-based model is applied

  18. Implementation of atomic layer etching of silicon: Scaling parameters, feasibility, and profile control

    SciTech Connect

    Ranjan, Alok Wang, Mingmei; Sherpa, Sonam D.; Rastogi, Vinayak; Koshiishi, Akira; Ventzek, Peter L. G.

    2016-05-15

    Atomic or layer by layer etching of silicon exploits temporally segregated self-limiting adsorption and material removal steps to mitigate the problems associated with continuous or quasicontinuous (pulsed) plasma processes: selectivity loss, damage, and profile control. Successful implementation of atomic layer etching requires careful choice of the plasma parameters for adsorption and desorption steps. This paper illustrates how process parameters can be arrived at through basic scaling exercises, modeling and simulation, and fundamental experimental tests of their predictions. Using chlorine and argon plasma in a radial line slot antenna plasma source as a platform, the authors illustrate how cycle time, ion energy, and radical to ion ratio can be manipulated to manage the deviation from ideality when cycle times are shortened or purges are incomplete. Cell based Monte Carlo feature scale modeling is used to illustrate profile outcomes. Experimental results of atomic layer etching processes are illustrated on silicon line and space structures such that iso-dense bias and aspect ratio dependent free profiles are produced. Experimental results also illustrate the profile control margin as processes move from atomic layer to multilayer by layer etching. The consequence of not controlling contamination (e.g., oxygen) is shown to result in deposition and roughness generation.

  19. Large-scale Phenotypic Profiling of Gene Deletion Mutants in Candida glabrata

    PubMed Central

    Tscherner, Michael; Kuchler, Karl

    2016-01-01

    Here, we describe a method enabling the phenotypic profiling of genome-scale deletion collections of fungal mutants to detect phenotypes for various stress conditions. These stress conditions include among many others antifungal drug susceptibility, temperature-induced and osmotic as well as heavy metal or oxidative stress. The protocol was extensively used to phenotype a collection of gene deletion mutants in the human fungal pathogen Candida glabrata (C. glabrata) (Schwarzmüller et al., 2014). PMID:27774498

  20. 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.

  1. Transcriptomic profiling of microglia reveals signatures of cell activation and immune response, during experimental cerebral malaria

    PubMed Central

    Capuccini, Barbara; Lin, Jingwen; Talavera-López, Carlos; Khan, Shahid M.; Sodenkamp, Jan; Spaccapelo, Roberta; Langhorne, Jean

    2016-01-01

    Cerebral malaria is a pathology involving inflammation in the brain. There are many immune cell types activated during this process, but there is little information on the response of microglia, in this severe complication. We examined microglia by genome wide transcriptomic analysis in a model of experimental cerebral malaria (ECM), in which C57BL/6 mice are infected with Plasmodium berghei ANKA. Thousands of transcripts were differentially expressed in microglia at two different time points during infection. Proliferation of microglia was a dominant feature before the onset of ECM, and supporting this, we observed an increase in numbers of these cells in the brain. When cerebral malaria symptoms were manifest, genes involved in immune responses and chemokine production were upregulated, which were possibly driven by Type I Interferon. Consistent with this hypothesis, in vitro culture of a microglial cell line with Interferon-β, but not infected red blood cells, resulted in production of several of the chemokines shown to be upregulated in the gene expression analysis. It appears that these responses are associated with ECM, as microglia from mice infected with a mutant P. berghei parasite (ΔDPAP3), which does not cause ECM, did not show the same level of activation or proliferation. PMID:27991544

  2. Transcriptomic profiling of microglia reveals signatures of cell activation and immune response, during experimental cerebral malaria.

    PubMed

    Capuccini, Barbara; Lin, Jingwen; Talavera-López, Carlos; Khan, Shahid M; Sodenkamp, Jan; Spaccapelo, Roberta; Langhorne, Jean

    2016-12-19

    Cerebral malaria is a pathology involving inflammation in the brain. There are many immune cell types activated during this process, but there is little information on the response of microglia, in this severe complication. We examined microglia by genome wide transcriptomic analysis in a model of experimental cerebral malaria (ECM), in which C57BL/6 mice are infected with Plasmodium berghei ANKA. Thousands of transcripts were differentially expressed in microglia at two different time points during infection. Proliferation of microglia was a dominant feature before the onset of ECM, and supporting this, we observed an increase in numbers of these cells in the brain. When cerebral malaria symptoms were manifest, genes involved in immune responses and chemokine production were upregulated, which were possibly driven by Type I Interferon. Consistent with this hypothesis, in vitro culture of a microglial cell line with Interferon-β, but not infected red blood cells, resulted in production of several of the chemokines shown to be upregulated in the gene expression analysis. It appears that these responses are associated with ECM, as microglia from mice infected with a mutant P. berghei parasite (ΔDPAP3), which does not cause ECM, did not show the same level of activation or proliferation.

  3. Leucocyte profiles and H/L ratios in chicks of Red-tailed Tropicbirds reflect the ontogeny of the immune system.

    PubMed

    Dehnhard, Nina; Quillfeldt, Petra; Hennicke, Janos C

    2011-07-01

    Immune defence is fundamentally important for the survival prospects of young animals. While innate immunity offers initial protection from a variety of pathogens, acquired immunity responds more specifically to pathogens, but is considered to be more costly and to respond slower. Moreover, the acquired immunity is not yet fully developed in neonatal chicks. Little is known about the ontogeny of the immune system of wild birds. Long-lived seabirds, with their slow chick development, are good models to investigate how young birds invest in both arms of their immune system. We determined leucocyte profiles and heterophil to lymphocyte (H/L) ratios of Red-tailed Tropicbirds (Phaeton rubricauda westralis) on Christmas Island, Indian Ocean. Young chicks (N = 10) had significantly higher H/L ratios than older chicks (N = 19), while adults (N = 47) showed intermediate values and did not differ from either chick age class. High H/L ratios in young chicks were caused by high initial numbers of heterophils per 10,000 erythrocytes that declined with age. In contrast, the number of lymphocytes per 10,000 erythrocytes was similar for young and older chicks. These data suggest that young chicks invested heavily in innate immunity to protect themselves from pathogens, while investment into acquired immunity became more important in older chicks with a functional acquired immune response. Body condition did not have a significant influence on any leucocyte parameter.

  4. 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

  5. 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

  6. 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

  7. The environmental quality of Doñana surrounding areas affects the immune transcriptional profile of inhabitant crayfish Procambarus clarkii.

    PubMed

    Osuna-Jiménez, Inmaculada; Abril, Nieves; Vioque-Fernández, Amalia; Gómez-Ariza, José Luis; Prieto-Álamo, María-José; Pueyo, Carmen

    2014-09-01

    This study aimed to identify differentially expressed genes in Procambarus clarkii crayfish collected from locations of different environmental qualities in the Doñana National Park surrounding areas. The pollution sustained by the crayfish was confirmed by their hepatopancreatic metal concentration. We generated forward and reverse libraries by suppression subtractive hybridization (SSH) to analyze the transcriptional profiles of crayfish from moderately and highly polluted zones in comparison with the control site within the Doñana Biological Reserve. Forty-three differentially expressed genes were detected, and most of them were identified as genes involved in a variety of biological functions, particularly in the innate immune response. To verify the SSH results and assess interindividual variability nine transcripts (ALP, AST, BTF3, CHIT, CTS, ferritin, HC, HC2, and SPINK4) were selected for absolute quantification by real-time qRT-PCR. The qRT-PCR data revealed substantial differences in the absolute amounts of the nine transcripts and confirmed their up- or down-regulation in the polluted sites. Additionally, a positive and significant linear correlation was found between the hepatopancreatic copper concentration and the levels of the transcripts encoding hemocyanins. Finally, the transcriptomic study was complemented with a detailed analysis of SNP profiles of the selected transcripts that revealed point mutations that might underlie adaptive response to environmental stress in P. clarkii. Overall, this work provides novel insights into the molecular pathways that could mediate the response to environmental pollutants in P. clarkii emphasizing the central role of the immune function and thus, should clearly benefit further immunotoxicological research in this organism.

  8. Pollen lipidomics: lipid profiling exposes a notable diversity in 22 allergenic pollen and potential biomarkers of the allergic immune response.

    PubMed

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

    2013-01-01

    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. 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. 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 lipids vary greatly among allergenic species and contain many molecules

  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. Immune-metabolic profiling of anorexic patients reveals an anti-oxidant and anti-inflammatory phenotype.

    PubMed

    Omodei, Daniela; Pucino, Valentina; Labruna, Giuseppe; Procaccini, Claudio; Galgani, Mario; Perna, Francesco; Pirozzi, Daniele; De Caprio, Carmela; Marone, Gianni; Fontana, Luigi; Contaldo, Franco; Pasanisi, Fabrizio; Matarese, Giuseppe; Sacchetti, Lucia

    2015-03-01

    Anorexia nervosa (AN) is an excessive form of calorie restriction (CR) associated with pathological weight loss and alterations of the immune system. However, AN patients seem to be protected from common viral infections. To investigate the metabolic and molecular adaptations induced by sustained extreme CR in the peripheral blood mononuclear cells (PBMCs) of patients with restrictive alimentary AN. Inflammatory cytokines and adipokines were measured in 15 young (age range, 15-24 years) AN female patients and 20 age-matched healthy controls. Isolated PBMCs were immunophenotyped by flow cytometry, and glycolysis and mitochondrial respiration were determined by measuring the extracellular acidification and oxygen consumption rate. Stress resistance to H2O2 and the antioxidant transcriptional profile of PBMCs and human fibroblasts incubated with sera from AN patients were also determined. Compared with controls, AN patients (BMI, 15.9±0.4 kg/m(2)) had significantly fewer leucocytes, lymphocytes and NK cells, lower serum concentrations of leptin, IGF-1 and sTNFR1, and higher levels of adiponectin, sCD40L and sICAM-1 (p<0.05). IL-1β, TNFα, and IL-6 produced by PBMC cultured with autologous serum for 48 h were significantly lower in AN patients than in controls (p<0.01). Moreover, glycolysis and mitochondrial respiration were lower, and the antioxidant transcriptional profile was higher in the PBMCs of AN patients. Fibroblasts cultured in serum from AN patients showed a 24% increase in resistance to H2O2 damage. Extreme CR in AN patients is associated with a reduction in several immune cell populations, but with higher antioxidant potential, stress resistance and an anti-inflammatory status. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Trancriptomic profiling revealed the signatures of acute immune response in tilapia (Oreochromis niloticus) following Streptococcus iniae challenge.

    PubMed

    Zhu, Jiajie; Li, Chao; Ao, Qiuwei; Tan, Yun; Luo, Yongju; Guo, Yafen; Lan, Ganqiu; Jiang, Hesheng; Gan, Xi

    2015-10-01

    Streptococcus iniae is the most significant bacterial disease of tilapia throughout the world, and commonly leads to tremendous economic losses. In contrast to other important fish species, our knowledge about the molecular mechanisms of tilapia in response to bacterial infection is still limited. Here, therefore, we utilized RNA-seq to first profiling of host responses in tilapia spleen following S. iniae infection at transcriptome level. A total of 223 million reads were obtained and assembled into 192,884 contigs with average length 844 bp. Gene expression analysis between control and infected samples at 5 h, 50 h, and 7 d revealed 1475 differentially expressed genes. In particular, the differentially expressed gene set was dramatically induced as early as 5 h, and rapidly declined to basal levels at 50 h. Enrichment and pathway analysis of the differentially expressed genes revealed the centrality of the pathogen attachment and recognition, cytoskeletal rearrangement and immune activation/inflammation in the pathogen entry and host inflammatory responses. Understanding of these responses can highlight mechanisms of tilapia host defense, and expand our knowledge of teleost immunology. Our findings will set a foundation of valuable biomarkers for future individual, strain, and family-level studies to evaluate immune effect of vaccine and individual response in host defense mechanisms to S. iniae infection, to select disease resistant families and strains.

  12. Transcriptional profile of the immune response in the lungs of patients with active tuberculosis.

    PubMed

    Grassi, Manuela; Bocchino, Marialuisa; Marruchella, Almerico; Volpe, Elisabetta; Saltini, Cesare; Colizzi, Vittorio; Mariani, Francesca

    2006-10-01

    Despite advances in diagnosis and treatment, Mycobacterium tuberculosis causes active disease in about 8 million people worldwide annually. The study of the interplay between the host and the pathogen at the site of infection in human TB may contribute to elucidate the pathogenesis of the disease. In this work, using macroarray technology and real-time PCR, we analyzed the modulation of 847 genes encoding immune-inflammatory mediators in BALF samples of patients affected by active pulmonary TB (PTB) and control patients affected by non-TB diseases. The data show that the PTB milieu contains a complex network of gene activation. Different genes with adhesive properties and involved in tissue repair and fibrosis were modulated. In TB patients, we observed the up-regulation of cytokines, including IFN-gamma and IFN-gamma pathway genes, of several apoptotic genes, and of potent transcriptional activators. These findings can contribute to elucidate the mechanisms of MTB pathogenicity in humans.

  13. Tumor immune profiling predicts response to anti–PD-1 therapy in human melanoma

    PubMed Central

    Daud, Adil I.; Loo, Kimberly; Pauli, Mariela L.; Sanchez-Rodriguez, Robert; Sandoval, Priscila Munoz; Taravati, Keyon; Tsai, Katy; Nosrati, Adi; Nardo, Lorenzo; Alvarado, Michael D.; Algazi, Alain P.; Pampaloni, Miguel H.; Lobach, Iryna V.; Hwang, Jimmy; Pierce, Robert H.; Gratz, Iris K.; Krummel, Matthew F.

    2016-01-01

    BACKGROUND. Immune checkpoint blockade is revolutionizing therapy for advanced cancer, but many patients do not respond to treatment. The identification of robust biomarkers that predict clinical response to specific checkpoint inhibitors is critical in order to stratify patients and to rationally select combinations in the context of an expanding array of therapeutic options. METHODS. We performed multiparameter flow cytometry on freshly isolated metastatic melanoma samples from 2 cohorts of 20 patients each prior to treatment and correlated the subsequent clinical response with the tumor immune phenotype. RESULTS. Increasing fractions of programmed cell death 1 high/cytotoxic T lymphocyte–associated protein 4 high (PD-1hiCTLA-4hi) cells within the tumor-infiltrating CD8+ T cell subset strongly correlated with response to therapy (RR) and progression-free survival (PFS). Functional analysis of these cells revealed a partially exhausted T cell phenotype. Assessment of metastatic lesions during anti–PD-1 therapy demonstrated a release of T cell exhaustion, as measured by an accumulation of highly activated CD8+ T cells within tumors, with no effect on Tregs. CONCLUSIONS. Our data suggest that the relative abundance of partially exhausted tumor-infiltrating CD8+ T cells predicts response to anti–PD-1 therapy. This information can be used to appropriately select patients with a high likelihood of achieving a clinical response to PD-1 pathway inhibition. FUNDING. This work was funded by a generous gift provided by Inga-Lill and David Amoroso as well as a generous gift provided by Stephen Juelsgaard and Lori Cook. PMID:27525433

  14. Beyond pattern recognition: five immune checkpoints for scaling the microbial threat.

    PubMed

    Blander, J Magarian; Sander, Leif E

    2012-02-24

    Pattern recognition by the innate immune system enables the detection of microorganisms, but how the level of microbial threat is evaluated - a process that is crucial for eliciting measured antimicrobial responses with minimal inflammatory tissue damage - is less well understood. New evidence has shown that features of microbial viability can be detected by the immune system and thereby induce robust responses that are not warranted for dead microorganisms. Here, we propose five immune checkpoints that, as defined here, collectively determine the gravity of microbial encounters.

  15. Evaluation of a DNA Aβ42 Vaccine in Aged NZW Rabbits: Antibody Kinetics and Immune Profile after Intradermal Immunization with Full-Length DNA Aβ42 Trimer

    PubMed Central

    Lambracht-Washington, Doris; Fu, Min; Wight-Carter, Mary; Riegel, Matthew; Rosenberg, Roger N.

    2017-01-01

    A pathological hallmark of Alzheimer’s disease (AD) are amyloid plaques in the brain consisting of aggregated amyloid-β 42 peptide (Aβ42) derived from cellular amyloid-β protein precursor (AβPP). Based on successful experiments in mouse AD models, active immunization with Aβ42 peptide and passive immunizations with anti-Aβ42 antibodies were started in clinical trials. Active Aβ42 peptide immunization in humans had led to an inflammatory autoimmune response, and the trial was stopped. Passive immunizations had shown some effects in slowing AD pathology. Active DNA Aβ42 immunizations administered with the gene gun into the skin elicits a different immune response and is non-inflammatory. While in rodents, good responses had been found for this type of immunization, positive results in larger mammals are missing. We present here results from sixteen New Zealand White Rabbits, which underwent intradermal DNA Aβ42 immunization via gene gun. The humoral immune response was analyzed from blood throughout the study, and cellular immune responses were determined from spleens at the end of the study. A good anti-Aβ antibody response was found in the rabbit model. The T cell response after re-stimulation in cell culture showed no IFNγ producing cells when ELISPOT assays were analyzed from PBMC, but low numbers of IFNγ and IL-17 producing cells were found in ELISPOTS from spleens (both 5 immunizations). Brains from immunized rabbits showed no signs of encephalitis. Based on these results, DNA Aβ42 immunization is highly likely to be safe and effective to test in a possible clinical AD prevention trial in patients. PMID:28222511

  16. Plasminogen Activator Inhibitor-1 4G/5G Polymorphism is Associated with Reproductive Failure: Metabolic, Hormonal, and Immune Profiles.

    PubMed

    Salazar Garcia, Maria D; Sung, Nayoung; Mullenix, Thomas M; Dambaeva, Svetlana; Beaman, Kenneth; Gilman-Sachs, Alice; Kwak-Kim, Joanne

    2016-07-01

    Association between PAI-1 4G/5G polymorphism and reproductive failures has been postulated. We aimed to investigate its impact on metabolic, hormonal, and immune profiles of women with reproductive failures. A retrospective study was carried out in 208 women with a history of reproductive failure. Study patients were divided into three groups: women with repeated implantation failure (RIF, n = 40), recurrent pregnancy loss (RPL, n = 113), and both RIF and RPL (n = 55). Fertile controls were 92. PAI-1 4G/4G was prevalent in RPL, RIF, and RIF/RPL groups when compared with controls (P = 0.003) and associated with increased risks of RIF, RPL, and RIF with RPL (OR = 4.5, 2.2 and 2.7). Women with PAI-1 4G/4G have significantly higher BMI, glucose, and PAI-1 levels and lower NK cytotoxicity when compared with women without PAI-1 4G/4G. PAI-1 4G/5G polymorphism plays a major role in the pathogenesis of RPL and RIF by altering metabolic and immunological profiles. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. 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.

  18. 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

  19. Whole Transcriptome Profiling of Successful Immune Response to Vibrio Infections in the Oyster Crassostrea gigas by Digital Gene Expression Analysis

    PubMed Central

    de Lorgeril, Julien; Zenagui, Reda; Rosa, Rafael D.; Piquemal, David; Bachère, Evelyne

    2011-01-01

    The cultivated Pacific oyster Crassostrea gigas has suffered for decades large scale summer mortality phenomenon resulting from the interaction between the environment parameters, the oyster physiological and/or genetic status and the presence of pathogenic microorganisms including Vibrio species. To obtain a general picture of the molecular mechanisms implicated in C. gigas immune responsiveness to circumvent Vibrio infections, we have developed the first deep sequencing study of the transcriptome of hemocytes, the immunocompetent cells. Using Digital Gene Expression (DGE), we generated a transcript catalog of up-regulated genes from oysters surviving infection with virulent Vibrio strains (Vibrio splendidus LGP32 and V. aestuarianus LPi 02/41) compared to an avirulent one, V. tasmaniensis LMG 20012T. For that an original experimental infection protocol was developed in which only animals that were able to survive infections were considered for the DGE approach. We report the identification of cellular and immune functions that characterize the oyster capability to survive pathogenic Vibrio infections. Functional annotations highlight genes related to signal transduction of immune response, cell adhesion and communication as well as cellular processes and defence mechanisms of phagocytosis, actin cytosqueleton reorganization, cell trafficking and autophagy, but also antioxidant and anti-apoptotic reactions. In addition, quantitative PCR analysis reveals the first identification of pathogen-specific signatures in oyster gene regulation, which opens the way for in depth molecular studies of oyster-pathogen interaction and pathogenesis. This work is a prerequisite for the identification of those physiological traits controlling oyster capacity to survive a Vibrio infection and, subsequently, for a better understanding of the phenomenon of summer mortality. PMID:21829707

  20. Whole transcriptome profiling of successful immune response to Vibrio infections in the oyster Crassostrea gigas by digital gene expression analysis.

    PubMed

    de Lorgeril, Julien; Zenagui, Reda; Rosa, Rafael D; Piquemal, David; Bachère, Evelyne

    2011-01-01

    The cultivated Pacific oyster Crassostrea gigas has suffered for decades large scale summer mortality phenomenon resulting from the interaction between the environment parameters, the oyster physiological and/or genetic status and the presence of pathogenic microorganisms including Vibrio species. To obtain a general picture of the molecular mechanisms implicated in C. gigas immune responsiveness to circumvent Vibrio infections, we have developed the first deep sequencing study of the transcriptome of hemocytes, the immunocompetent cells. Using Digital Gene Expression (DGE), we generated a transcript catalog of up-regulated genes from oysters surviving infection with virulent Vibrio strains (Vibrio splendidus LGP32 and V. aestuarianus LPi 02/41) compared to an avirulent one, V. tasmaniensis LMG 20012(T). For that an original experimental infection protocol was developed in which only animals that were able to survive infections were considered for the DGE approach. We report the identification of cellular and immune functions that characterize the oyster capability to survive pathogenic Vibrio infections. Functional annotations highlight genes related to signal transduction of immune response, cell adhesion and communication as well as cellular processes and defence mechanisms of phagocytosis, actin cytosqueleton reorganization, cell trafficking and autophagy, but also antioxidant and anti-apoptotic reactions. In addition, quantitative PCR analysis reveals the first identification of pathogen-specific signatures in oyster gene regulation, which opens the way for in depth molecular studies of oyster-pathogen interaction and pathogenesis. This work is a prerequisite for the identification of those physiological traits controlling oyster capacity to survive a Vibrio infection and, subsequently, for a better understanding of the phenomenon of summer mortality.

  1. 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.

  2. Profiling the human immune response to Mycobacterium tuberculosis by human cytokine array.

    PubMed

    Chen, Tao; Li, Zhenyan; Yu, Li; Li, Haicheng; Lin, Jinfei; Guo, Huixin; Wang, Wei; Chen, Liang; Zhang, Xianen; Wang, Yunxia; Chen, Yuhui; Liao, Qinghua; Tan, Yaoju; Shu, Yang; Huang, Wenyan; Cai, Changhui; Zhou, Zhongjing; Yu, Meiling; Li, Guozhou; Zhou, Lin; Zhong, Qiu; Bi, Lijun; Zhao, Meigui; Guo, Lina; Zhou, Jie

    2016-03-01

    Tuberculosis (TB) continues to be one of the most serious infectious diseases in the world, however, no effective biomarkers can be used for rapid screening of latent tuberculosis infection (LTBI) and active TB. In this study, serum cytokines were screened and tested as potential biomarker for TB diagnosis. Cytokine array was used to track the cytokine profile and its dynamic change after TB infection. The different expressions of cytokines were confirmed by ELISA assay. ROC curve analyses were used to evaluate the efficacy of a cytokine or cytokine combination for diagnosis. Eotaxin-2, ICAM-1, MCSF, IL-12p70, and IL-11 were significantly higher in the LTBI individuals. I-309, MIG, Eotaxin-2, IL-8, ICAM-1, IL-6sR, and Eotaxin were significantly higher in active TB patients. ROC curve analyses gave AUCs of 0.843, 0.898, and 0.888 for I-309, MIG, and IL-8, respectively, and 0.894 for the combination panel in active TB diagnosis. IFN-γ/IL-4 and IL-2/TNF-α ratios exhibit dynamic changes in the healthy control and LTBI to different stages of active TB. Serum cytokines, including I-309 and MIG, IL-8, Extoxin-2, ICAM-1 and combinations of cytokines, including IFN-γ/IL-4 and IL-2/TNF-α, can be used as serum biomarkers for LTBI and active TB screening, thus indicating prospective clinical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Gambiense human african trypanosomiasis and immunological memory: effect on phenotypic lymphocyte profiles and humoral immunity.

    PubMed

    Lejon, Veerle; Mumba Ngoyi, Dieudonné; Kestens, Luc; Boel, Luc; Barbé, Barbara; Kande Betu, Victor; van Griensven, Johan; Bottieau, Emmanuel; Muyembe Tamfum, Jean-Jacques; Jacobs, Jan; Büscher, Philippe

    2014-03-01

    In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and

  4. Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.

    PubMed

    Marschan, E; Kuitunen, M; Kukkonen, K; Poussa, T; Sarnesto, A; Haahtela, T; Korpela, R; Savilahti, E; Vaarala, O

    2008-04-01

    Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants. In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use. The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.

  5. 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.

  6. Immune system function, stress, exercise and nutrition profile can affect pregnancy outcome: Lessons from a Mediterranean cohort.

    PubMed

    Mparmpakas, D; Goumenou, A; Zachariades, E; Pados, G; Gidron, Y; Karteris, E

    2013-02-01

    Pregnancy is associated with major physiological and future psychosocial changes, and maternal adaptation to these changes is crucial for normal foetal development. Psychological stress in pregnancy predicts an earlier birth and lower birth weight. Pregnancy-specific stress contributes directly to preterm delivery. The importance of nutrition and exercise during pregnancy with regard to pregnancy outcome has long been acknowledged. This importance has only been further emphasized by the recent changes in food quality and availability, lifestyle changes and a new understanding of foetal programming's effects on adult outcomes. We hypothesised that for a successful pregnancy certain events at a nutritional, immune, psycho-emotional and genetic level should be tightly linked. Therefore, in this study we followed an 'integrative' approach to investigate how maternal stress, nutrition, pregnancy planning and exercise influence pregnancy outcome. A key finding of our study is that there was a significant reduction in the intake of alcohol, caffeine-containing and sugary drinks during pregnancy. However, passive smoking in the household remained unchanged. In terms of immune profile, a significant inverse correlation was noted between difficulty to 'fight' an infection and number of colds (r=-0.289, P=0.003) as well as the number of infections (r=-0.446, P<0.0001) during pregnancy. The vast majority of the pregnant women acquired a more sedentary lifestyle in the third trimester. In planned, but not in unplanned, pregnancies stress predicted infant weight, independent of age and body mass index (BMI). Notably, in mothers with negative attitudes towards the pregnancy, those with an unplanned pregnancy gave birth to infants with significantly higher weights than those with planned pregnancies. Collectively these data suggest that there is a higher order of complexity, possibly involving gene-environment interactions that work together to ensure a positive outcome for the

  7. Cerebrospinal fluid and serum cytokine profiling to detect immune control of infectious and inflammatory neurological and psychiatric diseases.

    PubMed

    Maxeiner, Horst-Guenter; Marion Schneider, E; Kurfiss, Sina-Tatjana; Brettschneider, Johannes; Tumani, Hayrettin; Bechter, Karl

    2014-09-01

    The present study aimed at profiling inflammatory cytokines for neurological and psychiatric diseases. A total of 86 patients with meningitis, multiple sclerosis, tension-type headache, idiopathic facial nerve palsy (IFNP), affective and schizophrenic disorders were tested for both, serum and cerebrospinal fluid (CSF) using a multiplexed cytokine ELISA for IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-8/CXCL8, IL-10, IL12p70, IL-13 and IL-17. Cases with viral and bacterial meningitis had unequivocally higher cytokine concentrations in the CSF when compared with serum. Bacterial meningitis was unique by extremely elevated IL-17, TNF-α and IL-1β, indicating a plethora of inflammatory pathways, selectively activated in the CSF. In relapsing multiple sclerosis, IFN-γ and IL-10 were elevated in both, serum and CSF, but IL-12p70, IL-5, IL-13, and TNF-α were more prominent in serum than in CSF. Qualitatively similar biomarker patterns were detected in patients with idiopathic facial nerve palsy and tension-type cephalgia. Affective and schizophrenic disorders clearly present with an inflammatory phenotype in the CSF and also serum, the cytokines determined were in general higher in schizophrenia. Except IFN-γ, schizophrenic patients had higher IL-12p70 and a trend of higher IL-10 and IL-13 in serum suggesting a more prominent TH2-type counter regulatory immune response than in affective disorders. These differences were also mirrored in the CSF. Elevated IL-8 appears to be the most sensitive marker for inflammation in the CSF of all diseases studied, whereas TNF-α was restricted to peripheral blood. With the exception of IL-8, all but viral and bacterial meningitis, studied, displayed higher means of elevated lymphokine concentrations in the serum than in the CSF. This observation supports the concept of immunological crosstalk between periphery and intrathecal immunity in neurological and psychiatric diseases.

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

    PubMed

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

    2010-04-01

    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.

  9. 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

  10. 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

  11. In silico modeling of the immune system: cellular and molecular scale approaches.

    PubMed

    Belfiore, Mariagrazia; Pennisi, Marzio; Aricò, Giuseppina; Ronsisvalle, Simone; Pappalardo, Francesco

    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.

  12. 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

  13. Large-scale image-based screening and profiling of cellular phenotypes.

    PubMed

    Bougen-Zhukov, Nicola; Loh, Sheng Yang; Lee, Hwee Kuan; Loo, Lit-Hsin

    2017-02-01

    Cellular phenotypes are observable characteristics of cells resulting from the interactions of intrinsic and extrinsic chemical or biochemical factors. Image-based phenotypic screens under large numbers of basal or perturbed conditions can be used to study the influences of these factors on cellular phenotypes. Hundreds to thousands of phenotypic descriptors can also be quantified from the images of cells under each of these experimental conditions. Therefore, huge amounts of data can be generated, and the analysis of these data has become a major bottleneck in large-scale phenotypic screens. Here, we review current experimental and computational methods for large-scale image-based phenotypic screens. Our focus is on phenotypic profiling, a computational procedure for constructing quantitative and compact representations of cellular phenotypes based on the images collected in these screens. © 2016 International Society for Advancement of Cytometry.

  14. 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.

  15. Gene expression profiles of hair and wool sheep reveal importance of Th2 immune mechanisms for increased resistance to.

    PubMed

    MacKinnon, K M; Bowdridge, S A; Kanevsky-Mullarky, I; Zajac, A M; Notter, D R

    2015-05-01

    Management of gastrointestinal parasites is a critical issue for sheep producers worldwide. Increases in the prevalence of drug-resistant worms have complicated parasite control and increased economic losses. Therefore, other methods of parasite control need to be assessed, including the use of genetically resistant animals in breeding programs. Hair sheep breeds such as the St. Croix have greater parasite resistance than conventional wool breeds. However, the immune mechanisms that control parasite resistance in hair or wool breeds have not yet been fully determined, and information on cytokine expression profiles for both wool sheep selected for increased resistance and hair sheep is limited. Our objective was to investigate gene expression differences in 24 parasite-resistant hair and 24 susceptible wool sheep to identify immune effectors associated with resistance to . One-half of the lambs were infected and sacrificed at 3 or 27 d after infection. Remaining lambs were not infected. Breed differences in expression of genes associated with Th1 and Th2 immune responses in lymph nodes and abomasal tissue were determined. Th2-associated genes included IL-4, IL-13, IL-5, IgE, the α chain of the IL-4 receptor, and the α chain of the high-affinity IgE receptor (FcεRI). Th1-associated genes included interferon gamma (IFN-γ), the p35 subunit of IL-12 (IL-12 p35), and the β1 and β2 chains of the IL-12 receptor (IL-12 Rβ1 and IL-12 Rβ2, respectively). In both hair and wool sheep, infection with resulted in greater expression of IgE, IL-13, IL-5, and IL-12 p35 and somewhat reduced expression of IFNγ in lymph nodes. In abomasal tissue, parasite infection resulted in greater IgE, IL-13, FcεRI, and IL-12 p35 expression in infected lambs compared with control lambs. Between breeds, hair sheep had a stronger Th2 response after infection than wool sheep, with increased expression of IgE and IL-13 and decreased expression of IFNγ in lymph nodes and increased expression

  16. Expression profiles of immune mediators in feline Coronavirus-infected cells and clinical samples of feline Coronavirus-positive cats.

    PubMed

    Safi, Nikoo; Haghani, Amin; Ng, Shing Wei; Selvarajah, Gayathri Thevi; Mustaffa-Kamal, Farina; Omar, Abdul Rahman

    2017-04-07

    There are two biotypes of feline coronavirus (FCoV): the self-limiting feline enteric coronavirus (FECV) and the feline infectious peritonitis virus (FIPV), which causes feline infectious peritonitis (FIP), a fatal disease associated with cats living in multi-cat environments. This study provides an insight on the various immune mediators detected in FCoV-positive cats which may be responsible for the development of FIP. In this study, using real-time PCR and multiplex bead-based immunoassay, the expression profiles of several immune mediators were examined in Crandell-Reese feline kidney (CRFK) cells infected with the feline coronavirus (FCoV) strain FIPV 79-1146 and in samples obtained from FCoV-positive cats. CRFK cells infected with FIPV 79-1146 showed an increase in the expression of interferon-related genes and pro-inflammatory cytokines such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, and IL8. In addition, an increase in the expression of the above cytokines as well as GM-CSF and IFNγ was also detected in the PBMC, serum, and peritoneal effusions of FCoV-positive cats. Although the expression of MX1 and viperin genes was variable between cats, the expression of these two genes was relatively higher in cats having peritoneal effusion compared to cats without clinically obvious effusion. Higher viral load was also detected in the supernatant of peritoneal effusions compared to in the plasma of FCoV-positive cats. As expected, the secretion of IL1β, IL6 and TNFα was readily detected in the supernatant of peritoneal effusions of the FCoV-positive cats. This study has identified various pro-inflammatory cytokines and interferon-related genes such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, IL8, GM-CSF and IFNγ in FCoV-positive cats. With the exception of MX1 and viperin, no distinct pattern of immune mediators was observed that distinguished between FCoV-positive cats with and without peritoneal effusion. Further studies based on definitive

  17. Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis.

    PubMed

    Sellner, J; Koczi, W; Harrer, A; Oppermann, K; Obregon-Castrillo, E; Pilz, G; Wipfler, P; Afazel, S; Haschke-Becher, E; Trinka, E; Kraus, J

    2013-09-01

    An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects. © 2013 British Society for Immunology.

  18. Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis

    PubMed Central

    Sellner, J; Koczi, W; Harrer, A; Oppermann, K; Obregon-Castrillo, E; Pilz, G; Wipfler, P; Afazel, S; Haschke-Becher, E; Trinka, E; Kraus, J

    2013-01-01

    An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing–remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3+CD8+, CD3+CD4+), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3+CD4+ T cells, B cells), VLA-4 (CD3+CD8+ T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3+CD4+) and VLA-4 (CD3+CD4+, CD3+CD8+, NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects. PMID:23611040

  19. Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray.

    PubMed

    Loebel, Madlen; Eckey, Maren; Sotzny, Franziska; Hahn, Elisabeth; Bauer, Sandra; Grabowski, Patricia; Zerweck, Johannes; Holenya, Pavlo; Hanitsch, Leif G; Wittke, Kirsten; Borchmann, Peter; Rüffer, Jens-Ulrich; Hiepe, Falk; Ruprecht, Klemens; Behrends, Uta; Meindl, Carola; Volk, Hans-Dieter; Reimer, Ulf; Scheibenbogen, Carmen

    2017-01-01

    Epstein-Barr-Virus (EBV) plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS) disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients. We performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform. Patients with multiple sclerosis (MS), systemic lupus erythematosus (SLE) and cancer-related fatigue served as controls. 3054 overlapping peptides were synthesised as 15-mers from 14 different EBV proteins. Array data was validated by ELISA for selected peptides. Prevalence of EBV serotypes was determined by qPCR from throat washing samples. EBV type 1 infections were found in patients and controls. EBV seroarray profiles between healthy controls and CFS were less divergent than that observed for MS or SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat region showed sequence homologies to various human proteins. Patients with CFS had a quite similar EBV IgG antibody response pattern as healthy controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against EBNA-6 protein is found in CFS patients. Homologous sequences of various human proteins with this EBNA-6 repeat sequence might be potential targets for antigenic mimicry.

  20. 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.

  1. 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.

  2. 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.

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

    PubMed Central

    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

  4. Large-scale similarity search profiling of ChEMBL compound data sets.

    PubMed

    Heikamp, Kathrin; Bajorath, Jürgen

    2011-08-22

    A large-scale similarity search investigation has been carried out on 266 well-defined compound activity classes extracted from the ChEMBL database. The analysis was performed using two widely applied two-dimensional (2D) fingerprints that mark opposite ends of the current performance spectrum of these types of fingerprints, i.e., MACCS structural keys and the extended connectivity fingerprint with bond diameter four (ECFP4). For each fingerprint, three nearest neighbor search strategies were applied. On the basis of these search calculations, a similarity search profile of the ChEMBL database was generated. Overall, the fingerprint search campaign was surprisingly successful. In 203 of 266 test cases (∼76%), a compound recovery rate of at least 50% was observed with at least the better performing fingerprint and one search strategy. The similarity search profile also revealed several general trends. For example, fingerprint searching was often characterized by an early enrichment of active compounds in database selection sets. In addition, compound activity classes have been categorized according to different similarity search performance levels, which helps to put the results of benchmark calculations into perspective. Therefore, a compendium of activity classes falling into different search performance categories is provided. On the basis of our large-scale investigation, the performance range of state-of-the-art 2D fingerprinting has been delineated for compound data sets directed against a wide spectrum of pharmaceutical targets.

  5. 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.

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

    DOE PAGES

    Xie, Shaocheng; Hume, Timothy; Jakob, Christian; ...

    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

  7. 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.

  8. 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.

  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. Immune Profiling of Pregnant Toxoplasma-Infected US and Colombia Patients Reveals Surprising Impacts of Infection on Peripheral Blood Cytokines

    PubMed Central

    Pernas, Lena; Ramirez, Raymund; Holmes, Tyson H.; Montoya, José G.; Boothroyd, John C.

    2014-01-01

    In North America (NA) and Europe, the majority of toxoplasmosis cases are benign and generally asymptomatic, whereas in South America (SA) toxoplasmosis is associated with much more severe symptoms in adults and congenitally infected children. The reasons for these differences remain unknown; currently, there is little information from patients in either region on how the immune system responds to infection with Toxoplasma gondii. Here, we report the relative abundance of 51 serum cytokines from acute and chronic toxoplasmosis cohorts of pregnant women from the United States, where approximately one-half of clinical isolates are Type II, and Colombia, where clinical isolates are generally “atypical” or Type I-like strains. Surprisingly, the results showed notably lower levels of 23 cytokines in acutely infected patients from the United States, relative to uninfected US controls. In acutely infected Colombian patients, however, only 8 cytokine levels differed detectably with 4 being lower and 4 higher relative to uninfected controls. Strikingly, there were also differences in the cytokine profiles of the chronically infected patients relative to uninfected controls in the US cohort. Hence, Toxoplasma appears to specifically impact levels of circulating cytokines, and our results may partly explain region-specific differences in the clinical spectrum of toxoplasmosis. PMID:24664173

  11. Discriminant Validity of the Vineland Scales: Score Profiles of Individuals with Mental Retardation and a Specific Disorder.

    ERIC Educational Resources Information Center

    Balboni, Giulia; Pedrabissi, Luigi; Molteni, Massimo; Villa, Susanna

    2001-01-01

    Utility of the Vineland Adaptive Behavior Scales-Expanded Form to discriminate among areas of adaptive behavior was substantiated by comparing profiles of scores obtained by 113 individuals with mental retardation and either a communication, social behavior, or motor disorder. Results support the use of the Vineland Scales in ecological evaluation…

  12. 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.…

  13. External Validation of the Personality Inventory for Children (PIC) Profile and Factor Scales: Parent, Teacher, and Clinician Ratings.

    ERIC Educational Resources Information Center

    Lachar, David; And Others

    1984-01-01

    Attempted to expand the construct validity of the profile and factor scales for the Personality Inventory for Children (PIC) by determining the relationship of these scales to empirically derived dimensions of problem behaviors in children and adolescents (N=691). Results provided substantial evidence of convergent and discriminant validity. (LLL)

  14. 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.…

  15. Comparing Longitudinal Profile Patterns of Mathematics and Reading in Early Child Longitudinal Study, Kindergarten: The Profile Analysis via Multidimensional Scaling (PAMS) Approach

    ERIC Educational Resources Information Center

    Kim, Se-Kang

    2010-01-01

    The aim of the study is to compare longitudinal patterns from Mathematics and Reading data from the direct child assessment of Early Child Longitudinal Study, Kindergarten (ECLS-K, US Department of Education, National Center for Education Statistics 2006), utilizing Profile Analysis via Multidimensional Scaling (PAMS). PAMS has been used initially…

  16. Distribution of scaled height in one-dimensional competitive growth profiles

    NASA Astrophysics Data System (ADS)

    de Assis, T. A.; de Castro, C. P.; de Brito Mota, F.; de Castilho, C. M. C.; Andrade, R. F. S.

    2012-11-01

    This work investigates the scaled height distribution, ρ(q), of irregular profiles that are grown based on two sets of local rules: those of the restricted solid on solid (RSOS) and ballistic deposition (BD) models. At each time step, these rules are respectively chosen with probability p and r=1-p. Large-scale Monte Carlo simulations indicate that the system behaves differently in three succeeding intervals of values of p: IB≈[0,0.75),IT≈(0.75,0.9), and IR≈(0.9,1.0]. In IB, the ballistic character prevails: the growth velocity υ∞ decreases with p in a linear way, and similar behavior is found for Γ∞(p), the amplitude of the t1/3-fluctuations, which is measured from the second-order height cumulant. The distribution of scaled height fluctuations follows the Gaussian orthogonal ensemble (GOE) Tracy-Widom (TW) distribution with resolution roughly close to 10-4. The skewness and kurtosis of the computed distribution coincide with those for TW distribution. Similar results are observed in the interval IR, with prevalent RSOS features. In this case, the skewness become negative. In the transition interval IT, the system goes smoothly from one regime to the other: the height distribution becomes apparently Gaussian, which motivates us to identify this phenomenon as a transition from Kardar-Parisi-Zhang (KPZ) behavior to Edwards-Wilkinson (EW) behavior back to KPZ behavior.

  17. Immune profiles and clinical outcomes between sepsis patients with or without active cancer requiring admission to intensive care units

    PubMed Central

    Lin, Chiung-Yu; Huang, Kuo-Tung; Kao, Hsu-Ching; Fang, Ying-Tang; Huang, Chi-Han; Chang, Ya-Ting; Wang, Yi-His; Wang, Chin-Chou

    2017-01-01

    Background Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis. It would be interesting to see if immune status was different in severe sepsis patients with or without active cancer. The aim of this study was to assess the differences in immune profiles, and clinical outcomes between severe sepsis patients with or without cancer admitted to ICU. Methods A combined retrospective and prospective observational study from a cohort of adult sepsis patients admitted to three medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August 2013 and June 2016. Results Of the 2744 patients admitted to the ICU, 532 patients with sepsis were included. Patients were divided into those with or without active cancer according to their medical history. Of the 532 patients, 95 (17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer history. Patients with active cancer were younger (p = 0.001) and were less likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or stroke (p = 0.002) compared to patients without active cancer. Patients with active cancer also exhibited higher baseline lactate levels (p = 0.038), and higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients without active cancer. The 14-day, 28-day and 90-day mortality rates were higher for patients with active cancer than those

  18. Immune profiles and clinical outcomes between sepsis patients with or without active cancer requiring admission to intensive care units.

    PubMed

    Fang, Wen-Feng; Chen, Yu-Mu; Lin, Chiung-Yu; Huang, Kuo-Tung; Kao, Hsu-Ching; Fang, Ying-Tang; Huang, Chi-Han; Chang, Ya-Ting; Wang, Yi-His; Wang, Chin-Chou; Lin, Meng-Chih

    2017-01-01

    Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis. It would be interesting to see if immune status was different in severe sepsis patients with or without active cancer. The aim of this study was to assess the differences in immune profiles, and clinical outcomes between severe sepsis patients with or without cancer admitted to ICU. A combined retrospective and prospective observational study from a cohort of adult sepsis patients admitted to three medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August 2013 and June 2016. Of the 2744 patients admitted to the ICU, 532 patients with sepsis were included. Patients were divided into those with or without active cancer according to their medical history. Of the 532 patients, 95 (17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer history. Patients with active cancer were younger (p = 0.001) and were less likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or stroke (p = 0.002) compared to patients without active cancer. Patients with active cancer also exhibited higher baseline lactate levels (p = 0.038), and higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients without active cancer. The 14-day, 28-day and 90-day mortality rates were higher for patients with active cancer than those without active cancer (P

  19. Effect of Dactylogyrus catlaius (Jain 1961) infection in Labeo rohita (Hamilton 1822): innate immune responses and expression profile of some immune related genes.

    PubMed

    Dash, Pujarini; Kar, Banya; Mishra, Arpita; Sahoo, P K

    2014-03-01

    The monogenean ectoparasite, Dactylogyrus sp. is a major pathogen in freshwater aquaculture. The immune responses in parasitized fish were analyzed by quantitation of innate immune factors (natural agglutinin level, haemolysin titre, antiprotease, lysozyme and myeloperoxidase activities) in serum and immune-relevant gene expression in gill and anterior kidney. The antiprotease activity and natural agglutinin level were found to be significantly higher and lysozyme activity was significantly lower in parasitized fish. Most of the genes viz., beta2-microglobulin (beta2M), major histocompatibility complex I (MHCI), MHCII, tumor necrosis factor alpha (TNFalpha) and toll-like receptor 22 (TLR22) in gill samples were significantly down-regulated in the experimental group. In the anterior kidney, the expression of superoxide dismutase and interleukin 1beta (IL1beta) were significantly up-regulated whereas a significant down regulation of MHCII and TNFalpha was also observed. The down-regulation of most of the genes viz, MHCI, beta2M, MHCII, TLR22 and TNFalpha in infected gills indicated a well evolved mechanism in this parasite to escape the host immune response. The modulation of innate and adaptive immunity by this parasite can be further explored to understand host susceptibility.

  20. Psychometric evaluation of a new sensory scale in immune-mediated polyneuropathies. Inflammatory Neuropathy Cause and Treatment (INCAT) Group.

    PubMed

    Merkies, I S; Schmitz, P I; van der Meché, F G; van Doorn, P A

    2000-02-22

    To perform a psychometric evaluation of the inflammatory neuropathy cause and treatment (INCAT) sensory sumscore (ISS) in sensory-motor immune-mediated polyneuropathies. This new sensory scale was evaluated to strive for uniformity in assessing sensory deficit in these disorders. The ISS comprises vibration and pinprick sense plus a two-point discrimination value and ranges from 0 (normal sensation) to 20 (maximum sensory deficit). Before its clinical use, a panel of expert neurologists concluded that the ISS has face and content validity. The construct validity of the ISS was investigated by correlation and regression studies with additional scales (Nine-Hole Peg Test, 10-Meter Walking Test, a disability sumscore). All scales were applied in 113 patients with a stable neurologic condition (83 patients who experienced Guillain-Barre syndrome [GBS] in the past, 22 with chronic inflammatory demyelinating polyneuropathy [CIDP], 8 patients with a monoclonal gammopathy associated polyneuropathy), and 10 patients with recently diagnosed GBS or CIDP with changing clinical conditions. Reliability of the ISS was evaluated in the stable patients. Its responsiveness was investigated in the patients examined longitudinally. A moderate to good validity was obtained for the ISS (stable group: r = 0.38 to 0.56, p < or = 0.006; longitudinal group: R = 0.60 to 0.82, p < or = 0.007, except for the association with the 10-Meter Walking Test [p = 0.08]). Acceptable internal consistency, and inter- and intraobserver reliability were demonstrated for the ISS (alpha = 0.68 to 0.87; R = 0.85 to 0.89, p < 0.0001). Standardized response mean scores for the ISS were high (> or =0.8), indicating good responsiveness. All psychometric requirements are provided for the the inflammatory neuropathy cause and treatment sensory sumscore. The use of this scale is therefore suggested for bedside evaluation of sensory deficit in the individual patient with a sensory-motor immune-mediated polyneuropathy

  1. Fine-scale thermohaline structure revealed by seismic reflection profiling in the Gulf of California.

    NASA Astrophysics Data System (ADS)

    Paramo, P.; Holbrook, W. S.; Pearse, S.; Schmitt, R. W.

    2003-12-01

    We present cross-sectional acoustic images of the ocean revealed by standard seismic-reflection profiling acquired in the Gulf of California. The data were acquired with a 6 km streamer, 480 channels and 20 gun array with a frequency content of 10-120 Hz. Seismic lines acquired in several different locations throughout the Gulf of California show similar characteristics. The images reveal acoustic reflections caused by fine-scale thermohaline structure. These reflections are prominent in the uppermost 500 m of the water column and become weaker with depth until they reach 1000 m, where they disappear as the abyssal waters become acoustically transparent. Time-lapse cross-sectional images show no overall change in reflectance characteristics in the uppermost 500m and in deeper waters, but the location of the reflections varies slightly between the images. We believe that these changes in location are consistent with the dynamics of internal waves.

  2. 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)

  3. 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)

  4. Targeting α- and β-Adrenergic Receptors Differentially Shifts Th1, Th2, and Inflammatory Cytokine Profiles in Immune Organs to Attenuate Adjuvant Arthritis

    PubMed Central

    Lubahn, Cheri L.; Lorton, Dianne; Schaller, Jill A.; Sweeney, Sarah J.; Bellinger, Denise L.

    2014-01-01

    The sympathetic nervous system (SNS) regulates host defense responses and restores homeostasis. SNS-immune regulation is altered in rheumatoid arthritis (RA) and rodent models of RA, characterized by nerve remodeling in immune organs and defective adrenergic receptor (AR) signaling to immune cell targets. The SNS typically promotes or suppresses inflammation via α- and β2-AR activation, respectively, and indirectly drives humoral immunity by blocking Th1 cytokine secretion. Here, we investigate how β2-AR stimulation and/or α-AR blockade at disease onset affects disease pathology and cytokine profiles in relevant immune organs from male Lewis rats with adjuvant-induced arthritis (AA). Rats challenged to induce AA were treated with terbutaline (TERB), a β2-AR agonist (600 μg/kg/day) and/or phentolamine (PHEN), an α-AR antagonist (5.0 mg/kg/day) or vehicle from disease onset through severe disease. We report that in spleen, mesenteric (MLN) and draining lymph node (DLN) cells, TERB reduces proliferation, an effect independent of IL-2. TERB also fails to shift T helper (Th) cytokines from a Th1 to Th2 profile in spleen and MLN (no effect on IFN-γ) and DLN (greater IFN-γ) cells. In splenocytes, TERB, PHEN, and co-treatment (PT) promotes an anti-inflammatory profile (greater IL-10) and lowers TNF-α (PT only). In DLN cells, drug treatments do not affect inflammatory profiles, except PT, which raised IL-10. In MLN cells, TERB or PHEN lowers MLN cell secretion of TNF-α or IL-10, respectively. Collectively, our findings indicate disrupted β2-AR, but not α-AR signaling in AA. Aberrant β2-AR signaling consequently derails the sympathetic regulation of lymphocyte expansion, Th cell differentiation, and inflammation in the spleen, DLNs and MLs that is required for immune system homeostasis. Importantly, this study provides potential mechanisms through which reestablished balance between α- and β2-AR function in the immune system ameliorates inflammation and

  5. 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

  6. 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.

  7. Large-scale investigation of human TF-miRNA relations based on coexpression profiles.

    PubMed

    Chien, Chia-Hung; Chiang-Hsieh, Yi-Fan; Tsou, Ann-Ping; Weng, Shun-Long; Chang, Wen-Chi; Huang, Hsien-Da

    2014-01-01

    Noncoding, endogenous microRNAs (miRNAs) are fairly well known for regulating gene expression rather than protein coding. Dysregulation of miRNA gene, either upregulated or downregulated, may lead to severe diseases or oncogenesis, especially when the miRNA disorder involves significant bioreactions or pathways. Thus, how miRNA genes are transcriptionally regulated has been highlighted as well as target recognition in recent years. In this study, a large-scale investigation of novel cis- and trans-elements was undertaken to further determine TF-miRNA regulatory relations, which are necessary to unravel the transcriptional regulation of miRNA genes. Based on miRNA and annotated gene expression profiles, the term "coTFBS" was introduced to detect common transcription factors and the corresponding binding sites within the promoter regions of each miRNA and its coexpressed annotated genes. The computational pipeline was successfully established to filter redundancy due to short sequence motifs for TFBS pattern search. Eventually, we identified more convinced TF-miRNA regulatory relations for 225 human miRNAs. This valuable information is helpful in understanding miRNA functions and provides knowledge to evaluate the therapeutic potential in clinical research. Once most expression profiles of miRNAs in the latest database are completed, TF candidates of more miRNAs can be explored by this filtering approach in the future.

  8. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Atomic-scale imaging of nanoengineered oxygen vacancy profiles in SrTiO3.

    PubMed

    Muller, David A; Nakagawa, Naoyuki; Ohtomo, Akira; Grazul, John L; Hwang, Harold Y

    2004-08-05

    At the heart of modern oxide chemistry lies the recognition that beneficial (as well as deleterious) materials properties can be obtained by deliberate deviations of oxygen atom occupancy from the ideal stoichiometry. Conversely, the capability to control and confine oxygen vacancies will be important to realize the full potential of perovskite ferroelectric materials, varistors and field-effect devices. In transition metal oxides, oxygen vacancies are generally electron donors, and in strontium titanate (SrTiO3) thin films, oxygen vacancies (unlike impurity dopants) are particularly important because they tend to retain high carrier mobilities, even at high carrier densities. Here we report the successful fabrication, using a pulsed laser deposition technique, of SrTiO3 superlattice films with oxygen doping profiles that exhibit subnanometre abruptness. We profile the vacancy concentrations on an atomic scale using annular-dark-field electron microscopy and core-level spectroscopy, and demonstrate absolute detection sensitivities of one to four oxygen vacancies. Our findings open a pathway to the microscopic study of individual vacancies and their clustering, not only in oxides, but in crystalline materials more generally.

  10. Searching for a neurologic injury's Wechsler Adult Intelligence Scale-Third Edition profile.

    PubMed

    Gonçalves, Marta A; Moura, Octávio; Castro-Caldas, Alexandre; Simões, Mário R

    2017-01-01

    This study aimed to investigate the presence of a Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) cognitive profile in a Portuguese neurologic injured sample. The Portuguese WAIS-III was administered to 81 mixed neurologic patients and 81 healthy matched controls selected from the Portuguese standardization sample. Although the mixed neurologic injury group performed significantly lower than the healthy controls for the majority of the WAIS-III scores (i.e., composite measures, discrepancies, and subtests), the mean scores were within the normal range and, therefore, at risk of being unobserved in a clinical evaluation. ROC curves analysis showed poor to acceptable diagnostic accuracy for the WAIS-III composite measures and subtests (Working Memory Index and Digit Span revealed the highest accuracy for discriminating between participants, respectively). Multiple regression analysis showed that both literacy and the presence of brain injury were significant predictors for all of the composite measures. In addition, multiple regression analysis also showed that literacy, age of injury onset, and years of survival predicted all seven composite measures for the mixed neurologic injured group. Despite the failure to find a WAIS-III cognitive profile for mixed neurologic patients, the results showed a significant influence of brain lesion and literacy in the performance of the WAIS-III.

  11. 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

  12. 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%).

  13. Deep immune profiling by mass cytometry links human T and NK cell differentiation and cytotoxic molecule expression patterns.

    PubMed

    Bengsch, Bertram; Ohtani, Takuya; Herati, Ramin Sedaghat; Bovenschen, Niels; Chang, Kyong-Mi; Wherry, E John

    2017-03-19

    The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer. Approaches capable of simultaneously evaluating expression of multiple cytotoxic molecules with detailed information on T and NK differentiation state, however, remain limited. Here, we established a high dimensional mass cytometry approach to comprehensively interrogate single cell proteomic expression of cytotoxic programs and lymphocyte differentiation. This assay identified a coordinated expression pattern of cytotoxic molecules linked to CD8 T cell differentiation stages. Coordinated high expression of perforin, granulysin, Gzm A, Gzm B and Gzm M was associated with markers of late effector memory differentiation and expression of chemokine receptor CX3CR1. However, classical gating and dimensionality reduction approaches also identified other discordant patterns of cytotoxic molecule expression in CD8 T cells, including reduced perforin, but high Gzm A, Gzm K and Gzm M expression. When applied to non-CD8 T cells, this assay identified different patterns of cytotoxic molecule co-expression by CD56(hi) versus CD56(dim) defined NK cell developmental stages; in CD4 T cells, low expression of cytotoxic molecules was found mainly in TH1 phenotype cells, but not in Tregs or T follicular helper cells (TFH). Thus, this comprehensive, single cell, proteomic assessment of cytotoxic protein co-expression patterns demonstrates specialized cytotoxic programs in T cells and NK cells linked to their differentiation

  14. PBMC transcriptome profiles identifies potential candidate genes and functional networks controlling the innate and the adaptive immune response to PRRSV vaccine in Pietrain pig.

    PubMed

    Islam, Md Aminul; Große-Brinkhaus, Christine; Pröll, Maren Julia; Uddin, Muhammad Jasim; Aqter Rony, Sharmin; Tesfaye, Dawit; Tholen, Ernst; Hoelker, Michael; Schellander, Karl; Neuhoff, Christiane

    2017-01-01

    The porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting swine production, health and welfare throughout the world. A synergistic action of the innate and the adaptive immune system of the host is essential for mounting a durable protective immunity through vaccination. Therefore, the current study aimed to investigate the transcriptome profiles of peripheral blood mononuclear cells (PBMCs) to characterize the innate and the adaptive immune response to PRRS Virus (PRRSV) vaccination in Pietrain pigs. The Affymetrix gene chip porcine gene 1.0 ST array was used for the transcriptome profiling of PBMCs collected at immediately before (D0), at one (D1) and 28 days (D28) post PRRSV vaccination with three biological replications. With FDR <0.05 and log2 fold change ±1.5 as cutoff criteria, 295 and 115 transcripts were found to be differentially expressed in PBMCs during the stage of innate and adaptive response, respectively. The microarray expression results were technically validated by qRT-PCR. The gene ontology terms such as viral life cycle, regulation of lymphocyte activation, cytokine activity and inflammatory response were enriched during the innate immunity; cytolysis, T cell mediated cytotoxicity, immunoglobulin production were enriched during adaptive immunity to PRRSV vaccination. Significant enrichment of cytokine-cytokine receptor interaction, signaling by interleukins, signaling by the B cell receptor (BCR), viral mRNA translation, IFN-gamma pathway and AP-1 transcription factor network pathways were indicating the involvement of altered genes in the antiviral defense. Network analysis revealed that four network modules were functionally involved with the transcriptional network of innate immunity, and five modules were linked to adaptive immunity in PBMCs. The innate immune transcriptional network was found to be regulated by LCK, STAT3, ATP5B, UBB and RSP17. While TGFß1, IL7R, RAD21, SP1 and GZMB are likely to

  15. PBMC transcriptome profiles identifies potential candidate genes and functional networks controlling the innate and the adaptive immune response to PRRSV vaccine in Pietrain pig

    PubMed Central

    Islam, Md. Aminul; Große-Brinkhaus, Christine; Pröll, Maren Julia; Uddin, Muhammad Jasim; Aqter Rony, Sharmin; Tesfaye, Dawit; Tholen, Ernst; Hoelker, Michael; Schellander, Karl; Neuhoff, Christiane

    2017-01-01

    The porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting swine production, health and welfare throughout the world. A synergistic action of the innate and the adaptive immune system of the host is essential for mounting a durable protective immunity through vaccination. Therefore, the current study aimed to investigate the transcriptome profiles of peripheral blood mononuclear cells (PBMCs) to characterize the innate and the adaptive immune response to PRRS Virus (PRRSV) vaccination in Pietrain pigs. The Affymetrix gene chip porcine gene 1.0 ST array was used for the transcriptome profiling of PBMCs collected at immediately before (D0), at one (D1) and 28 days (D28) post PRRSV vaccination with three biological replications. With FDR <0.05 and log2 fold change ±1.5 as cutoff criteria, 295 and 115 transcripts were found to be differentially expressed in PBMCs during the stage of innate and adaptive response, respectively. The microarray expression results were technically validated by qRT-PCR. The gene ontology terms such as viral life cycle, regulation of lymphocyte activation, cytokine activity and inflammatory response were enriched during the innate immunity; cytolysis, T cell mediated cytotoxicity, immunoglobulin production were enriched during adaptive immunity to PRRSV vaccination. Significant enrichment of cytokine-cytokine receptor interaction, signaling by interleukins, signaling by the B cell receptor (BCR), viral mRNA translation, IFN-gamma pathway and AP-1 transcription factor network pathways were indicating the involvement of altered genes in the antiviral defense. Network analysis revealed that four network modules were functionally involved with the transcriptional network of innate immunity, and five modules were linked to adaptive immunity in PBMCs. The innate immune transcriptional network was found to be regulated by LCK, STAT3, ATP5B, UBB and RSP17. While TGFß1, IL7R, RAD21, SP1 and GZMB are likely to

  16. 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.

  17. 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.

  18. 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

  19. Online estimation of the wavefront outer scale profile from adaptive optics telemetry

    NASA Astrophysics Data System (ADS)

    Guesalaga, A.; Neichel, B.; Correia, C. M.; Butterley, T.; Osborn, J.; Masciadri, E.; Fusco, T.; Sauvage, J.-F.

    2017-02-01

    We describe an online method to estimate the wavefront outer scale profile, L0(h), for very large and future extremely large telescopes. The stratified information on this parameter impacts the estimation of the main turbulence parameters [turbulence strength, Cn2(h); Fried's parameter, r0; isoplanatic angle, θ0; and coherence time, τ0) and determines the performance of wide-field adaptive optics (AO) systems. This technique estimates L0(h) using data from the AO loop available at the facility instruments by constructing the cross-correlation functions of the slopes between two or more wavefront sensors, which are later fitted to a linear combination of the simulated theoretical layers having different altitudes and outer scale values. We analyse some limitations found in the estimation process: (i) its insensitivity to large values of L0(h) as the telescope becomes blind to outer scales larger than its diameter; (ii) the maximum number of observable layers given the limited number of independent inputs that the cross-correlation functions provide and (iii) the minimum length of data required for a satisfactory convergence of the turbulence parameters without breaking the assumption of statistical stationarity of the turbulence. The method is applied to the Gemini South multiconjugate AO system that comprises five wavefront sensors and two deformable mirrors. Statistics of L0(h) at Cerro Pachón from data acquired during 3 yr of campaigns show interesting resemblance to other independent results in the literature. A final analysis suggests that the impact of error sources will be substantially reduced in instruments of the next generation of giant telescopes.

  20. 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.

  1. Large-scale pharmacological profiling of 3D tumor models of cancer cells.

    PubMed

    Mathews Griner, Lesley A; Zhang, Xiaohu; Guha, Rajarshi; McKnight, Crystal; Goldlust, Ian S; Lal-Nag, Madhu; Wilson, Kelli; Michael, Sam; Titus, Steve; Shinn, Paul; Thomas, Craig J; Ferrer, Marc

    2016-12-01

    The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery. To date, small-scale screens have demonstrated that pharmacological responses tend to differ between 2D and 3D cancer cell growth models. However, the limited scope of screens using 3D models has not provided a clear delineation of the cellular pathways and processes that differentially regulate cell survival and death in the different in vitro tumor models. Here we sought to further understand the differences in pharmacological responses between cancer tumor cells grown in different conditions by profiling a large collection of 1912 chemotherapeutic agents. We compared pharmacological responses obtained from cells cultured in traditional 2D monolayer conditions with those responses obtained from cells forming spheres versus cells already in 3D spheres. The target annotation of the compound library screened enabled the identification of those key cellular pathways and processes that when modulated by drugs induced cell death in all growth conditions or selectively in the different cell growth models. In addition, we also show that many of the compounds targeting these key cellular functions can be combined to produce synergistic cytotoxic effects, which in many cases differ in the magnitude of their synergism depending on the cellular model and cell type. The results from this work provide a high-throughput screening framework to profile the responses of drugs both as single agents and in pairwise combinations in 3D sphere models of cancer cells.

  2. Large-scale pharmacological profiling of 3D tumor models of cancer cells

    PubMed Central

    Mathews Griner, Lesley A; Zhang, Xiaohu; Guha, Rajarshi; McKnight, Crystal; Goldlust, Ian S; Lal-Nag, Madhu; Wilson, Kelli; Michael, Sam; Titus, Steve; Shinn, Paul; Thomas, Craig J; Ferrer, Marc

    2016-01-01

    The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery. To date, small-scale screens have demonstrated that pharmacological responses tend to differ between 2D and 3D cancer cell growth models. However, the limited scope of screens using 3D models has not provided a clear delineation of the cellular pathways and processes that differentially regulate cell survival and death in the different in vitro tumor models. Here we sought to further understand the differences in pharmacological responses between cancer tumor cells grown in different conditions by profiling a large collection of 1912 chemotherapeutic agents. We compared pharmacological responses obtained from cells cultured in traditional 2D monolayer conditions with those responses obtained from cells forming spheres versus cells already in 3D spheres. The target annotation of the compound library screened enabled the identification of those key cellular pathways and processes that when modulated by drugs induced cell death in all growth conditions or selectively in the different cell growth models. In addition, we also show that many of the compounds targeting these key cellular functions can be combined to produce synergistic cytotoxic effects, which in many cases differ in the magnitude of their synergism depending on the cellular model and cell type. The results from this work provide a high-throughput screening framework to profile the responses of drugs both as single agents and in pairwise combinations in 3D sphere models of cancer cells. PMID

  3. 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

  4. Equation of state, universal profiles, scaling and macroscopic quantum effects in warm dark matter galaxies

    NASA Astrophysics Data System (ADS)

    de Vega, H. J.; Sanchez, N. G.

    2017-02-01

    The Thomas-Fermi approach to galaxy structure determines self-consistently and non-linearly the gravitational potential of the fermionic warm dark matter (WDM) particles given their quantum distribution function f( E). This semiclassical framework accounts for the quantum nature and high number of DM particles, properly describing gravitational bounded and quantum macroscopic systems as neutron stars, white dwarfs and WDM galaxies. We express the main galaxy magnitudes as the halo radius r_h , mass M_h , velocity dispersion and phase space density in terms of the surface density which is important to confront to observations. From these expressions we derive the general equation of state for galaxies, i.e., the relation between pressure and density, and provide its analytic expression. Two regimes clearly show up: (1) Large diluted galaxies for M_h ≳ 2.3 × 10^6 M_⊙ and effective temperatures T_0 > 0.017 K described by the classical self-gravitating WDM Boltzman gas with a space-dependent perfect gas equation of state, and (2) Compact dwarf galaxies for 1.6 × 10^6 M_⊙ ≳ M_h ≳ M_{h,min} ˜eq 3.10 × 10^4 (2 {keV}/m)^{16/5} M_⊙, T_0 < 0.011 K described by the quantum fermionic WDM regime with a steeper equation of state close to the degenerate state. In particular, the T_0 = 0 degenerate or extreme quantum limit yields the most compact and smallest galaxy. In the diluted regime, the halo radius r_h , the squared velocity v^2(r_h) and the temperature T_0 turn to exhibit square-root of M_h scaling laws. The normalized density profiles ρ (r)/ρ (0) and the normalized velocity profiles v^2(r)/ v^2(0) are universal functions of r/r_h reflecting the WDM perfect gas behavior in this regime. These theoretical results contrasted to robust and independent sets of galaxy data remarkably reproduce the observations. For the small galaxies, 10^6 ≳ M_h ≥ M_{h,min} , the equation of state is galaxy mass dependent and the density and velocity profiles are not

  5. 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

  6. Atmospheric Profiles of Carbon Dioxide Obtained with a UAS: Constraints on Square Kilometre Scale Carbon Budgets

    NASA Astrophysics Data System (ADS)

    Kunz, M.; Lavric, J. V.; Grant, R. H.; Gerbig, C.; Heimann, M.; Flatt, J. E.; Zeeman, M. J.; Wolf, B.

    2016-12-01

    The exchange of carbon between biosphere and atmosphere is a topic of high interest, particularly because the magnitude of biospheric climate feedback is uncertain. Soil chambers and eddy covariance systems, the traditional tools for the measurement of exchange fluxes, are subject to inherent limitations: chambers cover only small areas of typically less than on square meter, and eddy covariance is not applicable under very low wind conditions. Complementary methods can help to deal with these limitations and provide more confidence in up-scaling. During the ScaleX 2016 campaign an ecosystem was studied with a combination of multiple measurement approaches, including soil chambers, an eddy covariance station, a weather station, quasi-continuous CO2 measurements on a 10 m tower, multiple UAS with different sensors and remote sensing of temperature, humidity and wind profiles. The campaign took place at Fendt in Southern Germany on a flat valley floor covered by grass. We deployed COCAP, a compact carbon dioxide analyser for airborne platforms developed at the Max Planck Institute for Biogeochemistry in Jena, on a commercial multicopter (DJI S1000). COCAP measures carbon dioxide dry air mole fraction to an accuracy of 2 ppm as well as ambient pressure, temperature and relative humidity. At a total mass of 1 kg it contains a GPS receiver, on-board data logging capabilities and a radio transmitter which allows for real-time data visualisation on a ground station computer. In consecutive vertical profile measurements at night-time, reaching up to a maximum height of 150 m, we see a strong build-up of CO2 close to the ground which we attribute to exchange fluxes from the surface into the atmosphere that are trapped below a nocturnal inversion. We estimate these fluxes from the change in observed column amount of CO2 over time and compare our results to other methods. Challenges in the measurement and data analysis as well as the influence of wind, rotor downwash and

  7. Gender-based measurement invariance of the substance use risk profile scale.

    PubMed

    Memetovic, Jasmina; Ratner, Pamela A; Richardson, Christopher G

    2014-03-01

    Gender may influence the psychometric properties of psychological and affect-related measures. The American Psychological Association has made recommendations to conduct tests of group-level measurement invariance (MI) before comparing scores between groups. Gender-based measurement invariance has been examined in many well-known psycho-social scales such as the CES-D and the Big Five Inventory. The Substance Use Risk Profile is a 23-item scale measuring affective- and personality-related traits known to increase risk for substance use, with 4 dimensions: anxiety sensitivity, hopelessness, sensation seeking and impulsivity. Despite similarities in the constructs assessed by the SURPS, the CES-D and the Big Five Inventory, gender-based measurement invariance of the SURPS has not yet been published. Multi-group confirmatory factor analysis was used to assess the measurement invariance of the four dimensions of the SURPS across gender. MI was conducted with M-Plus 6.2 using a 2-step analysis for ordinal variables suggested by Muthén and Muthén, and model fit was assessed using the comparative fit index (CFI) criteria recommended by Cheung and Rensvold. A single group confirmatory factor analysis (CFA) was also conducted. The sample was composed of 1352 adolescents (56% female, mean age of 14years) participating in the BC Adolescent Substance Use Survey, an online survey capturing substance use and psychosocial trends in secondary students across British Columbia, Canada. Measurement invariance across gender was demonstrated for the SURPS (ΔCFI=0.003), and the single group CFA supported a four-dimensional structure for the SURPS items (CFI=0.92, RMSEA=061, 95% CI=0.058-0.065).

  8. Constraining the Biological Pump on Seasonal Scales through Autonomous Oxygen Observations from Profiling Floats

    NASA Astrophysics Data System (ADS)

    Bittig, H. C.; Claustre, H.; Koertzinger, A.

    2016-02-01

    Understanding the biological pump is limited by our knowledge of the governing processes and drivers as well as by the scarcity of data related to its function. Autonomous float observations can help mitigate both by providing a cost-efficient way to obtain in-situ observations at improved temporal and spatial scales compared to traditional sampling methods. Oxygen observations are especially suited for this purpose because of the tight coupling between the oxygen (O2) and carbon (C) cycle and the availability of a reliable and accurate O2 sensor technology.On seasonal scales, oxygen remineralization below the euphotic zone causes an accumulation of an O2 deficit which provides a quantitative estimate of the mesopelagic C flux and its attenuation. This approach is insensitive to single export events of fast-sinking, large particles. Instead, it integrates over short-term variability in the break-up/remineralization of small particles because of its cumulative nature. As such, it provides a valuable comparison with event-focused flux estimates from, e.g., particle-based measurements.Complementing the mesopelagic, net community production (NCP) in the surface and sub-surface provides a bound to export production. NCP can be derived from a timeseries of observed O2 profiles in conjunction with a simple 1D mixing and gas exchange model. The examples of mesopelagic C flux and surface NCP presented here are based on Bio-Argo floats deployed in the subpolar North Atlantic as well as in the North and South Atlantic subtropical gyres. In addition, they are used to illustrate the limits that ocean physics (e.g., deep vs. shallow winter mixing) sets to the applicability of above analyses.

  9. E2 multimeric scaffold for vaccine formulation: immune response by intranasal delivery and transcriptome profile of E2-pulsed dendritic cells.

    PubMed

    Trovato, Maria; Maurano, Francesco; D'Apice, Luciana; Costa, Valerio; Sartorius, Rossella; Cuccaro, Fausta; McBurney, Sean P; Krebs, Shelly J; Prisco, Antonella; Ciccodicola, Alfredo; Rossi, Mauro; Haigwood, Nancy L; De Berardinis, Piergiuseppe

    2016-07-16

    The E2 multimeric scaffold represents a powerful delivery system able to elicit robust humoral and cellular immune responses upon systemic administrations. Here recombinant E2 scaffold displaying the third variable loop of HIV-1 Envelope gp120 glycoprotein was administered via mucosa, and the mucosal and systemic immune responses were analysed. To gain further insights into the molecular mechanisms that orchestrate the immune response upon E2 vaccination, we analysed the transcriptome profile of dendritic cells (DCs) exposed to the E2 scaffold with the aim to define a specific gene expression signature for E2-primed immune responses. The in vivo immunogenicity and the potential of E2 scaffold as a mucosal vaccine candidate were investigated in BALB/c mice vaccinated via the intranasal route. Fecal and systemic antigen-specific IgA antibodies, cytokine-producing CD4(+) and CD8(+) cells were induced assessing the immunogenicity of E2 particles via intranasal administration. The cytokine analysis identified a mixed T-helper cell response, while the systemic antibody response showed a prevalence of IgG1 isotype indicative of a polarized Th2-type immune response. RNA-Sequencing analysis revealed that E2 scaffold up-regulates in DCs transcriptional regulators of the Th2-polarizing cell response, defining a type 2 DC transcriptomic signature. The current study provides experimental evidence to the possible application of E2 scaffold as antigen delivery system for mucosal immunization and taking advantages of genome-wide approach dissects the type of response induced by E2 particles.

  10. The SF-36 component summary scales and the daytime diurnal cortisol profile.

    PubMed

    Hagger-Johnson, Gareth Edward; Whiteman, Martha C; Wawrzyniak, Andrew J; Holroyd, Warren G

    2010-06-01

    Higher daytime cortisol output has been associated with higher levels of perceived stress and worse mental and physical health outcomes. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation, such as elevated secretion of daytime cortisol, occurs in many mental and physical illnesses. However, the nature of the association between functional health status and daytime cortisol production has not been established. Healthy adult volunteers (n=68, 45 females) provided saliva samples 3, 6, 9 and 12 h after waking, for two consecutive days, in everyday settings. Bivariate correlations between log salivary cortisol concentrations were calculated, and the SF-36 component summary scores were calculated. Latent growth curve modeling was used to model the daytime profile and adjust for covariates (age, sex and waking time). Higher PCS scores were not associated with cortisol three hours after waking (cortisol intercept), or the diurnal decline (cortisol slope). Higher MCS scores were correlated with faster cortisol decline across the day (r=-.31, P<.01) but not with cortisol intercepts. In a latent growth curve model adjusting for age, sex and waking time, the association was no longer statistically significant. Large scale epidemiological studies involving salivary cortisol would benefit from measuring SF-36 component summary scores. Cortisol intercepts and slopes may be differentially related to the PCS and MCS, although greater statistical power is needed to test this hypothesis more fully. Associations between daytime cortisol and the PCS or MCS could reflect the regulatory competence of bodily systems, common causes or unmeasured confounding factors.

  11. 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

  12. 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; hide

    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.

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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

  20. 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

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

    PubMed

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

    2013-10-29

    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.

  2. 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

  3. Cyclin-dependent Kinase 8 Module Expression Profiling Reveals Requirement of Mediator Subunits 12 and 13 for Transcription of Serpent-dependent Innate Immunity Genes in Drosophila*

    PubMed Central

    Kuuluvainen, Emilia; Hakala, Heini; Havula, Essi; Sahal Estimé, Michelle; Rämet, Mika; Hietakangas, Ville; Mäkelä, Tomi P.

    2014-01-01

    The Cdk8 (cyclin-dependent kinase 8) module of Mediator integrates regulatory cues from transcription factors to RNA polymerase II. It consists of four subunits where Med12 and Med13 link Cdk8 and cyclin C (CycC) to core Mediator. Here we have investigated the contributions of the Cdk8 module subunits to transcriptional regulation using RNA interference in Drosophila cells. Genome-wide expression profiling demonstrated separation of Cdk8-CycC and Med12-Med13 profiles. However, transcriptional regulation by Cdk8-CycC was dependent on Med12-Med13. This observation also revealed that Cdk8-CycC and Med12-Med13 often have opposite transcriptional effects. Interestingly, Med12 and Med13 profiles overlapped significantly with that of the GATA factor Serpent. Accordingly, mutational analyses indicated that GATA sites are required for Med12-Med13 regulation of Serpent-dependent genes. Med12 and Med13 were also found to be required for Serpent-activated innate immunity genes in defense to bacterial infection. The results reveal a novel role for the Cdk8 module in Serpent-dependent transcription and innate immunity. PMID:24778181

  4. 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

  5. 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

  6. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

    PubMed Central

    Nichol, Kathryn E; Poon, Wayne W; Parachikova, Anna I; Cribbs, David H; Glabe, Charles G; Cotman, Carl W

    2008-01-01

    Background Inflammation is associated with Aβ pathology in Alzheimer's disease (AD) and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17–19 months) Tg2576 mice to a response that reduces Aβ pathology. Methods TG (n = 29) and WT (n = 27) mice were divided into sedentary (SED) and exercised (RUN) groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. Results IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TGSED) mice than in wildtype (WTSED) (p = 0.04, p = 0.006). Immune response proteins IFN-γ and MIP-1α are lower in TGSED mice than in WTSED (p = 0.03, p = 0.07). Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFN-γ and MIP-1α increased in TGRUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TGRUN animals compared to TGSED, as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TGRUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ40 (p = 0.01) and soluble fibrillar Aβ (p = 0.01) were observed in the exercised transgenic animals. Conclusion Exercise shifts the immune response from innate to an adaptive or alternative response

  7. Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response.

    PubMed

    Oskvig, Devon B; Elkahloun, Abdel G; Johnson, Kory R; Phillips, Terry M; Herkenham, Miles

    2012-05-01

    Maternal immune activation (MIA) is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment, with consequential effects on CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on gestational day 15. LPS significantly elevated pro-inflammatory cytokine levels in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-treated dams exhibited reduced social preference and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate the possible molecular mechanisms by which MIA affects the fetal brain. We observed dysregulation of 3285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons, including the Distal-less (Dlx) family of transcription factors required for tangential migration from progenitor pools within the ganglionic eminences into the cerebral cortex. Our results provide a novel mechanism by which MIA induces the widespread down-regulation of critical neurodevelopmental genes, including those previously associated with autism.

  8. Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response

    PubMed Central

    Oskvig, Devon B.; Elkahloun, Abdel G.; Johnson, Kory R.; Phillips, Terry M.; Herkenham, Miles

    2012-01-01

    Maternal immune activation (MIA) is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother’s immune system and alter the fetal environment, with consequential effects on CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on gestational day 15. LPS significantly elevated pro-inflammatory cytokine levels in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-treated dams exhibited reduced social preference and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate the possible molecular mechanisms by which MIA affects the fetal brain. We observed dysregulation of 3,285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons, including the Distal-less (Dlx) family of transcription factors required for tangential migration from progenitor pools within the ganglionic eminences into the cerebral cortex. Our results provide a novel mechanism by which MIA induces the widespread down-regulation of critical neurodevelopmental genes, including those previously associated with autism. PMID:22310921

  9. 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

  10. A simple and sensitive method for lipoprotein and lipids profiles analysis of individual micro-liter scale serum samples.

    PubMed

    Yang, Liu; Fan, Baoyan; Yang, Kangmin; Zhu, Haibo

    2012-02-01

    A simple and sensitive method to determine lipoprotein and lipids profiles in micro-liter scale individual serum sample is not presently available. Traditional lipoprotein separation techniques either by ultra-centrifugation or by liquid chromatography methods have their disadvantages in both lipoprotein separation and lipids component quantification. In this study we used small volume needing size-exclusion fast protein liquid chromatography to separate different lipoprotein subclasses in 50μL serum. And lipids contents, such as cholesterol, cholesterol ester and triacylglycerol, were measured by using two different fluorescence-based lipid detection methods. With this method, very low density lipoprotein, low density lipoprotein and high density lipoprotein could be easily separated, and follow-up lipid detection was completed by simple kinds of reactions. Serum lipoprotein and lipids profiling from C57BL/6 mice (n=5) and human (n=5) were analyzed. The elution profiles of five individuals were highly reproducible, and there were lipoprotein and lipids distribution variations between C57BL/6 mice and human beings. In conclusion, this method which combined small volume needing size-exclusion fast protein liquid chromatography and fluorescence-based lipids measurement, provided a simple, efficient, integrity and reproducible procedure for determining serum lipoprotein and lipids profiles in micro-liter scale levels. It becomes possible that determination of lipoprotein profiles and gaining information of lipids in different lipoproteins can be accomplished simultaneously. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. 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

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

    PubMed

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

    2015-07-01

    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. 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. 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 broysam@central.uh.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. 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.

  14. Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities

    PubMed Central

    2013-01-01

    The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate / inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell / antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease. PMID:23865616

  15. Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities.

    PubMed

    Gorgoglione, Bartolomeo; Wang, Tiehui; Secombes, Christopher J; Holland, Jason W

    2013-07-16

    The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate/inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease.

  16. Ontogenetic profile of innate immune related genes and their tissue-specific expression in brown trout, Salmo trutta (Linnaeus, 1758).

    PubMed

    Cecchini, Stefano; Paciolla, Mariateresa; Biffali, Elio; Borra, Marco; Ursini, Matilde V; Lioi, Maria B

    2013-09-01

    The innate immune system is a fundamental defense weapon of fish, especially during early stages of development when acquired immunity is still far from being completely developed. The present study aims at looking into ontogeny of innate immune system in the brown trout, Salmo trutta, using RT-PCR based approach. Total RNA extracted from unfertilized and fertilized eggs and hatchlings at 0, 1 h and 1, 2, 3, 4, 5, 6, 7 weeks post-fertilization was subjected to RT-PCR using self-designed primers to amplify some innate immune relevant genes (TNF-α, IL-1β, TGF-β and lysozyme c-type). The constitutive expression of β-actin was detected in all developmental stages. IL-1β and TNF-α transcripts were detected from 4 week post-fertilization onwards, whereas TGF-β transcript was detected only from 7 week post-fertilization onwards. Lysozyme c-type transcript was detected early from unfertilized egg stage onwards. Similarly, tissues such as muscle, ovary, heart, brain, gill, testis, liver, intestine, spleen, skin, posterior kidney, anterior kidney and blood collected from adult brown trout were subjected to detection of all selected genes by RT-PCR. TNF-α and lysozyme c-type transcripts were expressed in all tissues. IL-1β and TGF-β transcripts were expressed in all tissues except for the brain and liver, respectively. Taken together, our results show a spatial-temporal expression of some key innate immune-related genes, improving the basic knowledge of the function of innate immune system at early stage of brown trout. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Large scale profiles of galaxies at z=0-2 studied by stacking the HSC SSP survey data

    NASA Astrophysics Data System (ADS)

    Kubo, Mariko; Ouchi, Masami; Shibuya, Takatoshi

    2017-03-01

    We are carrying out the study of the evolution of radial surface brightness profiles of galaxies from z = 0 to 2 by stacking analysis using data corrected by the Hyper Suprime-Cam (HSC) Subaru Strategic Program (SSP). This will allow us to constrain the large scale average profiles of various galaxy populations at high redshift. From the stacking analysis of galaxies selected based on their photometric redshifts, we successfully detected the outer components of galaxies at z > 1 extending to at least ~80 kpc, which imply an early formation for the galaxy outskirts.

  18. Population differences in immune marker profiles associated with human T-lymphotropic virus type I infection in Japan and Jamaica

    PubMed Central

    Birmann, Brenda M; Breen, Elizabeth C; Stuver, Sherri; Cranston, Beverly; Martínez-Maza, Otoniel; Falk, Kerstin I; Okayama, Akihiko; Hanchard, Barrie; Mueller, Nancy; Hisada, Michie

    2009-01-01

    The natural history of human T-lymphotropic virus type I (HTLV-I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)-i.e., 51 HTLV-I-positive (“carriers”) and 51 HTLV-I-negative individuals (“non-carriers”) from each population-by age, sex, and blood collection year. We compared plasma concentrations of markers of T-cell-mediated (antigen-specific) and non-specific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV-I non-carriers, Japanese non-carriers had higher covariate-adjusted mean levels of T-cell activation markers, including antibody to Epstein-Barr virus nuclear antigen-1 (reciprocal titer 27 v. 71, respectively, p=0.005), soluble interleukin-2 receptor-α (477 v. 623 pg/mL, p=0.0008) and soluble CD30 (34 v. 46 U/mL, p=0.0001), and lower levels of C-reactive protein (1.1 v. 0.43 μg/mL, p=0.0004). HTLV-I infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons. The observed population differences in background and HTLV-I-related host immunity correspond closely to the divergent natural histories of infection observed among HTLV-I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk. PMID:18989900

  19. Expression Profiling of Human Immune Cell Subsets Identifies miRNA-mRNA Regulatory Relationships Correlated with Cell Type Specific Expression

    PubMed Central

    Bergauer, Tobias; Ravindran, Palanikumar; Rossier, Michel F.; Ebeling, Martin; Badi, Laura; Reis, Bernhard; Bitter, Hans; D'Asaro, Matilde; Chiappe, Alberto; Sridhar, Sriram; Pacheco, Gonzalo Duran; Burczynski, Michael E.; Hochstrasser, Denis; Vonderscher, Jacky; Matthes, Thomas

    2012-01-01

    Blood consists of different cell populations with distinct functions and correspondingly, distinct gene expression profiles. In this study, global miRNA expression profiling was performed across a panel of nine human immune cell subsets (neutrophils, eosinophils, monocytes, B cells, NK cells, CD4 T cells, CD8 T cells, mDCs and pDCs) to identify cell-type specific miRNAs. mRNA expression profiling was performed on the same samples to determine if miRNAs specific to certain cell types down-regulated expression levels of their target genes. Six cell-type specific miRNAs (miR-143; neutrophil specific, miR-125; T cells and neutrophil specific, miR-500; monocyte and pDC specific, miR-150; lymphoid cell specific, miR-652 and miR-223; both myeloid cell specific) were negatively correlated with expression of their predicted target genes. These results were further validated using an independent cohort where similar immune cell subsets were isolated and profiled for both miRNA and mRNA expression. miRNAs which negatively correlated with target gene expression in both cohorts were identified as candidates for miRNA/mRNA regulatory pairs and were used to construct a cell-type specific regulatory network. miRNA/mRNA pairs formed two distinct clusters in the network corresponding to myeloid (nine miRNAs) and lymphoid lineages (two miRNAs). Several myeloid specific miRNAs targeted common genes including ABL2, EIF4A2, EPC1 and INO80D; these common targets were enriched for genes involved in the regulation of gene expression (p<9.0E-7). Those miRNA might therefore have significant further effect on gene expression by repressing the expression of genes involved in transcriptional regulation. The miRNA and mRNA expression profiles reported in this study form a comprehensive transcriptome database of various human blood cells and serve as a valuable resource for elucidating the role of miRNA mediated regulation in the establishment of immune cell identity. PMID:22276136

  20. Surge in regulatory T cells does not prevent onset of hyperglycemia in NOD mice: immune profiles do not correlate with disease severity.

    PubMed

    Kaminitz, Ayelet; Mizrahi, Keren; Askenasy, Nadir

    2014-03-01

    Immune profiling of non-obese diabetic (NOD) is a widely employed tool to assess the mechanisms of inflammatory insulitis. Our analysis of the female NOD colony revealed similar distribution of lymphoid lineages to wild type mice, and at various ages of prediabetic and diabetic mice. The profiles of mesenteric and pancreatic lymph nodes differ and often change reciprocally due to directed migration of T cells towards the site of inflammation. Significant events in our colony include early decline in CD4(+)CD25(+)CD62L(+) Treg, accompanied by gradual increase in CD4(+)CD25(+)FoxP3(+) Treg in peripheral lymphoid organs and pancreatic infiltrates. Impressively, aged euglycemic mice display significant transient rise in CD4(+)CD25(-)FoxP3(+) Treg in the thymus, pancreas and draining lymph nodes. A significant difference was superior viability of effector and suppressor cells from new onset diabetics in the presence of high interleukin-2 (IL-2) concentrations in vitro as compared to cells of prediabetic mice. Overall, we found no correlation between FoxP3(+) Treg in the pancreatic lymph nodes and the inflammatory scores of individual NOD mice. CD25(-)FoxP3(+) Treg are markedly increased in the pancreatic infiltrates in late stages of inflammation, possibly an effort to counteract destructive insulitis. Considering extensive evidence that Treg in aged NOD mice are functionally sufficient, quantitative profiling evolves as an unreliable tool to assess mechanism and causes of inflammation under baseline conditions. Immune profiles are modulated by thymic output, cell migration, shedding of markers, proliferation, survival and in-situ evolution of regulatory cells.

  1. 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}⊙ . 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}⊙ -1015 {M}⊙ 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.

  2. 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…

  3. 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…

  4. 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)

  5. 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)

  6. 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

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

    PubMed

    Moreira, Rebeca; Milan, Massimo; Balseiro, Pablo; Romero, Alejandro; Babbucci, Massimiliano; Figueras, Antonio; Bargelloni, Luca; Novoa, Beatriz

    2014-04-07

    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. 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. Using a new version of the R. philippinarum oligo-microarray, a putative timing for the response against a Vibrio infection was established. The key point to overcome the

  8. Immune response and protective profile elicited by a multi-epitope chimeric protein derived from Leptospira interrogans.

    PubMed

    Fernandes, Luis G V; Teixeira, Aline F; Filho, Antonio F S; Souza, Gisele O; Vasconcellos, Silvio A; Heinemann, Marcos B; Romero, Eliete C; Nascimento, Ana L T O

    2017-04-01

    Pathogenic Leptospira is the causative agent of leptospirosis, a widely disseminated disease of human and veterinary concern. The development of vaccines that elicit cross-protective immunity through multiple leptospiral serovars has long been pursued. The aim of this study was to develop a novel chimeric multi-epitope fusion antigen, containing sequences of previously studied outer membrane proteins (OMPs) of Leptospira. The chimeric protein was designed based on the amino acid sequences of the LigA, Mce, Lsa45, OmpL1, and LipL41 proteins, cloned into pAE vector, the protein expressed in Escherichia coli, and its immune response evaluated in the hamster infection model. The recombinant chimeric protein (rChi) was recognized by antibodies present in serum samples of confirmed cases of human leptospirosis and experimentally infected hamsters, demonstrating that the rChi protein participates in the immune response activation during infection. However, despite high antibody titers achieved when the rChi protein was administered with either Alhydrogel or Bordetella pertussis monophosphoryl lipid A (MPLA), only 50% of the hamsters were protected against infection. Although a complete characterization of the immune response elicited by rChi/adjuvant in hamsters is required, it is believed that the construction of chimeric genes is an important attempt towards the generation of an effective vaccine against leptospirosis. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. Effects of novel vaccine/adjuvant complexes on the protective immunity against Eimeria acervulina and transcriptome profiles

    USDA-ARS?s Scientific Manuscript database

    This study investigated the ability of two novel adjuvant formulations, QCDC (Quil A/cholesterol/DDA/Carbopol) and QCDCR (QCDC/Bay R1005), in combination with a recombinant profilin vaccine, to modulate host protective immunity and to alter gene expression during experimental avian coccidiosis. Vac...

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  11. 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

  12. Understanding Herd Immunity.

    PubMed

    Metcalf, C J E; Ferrari, M; Graham, A L; Grenfell, B T

    2015-12-01

    Individual immunity is a powerful force affecting host health and pathogen evolution. Importantly, the effects of individual immunity also scale up to affect pathogen transmission dynamics and the success of vaccination campaigns for entire host populations. Population-scale immunity is often termed 'herd immunity'. Here we outline how individual immunity maps to population outcomes and discuss implications for control of infectious diseases. Particular immunological characteristics may be more or less likely to result in a population level signature of herd immunity; we detail this and also discuss other population-level outcomes that might emerge from individual-level immunity.

  13. Distinct Innate Immune Gene Expression Profiles in Non-Melanoma Skin Cancer of Immunocompetent and Immunosuppressed Patients

    PubMed Central

    Muehleisen, Beda; Jiang, Shang Brian; Gladsjo, Julie A.; Gerber, Monika; Hata, Tissa; Gallo, Richard L.

    2012-01-01

    Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most frequent skin cancers in humans. An intact immune system is critical for protection against SCC since organ transplant recipients (OTR) have a 60- to 100-fold higher risk for developing these tumors. The role of the innate immune system in tumor immunosurveillance is unclear. Our aim was to determine the expression of selected innate immune genes in BCC and SCC arising in immunocompetent and OTR patients. Lesional and peri-lesional skin from 28 SCC and 19 BCC were evaluated for mRNA expression of toll-like receptors (TLR) 1–9, downstream TLR signaling molecules, and antimicrobial peptides. 11 SCC occurring in OTR patients were included in the analysis. We found that SCC but not BCC showed significantly elevated expression of TLRs 1–3, 5–8, TRIF and TRAF1. TNF was increased in SCC compared to normal skin. BCC showed increased IFNγ. hBD1, hBD2 and psoriasin mRNA and protein expression were significantly higher in SCC than in normal skin and higher than in BCC. SCC from OTR showed only an increase in hBD2 but no increase in hBD1 or psoriasin. We conclude that innate immune gene expression in SCC is distinct from normal skin and BCC. BCC shows lesser induction of innate immune genes. SCC from OTR patients have depressed expression of hBD1 and psoriasin compared to SCC from immunocompetent patients. PMID:22808251

  14. Visceral fat adipocytes from obese and colorectal cancer subjects exhibit distinct secretory and ω6 polyunsaturated fatty acid profiles and deliver immunosuppressive signals to innate immunity cells

    PubMed Central

    Conti, Lucia; Scazzocchio, Beatrice; Varì, Rosaria; Donninelli, Gloria; Varano, Barbara; Giammarioli, Stefania; De Meo, Simone; Silecchia, Gianfranco; Pennestrì, Francesco; Persiani, Roberto; Masella, Roberta; Gessani, Sandra

    2016-01-01

    Obesity is a low-grade chronic inflammatory state representing an important risk factor for colorectal cancer (CRC). Adipocytes strongly contribute to inflammation by producing inflammatory mediators. In this study we investigated the role of human visceral fat adipocytes in regulating the functions of innate immunity cells. Adipocyte-conditioned media (ACM) from obese (n = 14) and CRC (lean, n = 14; obese, n = 13) subjects released higher levels of pro-inflammatory/immunoregulatory factors as compared to ACM from healthy lean subjects (n = 13). Dendritic cells (DC), differentiated in the presence of ACM from obese and CRC subjects, expressed elevated levels of the inhibitory molecules PD-L1 and PD-L2, and showed a reduced IL-12/IL-10 ratio in response to both TLR ligand- and γδ T lymphocyte-induced maturation. Furthermore, CRC patient-derived ACM inhibited DC-mediated γδ T cell activation. The immunosuppressive signals delivered by ACM from obese and CRC individuals were associated with a pro-inflammatory secretory and ω6 polyunsaturated fatty acid profile of adipocytes. Interestingly, STAT3 activation in adipocytes correlated with dihomo-γlinolenic acid content and was further induced by arachidonic acid, which conversely down-modulated PPARγ. These results provide novel evidence for a cross-talk between human adipocytes and innate immunity cells whose alteration in obesity and CRC may lead to immune dysfunctions, thus setting the basis for cancer development. PMID:27494857

  15. Spanish version of the Substance Use Risk Profile Scale: factor structure, reliability, and validity in Mexican adolescents.

    PubMed

    Robles-García, Rebeca; Fresán, Ana; Castellanos-Ryan, Natalie; Conrod, Patricia; Gómez, Diego; de Quevedo Y Domínguez, María Emilia G; Rafful, Claudia; Real, Tania; Vásquez, Lucía; Medina-Mora, María Elena

    2014-12-30

    To validate the Substance Use Risk Profile Scale (SURPS) in a sample of Mexican adolescents, this brief 23-item self-report questionnaire has been developed to screen four high-risk personality traits for substance misuse, to guide targeted approaches to prevention of addictions in adolescents. The scale has been previously validated in United Kingdom, Canada, Sri Lanka and China. A sample of 671 adolescents aged 11-17 completed a Spanish translation of the SURPS as well as other measures of personality and substance use. The Spanish translation of the SURPS has moderate internal consistency, and demonstrated a four-factor structure very similar to the original scale. The four subscales show good concurrent validity and three of the subscales were found to correlate with measures of substance use. The Spanish translation of the SURPS seems to be a valid and sensitive scale that can be used in a Mexican adolescent population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Understanding and predicting profile structure and parametric scaling of intrinsic rotation

    NASA Astrophysics Data System (ADS)

    Wang, W. X.; Grierson, B. A.; Ethier, S.; Chen, J.; Startsev, E.; Diamond, P. H.

    2017-09-01

    This paper reports on a recent advance in developing physical understanding and a first-principles-based model for predicting intrinsic rotation profiles in magnetic fusion experiments. It is shown for the first time that turbulent fluctuation-driven residual stress (a non-diffusive component of momentum flux) along with diffusive momentum flux can account for both the shape and magnitude of the observed intrinsic toroidal rotation profile. Both the turbulence intensity gradient and zonal flow E ×B shear are identified as major contributors to the generation of the k∥-asymmetry needed for the residual stress generation. The model predictions of core rotation based on global gyrokinetic simulations agree well with the experimental measurements of main ion toroidal rotation for a set of DIII-D ECH discharges. The validated model is further used to investigate the characteristic dependence of residual stress and intrinsic rotation profile structure on the multi-dimensional parametric space covering the turbulence type, q-profile structure, and up-down asymmetry in magnetic geometry with the goal of developing the physics understanding needed for rotation profile control and optimization. It is shown that in the flat-q profile regime, intrinsic rotations driven by ITG and TEM turbulence are in the opposite direction (i.e., intrinsic rotation reverses). The predictive model also produces reversed intrinsic rotation for plasmas with weak and normal shear q-profiles.

  17. 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

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

    2013-09-01

    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.

  18. 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.

  19. An Evaluation of and a Detail-Profile for the Vineland Social Maturity Scale.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    The Vineland Social Maturity Scale (VSMS) is a good measure of adaptive behavior for the pre-school child or the retardate of pre-school ability. It is an excellent clinical technqiue. It is more than a questionnaire and more than a rating scale. We recommend it as an interview and behavior-observation scale. We recommend it for treatment…

  20. Divergent response profile in activated cord blood T cells from first-born child implies birth-order-associated in utero immune programming.

    PubMed

    Kragh, M; Larsen, J M; Thysen, A H; Rasmussen, M A; Wolsk, H M; Bisgaard, H; Brix, S

    2016-03-01

    First-born children are at higher risk of developing a range of immune-mediated diseases. The underlying mechanism of 'birth-order effects' on disease risk is largely unknown, but in utero programming of the child's immune system may play a role. We studied the association between birth order and the functional response of stimulated cord blood T cells. Purified cord blood T cells were polyclonally activated with anti-CD3-/anti-CD28-coated beads in a subgroup of 28 children enrolled in the COPSAC2010 birth cohort. Expression levels of seven activation markers on helper and cytotoxic T cells as well as the percentage of CD4(+) CD25(+) T cells were assessed by flow cytometry. Production of IFN-γ, TNF-α, IL-17, IL-4, IL-5, IL-13, and IL-10 was measured in the supernatants. IL-10 secretion (P = 0.007) and CD25 expression on CD4(+) helper T cells (P = 0.0003) in the activated cord blood T cells were selectively reduced in first-born children, while the percentage of circulating CD4(+) CD25(+) cord blood T cells was independent of birth order. First-born infants display a reduced anti-inflammatory profile in T cells at birth. This possible in utero 'birth-order' T-cell programming may contribute to later development of immune-mediated diseases by increasing overall immune reactivity in first-born children as compared to younger siblings. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Ribosome profiling: a Hi-Def monitor for protein synthesis at the genome-wide scale.

    PubMed

    Michel, Audrey M; Baranov, Pavel V

    2013-01-01

    Ribosome profiling or ribo-seq is a new technique that provides genome-wide information on protein synthesis (GWIPS) in vivo. It is based on the deep sequencing of ribosome protected mRNA fragments allowing the measurement of ribosome density along all RNA molecules present in the cell. At the same time, the high resolution of this technique allows detailed analysis of ribosome density on individual RNAs. Since its invention, the ribosome profiling technique has been utilized in a range of studies in both prokaryotic and eukaryotic organisms. Several studies have adapted and refined the original ribosome profiling protocol for studying specific aspects of translation. Ribosome profiling of initiating ribosomes has been used to map sites of translation initiation. These studies revealed the surprisingly complex organization of translation initiation sites in eukaryotes. Multiple initiation sites are responsible for the generation of N-terminally extended and truncated isoforms of known proteins as well as for the translation of numerous open reading frames (ORFs), upstream of protein coding ORFs. Ribosome profiling of elongating ribosomes has been used for measuring differential gene expression at the level of translation, the identification of novel protein coding genes and ribosome pausing. It has also provided data for developing quantitative models of translation. Although only a dozen or so ribosome profiling datasets have been published so far, they have already dramatically changed our understanding of translational control and have led to new hypotheses regarding the origin of protein coding genes. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Ribosome profiling: a Hi-Def monitor for protein synthesis at the genome-wide scale

    PubMed Central

    Michel, Audrey M; Baranov, Pavel V

    2013-01-01

    Ribosome profiling or ribo-seq is a new technique that provides genome-wide information on protein synthesis (GWIPS) in vivo. It is based on the deep sequencing of ribosome protected mRNA fragments allowing the measurement of ribosome density along all RNA molecules present in the cell. At the same time, the high resolution of this technique allows detailed analysis of ribosome density on individual RNAs. Since its invention, the ribosome profiling technique has been utilized in a range of studies in both prokaryotic and eukaryotic organisms. Several studies have adapted and refined the original ribosome profiling protocol for studying specific aspects of translation. Ribosome profiling of initiating ribosomes has been used to map sites of translation initiation. These studies revealed the surprisingly complex organization of translation initiation sites in eukaryotes. Multiple initiation sites are responsible for the generation of N-terminally extended and truncated isoforms of known proteins as well as for the translation of numerous open reading frames (ORFs), upstream of protein coding ORFs. Ribosome profiling of elongating ribosomes has been used for measuring differential gene expression at the level of translation, the identification of novel protein coding genes and ribosome pausing. It has also provided data for developing quantitative models of translation. Although only a dozen or so ribosome profiling datasets have been published so far, they have already dramatically changed our understanding of translational control and have led to new hypotheses regarding the origin of protein coding genes. © 2013 John Wiley & Sons, Ltd. PMID:23696005

  3. 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.

  4. Anamnestic immunological response profile in laboratory animals after immunization with recombinant hepatitis B vaccines of different generations.

    PubMed

    Górska, Paulina; Michałkiewicz, Jacek; Bucholc, Bożenna

    2012-11-01

    Hepatitis B vaccines containing preS1 and preS2 fragments are assumed to be more immunogenic than those containing SHBs protein alone, which may be of importance for immunization of people with poorly induced or without any immunological response after vaccination. The aim of this study was to evaluate: The following conclusions can be drawn on the basis of obtained results:

  5. Transcriptome Profiling Analysis on Whole Bodies of Microbial Challenged Eriocheir sinensis Larvae for Immune Gene Identification and SNP Development

    PubMed Central

    Cui, Zhaoxia; Li, Xihong; Liu, Yuan; Song, Chengwen; Hui, Min; Shi, Guohui; Luo, Danli; Li, Yingdong

    2013-01-01

    To study crab immunogenetics of individuals, newly hatched Eriocheir sinensis larvae were stimulated with a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 108 cfu·mL-1). A total of 44,767,566 Illumina clean reads corresponding to 4.52 Gb nucleotides were generated and assembled into 100,252 unigenes (average length: 1,042 bp; range: 201-19,357 bp). 17,097 (26.09%) of 65,535 non-redundant unigenes were annotated in NCBI non-redundant protein (Nr) database. Moreover, 23,188 (35.38%) unigenes were assigned to three Gene Ontology (GO) categories, 15,071 (23.00%) to twenty-six Clusters of orthologous Groups (COG) and 8,574 (13.08%) to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. Numerous genes were further identified to be associated with multiple immune pathways, including Toll, immune deficiency (IMD), janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinase (MAPK) pathways. Some of them, such as tumor necrosis factor receptor associated factor 6 (TRAF6), fibroblast growth factor (FGF), protein-tyrosine phosphatase (PTP), JNK-interacting protein 1 (JIP1), were first identified in E. sinensis. TRAF6 was even first discovered in crabs. Additionally, 49,555 single nucleotide polymorphisms (SNPs) were developed from over 13,309 unigenes. This is the first transcriptome report of whole bodies of E. sinensis larvae after immune challenge. Data generated here not only provide detail information to identify novel genes in genome reference-free E. sinensis, but also facilitate our understanding on host immunity and defense mechanism of the crab at whole transcriptome level. PMID:24324760

  6. Transcriptome profiling analysis on whole bodies of microbial challenged Eriocheir sinensis larvae for immune gene identification and SNP development.

    PubMed

    Cui, Zhaoxia; Li, Xihong; Liu, Yuan; Song, Chengwen; Hui, Min; Shi, Guohui; Luo, Danli; Li, Yingdong

    2013-01-01

    To study crab immunogenetics of individuals, newly hatched Eriocheir sinensis larvae were stimulated with a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 10(8) cfu·mL(-1)). A total of 44,767,566 Illumina clean reads corresponding to 4.52 Gb nucleotides were generated and assembled into 100,252 unigenes (average length: 1,042 bp; range: 201-19,357 bp). 17,097 (26.09%) of 65,535 non-redundant unigenes were annotated in NCBI non-redundant protein (Nr) database. Moreover, 23,188 (35.38%) unigenes were assigned to three Gene Ontology (GO) categories, 15,071 (23.00%) to twenty-six Clusters of orthologous Groups (COG) and 8,574 (13.08%) to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. Numerous genes were further identified to be associated with multiple immune pathways, including Toll, immune deficiency (IMD), janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinase (MAPK) pathways. Some of them, such as tumor necrosis factor receptor associated factor 6 (TRAF6), fibroblast growth factor (FGF), protein-tyrosine phosphatase (PTP), JNK-interacting protein 1 (JIP1), were first identified in E. sinensis. TRAF6 was even first discovered in crabs. Additionally, 49,555 single nucleotide polymorphisms (SNPs) were developed from over 13,309 unigenes. This is the first transcriptome report of whole bodies of E. sinensis larvae after immune challenge. Data generated here not only provide detail information to identify novel genes in genome reference-free E. sinensis, but also facilitate our understanding on host immunity and defense mechanism of the crab at whole transcriptome level.

  7. 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.

  8. 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 Central

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

    2016-01-01

    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

  9. Dietary Lactobacillus acidophilus modulated skin mucus protein profile, immune and appetite genes expression in gold fish (Carassius auratus gibelio).

    PubMed

    Hosseini, Marjan; Kolangi Miandare, Hamed; Hoseinifar, Seyed Hossein; Yarahmadi, Peyman

    2016-12-01

    The objective of the present study was to investigate the effect of dietary Lactobacillus acidophilus on skin mucus protein pattern, immune and appetite related genes expression as well as growth performance in gold fish (Carassius auratus gibelio). Three hundred healthy gold fish (2.5 ± 0.05) juveniles were randomly distributed in 12 glass aquariums (400-L; 25 fish per aquaria) and fed experimental diets contain different levels of L. acidophilus (0, 1.5 × 10(8), 3 × 10(8) and 6 × 10(8)) for 8 weeks. SDS-PAGE analysis of skin mucus protein profile at the end of the feeding trial revealed differences in protein profile of probiotic fed fish and control group; even three new bands were observed in L. acidophilus treated groups. Furthermore, fish fed 6 × 10(8) CFU g(-1) supplemented diet showed up-regulation of both TNF-1α and TNF-2α gene expression (P < 0.05). Evaluation of appetite related gene expression showed down-regulation of ghrelin in probiotic fed fish compared those of control treatment (P < 0.05). However, administration of different levels of L. acidophilus had no significant effects on growth performance (P > 0.05). These results demonstrated that while no beneficial effects on growth performance, dietary L. acidophilus affects immune and appetite related genes expression as well as skin mucus protein profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. IRIS Si IV Line Profiles: An Indication for the Plasmoid Instability during Small-scale Magnetic Reconnection on the Sun

    NASA Astrophysics Data System (ADS)

    Innes, D. E.; Guo, L.-J.; Huang, Y.-M.; Bhattacharjee, A.

    2015-11-01

    Our understanding of the process of fast reconnection has undergone a dramatic change in the last 10 years driven, in part, by the availability of high-resolution numerical simulations that have consistently demonstrated the break-up of current sheets into magnetic islands, with reconnection rates that become independent of Lundquist number, challenging the belief that fast magnetic reconnection in flares proceeds via the Petschek mechanism which invokes pairs of slow-mode shocks connected to a compact diffusion region. The reconnection sites are too small to be resolved with images, but these reconnection mechanisms, Petschek and the plasmoid instability, have reconnection sites with very different density and velocity structures and so can be distinguished by high-resolution line-profile observations. Using IRIS spectroscopic observations we obtain a survey of typical line profiles produced by small-scale events thought to be reconnection sites on the Sun. Slit-jaw images are used to investigate the plasma heating and re-configuration at the sites. A sample of 15 events from 2 active regions is presented. The line profiles are complex with bright cores and broad wings extending to over 300 km s-1. The profiles can be reproduced with the multiple magnetic islands and acceleration sites that characterize the plasmoid instability but not by bi-directional jets that characterize the Petschek mechanism. This result suggests that if these small-scale events are reconnection sites, then fast reconnection proceeds via the plasmoid instability, rather than the Petschek mechanism during small-scale reconnection on the Sun.

  11. IRIS Si iv LINE PROFILES: AN INDICATION FOR THE PLASMOID INSTABILITY DURING SMALL-SCALE MAGNETIC RECONNECTION ON THE SUN

    SciTech Connect

    Innes, D. E.; Guo, L.-J.; Huang, Y.-M.; Bhattacharjee, A.

    2015-11-10

    Our understanding of the process of fast reconnection has undergone a dramatic change in the last 10 years driven, in part, by the availability of high-resolution numerical simulations that have consistently demonstrated the break-up of current sheets into magnetic islands, with reconnection rates that become independent of Lundquist number, challenging the belief that fast magnetic reconnection in flares proceeds via the Petschek mechanism which invokes pairs of slow-mode shocks connected to a compact diffusion region. The reconnection sites are too small to be resolved with images, but these reconnection mechanisms, Petschek and the plasmoid instability, have reconnection sites with very different density and velocity structures and so can be distinguished by high-resolution line-profile observations. Using IRIS spectroscopic observations we obtain a survey of typical line profiles produced by small-scale events thought to be reconnection sites on the Sun. Slit-jaw images are used to investigate the plasma heating and re-configuration at the sites. A sample of 15 events from 2 active regions is presented. The line profiles are complex with bright cores and broad wings extending to over 300 km s{sup −1}. The profiles can be reproduced with the multiple magnetic islands and acceleration sites that characterize the plasmoid instability but not by bi-directional jets that characterize the Petschek mechanism. This result suggests that if these small-scale events are reconnection sites, then fast reconnection proceeds via the plasmoid instability, rather than the Petschek mechanism during small-scale reconnection on the Sun.

  12. Establishing intra- and inter-rater agreement of the Face, Legs, Activity, Cry, Consolability scale for evaluating pain in toddlers during immunization

    PubMed Central

    Gomez, Rebecca J; Barrowman, Nick; Elia, Sonja; Manias, Elizabeth; Royle, Jenny; Harrison, Denise

    2013-01-01

    BACKGROUND: The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a five-item tool that was developed to assess postoperative pain in young children. The tool is frequently used as an outcome measure in studies investigating acute procedural pain in young children; however, there are limited published psychometric data in this context. OBJECTIVE: To establish inter-rater and intrarater agreement of the FLACC scale in toddlers during immunization. METHODS: Participants comprised a convenience sample of toddlers recruited from an immunization drop-in service, who were part of a larger pilot randomized controlled trial. Toddlers were video- and audiotaped during immunization procedures. The first rater scored each video twice in random order over a period of three weeks (intrarater agreement), while the second rater scored each video once and was blinded to the first rater’s scores (inter-rater agreement). The FLACC scale was scored at four time-points throughout the procedure. Intraclass correlation coefficients were used to assess agreement of the FLACC scale. RESULTS: Thirty toddlers between 12 and 18 months of age were recruited, and video data were available for 29. Intrarater agreement coefficients were 0.88 at baseline, 0.97 at insertion of first needle, and 0.80 and 0.81 at 15 s and 30 s following the final injection, respectively. Inter-rater coefficients were 0.40 at baseline, 0.95 at insertion of first needle, and 0.81 and 0.78 at 15 s and 30 s following the final injection, respectively. CONCLUSIONS: The FLACC scale has sufficient agreement in assessing pain in toddlers during immunizations, especially during the most painful periods of the procedure. PMID:24308028

  13. 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

  14. In Vitro Immune Toxicity of Depleted Uranium: Effects on Murine Macrophages, CD4+ T Cells, and Gene Expression Profiles

    PubMed Central

    Wan, Bin; Fleming, James T.; Schultz, Terry W.; Sayler, Gary S.

    2006-01-01

    Depleted uranium (DU) is a by-product of the uranium enrichment process and shares chemical properties with natural and enriched uranium. To investigate the toxic effects of environmental DU exposure on the immune system, we examined the influences of DU (in the form of uranyl nitrate) on viability and immune function as well as cytokine gene expression in murine peritoneal macrophages and splenic CD4+ T cells. Macrophages and CD4+ T cells were exposed to various concentrations of DU, and cell death via apoptosis and necrosis was analyzed using annexin-V/propidium iodide assay. DU cytotoxicity in both cell types was concentration dependent, with macrophage apoptosis and necrosis occurring within 24 hr at 100 μM DU exposure, whereas CD4+ T cells underwent cell death at 500 μM DU exposure. Noncytotoxic concentrations for macrophages and CD4+ T cells were determined as 50 and 100 μM, respectively. Lymphoproliferation analysis indicated that macrophage accessory cell function was altered with 200 μM DU after exposure times as short as 2 hr. Microarray and real-time reverse-transcriptase polymerase chain reaction analyses revealed that DU alters gene expression patterns in both cell types. The most differentially expressed genes were related to signal transduction, such as c-jun, NF-κ Bp65, neurotrophic factors (e.g., Mdk), chemokine and chemokine receptors (e.g., TECK/CCL25), and interleukins such as IL-10 and IL-5, indicating a possible involvement of DU in cancer development, autoimmune diseases, and T helper 2 polarization of T cells. The results are a first step in identifying molecular targets for the toxicity of DU and the elucidation of the molecular mechanisms for the immune modulation ability of DU. PMID:16393663

  15. 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. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. In vitro immune toxicity of depleted uranium: effects on murine macrophages, CD4+ T cells, and gene expression profiles.

    PubMed

    Wan, Bin; Fleming, James T; Schultz, Terry W; Sayler, Gary S

    2006-01-01

    Depleted uranium (DU) is a by-product of the uranium enrichment process and shares chemical properties with natural and enriched uranium. To investigate the toxic effects of environmental DU exposure on the immune system, we examined the influences of DU (in the form of uranyl nitrate) on viability and immune function as well as cytokine gene expression in murine peritoneal macrophages and splenic CD4+ T cells. Macrophages and CD4+ T cells were exposed to various concentrations of DU, and cell death via apoptosis and necrosis was analyzed using annexin-V/propidium iodide assay. DU cytotoxicity in both cell types was concentration dependent, with macrophage apoptosis and necrosis occurring within 24 hr at 100 microM DU exposure, whereas CD4+ T cells underwent cell death at 500 microM DU exposure. Noncytotoxic concentrations for macrophages and CD4+ T cells were determined as 50 and 100 microM, respectively. Lymphoproliferation analysis indicated that macrophage accessory cell function was altered with 200 microM DU after exposure times as short as 2 hr. Microarray and real-time reverse-transcriptase polymerase chain reaction analyses revealed that DU alters gene expression patterns in both cell types. The most differentially expressed genes were related to signal transduction, such as c-jun, NF- kappa Bp65, neurotrophic factors (e.g., Mdk), chemokine and chemokine receptors (e.g., TECK/CCL25), and interleukins such as IL-10 and IL-5, indicating a possible involvement of DU in cancer development, autoimmune diseases, and T helper 2 polarization of T cells. The results are a first step in identifying molecular targets for the toxicity of DU and the elucidation of the molecular mechanisms for the immune modulation ability of DU.

  17. Fine-scale measurements of microwave refractivity profiles with helicopter and low-cost rocket probes

    NASA Astrophysics Data System (ADS)

    Rowland, John R.; Babin, Steven M.

    1987-12-01

    The recent development of computer models that can accurately predict radar performance under ducting or other anomalous propagation conditions has produced a need for high-resolution profiles of microwave refractivity in the lower troposphere. This article contains a brief description of two systems that can make the required meteorological measurements for use in those models. The first system is helicopter-based and has been used for research purposes to verify model performance. The second uses a low-cost rocket to carry a lightweight telemetry package to the desired altitudes. The rocket system shows promise for shipboard use where accurate, high-resolution refractivity profiles near the ocean surface are required.

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

    PubMed

    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

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

    PubMed

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

    2015-01-01

    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. 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. 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). 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.

  20. Substrate controls on the longitudinal profile of bedrock channels: Implications for reach-scale roughness

    Treesearch

    Jaime R. Goode; Ellen Wohl

    2010-01-01

    In this paper we examine the relationships among bedrock properties and hydraulics in shaping bedrock channel morphology at the reach scale. The Ocoee River and four other bedrock streams in the Blue Ridge province of the southeastern United States, which have reach scale differences in bedrock erodibility controlled by lithologic and structural variation, are the...

  1. The speeding attitude scale and the role of sensation seeking in profiling young drivers at risk.

    PubMed

    Whissell, Robert W; Bigelow, Brian J

    2003-08-01

    Seven driving attitude scales representing driving behaviors and beliefs about driving were created and initially validated using 257 undergraduate students (168 females, 89 males) in Study 1. However, the Speeding Attitude Scale (SAS) accounted for most of the strength of the intercorrelations among these scales and discriminant classification analyses showed that SAS dominated the other scales as a sufficient explanation for having speeding tickets. Study 2, using 180 students (75 males, 105 females), replicated findings regarding the significant but low correlation between SAS and speeding tickets, and was significantly correlated with Zuckerman's Sensation Seeking Scale (SSS). Replication also showed that males had higher SAS scores and more speeding tickets. Accidents were typically a function of sex, increasing age, and variables related to recent accident history. Objective sources of speeding attitude confirmation may enhance the future validity of the SAS. Potential interventions for being a safe passenger and attitudinal control in the training of young drivers were discussed.

  2. 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 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

  3. Vesicular signalling and immune modulation as hedonic fingerprints: proteomic profiling in the chronic mild stress depression model.

    PubMed

    Bisgaard, Christina F; Bak, Steffen; Christensen, Trine; Jensen, Ole N; Enghild, Jan J; Wiborg, Ove

    2012-12-01

    Extensive preclinical research has focused at unravelling the underlying molecular mechanisms leading to depression and recovery. In this study, we investigated the quantitative changes in protein abundance in the ventral hippocampal granular cell layer. We compared different phenotypes from the chronic mild stress (CMS) model of depression using chronic administration with two selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline. We isolated granular cells using Laser-Capture Microdissection (LCM) and we identified their regulated proteins using two-dimensional (2D) differential gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS). The majority of the proteins we identified were enzymes involved in different metabolic activities. Additional proteins were functionally classified as vesicular proteins and immune system proteins. Rab GDP dissociation inhibitor alpha (GDIA) and syntaxin-binding protein 1 (STXB1) were potential markers for stress reactivity. Dynamin 1 (DYN1), glutathione S-transferase omega-1 (GSTO1) and peroxiredoxin (PRDX6) were associated with treatment response. In addition, an imbalance between different post-translationally modified versions of DYN1 and GSTO1 potentially accounted for SSRI treatment refraction. In the present study, we searched for new markers of stress reactivity and treatment response as well as any underlying molecular mechanisms correlating to the development of anhedonia and antidepressant therapy refraction. Our results pointed towards an essential role of post-translational modifications in both vesicular and immune protein systems.

  4. 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.

  5. 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…

  6. 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,…

  7. 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…

  8. Functional changes in vascular amputee patients: evaluation by Barthel Index, PULSES profile and ESCROW scale.

    PubMed

    O'Toole, D M; Goldberg, R T; Ryan, B

    1985-08-01

    This study evaluated the changes made by 60 peripheral vascular amputees from one month prior to admission to six months after attending a rehabilitation hospital. The Barthel index, PULSES profile, and ESCROW profile were used to measure functional status, social support, and rehabilitation progress. Statistical analysis consisted of t-tests to determine significant differences between the means of scores at varying intervals, and analysis of variance was added to determine interactions between amputation level, age, and sex as related to functional change. Amputees showed significant gains in Barthel scores from admission to discharge; this was attributed to rehabilitation intervention. They showed a significant decrease by the PULSES profile over the study period, indicating a decrease in independence from their premorbid function. Changes in ESCROW scores showed patients to have a greater need for social supports as they moved from admission to discharge. Age was a significant factor in mobility at discharge as measured by the Barthel index. As measured by the PULSES profile, men did better than women at six months follow-up. Unexpected results were that neither amputation level nor the presence or absence of diabetes mellitus had a significant impact on functional status as measured. The lack of significant differences by amputation level may be due to factors of age and sex, as well as to more depression in the below-knee group.

  9. 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…

  10. Rapid visualization and large-scale profiling of bacterial lipoproteins with chemical reporters

    PubMed Central

    Rangan, Kavita J.; Yang, Yu-Ying; Charron, Guillaume; Hang, Howard C.

    2011-01-01

    Lipoproteins are a largely uncharacterized class of proteins in bacteria. In this study, metabolic labeling of bacteria with fatty acid chemical reporters allowed rapid profiling of lipid-modified proteins. We identified many candidate lipoproteins in Escherichia coli and detected a novel modification on YjgF. This chemical approach should facilitate future characterization of lipoproteins. PMID:20230003

  11. 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,…

  12. 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…

  13. 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

  14. Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson's Disease

    PubMed Central

    Pereira, João Santos; Adachi, Marcelo; Greca, Denise; Cruz, Manuela; Malak, Ana Lara; Charchat-Fichman, Helenice; Spitz, Mariana

    2017-01-01

    Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients. PMID:28409050

  15. Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson's Disease.

    PubMed

    Vasconcellos, Luiz Felipe; Pereira, João Santos; Adachi, Marcelo; Greca, Denise; Cruz, Manuela; Malak, Ana Lara; Charchat-Fichman, Helenice; Spitz, Mariana

    2017-01-01

    Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients.

  16. 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

  17. [Dynamic expression profile of HBsAg according to hepatic parenchyma cells' volume at different liver fibrosis stages in the immune clearance phase].

    PubMed

    Wu, Zhe-bin; Cao, Hong; Liu, Ting; Wu, Ze-qian; Ke, Wei-min; Gao, Zhi-liang

    2012-10-01

    The aim of this study was to determine the dynamic expression profile of hepatitis B surface antigen (HBsAg) according to hepatic parenchyma cells' volume at different stages of liver fibrosis during the immune clearance phase. Eighty-nine patients with HBeAg-positive chronic hepatitis B (CHB) in the immune clearance stage were recruited for study. Each patient's serum HBsAg levels were detected by electrochemiluminescence. The serum HBsAg levels were apportioned according to hepatic parenchyma cells' volume at liver fibrosis stages 1, 2, 3, and 4 and compared by ANOVA. The unapportioned serum HBsAg levels (IU/mL) at liver fibrosis stages 1 (227.2+/-237.7), 2 (211.0+/-131.4), 3(300.1+/-144.6), and 4 (278.7+/-148.8) were not significantly different (all comparisons, P range: 0.061 to 0.759). However, when the serum HBsAg levels were apportioned by the same hepatic parenchyma cells' volume at liver fibrosis stages 1 (343.9+/-359.8), 2 (336.4+/-209.5), 3 (508.7+/-245.1), and 4 (525.2+/-274.8), the levels were significantly different (all comparisons, F = 3.045 and P = 0.033; stage 1 vs. 3, P = 0.041; stage 1 vs. 4, P = 0.046; stage 2 vs. 3, P = 0.028; stage 2 vs. 4, P = 0.034). During the immune clearance phase of chronic hepatitis B, increased HBsAg expression is associated with increased hepatic parenchyma cells' volume and progressive liver fibrosis stage.

  18. Gene Expression Profiling in Peripheral Blood Mononuclear Cells of Patients with Common Variable Immunodeficiency: Modulation of Adaptive Immune Response following Intravenous Immunoglobulin Therapy

    PubMed Central

    Barbieri, Alessandro; Tinazzi, Elisa; Rizzi, Monica; Beri, Ruggero; Argentino, Giuseppe; Ottria, Andrea; Lunardi, Claudio; Puccetti, Antonio

    2014-01-01

    Background Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice. Methods We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study. Results A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23−CD27−IgM−IgG− B cells (centrocytes). Conclusions Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency. PMID:24831519

  19. A specific immune and lymphatic profile characterizes the pre-metastatic state of the sentinel lymph node in patients with early cervical cancer.

    PubMed

    Balsat, Cédric; Blacher, Silvia; Herfs, Michael; Van de Velde, Maureen; Signolle, Nicolas; Sauthier, Philippe; Pottier, Charles; Gofflot, Stéphanie; De Cuypere, Marjolein; Delvenne, Philippe; Goffin, Frédéric; Noel, Agnès; Kridelka, Frédéric

    2017-01-01

    The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms. An original digital image analysis methodology was used to objectively determine whole slide densities and spatial distributions of immunostained structures. We observed a marked increase in lymphatic vessel density (LVD) and a specific capsular and subcapsular distribution in pre-metastatic SLN when compared with non-sentinel counterparts. Such features persisted in the presence of nodal metastatic colonization. The inflammatory profile attested by CD8(+), Foxp3, CD20 and PD-1expression was also significantly increased in pre-metastatic SLN. Remarkably, the densities of CD20(+) B cells and PD-1 expressing germinal centers were positively correlated with LVD. All together, these data strongly support the existence of a pre-metastatic dialog between the primary tumor and the first nodal relay. Both lymphatic and immune responses contribute to the elaboration of a specific pre-metastatic microenvironment in human SLN. Moreover, this work provides evidence that, in the context of early cervical cancer, a pre-metastatic lymphangiogenesis occurs within the SLN (pre-metastatic niche) and is associated with a specific humoral immune response.

  20. Dysregulated immune profiles for skin and dendritic cells are associated with increased host susceptibility to Haemophilus ducreyi infection in human volunteers.

    PubMed

    Humphreys, Tricia L; Li, Lang; Li, Xiaoman; Janowicz, Diane M; Fortney, Kate R; Zhao, Qianqian; Li, Wei; McClintick, Jeanette; Katz, Barry P; Wilkes, David S; Edenberg, Howard J; Spinola, Stanley M

    2007-12-01

    In experimentally infected human volunteers, the cutaneous immune response to Haemophilus ducreyi is orchestrated by serum, polymorphonuclear leukocytes, macrophages, T cells, and myeloid dendritic cells (DC). This response either leads to spontaneous resolution of infection or progresses to pustule formation, which is associated with the failure of phagocytes to ingest the organism and the presence of Th1 and regulatory T cells. In volunteers who are challenged twice, some subjects form at least one pustule twice (PP group), while others have all inoculated sites resolve twice (RR group). Here, we infected PP and RR subjects with H. ducreyi and used microarrays to profile gene expression in infected and wounded skin. The PP and RR groups shared a core response to H. ducreyi. Additional transcripts that signified effective immune function were differentially expressed in RR infected sites, while those that signified a hyperinflammatory, dysregulated response were differentially expressed in PP infected sites. To examine whether DC drove these responses, we profiled gene expression in H. ducreyi-infected and uninfected monocyte-derived DC. Both groups had a common response that was typical of a type 1 DC (DC1) response. RR DC exclusively expressed many additional transcripts indicative of DC1. PP DC exclusively expressed differentially regulated transcripts characteristic of DC1 and regulatory DC. The data suggest that DC from the PP and RR groups respond differentially to H. ducreyi. PP DC may promote a dysregulated T-cell response that contributes to phagocytic failure, while RR DC may promote a Th1 response that facilitates bacterial clearance.

  1. Virulence profiles and innate immune responses against highly lethal, multidrug-resistant nosocomial isolates of Acinetobacter baumannii from a tertiary care hospital in Mexico.

    PubMed

    Rosales-Reyes, Roberto; Gayosso-Vázquez, Catalina; Fernández-Vázquez, José Luis; Jarillo-Quijada, Ma Dolores; Rivera-Benítez, César; Santos-Preciado, José Ignacio; Alcántar-Curiel, María Dolores

    2017-01-01

    Virulence profiles and innate immune responses were studied in Acinetobacter baumannii from nosocomial infections collected over one year in a tertiary care hospital in Mexico. A. baumannii were identified by VITEK 2 System followed by susceptibility tests. Carbapenemase genes, active efflux mechanism to imipenem and meropenem and outer membrane proteins profile were analyzed to evaluate their role on the activity of carbapenem resistance. All isolates were genotyped by pulsed field gel electrophoresis. The ability to form biofilm was determined on a polystyrene surface. The resistance to complement was determined with a pooled human normal serum and TNFα release by infected macrophages was determined by ELISA. The 112 isolates from this study were associated with a 52% of mortality. All were resistance to β-lactams, fluoroquinolones, and trimethroprim-sulfamethoxal, 96 and 90% were resistant to meropenem and imipenem, respectively, but with high susceptibility to polymyxin B, colistin and tigecyclin. Isolates were classified in 11 different clones. Most isolates, 88% (99/112), were metallo-β-lactamases and carbapenemases producers, associated in 95% with the presence of blaOXA-72 gene. Only 4/99 and 1/99 of the carbapenem-resistant isolates were related to efflux mechanism to meropenem or imipenem resistance, respectively. The loss of expression of 22, 29, and/or 33-36-kDa proteins was detected in 8/11 of the clinical isolates with resistance to carbapenem. More than 96% (108/112) of the isolates were high producers of biofilms on biotic surfaces. Finally, all isolates showed variable resistance to normal human serum activity and were high inductors of TNFα release by macrophages. In summary, these results suggest that multidrug-resistant A. baumannii can persist in the hospital environment through its ability to form biofilms. The high mortality observed was due to their ability to survive normal human serum activity and capability to induce potent

  2. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Emerging Affinity-Based Proteomic Technologies for Large-Scale Plasma Profiling in Cardiovascular Disease.

    PubMed

    Smith, J Gustav; Gerszten, Robert E

    2017-04-25

    Plasma biomarkers that reflect molecular states of the cardiovascular system are central for clinical decision making. Routinely used plasma biomarkers include troponins, natriuretic peptides, and lipoprotein particles, yet interrogate only a modest subset of pathways relevant to cardiovascular disease. Systematic profiling of a larger portion of circulating plasma proteins (the plasma proteome) will provide opportunities for unbiased discovery of novel markers to improve diagnostic or predictive accuracy. In addition, proteomic profiling may inform pathophysiological understanding and point to novel therapeutic targets. Obstacles for comprehensive proteomic profiling include the immense size and structural heterogeneity of the proteome, and the broad range of abundance levels, as well. Proteome-wide, untargeted profiling can be performed in tissues and cells with tandem mass spectrometry. However, applications to plasma are limited by the need for complex preanalytical sample preparation stages limiting sample throughput. Multiplexing of targeted methods based on capture and detection of specific proteins are therefore receiving increasing attention in plasma proteomics. Immunoaffinity assays are the workhorse for measuring individual proteins but have been limited for proteomic applications by long development times, cross-reactivity preventing multiplexing, specificity issues, and incomplete sensitivity to detect proteins in the lower range of the abundance spectrum (below picograms per milliliter). Emerging technologies to address these issues include nucleotide-labeled immunoassays and aptamer reagents that can be automated for efficient multiplexing of thousands of proteins at high sample throughput, coupling of affinity capture methods to mass spectrometry for improved specificity, and ultrasensitive detection systems to measure low-abundance proteins. In addition, proteomics can now be integrated with modern genomics tools to comprehensively relate

  4. 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.

  5. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy

    PubMed Central

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi AJO; Moriguchi-Jeckel, Cristina M; de Vries, Erik FJ

    2017-01-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants. PMID:28653857

  6. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy.

    PubMed

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi Ajo; Moriguchi-Jeckel, Cristina M; de Vries, Erik Fj

    2017-09-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30-50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic-pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants.

  7. Evaluation of P2X7 receptor expression in peripheral lymphocytes and immune profile from patients with indeterminate form of Chagas disease.

    PubMed

    Souza, Viviane do Carmo Gonçalves; Dos Santos, Joabel Tonellotto; Cabral, Fernanda Licker; Barbisan, Fernanda; Azevedo, Maria Isabel; Dias Carli, Luiz Felipe; de Avila Botton, Sonia; Dos Santos Jaques, Jeandre Augusto; Rosa Leal, Daniela Bitencourt

    2017-03-01

    Chagas disease (CD) is caused by Trypanosoma cruzi, an intracellular protozoan which is a potent stimulator of cell-mediated immunity. In the indeterminate form of CD (IFCD) a modulation between pro- and anti-inflammatory responses establishes a host-parasite adaptation. It was previously demonstrated that purinergic ecto-enzymes regulates extracellular ATP and adenosine levels, influencing immune and inflammatory processes during IFCD. In inflammatory sites ATP, as well as its degradation product, adenosine, function as signaling molecules and immunoregulators through the activation of purinergic receptors. In this work, it was analyzed the gene and protein expression of P2X7 purinergic receptor in peripheral lymphocytes and serum immunoregulatory cytokines from IFCD patients. Gene and protein expression of P2X7 receptor (P2X7R), and serum cytokines (IL-2, IL-10, IL-17 and IFN-γ) were unaltered. However, IFCD group showed significantly higher IL-4 and IL-6 levels while TNF-α was significantly decreased. These results indicate that imune profile of IFCD patients displays anti-inflammatory characteristics, consistent with the establishment of an immunomodulatory response. Further study about the molecular knowledge of P2X7R in IFCD is useful to clarify the participation of purinergic system in the regulatory mechanism which avoid the progression of CD.

  8. Salecan protected against concanavalin A-induced acute liver injury by modulating T cell immune responses and NMR-based metabolic profiles.

    PubMed

    Sun, Qi; Xu, Xi; Yang, Xiao; Weng, Dan; Wang, Junsong; Zhang, Jianfa

    2017-02-15

    Salecan, a water-soluble extracellular β-glucan produced by Agrobacterium sp. ZX09, has been reported to exhibit a wide range of biological effects. The aims of the present study were to investigate the protective effect of salecan against Concanavalin A (ConA)-induced hepatitis, a well-established animal model of immune-mediated liver injury, and to search for possible mechanisms. C57BL/6 mice were pretreated with salecan followed by ConA injection. Salecan treatment significantly reduced ConA-induced acute liver injury, and suppressed the expression and secretion of inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-6 and IL-1β in ConA-induced liver injury model. The high expression levels of chemokines and adhesion molecules such as MIP-1α, MIP-1β, ICAM-1, MCP-1 and RANTES in the liver induced by ConA were also down-regulated after salecan treatment. Salecan inhibited the infiltration and activation of inflammatory cells, especially T cells, in the liver induced by ConA. Moreover, salecan reversed the metabolic profiles of ConA-treated mice towards the control group by partly recovering the metabolic perturbations induced by ConA. Our results suggest the preventive and therapeutic potential of salecan in immune-mediated hepatitis.

  9. Malathion-induced changes in the haematological profile, the immune response, and the oxidative/antioxidant status of Cyprinus carpio carpio: protective role of propolis.

    PubMed

    Yonar, Serpil Mişe; Ural, Mevlüt Şener; Silici, Sibel; Yonar, M Enis

    2014-04-01

    The present study investigated the potential ameliorative effects of propolis against malathion toxicity in the blood and various tissues of carp. The fish were exposed to sublethal concentrations of malathion (0.5 and 1 mg/L) for 10 days, and propolis (10 mg/kg of fish weight) was simultaneously administered. Blood and tissue (liver, kidney, and gill) samples were collected at the end of the experiment and analysed to determine the haematological profile (red blood cell count, haemoglobin concentration, haematocrit level, and erythrocyte indices: mean corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration), immune response (white blood cell count, oxidative radical production, nitroblue tetrazolium (NBT) activity, total plasma protein and total immunoglobulin levels, and the phagocytic activity), and oxidant/antioxidant status (malondialdehyde and reduced glutathione levels and superoxide dismutase, catalase, and glutathione peroxidase activities) of the fish. The findings of this study demonstrate that malathion has a negative effect on the haematological parameters, immune response, and antioxidant enzyme activities of the fish. However, the administration of propolis ameliorated the malathion-induced toxic effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Ataxia rating scales--psychometric profiles, natural history and their application in clinical trials.

    PubMed

    Saute, Jonas Alex Morales; Donis, Karina Carvalho; Serrano-Munuera, Carmen; Genis, David; Ramirez, Luís Torres; Mazzetti, Pilar; Pérez, Luis Velázquez; Latorre, Pilar; Sequeiros, Jorge; Matilla-Dueñas, Antoni; Jardim, Laura Bannach

    2012-06-01

    We aimed to perform a comprehensive systematic review of the existing ataxia scales. We described the disorders for which the instruments have been validated and used, the time spent in its application, its validated psychometric properties, and their use in studies of natural history and clinical trials. A search from 1997 onwards was performed in the MEDLINE, LILACS, and Cochrane databases. The web sites ClinicalTrials.gov and Orpha.net were also used to identify the endpoints used in ongoing randomized clinical trials. We identified and described the semiquantitative ataxia scales (ICARS, SARA, MICARS, BARS); semiquantitative ataxia and non-ataxia scales (UMSARS, FARS, NESSCA); a semiquantitative non-ataxia scale (INAS); quantitative ataxia scales (CATSYS 2000, AFCS, CCFS and CCFSw, and SCAFI); and the self-performed ataxia scale (FAIS). SARA and ICARS were the best studied and validated so far, and their reliability sustain their use. Ataxia and non-ataxia scores will probably provide a better view of the overall disability in long-term trials and studies of natural history. Up to now, no clear advantage has been disclosed for any of them; however, we recommend the use of specific measurements of gait since gait ataxia is the first significant manifestation in the majority of ataxia disorders and comment on the best scales to be used in specific ataxia forms. Quantitative ataxia scales will be needed to speed up evidence from phase II clinical trials, from trials focused on the early phase of diseases, and for secondary endpoints in phase III trials. Finally, it is worth remembering that estimation of the actual minimal clinically relevant difference is still lacking; this, together with changes in quality of life, will probably be the main endpoints to measure in future therapeutic studies.

  11. 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

  12. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT).

    PubMed

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

    2008-09-15

    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-gamma (IFN-gamma) 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-gamma 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-gamma. 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-gamma 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.

  14. 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.

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

    PubMed

    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 profile of Vineland-II age equivalent scores, but not standard scores, was found. Highest scores were in motor skills and lowest scores were in socialisation. The addition of the Autism Diagnostic Observation Schedule calibrated severity score did not contribute significant variance to Vineland-II scores beyond that accounted for by age and nonverbal ability. Limitations, future directions, and implications are discussed.

  16. Chemogenomic profiling on a genome-wide scale using reverse-engineered gene networks.

    PubMed

    di Bernardo, Diego; Thompson, Michael J; Gardner, Timothy S; Chobot, Sarah E; Eastwood, Erin L; Wojtovich, Andrew P; Elliott, Sean J; Schaus, Scott E; Collins, James J

    2005-03-01

    A major challenge in drug discovery is to distinguish the molecular targets of a bioactive compound from the hundreds to thousands of additional gene products that respond indirectly to changes in the activity of the targets. Here, we present an integrated computational-experimental approach for computing the likelihood that gene products and associated pathways are targets of a compound. This is achieved by filtering the mRNA expression profile of compound-exposed cells using a reverse-engineered model of the cell's gene regulatory network. We apply the method to a set of 515 whole-genome yeast expression profiles resulting from a variety of treatments (compounds, knockouts and induced expression), and correctly enrich for the known targets and associated pathways in the majority of compounds examined. We demonstrate our approach with PTSB, a growth inhibitory compound with a previously unknown mode of action, by predicting and validating thioredoxin and thioredoxin reductase as its target.

  17. 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.

  18. 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.

  19. Variability of the vertical profile of wind speed: characterization at various time scales and analytical approximation

    NASA Astrophysics Data System (ADS)

    Jourdier, Bénédicte; Plougonven, Riwal; Drobinski, Philippe; Dupont, Jean-Charles

    2014-05-01

    Wind measurements are key for the wind resource assessment. But as wind turbines get higher, wind measurement masts are often lower than the future wind turbine hub height. Therefore one of the first steps in the energy yield assessment is the vertical extrapolation of wind measurements. Such extrapolation is often done by approximating the vertical profile of wind speed with an analytical expression: either a logarithmic law which has a theoretical basis in Monin-Obukhov similarity theory; or a power law which is empirical. The present study analyzes the variability of the wind profile and how this variability affects the results of the vertical extrapolation methods. The study is conducted with data from the SIRTA observatory, 20km south of Paris (France). A large set of instrumentation is available, including sonic anemometers at 10 and 30 meters, a LIDAR measuring wind speeds from 40 to 200 meters and a SODAR measuring wind speeds starting from 100m up to 1km. The comparison between the instruments enables to characterize the measurements uncertainties. The observations show that close to the ground the wind is stronger during daytime and weaker at night while higher, around 150 m, the wind is weaker during daytime and stronger at night. Indeed the wind shear has a pronounced diurnal cycle. The vertical extrapolation methods currently used in the industry do not usually take into account the strong variability of the wind profile. The often fit the parameters of the extrapolation law, not on each time step, but on time-averaged profiles. The averaging period may be the whole measurement period or some part of it: there may be one constant parameter computed on the wind profile that was averaged on the whole year of measures, or the year of measures may be divided into a small number of cases (for example into night or daytime data, or into 4 seasons) and the parameter is adjusted for each case. The study analyzes thoroughly the errors generated by both

  20. Profile and scaling of the fractal exponent of percolations in complex networks

    NASA Astrophysics Data System (ADS)

    Hasegawa, T.; Nogawa, T.; Nemoto, K.

    2013-10-01

    We propose a novel finite-size scaling analysis for percolation transition observed in complex networks. While it is known that cooperative systems in growing networks often undergo an infinite-order transition with inverted Berezinskii-Kosterlitz-Thouless singularity, it is very hard for numerical simulations to determine the transition point precisely. Since the neighbor of the ordered phase is not a simple disordered phase but a critical phase, conventional finite-size scaling technique does not work. In our finite-size scaling, the forms of the scaling functions for the order parameter and the fractal exponent determine the transition point and critical exponents numerically for an infinite-order transition as well as a standard second-order transition. We confirm the validity of our scaling hypothesis through Monte Carlo simulations for bond percolations in some network models: the decorated (2,2)-flower and the random attachment growing network, where an infinite-order transition occurs, and the configuration model, where a second-order transition occurs.

  1. The Refractive Status and Vision Profile: evaluation of psychometric properties and comparison of Rasch and summated Likert-scaling.

    PubMed

    Garamendi, Estibaliz; Pesudovs, Konrad; Stevens, Michael J; Elliott, David B

    2006-04-01

    The psychometric properties of the Refractive Status and Vision Profile (RSVP) questionnaire were evaluated using Rasch analysis. Ninety-one myopic patients from a refractive surgery clinic and general optometric practice completed the RSVP. Rasch analysis of the RSVP ordinal data was performed to examine for unidimensionality and item reduction. The traditional Likert-scoring system was compared with a Rasch-scored RSVP and a reduced item Rasch-scored RSVP. Rasch analysis of the original RSVP showed poor targeting of item difficulty to patient quality of life, items with a ceiling effect and underutilized response categories. Combining the underutilized response scales and removal of redundant and misfitting items improved the internal consistency and targeting of the RSVP, and the reduced 20-item Rasch scored RSVP showed greater relative precision over standard Likert scoring in discriminating between the two subject groups. A Rasch scaled quality of life questionnaire is recommended for use in refractive outcomes research.

  2. Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling.

    PubMed

    Boyle, Patrick; Clement, Kendell; Gu, Hongcang; Smith, Zachary D; Ziller, Michael; Fostel, Jennifer L; Holmes, Laurie; Meldrim, Jim; Kelley, Fontina; Gnirke, Andreas; Meissner, Alexander

    2012-10-03

    Sequencing-based approaches have led to new insights about DNA methylation. While many different techniques for genome-scale mapping of DNA methylation have been employed, throughput has been a key limitation for most. To further facilitate the mapping of DNA methylation, we describe a protocol for gel-free multiplexed reduced representation bisulfite sequencing (mRRBS) that reduces the workload dramatically and enables processing of 96 or more samples per week. mRRBS achieves similar CpG coverage to the original RRBS protocol, while the higher throughput and lower cost make it better suited for large-scale DNA methylation mapping studies, including cohorts of cancer samples.

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

    PubMed

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

    2015-01-01

    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. 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. 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. 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.

  4. 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

  5. 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

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

    PubMed Central

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

    2016-01-01

    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-nitro-pyrene 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 R2 of 0.87 and cross-validated R2 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

  7. 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.

  8. 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

  9. Elevated profiles of Th22 cells and correlations with Th17 cells in patients with immune thrombocytopenia.

    PubMed

    Hu, Yu; Li, Haiyan; Zhang, Lei; Shan, Baozhong; Xu, Xingfang; Li, Hong; Liu, Xinguang; Xu, Shuqian; Yu, Shuang; Ma, Daoxin; Peng, Jun; Hou, Ming

    2012-06-01

    T-helper (Th) 22 and Th17 cells are implicated in the pathogenesis of autoimmune diseases. However, the role of Th22 cells in the pathophysiology of immune thrombocytopenia (ITP) remains unclear. Th22, Th17 and Th1 cells in both ITP patients and healthy controls were examined by flow cytometry. Plasma interleukin-22 (IL-22) level was measured by enzyme linked immunosorbent assay (ELISA). Signal transducers and activators of transcription 3 (STAT-3) and transcription factor RAR-related organ receptor C (RORC) messenger RNA (mRNA) expressions were examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Th22 cells, Th17 cells, Th1 cells and plasma IL-22 were significantly higher in ITP patients than in healthy controls. Moreover, Th22 cells showed a positive correlation with the levels of plasma IL-22 as well as Th17 and Th1 cells in ITP patients. Significant up-regulations of both STAT-3 and RORC transcription factors were also observed. Additionally, the percentage of Th22 cells was higher in autoantibody-negative ITP patients than in autoantibody-positive patients. Our results demonstrate a possible role of Th22 cells in ITP, and thus, the blockade of IL-22 may be a reasonable therapeutic strategy for ITP. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  10. Molecular Profiles of Contrasting Shade Response Strategies in Wild Plants: Differential Control of Immunity and Shoot Elongation.

    PubMed

    Gommers, Charlotte M M; Keuskamp, Diederik H; Buti, Sara; van Veen, Hans; Koevoets, Iko T; Reinen, Emilie; Voesenek, Laurentius A C J; Pierik, Ronald

    2017-02-01

    Plants growing at high densities elongate their shoots to reach for light, a response known as the shade avoidance syndrome (SAS). Phytochrome-mediated detection of far-red light reflection from neighboring plants activates growth-promoting molecular pathways leading to SAS However, it is unknown how plants that complete their life cycle in the forest understory and are shade tolerant prevent SAS when exposed to shade. Here, we show how two wild Geranium species from different native light environments regulate contrasting responses to light quality cues. A comparative RNA sequencing approach unveiled the molecular underpinnings of their contrasting growth responses to far-red light enrichment. It also identified differential phytochrome control of plant immunity genes and confirmed that far-red enrichment indeed contrastingly affects resistance against Botrytis cinerea between the two species. Furthermore, we identify a number of candidate regulators of differential shade avoidance. Three of these, the receptor-like kinases FERONIA and THESEUS1 and the non-DNA binding bHLH protein KIDARI, are functionally validated in Arabidopsis thaliana through gene knockout and/or overexpression studies. We propose that these components may be associated with either showing or not showing shade avoidance responses.

  11. Molecular Profiles of Contrasting Shade Response Strategies in Wild Plants: Differential Control of Immunity and Shoot Elongation[OPEN

    PubMed Central

    Keuskamp, Diederik H.; Buti, Sara; van Veen, Hans; Reinen, Emilie; Voesenek, Laurentius A.C.J.

    2017-01-01

    Plants growing at high densities elongate their shoots to reach for light, a response known as the shade avoidance syndrome (SAS). Phytochrome-mediated detection of far-red light reflection from neighboring plants activates growth-promoting molecular pathways leading to SAS. However, it is unknown how plants that complete their life cycle in the forest understory and are shade tolerant prevent SAS when exposed to shade. Here, we show how two wild Geranium species from different native light environments regulate contrasting responses to light quality cues. A comparative RNA sequencing approach unveiled the molecular underpinnings of their contrasting growth responses to far-red light enrichment. It also identified differential phytochrome control of plant immunity genes and confirmed that far-red enrichment indeed contrastingly affects resistance against Botrytis cinerea between the two species. Furthermore, we identify a number of candidate regulators of differential shade avoidance. Three of these, the receptor-like kinases FERONIA and THESEUS1 and the non-DNA binding bHLH protein KIDARI, are functionally validated in Arabidopsis thaliana through gene knockout and/or overexpression studies. We propose that these components may be associated with either showing or not showing shade avoidance responses. PMID:28138015

  12. Cellular immunity profile in children with congenital heart disease and bronchopneumonia: evaluation of lymphocyte subsets and regulatory T cells.

    PubMed

    Huang, Rui; Zhu, Lei; Guo, Huimin; Wang, Liyan; Zhang, Jinli; Li, Wenling; Ma, Lan

    2014-01-01

    Children with congenital heart disease (CHD) have a predisposition to suffer from respiratory tract infections, such as bronchopneumonia (BP). In this study we investigated the characterization of lymphocyte subsets and regulatory T cells (Tregs) in these children. The frequencies of lymphocyte subsets and regulatory T cells were detected in peripheral blood of 400 children patients [100 with BP only, 100 with BP and CHD (BPCHD), 100 with BP and heart failure (BPHF), 100 healthy volunteers] by using three-color flow cytometry. In BPHF and BPCHD groups, lymphocyte subsets characterization of patients was analogous, with lower levels of CD3+, CD3+CD4+, CD3+CD8+, and CD4+/CD8+ ratio but higher levels of CD19+ and CD3-CD16+CD56+ in comparison to BP patients. The differences of the frequencies of CD4+CD25+CD127- T-cells in the four groups were not statistically significant. It was concluded that the cellular immunity function of children with CHD was vulnerable to being damaged after having suffered from BP when compared with the children without CHD, which might be associated with blood circulation difficulties in the majority of children with CHD.

  13. A neurodegeneration-specific gene expression signature and immune profile of acutely isolated microglia from an ALS mouse model

    PubMed Central

    Chiu, Isaac M.; Morimoto, Emiko T.A.; Goodarzi, Hani; Liao, Jennifer T.; O’Keeffe, Sean; Phatnani, Hemali P.; Muratet, Michael; Carroll, Michael C.; Levy, Shawn; Tavazoie, Saeed; Myers, Richard M.; Maniatis, Tom

    2013-01-01

    Microglia are resident immune cells of the CNS that are activated by infection, neuronal injury and inflammation. Here we utilize flow cytometry and deep RNA sequencing of acutely isolated spinal cord microglia to define their activation in vivo. Analysis of resting microglia identified 29 genes that distinguish microglia from other CNS cells and peripheral macrophages/monocytes. We then analyzed molecular changes in microglia during neurodegenerative disease activation using the SOD1G93A mouse model of ALS. We find that SOD1G93A microglia are not derived from infiltrating monocytes, and that both potentially neuroprotective and toxic factors are concurrently up-regulated, including Alzheimer’s disease genes. Mutant microglia differed from SOD1WT, LPS activated microglia, and M1/M2 macrophages, that define an ALS-specific phenotype. Concurrent mRNA/FACS analysis revealed post-transcriptional regulation of microglia surface receptors, and T cell-associated changes in the transcriptome. These results provide insights into microglia biology and establish a resource for future studies of neuroinflammation. PMID:23850290

  14. Tolerogenic versus Immunogenic Lipidomic Profiles of CD11c(+) Immune Cells and Control of Immunogenic Dendritic Cell Ceramide Dynamics.

    PubMed

    Ocaña-Morgner, Carlos; Sales, Susanne; Rothe, Manuela; Shevchenko, Andrej; Jessberger, Rolf

    2017-06-01

    Lipids affect the membrane properties determining essential biological processes. Earlier studies have suggested a role of switch-activated protein 70 (SWAP-70) in lipid raft formation of dendritic cells. We used lipidomics combined with genetic and biochemical assays to analyze the role of SWAP-70 in lipid dynamics. TLR activation using LPS as a ligand represented a pathogenic immunogenic stimulus, physical disruption of cell-cell contacts a tolerogenic stimulus. Physical disruption, but not LPS, caused an increase of phosphatidylcholine ether and cholesteryl esters in CD11c(+) immune cells. An increase of ceramide (Cer) was a hallmark for LPS activation. SWAP-70 was required for regulating the increase and localization of Cers in the cell membrane. SWAP-70 controls Cer accumulation through the regulation of pH-dependent acid-sphingomyelinase activity and of RhoA-dependent transport of endosomal contents to the plasma membrane. Poor accumulation of Cers in Swap70(-/-) cells caused decreased apoptosis. This shows that two different pathways of activation, immunogenic and tolerogenic, induce different changes in the lipid composition of cultured CD11c(+) cells, and highlights the important role of SWAP-70 in Cer dynamics in dendritic cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  15. Multi-Scale In Vivo Systems Analysis Reveals the Influence of Immune Cells on TNF-α-Induced Apoptosis in the Intestinal Epithelium

    PubMed Central

    Lau, Ken S.; Cortez-Retamozo, Virna; Philips, Sarah R.; Pittet, Mikael J.; Lauffenburger, Douglas A.; Haigis, Kevin M.

    2012-01-01

    Intestinal epithelial cells exist within a complex environment that affects how they interpret and respond to stimuli. We have applied a multi-scale in vivo systems approach to understand how intestinal immune cells communicate with epithelial cells to regulate responses to inflammatory signals. Multivariate modeling analysis of a large dataset composed of phospho-signals, cytokines, and immune cell populations within the intestine revealed an intimate relationship between immune cells and the epithelial response to TNF-α. Ablation of lymphocytes in the intestine prompted a decrease in the expression of MCP-1, which in turn increased the steady state number of intestinal plasmacytoid dendritic cells (pDCs). This change in the immune compartment affected the intestinal cytokine milieu and subsequent epithelial cell signaling network, with cells becoming hypersensitive to TNF-α-induced apoptosis in a way that could be predicted by mathematical modeling. In summary, we have uncovered a novel cellular network that regulates the response of intestinal epithelial cells to inflammatory stimuli in an in vivo setting. PMID:23055830

  16. Clinical and Laboratory Profile of Persons Living with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and Histoplasmosis from a Colombian Hospital.

    PubMed

    Caceres, Diego H; Tobón, Angela M; Cleveland, Angela Ahlquist; Scheel, Christina M; Berbesi, Dedsy Y; Ochoa, Jesús; Restrepo, Angela; Brandt, Mary E; Chiller, Tom; Gómez, Beatriz L

    2016-10-05

    Histoplasmosis is common among persons living with human immunodeficiency virus/acquired immune deficiency syndrome (PLWHA) in Latin America, but its diagnosis is difficult and often nonspecific. We conducted prospective screening for histoplasmosis among PLWHA with signs or symptoms suggesting progressive disseminated histoplasmosis (PDH) and hospitalized in Hospital La María in Medellín, Colombia. The study's aim was to obtain a clinical and laboratory profile of PLWHA with PDH. During 3 years (May 2008 to August 2011), we identified 89 PLWHA hospitalized with symptoms suggestive of PDH, of whom 45 (51%) had histoplasmosis. We observed tuberculosis (TB) coinfection in a large proportion of patients with PDH (35%), so all analyses were performed adjusting for this coinfection and, alternatively, excluding histoplasmosis patients with TB. Results showed that the patients with PDH were more likely to have Karnofsky score ≤ 30 (prevalence ratio [PR] = 1.98, 95% confidence interval [CI] = 0.97-4.06), liver compromised with hepatomegaly and/or splenomegaly (PR = 1.77, CI = 1.03-3.06) and elevation in serum of alanine aminotransferase and aspartate aminotransferase to values > 40 mU/mL (PR = 2.06, CI = 1.09-3.88 and PR = 1.53, CI = 0.99-2.35, respectively). Using multiple correspondence analyses, we identified in patients with PDH a profile characterized by the presence of constitutional symptoms, namely weight loss and Karnofsky classification ≤ 30, gastrointestinal manifestations with alteration of liver enzymes and hepatosplenomegaly and/or splenomegaly, skin lesions, and hematological alterations. Study of the profiles is no substitute for laboratory diagnostics, but identifying clinical and laboratory indicators of PLWHA with PDH should allow development of strategies for reducing the time to diagnosis and thus mortality caused by Histoplasma capsulatum. © The American Society of Tropical Medicine and Hygiene.

  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.

  18. 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.

  19. First Comparison of Remote Vertical Profiles of Refractory Black Carbon between the Atlantic and Pacific Basins on Global Scales

    NASA Astrophysics Data System (ADS)

    Katich, J. M.; Schwarz, J. P.

    2016-12-01

    The NASA Atmospheric Tomography Mission (ATom) provides a first opportunity to obtain vertical profiles of refractory black carbon (rBC) mass mixing ratios over global scale ( 65S - 85 N latitude) in the remote atmosphere over both the Pacific and Atlantic basins. A NOAA single-particle soot photometer (SP2) will fly on the NASA DC-8 research aircraft over July/August of 2016, obtaining near- continuous vertical profiling ( 0.3 to 12 km) over most of the Earth's latitude range, akin to the NSF HIPPO campaign that occurred only over the Pacific basin during 2009-2011. HIPPO analysis suggested both that high altitude rBC mass mixing ratios (MMRs) were likely zonally well mixed, and that global model estimates of remote rBC MMR throughout the upper troposphere globally, and not just over the Pacific, were likely biased high. Here we will present an initial analysis of the new, more complete data set in which Atlantic rBC profiles will be used to assess these prior suppositions.

  20. Evaluation of Urban Local-Scale Aerodynamic Parameters: Implications for the Vertical Profile of Wind Speed and for Source Areas

    NASA Astrophysics Data System (ADS)

    Kent, Christoph W.; Grimmond, Sue; Barlow, Janet; Gatey, David; Kotthaus, Simone; Lindberg, Fredrik; Halios, Christos H.

    2017-08-01

    Nine methods to determine local-scale aerodynamic roughness length (z0) and zero-plane displacement (zd) are compared at three sites (within 60 m of each other) in London, UK. Methods include three anemometric (single-level high frequency observations), six morphometric (surface geometry) and one reference-based approach (look-up tables). A footprint model is used with the morphometric methods in an iterative procedure. The results are insensitive to the initial zd and z0 estimates. Across the three sites, zd varies between 5 and 45 m depending upon the method used. Morphometric methods that incorporate roughness-element height variability agree better with anemometric methods, indicating zd is consistently greater than the local mean building height. Depending upon method and wind direction, z0 varies between 0.1 and 5 m with morphometric z0 consistently being 2-3 m larger than the anemometric z0. No morphometric method consistently resembles the anemometric methods. Wind-speed profiles observed with Doppler lidar provide additional data with which to assess the methods. Locally determined roughness parameters are used to extrapolate wind-speed profiles to a height roughly 200 m above the canopy. Wind-speed profiles extrapolated based on morphometric methods that account for roughness-element height variability are most similar to observations. The extent of the modelled source area for measurements varies by up to a factor of three, depending upon the morphometric method used to determine zd and z0.

  1. 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

  2. Lithologic influences on groundwater recharge through incised glacial till from profile to regional scales: Evidence from glaciated Eastern Nebraska

    USGS Publications Warehouse

    Gates, John B.; Steele, Gregory V.; Nasta, Paolo; Szilagyi, Jozsef

    2014-01-01

    Variability in sediment hydraulic properties associated with landscape depositional and erosional features can influence groundwater recharge processes by affecting soil-water storage and transmission. This study considers recharge to aquifers underlying river-incised glaciated terrain where the distribution of clay-rich till is largely intact in upland locations but has been removed by alluvial erosion in stream valleys. In a stream-dissected glacial region in eastern Nebraska (Great Plains region of the United States), recharge estimates were developed for nested profile, aquifer, and regional scales using unsaturated zone profile measurements (matric potentials, Cl- and 3H), groundwater tracers (CFC-12 and SF6), and a remote sensing-assisted water balance model. Results show a consistent influence of till lithology on recharge rates across nested spatial scales despite substantial uncertainty in all recharge estimation methods, suggesting that minimal diffuse recharge occurs through upland glacial till lithology whereas diffuse recharge occurs in river valleys where till is locally absent. Diffuse recharge is estimated to account for a maximum of 61% of total recharge based on comparison of diffuse recharge estimated from the unsaturated zone (0-43 mm yr-1) and total recharge estimated from groundwater tracers (median 58 mm yr-1) and water balance modeling (median 56 mm yr-1). The results underscore the importance of lithologic controls on the distributions of both recharge rates and mechanisms.

  3. The Role of ITG/TEM/ETG Cross-Scale Coupling in Explaining Experimental Electron Heat Flux and Profile Stiffness

    NASA Astrophysics Data System (ADS)

    Howard, N. T.

    2015-11-01

    Anomalous electron thermal transport in tokamak plasmas is the ``great unsolved problem of tokamak transport physics'' [Batchelor Plasma Sci. Tec. 2007]. For years it has been speculated that short wavelength ETG turbulence plays a key role, but simulation capturing both ion and electron-scale turbulence simultaneously had never been tested quantitatively against experiment due to extreme computational requirements. Only recently have gyrokinetic codes and supercomputing resources together been able to capture the physics of cross-scale coupling between long wavelength ITG/TEM and short wavelength ETG turbulence. In C-Mod, long wavelength simulations often under-predict electron heat flux. As a result, dedicated experiments have been performed in L-mode plasmas to validate multi-scale nonlinear gyrokinetic simulations. In this talk, the first set of full-physics, multi-scale simulations of a tokamak plasma performed with the GYRO code are compared to experiment. The simulations include coupled ITG/TEM/ETG turbulence (kθρs < 48 . 0) at realistic mass ratio (mi/me = 3600), with experimental inputs for impurities, geometry, ExB shear, and collisions. 100M CPU hours were required for six simulations to scan the ITG and ETG drive terms (a/LTi and a/LTe) within experimental error bars. The multi-scale simulations show for the first time that ETG streamers coexist and nonlinearly couple with ITG and zonal flows. This nonlinear cross-scale coupling enhances both ion and electron heat fluxes by up to a factor of 10 above standard, long wavelength simulation, resulting in simulations that simultaneously match experimental ion and electron heat fluxes and electron profile stiffness. The new physics of ITG/ETG/zonal flow coupling has important implications for predictions of ITER performance and may be linked to phenomena such as confinement transitions and rotation reversals. This work was supported by DOE contract - DE-FC02-99ER54512-CMOD.

  4. Transcriptome profiling of antiviral immune and dietary fatty acid dependent responses of Atlantic salmon macrophage-like cells.

    PubMed

    Eslamloo, Khalil; Xue, Xi; Hall, Jennifer R; Smith, Nicole C; Caballero-Solares, Albert; Parrish, Christopher C; Taylor, Richard G; Rise, Matthew L

    2017-09-08

    diet with a lower level of fish oil, suggesting that they are important diet-responsive, immune-related biomarkers for future studies. Although the different levels of dietary fish and vegetable oils involved in this study affected the expression of some transcripts, the immune-related pathways and functions activated by the antiviral response of salmon MLCs in both groups were comparable overall. Moreover, the qPCR revealed transcripts responding early to pIC (e.g. lgp2, map3k8, socs1, dusp5 and cflar) and time-responsive transcripts (e.g. scarb1-a, csf1r, traf5a, cd80 and ctsf) in salmon MLCs. The present study provides a comprehensive picture of the putative molecular pathways (e.g. RLR-, TLR-, MAPK- and IFN-associated pathways) activated by the antiviral response of salmon MLCs.

  5. Genome-scale functional profiling of the mammalian AP-1 signaling pathway

    PubMed Central

    Chanda, Sumit K.; White, Suhaila; Orth, Anthony P.; Reisdorph, Richard; Miraglia, Loren; Thomas, Russell S.; DeJesus, Paul; Mason, Daniel E.; Huang, Qihong; Vega, Raquel; Yu, De-Hua; Nelson, Christian G.; Smith, Brendan M.; Terry, Robert; Linford, Alicia S.; Yu, Yang; Chirn, Gung-wei; Song, Chuanzheng; Labow, Mark A.; Cohen, Dalia; King, Frederick J.; Peters, Eric C.; Schultz, Peter G.; Vogt, Peter K.; Hogenesch, John B.; Caldwell, Jeremy S.

    2003-01-01

    Large-scale functional genomics approaches are fundamental to the characterization of mammalian transcriptomes annotated by genome sequencing projects. Although current high-throughput strategies systematically survey either transcriptional or biochemical networks, analogous genome-scale investigations that analyze gene function in mammalian cells have yet to be fully realized. Through transient overexpression analysis, we describe the parallel interrogation of ≈20,000 sequence annotated genes in cancer-related signaling pathways. For experimental validation of these genome data, we apply an integrative strategy to characterize previously unreported effectors of activator protein-1 (AP-1) mediated growth and mitogenic response pathways. These studies identify the ADP-ribosylation factor GTPase-activating protein Centaurin α1 and a Tudor domain-containing hypothetical protein as putative AP-1 regulatory oncogenes. These results provide insight into the composition of the AP-1 signaling machinery and validate this approach as a tractable platform for genome-wide functional analysis. PMID:14514886

  6. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib.

    PubMed

    Gullaksen, Stein-Erik; Skavland, Jørn; Gavasso, Sonia; Tosevski, Vinko; Warzocha, Krzysztof; Dumrese, Claudia; Ferrant, Augustin; Gedde-Dahl, Tobias; Hellmann, Andrzej; Janssen, Jeroen; Labar, Boris; Lang, Alois; Majeed, Waleed; Mihaylov, Georgi; Stentoft, Jesper; Stenke, Leif; Thaler, Josef; Thielen, Noortje; Verhoef, Gregor; Voglova, Jaroslava; Ossenkoppele, Gert; Hochhaus, Andreas; Hjorth-Hansen, Henrik; Mustjoki, Satu; Sopper, Sieghart; Giles, Francis; Porkka, Kimmo; Wolf, Dominik; Gjertsen, Bjørn Tore

    2017-08-01

    Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1(IS) at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials.gov identifier: 01061177). Copyright© 2017 Ferrata Storti Foundation.

  8. A diagnostic scale for Alzheimer’s disease based on cerebrospinal fluid biomarker profiles

    PubMed Central

    2014-01-01

    Introduction The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer’s disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer’s disease (AD) pathologic process. Methods For that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-β 42, tau, and p-tau(181) were tested to generate categories of patients with very low (<10%), low (<25%), high (>75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included. Results A prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale’s overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The

  9. Oxide scale depth profiling of lanthanum-deposited AISI-304: An ion beam analysis

    NASA Astrophysics Data System (ADS)

    Ager, F. J.; Respaldiza, M. A.; Paúl, A.; Odriozola, J. A.; da Silva, M. F.; Soares, J. C.

    1998-03-01

    A detailed study of the composition and evolution with time of oxide scales formed onto lanthanum-coated AISI-304 stainless steel specimens by means of the PYROSOL deposition method at 1173 K in air, has been done with the help of ion beam analysis techniques such as Rutherford backscattering spectrometry (RBS) and nuclear reaction analysis (NRA) of Cr and Mn. Complementary data have been obtained by means of other analytical techniques such as Scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) and thermogravimetric measurements (TG), proving the effectiveness of the deposition method for enhancing the refractory behaviour.

  10. 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

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

    PubMed

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

    2004-11-01

    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-alpha1, TNF-alpha2, IL-1beta1, IL-8, TGF-beta1 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-beta1. 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.

  12. 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.

  13. 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

  14. 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

  15. Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models.

    PubMed

    Yousefi, Safoora; Amrollahi, Fatemeh; Amgad, Mohamed; Dong, Chengliang; Lewis, Joshua E; Song, Congzheng; Gutman, David A; Halani, Sameer H; Vega, Jose Enrique Velazquez; Brat, Daniel J; Cooper, Lee A D

    2017-09-15

    Translating the vast data generated by genomic platforms into accurate predictions of clinical outcomes is a fundamental challenge in genomic medicine. Many prediction methods face limitations in learning from the high-dimensional profiles generated by these platforms, and rely on experts to hand-select a small number of features for training prediction models. In this paper, we demonstrate how deep learning and Bayesian optimization methods that have been remarkably successful in general high-dimensional prediction tasks can be adapted to the problem of predicting cancer outcomes. We perform an extensive comparison of Bayesian optimized deep survival models and other state of the art machine learning methods for survival analysis, and describe a framework for interpreting deep survival models using a risk backpropagation technique. Finally, we illustrate that deep survival models can successfully transfer information across diseases to improve prognostic accuracy. We provide an open-source software implementation of this framework called SurvivalNet that enables automatic training, evaluation and interpretation of deep survival models.

  16. Contamination profiles of antibiotic resistance genes in the sediments at a catchment scale.

    PubMed

    Su, Hao-Chang; Pan, Chang-Gui; Ying, Guang-Guo; Zhao, Jian-Liang; Zhou, Li-Jun; Liu, You-Sheng; Tao, Ran; Zhang, Rui-Quan; He, Liang-Ying

    2014-08-15

    The aim of this study was to investigate the contamination profiles of tetracycline, sulfonamide, and macrolide resistance genes, as well as integrons in sediments of Dongjiang River basin of South China by real time quantitative polymerase chain reaction. sul2 was the most abundant resistance gene, with the average concentration of 6.97×10(8) copies/g and 1.00×10(8) copies/g in the dry and wet seasons, respectively, followed by ermF, sul3, sul1, intI1, tetA, ermB, tetX, tetM, tetQ, tetO, tetW, tetS, ermC, and tetB. The abundance of intI2 gene was the lowest in the sediment samples. Significant correlations existed between the ARGs and sediment properties as well as metals (Cu and Zn) and corresponding antibiotic classes, suggesting that the contamination of ARGs is related to chemical pollution of the sediments in the river basin. Principal component analysis showed distinct groupings of the sampling sites, reflecting that human activities are the key player in the dissemination of ARGs in the catchment environment.

  17. Comparative analysis of transcriptional profiling of CD3+, CD4+ and CD8+ T cells identifies novel immune response players in T-Cell activation

    PubMed Central

    Wang, Min; Windgassen, Dirk; Papoutsakis, Eleftherios T

    2008-01-01

    Background T-cell activation is an essential step of the immune response and relies on the tightly controlled orchestration of hundreds of genes/proteins, yet the cellular and molecular events underlying this complex process are not fully understood, especially at the genome-scale. Significantly, a comparative genome-scale transcriptional analysis of two T-cell subsets (CD4+ and CD8+) against each other and against the naturally mixed population (CD3+ cells) remains unexplored. Results Comparison of the microarray-based gene expression patterns between CD3+ T cells, and the CD4+ and CD8+ subsets revealed largely conserved, but not identical, transcriptional patterns. We employed a Gene-Ontology-driven transcriptional analysis coupled with protein abundance assays in order to identify novel T-cell activation genes and cell-type-specific genes associated with the immune response. We identified potential genes involved in the communication between the two subsets (including IL23A, NR4A2, CD83, PSMB2, -8, MIF, IFI16, TNFAIP1, POU2AF1, and OTUB1) and would-be effector-function-specific genes (XCL2, SLAMF7, TNFSF4, -5, -9, CSF3, CD48 and CD244). Chemokines induced during T-cell activation, but not previously identified in T cells, include CCL20, CXCL9, -10, -11 (in all three populations), and XCL2 (preferentially in CD8+ T cells). Increased expression of other unexpected cytokines (GPI, OSM and MIF) suggests their involvement in T-cell activation with their functions yet to be examined. Differential expression of many receptors, not previously reported in the context of T-cell activation, including CCR5, CCR7, IL1R2, IL1RAP, IL6R, TNFRSF25 and TNFRSF1A, suggests their role in this immune process. Several receptors involved in TCR activation (CD3D, CD3G, TRAT1, ITGAL, ITGB1, ITGB2, CD8A and B (CD8+ T-cell specific) along with LCK, ZAP70 and TYROBP were synchronously downregulated. Members of cell-surface receptors (HLA-Ds and KLRs), none previously identified in the

  18. Comparative analysis of transcriptional profiling of CD3+, CD4+ and CD8+ T cells identifies novel immune response players in T-cell activation.

    PubMed

    Wang, Min; Windgassen, Dirk; Papoutsakis, Eleftherios T

    2008-05-16

    T-cell activation is an essential step of the immune response and relies on the tightly controlled orchestration of hundreds of genes/proteins, yet the cellular and molecular events underlying this complex process are not fully understood, especially at the genome-scale. Significantly, a comparative genome-scale transcriptional analysis of two T-cell subsets (CD4+ and CD8+) against each other and against the naturally mixed population (CD3+ cells) remains unexplored. Comparison of the microarray-based gene expression patterns between CD3+ T cells, and the CD4+ and CD8+ subsets revealed largely conserved, but not identical, transcriptional patterns. We employed a Gene-Ontology-driven transcriptional analysis coupled with protein abundance assays in order to identify novel T-cell activation genes and cell-type-specific genes associated with the immune response. We identified potential genes involved in the communication between the two subsets (including IL23A, NR4A2, CD83, PSMB2, -8, MIF, IFI16, TNFAIP1, POU2AF1, and OTUB1) and would-be effector-function-specific genes (XCL2, SLAMF7, TNFSF4, -5, -9, CSF3, CD48 and CD244). Chemokines induced during T-cell activation, but not previously identified in T cells, include CCL20, CXCL9, -10, -11 (in all three populations), and XCL2 (preferentially in CD8+ T cells). Increased expression of other unexpected cytokines (GPI, OSM and MIF) suggests their involvement in T-cell activation with their functions yet to be examined. Differential expression of many receptors, not previously reported in the context of T-cell activation, including CCR5, CCR7, IL1R2, IL1RAP, IL6R, TNFRSF25 and TNFRSF1A, suggests their role in this immune process. Several receptors involved in TCR activation (CD3D, CD3G, TRAT1, ITGAL, ITGB1, ITGB2, CD8A and B (CD8+ T-cell specific) along with LCK, ZAP70 and TYROBP were synchronously downregulated. Members of cell-surface receptors (HLA-Ds and KLRs), none previously identified in the context of T

  19. 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.

  20. Ant Plant (Myrmecodia tuberosa) Hypocotyl Extract Modulates TCD4+ and TCD8+ Cell Profile of Doxorubicin-Induced Immune-Suppressed Sprague Dawley Rats In Vivo

    PubMed Central

    Sumardi; Hertiani, Triana; Sasmito, Ediati

    2013-01-01

    Myrmecodia tuberosa Jack (Rubiaceae) has been used as part of traditional Indonesian remedies for a wide range of therapeutic usages in West Papua. Our preliminary study revealed the significant potency of these plant extracts and fractions as an immunomodulator by an in vitro technique on Balb/c mice. This study explored the effect of M. tuberosa hypocotyl ethanol extract on the TCD4+ and TCD8+ cell profiles of doxorubicin (Dox)-induced immune-suppressed Sprague Dawley (SD) rats by an in vivo method. Dried powder of M. tuberosa hypocotyl was macerated in 95% ethanol. Following solvent evaporation in a vacuum, the ethanol extract (EE) was partitioned to yield an n-hexane fraction (FH) and residue (FNH). FNH was further partitioned to yield ethyl acetate (FEtOAc) and water fractions (FW). The extract and fractions in the concentrations 10, 20, 50, and 100 μg/mL were tested on macrophage cells by the latex bead method, while the proliferation of lymphocyte cells was evaluated by the MTT assay. The total phenolic and flavonoid contents of those fractions were evaluated. The active fraction was administrated orally on Dox-induced SD rats for 28 days by an in vivo method to observe the TCD4+ and TCD8+ cell profiles. The in vivo assay showed that the FNH could maintain the number of TCD4+ cells, but not the number of TCD8+ cells. The ED50 observed was 24.24 mg/kg BW. Steroid/terpenoid compounds were detected in this fraction along with the phenolics and flavonoids. The FNH contained 3.548 ± 0.058% GAE of total phenolics and 0.656 ± 0.026% QE of total flavonoids. M. tuberosa hypocotyl extract is a potent immunomodulatory agent and may act as co-chemotherapy in Dox use. PMID:24482773