Sample records for hypersensitive response reveals

  1. Hypersensitive response-related death

    Microsoft Academic Search

    Michčle C. Heath

    2000-01-01

    The hypersensitive response (HR) of plants resistant to microbial pathogens involves a complex form of programmed cell death (PCD) that differs from developmental PCD in its consistent association with the induction of local and systemic defence responses. Hypersensitive cell death is commonly controlled by direct or indirect interactions between pathogen avirulence gene products and those of plant resistance genes and

  2. Suppressive subtractive hybridization approach revealed differential expression of hypersensitive response and reactive oxygen species production genes in tea (Camellia sinensis (L.) O. Kuntze) leaves during Pestalotiopsis thea infection.

    PubMed

    Senthilkumar, Palanisamy; Thirugnanasambantham, Krishnaraj; Mandal, Abul Kalam Azad

    2012-12-01

    Tea (Camellia sinensis (L.) O. Kuntze) is an economically important plant cultivated for its leaves. Infection of Pestalotiopsis theae in leaves causes gray blight disease and enormous loss to the tea industry. We used suppressive subtractive hybridization (SSH) technique to unravel the differential gene expression pattern during gray blight disease development in tea. Complementary DNA from P. theae-infected and uninfected leaves of disease tolerant cultivar UPASI-10 was used as tester and driver populations respectively. Subtraction efficiency was confirmed by comparing abundance of ?-actin gene. A total of 377 and 720 clones with insert size >250 bp from forward and reverse library respectively were sequenced and analyzed. Basic Local Alignment Search Tool analysis revealed 17 sequences in forward SSH library have high degree of similarity with disease and hypersensitive response related genes and 20 sequences with hypothetical proteins while in reverse SSH library, 23 sequences have high degree of similarity with disease and stress response-related genes and 15 sequences with hypothetical proteins. Functional analysis indicated unknown (61 and 59 %) or hypothetical functions (23 and 18 %) for most of the differentially regulated genes in forward and reverse SSH library, respectively, while others have important role in different cellular activities. Majority of the upregulated genes are related to hypersensitive response and reactive oxygen species production. Based on these expressed sequence tag data, putative role of differentially expressed genes were discussed in relation to disease. We also demonstrated the efficiency of SSH as a tool in enriching gray blight disease related up- and downregulated genes in tea. The present study revealed that many genes related to disease resistance were suppressed during P. theae infection and enhancing these genes by the application of inducers may impart better disease tolerance to the plants. PMID:23065401

  3. Lipid profiling of the Arabidopsis hypersensitive response reveals specific lipid peroxidation and fragmentation processes: biogenesis of pimelic and azelaic acid.

    PubMed

    Zoeller, Maria; Stingl, Nadja; Krischke, Markus; Fekete, Agnes; Waller, Frank; Berger, Susanne; Mueller, Martin J

    2012-09-01

    Lipid peroxidation (LPO) is induced by a variety of abiotic and biotic stresses. Although LPO is involved in diverse signaling processes, little is known about the oxidation mechanisms and major lipid targets. A systematic lipidomics analysis of LPO in the interaction of Arabidopsis (Arabidopsis thaliana) with Pseudomonas syringae revealed that LPO is predominantly confined to plastid lipids comprising galactolipid and triacylglyceride species and precedes programmed cell death. Singlet oxygen was identified as the major cause of lipid oxidation under basal conditions, while a 13-lipoxygenase (LOX2) and free radical-catalyzed lipid oxidation substantially contribute to the increase upon pathogen infection. Analysis of lox2 mutants revealed that LOX2 is essential for enzymatic membrane peroxidation but not for the pathogen-induced free jasmonate production. Despite massive oxidative modification of plastid lipids, levels of nonoxidized lipids dramatically increased after infection. Pathogen infection also induced an accumulation of fragmented lipids. Analysis of mutants defective in 9-lipoxygenases and LOX2 showed that galactolipid fragmentation is independent of LOXs. We provide strong in vivo evidence for a free radical-catalyzed galactolipid fragmentation mechanism responsible for the formation of the essential biotin precursor pimelic acid as well as of azelaic acid, which was previously postulated to prime the immune response of Arabidopsis. Our results suggest that azelaic acid is a general marker for LPO rather than a general immune signal. The proposed fragmentation mechanism rationalizes the pathogen-induced radical amplification and formation of electrophile signals such as phytoprostanes, malondialdehyde, and hexenal in plastids. PMID:22822212

  4. Elicitation of plant hypersensitive response by bacteria

    SciTech Connect

    He, Sheng Yang [Michigan State Univ., East Lansing, MI (United States)

    1996-11-01

    There appears to be two types of plant cell death associated with pathogen infections: a rapid death localized at the site of infection during an incompatible interaction between a resistant plant and an avirulent pathogen, and a slow normosensitive plant cell death that spreads beyond the site of infection during compatible interactions involving a susceptible plant and a virulent, necrogenic pathogen. Both can lead to a systemic, broad-spectrum resistance response called SAR, which is effective against subsequent infection by the same or different pathogens. This report describes how bacteria elicit hypersensitive cell death. 40 refs., 2 figs.

  5. Revealing the importance of meristems and roots for the development of hypersensitive responses and full foliar resistance to Phytophthora infestans in the resistant potato cultivar Sarpo Mira

    PubMed Central

    Or?owska, El?bieta; Llorente, Briardo

    2012-01-01

    The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots and roots grafted with the susceptible Bintje cultivar as well as non-grafted different parts of Sarpo Mira plants were inoculated with P. infestans. The progress of the infection and the number of HR lesions were monitored, and the regulation of PR genes was compared in detached and attached leaves. Additionally, the antimicrobial activity of plant extracts was assessed. The presented data show that roots are needed to achieve full pathogen resistance, that the removal of meristems in detached leaves inhibits the formation of HR lesions, that PR genes are differentially regulated in detached leaves compared with leaves of whole plants, and that antimicrobial compounds accumulate in leaves and roots of Sarpo Mira plants challenged with P. infestans. While meristems are necessary for the formation of HR lesions, the roots of Sarpo Mira plants participate in the production of defence-associated compounds that increase systemic resistance. Based on the literature and on the presented results, a model is proposed for mechanisms involved in Sarpo Mira resistance that may apply to other resistant potato cultivars. PMID:22844094

  6. Programmed cell death, mitochondria and the plant hypersensitive response

    Microsoft Academic Search

    Eric Lam; Naohiro Kato; Michael Lawton

    2001-01-01

    The plant response to attempted infection by microbial pathogens is often accompanied by rapid cell death in and around the initial infection site, a reaction known as the hypersensitive response. This response is associated with restricted pathogen growth and represents a form of programmed cell death (PCD). Recent pharmacological and molecular studies have provided functional evidence for the conservation of

  7. Cloning of tobacco genes that elicit the hypersensitive response

    Microsoft Academic Search

    Erik E. Karrer; Roger N. Beachy; Curtis A. Holt

    1998-01-01

    We used a functional screening method to isolate genes whose products elicit the hypersensitive response (HR) pathway of defense against plant pathogens. A cDNA library derived from tobacco leaves undergoing the HR was cloned into a tobacco mosaic virus (TMV)-based expression vector. Infectious transcripts were generated and used to inoculate tobacco plants lacking the N resistance gene (genotype Xanthi nn).

  8. Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis

    SciTech Connect

    Zipser, R.D.; Patterson, J.B.; Kao, H.W.; Hauser, C.J.; Locke, R.

    1985-10-01

    Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after ( UC)arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2, PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of UC-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.

  9. DELAYED HYPERSENSITIVITY

    PubMed Central

    Uhr, Jonathan W.; Scharff, Matthew

    1960-01-01

    The capacity to develop the delayed type of hypersensitivity to diphtheria toxoid and ovalbumin may persist in guinea pigs and rabbits that have received doses of x-ray sufficient to eliminate a detectable antibody response. Larger doses of x-irradiation can prevent development of delayed-type hypersensitivity in rabbits. PMID:13779030

  10. Markers for hypersensitive response and senescence show distinct patterns of expression.

    PubMed

    Pontier, D; Gan, S; Amasino, R M; Roby, D; Lam, E

    1999-04-01

    Controlled cellular suicide is an important process that can be observed in various organs during plant development. From the generation of proper sexual organs in monoecious plants to the hypersensitive response (HR) that occurs during incompatible pathogen interactions, programmed cell death (PCD) can be readily observed. Although several biochemical and morphological parameters have been described for various types of cell death in plants, the relationships existing between those different types of PCD events remain unclear. In this work, we set out to examine if two early molecular markers of HR cell death (HIN1 and HSR203J) as well as a senescence marker (SAG12) are coordinately induced during these processes. Our result indicates that although there is evidence of some cross-talk between both cell death pathways, spatial and temporal characteristics of activation for these markers during hypersensitive response and senescence are distinct. These observations indicate that these markers are relatively specific for different cell death programs. Interestingly, they also revealed that a senescence-like process seems to be triggered at the periphery of the HR necrotic lesion. This suggests that cells committed to die during the HR might release a signal able to induce senescence in the neighboring cells. This phenomenon could correspond to the establishment of a second barrier against pathogens. Lastly, we used those cell death markers to better characterize cell death induced by copper and we showed that this abiotic induced cell death presents similarities with HR cell death. PMID:10380810

  11. Dose response relationships in delayed hypersensitivity to quinoline dyes.

    PubMed

    Weaver, J E

    1983-07-01

    Repeat insult patch testing of the quinoline dyes, D & C Yellow No. 10 (Acid Yellow No. 3) and D & C Yellow No. 11 (Solvent Yellow No. 33) demonstrated that concentrations as high as 1,000 ppm of the former induced no delayed contact hypersensitivity, whereas, concentrations of 20 ppm and 10 ppm of D & C Yellow No. 11 induced delayed hypersensitivity reactions in human volunteer panelists. No definitive hypersensitivity resulted from testing with 5 ppm of this dye. 2 persons who had been demonstrated to have reacted allergically to the use of a soap bar that contained D & C Yellow No. 11 did not react to the ad libitum use of a soap bar in which this dye was replaced with D & C Yellow No. 10. PMID:6684531

  12. Calcium Efflux as a Component of Hypersensitive Response of Nicotiana benthamiana to Pseudomonas syringae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using a model plant Nicotiana benthamiana we have demonstrated that initial calcium uptake in response to HR (hypersensitive response)-causing pathogen, P. syringae pv syringae 61 is followed by the net calcium efflux initiated at about 12 hrs after the bacterial challenge and sustained for at least...

  13. A hypersensitive response-induced ATPase associated with various cellular activities (AAA) protein from tobacco plants

    Microsoft Academic Search

    Megumi Sugimoto; Yube Yamaguchi; Kimiyo Nakamura; Yuko Tatsumi; Hiroshi Sano

    2004-01-01

    The hypersensitive response (HR) is one of the most critical defense systems in higher plants. In order to understand its molecular basis, we have screened tobacco genes that are transcriptionally activated during the early stage of the HR by the differential display method. Among six genes initially identified, one was found encoding a 57?kDa polypeptide with 497 amino acids not

  14. USE OF THE RIBONUCLEASE PROTECTION ASSAY FOR IDENTIFYING CHEMICALS WHICH ELLICIT HYPERSENSITIVITY RESPONSES

    EPA Science Inventory

    Use of the Ribonuclease Protection Assay (RPA) for Identifying Chemicals that Elicit Hypersensitivity Responses. L.M. Plitnick, 1, D.M. Sailstad, 2, and R.J. Smialowicz, 2 1UNC, Curriculum in Toxicology, Chapel Hill, NC and 2USEPA, NHEERL, RTP, NC. The incidence of aller...

  15. Identification of responsible volatile chemicals that induce hypersensitive reactions to multiple chemical sensitivity patients

    Microsoft Academic Search

    Naohide Shinohara; Atsushi Mizukoshi; Yukio Yanagisawa

    2004-01-01

    Multiple chemical sensitivity (MCS) has become a serious problem as a result of airtight techniques in modern construction. The mechanism of the MCS, however, has not been clarified. Responsible chemicals and their exposure levels for patient's hypersensitive reactions need to be identified. We measured the exposure of 15 MCS patients to both carbonyl compounds and volatile organic compounds (VOCs) that

  16. Light-dependent hypersensitive response and resistance signaling against Turnip Crinkle Virus in Arabidopsis

    E-print Network

    Kachroo, Pradeep

    Light-dependent hypersensitive response and resistance signaling against Turnip Crinkle Virus.edu). Summary Resistance to Turnip Crinkle Virus (TCV) in Arabidopsis ecotype Dijon (Di)-17 is conferred: Turnip Crinkle Virus, salicylic acid, defense, Arabidopsis, signaling, ssi2, light. Introduction Plants

  17. Hypersensitivity Vasculitis

    MedlinePLUS

    Hypersensitivity Vasculitis joseph July 18, 2012 No Comments What is Hypersensitivity vasculitis? Hypersensitivity vasculitis (HV) is often used to describe ... vessels, called a leukocytoclastic vasculitis. What causes Hypersensitivity vasculitis? HV may be caused by a specific drug ...

  18. Signal interactions between nitric oxide and reactive oxygen intermediates in the plant hypersensitive disease resistance response

    PubMed Central

    Delledonne, Massimo; Zeier, Jürgen; Marocco, Adriano; Lamb, Chris

    2001-01-01

    Nitric oxide (NO) and reactive oxygen intermediates (ROIs) play key roles in the activation of disease resistance mechanisms both in animals and plants. In animals NO cooperates with ROIs to kill tumor cells and for macrophage killing of bacteria. Such cytotoxic events occur because unregulated NO levels drive a diffusion-limited reaction with O2? to generate peroxynitrite (ONOO?), a mediator of cellular injury in many biological systems. Here we show that in soybean cells unregulated NO production at the onset of a pathogen-induced hypersensitive response (HR) is not sufficient to activate hypersensitive cell death. The HR is triggered only by balanced production of NO and ROIs. Moreover, hypersensitive cell death is activated after interaction of NO not with O2? but with H2O2 generated from O2? by superoxide dismutase. Increasing the level of O2? reduces NO-mediated toxicity, and ONOO? is not a mediator of hypersensitive cell death. During the HR, superoxide dismutase accelerates O2? dismutation to H2O2 to minimize the loss of NO by reaction with O2? and to trigger hypersensitive cell death through NO/H2O2 cooperation. However, O2? rather than H2O2 is the primary ROI signal for pathogen induction of glutathione S-transferase, and the rates of production and dismutation of O2? generated during the oxidative burst play a crucial role in the modulation and integration of NO/H2O2 signaling in the HR. Thus although plants and animals use a similar repertoire of signals in disease resistance, ROIs and NO are deployed in strikingly different ways to trigger host cell death. PMID:11606758

  19. Primary Generalized Glucocorticoid Resistance and Hypersensitivity: The End-Organ Involvement in the Stress Response

    NSDL National Science Digital Library

    Evangelia Charmandari (University of Athens Medical School; REV)

    2012-10-02

    Primary generalized glucocorticoid resistance (PGGR or Chrousos syndrome) and primary generalized glucocorticoid hypersensitivity (PGGH) are rare genetic disorders characterized by generalized, partial target-tissue insensitivity or hypersensitivity to glucocorticoids, respectively, while also causing compensatory alterations in the activity of the hypothalamic-pituitary-adrenal axis. The molecular basis of Chrousos syndrome and PGGH has been ascribed to mutations in the gene encoding the human glucocorticoid receptor (hGR), which impair glucocorticoid signal transduction and alter tissue sensitivity to glucocorticoids. Alterations in hGR action may have important implications for many critical biological processes, such as the behavioral and physiologic responses to stress, immune responses, growth, and reproduction. This Presentation summarizes the pathophysiology, clinical manifestations, and molecular mechanisms of the PGGR and PGGH states.

  20. Harpin, Elicitor of the Hypersensitive Response Produced by the Plant Pathogen Erwinia amylovora

    Microsoft Academic Search

    Zhong-Min Wei; Ron J. Laby; Cathy H. Zumoff; David W. Bauer; Sheng Yang He; Alan Collmer; Steven V. Beer

    1992-01-01

    A proteinaceous elicitor of the plant defense reaction known as the hypersensitive response was isolated from Erwinia amylovora, the bacterium that causes fire blight of pear, apple, and other rosaceous plants. The elicitor, named harpin, is an acidic, heat-stable, cell-envelope-associated protein with an apparent molecular weight of 44 kilodaltons. Harpin caused tobacco leaf lamina to collapse and caused an increase

  1. Ralstonia solanacearum type III secretion system effector Rip36 induces a hypersensitive response in the nonhost wild eggplant Solanum torvum.

    PubMed

    Nahar, Kamrun; Matsumoto, Iyo; Taguchi, Fumiko; Inagaki, Yoshishige; Yamamoto, Mikihiro; Toyoda, Kazuhiro; Shiraishi, Tomonori; Ichinose, Yuki; Mukaihara, Takafumi

    2014-04-01

    Ralstonia solanacearum is a Gram-negative soil-borne bacterium that causes bacterial wilt disease in more than 200 plant species, including economically important Solanaceae species. In R.?solanacearum, the hypersensitive response and pathogenicity (Hrp) type III secretion system is required for both the ability to induce the hypersensitive response (HR) in nonhost plants and pathogenicity in host plants. Recently, 72 effector genes, called rip (Ralstonia protein injected into plant cells), have been identified in R.?solanacearum?RS1000. RS1002, a spontaneous nalixidic acid-resistant derivative of RS1000, induced strong HR in the nonhost wild eggplant Solanum torvum in an Hrp-dependent manner. An Agrobacterium-mediated transient expression system revealed that Rip36, a putative Zn-dependent protease effector of R.?solanacearum, induced HR in S.?torvum. A mutation in the putative Zn-binding motif (E149A) completely abolished the ability to induce HR. In agreement with this result, the RS1002-derived ?rip36 and rip36E149A mutants lost the ability to induce HR in S.?torvum. An E149A mutation had no effect on the translocation of Rip36 into plant cells. These results indicate that Rip36 is an avirulent factor that induces HR in S.?torvum and that a putative Zn-dependent protease motif is essential for this activity. PMID:24745046

  2. Sphingolipids as New Biomarkers for Assessment of Delayed-Type Hypersensitivity and Response to Triptolide

    PubMed Central

    Qu, Feng; Wu, Cai-Sheng; Hou, Jin-Feng; Jin, Ying; Zhang, Jin-Lan

    2012-01-01

    Background Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism. Methods High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation. Results As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation. Conclusions These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples. PMID:23300675

  3. Specific suppression of delayed hypersensitivity response to sheep erythrocytes by heterologous anti-lymphocyte serum.

    PubMed Central

    Reuben, C; Phondke, G P

    1979-01-01

    The development of a heterologous anti-lymphocyte serum (ALS) capable of specifically suppressing the delayed hypersensitivity (DH) response is reported. This ALS, termed ALS(CMI), was prepared against lymph node cells from rats which had been immunized against sheep erythrocytes (SRBC) following treatment with cyclophosphamide which is known to enhance the DH response and suppress the humoral immune response. The effect of ALS(CMI) on the primary DH response to SRBC using the footpad swelling test was studied. Its effect on the primary humoral immune response to SRBC was also studied using the Jerne plaque assay technique. ALS(CMI) suppressed the humoral antibody response to SRBC and the DH response to a third party antigen only when administered before the antigen, having no effect when administered post-antigenically. On the other hand, ALS(CMI) significantly suppressed the primary DH response to SRBC when administered either before or after the antigen. Images Figure 1 PMID:391699

  4. Polyamines as a common source of hydrogen peroxide in host- and nonhost hypersensitive response during pathogen infection.

    PubMed

    Yoda, Hiroshi; Fujimura, Kazuki; Takahashi, Hideyuki; Munemura, Ikuko; Uchimiya, Hirofumi; Sano, Hiroshi

    2009-05-01

    The hypersensitive response (HR) is a powerful resistance system that plants have developed against pathogen attack. There are two major pathways for HR induction; one is through recognition of the pathogen by a specific host protein, and is known as the host HR. The other is through common biochemical changes upon infection--the nonhost HR. We previously demonstrated that hydrogen peroxide derived from polyamine degradation by polyamine oxidase triggers the typical host HR in tobacco plants upon infection with tobacco mosaic virus. However, it remains to be determined whether or not polyamines are involved in the nonhost HR in tobacco, and in the host HR in other plant species. When tobacco plants were infected with Pseudomonas cichorii, a representative nonhost pathogen, transcripts for six genes encoding enzymes for polyamine metabolism were simultaneously induced, and polyamines were accumulated in apoplasts. Hydrogen peroxide was concomitantly produced and hypersensitive cell death occurred at infected sites. Silencing of polyamine oxidase by the virus-induced gene silencing method resulted in suppression of hydrogen peroxide production and in disappearance of visible hypersensitive cell death with an increase in bacterial growth. Our results indicated that polyamines served as the source of hydrogen peroxide during the nonhost HR in tobacco plants. Further analysis revealed that polyamines were accumulated in apoplasts of Arabidopsis thaliana infected with Pseudomonas syringae, and of rice infected with Magnaporthe grisea, both causing the typical host HR. As in tobacco, it is conceivable that the same mechanism operates for nonhost HR in these plants. Our present observations thus suggested that polyamines are commonly utilized as the source of hydrogen peroxide during host- and nonhost HRs in higher plants. PMID:19190986

  5. Reduced recruitment of inflammatory cells in a contact hypersensitivity response in P-selectin-deficient mice

    PubMed Central

    1995-01-01

    The inflammatory response at sites of contact hypersensitivity induced by oxazolone was examined in the ears of P-selectin-deficient and wild- type mice. Accumulation of CD4+ T lymphocytes, monocytes, and neutrophils was reduced significantly in the mutant mice, as well as mast cell degranulation. In contrast, there was no significant difference in vascular permeability or edema between the two genotypes. The results demonstrate a role for P-selectin in recruitment of CD4+ T lymphocytes and show that P-selectin plays a role in long-term inflammation as well as in acute responses. PMID:7539046

  6. Transcriptomic Analysis of Prunus domestica Undergoing Hypersensitive Response to Plum Pox Virus Infection

    PubMed Central

    Rodamilans, Bernardo; San León, David; Mühlberger, Louisa; Candresse, Thierry; Neumüller, Michael; Oliveros, Juan Carlos; García, Juan Antonio

    2014-01-01

    Plum pox virus (PPV) infects Prunus trees around the globe, posing serious fruit production problems and causing severe economic losses. One variety of Prunus domestica, named ‘Jojo’, develops a hypersensitive response to viral infection. Here we compared infected and non-infected samples using next-generation RNA sequencing to characterize the genetic complexity of the viral population in infected samples and to identify genes involved in development of the resistance response. Analysis of viral reads from the infected samples allowed reconstruction of a PPV-D consensus sequence. De novo reconstruction showed a second viral isolate of the PPV-Rec strain. RNA-seq analysis of PPV-infected ‘Jojo’ trees identified 2,234 and 786 unigenes that were significantly up- or downregulated, respectively (false discovery rate; FDR?0.01). Expression of genes associated with defense was generally enhanced, while expression of those related to photosynthesis was repressed. Of the total of 3,020 differentially expressed unigenes, 154 were characterized as potential resistance genes, 10 of which were included in the NBS-LRR type. Given their possible role in plant defense, we selected 75 additional unigenes as candidates for further study. The combination of next-generation sequencing and a Prunus variety that develops a hypersensitive response to PPV infection provided an opportunity to study the factors involved in this plant defense mechanism. Transcriptomic analysis presented an overview of the changes that occur during PPV infection as a whole, and identified candidates suitable for further functional characterization. PMID:24959894

  7. Expression of Potato virus A coat protein gene in a resistant potato cultivar disrupts the virus induced hypersensitive responses

    Microsoft Academic Search

    Xianzhou Nie; Rudra P. Singh; Janet E. A. Seabrook; C. Jan Zeng; Teresa A. Molen; Mathuresh Singh; Katheryn Douglass

    2008-01-01

    Graft inoculation of potato (Solanum tuberosum) ‘Shepody’ plants with Potato virus A (PVA) results in hypersensitive resistance responses (HR) in tubers with characteristic necrosis. Increasing the number of PVA-containing scions or increasing the duration of scions on the ‘Shepody’ rootstock plants resulted in an increased number of tubers showing necrosis. Transgenic ‘Shepody’ plants with a sense or an antisense copy

  8. Formation of oxidized phosphatidylinositol and 12-oxo-phytodienoic acid containing acylated phosphatidylglycerol during the hypersensitive response in Arabidopsis.

    PubMed

    Nilsson, Anders K; Johansson, Oskar N; Fahlberg, Per; Steinhart, Feray; Gustavsson, Mikael B; Ellerström, Mats; Andersson, Mats X

    2014-05-01

    Plant membranes are composed of a wide array of polar lipids. The functionality of these extends far beyond a pure structural role. Membrane lipids function as enzyme co-factors, establish organelle identity and as substrates for enzymes such as lipases and lipoxygenases. Enzymatic degradation or oxidation (enzymatic or non-enzymatic) of membrane lipids leads to the formation of a diverse group of bioactive compounds. Plant defense reactions provoked by pathogenic microorganisms are often associated with substantial modifications of the lipidome. In this study, we profiled changes in phospholipids during the hypersensitive response triggered by recognition of the bacterial effector protein AvrRpm1 in Arabidopsis thaliana. A simple and robust LC-MS based method for profiling plant lipids was designed to separate all the major species of glycerolipids extracted from Arabidopsis leaf tissue. The method efficiently separated several isobaric and near isobaric lipid species, which otherwise are difficult to quantify in direct infusion based profiling. In addition to the previously reported OPDA-containing galactolipids found to be induced during hypersensitive response in Arabidopsis, three OPDA-containing sulfoquinovosyl diacylglycerol species, one phosphatidylinositol species as well as two acylated OPDA-containing phosphatidylglycerol species were found to accumulate during the hypersensitive response in Arabidopsis. Our study confirms and extends on the notion that the hypersensitive response in Arabidopsis triggers a unique profile of Allene Oxide Synthase dependent oxidation of membrane lipids. Primary targets of this oxidation seem to be uncharged and anionic lipid species. PMID:24559746

  9. Reduced sleep, stress responsivity, and female sex contribute to persistent inflammation-induced mechanical hypersensitivity in rats.

    PubMed

    Page, Gayle G; Opp, Mark R; Kozachik, Sharon L

    2014-08-01

    Studies in humans suggest that female sex, reduced sleep opportunities and biological stress responsivity increase risk for developing persistent pain conditions. To investigate the relative contribution of these three factors to persistent pain, we employed the Sciatic Inflammatory Neuritis (SIN) model of repeated left sciatic perineurial exposures to zymosan, an inflammatory stimulus, to determine their impact upon the development of persistent mechanical hypersensitivity. Following an initial moderate insult, a very low zymosan dose was infused daily for eight days to model a sub-threshold inflammatory perturbation to which only susceptible animals would manifest or maintain mechanical hypersensitivity. Using Sprague Dawley rats, maintaining wakefulness throughout the first one-half of the 12-h light phase resulted in a bilateral reduction in paw withdrawal thresholds (PWTs); zymosan infusion reduced ipsilateral PWTs in all animals and contralateral PWTs only in females. This sex difference was validated in Fischer 344, Lewis and Sprague Dawley rats, suggesting that females are the more susceptible phenotype for both local and centrally driven responses to repeated low-level inflammatory perturbations. Hypothalamic-pituitary-adrenal (HPA) axis hyporesponsive Lewis rats exhibited the most robust development of mechanical hypersensitivity and HPA axis hyperresponsive Fischer 344 rats matched the Lewis rats' mechanical hypersensitivity throughout the latter four days of the protocol. If HPA axis phenotype does indeed influence these findings, the more balanced responsivity of Sprague Dawley rats would seem to promote resilience in this paradigm. Taken together, these findings are consistent with what is known regarding persistent pain development in humans. PMID:24594386

  10. System-Wide Hypersensitive Response-Associated Transcriptome and Metabolome Reprogramming in Tomato1[W][OA

    PubMed Central

    Etalo, Desalegn W.; Stulemeijer, Iris J.E.; Peter van Esse, H.; de Vos, Ric C.H.; Bouwmeester, Harro J.; Joosten, Matthieu H.A.J.

    2013-01-01

    The hypersensitive response (HR) is considered to be the hallmark of the resistance response of plants to pathogens. To study HR-associated transcriptome and metabolome reprogramming in tomato (Solanum lycopersicum), we used plants that express both a resistance gene to Cladosporium fulvum and the matching avirulence gene of this pathogen. In these plants, massive reprogramming occurred, and we found that the HR and associated processes are highly energy demanding. Ubiquitin-dependent protein degradation, hydrolysis of sugars, and lipid catabolism are used as alternative sources of amino acids, energy, and carbon skeletons, respectively. We observed strong accumulation of secondary metabolites, such as hydroxycinnamic acid amides. Coregulated expression of WRKY transcription factors and genes known to be involved in the HR, in addition to a strong enrichment of the W-box WRKY-binding motif in the promoter sequences of the coregulated genes, point to WRKYs as the most prominent orchestrators of the HR. Our study has revealed several novel HR-related genes, and reverse genetics tools will allow us to understand the role of each individual component in the HR. PMID:23719893

  11. Immunity to Brugia pahangi in athymic nude and normal mice: eosinophilia, antibody and hypersensitivity responses.

    PubMed

    Vickery, A C; Vincent, A L

    1984-11-01

    Congenitally athymic nude (nu/nu) mice, immunologically reconstituted by thymus grafting before inoculation with infective larvae, and mice heterozygous for the nu gene (nu/+), mounted potent protective humoral and cellular immune responses to Brugia pahangi. Although responses were not identical, both groups of mice produced IgM, IgG and IgE antibodies specific for adult worm antigen (S-Ag) present in a crude aqueous extract, made immediate and delayed hypersensitivity footpad swelling responses when challenged with S-Ag and eliminated their infection in the early larval stages. Heterozygotes also exhibited a marked eosinophilia which peaked coincident with larval killing. In contrast, thymus grafting of patent nudes had no effect upon microfilaraemias or adult worm burdens and did not completely protect against a challenge larval inoculum although antibodies specific for S-Ag were produced. With the occasional exceptions of moderate immediate footpad swelling and very low titres of IgM specific for S-Ag, no specific immune responses to B. pahangi were found in ungrafted nude mice which allowed full development of adult worms and supported patent infections. PMID:6522098

  12. A translationally controlled tumor protein negatively regulates the hypersensitive response in Nicotiana benthamiana.

    PubMed

    Gupta, Meenu; Yoshioka, Hirofumi; Ohnishi, Kouhei; Mizumoto, Hiroyuki; Hikichi, Yasufumi; Kiba, Akinori

    2013-08-01

    We have been isolating and characterizing Ralstonia solanacearum-responsive genes (RsRGs) in Nicotiana plants. In this study we focused on RsRG308, which we renamed NbTCTP (N. benthamiana translationally controlled tumor protein) because it encodes a polypeptide showing similarity to translationally controlled tumor proteins. Induction of the hypersensitive response (HR) was accelerated in NbTCTP-silenced N. benthamiana plants challenged with R. solanacearum 8107 (Rs8107). The Rs8107 population decreased significantly, whereas hin1 gene expression was enhanced in the silenced plant. Accelerated induction of HR was observed in NbTCTP-silenced plants inoculated with Pseudomonas cichorii and P. syringae pv. syringae. Silencing of NbTCTP also accelerated the induction of HR cell death by Agrobacterium-mediated transient expression of HR inducers, such as AvrA, BAX, INF1 and NbMEK2(DD). NbTCTP silencing enhanced NbrbohB- and NbMEK2-mediated reactive oxygen species production, leading to HR. Transient expression of both the full-length sequence and the Bcl-xL domain of NbTCTP decreased HR cell death induced by Agrobacterium-mediated transient expression of HR inducers. NbTCTP-silenced plants also showed slightly dwarf phenotypes. Therefore, NbTCTP might have a role in cell death regulation during HR to fine-tune programmed cell death-associated plant defense responses. PMID:23788648

  13. Structural basis of metal hypersensitivity

    PubMed Central

    Wang, Yang

    2014-01-01

    Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). ?? T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific ?? T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101, DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells. PMID:22983897

  14. Hypersensitive response to Aphis gossypii Glover in melon genotypes carrying the Vat gene.

    PubMed

    Villada, Emilio Sarria; González, Elisa Garzo; López-Sesé, Ana Isabel; Castiel, Alberto Fereres; Gómez-Guillamón, María Luisa

    2009-01-01

    Aphis gossypii Glover causes direct and indirect damage to Cucumis melo L. crops. To decrease the harmful effects of this pest, one of the most economically and environmentally acceptable options is to use genetically resistant melon varieties. To date, several sources of resistance carrying the Vat gene are used in melon breeding programmes that aim to prevent A. gossypii colonization and the subsequent aphid virus transmission. The results suggest that the resistance conferred by this gene is associated with a microscopic hypersensitive response specific against A. gossypii. Soon after aphid infestation, phenol synthesis, deposits of callose and lignin in the cell walls, damage to the plasmalemma, and a micro-oxidative burst were detected in genotypes carrying the Vat gene. According to electrical penetration graph experiments, this response seems to occur after aphid stylets puncture the plant cells and not during intercellular stylet penetration. This type of plant tissue reaction was not detected in melon plants infested with Bemisia tabaci Gennadius nor Myzus persicae Sulzer. PMID:19474089

  15. Enhanced cutaneous hypersensitivity reactions are associated with ovine high and low cortisol responsiveness to acute endotoxin challenge.

    PubMed

    You, Qiumei; Karrow, Niel A; Quinton, Margaret; Mallard, Bonnie A; Boermans, Herman J

    2008-06-01

    Inbred rodent studies have demonstrated that cutaneous hypersensitivity reactions are exacerbated in stress-susceptible, and attenuated in stress-resistant strains of mice. This physiological response was, in part, mediated by activation of the hypothalamic-pituitary-adrenal axis during the acute restraint stress. A study was conducted to examine whether or not cutaneous hypersensitivity reactions are also associated with variable cortisol responsiveness to inflammatory stress in an outbred ovine population. High (H), medium (M), and low (L) cortisol responsive sheep were identified from a population of 110 females based on their estimated breeding values for cortisol concentration measured 4 h post-systemic challenge with Escherichia coli endotoxin (400 ng kg(-1)). Cutaneous hypersensitivity reactions to phytohaemagglutinin (PHA), 1-chloro-2, 4-dinitrobenzene (DNCB), and Candida albicans cellular antigen (CAA) were measured in these variable cortisol-responding sheep, in addition to serum interleukin (IL)-6, interferon (IFN)-gamma, and ovalbumin (OVA)-specific IgG concentrations. When compared to the M cortisol responders, both H and L cortisol responders had significantly greater cutaneous swelling during the elicitation phase in response to DNCB (P < 0.05) and CAA (P < 0.05); a similar but not significant trend was observed during the PHA challenge. The primary, but not the secondary, IgG response to OVA was significantly lower in the H and L cortisol responders when compared to the M cortisol responders. Differences in serum IL-6 or IFN-gamma concentration were not observed across variable cortisol-responsive groups. Together, these results demonstrate that cutaneous hypersensitivity reactions are enhanced in outbred H and L cortisol-responding sheep, independent of systemic modulation by IL-6 and IFN-gamma. PMID:18477334

  16. Phenotypic and genetic parameters of antibody and delayed-type hypersensitivity responses of lactating Holstein cows.

    PubMed

    Heriazon, Armando; Quinton, Margaret; Miglior, Filippo; Leslie, Keneth E; Sears, William; Mallard, Bonnie A

    2013-08-15

    Breeding dairy cattle using diverse phenotypic markers has been suggested as a feasible approach to improve health and decrease the deleterious consequences of infectious diseases. Studies conducted in pigs have demonstrated the value of antibody (AMIR)- and cell (CMIR)-mediated immune responses as quantitative traits for improving immune responsiveness by selecting livestock using estimated breeding values (EBV) for immune response (IR) traits. Studies of cattle have tested the possibility of using IR traits as phenotypic markers to classify cows as high (HR), average (AR) and low (LR) responders. Information is scarce or unavailable about either genetic parameters of AMIR and CMIR or their phenotypic and genetic associations with production, conformation, fertility or health traits in lactating dairy cattle. The objectives of the current study were to evaluate phenotypic and genetic parameters of both AMIR and CMIR as quantitative immunological traits (n=6) in comparison with production, fertility and health traits in dairy cattle for their use in a selection index intended to improve bovine health. Results of this study showed significant AMIR and CMIR responses. Most phenotypic correlations between IR traits and production, health or fertility traits were not significant. The highest heritabilities (h(2)) were observed for delayed-type hypersensitivity (DTH) to killed Candida albicans whole cell (CaWC) at 48 h (0.54) and AMIR day 14 (0.42). The highest genetic correlations were observed between AMIR 14 and AMIR 21 (0.99) and between DTH to CaWC 24h and DTH to CaWC 48 h (0.93). Two important and significant sire EBV correlations were noted between AMIR and fat % (0.18), and between CMIR and protein % (-0.15). In conclusion, this study demonstrated that both AMIR and CMIR are heritable traits in cattle and could be considered for their inclusion in a selection index intended to improve health. PMID:23747204

  17. Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs

    Microsoft Academic Search

    Santiago Cerrato; Pilar Brazis; Maria Federica della Valle; Alda Miolo; Stefania Petrosino; Vincenzo Di Marzo; Anna Puigdemont

    Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti-inflammatory and anti-hyperalgesic properties. The main objective of the present study was to evaluate the effects of PEA on the cutaneous allergic inflammatory reaction induced by different immunological and non-immunological stimuli in hypersensitive dogs. Six spontaneously Ascaris hypersensitive Beagle dogs were challenged with intradermal injections of Ascaris suum extract, substance P and

  18. Bax-induced cell death in tobacco is similar to the hypersensitive response

    PubMed Central

    Lacomme, Christophe; Santa Cruz, Simon

    1999-01-01

    Bax, a death-promoting member of the Bcl-2 family of proteins, triggered cell death when expressed in plants from a tobacco mosaic virus vector. Analysis of Bax deletion mutants demonstrated a requirement for the BH1 and BH3 domains in promoting rapid cell death, whereas deletion of the carboxyl-terminal transmembrane domain completely abolished the lethality of Bax in plants. The phenotype of cell death induced by Bax closely resembled the hypersensitive response induced by wild-type tobacco mosaic virus in tobacco plants carrying the N gene. The cell death-promoting function of Bax in plants correlated with accumulation of the defense-related protein PR1, suggesting Bax activated an endogenous cell-death program in plants. In support of this view, both N gene- and Bax-mediated cell death was blocked by okadaic acid, an inhibitor of protein phosphatase activity. The ability of Bax to induce cell death and a defense reaction in plants suggests that some features of animal and plant cell death processes may be shared. PMID:10393929

  19. The Relationship between Photosynthesis and a Mastoparan-Induced Hypersensitive Response in Isolated Mesophyll Cells1

    PubMed Central

    Allen, Lisa J.; MacGregor, Kennaway B.; Koop, Randall S.; Bruce, Doug H.; Karner, Julie; Bown, Alan W.

    1999-01-01

    The G-protein activator mastoparan (MP) was found to elicit the hypersensitive response (HR) in isolated Asparagus sprengeri mesophyll cells at micromolar concentrations. The HR was characterized by cell death, extracellular alkalinization, and an oxidative burst, indicated by the reduction of molecular O2 to O2??. To our knowledge, this study was the first to monitor photosynthesis during the HR. MP had rapid and dramatic effects on photosynthetic electron transport and excitation energy transfer as determined by variable chlorophyll a fluorescence measurements. A large increase in nonphotochemical quenching of chlorophyll a fluorescence accompanied the initial stages of the oxidative burst. The minimal level of fluorescence was also quenched, which suggests the origin of this nonphotochemical quenching to be a decrease in the antenna size of photosystem II. In contrast, photochemical quenching of fluorescence decreased dramatically during the latter stages of the oxidative burst, indicating a somewhat slower inhibition of photosystem II electron transport. The net consumption of O2 and the initial rate of O2 uptake, elicited by MP, were higher in the light than in the dark. These data indicate that light enhances the oxidative burst and suggest a complex relationship between photosynthesis and the HR. PMID:10198081

  20. Changes in cytosolic ATP levels and intracellular morphology during bacteria-induced hypersensitive cell death as revealed by real-time fluorescence microscopy imaging.

    PubMed

    Hatsugai, Noriyuki; Perez Koldenkova, Vadim; Imamura, Hiromi; Noji, Hiroyuki; Nagai, Takeharu

    2012-10-01

    Hypersensitive cell death is known to involve dynamic remodeling of intracellular structures that uses energy released during ATP hydrolysis. However, the relationship between intracellular structural changes and ATP levels during hypersensitive cell death remains unclear. Here, to visualize ATP dynamics directly in real time in individual living plant cells, we applied a genetically encoded Förster resonance energy transfer (FRET)-based fluorescent ATP indicator, ATeam1.03-nD/nA, for plant cells. Intracellular ATP levels increased approximately 3 h after inoculation with the avirulent strain DC3000/avrRpm1 of Pseudomonas syringae pv. tomato (Pst), which was accompanied by the simultaneous disappearance of transvacuolar strands and appearance of bulb-like structures within the vacuolar lumen. Approximately 5 h after bacterial inoculation, the bulb-like structures disappeared and ATP levels drastically decreased. After another 2 h, the large central vacuole was disrupted. In contrast, no apparent changes in intracellular ATP levels were observed in the leaves inoculated with the virulent strain Pst DC3000. The Pst DC3000/avrRpm1-induced hypersensitive cell death was strongly suppressed by inhibiting ATP synthesis after oligomycin A application within 4 h after bacterial inoculation. When the inhibitor was applied 7 h after bacterial inoculation, cell death was unaffected. These observations show that changes in intracellular ATP levels correlate with intracellular morphological changes during hypersensitive cell death, and that ATP is required just before vacuolar rupture in response to bacterial infection. PMID:22942251

  1. Polyamines as a common source of hydrogen peroxide in host- and nonhost hypersensitive response during pathogen infection

    Microsoft Academic Search

    Hiroshi Yoda; Kazuki Fujimura; Hideyuki Takahashi; Ikuko Munemura; Hirofumi Uchimiya; Hiroshi Sano

    2009-01-01

    The hypersensitive response (HR) is a powerful resistance system that plants have developed against pathogen attack. There\\u000a are two major pathways for HR induction; one is through recognition of the pathogen by a specific host protein, and is known\\u000a as the host HR. The other is through common biochemical changes upon infection—the nonhost HR. We previously demonstrated\\u000a that hydrogen peroxide

  2. Molecular characterization of Pvr9 that confers a hypersensitive response to Pepper mottle virus (a potyvirus) in Nicotiana benthamiana.

    PubMed

    Tran, Phu-Tri; Choi, Hoseong; Choi, Doil; Kim, Kook-Hyung

    2015-07-01

    There are some R genes against potyviruses which were mapped in pepper. However, none of them has been characterized at the molecular level. In this study, we characterized Pvr9 which is an Rpi-blb2 ortholog from pepper and confers a hypersensitive response to Pepper mottle virus (PepMoV) in a transient expression system in Nicotiana benthamiana. This gene putatively encoded for 1298 amino acids and is located on pepper chromosome 6. PepMoV NIb was the elicitor of the Pvr9-mediated hypersensitive response. NIb from several other potyviruses also elicited the hypersensitive response. Inoculation of pepper with PepMoV resulted in a minor increase in Pvr9 transcription in the resistant cultivar CM334 and a slight down-regulation in the susceptible cultivar Floral Gem. The 5' upstream region of Pvr9 from cultivar CM334 had higher transcription activity than the region from cultivar Floral Gem. The cultivars CM334 and Floral Gem had non-functional Pvr9 homologs with loss-of-function mutations. PMID:25776758

  3. Sulfate supply influences compartment specific glutathione metabolism and confers enhanced resistance to Tobacco mosaic virus during a hypersensitive response.

    PubMed

    Király, Lóránt; Künstler, András; Höller, Kerstin; Fattinger, Maria; Juhász, Csilla; Müller, Maria; Gullner, Gábor; Zechmann, Bernd

    2012-10-01

    Sufficient sulfate supply has been linked to the development of sulfur induced resistance or sulfur enhanced defense (SIR/SED) in plants. In this study we investigated the effects of sulfate (S) supply on the response of genetically resistant tobacco (Nicotiana tabacum cv. Samsun NN) to Tobacco mosaic virus (TMV). Plants grown with sufficient sulfate (+S plants) developed significantly less necrotic lesions during a hypersensitive response (HR) when compared to plants grown without sulfate (-S plants). In +S plants reduced TMV accumulation was evident on the level of viral RNA. Enhanced virus resistance correlated with elevated levels of cysteine and glutathione and early induction of a Tau class glutathione S-transferase and a salicylic acid-binding catalase gene. These data indicate that the elevated antioxidant capacity of +S plants was able to reduce the effects of HR, leading to enhanced virus resistance. Expression of pathogenesis-related genes was also markedly up-regulated in +S plants after TMV-inoculation. On the subcellular level, comparison of TMV-inoculated +S and -S plants revealed that +S plants contained 55-132 % higher glutathione levels in mitochondria, chloroplasts, nuclei, peroxisomes and the cytosol than -S plants. Interestingly, mitochondria were the only organelles where TMV-inoculation resulted in a decrease of glutathione levels when compared to mock-inoculated plants. This was particularly obvious in -S plants, where the development of necrotic lesions was more pronounced. In summary, the overall higher antioxidative capacity and elevated activation of defense genes in +S plants indicate that sufficient sulfate supply enhances a preexisting plant defense reaction resulting in reduced symptom development and virus accumulation. PMID:22122784

  4. Kinetics of the delayed-type hypersensitivity response in tuberculous guinea pigs and mice tested with several mycobacterial antigen preparations.

    PubMed

    Collins, F M

    1983-05-01

    Specific pathogen-free B6D2 mice and Hartley guinea pigs were infected subcutaneously with selected strains of Mycobacterium tuberculosis, M. bovis, M. kansasii, the MAIS complex, M. nonchromogenicum, and M. vaccae, and the in vivo growth behavior of the organisms was correlated with the level of tuberculin hypersensitivity and immunity to tuberculosis that subsequently developed. The peak level of tuberculin hypersensitivity varied depending on the host species, the immunogenicity of the infecting organism, and the dose and route of inoculation. However, the skin or footpad swelling profiles observed in mice and guinea pigs sensitized with live or heat-killed M. tuberculosis (persistor) or M. vaccae (nonpersistor) were very similar when a soluble test antigen was used, peaking between 24 and 36 h and already declining by 48 h. However, if sonically disrupted or whole-cell antigens were used, the swelling response was skewed significantly, with some residual swelling still present at 72 h. However, no evidence for two distinct cellular hypersensitivity responses was obtained in either mice or guinea pigs, regardless of the growth behavior of the mycobacteria in vivo. PMID:6221679

  5. Glucocorticoid effects on contact hypersensitivity and on the cutaneous response to ultraviolet light in the mouse

    SciTech Connect

    Ross, P.M.; Walberg, J.A.; Bradlow, H.L.

    1988-03-01

    A single exposure to 254 nm ultraviolet irradiation (UV) can systemically suppress experimental sensitization to the simple allergen 2,4-dinitro, 1-chlorobenzene (DNCB) in the mouse. We show here that topical application at the site of irradiation of the 21-oic acid methyl ester derivative of the synthetic glucocorticoid triamcinolone acetonide (TAme) prevents UV suppression of sensitization. That is, mice painted with TAme at the site of UV exposure developed normal contact hypersensitivity (CH); mice exposed to UV only, like mice treated with the parent compound triamcinolone acetonide (TA), failed to be sensitized by DNCB applied to a distal site. TAme is inactivated rapidly by plasma esterases, so its effect is thought to be confined to the skin. Apparently, TAme blocked the cutaneous signal(s) for systemic suppression of CH. Histologically, irradiated skin exhibited mild inflammation and hyperproliferation, but these effects were greatly exaggerated and prolonged in the UV + TAme-treated skin, independent of sensitization at the distal site. The infiltrate consisted mostly of neutrophils and lacked the round cells characteristic of cell-mediated immunity. Apparently, normal immune suppression by UV prevented this vigorous reaction to irradiated skin. Applied together with DNCB. TAme blocked sensitization. It also prevented response to challenge by DNCB in previously sensitized animals. However, unlike the parent compound triamcinolone acetonide (TA), Budesonide or Beclomethasone diproprionate, each of which can penetrate the epidermis in active form, TAme had no effect on sensitization when applied at a distal site. Likewise, TAme did not affect plasma B (17-desoxycortisol) levels, whereas the other three compounds reduced plasma B tenfold, as expected of compounds causing adrenal-pituitary suppression.

  6. ?2?-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

    PubMed Central

    Patel, Ryan; Bauer, Claudia S.; Nieto-Rostro, Manuela; Margas, Wojciech; Ferron, Laurent; Chaggar, Kanchan; Crews, Kasumi; Ramirez, Juan D.; Bennett, David L. H.; Schwartz, Arnold; Dickenson, Anthony H.

    2013-01-01

    The ?2?-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and is also the therapeutic target of gabapentinoid drugs. It is therefore likely to play a key role in the development of neuropathic pain. In this study, we have examined mice in which ?2?-1 gene expression is disrupted, to determine whether ?2?-1 is involved in various modalities of nociception, and for the development of behavioral hypersensitivity after partial sciatic nerve ligation (PSNL). We find that naive ?2?-1?/? mice show a marked behavioral deficit in mechanical and cold sensitivity, but no change in thermal nociception threshold. The lower mechanical sensitivity is mirrored by a reduced in vivo electrophysiological response of dorsal horn wide dynamic range neurons. The CaV2.2 level is reduced in brain and spinal cord synaptosomes from ?2?-1?/? mice, and ?2?-1?/? DRG neurons exhibit lower calcium channel current density. Furthermore, a significantly smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL, ?2?-1?/? mice show delayed mechanical hypersensitivity, which only develops at 11 d after surgery, whereas in wild-type littermates it is maximal at the earliest time point measured (3 d). There is no compensatory upregulation of ?2?-2 or ?2?-3 after PSNL in ?2?-1?/? mice, and other transcripts, including neuropeptide Y and activating transcription factor-3, are upregulated normally. Furthermore, the ability of pregabalin to alleviate mechanical hypersensitivity is lost in PSNL ?2?-1?/? mice. Thus, ?2?-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. PMID:24133248

  7. New ABA-Hypersensitive Arabidopsis Mutants Are Affected in Loci Mediating Responses to Water Deficit and Dickeya dadantii Infection

    PubMed Central

    Plessis, Anne; Cournol, Raphaël; Effroy, Delphine; Silva Pérez, Viridiana; Botran, Lucy; Kraepiel, Yvan; Frey, Anne; Sotta, Bruno; Cornic, Gabriel; Leung, Jeffrey; Giraudat, Jérôme; Marion-Poll, Annie; North, Helen M.

    2011-01-01

    On water deficit, abscisic acid (ABA) induces stomata closure to reduce water loss by transpiration. To identify Arabidopsis thaliana mutants which transpire less on drought, infrared thermal imaging of leaf temperature has been used to screen for suppressors of an ABA-deficient mutant (aba3-1) cold-leaf phenotype. Three novel mutants, called hot ABA-deficiency suppressor (has), have been identified with hot-leaf phenotypes in the absence of the aba3 mutation. The defective genes imparted no apparent modification to ABA production on water deficit, were inherited recessively and enhanced ABA responses indicating that the proteins encoded are negative regulators of ABA signalling. All three mutants showed ABA-hypersensitive stomata closure and inhibition of root elongation with little modification of growth and development in non-stressed conditions. The has2 mutant also exhibited increased germination inhibition by ABA, while ABA-inducible gene expression was not modified on dehydration, indicating the mutated gene affects early ABA-signalling responses that do not modify transcript levels. In contrast, weak ABA-hypersensitivity relative to mutant developmental phenotypes suggests that HAS3 regulates drought responses by both ABA-dependent and independent pathways. has1 mutant phenotypes were only apparent on stress or ABA treatments, and included reduced water loss on rapid dehydration. The HAS1 locus thus has the required characteristics for a targeted approach to improving resistance to water deficit. In contrast to has2, has1 exhibited only minor changes in susceptibility to Dickeya dadantii despite similar ABA-hypersensitivity, indicating that crosstalk between ABA responses to this pathogen and drought stress can occur through more than one point in the signalling pathway. PMID:21633512

  8. Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection

    Microsoft Academic Search

    S M B Jeronimo; A K B Holst; S E Jamieson; R Francis; D R A Martins; F L Bezerra; N A Ettinger; E T Nascimento; G R Monteiro; H G Lacerda; E N Miller; H J Cordell; P Duggal; T H Beaty; J M Blackwell; M E Wilson; ME Wilson

    2007-01-01

    Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to disease, clusters in families and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3–q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH?; 123 VL individuals) from

  9. Purification and Characterization of a Novel Hypersensitive Response-Inducing Elicitor from Magnaporthe oryzae that Triggers Defense Response in Rice

    PubMed Central

    Chen, Mingjia; Zeng, Hongmei; Qiu, Dewen; Guo, Lihua; Yang, Xiufen; Shi, Huaixing; Zhou, Tingting; Zhao, Jing

    2012-01-01

    Background Magnaporthe oryzae, the rice blast fungus, might secrete certain proteins related to plant-fungal pathogen interactions. Methodology/Principal Findings In this study, we report the purification, characterization, and gene cloning of a novel hypersensitive response-inducing protein elicitor (MoHrip1) secreted by M. oryzae. The protein fraction was purified and identified by de novo sequencing, and the sequence matched the genomic sequence of a putative protein from M. oryzae strain 70-15 (GenBank accession No. XP_366602.1). The elicitor-encoding gene mohrip1 was isolated; it consisted of a 429 bp cDNA, which encodes a polypeptide of 142 amino acids with a molecular weight of 14.322 kDa and a pI of 4.53. The deduced protein, MoHrip1, was expressed in E. coli. And the expression protein collected from bacterium also forms necrotic lesions in tobacco. MoHrip1 could induce the early events of the defense response, including hydrogen peroxide production, callose deposition, and alkalization of the extracellular medium, in tobacco. Moreover, MoHrip1-treated rice seedlings possessed significantly enhanced systemic resistance to M. oryzae compared to the control seedlings. The real-time PCR results indicated that the expression of some pathogenesis-related genes and genes involved in signal transduction could also be induced by MoHrip1. Conclusion/Significance The results demonstrate that MoHrip1 triggers defense responses in rice and could be used for controlling rice blast disease. PMID:22624059

  10. Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses

    Microsoft Academic Search

    Maurice W. van der Heijden; Mirjam Kool; Bianca M. Heijdra; Johan Garssen; Aletta D. Kraneveld; Henk Van Loveren; Paul Roholl; Takashi Saito; J. Sjef Verbeek; Jill Claassens; Andries S. Koster; Frans P. Nijkamp; Frank A. Redegeld

    2002-01-01

    Immunoglobulin (Ig)-free light chains IgLC are present in serum and their production is augmented under pathological conditions such as multiple sclerosis, rheumatoid arthritis and neurological disorders. Until now, no (patho)physiological function has been ascribed to circulating Ig light chains. Here we show that IgLCs can confer mast cell–dependent hypersensitivity in mice. Antigenic stimulation results in plasma extravasation, cutaneous swelling and

  11. The purification and characterization of a novel hypersensitive-like response-inducing elicitor from Verticillium dahliae that induces resistance responses in tobacco

    Microsoft Academic Search

    Bingnan Wang; Xiufen Yang; Hongmei Zeng; Hua Liu; Tingting Zhou; Beibei Tan; Jingjing Yuan; Lihua Guo; Dewen Qiu

    PevD1, a novel protein elicitor from the pathogenic cotton verticillium wilt fungus, Verticillium dahliae, induced a hypersensitive response in tobacco plants. In this paper, the elicitor was purified and analyzed using de novo\\u000a sequencing. The protein-encoding pevD1 gene consists of a 468-bp open reading frame that produces a polypeptide of 155 amino acids, with a theoretical molecular\\u000a weight of 16.23 kDa.

  12. Protein(s) from the Gram-Positive Bacterium Clavibacter michiganensis subsp. michiganensis Induces a Hypersensitive Response in Plants.

    PubMed

    Alarcón, C; Castro, J; Muńoz, F; Arce-Johnson, P; Delgado, J

    1998-04-01

    ABSTRACT The gram-positive tomato pathogen Clavibacter michiganensis subsp. michiganensis induced a local necrotic response on four-o'clock (Mirabilis jalapa) and tobacco (Nicotiana tabacum) plants. This necrosis response was characteristic of the hypersensitive response (HR). The cell-free culture supernatant from strain CMM623 also induced a necrosis that was phenotypically similar to that induced by the bacteria. Inhibitors of plant metabolism suppressed the necrotic reaction of both M. jalapa and tobacco. The HR-inducing activity present in the supernatant was heat stable, sensitive to proteases, and had an apparent molecular mass in the range of 35 to 50 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The properties observed for the necrosis-inducing activity resembled harpin and PopA described from gram-negative phytopathogenic bacteria. PMID:18944953

  13. CgDN3: an essential pathogenicity gene of colletotrichum gloeosporioides necessary to avert a hypersensitive-like response in the host Stylosanthes guianensis.

    PubMed

    Stephenson, S A; Hatfield, J; Rusu, A G; Maclean, D J; Manners, J M

    2000-09-01

    A gene of Colletotrichum gloeosporioides that is induced by nitrogen starvation in axenic culture and is expressed at the early stages of infection of the host Stylosanthes guianensis has been identified and its role in pathogenicity tested. The sequence of this gene, named CgDN3, indicated that it encodes a protein of 74 amino acids that contains a predicted 18 amino acid signal sequence for secretion of a basic 54 amino acid mature protein with weak homology to an internal region of plant wall-associated receptor kinases. Mutants of C. gloeosporioides were produced by homologous recombination in which part of the coding sequence and promoter region of the CgDN3 gene was replaced with a hygromycin-resistance gene cassette. Mutations in the CgDN3 gene were confirmed in two independent transformants and Northern (RNA) analysis demonstrated the disrupted CgDN3 gene was not expressed. The mutants had faster mycelial growth rates in vitro but produced spores that germinated to form appressoria normally on the leaf surface. However, the CgDN3 mutants were unable to infect and reproduce on intact host leaves. Microscopic analysis revealed small clusters of necrotic host cells at inoculation sites on leaves, suggesting that these mutants elicited a localized, host hypersensitive-like response. The mutants were able to grow necrotrophically and reproduce on leaves when conidia were inoculated directly onto wound sites. The putative promoter region of the CgDN3 gene was fused to a gene encoding a modified jellyfish green fluorescent protein and introduced into the fungus. Following inoculation, strong expression of green fluorescent protein was observed in primary infection vesicles in infected epidermal cells with weaker expression evident in hyphae growing within infected leaf tissue. These findings indicate that CgDN3 encodes a novel pathogenicity determinant associated with the biotrophic phase of primary infection and required to avert a hypersensitive-like response by a compatible host. PMID:10975650

  14. A MYB Transcription Factor Regulates Very-Long-Chain Fatty Acid Biosynthesis for Activation of the Hypersensitive Cell Death Response in Arabidopsis[W][OA

    PubMed Central

    Raffaele, Sylvain; Vailleau, Fabienne; Léger, Amandine; Joubčs, Jérôme; Miersch, Otto; Huard, Carine; Blée, Elisabeth; Mongrand, Sébastien; Domergue, Frédéric; Roby, Dominique

    2008-01-01

    Plant immune responses to pathogen attack include the hypersensitive response (HR), a form of programmed cell death occurring at invasion sites. We previously reported on Arabidopsis thaliana MYB30, a transcription factor that acts as a positive regulator of a cell death pathway conditioning the HR. Here, we show by microarray analyses of Arabidopsis plants misexpressing MYB30 that the genes encoding the four enzymes forming the acyl-coA elongase complex are putative MYB30 targets. The acyl-coA elongase complex synthesizes very-long-chain fatty acids (VLCFAs), and the accumulation of extracellular VLCFA-derived metabolites (leaf epidermal wax components) was affected in MYB30 knockout mutant and overexpressing lines. In the same lines, a lipid extraction procedure allowing high recovery of sphingolipids revealed changes in VLCFA contents that were amplified in response to inoculation. Finally, the exacerbated HR phenotype of MYB30-overexpressing lines was altered by the loss of function of the acyl-ACP thioesterase FATB, which causes severe defects in the supply of fatty acids for VLCFA biosynthesis. Based on these findings, we propose a model in which MYB30 modulates HR via VLCFAs by themselves, or VLCFA derivatives, as cell death messengers in plants. PMID:18326828

  15. Electromagnetic Hypersensitivity

    Microsoft Academic Search

    Norbert Leitgeb

    \\u000a Electromagnetic hypersensitive persons (EHS) attribute their nonspecific health symptoms to environmental electromagnetic\\u000a fields (EMF) of different sources in or outside their homes. In general, causal attribution is not restricted to specific\\u000a EMF frequencies but involves a wide range from extremely low frequencies (ELF) up to radio frequencies (RF) including mobile\\u000a telecommunication microwaves and radar. EHS argue that existing exposure limits

  16. Hypersensitivity Disorders

    Microsoft Academic Search

    Herbert B. Allen

    \\u000a The classic hypersensitivity disease is a drug eruption; such eruptions can assume many forms and are included in all dermatologic\\u000a differential diagnoses including bullous diseases. Other diseases included on many differential listings include syphilis,\\u000a lupus erythematosus, sarcoidosis, and Hansen disease (leprosy); but with the exception of lupus and special situations in\\u000a syphilis (congenital syphilis and HIV infection), bullous lesions are

  17. Irisflorentin modifies properties of mouse bone marrow-derived dendritic cells and reduces the allergic contact hypersensitivity responses.

    PubMed

    Fu, Ru-Huei; Tsai, Chia-Wen; Tsai, Rong-Tzong; Liu, Shih-Ping; Chan, Tzu-Min; Ho, Yu-Chen; Lin, Hsin-Lien; Chen, Yue-Mi; Hung, Huey-Shan; Chiu, Shao-Chih; Tsai, Chang-Hai; Wang, Yu-Chi; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2015-01-01

    Irisflorentin is an isoflavone component derived from the roots of Belamcanda chinensis (L.) DC. In traditional Chinese medicine, this herb has pharmacological properties to treat inflammatory disorders. Dendritic cells (DCs) are crucial modulators for the development of optimal T-cell immunity and maintenance of tolerance. Aberrant activation of DCs can induce harmful immune responses, and so agents that effectively improve DC properties have great clinical value. We herein investigated the effects of irisflorentin on lipopolysaccharide (LPS)-stimulated maturation of mouse bone marrow-derived DCs in vitro and in the contact hypersensitivity response (CHSR) in vivo. Our results demonstrated that treatment with up to 40 ?M irisflorentin does not cause cellular toxicity. Irisflorentin significantly lessened the proinflammatory cytokine production (tumor necrosis factor-?, interleukin-6, and interleukin-12p70) by LPS-stimulated DCs. Irisflorentin also inhibited the expression of LPS-induced major histocompatibility complex class II and costimulatory molecules (CD40 and CD86) on LPS-stimulated DCs. In addition, irisflorentin diminished LPS-stimulated DC-elicited allogeneic T-cell proliferation. Furthermore, irisflorentin significantly interfered with LPS-induced activation of I?B kinase, c-Jun N-terminal kinase, and p38, as well as the nuclear translocation of NF-?B p65. Subsequently, treatment with irisflorentin obviously weakened 2,4-dinitro-1-fluorobenzene-induced delayed-type hypersensitivity. These findings suggest new insights into the role of irisflorentin as an immunotherapeutic adjuvant through its capability to modulate the properties of DCs. PMID:25654487

  18. The role of respiratory burst oxidase homologues in elicitor-induced stomatal closure and hypersensitive response in Nicotiana benthamiana

    PubMed Central

    Zhang, Huajian; Fang, Qin; Zhang, Zhengguang; Wang, Yuanchao; Zheng, Xiaobo

    2009-01-01

    Active oxygen species (AOS) are central components of the defence reactions of plants against pathogens. Plant respiratory burst oxidase homologues (RBOH) of gp91phox, a plasma membrane protein of the neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, play a prominent role in AOS production. The role of two RBOH from Nicotiana benthamiana, NbrbohA and NbrbohB that encode plant NADPH oxidase in the process of elicitor-induced stomatal closure and hypersensitive cell death is described here. NbrbohA was constitutively expressed at a low level, whereas NbrbohB was induced when protein elicitors exist (such as boehmerin, harpin, or INF1). The virus-induced gene-silencing (VIGS) method was used to produce single-silenced (NbrbohA or NbrbohB) and double-silenced (NbrbohA and NbrbohB) N. benthamiana plants. The hypersensitive response (HR) of cell death and pathogenesis-related (PR) gene expression of these gene-silenced N. benthamiana plants, induced by various elicitors, are examined. The HR cell death and transcript accumulation of genes related to the defence response (PR1) were slightly affected, suggesting that RBOH are not essential for elicitor-induced HR and activation of these genes. Interestingly, gene-silenced plants impaired elicitor-induced stomatal closure and elicitor-promoted nitric oxide (NO) production, but not elicitor-induced cytosolic calcium ion accumulation and elicitor-triggered AOS production in guard cells. These results indicate that RBOH from N. benthamiana function in elicitor-induced stomatal closure, but not in elicitor-induced HR. PMID:19454596

  19. Artificial light at night alters delayed-type hypersensitivity reaction in response to acute stress in Siberian hamsters.

    PubMed

    Bedrosian, Tracy A; Aubrecht, Taryn G; Kaugars, Katherine E; Weil, Zachary M; Nelson, Randy J

    2013-11-01

    Several physiological and behavioral processes rely on precisely timed light information derived from the natural solar cycle. Using this information, traits have adapted to allow individuals within specific niches to optimize survival and reproduction, but urbanization by humans has significantly altered natural habitats. Nighttime light exposure alters immune function in several species, which could lead to decreased fitness or survival, particularly in the face of an environmental challenge. We exposed male Siberian hamsters (Phodopus sungorus) to five lux of light at night for four weeks, and then administered six hours of acute restraint stress. Delayed-type hypersensitivity (DTH) response was assessed immediately following stress. Acute restraint increased the DTH reaction in dark nights, but exposure to nighttime light prevented this response. Exposure to light at night prolonged the DTH response in non-stressed control hamsters. These results suggest that light pollution may significantly alter physiological responses in Siberian hamsters, particularly in response to a salient environmental challenge such as stress. PMID:23743259

  20. Dibutyl Phthalate (DBP) Induced Thymic Stromal Lymphopoietin (TSLP) Is Required for Th2 Contact Hypersensitivity Responses1

    PubMed Central

    Larson, Ryan P.; Zimmerli, Simone C.; Comeau, Michael R.; Itano, Andrea; Omori, Miyuki; Iseki, Masanori; Hauser, Conrad; Ziegler, Steven F.

    2010-01-01

    Thymic stromal lymphopoietin (TSLP) is an IL-7 related cytokine, produced by epithelial cells, that has been linked to atopic dermatitis and asthma; however, it remains unclear how TSLP shapes the adaptive immune response that causes these allergic disorders. Here we demonstrate a role for TSLP in a Th2 model of contact hypersensitivity (CHS) in mice. TSLP is required for the development of Th2-type CHS induced by the hapten fluorescein isothiocyanate (FITC) in combination with the sensitizing agent dibutyl phthalate (DBP). TSLPR?/? mice exhibited a dramatically reduced response, including markedly reduced local infiltration by eosinophils, Th2 cytokine production, and serum IgE levels, following FITC sensitization and challenge. The reduced response by TSLPR?/? mice is likely due to decreased frequency, and reduced T cell stimulatory function, of skin-derived antigen-bearing FITC+CD11c+ dendritic cells (DCs) in draining lymph nodes following FITC sensitization. These data suggest that skin-derived DCs are direct or indirect targets of TSLP in the development of type-2 immune responses in the skin, where TSLP drives their maturation, accumulation in skin draining lymph nodes, and ability to induce proliferation of naďve allergen-specific T cells. PMID:20173025

  1. Inhibition of UV-induced uric acid production using allopurinol prevents suppression of the contact hypersensitivity response.

    PubMed

    Leighton, Sarah; Kok, Lai-Fong; Halliday, Gary M; Byrne, Scott N

    2013-03-01

    Exposure to solar ultraviolet (UV) radiation suppresses adaptive immune responses. This contributes to skin carcinogenesis but may protect from some autoimmune diseases. However, the molecular changes occurring within UV-exposed skin that precipitate the downstream events leading to immune suppression are not fully understood. Using a combination of in vitro and in vivo mouse models, we have discovered that UV induces significant cutaneous production of immune suppressive uric acid. The ability of UV-induced uric acid to inhibit a contact hypersensitivity response was successfully blocked by the gout-treating drug Allopurinol. Up-regulation of NLRP3 mRNA by UV was also found to be dependent on UV-induced uric acid. This suggested that the target of UV-induced uric acid included proteins involved in the formation and activation of the NLRP3-inflammasome. However, in contrast to NLRP3, the adaptor protein ASC, which is required for formation of the NLRP3-inflammasome, was significantly down-regulated. Furthermore, this down-regulation was not dependent on UV-induced uric acid production because Allopurinol treatment failed to prevent the reduction in ASC. Hence, our results identify uric acid as an important molecule involved in sterile UV-induced inflammation and immune suppression. UV-induced uric acid may therefore offer a unique therapeutic target for preventing and treating skin cancer. PMID:23387472

  2. LhnR and upstream operon LhnABC in Agrobacterium vitis regulate the induction of tobacco hypersensitive responses, grape necrosis and swarming motility.

    PubMed

    Zheng, Desen; Hao, Guixia; Cursino, Luciana; Zhang, Hongsheng; Burr, Thomas J

    2012-09-01

    The characterization of Tn5 transposon insertional mutants of Agrobacterium vitis strain F2/5 revealed a gene encoding a predicted LysR-type transcriptional regulator, lhnR (for 'LysR-type regulator associated with HR and necrosis'), and an immediate upstream operon consisting of three open reading frames (lhnABC) required for swarming motility, surfactant production and the induction of a hypersensitive response (HR) on tobacco and necrosis on grape. The operon lhnABC is unique to A. vitis among the sequenced members in Rhizobiaceae. Mutagenesis of lhnR and lhnABC by gene disruption and complementation of ?lhnR and ?lhnABC confirmed their roles in the expression of these phenotypes. Mutation of lhnR resulted in complete loss of HR, swarming motility, surfactant production and reduced necrosis, whereas mutation of lhnABC resulted in loss of swarming motility, delayed and reduced HR development and reduced surfactant production and necrosis. The data from promoter-green fluorescent protein (gfp) fusions showed that lhnR suppresses the expression of lhnABC and negatively autoregulates its own expression. It was also shown that lhnABC negatively affects its own expression and positively affects the transcription of lhnR. lhnR and lhnABC constitute a regulatory circuit that coordinates the transcription level of lhnR, resulting in the expression of swarming, surfactant, HR and necrosis phenotypes. PMID:22212449

  3. In vitro elicitation of intestinal immune responses in teleost fish: evidence for a type IV hypersensitivity reaction in rainbow trout.

    PubMed

    Jirillo, F; Passantino, G; Massaro, M A; Cianciotta, A; Crasto, A; Perillo, A; Passantino, L; Jirillo, E

    2007-01-01

    In fish the gut immune system has been the subject of few investigations until now. Here, we provide novel morphological and immunological data on the gut isolated from rainbow trout Salmo gairdneri. The pyloric (P) and terminal (T) segments of trout gut, when morphologically examined, evidenced lymphocytes and macrophages (MŘ) loosely dispersed in the intestinal mucosa and in the lamina propria in the absence of typical Peyer's patches-like structures. Furthermore, incubation of P and T sections with Candida albicans (Ca) and functional analysis of supernatants generated some interesting results. In fact, active supernatants, when compared with controls, exhibited cytokine-like activities attributable to the presence of interferon (IFN)-gamma and migration inhibiting factor (MIF), respectively. In particular, IFN-gamma-like activity gave rise to an enhancement of Ca phagocytosis by MŘ, whereas MIF inhibited MŘ migration in agarose. Taken together, these in vitro data suggest that the gut-associated lymphoreticular tissue in fish possesses the appropriate armamentarium to mount a type IV hypersensitivity response when challenged by microbial antigens. PMID:17464768

  4. Differential expression of the TMV resistance gene N prevents a hypersensitive response in seeds and during germination.

    PubMed

    Niemeyer, Julia; Ruhe, Jonas; Machens, Fabian; Hehl, Reinhard

    2013-03-01

    The dominant tobacco mosaic virus (TMV) resistance gene N confers a hypersensitive response (HR) at the site of TMV infection and protects tobacco against systemic spread of the virus. To study N gene activity in seeds and early seedling development, the avirulence gene of N, the helicase domain (p50) of the TMV replicase, was constitutively expressed in a tobacco genotype without N (nn). Transgenic F1 expressing N and p50 were generated by crossing with an NN genotype. Surprisingly, Nn F1 seeds expressing p50 are viable and germinate. Only about 5 days after sowing, seedlings started to show an HR. This paralleled the upregulation of several pathogenesis-related and HR genes. The timing of the HR is consistent with the upregulation of N gene transcript 4-6 days after sowing. The expression of p50 has a stimulating effect on the N gene transcript level during germination. These results show that tobacco seeds and very young seedlings do not express a functional N gene product. PMID:23291787

  5. Single amino acid alterations in Arabidopsis thaliana RCY1 compromise resistance to Cucumber mosaic virus , but differentially suppress hypersensitive response-like cell death

    Microsoft Academic Search

    Ken-Taro Sekine; Takeaki Ishihara; Shu Hase; Tomonobu Kusano; Jyoti Shah; Hideki Takahashi

    2006-01-01

    Resistance to an yellow strain of Cucumber mosaic virus [CMV(Y)] in Arabidopsis thaliana ecotype C24 is conferred by the CC-NBS-LRR type R gene, RCY1. RCY1-conferred resistance is accompanied by a hypersensitive response (HR), which is characterized by the development of necrotic local lesion (NLL) at the site of infection that restricts viral spread. To further characterize the role of RCY1

  6. A Genome-Wide Association Study of the Maize Hypersensitive Defense Response Identifies Genes That Cluster in Related Pathways

    PubMed Central

    Venkata, Bala P.; Marla, Sandeep; Ji, Jiabing; Gachomo, Emma; Chu, Kevin; Negeri, Adisu; Benson, Jacqueline; Nelson, Rebecca; Bradbury, Peter; Nielsen, Dahlia; Holland, James B.; Balint-Kurti, Peter J.; Johal, Gurmukh

    2014-01-01

    Much remains unknown of molecular events controlling the plant hypersensitive defense response (HR), a rapid localized cell death that limits pathogen spread and is mediated by resistance (R-) genes. Genetic control of the HR is hard to quantify due to its microscopic and rapid nature. Natural modifiers of the ectopic HR phenotype induced by an aberrant auto-active R-gene (Rp1-D21), were mapped in a population of 3,381 recombinant inbred lines from the maize nested association mapping population. Joint linkage analysis was conducted to identify 32 additive but no epistatic quantitative trait loci (QTL) using a linkage map based on more than 7000 single nucleotide polymorphisms (SNPs). Genome-wide association (GWA) analysis of 26.5 million SNPs was conducted after adjusting for background QTL. GWA identified associated SNPs that colocalized with 44 candidate genes. Thirty-six of these genes colocalized within 23 of the 32 QTL identified by joint linkage analysis. The candidate genes included genes predicted to be in involved programmed cell death, defense response, ubiquitination, redox homeostasis, autophagy, calcium signalling, lignin biosynthesis and cell wall modification. Twelve of the candidate genes showed significant differential expression between isogenic lines differing for the presence of Rp1-D21. Low but significant correlations between HR-related traits and several previously-measured disease resistance traits suggested that the genetic control of these traits was substantially, though not entirely, independent. This study provides the first system-wide analysis of natural variation that modulates the HR response in plants. PMID:25166276

  7. Genes at Human Chromosome 5q31.1 Regulate Delayed Type Hypersensitivity Responses Associated with Leishmania chagasi Infection

    PubMed Central

    Jeronimo, Selma M. B.; Holst, Ashlee K. B.; Jamieson, Sarra E.; Francis, Richard; Martins, Daniella R. A.; Ettinger, Nicholas; Nascimento, Eliana T.; Miller, E. Nancy; Cordell, Heather J.; Duggal, Priya; Beaty, Terri H.; Blackwell, Jenefer M.; Wilson, Mary E.

    2008-01-01

    Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to disease, clusters in families, and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3-q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH?; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analysed for association with DTH+/? status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH+ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P=0.005; 95% CI=1.28-3.97) and TGFBI (OR 1.94; P=0.003; 95% CI=1.24-3.03). VL child/parent trios gave no evidence of linkage and association, but the DTH? phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P=0.006; 95% CI=1.38-7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P=0.042; 95% CI=1.04-8.65). These results indicate several genes in the immune response gene cluster at 5q23.3-q31.1 influence outcomes of L. chagasi infection in this region of Brazil. PMID:17713557

  8. Nitric Oxide-Mediated Signaling Functions During the Plant Hypersensitive Response

    Microsoft Academic Search

    Matteo De Stefano; Elodie Vandelle; Annalisa Polverari; Alberto Ferrarini; Massimo Delledonne

    Growing evidence suggests that nitric oxide (NO) is a central molecule in several physiological\\u000a functions, ranging from plant development to defence responses. Plants use NO as a signaling molecule\\u000a in pathways comparable to those of mammals, suggesting the existence of many commonalities between the action\\u000a of NO in plants and animals.\\u000a \\u000a \\u000a In this chapter, we examine the mechanisms through which plants respond

  9. Elicitation of hypersensitive responses in Nicotiana glutinosa by the suppressor of RNA silencing protein P0 from poleroviruses.

    PubMed

    Wang, Ken-Der; Empleo, Roman; Nguyen, Tan Tri V; Moffett, Peter; Sacco, Melanie Ann

    2015-06-01

    Plant disease resistance (R) proteins that confer resistance to viruses recognize viral gene products with diverse functions, including viral suppressors of RNA silencing (VSRs). The P0 protein from poleroviruses is a VSR that targets the ARGONAUTE1 (AGO1) protein for degradation, thereby disrupting RNA silencing and antiviral defences. Here, we report resistance against poleroviruses in Nicotiana glutinosa directed against Turnip yellows virus (TuYV) and Potato leafroll virus (PLRV). The P0 proteins from TuYV (P0(T) (u) ), PLRV (P0(PL) ) and Cucurbit aphid-borne yellows virus (P0(CA) ) were found to elicit a hypersensitive response (HR) in N.?glutinosa accession TW59, whereas other accessions recognized P0(PL) only. Genetic analysis showed that recognition of P0(T) (u) by a resistance gene designated RPO1 (Resistance to POleroviruses 1) is inherited as a dominant allele. Expression of P0 from a Potato virus X (PVX) expression vector transferred recognition to the recombinant virus on plants expressing RPO1, supporting P0 as the unique Polerovirus factor eliciting resistance. The induction of HR required a functional P0 protein, as P0(T) (u) mutants with substitutions in the F-box motif that abolished VSR activity were unable to elicit HR. We surmised that the broad P0 recognition seen in TW59 and the requirement for the F-box protein motif could indicate detection of P0-induced AGO1 degradation and disruption of RNA silencing; however, other viral silencing suppressors, including the PVX P25 that also causes AGO1 degradation, failed to elicit HR in N.?glutinosa. Investigation of P0 elicitation of RPO1 could provide insight into P0 activities within the cell that trigger resistance. PMID:25187258

  10. Ectopically expressed sweet pepper ferredoxin PFLP enhances disease resistance to Pectobacterium carotovorum subsp. carotovorum affected by harpin and protease-mediated hypersensitive response in Arabidopsis.

    PubMed

    Ger, Mang-Jye; Louh, Guan-Yu; Lin, Yi-Hsien; Feng, Teng-Yung; Huang, Hsiang-En

    2014-12-01

    Plant ferredoxin-like protein (PFLP) is a photosynthesis-type ferredoxin (Fd) found in sweet pepper. It contains an iron-sulphur cluster that receives and delivers electrons between enzymes involved in many fundamental metabolic processes. It has been demonstrated that transgenic plants overexpressing PFLP show a high resistance to many bacterial pathogens, although the mechanism remains unclear. In this investigation, the PFLP gene was transferred into Arabidopsis and its defective derivatives, such as npr1 (nonexpresser of pathogenesis-related gene 1) and eds1 (enhanced disease susceptibility 1) mutants and NAHG-transgenic plants. These transgenic plants were then infected with the soft-rot bacterial pathogen Pectobacterium carotovorum subsp. carotovorum (Erwinia carotovora ssp. carotovora, ECC) to investigate the mechanism behind PFLP-mediated resistance. The results revealed that, instead of showing soft-rot symptoms, ECC activated hypersensitive response (HR)-associated events, such as the accumulation of hydrogen peroxide (H2 O2 ), electrical conductivity leakage and expression of the HR marker genes (ATHSR2 and ATHSR3) in PFLP-transgenic Arabidopsis. This PFLP-mediated resistance could be abolished by inhibitors, such as diphenylene iodonium (DPI), 1-l-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (E64) and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), but not by myriocin and fumonisin. The PFLP-transgenic plants were resistant to ECC, but not to its harpin mutant strain ECCAC5082. In the npr1 mutant and NAHG-transgenic Arabidopsis, but not in the eds1 mutant, overexpression of the PFLP gene increased resistance to ECC. Based on these results, we suggest that transgenic Arabidopsis contains high levels of ectopic PFLP; this may lead to the recognition of the harpin and to the activation of the HR and other resistance mechanisms, and is dependent on the protease-mediated pathway. PMID:24796566

  11. DOLICHOL PHOSPHATE MANNOSE SYNTHASE1 Mediates the Biogenesis of Isoprenyl-Linked Glycans and Influences Development, Stress Response, and Ammonium Hypersensitivity in Arabidopsis[W

    PubMed Central

    Jadid, Nurul; Mialoundama, Alexis Samba; Heintz, Dimitri; Ayoub, Daniel; Erhardt, Mathieu; Mutterer, Jérôme; Meyer, Denise; Alioua, Abdelmalek; Van Dorsselaer, Alain; Rahier, Alain; Camara, Bilal; Bouvier, Florence

    2011-01-01

    The most abundant posttranslational modification in nature is the attachment of preassembled high-mannose-type glycans, which determines the fate and localization of the modified protein and modulates the biological functions of glycosylphosphatidylinositol-anchored and N-glycosylated proteins. In eukaryotes, all mannose residues attached to glycoproteins from the luminal side of the endoplasmic reticulum (ER) derive from the polyprenyl monosaccharide carrier, dolichol P-mannose (Dol-P-Man), which is flipped across the ER membrane to the lumen. We show that in plants, Dol-P-Man is synthesized when Dol-P-Man synthase1 (DPMS1), the catalytic core, interacts with two binding proteins, DPMS2 and DPMS3, that may serve as membrane anchors for DPMS1 or provide catalytic assistance. This configuration is reminiscent of that observed in mammals but is distinct from the single DPMS protein catalyzing Dol-P-Man biosynthesis in bakers’ yeast and protozoan parasites. Overexpression of DPMS1 in Arabidopsis thaliana results in disorganized stem morphology and vascular bundle arrangements, wrinkled seed coat, and constitutive ER stress response. Loss-of-function mutations and RNA interference–mediated reduction of DPMS1 expression in Arabidopsis also caused a wrinkled seed coat phenotype and most remarkably enhanced hypersensitivity to ammonium that was manifested by extensive chlorosis and a strong reduction of root growth. Collectively, these data reveal a previously unsuspected role of the prenyl-linked carrier pathway for plant development and physiology that may help integrate several aspects of candidate susceptibility genes to ammonium stress. PMID:21558543

  12. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein.

    PubMed

    Morrison, R P; Belland, R J; Lyng, K; Caldwell, H D

    1989-10-01

    Chlamydia trachomatis infection of humans is commonly a localized inflammation that can result in infertility, blindness, and perhaps arthritis. The pathogenic process(es) that cause these sequelae are thought to be immunological. A 57-kD protein that is common among Chlamydia elicits ocular inflammation when introduced onto the conjunctivae of guinea pigs or nonhuman primates previously sensitized by chlamydial infection. This protein is thought to mediate the immunopathology that follows chlamydial infection. To more thoroughly characterize this chlamydial component, we cloned its gene from a C. psittaci strain and identified a particular recombinant that produced the 57-kD polypeptide. The recombinant gene product was immunoreactive with a monospecific anti-57-kD serum, and elicited an ocular inflammation similar to that produced by the 57-kD antigen isolated from chlamydiae. Sequencing identified two ORFs that encode polypeptides of 11.2 and 58.1 kD and are co-transcribed. These two polypeptides show homology with Escherichia coli groE and Coxiella burnetii htp heat-shock proteins. Striking homology (greater than 50%) was found between the 57-kD protein and the HtpB, GroEL, 65-k Mycobacterium tuberculosis and Hsp60 proteins. Thus, the 57-kD chlamydial protein, previously implicated as mediating a deleterious immunologic response to chlamydial infections, is a stress-induced protein similar to those that occur universally in both prokaryotic and eukaryotic organisms. PMID:2571668

  13. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein

    PubMed Central

    1989-01-01

    Chlamydia trachomatis infection of humans is commonly a localized inflammation that can result in infertility, blindness, and perhaps arthritis. The pathogenic process(es) that cause these sequelae are thought to be immunological. A 57-kD protein that is common among Chlamydia elicits ocular inflammation when introduced onto the conjunctivae of guinea pigs or nonhuman primates previously sensitized by chlamydial infection. This protein is thought to mediate the immunopathology that follows chlamydial infection. To more thoroughly characterize this chlamydial component, we cloned its gene from a C. psittaci strain and identified a particular recombinant that produced the 57-kD polypeptide. The recombinant gene product was immunoreactive with a monospecific anti-57-kD serum, and elicited an ocular inflammation similar to that produced by the 57-kD antigen isolated from chlamydiae. Sequencing identified two ORFs that encode polypeptides of 11.2 and 58.1 kD and are co-transcribed. These two polypeptides show homology with Escherichia coli groE and Coxiella burnetii htp heat-shock proteins. Striking homology (greater than 50%) was found between the 57-kD protein and the HtpB, GroEL, 65-k Mycobacterium tuberculosis and Hsp60 proteins. Thus, the 57-kD chlamydial protein, previously implicated as mediating a deleterious immunologic response to chlamydial infections, is a stress-induced protein similar to those that occur universally in both prokaryotic and eukaryotic organisms. PMID:2571668

  14. Immunologic Evaluation of Ofloxacin Hypersensitivity

    PubMed Central

    Nam, Young-Hee; Kim, Jeong Eun; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Shin, Yoo Seob; Ye, Young-Min

    2012-01-01

    Quinolone hypersensitivity, most of which is immediate type, is rare but has increased in recent years. The pathogenic mechanisms underlying immediate reactions are not defined clearly. This study was aimed to observe the clinical characteristics of immediate hypersensitivity to ofloxacin and to investigate the pathogenic mechanism with detection of serum specific IgE to ofloxacin using an enzyme-linked immunoasorbent assay (ELISA). We recruited 5 patients with immediate hypersensitivity reactions to ofloxacin (group I), and as control groups, 5 subjects with ciprofloxacin hypersensitivity (group II) and 20 healthy subjects with no history of drug allergy. Serum specific-IgE to ofloxacin-human serum albumin (HSA) conjugate was detectable in four group I subjects (80%) and three group II subjects (60%). The ELISA inhibition test showed significant inhibition with both ofloxacin-HSA conjugate and free ofloxacin in a dose-dependent manner. As to ciprofloxacin, significant inhibition was noted upon addition of free ciprofloxacin in one subject, while minimal inhibition was noted in the other. We confirmed that an IgE-mediated response is a major pathogenic mechanism of ofloxacin hypersensitivity. Cross reactivity between ofloxacin and ciprofloxacin was noted with individual difference. PMID:23115735

  15. De Novo Foliar Transcriptome of Chenopodium amaranticolor and Analysis of Its Gene Expression During Virus-Induced Hypersensitive Response

    PubMed Central

    Zhang, Yongqiang; Pei, Xinwu; Zhang, Chao; Lu, Zifeng; Wang, Zhixing; Jia, Shirong; Li, Weimin

    2012-01-01

    Background The hypersensitive response (HR) system of Chenopodium spp. confers broad-spectrum virus resistance. However, little knowledge exists at the genomic level for Chenopodium, thus impeding the advanced molecular research of this attractive feature. Hence, we took advantage of RNA-seq to survey the foliar transcriptome of C. amaranticolor, a Chenopodium species widely used as laboratory indicator for pathogenic viruses, in order to facilitate the characterization of the HR-type of virus resistance. Methodology and Principal Findings Using Illumina HiSeq™ 2000 platform, we obtained 39,868,984 reads with 3,588,208,560 bp, which were assembled into 112,452 unigenes (3,847 clusters and 108,605 singletons). BlastX search against the NCBI NR database identified 61,698 sequences with a cut-off E-value above 10?5. Assembled sequences were annotated with gene descriptions, GO, COG and KEGG terms, respectively. A total number of 738 resistance gene analogs (RGAs) and homology sequences of 6 key signaling proteins within the R proteins-directed signaling pathway were identified. Based on this transcriptome data, we investigated the gene expression profiles over the stage of HR induced by Tobacco mosaic virus and Cucumber mosaic virus by using digital gene expression analysis. Numerous candidate genes specifically or commonly regulated by these two distinct viruses at early and late stages of the HR were identified, and the dynamic changes of the differently expressed genes enriched in the pathway of plant-pathogen interaction were particularly emphasized. Conclusions To our knowledge, this study is the first description of the genetic makeup of C. amaranticolor, providing deep insight into the comprehensive gene expression information at transcriptional level in this species. The 738 RGAs as well as the differentially regulated genes, particularly the common genes regulated by both TMV and CMV, are suitable candidates which merit further functional characterization to dissect the molecular mechanisms and regulatory pathways of the HR-type of virus resistance in Chenopodium. PMID:23029338

  16. Cytosolic HSP90 and HSP70 are essential components of INF1-mediated hypersensitive response and non-host resistance to Pseudomonas cichorii in Nicotiana benthamiana.

    PubMed

    Kanzaki, H; Saitoh, H; Ito, A; Fujisawa, S; Kamoun, S; Katou, S; Yoshioka, H; Terauchi, R

    2003-09-01

    SUMMARY Mitogen-activated protein kinases (MAPKs) play pivotal roles in the signal transduction pathway of plant defence responses against pathogens. A search for MAPK-interacting proteins revealed an interaction between a Nicotiana benthamiana MAPK, SIPK (NbSIPK) and cytosolic Hsp90 (NbHsp90c-1) in yeast two-hybrid assay. To study the function of Hsp90 in disease resistance, we silenced NbHsp90c-1 in N. benthamiana by virus-induced gene silencing (VIGS) with Potato virus X (PVX). NbHsp90c-1 silenced plants exhibited: (1) a stunted phenotype, (2) no hypersensitive response (HR) development after infiltration with the Phytophthora infestans protein INF1 and a non-host pathogen Pseudomonas cichorii that normally triggers HR in N. benthamiana, (3) compromised non-host resistance to P. cichorii, and (4) consistently reduced transcription levels of PR (pathogenesis related) protein genes. Similar phenotypes were observed also for plants in which a cytosolic Hsp70 (NbHsp70c-1), a gene for another class of molecular chaperon, was silenced. Hsp90 was isolated as a MAPK-interacting protein in yeast two-hybrid assay, therefore we tested the effect of NbHsp90c-1 silencing as well as NbHsp70c-1 silencing on the HR development caused by infiltration of a hyperactive potato MAPKK (StMEK1(DD)). No difference in the timing or extent of HR was found among NbHsp90c-1 silenced, NbHsp70c-1 silenced and control plants. This result indicates that observed impairment of INF1- and P. cichorii-mediated HR development in NbHsp90c-1 silenced and NbHsp70c-1 silenced plants was not caused by the abrogation in MAPK function downstream of active MAPKK that leads to HR. These findings suggest essential roles of Hsp90 and Hsp70 in plant defence signal transduction pathway upstream or independent of the MAPK cascade. PMID:20569398

  17. Acupoint Specificity on Colorectal Hypersensitivity Alleviated by Acupuncture and the Correlation with the Brain-Gut Axis.

    PubMed

    Wang, Shao-Jun; Yang, Hao-Yan; Wang, Fang; Li, Si-Ting

    2015-06-01

    This project was focused on the study of the effect of the different acupoints on visceral hypersensitivity and the correlation with the brain-gut axis. By using a mouse model of zymosan-induced colorectal hypersensitivity, and observing the response of hypersensitivity model to colorectal distension stimulation in acupuncture at different acupoints, we selected the specific acupoints. With immunohistochemical staining method, we observed c-fos expression, distribution and changes after acupuncture on sensory pathway, including colorectum, spinal dorsal horn and different regions of brain center in the model with colorectal distension stimulation, and evaluated the acupuncture effect on brain-gut axis. The results revealed that the effectiveness of acupuncture for alleviating visceral hypersensitivity was different at individual acupoint, meaning Tianshu (ST25), Zusanli (ST36) and Shangjuxu (ST37) > Quchi (LI11) and Dachangshu (BL25) > Ciliao (BL32). C-fos expression was concentrated in anterior cingulate cortex, hypothalamus, spinal dorsal horn and colorectum in model of zymosan-induced colorectal hypersensitivity and it was down-regulated after acupuncture. The results demonstrates that the acupoint specificity presents in acupuncture for relieving visceral hypersensitivity and the effects are more predominated at the acupoints on stomach meridian innervated by the same or adjacent spinal ganglion segments. The model of zymosan-induced colorectal hypersensitivity can be the animal model simulating brain-gut interaction. PMID:25968478

  18. Loss and Gain of Elicitor Function of Soybean Mosaic Virus G7 Provoking Rsv1-Mediated Lethal Systemic Hypersensitive Response Maps to P3

    PubMed Central

    Hajimorad, M. R.; Eggenberger, A. L.; Hill, J. H.

    2005-01-01

    Rsv1, a single dominant resistance gene in soybean PI 96983 (Rsv1), confers extreme resistance against all known American strains of Soybean mosaic virus (SMV), except G7 and G7d. SMV-G7 provokes a lethal systemic hypersensitive response (LSHR), whereas SMV-G7d, an experimentally evolved variant of SMV-G7, induces systemic mosaic. To identify the elicitor of Rsv1-mediated LSHR, chimeras were constructed by exchanging fragments between the molecularly cloned SMV-G7 (pSMV-G7) and SMV-G7d (pSMV-G7d), and their elicitor functions were assessed on PI 96983 (Rsv1). pSMV-G7-derived chimeras containing only P3 of SMV-G7d lost the elicitor function, while the reciprocal chimera of pSMV-G7d gained the function. The P3 regions of the two viruses differ by six nucleotides, of which two are translationally silent. The four amino acid differences are located at positions 823, 915, 953, and 1112 of the precursor polypeptide. Analyses of the site-directed point mutants of both the viruses revealed that nucleotide substitutions leading to translationally silent mutations as well as reciprocal amino acid substitution at position 915 did not influence the loss or gain of the elicitor function. pSMV-G7-derived mutants with amino acid substitutions at any of the other three positions lost the ability to provoke LSHR but induced SHR instead. Two concomitant amino acid substitutions at positions 823 (V to M) and 953 (K to E) abolished pSMV-G7 elicitor function, provoking Rsv1-mediated SHR. Conversely, pSMV-G7d gained the elicitor function of Rsv1-mediated LSHR by a single amino acid substitution at position 823 (M to V), and mutants with amino acid substitutions at position 953 or 1112 induced SHR instead of mosaic. Taken together, the data suggest that strain-specific P3 of SMV is the elicitor of Rsv1-mediated LSHR. PMID:15613348

  19. Loss and gain of elicitor function of soybean mosaic virus G7 provoking Rsv1-mediated lethal systemic hypersensitive response maps to P3.

    PubMed

    Hajimorad, M R; Eggenberger, A L; Hill, J H

    2005-01-01

    Rsv1, a single dominant resistance gene in soybean PI 96983 (Rsv1), confers extreme resistance against all known American strains of Soybean mosaic virus (SMV), except G7 and G7d. SMV-G7 provokes a lethal systemic hypersensitive response (LSHR), whereas SMV-G7d, an experimentally evolved variant of SMV-G7, induces systemic mosaic. To identify the elicitor of Rsv1-mediated LSHR, chimeras were constructed by exchanging fragments between the molecularly cloned SMV-G7 (pSMV-G7) and SMV-G7d (pSMV-G7d), and their elicitor functions were assessed on PI 96983 (Rsv1). pSMV-G7-derived chimeras containing only P3 of SMV-G7d lost the elicitor function, while the reciprocal chimera of pSMV-G7d gained the function. The P3 regions of the two viruses differ by six nucleotides, of which two are translationally silent. The four amino acid differences are located at positions 823, 915, 953, and 1112 of the precursor polypeptide. Analyses of the site-directed point mutants of both the viruses revealed that nucleotide substitutions leading to translationally silent mutations as well as reciprocal amino acid substitution at position 915 did not influence the loss or gain of the elicitor function. pSMV-G7-derived mutants with amino acid substitutions at any of the other three positions lost the ability to provoke LSHR but induced SHR instead. Two concomitant amino acid substitutions at positions 823 (V to M) and 953 (K to E) abolished pSMV-G7 elicitor function, provoking Rsv1-mediated SHR. Conversely, pSMV-G7d gained the elicitor function of Rsv1-mediated LSHR by a single amino acid substitution at position 823 (M to V), and mutants with amino acid substitutions at position 953 or 1112 induced SHR instead of mosaic. Taken together, the data suggest that strain-specific P3 of SMV is the elicitor of Rsv1-mediated LSHR. PMID:15613348

  20. Plant Innate Immunity Induced by Flagellin Suppresses the Hypersensitive Response in Non-Host Plants Elicited by Pseudomonas syringae pv. averrhoi

    PubMed Central

    Wei, Chia-Fong; Hsu, Shih-Tien; Deng, Wen-Ling; Wen, Yu-Der; Huang, Hsiou-Chen

    2012-01-01

    A new pathogen, Pseudomonas syringae pv. averrhoi (Pav), which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR) in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta), glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant Pta?fliC, PA5?fliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5?fliC. PA5?fgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5?fliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns) contributed to induce the PAMP-triggered immunity (PTI). Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction. PMID:22911741

  1. Clinical Features of Immediate Hypersensitivity to Isopropylantipyrine

    PubMed Central

    Hwang, Eui-Kyung; Nam, Young-Hee; Jin, Hyun Jung; Shin, Yoo Seob; Ye, Young-Min

    2013-01-01

    Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs (NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediate hypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity; and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation tests with IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestations were cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patients showed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. The response time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and cross-intolerant NSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs. PMID:23277879

  2. Distractibility and hypersensitivity

    Microsoft Academic Search

    James B. Victor; Charles F. Halverson

    1975-01-01

    The present paper reports on the development of a modified problem checklist for use in normal samples of elementary school children. The two factors, Hypersensitivity and Distractibility, replicated over male and female samples. Hypersensitivity showed a significant grade effect, with a decrease between the first and second grade for both boys and girls. In contrast, boys scored higher than girls

  3. Treating dentin hypersensitivity

    PubMed Central

    Cunha-Cruz, Joana; Wataha, John C.; Zhou, Lingmei; Manning, Walter; Trantow, Michael; Bettendorf, Meishan M.; Heaton, Lisa J.; Berg, Joel

    2011-01-01

    Background Methods used by dental practitioners to diagnose and treat dentin hypersensitivity are not well documented. The authors conducted a survey of dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) to ascertain the treatment methods they used. Methods Via an Internet survey, the authors collected data regarding methods used for diagnosis and treatment of dentin hypersensitivity from 209 Northwest PRECEDENT dentists. Results The PRECEDENT dentists indicated that they most often used fluoride varnishes and gels, advice regarding toothbrushing and diet, bonding agents, restorative materials and glutaraldehyde/2-hydroxyethyl methacrylate (HEMA) to treat dentin hypersensitivity. They reported that the most successful treatments were fluorides, glutaraldehyde/HEMA, bonding agents, potassium nitrates and restorative treatments; they considered observation, advice regarding toothbrushing and diet and laser therapy to be the least successful. Dentists listed fluorides, calcium phosphates, glutaraldehyde/HEMA and bonding agents as the treatments most desirable for inclusion in a future randomized clinical trial of dental hypersensitivity treatments. Conclusions Dentists rely on patients to assess the severity of dentin hypersensitivity. Modalities for the diagnosis and treatment of hypersensitivity are diverse. Methods used to diagnose and treat dentin hypersensitivity in practice are challenging to justify. Clinical Implications Practitioners should be aware of the diversity of methods available for diagnosing and treating dentin hypersensitivity as they manage the care of their patients with this condition. PMID:20807910

  4. Strain-specific cylindrical inclusion protein of soybean mosaic virus elicits extreme resistance and a lethal systemic hypersensitive response in two resistant soybean cultivars.

    PubMed

    Seo, Jang-Kyun; Lee, Suk-Ha; Kim, Kook-Hyung

    2009-09-01

    In the Soybean mosaic virus (SMV)-soybean pathosystem, three independent genes (Rsv1, Rsv3, and Rsv4) conferring resistance to SMV have been identified. Recently, we constructed infectious cDNA clones of SMV G7H and G5H strains and found that these two strains differ in their ability to infect soybean genotypes possessing different SMV resistance genes despite a difference of only 33 amino acids. In particular, pSMV-G7H induced mosaic symptoms systemically in L29 (Rsv3) and provoked a lethal systemic hypersensitive response (LSHR) in Jinpumkong-2, whereas pSMV-G5H could not infect these soybean genotypes. To identify the responsible pathogenic determinants of SMV, we exploited the differential responses of pSMV-G7H- and pSMV-G5H-derived chimeric viruses and amino acid substitution mutant viruses in several soybean genotypes and demonstrated that cylindrical inclusion (CI) protein is the elicitor of Rsv3-mediated extreme resistance and a pathogenic determinant provoking LSHR in Jinpumkong-2. A single amino acid substitution in CI was found to be responsible for gain or loss of elicitor function of CI. Our finding provides a role for CI as a pathogenic determinant in the SMV-soybean pathosystem, and increases the understanding of the basis of the different disease responses of SMV strains. PMID:19656049

  5. Comparative analysis of induction pattern of programmed cell death and defense-related responses during hypersensitive cell death and development of bacterial necrotic leaf spots in eggplant.

    PubMed

    Kiba, Akinori; Takata, Osamu; Ohnishi, Kouhei; Hikichi, Yasufumi

    2006-10-01

    Pseudomonas cichorii causes necrotic leaf spots (NLS), while Pseudomonas syringae pv. tabaci induces a hypersensitive response (HR) in eggplant. P. cichorii induced cell death at 9 h after inoculation (HAI), reaching a maximum of around 24-30 HAI. On the other hand, cell death was induced 6 HAI with P. syringae pv. tabaci, reaching a maximum of around 12-18 HAI. Superoxide generation was observed in eggplant inoculated with both bacteria. DNA fragmentation, cytochrome c release into the cytosol and expression of defense-related genes such as PR-1 and hsr203J was also induced by inoculation with both bacteria, but these plant reactions were more rapidly induced in eggplant inoculated with P. syringae pv. tabaci rather than those with P. cichorii. Lipid peroxidation and induction of lipoxygenase (LOX) was drastically induced in eggplant inoculated with P. syringae pv. tabaci compared to P. cichorii-inoculated eggplant. Pharmacological studies showed that induction of the cell death, and the NLS or the HR in response to both bacteria was commonly associated with de novo protein synthesis, reactive oxygen species and caspase III-like protease. Interestingly, involvement of lipid peroxidation, LOX, serine protease, and DNase differed between induction of NLS and HR. These results suggest that programmed cell death might be closely associated not only with the HR but also NLS. However, there may be differences not only in the induction kinetics and level of plant responses but also in the infection-related responses between HR and NLS. PMID:16614819

  6. Resistance of sunflower to the biotrophic oomycete Plasmopara halstedii is associated with a delayed hypersensitive response within the hypocotyls.

    PubMed

    Radwan, O; Mouzeyar, S; Venisse, J S; Nicolas, P; Bouzidi, M F

    2005-10-01

    The biotrophic oomycete Plasmopara halstedii is the causal agent of downy mildew in sunflower. It penetrates the roots of both susceptible and resistant sunflower lines and grows through the hypocotyls towards the upper part of the seedling. RT-PCR analysis has shown that resistance is associated with the activation of a hsr203J-like gene, which is a molecular marker of the hypersensitive reaction in tobacco. Activation of this gene was specifically observed during the incompatible interaction and coincided with cell collapse in the hypocotyls. This HR was also associated with the early and local activation of the NPR1 gene which is a key component in the establishment of the SAR. No such HR or a significant activation of the hsr203J-like gene were observed during the compatible combination. These results suggest that the resistance of sunflower to P. halstedii is associated with an HR which fails to halt the parasite. By contrast, this HR triggers a SAR which takes places in the upper part of the hypocotyls and eventually leads to the arrest of parasite growth. A model describing the resistance of plants to root-infecting oomycetes is proposed. PMID:16143719

  7. Oral Hypersensitivity Reactions

    MedlinePLUS

    ... of substances. The most common causes are food, food additives, drugs, oral hygiene products, and dental materials. Q: Are there any specific foods that are more commonly implicated in intraoral hypersensitivity ...

  8. Contaminant-related suppression of delayed-type hypersensitivity and antibody responses in harbor seals fed herring from the Baltic Sea.

    PubMed Central

    Ross, P S; De Swart, R L; Reijnders, P J; Van Loveren, H; Vos, J G; Osterhaus, A D

    1995-01-01

    Recent mass mortalities among several marine mammal populations have led to speculation about increased susceptibility to viral infections as a result of contaminant-induced immunosuppression. In a 2.5-year study, we fed herring from either the relatively uncontaminated Atlantic Ocean or the contaminated Baltic Sea to two groups of captive harbor seals and monitored immune function in the seals. Seals fed the contaminated fish were less able to mount a specific immunological response to ovalbumin, as measured by in vivo delayed-type hypersensitivity (DTH) reactions and antibody responses. The skin reaction to this protein antigen was characterized by the appearance of mononuclear cells which peaked at 24 hr after intradermal administration, characteristic of DTH reactions in other animals studied. These DTH responses correlated well with in vitro tests of T-lymphocyte function, implicating this cell type in the reaction. Aryl-hydrocarbon (Ah) receptor-dependent toxic equivalent (TEQ) profiles in blubber biopsies taken from the seals implicated polychlorinated biphenyls rather than dioxins or furans in the observed immunosuppression. Marine mammal populations currently inhabiting polluted coastal environments in Europe and North America may therefore have an increased susceptibility to infections, and pollution may have played a role in recent virus-induced mass mortalities. Images p162-a Figure 1. Figure 2. A Figure 2. B Figure 2. C Figure 3. Figure 4. PMID:7737064

  9. Hall viscosity revealed via density response

    NASA Astrophysics Data System (ADS)

    Huang, Biao

    2015-06-01

    Quantum Hall systems have recently been shown to possess a quantity sensitive to the spatial geometry and topology of the system, dubbed the Hall viscosity ?H. Despite the extensive theoretical discussions on its properties, the question of how to measure ?H still poses a challenge. In this paper, we present a general relation between Hall viscosity and susceptibility for systems with Galilean invariance. Thus, it allows for determination of ?H through density response signatures. The relations are verified in the integer quantum Hall example and are further illustrated in an effective hydrodynamic analysis. Since the derivation is based on Kubo formulas and assumes no more than conservation laws and translational symmetry, the results are applicable to a wide range of systems.

  10. Alveolar Macrophage Innate Response to Mycobacterium immunogenum, the Etiological Agent of Hypersensitivity Pneumonitis: Role of JNK and p38 MAPK Pathways

    PubMed Central

    Yadav, Jagjit S.

    2013-01-01

    Mycobacterium immunogenum is an emerging pathogen of the immune-mediated lung disease hypersensitivity pneumonitis (HP) reported in machinists occupationally exposed to contaminated metal working fluid (MWF). However, the mechanism of its interaction with the host lung is unclear. Considering that alveolar macrophages play a central role in host defense in the exposed lung, understanding their interaction with the pathogen could provide initial insights into the underlying immunopathogenesis events and mechanisms. In the current study, M. immunogenum 700506, a predominant genotype isolated from HP-linked fluids, was shown to multiply intracellularly, induce proinflammatory mediators (TNF-?, IL-1?, IL-1?, IL-6, GM-CSF, NO) and cause cytotoxicity/cell death in the cultured murine alveolar macrophage cell line MH-S in a dose- and time-dependent manner. The responses were detected as early as 3h post-infection. Comparison of this and four additional genotypes of M. immunogenum (MJY-3, MJY-4, MJY-12, MJY-14) using an effective dose-time combination (100 MOI for 24h) showed these macrophage responses in the following order (albeit with some variations for individual response indicators). Inflammatory: MJY-3 ? 700506 > MJY-4 ? MJY-14 ? MJY-12; Cytotoxic: 700506 ? MJY-3 > MJY-4 ? MJY-12 ? MJY-14. In general, 700506 and MJY-3 showed a more aggressive response than other genotypes. Chemical blocking of either p38 or JNK inhibited the induction of proinflammatory mediators (cytokines, NO) by 700506. However, the cellular responses showed a somewhat opposite effect. This is the first report on M. immunogenum interactions with alveolar macrophages and on the identification of JNK- and p38- mediated signaling and its role in mediating the proinflammatory responses during these interactions. PMID:24349452

  11. Suppression of hapten-specific delayed-type hypersensitivity responses in mice by idiotype-specific suppressor T cells after administration of anti-idiotypic antibodies

    PubMed Central

    1979-01-01

    Delayed-type hypersensitivity (DTH) responses specific for the phosphorylcholine (PC) hapten were induced in BALB/c mice by immunization with syngeneic peritoneal exudate cells (PEC) coupled with diazotized phenyl-phosphoryl-choline. PC-specific DTH responses were elicited in such immunized mice after footpad challenge with PC- derivatized syngeneic spleen cells. Moreover, PC-immune lymph node cells could passively transfer PC-specific DTH responses to naive BALB/c mice and it was possible to demonstrate that the cells responsible for such passively transferred responses were T lymphocytes. Because the T-15 idiotypic determinant displayed on the TEPC-15 PC-binding myeloma protein is known to be a dominant idiotype associated with anti-PC antibody responses in BALB/c mice, an analysis was made of the effects of anti-T-15 idiotypic antibodies on the induction and expression of murine PC-specific DTH responses. Repeated injections of anti-T-15 idiotypic antiserum, raised in A/J mice by immunization with TEPC-15 myeloma protein, into recipient BALB/c mice both immediately before and after sensitization with PC-PEC virtually abolished the development of PC-specific DTH responses. Although administration of anti-T-15 antiserum effectively inhibited the induction phase of PC-specific DTH responses, these anti-idiotypic antibodies had no suppressive activity at the effector phase of these responses. The inhibition observed with anti-T-15 antibodies was highly specific for the PC hapten, and for PC-specific DTH responses of BALB/c but not A/J mice. Studies were conducted to address the possibility that anti-Id treatment induced suppressor T lymphocytes capable of specifically inhibiting the activity of PC-specific T cells participating in DTH responses. The results demonstrate that idiotype- specific suppressor T cells are, indeed, induced by treatment with anti- Id; moreover, such suppressor T cells, once induced, are highly effective in abrogating both the induction and the effector phases of PC-specific T cell-mediated DTH responses in BALB/c mice. PMID:92519

  12. Suppression of the AvrBs1-specific hypersensitive response by the YopJ effector homolog AvrBsT from Xanthomonas depends on a SNF1-related kinase.

    PubMed

    Szczesny, Robert; Büttner, Daniela; Escolar, Lucia; Schulze, Sebastian; Seiferth, Anja; Bonas, Ulla

    2010-09-01

    *Pathogenicity of the Gram-negative plant pathogen Xanthomonas campestris pv. vesicatoria (Xcv) depends on a type III secretion system that translocates a cocktail of > 25 type III effector proteins into the plant cell. *In this study, we identified the effector AvrBsT as a suppressor of specific plant defense. AvrBsT belongs to the YopJ/AvrRxv protein family, members of which are predicted to act as proteases and/or acetyltransferases. *AvrBsT suppresses the hypersensitive response (HR) that is elicited by the effector protein AvrBs1 from Xcv in resistant pepper plants. HR suppression occurs inside the plant cell and depends on a conserved predicted catalytic residue of AvrBsT. Yeast two-hybrid based analyses identified plant interaction partners of AvrBs1 and AvrBsT, including a putative regulator of sugar metabolism, SNF1-related kinase 1 (SnRK1), as interactor of AvrBsT. Intriguingly, gene silencing experiments revealed that SnRK1 is required for the induction of the AvrBs1-specific HR. *We therefore speculate that SnRK1 is involved in the AvrBsT-mediated suppression of the AvrBs1-specific HR. PMID:20609114

  13. PopA1, a protein which induces a hypersensitivity-like response on specific Petunia genotypes, is secreted via the Hrp pathway of Pseudomonas solanacearum.

    PubMed Central

    Arlat, M; Van Gijsegem, F; Huet, J C; Pernollet, J C; Boucher, C A

    1994-01-01

    This paper describes the identification of a new class of extracellular bacterial proteins, typified by PopA1 and its derivative PopA3, which act as specific hypersensitive response (HR) elicitors. These two heat-stable proteins, with HR-like elicitor activities on tobacco (non-host plant) but without activity on tomato (host plant), have been characterized from the supernatant of the plant pathogenic bacterium Pseudomonas solanacearum strain GMI1000. These two proteins induced the same pattern of response on Petunia, as a function of the genotypes tested. popA, the structural gene for PopA1, maps outside of the hrp gene cluster but belongs to the hrp regulon. The amino acid sequence of PopA1 does not show homology to any characterized proteins. Its secretion is dependent on hrp genes and is followed by stepwise removal of the 93 amino-terminal amino acids, producing the protein PopA3. Petunia lines responsive to PopA3 and its precursors were resistant to infection by strain GMI1000, whereas non-responsive lines were sensitive, suggesting that popA could be an avirulence gene. A popA mutant remained fully pathogenic on sensitive plants, indicating that this gene is not essential for pathogenicity. While lacking PopA1, this mutant, which remained avirulent on tobacco and on resistant Petunia lines, still produced additional extracellular necrogenic compounds. On the basis of both their structural features and the biological properties of the popA mutant, PopA1 and PopA3 clearly differ from hairpins characterized in other plant pathogenic bacteria. Images PMID:8313899

  14. Oligomerization, Conformational Stability and Thermal Unfolding of Harpin, HrpZPss and Its Hypersensitive Response-Inducing C-Terminal Fragment, C-214-HrpZPss

    PubMed Central

    Tarafdar, Pradip K.; Vedantam, Lakshmi Vasudev; Sankhala, Rajeshwer S.; Purushotham, Pallinti; Podile, Appa Rao; Swamy, Musti J.

    2014-01-01

    HrpZ—a harpin from Pseudomonas syringae—is a highly thermostable protein that exhibits multifunctional abilities e.g., it elicits hypersensitive response (HR), enhances plant growth, acts as a virulence factor, and forms pores in plant plasma membranes as well as artificial membranes. However, the molecular mechanism of its biological activity and high thermal stability remained poorly understood. HR inducing abilities of non-overlapping short deletion mutants of harpins put further constraints on the ability to establish structure-activity relationships. We characterized HrpZPss from Pseudomonas syringae pv. syringae and its HR inducing C-terminal fragment with 214 amino acids (C-214-HrpZPss) using calorimetric, spectroscopic and microscopic approaches. Both C-214-HrpZPss and HrpZPss were found to form oligomers. We propose that leucine-zipper-like motifs may take part in the formation of oligomeric aggregates, and oligomerization could be related to HR elicitation. CD, DSC and fluorescence studies showed that the thermal unfolding of these proteins is complex and involves multiple steps. The comparable conformational stability at 25°C (?10.0 kcal/mol) of HrpZPss and C-214-HrpZPss further suggest that their structures are flexible, and the flexibility allows them to adopt proper conformation for multifunctional abilities. PMID:25502017

  15. Hypersensitivity to hypercapnia: definition/(s).

    PubMed

    Vickers, Kristin

    2012-05-15

    Empirical evidence indicates that panic disorder (PD) patients experience hypersensitivity to hypercapnia, a condition in which the blood level of carbon dioxide exceeds the normal value. The importance of this research line is substantial and indeed, hypercapnic hypersensitivity has been advanced as a possible endophenotype of panic. Definitions of "hypersensitivity," however, have varied. The purpose of this brief review is to delineate and critique different definitions of hypercapnic hypersensitivity. Several definitions - panic attack rate, panic symptoms including dyspnea, subjective anxiety, and respiratory disturbance - are explored. The review concludes that although no ideal definition has emerged, marked anxiety post-hypercapnia has substantial support as a putative trait marker of PD. The term "subjective hypersensitivity" (Coryell et al., 2001) is re-introduced to denote pronounced anxiety post-hypercapnia and recommended for use along with its previous definition: increased self-reported anxiety measured on a continuous visual analog scale, already widely in use. Due to the well-established link between panic and respiration, definitional candidates focusing on aberrant respiratory response - less investigated as trait markers of PD in high risk studies - warrant scrutiny as well. Several reasons why definitional clarity might be beneficial are presented, along with ideas for future research. PMID:22401967

  16. Electrosensibility and electromagnetic hypersensitivity.

    PubMed

    Leitgeb, Norbert; Schröttner, Jörg

    2003-09-01

    Electromagnetic sensibility, the ability to perceive electric and electromagnetic exposure, and electromagnetic hypersensitivity (EHS), developing health symptoms due to exposure to environmental electromagnetic fields, need to be distinguished. Increased electrosensibility is a necessary, however, not a sufficient condition for electromagnetic hypersensitivity. At an extended sample of the general population of 708 adults, including 349 men and 359 women aged between 17 and 60 years, electrosensibility was investigated and characterized by perception threshold and its standard deviation. By analyzing the probability distributions of the perception threshold of electric 50 Hz currents, evidence could be found for the existence of a subgroup of people with significantly increased electrosensibility (hypersensibility) who as a group could be differentiated from the general population. The presented data show that the variation of the electrosensibility among the general population is significantly larger than has yet been estimated by nonionizing radiation protection bodies, but much smaller than claimed by hypersensitivity self-aid groups. These quantitative results should contribute to a less emotional discussion of this problem. The investigation method presented, is capable of exclusion diagnostics for persons suffering from the hypersensitivity syndrome. PMID:12929157

  17. Hypersensitive cell death and post-haustorial defence responses arrest the orange rust ( Hemileia vastatrix) growth in resistant coffee leaves

    Microsoft Academic Search

    M. C. Silva; M. Nicole; L. Guerra-GuimarĂes; C. J. Rodrigues

    2002-01-01

    The growth of a coffee orange rust fungus (Hemileia vastatrix Berk and Br.) isolate (race II) and the sequence of responses it induced in leaves of resistant Coffea arabica L. and C. congensis Froehner as well as on a susceptible C. arabica were investigated cytologically and biochemically. The percentages of germinated urediospores and of appressoria formed over stomata as well

  18. Novel Antibodies Reactive with Sialyl Lewis X in Both Humans and Mice Define Its Critical Role in Leukocyte Trafficking and Contact Hypersensitivity Responses.

    PubMed

    Matsumura, Ryuji; Hirakawa, Jotaro; Sato, Kaori; Ikeda, Toshiaki; Nagai, Motoe; Fukuda, Minoru; Imai, Yasuyuki; Kawashima, Hiroto

    2015-06-12

    Sialyl Lewis X (sLe(x)) antigen functions as a common carbohydrate determinant recognized by all three members of the selectin family. However, its expression and function in mice remain undefined due to the poor reactivity of conventional anti-sLe(x) monoclonal antibodies (mAbs) with mouse tissues. Here, we developed novel anti-sLe(x) mAbs, termed F1 and F2, which react well with both human and mouse sLe(x), by immunizing fucosyltransferase (FucT)-IV and FucT-VII doubly deficient mice with 6-sulfo-sLe(x)-expressing cells transiently transfected with an expression vector encoding CMP-N-acetylneuraminic acid hydroxylase. F1 and F2 specifically bound both the N-acetyl and the N-glycolyl forms of sLe(x) as well as 6-sulfo-sLe(x), a major ligand for L-selectin expressed in high endothelial venules, and efficiently blocked physiological lymphocyte homing to lymph nodes in mice. Importantly, both of the mAbs inhibited contact hypersensitivity responses not only when administered in the L-selectin-dependent sensitization phase but also when administered in the elicitation phase in mice. When administered in the latter phase, F1 and F2 efficiently blocked rolling of mouse leukocytes along blood vessels expressing P- and E-selectin in the auricular skin in vivo. Consistent with these findings, the mAbs blocked P- and E-selectin-dependent leukocyte rolling in a flow chamber assay. Taken together, these results indicate that novel anti-sLe(x) mAbs reactive with both human and mouse tissues, with the blocking ability against leukocyte trafficking mediated by all three selectins, have been established. These mAbs should be useful in determining the role of sLe(x) antigen under physiological and pathological conditions. PMID:25944902

  19. Induction of Shrimp Tropomyosin-Specific Hypersensitivity in Mice

    Microsoft Academic Search

    Patrick S. C. Leung; Yuen Shan Lee; Chi Yan Tang; Wing Yee Kung; Ya-Hui Chuang; Bor-Luen Chiang; Ming Chiu Fung; Ka Hou Chu

    2008-01-01

    Background: Shellfish hypersensitivity is amongst the most common food allergies. The major shellfish allergen was identified as tropomyosin. Here, we investigated the immediate hypersensitivity responses, IgE and cell-mediated immune response in mice sensitized with recombinant shrimp tropomyosin. Methods: Shrimp tropomyosin was cloned and expressed as a His-tagged fusion recombinant protein in Escherichia coli. Three- to 4-week-old BALB\\/c mice were sensitized

  20. [Cephalic hypersensitivity syndrome].

    PubMed

    Shimizu, Toshihiko; Hirata, Koichi; Manaka, Shinya; Arakawa, Ichiro

    2012-01-01

    The number of patients suffering from chronic headache accompanied by dizziness and cephalic ringing is gradually increasing. Pathophysiology of migraine has been commonly explained by trigeminovascular theory, although recent studies have suggested that the cause of the migraine stems from cortical hyperexcitability. We measured EEG in 1,000 patients suffering from daily headache accompanied by dizziness and cephalic ringing. Here we defined a new syndrome,"cephalic hypersensitivity syndrome" as a subliminal cortical hyperexcitability which itself is invisible but apparently seen as some symptoms such as dizziness and cephalic ringing. The cephalic hypersensitivity syndrome should be treated to attenuate the excitability by an appropriate triptan medication during attacks so as to exhibit its recurrence. PMID:22413510

  1. Targeting a Cross-Reactive Gly m 5 Soy Peptide as Responsible for Hypersensitivity Reactions in a Milk Allergy Mouse Model

    PubMed Central

    Curciarello, Renata; Smaldini, Paola L.; Candreva, Angela M.; González, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A.

    2014-01-01

    Background Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity. Methods Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (?), a truncated fragment containing the C-terminal domain (?-T) and peptides of ?-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy. Results Both ? and ?-T reacted with the different CMP-specific antibodies. ?-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the ?-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice. Conclusions Gly m 5 is a cross-reactive soy allergen and the ?-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide. PMID:24416141

  2. Hypersensitivity reactions to vaccine components.

    PubMed

    Heidary, Noushin; Cohen, David E

    2005-09-01

    Vaccines are responsible for the control of many infectious diseases that were once common in the United States, including polio, measles, diphtheria, pertussis (whooping cough), rubella (German measles), mumps, tetanus, and Haemophilus influenzae type b. National efforts to generate collaboration between federal, state, and local governments and public and private health care providers have resulted in record high levels of vaccination coverage in the United States. The high rate of US vaccinations is paralleled by growing concerns about the safety of their delivery. The variety of substances used in vaccines sometimes causes the development of cutaneous reactions in susceptible adults and children. This article will review adverse cutaneous events consistent with hypersensitivity reactions to the following ingredients in vaccines: aluminum, thimerosal, 2-phenoxyethanol, formaldehyde, and neomycin. PMID:16242081

  3. Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength

    PubMed Central

    Paskin, Taylor R.; Jellies, John; Bacher, Jessica; Beane, Wendy S.

    2014-01-01

    Planarians are free-living aquatic flatworms that possess a well-documented photophobic response to light. With a true central nervous system and simple cerebral eyes (ocelli), planarians are an emerging model for regenerative eye research. However, comparatively little is known about the physiology of their photoreception or how their behavior is affected by various wavelengths. Most phototactic studies have examined planarian behavior using white light. Here, we describe a novel planarian behavioral assay to test responses to small ranges of visible wavelengths (red, blue, green), as well as ultraviolet (UV) and infrared (IR) which have not previously been examined. Our data show that planarians display behavioral responses across a range of wavelengths. These responses occur in a hierarchy, with the shortest wavelengths (UV) causing the most intense photophobic responses while longer wavelengths produce no effect (red) or an apparent attraction (IR). In addition, our data reveals that planarian photophobia is comprised of both a general photophobic response (that drives planarians to escape the light source regardless of wavelength) and wavelength-specific responses that encompass specific behavioral reactions to individual wavelengths. Our results serve to improve the understanding of planarian phototaxis and suggest that behavioral studies performed with white light mask a complex behavioral interaction with the environment. PMID:25493551

  4. Arabidopsis thaliana natural variation reveals connections between UV radiation stress and plant pathogen-like defense responses.

    PubMed

    Piofczyk, Thomas; Jeena, Ganga; Pecinka, Ales

    2015-08-01

    UV radiation is a ubiquitous component of solar radiation that affects plant growth and development. Here we studied growth related traits of 345 Arabidopsis thaliana accessions in response to UV radiation stress. We analyzed the genetic basis of this natural variation by genome-wide association studies, which suggested a specific candidate genomic region. RNA-sequencing of three sensitive and three resistant accessions combined with mutant analysis revealed five large effect genes. Mutations in PHE AMMONIA LYASE 1 (PAL1) and putative kinase At1g76360 rendered Arabidopsis hypersensitive to UV stress, while loss of function from putative methyltransferase At4g22530, NOVEL PLANT SNARE 12 (NPSN12) and defense gene ACTIVATED DISEASE RESISTANCE 2 (ADR2) conferred higher UV stress resistance. Three sensitive accessions showed strong ADR2 transcriptional activation, accumulation of salicylic acid (SA) and dwarf growth upon UV stress, while these phenotypes were much less affected in resistant plants. The phenotype of sensitive accessions resembles autoimmune reactions due to overexpression of defense related genes, and suggests that natural variation in response to UV radiation stress is driven by pathogen-like responses in Arabidopsis. PMID:25656510

  5. Cytosolic HSP90 and HSP70 are essential components of INF1-mediated hypersensitive response and non-host resistance to Pseudomonas cichorii in Nicotiana benthamiana

    Microsoft Academic Search

    H. Kanzaki; H. Saitoh; A. Ito; S. Fujisawa; S. Kamoun; S. Katou; H. Yoshioka; R. Terauchi

    2003-01-01

    SUMMARY Mitogen-activated protein kinases (MAPKs) play pivotal roles in the signal transduction pathway of plant defence responses against pathogens. A search for MAPK-interacting proteins revealed an interaction between a Nicotiana benthamiana MAPK, SIPK (NbSIPK) and cytosolic Hsp90 (NbHsp90c-1) in yeast two- hybrid assay. To study the function of Hsp90 in disease resistance, we silenced NbHsp90c-1 in N. benthamiana by virus-induced

  6. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

    Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

  7. Hypersensitivity pneumonitis after exposure to isocyanates.

    PubMed Central

    Charles, J; Bernstein, A; Jones, B; Jones, D J; Edwards, J H; Seal, R M; Seaton, A

    1976-01-01

    Four patients exposed to isocyanate vapour developed dyspnoea associated with restriction and reduced gas transfer as well as moderate airways obstruction on lung function testing. In one patient bilateral radiographic shadowing was present and an open lung biopsy was performed. The microscopic appearances ranged from acute inflammation to end-stage fibrosis but the centribular accentuation of disease and the presence of areas resembling bronchopulmonary aspergillosis suggested that the process was a hypersensitivity response to inhaled allergen. Challenge tests with albumin and toluene diisocyanate-albumin were carried out in sensitized and control rabbits. The sensitized animals developed extensive lung damage of the type associated with an Arthus reaction. It is suggested that patients exposed to isocyanates may occasionally develop a hypersensitivity pneumonitis rather than the more usual asthmatic syndrome. Images PMID:181861

  8. Metabolomics reveals insect metabolic responses associated with fungal infection.

    PubMed

    Xu, Yong-Jiang; Luo, Feifei; Gao, Qiang; Shang, Yanfang; Wang, Chengshu

    2015-06-01

    The interactions between insects and pathogenic fungi are complex. We employed metabolomic techniques to profile insect metabolic dynamics upon infection by the pathogenic fungus Beauveria bassiana. Silkworm larvae were infected with fungal spores and microscopic observations demonstrated that the exhaustion of insect hemocytes was coupled with fungal propagation in the insect body cavity. Metabolomic analyses revealed that fungal infection could significantly alter insect energy and nutrient metabolisms as well as the immune defense responses, including the upregulation of carbohydrates, amino acids, fatty acids, and lipids, but the downregulation of eicosanoids and amines. The insect antifeedant effect of the fungal infection was evident with the reduced level of maclurin (a component of mulberry leaves) in infected insects but elevated accumulations in control insects. Insecticidal and cytotoxic mycotoxins like oosporein and beauveriolides were also detected in insects at the later stages of infection. Taken together, the metabolomics data suggest that insect immune responses are energy-cost reactions and the strategies of nutrient deprivation, inhibition of host immune responses, and toxin production would be jointly employed by the fungus to kill insects. The data obtained in this study will facilitate future functional studies of genes and pathways associated with insect-fungus interactions. PMID:25895944

  9. Bacterial evolution of antibiotic hypersensitivity

    PubMed Central

    Lázár, Viktória; Pal Singh, Gajinder; Spohn, Réka; Nagy, István; Horváth, Balázs; Hrtyan, Mónika; Busa-Fekete, Róbert; Bogos, Balázs; Méhi, Orsolya; Csörg?, Bálint; Pósfai, György; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs; Papp, Balázs; Pál, Csaba

    2013-01-01

    The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large-scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole-genome sequencing of laboratory-evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton-motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF-dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade-offs under antibiotic selection. PMID:24169403

  10. Suppressive subtraction hybridization reveals that rice gall midge attack elicits plant-pathogen-like responses in rice.

    PubMed

    Rawat, Nidhi; Himabindu, Kudapa; Neeraja, Chiruvuri Naga; Nair, Suresh; Bentur, Jagadish S

    2013-02-01

    The Asian rice gall midge, Orseolia oryzae (Diptera: Cecidomyiidae), is the third most destructive insect pest of rice (Oryza sativa L.). Till date, 11 gall midge resistance gene loci have been characterized in different rice varieties. To elucidate molecular basis of incompatible (hypersensitive response plus [HR+] type) and compatible rice-gall midge interactions, two suppressive subtraction hybridization cDNA libraries were constructed. These were enriched for differentially expressed transcripts after gall midge infestation in two rice varieties (resistant Suraksha and susceptible TN1). In total, 2784 ESTs were generated and sequenced from the two libraries, of which 1536 were from the resistant Suraksha and 1248 were from the susceptible TN1. Majority (80%) of the ESTs was non-redundant sequences with known functions and was classified into three principal gene ontology (GO) categories and 12 groups. Upregulation of NBS-LRR, Cytochrome P450, heat shock proteins, phenylalanine ammonia lyase and OsPR10? genes from the Suraksha library, as revealed by real-time PCR, indicated that R gene mediated, salicylic acid related defense pathway is likely to be involved in gall midge resistance. Present study suggested that resistance in Suraksha against gall midge is similar in nature to the resistance observed in plants against pathogens. However, in TN1, genes related to primary metabolism and redox were induced abundantly. Results suggested that genes encoding translationally controlled tumor protein and NAC domain proteins are likely to be involved in the gall midge susceptibility. PMID:23257077

  11. The absence of delayed-type hypersensitivity reactivity in a syngeneic murine tumour system.

    PubMed Central

    Los, G; De Weger, R A; Moberts, R M; Van Loveren, H; Sakkers, R J; Den Otter, W

    1987-01-01

    In different murine systems, delayed-type hypersensitivity (DTH) swelling responses at 24-48 hr after antigen challenge were preceded by an early 2-hr swelling response. The 24-hr DTH response is thought to depend on this early (DTH-initiating) hypersensitivity response. In this paper we show that in the syngeneic DBA/2-SL2 murine tumour system only an early 2-hr swelling response can be evoked. This early hypersensitivity response was tumour specific and serotonin dependent. The early hypersensitivity response in contact hypersensitivity has been ascribed to antigen-specific T-cell factors. To test whether similar T-cell factors were involved in the early hypersensitivity response in this syngeneic tumour system, we have transferred lymph node, spleen lymphocytes and serum from immunized mice into naive recipients. The serum was fractionated in two fractions, a 50,000-80,000 MW fraction, and a 120,000-190,000 MW fraction. In recipients of lymphocytes, total serum and the 50,000-80,000 MW fraction of the serum, an early hypersensitivity response can be evoked. So, these data suggest the involvement of specific T-cell factors in the development of an early hypersensitivity response against syngeneic tumour cells. Despite the development of an early (DTH initiating) hypersensitivity swelling response these immunized animals cannot develop a classical 24-hr swelling response. This absence of the 24-hr response in the presence of the 2-hr response is discussed in relation to the frequently observed immune suppression in tumour-bearing mice. PMID:3498686

  12. A dominant repressor version of the tomato Sl-ERF.B3 gene confers ethylene hypersensitivity via feedback regulation of ethylene signaling and response components.

    PubMed

    Liu, Mingchun; Pirrello, Julien; Kesari, Ravi; Mila, Isabelle; Roustan, Jean-Paul; Li, Zhengguo; Latché, Alain; Pech, Jean-Claude; Bouzayen, Mondher; Regad, Farid

    2013-11-01

    Ethylene Response Factors (ERFs) are downstream components of the ethylene signal transduction pathway, although their role in ethylene-dependent developmental processes remains poorly understood. As the ethylene-inducible tomato Sl-ERF.B3 has been shown previously to display a strong binding affinity to GCC-box-containing promoters, its physiological significance was addressed here by a reverse genetics approach. However, classical up- and down-regulation strategies failed to give clear clues to its roles in planta, probably due to functional redundancy among ERF family members. Expression of a dominant repressor ERF.B3-SRDX version of Sl-ERF.B3 in the tomato resulted in pleiotropic ethylene responses and vegetative and reproductive growth phenotypes. The dominant repressor etiolated seedlings displayed partial constitutive ethylene response in the absence of ethylene and adult plants exhibited typical ethylene-related alterations such as leaf epinasty, premature flower senescence and accelerated fruit abscission. The multiple symptoms related to enhanced ethylene sensitivity correlated with the altered expression of ethylene biosynthesis and signaling genes and suggested the involvement of Sl-ERF.B3 in a feedback mechanism that regulates components of ethylene production and response. Moreover, Sl-ERF.B3 was shown to modulate the transcription of a set of ERFs and revealed the existence of a complex network interconnecting different ERF genes. Overall, the study indicated that Sl-ERF.B3 had a critical role in the regulation of multiple genes and identified a number of ERFs among its primary targets, consistent with the pleiotropic phenotypes displayed by the dominant repression lines. PMID:23931552

  13. The Arabidopsis hrl1 mutation reveals novel overlapping roles for salicylic acid, jasmonic acid and ethylene

    E-print Network

    Raina, Ramesh

    molecules: salicylic acid (SA), jasmonic acid (JA) and ethylene (ET). The hrl1 (hypersensitive response of reactive oxygen species, constitutive expression of SA- and ET/JA-responsive defence genes, and enhanced and SA- depleted nahG plants revealed novel interactions between SA and ET/JA signalling pathways

  14. Hypersensitivity pneumonitis induced by Shiitake mushroom spores.

    PubMed

    Ampere, Alexandre; Delhaes, Laurence; Soots, Jacques; Bart, Frederic; Wallaert, Benoit

    2012-08-01

    Hypersensitivity pneumonitis (HP) is a pulmonary granulomatosis involving an immunoallergic mechanism caused by chronic inhalation of antigens, most frequently organic substances, as well as chemicals. We report the first European case of hypersensitivity pneumonitis due to the inhalation of Shiitake mushroom spores. A 37-year-old French Caucasian man with a one-month history of persistent dry cough, shortness of breath and loss of weight was admitted to our hospital on December 2010. Anamnesis showed he was involved in mushroom production beginning in the summer of 2010. His temperature on admission was 36.6°C and he had a normal blood pressure (135/90 mmHg). Bilateral fine crackles were audible in the base of both lungs. Pulmonary function tests showed a mild restrictive pattern with decreased DLco and a PaO(2) of 65 mmHg, Chest CT scan revealed reticulo-nodular shadows, slight ground glass opacities, liner atelectasis, and subpleural opacities in both lung fields. Bronchoscopy was normal but cytological examination of BAL revealed a predominant lymphocytosis (55%). Serum precipitins to the Shiitake mushroom spores were positive (3 precipitins arcs with high intensity) and as a result we advised the patient to cease his mushroom production activities. The diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was established as a result of the improvement of all of his clinical symptoms, i.e., cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and reticulo-nodular shadows on chest CT, once exposure was eliminated. Recent interest in exotic mushrooms varieties, e.g., Shiitake, in developed countries because of their possible medicinal properties might increase the potential risk of HP among mushrooms workers. Therefore, healthcare professionals have to take this new potential respiratory disease into account. PMID:22329454

  15. Hypersensitivity vasculitis induced by cefoperazone/sulbactam

    PubMed Central

    Islek, Ismail; Baris, Sancar; Katranci, Ali O; Ariturk, Ender; Gurses, Nuran

    2003-01-01

    Background Cefoperazone has not been reported to cause vasculitic complications before. Here, we report a case of hypersensitivity vasculitis associated with cefoperazone/sulbactam. Case presentation A 13-year-old girl with appendicitis developed hypersensitivity vasculitis on the fifth day of cefoperazone/sulbactam therapy. Hypersensitivity vasculitis resolved gradually after removal of the agent on the seventh day and did not recur. Although hypersensitivity vasculitis has multiple causes, coexistence of hypersensitivity vasculitis and cefoperazone treatment, and the quite resolution of the disease after removal of the drug, strongly favours a causative relationship. Conclusion To our knowledge, this is the first report of a hypersensitivity vasculitis associated with cefoperazone. PMID:12556245

  16. Immediate hypersensitivity reaction with mango.

    PubMed

    Shah, Ashok; Gera, Kamal

    2014-01-01

    Hypersensitivity to the fruit mango is extremely rare and can exhibit either as immediate or delayed reactions. Since 1939, only 22 patients (10 with immediate type I reactions and 12 with delayed) have been documented with allergy to mango. History of atopy and geographical region may influence the type of reaction. Immediate reactions occurred most often in patients with history of atopy, while delayed reactions developed in non-atopic individuals. Clustering of delayed hypersensitivity reports from Australia and immediate reactions from Europe has been documented. We report a 50-year-old man with immediate type I hypersensitivity to mango, who developed cough, wheezing dyspnoea, generalised itching and abdominal discomfort after ingestion of mango. Life threatening event can also happen making it imperative to diagnose on time, so as to prevent significant morbidity and potential mortality. PMID:25133813

  17. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    SciTech Connect

    Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-03-01

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with /sup 14/C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A/sub 2/ (TXA/sub 2/) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more /sup 14/C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p < 0.001; /sup 14/C release: 1.5 +/- 0.5%, p < 0.002) in response to thrombin (0.075 U/ml). Thus, a pathway independent of released ADP or TXA/sub 2/ formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of /sup 125/I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA/sub 2/ formation, the action of released ADP or increased thrombin binding.

  18. Flower Development under Drought Stress: Morphological and Transcriptomic Analyses Reveal Acute Responses and Long-Term Acclimation in Arabidopsis[C][W

    PubMed Central

    Su, Zhao; Ma, Xuan; Guo, Huihong; Sukiran, Noor Liyana; Guo, Bin; Assmann, Sarah M.; Ma, Hong

    2013-01-01

    Drought dramatically affects plant growth and crop yield, but previous studies primarily examined responses to drought during vegetative development. Here, to study responses to drought during reproductive development, we grew Arabidopsis thaliana plants with limited water, under conditions that allowed the plants to initiate and complete reproduction. Drought treatment from just after the onset of flowering to seed maturation caused an early arrest of floral development and sterility. After acclimation, plants showed reduced fertility that persisted throughout reproductive development. Floral defects included abnormal anther development, lower pollen viability, reduced filament elongation, ovule abortion, and failure of flowers to open. Drought also caused differential expression of 4153 genes, including flowering time genes FLOWERING LOCUS T, SUPPRESSOR OF OVEREXPRESSION OF CO1, and LEAFY, genes regulating anther and pistil development, and stress-related transcription factors. Mutant phenotypes of hypersensitivity to drought and fewer differentially expressed genes suggest that DEHYDRATION RESPONSE ELEMENT B1A may have an important function in drought response in flowers. A more severe filament elongation defect under drought in myb21 plants demonstrated that appropriate stamen development requires MYB DOMAIN PROTEIN 21 under drought conditions. Our study reveals a regulatory cascade in reproductive responses and acclimation under drought. PMID:24179129

  19. Management of hypersensitivity reactions to anti-D immunoglobulin preparations.

    PubMed

    Rutkowski, K; Nasser, S M

    2014-11-01

    RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh isoimmunization. Its use has significantly reduced the incidence of haemolytic disease of the foetus and newborn previously responsible for one death in every 2200 births. In pregnancy, acute drug-induced hypersensitivity reactions including anaphylaxis can have serious deleterious effects on the mother and foetus/neonate. Women can be erroneously labelled as drug allergic as the investigation of hypersensitivity reactions in pregnancy is complex and drug challenges are usually contraindicated. We present three cases of suspected anti-D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion-related reaction. We also propose a new algorithm for the investigations of such reaction. It relies on detailed history, cautious interpretation of skin tests, foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges. This is not to deprive women of anti-D which might put their future pregnancies at risk. PMID:25066207

  20. Modulation of Th1/Th2 immune responses by killed Propionibacterium acnes and its soluble polysaccharide fraction in a type I hypersensitivity murine model: induction of different activation status of antigen-presenting cells.

    PubMed

    Squaiella-Baptistăo, Carla Cristina; Teixeira, Daniela; Mussalem, Juliana Sekeres; Ishimura, Mayari Eika; Longo-Maugéri, Ieda Maria

    2015-01-01

    Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model. PMID:25973430

  1. Modulation of Th1/Th2 Immune Responses by Killed Propionibacterium acnes and Its Soluble Polysaccharide Fraction in a Type I Hypersensitivity Murine Model: Induction of Different Activation Status of Antigen-Presenting Cells

    PubMed Central

    Mussalem, Juliana Sekeres; Ishimura, Mayari Eika; Longo-Maugéri, Ieda Maria

    2015-01-01

    Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model. PMID:25973430

  2. Virus-induced silencing of WIPK and SIPK genes reduces resistance to a bacterial pathogen, but has no effect on the INF1-induced hypersensitive response (HR) in Nicotiana benthamiana.

    PubMed

    Sharma, P C; Ito, A; Shimizu, T; Terauchi, R; Kamoun, S; Saitoh, H

    2003-08-01

    Activation of two mitogen-activated protein kinases (MAPKs), wound-induced protein kinase (WIPK) and salicylic acid-induced protein kinase (SIPK), is one of the earliest responses that occur in tobacco plants that have been wounded, treated with pathogen-derived elicitors or challenged with avirulent pathogens. We isolated cDNAs for these MAPKs (NbWIPKand NbSIPK) from Nicotiana benthamiana. The function of NbWIPK and NbSIPK in mediating the hypersensitive response (HR) triggered by infiltration with INF1 protein (the major elicitin secreted by Phytophthora infestans), and the defense response to an incompatible bacterial pathogen (Pseudomonas cichorii), was investigated by employing virus-induced gene silencing (VIGS) to inhibit expression of the WIPK and SIPK genes in N. benthamiana. Silencing of WIPK or SIPK, or both genes simultaneously, resulted in reduced resistance to P. cichorii, but no change was observed in the timing or extent of HR development after treatment with INF1. PMID:12838412

  3. The Multi-Resistant Reaction of Drought-Tolerant Coffee 'Conilon Clone 14' to Meloidogyne spp. and Late Hypersensitive-Like Response in Coffea canephora.

    PubMed

    Lima, Edriana A; Furlanetto, Cleber; Nicole, Michel; Gomes, Ana C M M; Almeida, Maria R A; Jorge-Júnior, Aldemiro; Correa, Valdir R; Salgado, Sônia Maria; Ferrăo, Maria A G; Carneiro, Regina M D G

    2015-06-01

    Root-knot nematodes (RKN), Meloidogyne spp., have major economic impact on coffee production in Central and South America. Genetic control of RKN constitutes an essential part for integrated pest management strategy. The objective of this study was to evaluate the resistance of Coffea canephora genotypes (clones) to Meloidogyne spp. Sensitive and drought-tolerant coffee genotypes were used to infer their resistance using nematode reproduction factor and histopathology. Eight clonal genotypes were highly resistant to M. paranaensis. 'Clone 14' (drought-tolerant) and 'ESN2010-04' were the only genotypes highly resistant and moderately resistant, respectively, to both M. incognita races 3 and 1. Several clones were highly resistant to both avirulent and virulent M. exigua. Clone 14 and ESN2010-04 showed multiple resistance to major RKNs tested. Roots of 'clone 14' (resistant) and 'clone 22' (susceptible) were histologically studied against infection by M. incognita race 3 and M. paranaensis. Reduction of juvenile (J2) penetration in clone 14 was first seen at 2 to 6 days after inoculation (DAI). Apparent early hypersensitive reaction (HR) was seen in root cortex between 4 and 6 DAI, which led to cell death and prevention of some nematode development. At 12 to 20 DAI, giant cells formed in the vascular cylinder, besides normal development into J3/J4. From 32 to 45 DAI, giant cells were completely degenerated. Late, intense HR and cell death were frequently observed around young females and giant cells reported for the first time in coffee pathosystem. These results provide rational bases for future studies, including prospection, characterization, and expression profiling of genomic loci involved in both drought tolerance and resistance to multiple RKN species. PMID:25738554

  4. Monoclonal antibodies: Longitudinal prescribing information analysis of hypersensitivity reactions

    PubMed Central

    Kleyman, Konstantin; Weintraub, Debra S.

    2012-01-01

    Monoclonal antibodies (mAbs) are known to cause hypersensitivity reactions (HSRs). The reactions pose a significant challenge to investigators, regulators, and health providers. Because HSRs cannot be predicted through the pharmacological basis of a therapy, clinical data are often relied upon to detect the reactions. Unfortunately, clinical studies are often unable to adequately characterize HSRs especially in therapies for orphan diseases. HSRs can go undetected until post-marketing safety surveillance when a large number of patients have been exposed to the therapy. The presented data demonstrates how hypersensitivity reaction warnings have changed over time in the prescribing information (PI), i.e., the drug package insert, through August 1, 2011 for 28 US-marketed mAbs. Tracking all PI revisions for each mAb over time revealed that hypersensitivity warning statements were expanded to include more severe manifestations. Over the course of a mAb therapy’s life cycle, the hypersensitivity warning is twice more likely to be upgraded than downgraded in priority. Approximately 85% of hypersensitivity-associated fatality warnings were added in PI revisions as a result of post-marketing experience. Over 60% (20/33) of revisions to hypersensitivity warnings occurred within 3–4 y of product approval. While HSRs are generally recognized and described in the initial PI of mAbs, fatal HSRs are most commonly observed in post-marketing surveillance. Results of this study suggest that initial product labeling information may not describe rare but clinically significant occurrences of severe or fatal HSRs, but subsequent label revisions include rare events observed during post-marketed product use. PMID:22531444

  5. Regulation of delayed-type hypersensitivity-like responses in the mouse lung, determined with histological procedures: serotonin, T-cell suppressor-inducer factor and high antigen dose tolerance regulate the magnitude of T-cell dependent inflammatory reactions.

    PubMed Central

    Garssen, J; Nijkamp, F P; Wagenaar, S S; Zwart, A; Askenase, P W; Van Loveren, H

    1989-01-01

    We have studied delayed-type hypersensitivity (DTH) responses to picryl chloride (PCl) in the lungs of mice. Intranasal challenge with 0.6% picryl sulphonic acid (PSA), a water soluble form of PCl, of BALB/c mice, sensitized with PCl epicutaneously 1 week earlier, induced an accumulation of mononuclear inflammatory cells around bronchioli and blood vessels. Maximal inflammatory responses were seen 48 hr after challenge. These responses were antigen-specific, and also T-cell dependent, since athymic nude mice failed to show this reaction. A role for mast cells in the responses was studied using two strains of mast cell-deficient mice. In one of these (W/Wv) lung DTH responses to PCl were reduced severely. In the other strain (S1/S1d) the responses around vessels were decreased slightly, whereas the responses in the interstitial tissue and around bronchioli were similar to those in +/+ littermate controls. Involvement of serotonin was investigated using two serotonin receptor antagonists, i.e. methysergide and ketanserin. Treatment of mice with either of the antagonists prevented occurrence of the DTH-like reaction in the lung after intranasal antigen challenge. In the lungs of sensitized mice, significantly increased permeability was established 2 hr after antigen challenge. It was concluded that release of serotonin in the lung may provide an environment that comprises local vascular permeability and that facilitates the local recruitment and possibly the activation of DTH effector T cells, leading to subsequent attraction of mononuclear leucocytes into the lung. Immunological regulation of the DTH-like reactions in the lung was similar to that of contact sensitivity in the skin, since intravenous injection of an antigen-specific T-cell suppressor inducer factor prior to sensitization or pretreatment with a high dose of picryl sulphonic acid intravenously both resulted in reduction of the DTH-like lung histological response to picryl sulphonic acid. From these findings it was concluded that DTH-like lung responses are similar to DTH responses in the skin. Images Figure 1 Figure 3 PMID:2807371

  6. Membrane properties revealed by spatiotemporal response to a local inhomogeneity

    E-print Network

    Fournier, Jean-Baptiste - Laboratoire Matičre et Systčmes Complexes, Université Paris 7

    pH difference across the membrane to synthesize adenosine tri- phosphate, the cell's fuel in chemotaxis or in paracrine signaling. It is therefore of great interest to study the response of a bio membrane dynamics in the spirit of Ref. [8]. While our first works focused on the simple case of a constant

  7. Genotyping for Severe Drug Hypersensitivity

    PubMed Central

    Karlin, Eric; Phillips, Elizabeth

    2014-01-01

    Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety. PMID:24429903

  8. Genotyping for severe drug hypersensitivity.

    PubMed

    Karlin, Eric; Phillips, Elizabeth

    2014-03-01

    Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety. PMID:24429903

  9. What boxing-related stimuli reveal about response behaviour.

    PubMed

    Ottoboni, Giovanni; Russo, Gabriele; Tessari, Alessia

    2015-01-01

    When two athletes meet inside the ropes of the boxing ring to fight, their cognitive systems have to respond as quickly as possible to a manifold of stimuli to assure victory. In the present work, we studied the pre-attentive mechanisms, which form the basis of an athlete's ability in reacting to an opponent's punches. Expert boxers, beginner boxers and people with no experience of boxing performed a Simon-like task where they judged the colour of the boxing gloves worn by athletes in attack postures by pressing two lateralised keys. Although participants were not instructed to pay attention to the direction of the punches, beginner boxers' responses resembled a defence-related pattern, expert boxers' resembled counterattacks, whereas non-athletes' responses were not influenced by the unrelated task information. Results are discussed in the light of an expertise-related action simulation account. PMID:25385452

  10. Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols.

    PubMed

    Katiyar, S K; Elmets, C A; Agarwal, R; Mukhtar, H

    1995-11-01

    Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a polyphenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280-320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. Topical application of GTP (1-6 mg/animal), 30 min prior to or 30 min after exposure to a single dose of UVB (2 kJ/m2) resulted in significant protection against local (25-90%) and systemic suppression (23-95%) of CHS and inflammation in mouse dorsal skin (70-80%). These protective effects were dependent on the dose of GTP employed; increasing the dose (1-6 mg/animal) resulted in an increased protective effect (25-93%). The protective effects were also dependent on the dose of UVB (2-32 kJ/m2). Among the four major epicatechin derivatives present in GTP, (-)-epigallocatechin-3-gallate, the major constituent in GTP, was found to be the most effective in affording protection against UVB-caused CHS and inflammatory responses. Our study suggests that green tea, specifically polyphenols present therein, may be useful against inflammatory dermatoses and immunosuppression caused by solar radiation. PMID:8570723

  11. Hypersensitivity to latex, chestnut, and banana.

    PubMed

    Rodríguez, M; Vega, F; García, M T; Panizo, C; Laffond, E; Montalvo, A; Cuevas, M

    1993-01-01

    The incidence of latex-allergic patients is probably higher than suspected. A spectrum of IgE-dependent allergic reactions to latex products including urticaria, rhinitis, asthma, angioedema, and life-threatening anaphylaxis has been increasingly reported in recent years. We describe three patients with rubber hypersensitivity and allergy to fruit (banana and chestnut). Immediate positive responses were obtained in prick tests with latex, banana, and chestnut extracts. Histamine release was positive and specific IgE antibodies to all three extracts were detected by fluorescence radioimmunoassay. In the RAST-inhibition studies, the extract of latex inhibited the binding of chestnut and banana, but chestnut and banana extracts did not inhibit the binding of latex. These results suggest a sensitivity to crossreacting antigens in latex allergy associated with allergy to certain fruits. PMID:7678723

  12. Angioneurotic edema: a rare case of hypersensitivity to metoclopramide

    PubMed Central

    Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

    2013-01-01

    The case of a 30-year-old woman who had already experienced two incidents of angioneurotic edema and urticaria caused by drugs during the acute gastroenteritis. The allergological workup revealed hypersensitivity to metoclopramide. This case documents that metoclopramide, a drug commonly used to inhibit the vomiting, may cause not only bronchospastic reaction in an asthmatic patient but also angioneurotic edema of the tongue and larynx as well as urticaria. No similar cases in the literature were found. PMID:24278059

  13. Pharmacometabolomics reveals racial differences in response to atenolol treatment.

    PubMed

    Wikoff, William R; Frye, Reginald F; Zhu, Hongjie; Gong, Yan; Boyle, Stephen; Churchill, Erik; Cooper-Dehoff, Rhonda M; Beitelshees, Amber L; Chapman, Arlene B; Fiehn, Oliver; Johnson, Julie A; Kaddurah-Daouk, Rima

    2013-01-01

    Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug. PMID:23536766

  14. Accumulation of Pgip, a Leucine-Rich Receptor-Like Protein, Correlates with the Hypersensitive Response in Race-Cultivar Interactions

    Microsoft Academic Search

    F. Cervone; G. Lorenzo; D. Bellincampi; C. Caprari; A. J. Clark; A. Desiderio; A. Devoto; F. Leckie; L. Nuss; G. Salvi

    \\u000a The interaction between fungal endopolygalacturonases and a plant cell wall PGIP (PolyGalacturonase-Inhibiting Protein) in\\u000a plant-pathogen recognition is being investigated. This protein-protein interaction has been shown to favour the formation\\u000a of oligogalacturonides able to elicit plant defense responses. Accumulation of pgip mRNA has been followed in different race-cultivar interactions (either compatible or incompatible) between Colletotrichum lindemuthianum and Phaseolus vulgaris by Northern

  15. Function of the Oxidative Burst in Hypersensitive Disease Resistance

    Microsoft Academic Search

    Raimund Tenhaken; Alex Levine; Louise F. Brisson; Richard A. Dixon; Chris Lamb

    1995-01-01

    Microbial elicitors or attempted infection with an avirulent pathogen strain causes the rapid production of reactive oxygen intermediates. Recent findings indicate that H_2O_2 from this oxidative burst plays a central role in the orchestration of the hypersensitive response: (i) as the substrate driving the cross-linking of cell wall structural proteins to slow microbial ingress prior to the deployment of transcription-dependent

  16. Paediatric feather duvet hypersensitivity pneumonitis.

    PubMed

    Jordan, Louise E; Guy, Emma

    2015-01-01

    A previously well 12-year-old boy was admitted with a second insidious episode of dyspnoea, dry cough, anorexia, weight loss and chest pain. At admission, he had an oxygen requirement, significantly impaired lung function and reduced exercise tolerance. Initial forced expiratory volume in 1?s was 26%; a 3?min exercise test stopped at 1?min 50 when saturations dropped to 85%. CT scan showed ground-glass nodularity with lymphadenopathy. Bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia and viruses were negative, and microbiology results for the BAL were reported in the absence of histology. This is because at the time the BAL samples were collected, a lung biopsy was performed. The biopsy was consistent with hypersensitivity pneumonitis. Echo was normal and CT pulmonary angiography negative. After taking a thorough history, exposure to feather duvets prior to each episode was elicited. IgG of avian precipitants was raised at 10.6?mgA/L (normal <10?mgA/L). Clinical improvement began with avoidance of exposure, while the boy was an inpatient. Antigen avoidance continued on discharge. He continues to improve since discharge. The condition was diagnosed as hypersensitivity pneumonitis secondary to exposure to antigens from feather duvets. PMID:26113584

  17. Hypersensitivity reactions to HIV therapy

    PubMed Central

    Chaponda, Mas; Pirmohamed, Munir

    2011-01-01

    Many drugs used for the treatment of HIV disease (including the associated opportunistic infections) can cause drug hypersensitivity reactions, which vary in severity, clinical manifestations and frequency. These reactions are not only seen with the older compounds, but also with the newer more recently introduced drugs. The pathogenesis is unclear in most cases, but there is increasing evidence to support that many of these are mediated through a combination of immunologic and genetic factors through the major histocompatibility complex (MHC). Genetic predisposition to the occurrence of these allergic reactions has been shown for some of the drugs, notably abacavir hypersensitivity which is strongly associated with the class I MHC allele, HLA-B*5701. Testing before the prescription of abacavir has been shown to be of clinical utility, has resulted in a change in the drug label, is now recommended in clinical guidelines and is practiced in most Western countries. For most other drugs, however, there are no good methods of prevention, and clinical monitoring with appropriate (usually supportive and symptomatic) treatment is required. There is a need to undertake further research in this area to increase our understanding of the mechanisms, which may lead to better preventive strategies through the development of predictive genetic biomarkers or through guiding the design of drugs less likely to cause these types of adverse drug reactions. PMID:21480946

  18. Severe type IV hypersensitivity to ‘black henna’ tattoo

    PubMed Central

    Vasilakis, Vasileios; Knight, Bernice; Lidder, Satnam; Frankton, Sarah

    2010-01-01

    A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as ‘black henna’, darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo. PMID:22778139

  19. Severe type IV hypersensitivity to 'black henna' tattoo.

    PubMed

    Vasilakis, Vasileios; Knight, Bernice; Lidder, Satnam; Frankton, Sarah

    2010-01-01

    A 16-year-old Bangladeshi girl presented with a 9-day history of an extensive pruritic, erythematous, papulovesicular skin eruption to both forearms. Appearance was 5 days following application of a home-made henna preparation. Examination revealed ulceration and scabbing along the whole henna pattern and early keloid formation. A diagnosis of type IV delayed hypersensitivity reaction superimposed by infection was initially made. As in this case, home-made henna preparations commonly combine commercial henna with black hair dye, paraphenylenediamine (PPD). PPD, widely known as 'black henna', darkens the pigment and precipitates the drying process. PPD is a potent contact allergen associated with a high incidence of hypersensitivity reactions. Despite treatment the patient was left with extensive keloid scarring in the pattern of the henna tattoo. PMID:22778139

  20. Provocation tests in diagnosing drug hypersensitivity.

    PubMed

    Bousquet, Philippe-Jean; Gaeta, Francesco; Bousquet-Rouanet, Laure; Lefrant, Jean-Yves; Demoly, Pascal; Romano, Antonino

    2008-01-01

    A position paper by the European Network for Drug Allergy (ENDA), the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity, defines drug provocation tests (DPTs) as "the controlled administration of a drug in order to diagnose drug hypersensitivity reactions". The DPT is widely considered to be the "gold standard" to establish or exclude the diagnosis of hypersensitivity to a certain substance, as it not only reproduces hypersensitivity symptoms, but also any other adverse clinical manifestation, irrespective of the mechanism. The DPT can be harmful and thus should only be considered after balancing the risk-benefit ratio in the individual patient. The ENDA position paper specifies two main indications for DPTs with the suspected compounds: 1. to exclude hypersensitivity in non-suggestive histories of drug hypersensitivity and in patients with non-specific symptoms, such as vagal symptoms under local anesthesia; 2. to establish a firm diagnosis in suggestive histories of drug hypersensitivity with negative, non-conclusive, or non-available allergologic tests. A positive DPT result optimizes allergen avoidance, while a negative one allows a false label of drug hypersensitivity to be removed. For these reasons, DPTs are often carried out to exclude a diagnosis of hypersensitivity to beta-lactams when other allergologic tests are negative. DPTs are also performed when the sensitivity of allergologic tests for evaluating allergic reactions to certain drugs, such as non-beta-lactam antibiotics, heparins, and glucocorticoids, is limited. On the other hand, DPTs are also performed to diagnose hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in subjects with the cross-reactive pattern, because both skin tests and in vitro diagnostic methods are ineffective in such patients. PMID:18991698

  1. Correlation between the Constitution of Sasang and Sexual Difference in the Hypersensitive Reaction of Sweet Bee Venom

    PubMed Central

    Lee, Kwangho

    2012-01-01

    Objectives: The aim of this study is to investigate the correlation between the constitution of Sasang and the bee venom hypersensitive reaction, as well as the hypersensitive reaction occurrence ratio between males and females, for patients treated with sweet bee venom (SBV) and who had undergone an examination of the constitution of the Sasang. Methods: All 81 patients enrolled in the study were treated with SBV and underwent an examination of the constitution of Sasang from January 2010 to July 2012. We divided them into two groups for the hypersensitive reaction and no response and compared the distributions of the Sasang-constitution types for the two groups as well as the hypersensitive reaction occurrence ratio between males and females. Results: No significant differences were found between the hypersensitive-reaction group and the no-response group (p= 0.390), but the hypersensitive-reaction occurrence ratio was statistically higher in females than in males (p= 0.001). Conclusions: Hypersensitive reactions do not seem to be related to the Sasang-constitution types, but the possibility of hypersensitive reactions among females seems to be higher than it is among males. PMID:25780647

  2. [In vitro immunologic diagnosis of hypersensitivity to vegetables].

    PubMed

    Carrillo Díaz, T; Cuevas Agustín, M; Luz Díez Gómez, M; Losada Cosme, E; Moneo Goiri, I

    1986-01-01

    Acute reaction to food allergens is a fairly common problem that is often seen in the allergist's office, its incidence being specially high in childhood. Milk and eggs are the most common sensitizing foods, but usually the type of food allergens responsible for these reactions varies according to food habits in different countries. Legumes occupy an important role in the Spanish diet, being responsible for a large number of allergic reactions. It has been shown that legumes occupy the fourth place in importance among the food allergens, inducing hypersensitivity reactions in Spanish children. This article describes five patients with clinical features suggestive of being mediated by IgE antibodies specific for different legumes. In all the cases, disorders appeared immediately after the ingestion or even the inhalation of vapours from cooked legumes (lentil, bean or chick-pea). Clinical features consisted of: urticaria, angioedema, abdominal symptoms and rhinoconjunctivitis and/or asthma. The five patients required hospital emergency care on several occasions. Two patients suffered also from seasonal pollinosis with rhinoconjunctivitis and asthma. All the patients complained of these type of disorders with any legume, but lentil was found to induce the most severe reactions and it was therefore selected for this study. The presence of specific IgE antibodies was demonstrated in vivo in all the patients by means of skin prick-test. It was performed using a lentil extract prepared in our laboratory. Negative controls were also included. A reverse enzymeimmunoassay (REIA) revealed the presence of specific IgE antibodies in the sera of the five subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3521239

  3. Expert opinion on the cough hypersensitivity syndrome in respiratory medicine.

    PubMed

    Morice, Alyn H; Millqvist, Eva; Belvisi, Maria G; Bieksiene, Kristina; Birring, Surinder S; Chung, Kian Fan; Dal Negro, Roberto W; Dicpinigaitis, Peter; Kantar, Ahmad; McGarvey, Lorcan P; Pacheco, Adalberto; Sakalauskas, Raimundas; Smith, Jaclyn A

    2014-11-01

    In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area. PMID:25142479

  4. Contribution of hyperpolarization-activated channels to heat hypersensitivity and ongoing activity in the neuritis model.

    PubMed

    Richards, N; Dilley, A

    2015-01-22

    Neuritis can cause pain hypersensitivities in the absence of axonal degeneration. Such hypersensitivities are reputed to be maintained by ongoing activity into the spinal cord, which, in the neuritis model, is mainly generated from intact C-fiber neurons. The hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels has been implicated in nerve injury-induced pain hypersensitivities. The present study has examined the role of these channels in the development of heat and mechanical hypersensitivities in the neuritis model. The systemic administration of the HCN-specific blocker ZD7288 produced a reversal of heat but not mechanical hypersensitivity within one hour post-administration. Recordings from C-fiber neurons were performed to determine whether ZD7288 acts by inhibiting ongoing activity. ZD7288 (0.5mM) caused a 44.1% decrease in the ongoing activity rate following its application to the neuritis site. Immunohistochemical examination of the HCN2 channel subtype within the L5 dorsal root ganglia revealed an increase in expression in neuronal cell bodies of all sizes post-neuritis. In conclusion, HCN channels contribute to the development of neuritis-induced heat hypersensitivity and ongoing activity. Drugs that target HCN channels may be beneficial in the treatment of neuropathic pain in patients with nerve inflammation. PMID:25290015

  5. In vitro analysis of metabolic predisposition to drug hypersensitivity reactions.

    PubMed Central

    Riley, R J; Leeder, J S

    1995-01-01

    Idiosyncratic hypersensitivity reactions may account for up to 25% of all adverse reactions, and pose a constant problem to physicians because of their unpredictable nature, potentially fatal outcome and resemblance to other disease processes. Current understanding of how drug allergy arises is based largely on the hapten hypothesis: since most drugs are not chemically reactive per se, they must be activated metabolically to reactive species which may become immunogenic through interactions with cellular macromolecules. The role of drug metabolism is thus pivotal to the hapten hypothesis both in activation of the parent compound and detoxification of the reactive species. Although conjugation reactions may occasionally produce potential immunogens (for example, the generation of acylglucuronides from non-steroidal anti-inflammatory drugs such as diclofenac), bioactivation is catalysed most frequently by cytochrome P450 (P450) enzymes. The multifactorial nature of hypersensitivity reactions, particularly the role of often unidentified, reactive drug metabolites in antigen generation, has hampered the routine diagnosis of these disorders by classical immunological methods designed to detect circulating antibodies or sensitized T cells. Similarly, species differences in drug metabolism and immune system regulation have largely precluded the establishment of appropriate animal models with which to examine the immunopathological mechanisms of these toxicities. However, the combined use of in vitro toxicity assays incorporating human tissues and in vivo phenotyping (or, ultimately, in vitro genotyping) methods for drug detoxification pathways may provide the metabolic basis for hypersensitivity reactions to several drugs. This brief review highlights recent efforts to unravel the bases for hypersensitivity reactions to these therapeutic agents (which include anticonvulsants and sulphonamides) using drug metabolism and immunochemical approaches. In particular, examples are provided which illustrate breakthroughs in the identification of the chemical nature of the reactive metabolites which become bound to cellular macromolecules, the enzyme systems responsible for their generation and (possibly) detoxification, and the target proteins implicated in the subsequent immune response. PMID:7813099

  6. Genetic Variation Associated with Hypersensitivity to Mercury

    PubMed Central

    Austin, David William; Spolding, Briana; Gondalia, Shakuntla; Shandley, Kerrie; Palombo, Enzo A.; Knowles, Simon; Walder, Ken

    2014-01-01

    Objectives: Very little is known about mechanisms of idiosyncratic sensitivity to the damaging effects of mercury (Hg); however, there is likely a genetic component. The aim of the present study was to search for genetic variation in genes thought to be involved in Hg metabolism and transport in a group of individuals identified as having elevated Hg sensitivity compared to a normal control group. Materials and Methods: Survivors of pink disease (PD; infantile acrodynia) are a population of clinically identifiable individuals who are Hg sensitive. In the present study, single nucleotide polymorphisms in genes thought to be involved in Hg transport and metabolism were compared across two groups: (i) PD survivors (n = 25); and (ii) age- and sex-matched healthy controls (n = 25). Results: Analyses revealed significant differences between groups in genotype frequencies for rs662 in the gene encoding paraoxanase 1 (PON1) and rs1801131 in the gene encoding methylenetetrahydrofolate reductase (MTHFR). Conclusions: We have identified two genetic polymorphisms associated with increased sensitivity to Hg. Genetic variation in MTHFR and PON1 significantly differentiated a group formerly diagnosed with PD (a condition of Hg hypersensitivity) with age- and gender-matched healthy controls. PMID:25948960

  7. Sympathoinhibition and hypotension in carotid sinus hypersensitivity

    NASA Technical Reports Server (NTRS)

    Smith, M. L.; Ellenbogen, K. A.; Eckberg, D. L.

    1992-01-01

    Carotid sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sympathoinhibition measured directly directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensitivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypotension. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibition to hypotension in patients with carotid sinus hypersensitivity in the upright position.

  8. Genome-wide analysis links NFATC2 with asparaginase hypersensitivity.

    PubMed

    Fernandez, Christian A; Smith, Colton; Yang, Wenjian; Mullighan, Charles G; Qu, Chunxu; Larsen, Eric; Bowman, W Paul; Liu, Chengcheng; Ramsey, Laura B; Chang, Tamara; Karol, Seth E; Loh, Mignon L; Raetz, Elizabeth A; Winick, Naomi J; Hunger, Stephen P; Carroll, William L; Jeha, Sima; Pui, Ching-Hon; Evans, William E; Devidas, Meenakshi; Relling, Mary V

    2015-07-01

    Asparaginase is used to treat acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions can lead to suboptimal asparaginase exposure. Our objective was to use a genome-wide approach to identify loci associated with asparaginase hypersensitivity in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols Total XIIIA (n = 154), Total XV (n = 498), and Total XVI (n = 271), or Children's Oncology Group protocols POG 9906 (n = 222) and AALL0232 (n = 2163). Germline DNA was genotyped using the Affymetrix 500K, Affymetrix 6.0, or the Illumina Exome BeadChip array. In multivariate logistic regression, the intronic rs6021191 variant in nuclear factor of activated T cells 2 (NFATC2) had the strongest association with hypersensitivity (P = 4.1 × 10(-8); odds ratio [OR] = 3.11). RNA-seq data available from 65 SJCRH ALL tumor samples and 52 Yoruba HapMap samples showed that samples carrying the rs6021191 variant had higher NFATC2 expression compared with noncarriers (P = 1.1 × 10(-3) and 0.03, respectively). The top ranked nonsynonymous polymorphism was rs17885382 in HLA-DRB1 (P = 3.2 × 10(-6); OR = 1.63), which is in near complete linkage disequilibrium with the HLA-DRB1*07:01 allele we previously observed in a candidate gene study. The strongest risk factors for asparaginase allergy are variants within genes regulating the immune response. PMID:25987655

  9. Hypersensitivity pneumonitis and exposure to zirconium silicate in a young ceramic tile worker.

    PubMed

    Liippo, K K; Anttila, S L; Taikina-Aho, O; Ruokonen, E L; Toivonen, S T; Tuomi, T

    1993-10-01

    We describe a nonsmoking ceramic tile worker 25 yr of age who developed a worsening dry cough and dyspnea after 3.5 yr as a sorter and glazer of tiles. Open lung biopsy revealed an intense granulomatous interstitial pneumonia with mild fibrosis, compatible with hypersensitivity pneumonitis, and numerous very small birefringent crystals around the terminal airways and occasionally in granulomas. Pulmonary particle analysis revealed an inhaled dust burden nearly 100-fold the normal background level, mainly consisting of clay minerals and zirconium silicate. The patient had no history or clinical or laboratory findings suggesting any organic etiologic agent. A sarcoid granulomatosis type of chronic pulmonary hypersensitivity reaction is known after long-term exposure to zirconium, but this case demonstrates that zirconium can also cause an acute and fulminant allergic alveolitislike hypersensitivity reaction. PMID:8214930

  10. Cockatiel-induced hypersensitivity pneumonitis.

    PubMed

    McCluskey, James D; Haight, Robert R; Brooks, Stuart M

    2002-07-01

    Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis. PMID:12117652

  11. Spatial Organization of Embryonic Stem Cell Responsiveness to Autocrine Gp130 Ligands Reveals an Autoregulatory Stem

    E-print Network

    Zandstra, Peter W.

    Spatial Organization of Embryonic Stem Cell Responsiveness to Autocrine Gp130 Ligands Reveals an Autoregulatory Stem Cell Niche RYAN E. DAVEY,a PETER W. ZANDSTRA a,b a Institute of Biomaterials and Biomedical, Ontario, Canada Key Words. Autocrine signaling · Embryonic stem cell · Niche · Self-renewal · Stem cell

  12. COGNITIVE NEUROSCIENCE Stimulus-locked responses on human arm muscles reveal a

    E-print Network

    Munoz, Douglas Perry

    COGNITIVE NEUROSCIENCE Stimulus-locked responses on human arm muscles reveal a rapid neural pathway linking visual input to arm motor output J. Andrew Pruszynski,1 * Geoffrey L. King,1 * Lysa Boisse,1 capable of initiating arm movements towards visual stimuli at extremely short latencies, implying

  13. ORIGINAL PAPER Zircon response to high-grade metamorphism as revealed

    E-print Network

    Siebel, Wolfgang

    ORIGINAL PAPER Zircon response to high-grade metamorphism as revealed by U / Accepted: 28 March 2012 Ó Springer-Verlag 2012 Abstract Correct interpretation of zircon ages from high transformations and textural properties of the zircon crystals have to be explored. A large (c. 450 km2 ) coherent

  14. Involvement of protein kinase ? in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity

    PubMed Central

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin

    2015-01-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ? (PKM?) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKM? is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ?-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKM? (p-PKM?) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5–2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKM? might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity. PMID:25761958

  15. Involvement of protein kinase ? in the maintenance of hippocampal long-term potentiation in rats with chronic visceral hypersensitivity.

    PubMed

    Chen, Aiqin; Bao, Chengjia; Tang, Ying; Luo, Xiaoqing; Guo, Lixia; Liu, Bin; Lin, Chun

    2015-05-01

    The hippocampal long-term potentiation (LTP) was implicated in the formation of visceral hypersensitivity in rats with irritable bowel syndrome in our previous study. Recent studies have shown that protein kinase M ? (PKM?) may be responsible for the maintenance of LTP in memory formation. However, it remains unclear whether PKM? is involved in the visceral hypersensitivity. In this study, a rat model of visceral hypersensitivity was generated by neonatal maternal separation (NMS). The visceral hypersensitivity was assessed by recording responses of the external oblique abdominal muscle to colorectal distension. Our results demonstrated that hippocampal LTP and visceral hypersensitivity were enhanced significantly in rats of NMS. ?-Pseudosubstrate inhibitory peptide (ZIP) could dose dependently inhibit the maintenance of Cornu Ammonis area 1 LTP in rats of NMS. Furthermore, Western blot data showed that the expression of hippocampal phosphorylated PKM? (p-PKM?) significantly increased in rats of NMS. In addition, bilateral intrahippocampal injections of ZIP attenuated the visceral hypersensitivity dose dependently in rats of NMS. The maximal inhibition was observed at 30 min, and significant inhibition lasted for 1.5-2 h after ZIP application. Besides, data from the open-field test and Morris water maze showed that ZIP did not influence the movement and spatial procedural memory in rats of NMS. In conclusion, p-PKM? might be a critical protein in the maintenance of hippocampal LTP, which could result in visceral hypersensitivity. PMID:25761958

  16. Genome-wide analysis of light-inducible responses reveals hierarchical light signalling in Neurospora

    PubMed Central

    Chen, Chen-Hui; Ringelberg, Carol S; Gross, Robert H; Dunlap, Jay C; Loros, Jennifer J

    2009-01-01

    White collar-1 (WC-1) and white collar-2 (WC-2) are essential for light-mediated responses in Neurospora crassa, but the molecular mechanisms underlying gene induction and the roles of other real and putative photoreceptors remain poorly characterized. Unsupervised hierarchical clustering of genome-wide microarrays reveals 5.6% of detectable transcripts, including several novel mediators, that are either early or late light responsive. Evidence is shown for photoreception in the absence of the dominant, and here confirmed, white collar complex (WCC) that regulates both types of light responses. VVD primarily modulates late responses, whereas light-responsive submerged protoperithecia-1 (SUB-1), a GATA family transcription factor, is essential for most late light gene expression. After a 15-min light stimulus, the WCC directly binds the sub-1 promoter. Bioinformatics analysis detects many early light response elements (ELREs), as well as identifying a late light response element (LLRE) required for wild-type activity of late light response promoters. The data provide a global picture of transcriptional response to light, as well as illuminating the cis- and trans-acting elements comprising the regulatory signalling cascade that governs the photobiological response. PMID:19262566

  17. Ultraviolet Radiation-Induced Impairment of the Early Initiating and the Late Effector Phases of Contact Hypersensitivity to Picrylcholoride: Regulation by Different Mechanisms

    Microsoft Academic Search

    Yvonne Sontag; Johan Garssen; Frank R. de Gruijl; Jan C. van der Leun; Willem A. van Vloten; Henk Van Loveren

    1994-01-01

    Two types of antigen-specific T cells are needed for the elicitation of contact hypersensitivity reactions. They act in an obligate sequence to mediate the early initiating and late effector phases of contact hypersensitivity, which are accompanied by skin-swelling responses at 2 and 24 h after challenge, respectively. The magnitude of the late ear swelling depends on that of the early

  18. Heat-rekindling in UVB-irradiated skin above NGF-sensitized muscle: experimental models of prolonged mechanical hypersensitivity.

    PubMed

    Vecchio, Silvia Lo; Finocchietti, Sara; Gazerani, Parisa; Petersen, Lars J; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas

    2014-01-01

    Experimental models of prolonged pain hypersensitivity in humans are desirable for screening novel analgesic compounds. In this study, heat stimuli were applied in ultraviolet-B (UVB)-irradiated skin and in the UVB-irradiated skin combined with nerve growth factor (NGF)-injected muscle to investigate 1) whether the evoked mechanical hypersensitivity by UVB irradiation would be prolonged or enhanced following heat rekindling, and 2) whether the combination between cutaneous and muscle hypersensitivity may influence the rekindling effects. Skin sensitization was induced in 25 volunteers by UVB irradiation in areas above the upper-trapezius muscle, low-back or forearm. Muscle sensitization was induced in the low back by bilateral injections of NGF. The area of cutaneous hyperalgesia was evaluated 3 days after the irradiation by mechanical pin-prick stimulation whereas the areas of allodynia were evaluated 1, 2 and 3 days after irradiation by von Frey hair assessments. Cutaneous heat stimulation (40°C for 5 min) was performed on the 3(rd) day to investigate its effect on the areas of cutaneous allodynia and hyperalgesia. Findings revealed that 1) allodynia and hyperalgesia developed following UVB irradiation, 2) heat stimulation of the UVB-irradiated skin enlarged both hyperalgesic and allodynic areas (P < 0.01), and 3) muscle sensitization did not influence the effect of UVB on allodynia or the response to heat rekindling. These data suggest that heat rekindling applied to an UVB-sensitized skin can maintain or facilitate allodynia and hyperalgesia for a longer period offering a suitable model for testing analgesic compounds when sufficient duration of time is needed for investigation of drug efficacy. PMID:25349637

  19. Genome-Wide RNAi of C. elegans Using the Hypersensitive rrf-3 Strain

    E-print Network

    Ahringe, Julie

    Genome-Wide RNAi of C. elegans Using the Hypersensitive rrf-3 Strain Reveals Novel Gene Functions-mediated interference (RNAi) is a method to inhibit gene function by introduction of double-stranded RNA (dsRNA). Recently, an RNAi library was constructed that consists of bacterial clones expressing dsRNA, corresponding

  20. Hypersensitivity manifestations to the fruit mango.

    PubMed

    Sareen, Richa; Shah, Ashok

    2011-04-01

    The objectives of this study are 1) To review the published data and document the current knowledge on allergic manifestations to the fruit mango 2) To highlight the two distinct clinical presentations of hypersensitivity reactions caused by mango 3) To discuss the role of cross-reactivity 4) To increase awareness of potentially life threatening complications that can be caused by allergy to mango. An extensive search of the literature was performed in Medline/PubMed with the key terms "mango", "anaphylaxis", "contact dermatitis", "cross-reactivity", "food hypersensitivity", "oral allergy syndrome" and "urticaria". The bibliographies of all papers thus located were searched for further relevant articles. A total of 17 reports describing 22 patients were documented, including ten patients with immediate hypersensitivity reaction and twelve patients with delayed hypersensitivity reaction to mango. Ten of these patients (four with immediate reaction; six with delayed reaction) were from geographical areas cultivating mango, whereas twelve patients (six with immediate reaction; six with delayed reaction) were from the countries where large scale mango cultivation does not occur. The clinical features, pathogenesis and diagnostic modalities of both these presentations are highlighted. The fruit mango can cause immediate and delayed hypersensitivity reactions, as also "oral allergy syndrome". Although rare, it can even result in a life threatening event. Reactions may even occur in individuals without prior exposure to mango, owing to cross reactivity. It is imperative to recognize such a phenomenon early so as to avoid potentially severe clinical reactions in susceptible patients. PMID:22053296

  1. Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response

    PubMed Central

    Brucklacher, Robert M; Patel, Kruti M; VanGuilder, Heather D; Bixler, Georgina V; Barber, Alistair J; Antonetti, David A; Lin, Cheng-Mao; LaNoue, Kathryn F; Gardner, Thomas W; Bronson, Sarah K; Freeman, Willard M

    2008-01-01

    Background Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes. Results Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals. Conclusion These changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics. PMID:18554398

  2. Prevention of Ultraviolet Radiation-Induced Suppression of Contact and Delayed Hypersensitivity by Aloe barbadensis Gel Extract

    Microsoft Academic Search

    Faith M. Strickland; Ronald P. Pelley; Margaret L. Kripke

    1994-01-01

    We investigated the ability of Aloe barbadensis gel extract to prevent suppression of contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH) responses in mice by ultraviolet (UV) irradiation. Local immune suppression was induced in C3H mice by exposure to four daily doses of 400 J\\/m2 UV-B (280 – 320 nm) radiation from FS40 sunlamps, followed by sensitization with 0.5% fluorescein isothiocyanate

  3. TRPA1 Contributes to Cold Hypersensitivity

    PubMed Central

    Camino, Donato del; Murphy, Sarah; Heiry, Melissa; Barrett, Lee B.; Earley, Taryn J.; Cook, Colby A.; Petrus, Matt J.; Zhao, Michael; D'Amours, Marc; Deering, Nate; Brenner, Gary J.; Costigan, Michael; Hayward, Neil J.; Chong, Jayhong A.; Fanger, Christopher M.; Woolf, Clifford J.; Patapoutian, Ardem; Moran, Magdalene M.

    2010-01-01

    TRPA1 is a non-selective cation channel expressed by nociceptors. While it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions where reactive oxygen species and pro-inflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1-/- mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain. PMID:21068322

  4. Drug hypersensitivities: definition, epidemiology and risk factors.

    PubMed

    Demoly, P; Gomes, E Rebelo

    2005-06-01

    Drug hypersensitivity reactions are the adverse effects of drugs taken at a dose which is tolerated by normal subjects, and which clinically resemble allergy. There is few true epidemiological data on drug hypersensitivity reactions. The available information requires a cautious interpretation as they are rarely proven. Both under diagnosis and over diagnosis must be taken into account. Drug hypersensitivity reactions represent one third of adverse drug reactions, can be life threatening and motivate changes on drug prescription. They concern more than 7% of the general population, therefore being an important public health problem. A few risk factors are already pinpointed. Future progress in genetics can help the identification of populations at risk for specific reactions. This review describes currently known data on incidence,prevalence, mor tality and risk factors of these reactions. PMID:16156397

  5. Basic Aspects of Allergy and Hypersensitivity Reactions

    Microsoft Academic Search

    Isabella Pali-Schöll; Erika Jensen-Jarolim

    Key players within immunologically mediated hypersensitivity reactions are allergen-specific IgE or IgG antibodies, immune\\u000a complexes, or lymphocytes. According to these diverse pathophysiological mechanisms behind the clinical appearance, hypersensitivity\\u000a reactions are classified into type I through IV. The focus of this chapter lies on the characterization of type I, i.e. IgE-mediated\\u000a reactions.\\u000a \\u000a In addition to small size and solubility of type

  6. Characterization of drug-specific T cells in lamotrigine hypersensitivity

    Microsoft Academic Search

    Dean J. Naisbitt; John Farrell; Gavin Wong; Jan p. H. Depta; Charlotte C. Dodd; Josephine E. Hopkins; Claire A. Gibney; David W. Chadwick; Werner J. Pichler; Munir Pirmohamed; B. Kevin Park

    2003-01-01

    Background: Lamotrigine is associated with hypersensitivity reactions, which are most commonly characterized by skin rash. An immune etiology has been postulated, though the nature of this is unclear. Objectives: The aim of this study was to characterize the role of T cells in lamotrigine hypersensitivity. Methods: A lymphocyte transformation test was performed on 4 hypersensitive patients. Lymphocytes from 3 of

  7. Time-Course Proteome Analysis Reveals the Dynamic Response of Cryptococcus gattii Cells to Fluconazole

    PubMed Central

    Chong, Hin Siong; Campbell, Leona; Padula, Matthew P.; Hill, Cameron; Harry, Elizabeth; Li, Simone S.; Wilkins, Marc R.; Herbert, Ben; Carter, Dee

    2012-01-01

    Cryptococcus gattii is an encapsulated fungus capable of causing fatal disease in immunocompetent humans and animals. As current antifungal therapies are few and limited in efficacy, and resistance is an emerging issue, the development of new treatment strategies is urgently required. The current study undertook a time-course analysis of the proteome of C. gattii during treatment with fluconazole (FLC), which is used widely in prophylactic and maintenance therapies. The aims were to analyze the overall cellular response to FLC, and to find fungal proteins involved in this response that might be useful targets in therapies that augment the antifungal activity of FLC. During FLC treatment, an increase in stress response, ATP synthesis and mitochondrial respiratory chain proteins, and a decrease in most ribosomal proteins was observed, suggesting that ATP-dependent efflux pumps had been initiated for survival and that the maintenance of ribosome synthesis was differentially expressed. Two proteins involved in fungal specific pathways were responsive to FLC. An integrative network analysis revealed co-ordinated processes involved in drug response, and highlighted hubs in the network representing essential proteins that are required for cell viability. This work demonstrates the dynamic cellular response of a typical susceptible isolate of C. gattii to FLC, and identified a number of proteins and pathways that could be targeted to augment the activity of FLC. PMID:22880118

  8. Norepinephrine-induced nociception and vasoconstrictor hypersensitivity in rats with chronic post-ischemia pain

    PubMed Central

    Xanthos, Dimitris N.; Bennett, Gary J.; Coderre, Terence J.

    2015-01-01

    Painful hypersensitivity to norepinephrine (NE) has been reported in various chronic pain conditions that exhibit sympathetically-maintained pain (SMP), particularly CRPS-I and II. We investigated the parallels between the nociceptive and vascular sensitivity to NE in rats with chronic post-ischemia pain (CPIP), an animal model of CRPS-I induced by hind paw ischemia-reperfusion injury. Intradermal injections of NE to the affected hind paw induced dose-dependent nociceptive behaviours in CPIP rats, but not sham animals. These behaviours were blocked by ?1- and ? 2-adrenergic receptor antagonists, or a nitric oxide (NO) donor. Using laser Doppler flowmetry, we detected vasoconstrictor hypersensitivity in the ipsilateral CPIP hind paw, as compared to responses in sham animals or the contralateral hind paw. The vasoconstrictor hypersensitivity was also attenuated by adrenergic antagonists. Intradermal injection of [Arg8] vasopressin (AVP) or the endothelial NO synthase (eNOS) inhibitor, L-NIO, to the affected paw also induced nociceptive behaviours in CPIP rats, but not sham rats. These results suggest CPIP rats display abnormal nociceptive responses to adrenergic and non-adrenergic vasoconstrictive agents. Furthermore, the nociceptive responses to NE in CPIP rats are paralleled by enhanced vasoconstrictive responses to NE, and are relieved by ?-adrenergic antagonists or a vasodilator. We conclude that persistent tissue ischemia and hypersensitivity to sympathetic vasoconstriction are important mechanisms for pain in CPIP rats, and that either reducing vasoconstriction or enhancing vasodilatation may be effective methods of relieving the pain of CRPS-I. PMID:18079061

  9. The induction and control of delayed type hypersensitivity reactions induced in chickens by infectious bronchitis virus

    Microsoft Academic Search

    R. Chubb; V. Huynh; R. Bradley

    1988-01-01

    Infectious bronchitis virus (IBV) was shown to induce delayed type hypersensitivity (DTH) reactions in the wattle, or to inhibit migration in a macrophage migration inhibition test (MIT) in sensitised birds. The magnitude of the reactions was related to the sensitising dose of the virus. The optimal dose for the cold attenuated A3?IBV was 10 EID50, higher doses giving lower responses.

  10. Salicylic acid in the machinery of hypersensitive cell death and disease resistance

    Microsoft Academic Search

    María Elena Alvarez

    2000-01-01

    Although extensive data has described the key role of salicylic acid (SA) in signaling pathogen-induced disease resistance, its function in physiological processes related to cell death is still poorly understood. Recent studies have explored the requirement of SA for mounting the hypersensitive response (HR) against an invading pathogen, where a particular cell death process is activated at the site of

  11. Contact hypersensitivity to topical antibacterial agents.

    PubMed

    Bajaj, A K; Gupta, S C

    1986-03-01

    Three hundred ninety patients with suspected contact dermatitis to topical medicaments were patch tested with various commercially available antibacterial agents to evaluate the incidence of contact hypersensitivity. The common sensitizers were nitrofurazone, neomycin, oxytetracycline, cetrimide, and framycetin. The least common sensitizers were sodium fusidate, chlorhexidine hydrochloride, and gentian violet. Cross-sensitivity was observed between neomycin, framycetin, and gentamicin. PMID:3699951

  12. Clinical and Radiologic Manifestations of Hypersensitivity Pneumonitis

    Microsoft Academic Search

    Craig S. Glazer; Cecile S. Rose; David A. Lynch

    Summary: Hypersensitivity pneumonitis (HP) is an inflammatory interstitial lung disease caused by recurring exposure to a variety of occupational and environmental antigens. It features widely variable clinical, radiologic, and histopathologic findings. Because the clinical findings of HP mimic multiple other diseases, a high degree of clinical suspicion and a thorough occupational and environmental history are essential for accurate diagnosis. There

  13. Quantitative Proteomics Reveals That Hsp90 Inhibition Preferentially Targets Kinases and the DNA Damage Response*

    PubMed Central

    Sharma, Kirti; Vabulas, R. Martin; Macek, Boris; Pinkert, Stefan; Cox, Jürgen; Mann, Matthias; Hartl, F. Ulrich

    2012-01-01

    Despite the increasing importance of heat shock protein 90 (Hsp90) inhibitors as chemotherapeutic agents in diseases such as cancer, their global effects on the proteome remain largely unknown. Here we use high resolution, quantitative mass spectrometry to map protein expression changes associated with the application of the Hsp90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG). In depth data obtained from five replicate SILAC experiments enabled accurate quantification of about 6,000 proteins in HeLa cells. As expected, we observed activation of a heat shock response with induced expression of molecular chaperones, which refold misfolded proteins, and proteases, which degrade irreparably damaged polypeptides. Despite the broad range of known Hsp90 substrates, bioinformatics analysis revealed that particular protein classes were preferentially affected. These prominently included proteins involved in the DNA damage response, as well as protein kinases and especially tyrosine kinases. We followed up on this observation with a quantitative phosphoproteomic analysis of about 4,000 sites, which revealed that Hsp90 inhibition leads to much more down- than up-regulation of the phosphoproteome (34% down versus 6% up). This study defines the cellular response to Hsp90 inhibition at the proteome level and sheds light on the mechanisms by which it can be used to target cancer cells. PMID:22167270

  14. Treatments for hypersensitive noncarious cervical lesions

    PubMed Central

    Veitz-Keenan, Analia; Barna, Julie Ann; Strober, Brad; Matthews, Abigail G.; Collie, Damon; Vena, Donald; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant. Methods Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly. Evaluations were conducted at baseline and at one, three and six months thereafter. Primary outcomes were the reduction or elimination of hypersensitivity as measured clinically and by means of patient-reported outcomes. Results Lesion depth and pretreatment sensitivity (mean, 5.3 on a 0- to 10-point scale) were balanced across treatments, as was sleep bruxism (present in 42.2 percent of participants). The six-month participant recall rate was 99 percent. Treatments significantly reduced mean sensitivity (P < .01), with the sealant and restoration groups displaying a significantly higher reduction (P < .01) than did the dentifrice group. The dentifrice group’s mean (standard deviation) sensitivity at six months was 2.1 (2.1); those of the sealant and restoration groups were 1.0 (1.6) and 0.8 (1.4), respectively. Patient-reported sensitivity (to cold being most pronounced) paralleled clinical measurements at each evaluation. Conclusions Sealing and restoration treatments were effective overall in reducing NCCL hypersensitivity. The potassium nitrate dentifrice reduced sensitivity with increasing effectiveness through six months but not to the degree offered by the other treatments. Practical Implications Sealant or restoration placement is an effective method of immediately reducing NCCL sensitivity. Although a potassium nitrate dentifrice did reduce sensitivity slowly across six months, at no time was the reduction commensurate with that of sealants or restorations. PMID:23633698

  15. Hypersensitivity reactions after respiratory sensitization: Effect of intranasal peptides containing T-cell epitopes

    Microsoft Academic Search

    Andrew G. Jarnicki; Takao Tsuji; Wayne R. Thomas

    2002-01-01

    Background: The intranasal administration of peptides containing T-cell epitopes has been shown to inhibit T-cell and antibody responses of mice injected with allergen, but responses to respiratory sensitization might be regulated differently. Objective: This study was designed to examine the effect of intranasal peptide on antigen-induced lung inflammatory responses and delayed hypersensitivity after sensitization by the respiratory mucosa or without

  16. Global analysis of neutrophil responses to Neisseria gonorrhoeae reveals a self-propagating inflammatory program.

    PubMed

    Sintsova, Anna; Sarantis, Helen; Islam, Epshita A; Sun, Chun Xiang; Amin, Mohsen; Chan, Carlos H F; Stanners, Clifford P; Glogauer, Michael; Gray-Owen, Scott D

    2014-09-01

    An overwhelming neutrophil-driven response causes both acute symptoms and the lasting sequelae that result from infection with Neisseria gonorrhoeae. Neutrophils undergo an aggressive opsonin-independent response to N. gonorrhoeae, driven by the innate decoy receptor CEACAM3. CEACAM3 is exclusively expressed by human neutrophils, and drives a potent binding, phagocytic engulfment and oxidative killing of Opa-expressing bacteria. In this study, we sought to explore the contribution of neutrophils to the pathogenic inflammatory process that typifies gonorrhea. Genome-wide microarray and biochemical profiling of gonococcal-infected neutrophils revealed that CEACAM3 engagement triggers a Syk-, PKC?- and Tak1-dependent signaling cascade that results in the activation of an NF-?B-dependent transcriptional response, with consequent production of pro-inflammatory cytokines. Using an in vivo model of N. gonorrhoeae infection, we show that human CEACAM-expressing neutrophils have heightened migration toward the site of the infection where they may be further activated upon Opa-dependent binding. Together, this study establishes that the role of CEACAM3 is not restricted to the direct opsonin-independent killing by neutrophils, since it also drives the vigorous inflammatory response that typifies gonorrhea. By carrying the potential to mobilize increasing numbers of neutrophils, CEACAM3 thereby represents the tipping point between protective and pathogenic outcomes of N. gonorrhoeae infection. PMID:25188454

  17. Predicting invasive species impacts: a community module functional response approach reveals context dependencies.

    PubMed

    Paterson, Rachel A; Dick, Jaimie T A; Pritchard, Daniel W; Ennis, Marilyn; Hatcher, Melanie J; Dunn, Alison M

    2014-09-29

    Predatory functional responses play integral roles in predator-prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species. Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator-prey interactions and thus the predictive capability of the comparative functional response approach. We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses. Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator. Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator. This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies. PMID:25265905

  18. Transcriptomic Analysis of Human Retinal Detachment Reveals Both Inflammatory Response and Photoreceptor Death

    PubMed Central

    Delyfer, Marie-Noëlle; Raffelsberger, Wolfgang; Mercier, David; Korobelnik, Jean-François; Gaudric, Alain; Charteris, David G.; Tadayoni, Ramin; Metge, Florence; Caputo, Georges; Barale, Pierre-Olivier; Ripp, Raymond; Muller, Jean-Denis; Poch, Olivier; Sahel, José-Alain; Léveillard, Thierry

    2011-01-01

    Background Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. Methodology/Principal Findings Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. Conclusions/Significance This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery. PMID:22174898

  19. Transgenic Zebrafish Reveal Tissue-Specific Differences in Estrogen Signaling in Response to Environmental Water Samples

    PubMed Central

    Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki S.; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. Results: We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ER? was expressed in developing heart valves but not in the liver, whereas ER?2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves. Citation: Gorelick DA, Iwanowicz LR, Hung AL, Blazer VS, Halpern ME. 2014. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples. Environ Health Perspect 122:356–362;?http://dx.doi.org/10.1289/ehp.1307329 PMID:24425189

  20. Metabolomics reveals comprehensive reprogramming involving two independent metabolic responses of Arabidopsis to UV-B light.

    PubMed

    Kusano, Miyako; Tohge, Takayuki; Fukushima, Atsushi; Kobayashi, Makoto; Hayashi, Naomi; Otsuki, Hitomi; Kondou, Youichi; Goto, Hiroto; Kawashima, Mika; Matsuda, Fumio; Niida, Rie; Matsui, Minami; Saito, Kazuki; Fernie, Alisdair R

    2011-07-01

    Because of ever-increasing environmental deterioration it is likely that the influx of UV-B radiation (280-320 nm) will increase as a result of the depletion of stratospheric ozone. Given this fact it is essential that we better understand both the rapid and the adaptive responses of plants to UV-B stress. Here, we compare the metabolic responses of wild-type Arabidopsis with that of mutants impaired in flavonoid (transparent testa 4, tt4; transparent testa 5, tt5) or sinapoyl-malate (sinapoylglucose accumulator 1, sng1) biosynthesis, exposed to a short 24-h or a longer 96-h exposure to this photo-oxidative stress. In control experiments we subjected the genotypes to long-day conditions as well as to 24- and 96-h treatments of continuous light. Following these treatments we evaluated the dynamic response of metabolites including flavonoids, sinapoyl-malate precursors and ascorbate, which are well known to play a role in cellular protection from UV-B stress, as well as a broader range of primary metabolites, in an attempt to more fully comprehend the metabolic shift following the cellular perception of this stress. Our data reveals that short-term responses occur only at the level of primary metabolites, suggesting that these effectively prime the cell to facilitate the later production of UV-B-absorbing secondary metabolites. The combined results of these studies together with transcript profiles using samples irradiated by 24-h UV-B light are discussed in the context of current models concerning the metabolic response of plants to the stress imposed by excessive UV-B irradiation. PMID:21466600

  1. [Hypersensitivity pneumonitis caused by isocyanate exposure during recreational painting].

    PubMed

    Tabata, Hisako; Mochizuki, Yoshiro; Nakahara, Yasuharu; Kobashi, Yoichiro; Kawamur, Tetuji; Sasaki, Shin

    2009-11-01

    A 36-year-old man began painting his car as a hobby every weekend in early February 2007 using a paint containing isocyanate. In March, 2007, he developed a dry cough, dyspnea and fever of 40 degrees C. These symptoms appeared repeatedly several hours after engaging in painting activity. His chest X-ray film showed diffuse small granular and reticular shadows in bilateral lung fields. His computed tomogram showed ground glass images in bilateral lung fields. Pulmonary function tests showed significantly decreased DLco. Histological findings of transbronchial lung biopsy revealed cellular interstitial pneumonia. These symptoms improved after cessation of painting and administration of prednisolone. Based on these results, we diagnosed this patient's illness as hypersensitivity pneumonitis due to isocyanate exposure. PMID:19994595

  2. Immunologic Evaluation of Immediate Hypersensitivity to Cefaclor

    PubMed Central

    Yoo, Hye-Soo; Kim, Seung-Hyun; Kwon, Hyouk-Soo; Kim, Tae-Bum; Nam, Young-Hee; Ye, Young-Min

    2014-01-01

    Purpose Cefaclor is widely prescribed for various infectious diseases. As its consumption increases, the number of hypersensitivity reactions to cefaclor has increased. This study aimed to evaluate the immunologic findings of immediate hypersensitivity to cefaclor. Materials and Methods We enrolled 47 patients with immediate hypersensitivity to cefaclor from Ajou University Hospital and Asan Medical Center. Serum specific IgE, IgG1, and IgG4 antibodies to cefaclor-human serum albumin (HSA) conjugate were measured by enzyme-linked immunosorbent assay (ELISA). Results The most common phenotype was anaphylaxis (Group I, 78.7%), followed by urticaria (Group II, 21.3%). The detection of specific IgE, IgG1, and IgG4 to cefaclor-HSA conjugate by ELISA tended to be higher in Group I (40.5%, 41.7%, 21.6%) than in Group II (20.0%, 20.0%, 0%) with no statistical significance. Significant associations were found between specific IgE and IgG1 or IgG4 (p<0.001, p=0.019). ELISA inhibition tests showed significant inhibitions by both free cefaclor and cefaclor-HSA conjugate. For basophil activation tests in patients having no specific IgE antibody, the CD63 expression level on basophils increased with incubations of free cefaclor. Conclusion The most common manifestation of immediate hypersensitivity to cefaclor was anaphylaxis, most of which was mediated by IgE; however, a non-IgE mediated direct basophil activation mechanism was suggested in a subset of anaphylaxis patients. PMID:25323882

  3. Dentin hypersensitivity and oxalates: a systematic review.

    PubMed

    Cunha-Cruz, J; Stout, J R; Heaton, L J; Wataha, J C

    2011-03-01

    Treatment of dentin hypersensitivity with oxalates is common, but oxalate efficacy remains unclear. Our objective was to systematically review clinical trials reporting an oxalate treatment compared with no treatment or placebo with a dentin hypersensitivity outcome. Risk-of-bias assessment and data extraction were performed independently by two reviewers. Standardized mean differences (SMD) were estimated by random-effects meta-analysis. Of 677 unique citations, 12 studies with high risk-of-bias were included. The summary SMD for 3% monohydrogen-monopotassium oxalate (n = 8 studies) was -0.71 [95% Confidence Interval: -1.48, 0.06]. Other treatments, including 30% dipotassium oxalate (n = 1), 30% dipotassium oxalate plus 3% monohydrogen monopotassium oxalate (n = 3), 6% monohydrogen monopotassium oxalate (n = 1), 6.8% ferric oxalate (n = 1), and oxalate-containing resin (n = 1), also were not statistically significantly different from placebo treatments. With the possible exception of 3% monohydrogen monopotassium oxalate, available evidence currently does not support the recommendation of dentin hypersensitivity treatment with oxalates. PMID:21191127

  4. Hypersensitivity Pneumonitis Caused by Cephalosporins With Identical R1 Side Chains.

    PubMed

    Lee, Sang Hee; Kim, Mi Hyun; Lee, Kwangha; Jo, Eun Jung; Park, Hye Kyung

    2015-09-01

    Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient's hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins. PMID:25749765

  5. Comparative Transcriptomic Analysis Reveals Similarities and Dissimilarities in Saccharomyces cerevisiae Wine Strains Response to Nitrogen Availability

    PubMed Central

    Barbosa, Catarina; García-Martínez, José; Pérez-Ortín, José E.; Mendes-Ferreira, Ana

    2015-01-01

    Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape-musts and the development of strategies to optimize yeast performance in industrial fermentations. PMID:25884705

  6. Transcriptome analysis reveals strong and complex antiviral response in a mollusc.

    PubMed

    He, Yan; Jouaux, Aude; Ford, Susan E; Lelong, Christophe; Sourdaine, Pascal; Mathieu, Michel; Guo, Ximing

    2015-09-01

    Viruses are highly abundant in the oceans, and how filter-feeding molluscs without adaptive immunity defend themselves against viruses is not well understood. We studied the response of a mollusc Crassostrea gigas to Ostreid herpesvirus 1 µVar (OsHV-1?Var) infections using transcriptome sequencing. OsHV-1?Var can replicate extremely rapidly after challenge of C. gigas as evidenced by explosive viral transcription and DNA synthesis, which peaked at 24 and 48 h post-inoculation, respectively, accompanied by heavy oyster mortalities. At 120 h post-injection, however, viral gene transcription and DNA load, and oyster mortality, were greatly reduced indicating an end of active infections and effective control of viral replication in surviving oysters. Transcriptome analysis of the host revealed strong and complex responses involving the activation of all major innate immune pathways that are equipped with expanded and often novel receptors and adaptors. Novel Toll-like receptor (TLR) and MyD88-like genes lacking essential domains were highly up-regulated in the oyster, possibly interfering with TLR signal transduction. RIG-1/MDA5 receptors for viral RNA, interferon-regulatory factors, tissue necrosis factors and interleukin-17 were highly activated and likely central to the oyster's antiviral response. Genes related to anti-apoptosis, oxidation, RNA and protein destruction were also highly up-regulated, while genes related to anti-oxidation were down-regulated. The oxidative burst induced by the up-regulation of oxidases and severe down-regulation of anti-oxidant genes may be important for the destruction of viral components, but may also exacerbate oyster mortality. This study provides unprecedented insights into antiviral response in a mollusc. The mobilization and complex regulation of expanded innate immune-gene families highlights the oyster genome's adaptation to a virus-rich marine environment. PMID:26004318

  7. Global phosphoproteome profiling reveals unanticipated networks responsive to cisplatin treatment of embryonic stem cells.

    PubMed

    Pines, Alex; Kelstrup, Christian D; Vrouwe, Mischa G; Puigvert, Jordi C; Typas, Dimitris; Misovic, Branislav; de Groot, Anton; von Stechow, Louise; van de Water, Bob; Danen, Erik H J; Vrieling, Harry; Mullenders, Leon H F; Olsen, Jesper V

    2011-12-01

    Cellular responses to DNA-damaging agents involve the activation of various DNA damage signaling and transduction pathways. Using quantitative and high-resolution tandem mass spectrometry, we determined global changes in protein level and phosphorylation site profiles following treatment of SILAC (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected. Although the ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) consensus sequence (S/T-Q motif) was significantly overrepresented among hyperphosphorylated peptides, about half of the >2-fold-upregulated phosphorylation sites based on the consensus sequence were not direct substrates of ATM and ATR. Eleven protein kinases mainly belonging to the mitogen-activated protein kinase (MAPK) family were identified as being regulated in their kinase domain activation loop. The biological importance of three of these kinases (cyclin-dependent kinase 7 [CDK7], Plk1, and KPCD1) in the protection against cisplatin-induced cytotoxicity was demonstrated by small interfering RNA (siRNA)-mediated knockdown. Our results indicate that the cellular response to cisplatin involves a variety of kinases and phosphatases not only acting in the nucleus but also regulating cytoplasmic targets, resulting in extensive cytoskeletal rearrangements. Integration of transcriptomic and proteomic data revealed a poor correlation between changes in the relative levels of transcripts and their corresponding proteins, but a large overlap in affected pathways at the levels of mRNA, protein, and phosphoprotein. This study provides an integrated view of pathways activated by genotoxic stress and deciphers kinases that play a pivotal role in regulating cellular processes other than the DNA damage response. PMID:22006019

  8. Comprehensive transcriptional profiling of NaCl-stressed Arabidopsis roots reveals novel classes of responsive genes

    PubMed Central

    Jiang, Yuanqing; Deyholos, Michael K

    2006-01-01

    Background Roots are an attractive system for genomic and post-genomic studies of NaCl responses, due to their primary importance to agriculture, and because of their relative structural and biochemical simplicity. Excellent genomic resources have been established for the study of Arabidopsis roots, however, a comprehensive microarray analysis of the root transcriptome following NaCl exposure is required to further understand plant responses to abiotic stress and facilitate future, systems-based analyses of the underlying regulatory networks. Results We used microarrays of 70-mer oligonucleotide probes representing 23,686 Arabidopsis genes to identify root transcripts that changed in relative abundance following 6 h, 24 h, or 48 h of hydroponic exposure to 150 mM NaCl. Enrichment analysis identified groups of structurally or functionally related genes whose members were statistically over-represented among up- or down-regulated transcripts. Our results are consistent with generally observed stress response themes, and highlight potentially important roles for underappreciated gene families, including: several groups of transporters (e.g. MATE, LeOPT1-like); signalling molecules (e.g. PERK kinases, MLO-like receptors), carbohydrate active enzymes (e.g. XTH18), transcription factors (e.g. members of ZIM, WRKY, NAC), and other proteins (e.g. 4CL-like, COMT-like, LOB-Class 1). We verified the NaCl-inducible expression of selected transcription factors and other genes by qRT-PCR. Conclusion Micorarray profiling of NaCl-treated Arabidopsis roots revealed dynamic changes in transcript abundance for at least 20% of the genome, including hundreds of transcription factors, kinases/phosphatases, hormone-related genes, and effectors of homeostasis, all of which highlight the complexity of this stress response. Our identification of these transcriptional responses, and groups of evolutionarily related genes with either similar or divergent transcriptional responses to stress, will facilitate mapping of regulatory networks and extend our ability to improve salt tolerance in plants. PMID:17038189

  9. Excess fertilizer responsive miRNAs revealed in Linum usitatissimum L.

    PubMed

    Melnikova, Nataliya V; Dmitriev, Alexey A; Belenikin, Maxim S; Speranskaya, Anna S; Krinitsina, Anastasia A; Rachinskaia, Olga A; Lakunina, Valentina A; Krasnov, George S; Snezhkina, Anastasiya V; Sadritdinova, Asiya F; Uroshlev, Leonid A; Koroban, Nadezda V; Samatadze, Tatiana E; Amosova, Alexandra V; Zelenin, Alexander V; Muravenko, Olga V; Bolsheva, Nadezhda L; Kudryavtseva, Anna V

    2015-02-01

    Effective fertilizer application is necessary to increase crop yields and reduce risk of plant overdosing. It is known that expression level of microRNAs (miRNAs) alters in plants under different nutrient concentrations in soil. The aim of our study was to identify and characterize miRNAs with expression alterations under excessive fertilizer in agriculturally important crop - flax (Linum usitatissimum L.). We have sequenced small RNAs in flax grown under normal and excessive fertilizer using Illumina GAIIx. Over 14 million raw reads was obtained for two small RNA libraries. 84 conserved miRNAs from 20 families were identified. Differential expression was revealed for several flax miRNAs under excessive fertilizer according to high-throughput sequencing data. For 6 miRNA families (miR395, miR169, miR408, miR399, miR398 and miR168) expression level alterations were evaluated on the extended sampling using qPCR. Statistically significant up-regulation was revealed for miR395 under excessive fertilizer. It is known that target genes of miR395 are involved in sulfate uptake and assimilation. However, according to our data alterations of the expression level of miR395 could be associated not only with excess sulfur application, but also with redundancy of other macro- and micronutrients. Furthermore expression level was evaluated for miRNAs and their predicted targets. The negative correlation between miR399 expression and expression of its predicted target ubiquitin-conjugating enzyme E2 gene was shown in flax for the first time. So we suggested miR399 involvement in phosphate regulation in L. usitatissimum. Revealed in our study expression alterations contribute to miRNA role in flax response to excessive fertilizer. PMID:25483925

  10. Electrophysiological dynamics reveal distinct processing of stimulus-stimulus and stimulus-response conflicts.

    PubMed

    Li, Qi; Wang, Kai; Nan, Weizhi; Zheng, Ya; Wu, Haiyan; Wang, Hongbin; Liu, Xun

    2015-04-01

    The present study examined electroencephalogram profiles on a novel stimulus-response compatibility (SRC) task in order to elucidate the distinct brain mechanisms of stimulus-stimulus (S-S) and stimulus-response (S-R) conflict processing. The results showed that the SRC effects on reaction times (RTs) and N2 amplitudes were additive when both S-S and S-R conflicts existed. We also observed that, for both RTs and N2 amplitudes, the conflict adaptation effects-the reduced SRC effect following an incongruent trial versus a congruent trial-were present only when two consecutive trials involved the same type of conflict. Time-frequency analysis revealed that both S-S and S-R conflicts modulated power in the theta band, whereas S-S conflict additionally modulated power in the alpha and beta bands. In summary, our findings provide insight into the domain-specific conflict processing and the modular organization of cognitive control. PMID:25395309

  11. Chronic vulvovaginal Candida hypersensitivity: An underrecognized and undertreated disorder by allergists

    PubMed Central

    Seidu, Luqman

    2015-01-01

    Vulvovaginal candidiasis infections are estimated to occur at least once during the lifetime of 75% of the female population. It has been proposed that some women with recurrent vulvovaginal candidiasis (RVVC) develop sensitization to Candida albicans and clinically improve in response to Candida immunotherapy. Here, we report a case series of 12 women diagnosed with chronic vulvovaginal Candida hypersensitivity subsequently treated with Candida immunotherapy and review potential systemic and localized host immune defense mechanisms involved in C. albicans overgrowth and sensitization. A retrospective review of vulvovaginal Candida hypersensitivity in women who were treated with C. albicans immunotherapy over the past eight years was conducted. Twelve women who qualified for a diagnosis of vulvovaginal Candida hypersensitivity were treated with Candida immunotherapy. Eleven of the 12 (92%) women reported clinical improvement after immunotherapy. The majority of these women were not sensitized to seasonal or perennial aeroallergens and clinically responded to lower concentrations of C. albicans allergen than what has been previously reported. In general, Candida immunotherapy was well tolerated. Chronic vulvovaginal Candida hypersensitivity is an underrecognized disorder by primary care physicians and therefore an undertreated disorder by allergists. A double-blinded, placebo-controlled randomized trial is necessary to firmly establish the efficacy of treatment with Candida immunotherapy. This investigation should be designed to include mechanistic studies that would help to better understand the etiology of this disorder. PMID:25860170

  12. DNase I hypersensitive sites flank the mouse class II major histocompatibility complex during B cell development.

    PubMed

    Carson, S

    1991-09-25

    The mouse class II major histocompatibility complex (MHC) encodes a polymorphic, multigene family important in the immune response, and is expressed mainly on mature B cells, on certain types of dendritic cells and is also inducible by gamma-interferon on antigen presenting cells. To study the regulatory elements which control this expression pattern, we have examined the chromatin structure flanking the class II MHC region, in particular during B cell differentiation. Using a panel of well-characterised mouse cell lines specific for different stages of B cell development (pre-B, B, plasma cell) as well as non-B cell lines, we have mapped the DNase I hypersensitive (DHS) sites adjacent to the mouse MHC class II region. The results presented show, for the first time that there are specific hypersensitive sites flanking the class II MHC locus during pre B cell, B cell and plasma cell stages of B cell differentiation, irrespective of the status of class II MHC expression. These hypersensitive sites are not found in T cell, fibroblast or uninduced myelomonocytic cell lines. This suggests that these DHS sites define a developmentally stable, chromatin structure, which can be used as a marker of B cell lineage commitment and may indicate that a combination of these hypersensitive sites reflect regulatory proteins involved in the immediate expression of a particular class II MHC gene or possibly control of the entire locus. PMID:1923768

  13. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    SciTech Connect

    Fang, Liang [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China); Zhao, Fang; Shen, Xuefeng [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China); Ouyang, Weiming [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States)] [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States); Liu, Xinqin; Xu, Yan; Yu, Tao [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China); Jin, Boquan [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Immunology, Fourth Military Medical University, Xi'an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)] [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032 (China)

    2012-12-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup ?} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ? Pb exposure impaired CD4{sup +} thymic T cell development. ? Peripheral T lymphocytes were reduced following Pb exposure. ? Pb exposure increases thymic and peripheral Treg cells in rats. ? Tregs played a critical role in Pb-exposure-induced immune suppression.

  14. Glycerol hypersensitivity in a Drosophila model for glycerol kinase deficiency is affected by mutations in eye pigmentation genes.

    PubMed

    Wightman, Patrick J; Jackson, George R; Dipple, Katrina M

    2012-01-01

    Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency. PMID:22427807

  15. Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity.

    PubMed

    Ferrusquía, José; Pérez-Martínez, Isabel; Gómez de la Torre, Ricardo; Fernández-Almira, María Luisa; de Francisco, Ruth; Rodrigo, Luis; Riestra, Sabino

    2015-04-01

    Mesalazine is a 5-aminosalicylic acid derivative that has been widely used to treat patients with inflammatory bowel disease. Accumulating evidence indicates that mesalazine has a very low rate of adverse drug reactions and is well tolerated by patients. However, a few cases of pulmonary and cardiac disease related to mesalazine have been reported in the past, though infrequently, preventing clinicians from diagnosing the conditions early. We describe the case of a 32-year-old man with ulcerative colitis who was admitted with a two-month history of persistent fever following mesalazine treatment initiated 14 mo earlier. At the time of admission, mesalazine dose was increased from 1.5 to 3.0 g/d, and antibiotic therapy was started with no improvement. Three weeks after admission, the patient developed dyspnea, non-productive cough, and chest pain. Severe eosinophilia was detected in laboratory tests, and a computed tomography scan revealed interstitial infiltrates in both lungs, as well as a large pericardial effusion. The bronchoalveolar lavage reported a CD4/CD8 ratio of 0.5, and an increased eosinophil count. Transbronchial biopsy examination showed a severe eosinophilic infiltrate of the lung tissue. Mesalazine-induced cardiopulmonary hypersensitivity was suspected after excluding other possible etiologies. Consequently, mesalazine treatment was suspended, and corticosteroid therapy was initiated, resulting in resolution of symptoms and radiologic abnormalities. We conclude that mesalazine-induced pulmonary and cardiac hypersensitivity should always be considered in the differential diagnosis of unexplained cardiopulmonary symptoms and radiographic abnormalities in patients with inflammatory bowel disease. PMID:25852295

  16. Food hypersensitivity among Caucasian and non-Caucasian children.

    PubMed

    Dias, Renuka P; Summerfield, Alison; Khakoo, G A

    2008-02-01

    There are little data regarding the frequency of different foods that cause hypersensitivity in the UK. Furthermore, there are no data regarding food hypersensitivity related to ethnic variations. This prospective study involved 76 children with IgE-mediated food allergy presenting consecutively over 18 months to a Paediatric Allergy Clinic serving a well-defined population that is 21% non-Caucasian. A total of 52.6% of the paediatric allergy clinic population was non-Caucasian compared with 35.9% in General Paediatric Clinics giving a mean difference in percentage of 16.7 (5.6, 27.8), p < 0.01. The average number of food allergens per child in the non-Caucasian group was 2.05 vs. 1.22 in the Caucasian group, mean difference 0.83, which is significant (t = 4.15, d.f. = 74, p < 0.01). Analysis of other allergic conditions revealed no significant increase in the non-Caucasian group. The mean age of first reaction to any food was 2.6 yr (range 0.3-12 yr) in Caucasian, and 1.7 yr (range 0.3-8 yr) in non-Caucasian, children (p < 0.05). There were 125 reactions in the study population, with egg, peanut, tree nut, cow milk and cod being the commonest food allergens. Some novel foods, such as kiwi, lentil and sesame, were also represented in the top 10 food allergies, particularly in the non-Caucasian population. Ethnic minorities are over-represented in terms of the number of children with food allergy and number of food allergies per child, present at an earlier age with food allergy, and possibly have a greater variety of food allergies compared with Caucasians. This is important in terms of health education. Our findings need confirmation by a more detailed population based study, ideally using food challenges in addition to history and skin prick testing. PMID:18086219

  17. Metagenome, metatranscriptome and single-cell sequencing reveal microbial response to Deepwater Horizon oil spill.

    PubMed

    Mason, Olivia U; Hazen, Terry C; Borglin, Sharon; Chain, Patrick S G; Dubinsky, Eric A; Fortney, Julian L; Han, James; Holman, Hoi-Ying N; Hultman, Jenni; Lamendella, Regina; Mackelprang, Rachel; Malfatti, Stephanie; Tom, Lauren M; Tringe, Susannah G; Woyke, Tanja; Zhou, Jizhong; Rubin, Edward M; Jansson, Janet K

    2012-09-01

    The Deepwater Horizon oil spill in the Gulf of Mexico resulted in a deep-sea hydrocarbon plume that caused a shift in the indigenous microbial community composition with unknown ecological consequences. Early in the spill history, a bloom of uncultured, thus uncharacterized, members of the Oceanospirillales was previously detected, but their role in oil disposition was unknown. Here our aim was to determine the functional role of the Oceanospirillales and other active members of the indigenous microbial community using deep sequencing of community DNA and RNA, as well as single-cell genomics. Shotgun metagenomic and metatranscriptomic sequencing revealed that genes for motility, chemotaxis and aliphatic hydrocarbon degradation were significantly enriched and expressed in the hydrocarbon plume samples compared with uncontaminated seawater collected from plume depth. In contrast, although genes coding for degradation of more recalcitrant compounds, such as benzene, toluene, ethylbenzene, total xylenes and polycyclic aromatic hydrocarbons, were identified in the metagenomes, they were expressed at low levels, or not at all based on analysis of the metatranscriptomes. Isolation and sequencing of two Oceanospirillales single cells revealed that both cells possessed genes coding for n-alkane and cycloalkane degradation. Specifically, the near-complete pathway for cyclohexane oxidation in the Oceanospirillales single cells was elucidated and supported by both metagenome and metatranscriptome data. The draft genome also included genes for chemotaxis, motility and nutrient acquisition strategies that were also identified in the metagenomes and metatranscriptomes. These data point towards a rapid response of members of the Oceanospirillales to aliphatic hydrocarbons in the deep sea. PMID:22717885

  18. Metagenomics, metatranscriptomics and single cell genomics reveal functional response of active Oceanospirillales to Gulf oil spill

    SciTech Connect

    Mason, Olivia U.; Hazen, Terry C.; Borglin, Sharon; Chain, Patrick S. G.; Dubinsky, Eric A.; Fortney, Julian L.; Han, James; Holman, Hoi-Ying N.; Hultman, Jenni; Lamendella, Regina; Mackelprang, Rachel; Malfatti, Stephanie; Tom, Lauren M.; Tringe, Susannah G.; Woyke, Tanja; Zhou, Jizhong; Rubin, Edward M.; Jansson, Janet K.

    2012-06-12

    The Deepwater Horizon oil spill in the Gulf of Mexico resulted in a deep-sea hydrocarbon plume that caused a shift in the indigenous microbial community composition with unknown ecological consequences. Early in the spill history, a bloom of uncultured, thus uncharacterized, members of the Oceanospirillales was previously detected, but their role in oil disposition was unknown. Here our aim was to determine the functional role of the Oceanospirillales and other active members of the indigenous microbial community using deep sequencing of community DNA and RNA, as well as single-cell genomics. Shotgun metagenomic and metatranscriptomic sequencing revealed that genes for motility, chemotaxis and aliphatic hydrocarbon degradation were significantly enriched and expressed in the hydrocarbon plume samples compared with uncontaminated seawater collected from plume depth. In contrast, although genes coding for degradation of more recalcitrant compounds, such as benzene, toluene, ethylbenzene, total xylenes and polycyclic aromatic hydrocarbons, were identified in the metagenomes, they were expressed at low levels, or not at all based on analysis of the metatranscriptomes. Isolation and sequencing of two Oceanospirillales single cells revealed that both cells possessed genes coding for n-alkane and cycloalkane degradation. Specifically, the near-complete pathway for cyclohexane oxidation in the Oceanospirillales single cells was elucidated and supported by both metagenome and metatranscriptome data. The draft genome also included genes for chemotaxis, motility and nutrient acquisition strategies that were also identified in the metagenomes and metatranscriptomes. These data point towards a rapid response of members of the Oceanospirillales to aliphatic hydrocarbons in the deep sea.

  19. Metagenome, metatranscriptome and single-cell sequencing reveal microbial response to Deepwater Horizon oil spill

    PubMed Central

    Mason, Olivia U; Hazen, Terry C; Borglin, Sharon; Chain, Patrick S G; Dubinsky, Eric A; Fortney, Julian L; Han, James; Holman, Hoi-Ying N; Hultman, Jenni; Lamendella, Regina; Mackelprang, Rachel; Malfatti, Stephanie; Tom, Lauren M; Tringe, Susannah G; Woyke, Tanja; Zhou, Jizhong; Rubin, Edward M; Jansson, Janet K

    2012-01-01

    The Deepwater Horizon oil spill in the Gulf of Mexico resulted in a deep-sea hydrocarbon plume that caused a shift in the indigenous microbial community composition with unknown ecological consequences. Early in the spill history, a bloom of uncultured, thus uncharacterized, members of the Oceanospirillales was previously detected, but their role in oil disposition was unknown. Here our aim was to determine the functional role of the Oceanospirillales and other active members of the indigenous microbial community using deep sequencing of community DNA and RNA, as well as single-cell genomics. Shotgun metagenomic and metatranscriptomic sequencing revealed that genes for motility, chemotaxis and aliphatic hydrocarbon degradation were significantly enriched and expressed in the hydrocarbon plume samples compared with uncontaminated seawater collected from plume depth. In contrast, although genes coding for degradation of more recalcitrant compounds, such as benzene, toluene, ethylbenzene, total xylenes and polycyclic aromatic hydrocarbons, were identified in the metagenomes, they were expressed at low levels, or not at all based on analysis of the metatranscriptomes. Isolation and sequencing of two Oceanospirillales single cells revealed that both cells possessed genes coding for n-alkane and cycloalkane degradation. Specifically, the near-complete pathway for cyclohexane oxidation in the Oceanospirillales single cells was elucidated and supported by both metagenome and metatranscriptome data. The draft genome also included genes for chemotaxis, motility and nutrient acquisition strategies that were also identified in the metagenomes and metatranscriptomes. These data point towards a rapid response of members of the Oceanospirillales to aliphatic hydrocarbons in the deep sea. PMID:22717885

  20. Growth and carbon isotopes of Mediterranean trees reveal contrasting responses to increased carbon dioxide and drought.

    PubMed

    Granda, Elena; Rossatto, Davi Rodrigo; Camarero, J Julio; Voltas, Jordi; Valladares, Fernando

    2014-01-01

    Forest dynamics will depend upon the physiological performance of individual tree species under more stressful conditions caused by climate change. In order to compare the idiosyncratic responses of Mediterranean tree species (Quercus faginea, Pinus nigra, Juniperus thurifera) coexisting in forests of central Spain, we evaluated the temporal changes in secondary growth (basal area increment; BAI) and intrinsic water-use efficiency (iWUE) during the last four decades, determined how coexisting species are responding to increases in atmospheric CO2 concentrations (C(a)) and drought stress, and assessed the relationship among iWUE and growth during climatically contrasting years. All species increased their iWUE (ca. +15 to +21%) between the 1970s and the 2000s. This increase was positively related to C(a) for J. thurifera and to higher C(a) and drought for Q. faginea and P. nigra. During climatically favourable years the study species either increased or maintained their growth at rising iWUE, suggesting a higher CO2 uptake. However, during unfavourable climatic years Q. faginea and especially P. nigra showed sharp declines in growth at enhanced iWUE, likely caused by a reduced stomatal conductance to save water under stressful dry conditions. In contrast, J. thurifera showed enhanced growth also during unfavourable years at increased iWUE, denoting a beneficial effect of C(a) even under climatically harsh conditions. Our results reveal significant inter-specific differences in growth driven by alternative physiological responses to increasing drought stress. Thus, forest composition in the Mediterranean region might be altered due to contrasting capacities of coexisting tree species to withstand increasingly stressful conditions. PMID:23928889

  1. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    PubMed Central

    2012-01-01

    Background Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite hypersensitivity. Therefore, the aim of our study was to identify and quantify genomic associations with insect bite hypersensitivity in Shetland pony mares and Icelandic horses in the Netherlands. Methods Data on 200 Shetland pony mares and 146 Icelandic horses were collected according to a matched case–control design. Cases and controls were matched on various factors (e.g. region, sire) to minimize effects of population stratification. Breed-specific genome-wide association studies were performed using 70 k single nucleotide polymorphisms genotypes. Bayesian variable selection method Bayes-C with a threshold model implemented in GenSel software was applied. A 1 Mb non-overlapping window approach that accumulated contributions of adjacent single nucleotide polymorphisms was used to identify associated genomic regions. Results The percentage of variance explained by all single nucleotide polymorphisms was 13% in Shetland pony mares and 28% in Icelandic horses. The 20 non-overlapping windows explaining the largest percentages of genetic variance were found on nine chromosomes in Shetland pony mares and on 14 chromosomes in Icelandic horses. Overlap in identified associated genomic regions between breeds would suggest interesting candidate regions to follow-up on. Such regions common to both breeds (within 15 Mb) were found on chromosomes 3, 7, 11, 20 and 23. Positional candidate genes within 2 Mb from the associated windows were identified on chromosome 20 in both breeds. Candidate genes are within the equine lymphocyte antigen class II region, which evokes an immune response by recognizing many foreign molecules. Conclusions The genome-wide association study identified several genomic regions associated with insect bite hypersensitivity in Shetland pony mares and Icelandic horses. On chromosome 20, associated genomic regions in both breeds were within 2 Mb from the equine lymphocyte antigen class II region. Increased knowledge on insect bite hypersensitivity associated genes will contribute to our understanding of its biology, enabling more efficient selection, therapy and prevention to decrease insect bite hypersensitivity prevalence. PMID:23110538

  2. Food Hypersensitivity Reactions Visualised by Ultrasonography and Magnetic Resonance Imaging in a Patient Lacking Systemic Food-Specific IgE

    Microsoft Academic Search

    Gülen Arslan; Kristine Lillestřl; Arna Mulahasanovic; Erik Florvaag; Arnold Berstad

    2006-01-01

    Background: Abdominal complaints related to food intake might be due to hypersensitivity. A firm diagnosis of food allergy is often difficult to establish, particularly in the absence of systemic food-specific IgE. Using ultrasonography and magnetic resonance imaging (MRI) we were able to visualise the intestinal response in one such case. Methods: A 24-year-old female presented with self-reported food hypersensitivity, particularly

  3. Genetic structure along an elevational gradient in Hawaiian honeycreepers reveals contrasting evolutionary responses to avian malaria

    USGS Publications Warehouse

    Eggert, L.S.; Terwilliger, L.A.; Woodworth, B.L.; Hart, P.J.; Palmer, D.; Fleischer, R.C.

    2008-01-01

    Background. The Hawaiian honeycreepers (Drepanidinae) are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens), the apapane (Himatione sanguinea), and the iiwi (Vestiaria coccinea) were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results. Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion. Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent. ?? 2008 Eggert et al; licensee BioMed Central Ltd.

  4. Plasminogen activator urokinase expression reveals TRAIL responsiveness and supports fractional survival of cancer cells

    PubMed Central

    Pavet, V; Shlyakhtina, Y; He, T; Ceschin, D G; Kohonen, P; Perälä, M; Kallioniemi, O; Gronemeyer, H

    2014-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10/Apo2L) holds promise for cancer therapy as it induces apoptosis in a large variety of cancer cells while exerting negligible toxicity in normal ones. However, TRAIL can also induce proliferative and migratory signaling in cancer cells resistant to apoptosis induced by this cytokine. In that regard, the molecular mechanisms underlying the tumor selectivity of TRAIL and those balancing apoptosis versus survival remain largely elusive. We show here that high mRNA levels of PLAU, which encodes urokinase plasminogen activator (uPA), are characteristic of cancer cells with functional TRAIL signaling. Notably, decreasing uPA levels sensitized cancer cells to TRAIL, leading to markedly increased apoptosis. Mechanistic analyses revealed three molecular events taking place in uPA-depleted cells: reduced basal ERK1/2 prosurvival signaling, decreased preligand decoy receptor 2 (DcR2)-death receptor 5 (DR5) interaction and attenuated recruitment of DcR2 to the death-inducing signaling complex upon TRAIL challenge. These phenomena were accompanied by increased FADD and procaspase-8 recruitment and processing, thus guiding cells toward a caspase-dependent cell death that is largely independent of the intrinsic apoptosis pathway. Collectively, our results unveil PLAU mRNA levels as marker for the identification of TRAIL-responsive tumor cells and highlight a key role of uPA signaling in ‘apoptosis versus survival' decision-making processes upon TRAIL challenge. PMID:24481457

  5. The Response-Signal Method Reveals Age-Related Changes in Object Working Memory

    PubMed Central

    Kumar, Arjun; Rakitin, Brian C.; Nambisan, Rohit; Habeck, Christian; Stern, Yaakov

    2009-01-01

    Sixteen healthy young adults (ages 18–32) and 16 healthy older adults (ages 67–81) completed a delayed response task in which they saw the following visual sequence: memory stimuli (2 abstract shapes; 3,000 ms), a blank delay (5,000 ms), a probe stimulus of variable duration (one abstract shape; 125, 250, 500, 1,000, or 2,000 ms), and a mask (500 ms). Subjects decided whether the probe stimulus matched either of the memory stimuli; they were instructed to respond during the mask, placing greater emphasis on speed than accuracy. The authors used D. L. Hintzman & T. Curran’s (1994) 3-parameter compound bounded exponential model of speed–accuracy tradeoff to describe changes in discriminability associated with total processing time. Group-level analysis revealed a higher rate parameter and a higher asymptote parameter for the young adult group, but no difference across groups in x-intercept. Proxy measures of cognitive reserve (Y. Stern et al., 2005) predicted the rate parameter value, particularly in older adults. Results suggest that in working memory, aging impairs both the maximum capacity for discriminability and the rate of information accumulation, but not the temporal threshold for discriminability. PMID:18573006

  6. Time-series analysis reveals genetic responses to intensive management of razorback sucker (Xyrauchen texanus).

    PubMed

    Dowling, Thomas E; Turner, Thomas F; Carson, Evan W; Saltzgiver, Melody J; Adams, Deborah; Kesner, Brian; Marsh, Paul C

    2014-03-01

    Time-series analysis is used widely in ecology to study complex phenomena and may have considerable potential to clarify relationships of genetic and demographic processes in natural and exploited populations. We explored the utility of this approach to evaluate population responses to management in razorback sucker, a long-lived and fecund, but declining freshwater fish species. A core population in Lake Mohave (Arizona-Nevada, USA) has experienced no natural recruitment for decades and is maintained by harvesting naturally produced larvae from the lake, rearing them in protective custody, and repatriating them at sizes less vulnerable to predation. Analyses of mtDNA and 15 microsatellites characterized for sequential larval cohorts collected over a 15-year time series revealed no changes in geographic structuring but indicated significant increase in mtDNA diversity for the entire population over time. Likewise, ratios of annual effective breeders to annual census size (N b /N a) increased significantly despite sevenfold reduction of N a. These results indicated that conservation actions diminished near-term extinction risk due to genetic factors and should now focus on increasing numbers of fish in Lake Mohave to ameliorate longer-term risks. More generally, time-series analysis permitted robust testing of trends in genetic diversity, despite low precision of some metrics. PMID:24665337

  7. Genetic Ablation of Caveolin-1 Drives Estrogen-Hypersensitivity and the Development of DCIS-Like Mammary Lesions

    PubMed Central

    Mercier, Isabelle; Casimiro, Mathew C.; Zhou, Jie; Wang, Chenguang; Plymire, Christopher; Bryant, Kelly G.; Daumer, Kristin M.; Sotgia, Federica; Bonuccelli, Gloria; Witkiewicz, Agnieszka K.; Lin, Justin; Hong Tran, Thai; Milliman, Janet; Frank, Philippe G.; Jasmin, Jean-François; Rui, Hallgeir; Pestell, Richard G.; Lisanti, Michael P.

    2009-01-01

    Caveolin-1 (Cav-1) loss-of-function mutations are exclusively associated with estrogen receptor-positive (ER(+)) human breast cancers. To dissect the role of Cav-1 loss-of-function in the pathogenesis of human breast cancers, we used Cav-1?/? null mice as a model system. First, we demonstrated that Cav-1?/? mammary epithelia overexpress two well-established ER co-activator genes, CAPER and Foxa1, in addition to ER-?. Thus, the functional loss of Cav-1 may be sufficient to confer estrogen-hypersensitivity in the mammary gland. To test this hypothesis directly, we subjected Cav-1?/? mice to ovariectomy and estrogen supplementation. As predicted, Cav-1?/? mammary glands were hyper-responsive to estrogen and developed dysplastic mammary lesions with adjacent stromal angiogenesis that resemble human ductal carcinoma in situ. Based on an extensive biomarker analysis, these Cav-1?/? mammary lesions contain cells that are hyperproliferative and stain positively with nucleolar (B23/nucleophosmin) and stem/progenitor cell markers (SPRR1A and ?-catenin). Genome-wide transcriptional profiling identified many estrogen-related genes that were over-expressed in Cav-1?/? mammary glands, including CAPER—an ER co-activator gene and putative stem/progenitor cell marker. Analysis of human breast cancer samples revealed that CAPER is overexpressed and undergoes a cytoplasmic-to-nuclear shift during the transition from pre-malignancy to ductal carcinoma in situ. Thus, Cav-1?/? null mice are a new preclinical model for studying the molecular paradigm of estrogen hypersensitivity and the development of estrogen-dependent ductal carcinoma in situ lesions. PMID:19342371

  8. Hypersensitivity Pneumonitisamong Workers CultivatingTricholoma conglobatum (Shimeji)

    Microsoft Academic Search

    Norikazu Akizuki; Naohiko Inase; Nobuo Ishiwata; Yasuto Jin; Kenichi Atarashi; Masahiko Ichioka; Yasuyuki Yoshizawa; Fumiaki Marumo

    1999-01-01

    We report five cases of hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji). After having worked for 5 to 20 years, they began to notice symptoms of cough, sputum, and dyspnea. They were diagnosed as having a hypersensitivity pneumonitis based on clinical features, bronchoalveolar lavage and transbronchial lung biopsy. By the double immunodiffusion test, precipitating lines between shimeji spore antigen

  9. Procarbazine hypersensitivity manifested as a fixed drug eruption.

    PubMed

    Giguere, J K; Douglas, D M; Lupton, G P; Baker, J R; Weiss, R B

    1988-01-01

    A case of a previously unrecognized form of hypersensitivity to procarbazine characterized by a nonpigmented fixed drug eruption is reported. Despite skin testing, association of the skin lesion to procarbazine could be determined only by drug rechallenge. Various aspects of procarbazine hypersensitivity reactions as well as the pathogenesis and importance of the fixed drug eruption are discussed. PMID:2462159

  10. Pharmacogenetics of antiepileptic drug-induced hypersensitivity.

    PubMed

    Bloch, Katarzyna M; Sills, Graeme J; Pirmohamed, Munir; Alfirevic, Ana

    2014-04-01

    Antiepileptic drugs can induce potentially life-threatening hypersensitivity reactions such as Stevens-Johnson syndrome at a frequency of one in 10,000 to one in 1000 treated patients. There is a considerable cross-reactivity among different antiepileptic drugs but the mechanisms are not known. In this review we have summarized current evidence on antiepileptic drug-induced hypersensitivity reactions and performed meta-analyses of published case-control studies that investigated associations between HLA alleles and several antiepileptic drugs in diverse populations. As the heterogeneity between studies was high, we conducted subsequent subgroup analyses and showed that HLA-B*15:02 was associated with carbamazepine, lamotrigine and phenytoin-induced Stevens-Johnson syndrome in Asian populations indicating that pretreatment testing may prevent cross-reactivity. Additionally, we explored the potential of new, high-throughput technologies that may help to understand the mechanisms and predict the risk of adverse drug reactions in the future. PMID:24897291

  11. Radiocontrast media hypersensitivity in the Asia Pacific region

    PubMed Central

    Lee, Suh-Young; Lim, Kyoung-Whan

    2014-01-01

    Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region. PMID:24809018

  12. Plant physiology and proteomics reveals the leaf response to drought in alfalfa (Medicago sativa L.)

    PubMed Central

    Aranjuelo, Iker; Molero, Gemma; Erice, Gorka; Avice, Jean Christophe; Nogués, Salvador

    2011-01-01

    Despite its relevance, protein regulation, metabolic adjustment, and the physiological status of plants under drought is not well understood in relation to the role of nitrogen fixation in nodules. In this study, nodulated alfalfa plants were exposed to drought conditions. The study determined the physiological, metabolic, and proteomic processes involved in photosynthetic inhibition in relation to the decrease in nitrogenase (Nase) activity. The deleterious effect of drought on alfalfa performance was targeted towards photosynthesis and Nase activity. At the leaf level, photosynthetic inhibition was mainly caused by the inhibition of Rubisco. The proteomic profile and physiological measurements revealed that the reduced carboxylation capacity of droughted plants was related to limitations in Rubisco protein content, activation state, and RuBP regeneration. Drought also decreased amino acid content such as asparagine, and glutamic acid, and Rubisco protein content indicating that N availability limitations were caused by Nase activity inhibition. In this context, drought induced the decrease in Rubisco binding protein content at the leaf level and proteases were up-regulated so as to degrade Rubisco protein. This degradation enabled the reallocation of the Rubisco-derived N to the synthesis of amino acids with osmoregulant capacity. Rubisco degradation under drought conditions was induced so as to remobilize Rubisco-derived N to compensate for the decrease in N associated with Nase inhibition. Metabolic analyses showed that droughted plants increased amino acid (proline, a major compound involved in osmotic regulation) and soluble sugar (D-pinitol) levels to contribute towards the decrease in osmotic potential (?s). At the nodule level, drought had an inhibitory effect on Nase activity. This decrease in Nase activity was not induced by substrate shortage, as reflected by an increase in total soluble sugars (TSS) in the nodules. Proline accumulation in the nodule could also be associated with an osmoregulatory response to drought and might function as a protective agent against ROS. In droughted nodules, the decrease in N2 fixation was caused by an increase in oxygen resistance that was induced in the nodule. This was a mechanism to avoid oxidative damage associated with reduced respiration activity and the consequent increase in oxygen content. This study highlighted that even though drought had a direct effect on leaves, the deleterious effects of drought on nodules also conditioned leaf responsiveness. PMID:20797998

  13. Avidity determines T-cell reactivity in abacavir hypersensitivity.

    PubMed

    Adam, Jacqueline; Eriksson, Klara K; Schnyder, Benno; Fontana, Stefano; Pichler, Werner J; Yerly, Daniel

    2012-07-01

    The antiretroviral drug abacavir (abc) elicits severe drug hypersensitivity reactions in HLA-B*5701(+) individuals. To understand the abc-specific activation of CD8(+) T cells, we generated abc-specific T-cell clones (abc-TCCs). Abc reactivity could not be linked to the metabolism and/or processing of the drug, since abc metabolizing enzymes were not expressed in immune cells and inhibition of the proteasome in APCs did not affect TCC reactivity. Ca(2+) influx assays revealed different reactivity patterns of abc-TCCs. While all TCCs reacted to abc presented on HLA-B*5701 molecules, a minority also reacted immediately to abc in solution. Titration experiments showed that the ability to react immediately to abc correlated significantly with the TCR avidity of the T cells. Modifications of soluble abc concentrations revealed that the reactivity patterns of abc-TCCs were not fixed but dynamic. When TCCs with an intermediate TCR avidity were stimulated with increasing abc concentrations, they showed an accelerated activation kinetic. Thus, they reacted immediately to the drug, similar to the reaction of TCCs of high avidity. The observed immediate activation and the noninvolvement of the proteasome suggest that, in contrast to haptens, abc-specific T-cell stimulation does not require the formation of covalent bonds to produce a neo-antigenic determinant. PMID:22585534

  14. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw

    USGS Publications Warehouse

    MacKelprang, R.; Waldrop, M.P.; Deangelis, K.M.; David, M.M.; Chavarria, K.L.; Blazewicz, S.J.; Rubin, E.M.; Jansson, J.K.

    2011-01-01

    Permafrost contains an estimated 1672????????Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 ??C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  15. Comparison of Transcriptional Changes to Chloroplast and Mitochondrial Perturbations Reveals Common and Specific Responses in Arabidopsis

    PubMed Central

    Van Aken, Olivier; Whelan, James

    2012-01-01

    Throughout the life of a plant, the biogenesis and fine-tuning of energy organelles is essential both under normal growth and stress conditions. Communication from organelle to nucleus is essential to adapt gene regulation and protein synthesis specifically to the current needs of the plant. This organelle-to-nuclear communication is termed retrograde signaling and has been studied extensively over the last decades. In this study we have used large-scale gene expression data sets relating to perturbations of chloroplast and mitochondrial function to gain further insights into plant retrograde signaling and how mitochondrial and chloroplast retrograde pathways interact and differ. Twenty seven studies were included that assess transcript profiles in response to chemical inhibition as well as genetic mutations of organellar proteins. The results show a highly significant overlap between gene expression changes triggered by chloroplast and mitochondrial perturbations. These overlapping gene expression changes appear to be common with general abiotic, biotic, and nutrient stresses. However, retrograde signaling pathways are capable of distinguishing the source of the perturbation as indicated by a statistical overrepresentation of changes in genes encoding proteins of the affected organelle. Organelle-specific overrepresented functional categories among others relate to energy metabolism and protein synthesis. Our analysis also suggests that WRKY transcription factors play a coordinating role on the interface of both organellar signaling pathways. Global comparison of the expression profiles for each experiment revealed that the recently identified chloroplast retrograde pathway using phospho-adenosine phosphate is possibly more related to mitochondrial than chloroplast perturbations. Furthermore, new marker genes have been identified that respond specifically to mitochondrial and/or chloroplast dysfunction. PMID:23269925

  16. Immunoglobulin E-mediated hypersensitivity in food-producing animals.

    PubMed

    Gershwin, L J

    2001-11-01

    Type I hypersensitivity has been described as a cause of allergic reactivity to inhalants, injectables, endoparasites, and ectoparasites in food animal species. In addition, IgE is credited with showing some host-sparing effect when produced in response to certain gastrointestinal and other parasites. Recently, the sophistication of diagnostic procedures has increased with the elucidation of epsilon heavy chain sequences, expressed protein, development of chimeric IgE antibodies, and production of species-specific anti-IgE reagents. Application of ELISA and Western blotting has replaced the passive cutaneous anaphylaxis test for demonstration of antigen-specific IgE in serum. Regulation of the IgE response is complex, and its dependence on induction of T helper cell type 2 cytokines is now established. The next frontier in IgE research, as for many inherited diseases, lies in understanding the genetic make-up of the animal and which genes are important in controlling the IgE response. PMID:11692511

  17. Stimulus-locked responses on human arm muscles reveal a rapid neural pathway linking visual input to arm motor

    E-print Network

    Flanagan, Randy

    Stimulus-locked responses on human arm muscles reveal a rapid neural pathway linking visual input to arm motor output J. Andrew Pruszynski,1 * Geoffrey L. King,1 * Lysa Boisse,1,2 Stephen H. Scott,1-reticulo-spinal pathway Abstract Previous studies have demonstrated that humans are sometimes capable of initiating arm

  18. Pain hypersensitivity mechanisms at a glance

    PubMed Central

    Gangadharan, Vijayan; Kuner, Rohini

    2013-01-01

    There are two basic categories of pain: physiological pain, which serves an important protective function, and pathological pain, which can have a major negative impact on quality of life in the context of human disease. Major progress has been made in understanding the molecular mechanisms that drive sensory transduction, amplification and conduction in peripheral pain-sensing neurons, communication of sensory inputs to spinal second-order neurons, and the eventual modulation of sensory signals by spinal and descending circuits. This poster article endeavors to provide an overview of how molecular and cellular mechanisms underlying nociception in a physiological context undergo plasticity in pathophysiological states, leading to pain hypersensitivity and chronic pain. PMID:23828645

  19. Azathioprine hypersensitivity presenting as septic shock with encephalopathy

    PubMed Central

    James, Antonia; Blagojevic, Jelena; Benham, Stuart W; Cornall, Richard; Frater, John

    2013-01-01

    We present a case of azathioprine hypersensitivity presenting as septic shock with associated encephalopathy. The patient was presented with rapid onset of fever, hypotension, confusion and a rapidly declining conscious level. He was admitted to the intensive care unit where he received numerous invasive investigations and treatments with broad-spectrum antibiotics, antivirals and antifungals. All microbial cultures were negative. The patient—consistent with azathioprine hypersensitivity—made a spontaneous recovery after 7?days. The case shows that a time line of drug initiation is a key part of the medical history and consideration of azathioprine hypersensitivity could avoid unnecessary interventions and excessive antimicrobial use. PMID:23513015

  20. Conditioned fear as revealed by magnitude of startle response to an auditory stimulus

    Microsoft Academic Search

    Judson S. Brown; Harry I. Kalish; I. E. Farber

    1951-01-01

    Male rats were trained on buzzer-shock presentations. In 15 animals, conditions produced a conditioned pain response; in the controls, conditions reduced or prevented formation of fear. The experimental group showed a significant progressive increase, extinction and spontaneous recovery in the average startle response whereas the controls changed but little.

  1. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    ERIC Educational Resources Information Center

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  2. Response to intervals as revealed by brainwave measurement and verbal means

    Microsoft Academic Search

    Dalia Cohen; Joseph Mendel; Hillel Prat; Anat Bamea

    1994-01-01

    The purpose of this study was to enhance understanding of the meaning of the interval as a musical parameter. This was done by examining both verbal reports and brainwave (Event?Related Potential, or ERP) responses to intervals. In an experiment with ERP (the oddball task), we examined the responses of listeners trained in Western music to isolated harmonic intervals. In the

  3. Mining large-scale response networks reveals ‘topmost activities’ in Mycobacterium tuberculosis infection

    PubMed Central

    Sambarey, Awanti; Prashanthi, Karyala; Chandra, Nagasuma

    2013-01-01

    Mycobacterium tuberculosis owes its high pathogenic potential to its ability to evade host immune responses and thrive inside the macrophage. The outcome of infection is largely determined by the cellular response comprising a multitude of molecular events. The complexity and inter-relatedness in the processes makes it essential to adopt systems approaches to study them. In this work, we construct a comprehensive network of infection-related processes in a human macrophage comprising 1888 proteins and 14,016 interactions. We then compute response networks based on available gene expression profiles corresponding to states of health, disease and drug treatment. We use a novel formulation for mining response networks that has led to identifying highest activities in the cell. Highest activity paths provide mechanistic insights into pathogenesis and response to treatment. The approach used here serves as a generic framework for mining dynamic changes in genome-scale protein interaction networks. PMID:23892477

  4. Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity

    PubMed Central

    Asnaashari, Mohammad; Moeini, Masoumeh

    2013-01-01

    Dentin hypersensitivity (DH) is a relatively common painful condition among dental problems. Although many studies have been performed regarding the diagnosis and treatment of DH, dental practitioners are still confused about the definite diagnosis and treatment.The use of lasers as a treatment for dentin hypersensitivity was first introduced in 1985.Laser treatment in dentin hypersensitivity is an interesting and controversial issue and many investigations have been done on its mechanism of action, advantages, and unclear points.The present literature review tries to go over the definition, diagnosis, etiology , predisposing factors, various laser types in the treatment of DH alone or in combination with topical desensitizing agents. Since a certain treatment has not yet introduced for dentin hypersensitivity, a combination of laser therapy and topical desensitizing factors ,can increase the success of the treatment compared with either treatments alone. PMID:25606300

  5. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

  6. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

  7. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

  8. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

  9. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...DEVICES Immunological Test Systems § 866.5500 Hypersensitivity...pneumonitis immunological test system. (a) Identification...pneumonitis immunological test system is a device that consists...with such dusts in the lung, immune complexes precipitate...

  10. A World Allergy Organization International Survey on Diagnostic Procedures and Therapies in Drug Allergy/Hypersensitivity

    PubMed Central

    Mirakian, Rita; Castells, Mariana; Pichler, Werner; Romano, Antonino; Bonadonna, Patrizia; Diana, Deleanu; Kowalski, Marek; Yanez, Anahi; Lleonart, Ramon; Sanchez-Borges, Mario; Demoly, Pascal

    2011-01-01

    Objective To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). Methods A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009. Results Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro–specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens–Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. Conclusions Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies. PMID:23268453

  11. HLA-B*5701 Screening for Hypersensitivity to Abacavir

    Microsoft Academic Search

    Simon Mallal; Elizabeth Phillips; Giampiero Carosi; Jean-Michel Molina; Cassy Workman; Eva Jägel-Guedes; Sorin Rugina; Oleg Kozyrev; Juan Flores Cid; Phillip Hay; David Nolan; Sara Hughes; Arlene Hughes; Susanna Ryan; Nicholas Fitch; Daren Thorborn; Alastair Benbow; Hôpital Saint Louis

    2010-01-01

    Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospec- tive HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir. Methods This double-blind, prospective, randomized study involved 1956 patients from 19 coun- tries, who were infected with human immunodeficiency virus type 1 and who had not

  12. Virus-induced silencing of WIPK and SIPK genes reduces resistance to a bacterial pathogen, but has no effect on the INF1-induced hypersensitive response (HR) in Nicotiana benthamiana

    Microsoft Academic Search

    P. C. Sharma; A. Ito; T. Shimizu; R. Terauchi; S. Kamoun; H. Saitoh

    2003-01-01

    Activation of two mitogen-activated protein kinases (MAPKs), wound-induced protein kinase (WIPK) and salicylic acid-induced protein kinase (SIPK), is one of the earliest responses that occur in tobacco plants that have been wounded, treated with pathogen-derived elicitors or challenged with avirulent pathogens. We isolated cDNAs for these MAPKs ( NbWIPKand NbSIPK) from Nicotiana benthamiana. The function of NbWIPK and NbSIPK in

  13. Closed-loop measurements of iso-response stimuli reveal dynamic nonlinear stimulus integration in the retina.

    PubMed

    Bölinger, Daniel; Gollisch, Tim

    2012-01-26

    Neurons often integrate information from multiple parallel signaling streams. How a neuron combines these inputs largely determines its computational role in signal processing. Experimental assessment of neuronal signal integration, however, is often confounded by cell-intrinsic nonlinear processes that arise after signal integration has taken place. To overcome this problem and determine how ganglion cells in the salamander retina integrate visual contrast over space, we used automated online analysis of recorded spike trains and closed-loop control of the visual stimuli to identify different stimulus patterns that give the same neuronal response. These iso-response stimuli revealed a threshold-quadratic transformation as a fundamental nonlinearity within the receptive field center. Moreover, for a subset of ganglion cells, the method revealed an additional dynamic nonlinearity that renders these cells particularly sensitive to spatially homogeneous stimuli. This function is shown to arise from a local inhibition-mediated dynamic gain control mechanism. PMID:22284187

  14. Gene response profiles for Daphnia pulex exposed to the environmental stressor cadmium reveals novel crustacean metallothioneins

    Microsoft Academic Search

    Joseph R Shaw; John K Colbourne; Jennifer C Davey; Stephen P Glaholt; Thomas H Hampton; Celia Y Chen; Carol L Folt; Joshua W Hamilton

    2007-01-01

    BACKGROUND: Genomic research tools such as microarrays are proving to be important resources to study the complex regulation of genes that respond to environmental perturbations. A first generation cDNA microarray was developed for the environmental indicator species Daphnia pulex, to identify genes whose regulation is modulated following exposure to the metal stressor cadmium. Our experiments revealed interesting changes in gene

  15. DNA Microarray Analysis of Anaerobic Methanosarcina Barkeri Reveals Responses to Heat Shock and Air Exposure

    SciTech Connect

    Zhang, Weiwen; Culley, David E.; Nie, Lei; Brockman, Fred J.

    2006-04-08

    Summary Methanosarcina barkeri can grow only under strictly anoxic conditions because enzymes in methane formation pathways of are very oxygen sensitive. However, it has been determined that M. barkeri can survive oxidative stress. To obtain further knowledge of cellular changes in M. barkeri in responsive to oxidative and other environmental stress, a first whole-genome M. barkeri oligonucleotide microarray was constructed according to the draft genome sequence that contains 5072 open reading frames (ORFs) and was used to investigate the global transcriptomic response of M. barkeri to oxidative stress and heat shock. The result showed that 552 genes in the M. barkeri genome were responsive to oxidative stress, while 177 genes responsive to heat-shock, respectively using a cut off of 2.5 fold change. Among them, 101 genes were commonly responsive to both environmental stimuli. In addition to various house-keeping genes, large number of functionally unknown genes (38-57% of total responsive genes) was regulated by both stress conditions. The result showed that the Hsp60 (GroEL) system, which was previously thought not present in archaea, was up-regulated and may play important roles in protein biogenesis in responsive to heat shock in M. barkeri. No gene encoding superoxide dismutase, catalase, nonspecific peroxidases or thioredoxin reductase was differentially expressed when subjected to oxidative stress. Instead, significant downregulation of house-keeping genes and up-regulation of genes encoding transposase was found in responsive to oxidative stress, suggesting that M. barkeri may be adopting a passive protective mechanism by slowing down cellular activities to survive the stress rather than activating a means against oxidative stress.

  16. Nonlinear V1 responses to natural scenes revealed by neural network analysis

    Microsoft Academic Search

    Ryan J. Prenger; Michael C.-K. Wu; Stephen V. David; Jack L. Gallant

    2004-01-01

    Abstract A key goal in the study of visual processing is to obtain a comprehensive,description of the relationship between,visual stimuli and neuronal responses. One way to guide the search for models is to use a general nonparametric regression algorithm, such as a neural network. We have developed,a multilayer feed-forward network,algorithm that can be used to characterize nonlinear stimulus-response mapping functions

  17. Transgenic AEQUORIN reveals organ-specific cytosolic Ca2+ responses to anoxia and Arabidopsis thaliana seedlings.

    PubMed

    Sedbrook, J C; Kronebusch, P J; Borisy, G G; Trewavas, A J; Masson, P H

    1996-05-01

    Using the transgenic AEQUORIN system, we showed that the cotyledons and leaves of Arabidopsis thaliana seedlings developed a biphasic luminescence response to anoxia, indicating changes in cytosolic Ca2+ levels. A fast and transient luminescence peak occurred within minutes of anoxia, followed by a second, prolonged luminescence response that lasted 1.5 to 4 h. The Ca2+ channel blockers Gd3+, La3+, and ruthenium red (RR) partially inhibited the first response and promoted a larger and earlier second response, suggesting different origins for these responses. Both Gd3+ and RR also partially inhibited anaerobic induction of alcohol dehydrogenase gene expression. However, although anaerobic alcohol dehydrogenase gene induction occurred in seedlings exposed to water-agar medium and in roots, related luminescence responses were absent. Upon return to normoxia, the luminescence of cotyledons, leaves, and roots dropped quickly, before increasing again in a Gd3+, La3+, ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-, and RR-sensitive fashion. PMID:8685265

  18. Transgenic AEQUORIN reveals organ-specific cytosolic Ca2+ responses to anoxia and Arabidopsis thaliana seedlings

    NASA Technical Reports Server (NTRS)

    Sedbrook, J. C.; Kronebusch, P. J.; Borisy, G. G.; Trewavas, A. J.; Masson, P. H.

    1996-01-01

    Using the transgenic AEQUORIN system, we showed that the cotyledons and leaves of Arabidopsis thaliana seedlings developed a biphasic luminescence response to anoxia, indicating changes in cytosolic Ca2+ levels. A fast and transient luminescence peak occurred within minutes of anoxia, followed by a second, prolonged luminescence response that lasted 1.5 to 4 h. The Ca2+ channel blockers Gd3+, La3+, and ruthenium red (RR) partially inhibited the first response and promoted a larger and earlier second response, suggesting different origins for these responses. Both Gd3+ and RR also partially inhibited anaerobic induction of alcohol dehydrogenase gene expression. However, although anaerobic alcohol dehydrogenase gene induction occurred in seedlings exposed to water-agar medium and in roots, related luminescence responses were absent. Upon return to normoxia, the luminescence of cotyledons, leaves, and roots dropped quickly, before increasing again in a Gd3+, La3+, ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-, and RR-sensitive fashion.

  19. Dentin hypersensitivity: Recent trends in management

    PubMed Central

    Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

    2010-01-01

    Dentinal hypersensitivity (DH) is a common clinical condition usually associated with exposed dentinal surfaces. It can affect patients of any age group and most commonly affects the canines and premolars of both the arches. This article concisely reviews the patho-physiology, mechanism and clinical management of the DH. Treatment of DH should start with an accurate diagnosis. Differential diagnosis should be made and all other probable causes should be excluded. An often neglected phase of clinical management of DH is the identification and treatment of the causative factors of DH. By removing the etiological factors, the condition can be even prevented from occurring or recurring. There are various treatment modalities available which can be used at home or may be professionally applied. The “at home” desensitizing agents include toothpastes, mouthwashes or chewing gums and they act by either occluding the dentinal tubules or blocking the neural transmission. This article also discusses the recent treatment options like bioglass, Portland cement, lasers and casein phosphopeptide. PMID:21217949

  20. Differential reproductive responses to stress reveal the role of life-history strategies within a species.

    PubMed

    Schultner, J; Kitaysky, A S; Gabrielsen, G W; Hatch, S A; Bech, C

    2013-11-22

    Life-history strategies describe that 'slow'- in contrast to 'fast'-living species allocate resources cautiously towards reproduction to enhance survival. Recent evidence suggests that variation in strategies exists not only among species but also among populations of the same species. Here, we examined the effect of experimentally induced stress on resource allocation of breeding seabirds in two populations with contrasting life-history strategies: slow-living Pacific and fast-living Atlantic black-legged kittiwakes. We tested the hypothesis that reproductive responses in kittiwakes under stress reflect their life-history strategies. We predicted that in response to stress, Pacific kittiwakes reduce investment in reproduction compared with Atlantic kittiwakes. We exposed chick-rearing kittiwakes to a short-term (3-day) period of increased exogenous corticosterone (CORT), a hormone that is released during food shortages. We examined changes in baseline CORT levels, parental care and effects on offspring. We found that kittiwakes from the two populations invested differently in offspring when facing stress. In response to elevated CORT, Pacific kittiwakes reduced nest attendance and deserted offspring more readily than Atlantic kittiwakes. We observed lower chick growth, a higher stress response in offspring and lower reproductive success in response to CORT implantation in Pacific kittiwakes, whereas the opposite occurred in the Atlantic. Our findings support the hypothesis that life-history strategies predict short-term responses of individuals to stress within a species. We conclude that behaviour and physiology under stress are consistent with trade-off priorities as predicted by life-history theory. We encourage future studies to consider the pivotal role of life-history strategies when interpreting inter-population differences of animal responses to stressful environmental events. PMID:24089339

  1. Differential reproductive responses to stress reveal the role of life-history strategies within a species

    PubMed Central

    Schultner, J.; Kitaysky, A. S.; Gabrielsen, G. W.; Hatch, S. A.; Bech, C.

    2013-01-01

    Life-history strategies describe that ‘slow’- in contrast to ‘fast’-living species allocate resources cautiously towards reproduction to enhance survival. Recent evidence suggests that variation in strategies exists not only among species but also among populations of the same species. Here, we examined the effect of experimentally induced stress on resource allocation of breeding seabirds in two populations with contrasting life-history strategies: slow-living Pacific and fast-living Atlantic black-legged kittiwakes. We tested the hypothesis that reproductive responses in kittiwakes under stress reflect their life-history strategies. We predicted that in response to stress, Pacific kittiwakes reduce investment in reproduction compared with Atlantic kittiwakes. We exposed chick-rearing kittiwakes to a short-term (3-day) period of increased exogenous corticosterone (CORT), a hormone that is released during food shortages. We examined changes in baseline CORT levels, parental care and effects on offspring. We found that kittiwakes from the two populations invested differently in offspring when facing stress. In response to elevated CORT, Pacific kittiwakes reduced nest attendance and deserted offspring more readily than Atlantic kittiwakes. We observed lower chick growth, a higher stress response in offspring and lower reproductive success in response to CORT implantation in Pacific kittiwakes, whereas the opposite occurred in the Atlantic. Our findings support the hypothesis that life-history strategies predict short-term responses of individuals to stress within a species. We conclude that behaviour and physiology under stress are consistent with trade-off priorities as predicted by life-history theory. We encourage future studies to consider the pivotal role of life-history strategies when interpreting inter-population differences of animal responses to stressful environmental events. PMID:24089339

  2. Response of swine spleen to Streptococcus suis infection revealed by transcription analysis

    PubMed Central

    2010-01-01

    Astract Background Streptococcus suis serotype 2 (SS2), a major swine pathogen and an emerging zoonotic agent, has greatly challenged global public health. Systematical information about host immune response to the infection is important for understanding the molecular mechanism of diseases. Results 104 and 129 unique genes were significantly up-regulated and down-regulated in the spleens of pigs infected with SS2 (WT). The up-regulated genes were principally related to immune response, such as genes involved in inflammatory response; acute-phase/immune response; cell adhesion and response to stress. The down-regulated genes were mainly involved in transcription, transport, material and energy metabolism which were representative of the reduced vital activity of SS2-influenced cells. Only a few genes showed significantly differential expression when comparing avirulent isogenic strain (?HP0197) with mock-infected samples. Conclusions Our findings indicated that highly pathogenic SS2 could persistently induce cytokines mainly by Toll-like receptor 2 (TLR2) pathway, and the phagocytosis-resistant bacteria could induce high level of cytokines and secrete toxins to destroy deep tissues, and cause meningitis, septicaemia, pneumonia, endocarditis, and arthritis. PMID:20937098

  3. EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness.

    PubMed

    Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

    2015-01-01

    Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly "domain general" conflict processing mechanisms, instead of conflict source specific effects. PMID:26169473

  4. EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness

    PubMed Central

    Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

    2015-01-01

    Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly “domain general” conflict processing mechanisms, instead of conflict source specific effects. PMID:26169473

  5. Experimental test for adaptive differentiation of ginseng populations reveals complex response to temperature

    PubMed Central

    Souther, Sara; Lechowicz, Martin J.; McGraw, James B.

    2012-01-01

    Background and Aims Local climatic adaptation can influence species' response to climate change. If populations within a species are adapted to local climate, directional change away from mean climatic conditions may negatively affect fitness of populations throughout the species' range. Methods Adaptive differentiation to temperature was tested for in American ginseng (Panax quinquefolius) by reciprocally transplanting individuals from two populations, originating at different elevations, among temperature treatments in a controlled growth chamber environment. Fitness-related traits were measured in order to test for a population × temperature treatment interaction, and key physiological and phenological traits were measured to explain population differences in response to temperature. Key Results Response to temperature treatments differed between populations, suggesting genetic differentiation of populations. However, the pattern of response of fitness-related variables generally did not suggest ‘home temperature’ advantage, as would be expected if populations were locally adapted to temperature alone. Conclusions Failure consistently to detect a ‘home temperature’ advantage response suggests that adaptation to temperature is complex, and environmental and biotic factors that naturally covary with temperature in the field may be critical to understanding the nature of adaptation to temperature. PMID:22811509

  6. Simultaneous dual-task performance reveals parallel response selection after practice

    NASA Technical Reports Server (NTRS)

    Hazeltine, Eliot; Teague, Donald; Ivry, Richard B.

    2002-01-01

    E. H. Schumacher, T. L. Seymour, J. M. Glass, D. E. Kieras, and D. E. Meyer (2001) reported that dual-task costs are minimal when participants are practiced and give the 2 tasks equal emphasis. The present research examined whether such findings are compatible with the operation of an efficient response selection bottleneck. Participants trained until they were able to perform both tasks simultaneously without interference. Novel stimulus pairs produced no reaction time costs, arguing against the development of compound stimulus-response associations (Experiment 1). Manipulating the relative onsets (Experiments 2 and 4) and durations (Experiments 3 and 4) of response selection processes did not lead to dual-task costs. The results indicate that the 2 tasks did not share a bottleneck after practice.

  7. Heterogeneous water table response to climate revealed by 60 years of ground water data

    NASA Astrophysics Data System (ADS)

    Weider, Kaitlyn; Boutt, David F.

    2010-12-01

    Recent findings suggest that climate change will lead to modifications in the timing and nature of precipitation, giving rise to an altered hydrologic cycle. The response of subsurface hydrology to decadal climate and longer-term climate change to date has been investigated via site specific analyses, modeling studies, and proxy analysis. Here we present the first instrumental long-term regional compilation and analysis of the water table response to the last 60 years of climate in New England. Ground water trends are calculated as normalized anomalies and analyzed with respect to regional compiled precipitation, temperature, and streamflow. The time-series display decadal patterns with ground water levels being more variable and lagging that of precipitation and streamflow pointing to site specific and non-linear response to changes in climate. Recent trends (i.e., last 10 years) suggest statistically significant increasing water tables, which could lead to a higher risk for flooding in New England.

  8. The TRPM8 channel forms a complex with the 5-HT(1B) receptor and phospholipase D that amplifies its reversal of pain hypersensitivity.

    PubMed

    Vinuela-Fernandez, Ignacio; Sun, Liting; Jerina, Helen; Curtis, John; Allchorne, Andrew; Gooding, Hayley; Rosie, Roberta; Holland, Pamela; Tas, Basak; Mitchell, Rory; Fleetwood-Walker, Sue

    2014-04-01

    Effective relief from chronic hypersensitive pain states remains an unmet need. Here we report the discovery that the TRPM8 ion channel, co-operating with the 5-HT(1B) receptor (5-HT(1B)R) in a subset of sensory afferents, exerts an influence at the spinal cord level to suppress central hypersensitivity in pain processing throughout the central nervous system. Using cell line models, ex vivo rat neural tissue and in vivo pain models, we assessed functional Ca(2+) fluorometric responses, protein:protein interactions, immuno-localisation and reflex pain behaviours, with pharmacological and molecular interventions. We report 5-HT(1B)R expression in many TRPM8-containing afferents and direct interaction of these proteins in a novel multi-protein signalling complex, which includes phospholipase D1 (PLD1). We provide evidence that the 5-HT(1B)R activates PLD1 to subsequently activate PIP 5-kinase and generate PIP2, an allosteric enhancer of TRPM8, achieving a several-fold increase in potency of TRPM8 activation. The enhanced activation responses of synaptoneurosomes prepared from spinal cord and cortical regions of animals with a chronic inflammatory pain state are inhibited by TRPM8 activators that were applied in vivo topically to the skin, an effect potentiated by co-administered 5-HT(1B)R agonists and attenuated by 5-HT(1B)R antagonists, while 5-HT(1B)R agents alone had no detectable effect. Corresponding results are seen when assessing reflex behaviours in inflammatory and neuropathic pain models. Control experiments with alternative receptor/TRP channel combinations reveal no such synergy. Identification of this novel receptor/effector/channel complex and its impact on nociceptive processing give new insights into possible strategies for enhanced analgesia in chronic pain. PMID:24269608

  9. Menthol suppresses laryngeal C-fiber hypersensitivity to cigarette smoke in a rat model of gastroesophageal reflux disease: the role of TRPM8.

    PubMed

    Liu, Bi-Yu; Lin, Yu-Jung; Lee, Hung-Fu; Ho, Ching-Yin; Ruan, Ting; Kou, Yu Ru

    2015-03-01

    Patients with gastroesophageal reflux disease (GERD) display enhanced laryngeal reflex reactivity to stimuli that may be due to sensitization of the laryngeal C-fibers by acid and pepsin. Menthol, a ligand of transient receptor potential melastatin-8 (TRPM8), relieves throat irritation. However, the possibility that GERD induces laryngeal C-fiber hypersensitivity to cigarette smoke (CS) and that menthol suppresses this event has not been investigated. We delivered CS into functionally isolated larynxes of 160 anesthetized rats. Laryngeal pH 5-pepsin treatment, but not pH 5-denatured pepsin, augmented the apneic response to CS, which was blocked by denervation or perineural capsaicin treatment (a procedure that blocks the conduction of C fibers) of the superior laryngeal nerves. This augmented apnea was partially attenuated by capsazepine [an transient receptor potential vanilloid 1 (TRPV1) antagonist], SB-366791 (a TRPV1 antagonist), and HC030031 [a transient receptor potential ankyrin 1 (TRPA1) antagonist] and was completely prevented by a combination of TRPV1 and TRPA1 antagonists. Local application of menthol significantly suppressed the augmented apnea and this effect was reversed by pretreatment with AMTB (a TRPM8 antagonist). Our electrophysiological studies consistently revealed that laryngeal pH 5-pepsin treatment increased the sensitivity of laryngeal C-fibers to CS. Likewise, menthol suppressed this laryngeal C-fiber hypersensitivity and its effect could be reversed by pretreatment with AMTB. Our results suggest that laryngeal pH 5-pepsin treatment increases sensitivity to CS of both TRPV1 and TRPA1, which are presumably located at the terminals of laryngeal C-fibers. This sensory sensitization leads to enhanced laryngeal reflex reactivity and augmentation of the laryngeal C-fiber responses to CS, which can be suppressed by menthol acting via TRPM8. PMID:25539933

  10. Dissecting CD8+ NKT Cell Responses to Listeria Infection Reveals a Component of Innate Resistance.

    PubMed

    Seregin, Sergey S; Chen, Grace Y; Laouar, Yasmina

    2015-08-01

    A small pool of NK1.1(+) CD8(+) T cells is harbored among the conventional CD8(+) T cell compartment. Conclusions drawn from the analysis of immune responses mediated by cytotoxic CD8(+) T cells are often based on the total population, which includes these contaminating NK1.1(+) CD8(+) T cells. An unresolved question is whether NK1.1(+) CD8(+) cells are conventional T cells that acquire NK1.1 expression upon activation or delineation into memory phenotype or whether they are a distinct cell population that induces immune responses in a different manner than conventional T cells. To address this question, we used the Listeria monocytogenes model of infection and followed CD8(+) NK1.1(+) T cells and NK1.1(-) CD8(+) T cells during each phase of the immune response: innate, effector, and memory. Our central finding is that CD8(+) NK1.1(+) cells and conventional NK1.1(-) CD8(+) T cells both contribute to the adaptive immune response to Listeria, but only CD8(+) NK1.1(+) cells were equipped with the ability to provide a rapid innate immune response, as demonstrated by early and Ag-independent IFN-? production, granzyme B expression, and degranulation. More importantly, purified conventional CD8(+) T cells alone, in the absence of any contaminating CD8(+) NK1.1(+) cells, were not sufficient to provide early protection to lethally infected mice. These results highlight the role of CD8(+) NK1.1(+) T cells in mounting early innate responses that are important for host defense and support the therapeutic potential of this subset to improve the effectiveness of protective immunity. PMID:26116500

  11. Linear response in infinite nuclear matter as a tool to reveal finite size instabilities

    E-print Network

    A. Pastore; K. Bennaceur; D. Davesne; J. Meyer

    2011-10-28

    Nuclear effective interactions are often modelled by simple analytical expressions such as the Skyrme zero-range force. This effective interaction depends on a limited number of parameters that are usually fitted using experimental data obtained from doubly magic nuclei. It was recently shown that many Skyrme functionals lead to the appearance of instabilities, in particular when symmetries are broken, for example unphysical polarization of odd-even or rotating nuclei. In this article, we show how the formalism of the linear response in infinite nuclear matter can be used to predict and avoid the regions of parameters that are responsible for these unphysical instabilities.

  12. Genome wide transcriptome analysis reveals ABA mediated response in Arabidopsis during gold (AuCl?4) treatment

    PubMed Central

    Shukla, Devesh; Krishnamurthy, Sneha; Sahi, Shivendra V.

    2014-01-01

    The unique physico-chemical properties of gold nanoparticles (AuNPs) find manifold applications in diagnostics, medicine and catalysis. Chemical synthesis produces reactive AuNPs and generates hazardous by-products. Alternatively, plants can be utilized to produce AuNPs in an eco-friendly manner. To better control the biosynthesis of AuNPs, we need to first understand the detailed molecular response induced by AuCl?4 In this study, we carried out global transcriptome analysis in root tissue of Arabidopsis grown for 12- h in presence of gold solution (HAuCl4) using the novel unbiased Affymetrix exon array. Transcriptomics analysis revealed differential regulation of a total of 704 genes and 4900 exons. Of these, 492 and 212 genes were up- and downregulated, respectively. The validation of the expressed key genes, such as glutathione-S-transferases, auxin responsive genes, cytochrome P450 82C2, methyl transferases, transducin (G protein beta subunit), ERF transcription factor, ABC, and MATE transporters, was carried out through quantitative RT-PCR. These key genes demonstrated specific induction under AuCl4? treatment relative to other heavy metals, suggesting a unique plant-gold interaction. GO enrichment analysis reveals the upregulation of processes like oxidative stress, glutathione binding, metal binding, transport, and plant hormonal responses. Changes predicted in biochemical pathways indicated major modulation in glutathione mediated detoxification, flavones and derivatives, and plant hormone biosynthesis. Motif search analysis identified a highly significant enriched motif, ACGT, which is an abscisic acid responsive core element (ABRE), suggesting the possibility of ABA- mediated signaling. Identification of abscisic acid response element (ABRE) points to the operation of a predominant signaling mechanism in response to AuCl?4 exposure. Overall, this study presents a useful picture of plant-gold interaction with an identification of candidate genes involved in nanogold synthesis. PMID:25506348

  13. DNA microarray analysis of anaerobic Methanosarcina barkeri reveals responses to heat shock and air exposure

    Microsoft Academic Search

    Weiwen Zhang; David E. Culley; Lei Nie; Fred J. Brockman

    2006-01-01

    Methanosarcina barkeri is a methanogenic archaeon that can digest cellulose and other polysaccharides to produce methane. It can only grow under strictly anoxic conditions, but which can survive air exposure. To obtain further knowledge of cellular changes occurring in M. barkeri in response to air exposure and other environmental stresses, we constructed the first oligonucleotide microarray for M. barkeri and

  14. Multimodal Stimulation of Colorado Potato Beetle Reveals Modulation of Pheromone Response by Yellow Light

    PubMed Central

    Otálora-Luna, Fernando; Dickens, Joseph C.

    2011-01-01

    Orientation of insects to host plants and conspecifics is the result of detection and integration of chemical and physical cues present in the environment. Sensory organs have evolved to be sensitive to important signals, providing neural input for higher order multimodal processing and behavioral output. Here we report experiments to determine decisions made by Colorado potato beetle (CPB), Leptinotarsa decemlineata, in response to isolated stimuli and multimodal combinations of signals on a locomotion compensator. Our results show that in complete darkness and in the absence of other stimuli, pheromonal stimulation increases attraction behavior of CPB as measured in oriented displacement and walking speed. However, orientation to the pheromone is abolished when presented with the alternative stimulation of a low intensity yellow light in a dark environment. The ability of the pheromone to stimulate these diurnal beetles in the dark in the absence of other stimuli is an unexpected but interesting observation. The predominance of the phototactic response over that to pheromone when low intensity lights were offered as choices seems to confirm the diurnal nature of the insect. The biological significance of the response to pheromone in the dark is unclear. The phototactic response will play a key role in elucidating multimodal stimulation in the host-finding process of CPB, and perhaps other insects. Such information might be exploited in the design of applications to attract and trap CPB for survey or control purposes and other insect pests using similar orientation mechanisms. PMID:21695167

  15. Arabidopsis thaliana mutant lpsi reveals impairment in the root responses to local phosphate availability.

    PubMed

    Karthikeyan, Athikkattuvalasu S; Jain, Ajay; Nagarajan, Vinay K; Sinilal, Bhaskaran; Sahi, Shivendra V; Raghothama, Kashchandra G

    2014-04-01

    Phosphate (Pi) deficiency triggers local Pi sensing-mediated inhibition of primary root growth and development of root hairs in Arabidopsis (Arabidopsis thaliana). Generation of activation-tagged T-DNA insertion pools of Arabidopsis expressing the luciferase gene (LUC) under high-affinity Pi transporter (Pht1;4) promoter, is an efficient approach for inducing genetic variations that are amenable for visual screening of aberrations in Pi deficiency responses. Putative mutants showing altered LUC expression during Pi deficiency were identified and screened for impairment in local Pi deficiency-mediated inhibition of primary root growth. An isolated mutant was analyzed for growth response, effects of Pi deprivation on Pi content, primary root growth, root hair development, and relative expression levels of Pi starvation-responsive (PSR) genes, and those implicated in starch metabolism and Fe and Zn homeostasis. Pi deprived local phosphate sensing impaired (lpsi) mutant showed impaired primary root growth and attenuated root hair development. Although relative expression levels of PSR genes were comparable, there were significant increases in relative expression levels of IRT1, BAM3 and BAM5 in Pi deprived roots of lpsi compared to those of the wild-type. Better understanding of molecular responses of plants to Pi deficiency or excess will help to develop suitable remediation strategies for soils with excess Pi, which has become an environmental concern. Hence, lpsi mutant will serve as a valuable tool in identifying molecular mechanisms governing adaptation of plants to Pi deficiency. PMID:24561248

  16. Adaptive responses reveal contemporary and future ecotypes in a desert shrub

    USGS Publications Warehouse

    Richardson, Bryce A.; Kitchen, Stanley G.; Pendleton, Rosemary L.; Pendleton, Burton K.; Germino, Matthew J.; Rehfeldt, Gerald E.; Meyer, Susan E.

    2014-01-01

    Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species–climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep clines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are needed to inform restoration and management planning. We propose four transfer zones in blackbrush that correspond to areas currently dominated by cool-adapted and warm-adapted ecotypes in each of the two ecoregions.

  17. Meta-analysis reveals profound responses of plant traits to glacial CO2 levels

    PubMed Central

    Temme, A A; Cornwell, W K; Cornelissen, J H C; Aerts, R

    2013-01-01

    A general understanding of the links between atmospheric CO2 concentration and the functioning of the terrestrial biosphere requires not only an understanding of plant trait responses to the ongoing transition to higher CO2 but also the legacy effects of past low CO2. An interesting question is whether the transition from current to higher CO2 can be thought of as a continuation of the past trajectory of low to current CO2 levels. Determining this trajectory requires quantifying the effect sizes of plant response to low CO2. We performed a meta-analysis of low CO2 growth experiments on 34 studies with 54 species. We quantified how plant traits vary at reduced CO2 levels and whether C3 versus C4 and woody versus herbaceous plant species respond differently. At low CO2, plant functioning changed drastically: on average across all species, a 50% reduction in current atmospheric CO2 reduced net photosynthesis by 38%; increased stomatal conductance by 60% and decreased intrinsic water use efficiency by 48%. Total plant dry biomass decreased by 47%, while specific leaf area increased by 17%. Plant types responded similarly: the only significant differences being no increase in SLA for C4 species and a 16% smaller decrease in biomass for woody C3 species at glacial CO2. Quantitative comparison of low CO2 effect sizes to those from high CO2 studies showed that the magnitude of response of stomatal conductance, water use efficiency and SLA to increased CO2 can be thought of as continued shifts along the same line. However, net photosynthesis and dry weight responses to low CO2 were greater in magnitude than to high CO2. Understanding the causes for this discrepancy can lead to a general understanding of the links between atmospheric CO2 and plant responses with relevance for both the past and the future. PMID:24340192

  18. Foreign Body or Hypersensitivity Granuloma of the Inner Ear following Cochlear Implantation. One possible cause of a soft failure?

    PubMed Central

    Nadol, Joseph B.; Eddington, Donald K.; Burgess, Barbara J.

    2014-01-01

    Hypothesis A tissue response in the form of foreign body or a hypersensitivity reaction to cochlear implantation is common and may be one possible cause of a soft failure of cochlear implantation. Background Following a successful cochlear implantation, delayed failure may occur. The causes of a “soft” failure, that is one in which device malfunction cannot be proven, are unknown. Methods The histopathology of the temporal bones of a patient who in life had suffered a soft failure following cochlear implantation was described. In addition, the temporal bones of 8 other subjects who in life had undergone cochlear implantation were studied for evidence of a foreign body or hypersensitivity reaction. Results In the case report, a necrotizing granulomatous giant cell reaction surrounded the cochlear implant electrode track through the mastoid, middle ear, and into the cochlea in both ears. There was osteolysis of the cribrose area, otic capsule and bone between the facial nerve and cochlea, and destruction of the organ of Corti and spiral ganglion. In the additional 8 cases studied, a similar, although less pronounced, foreign body or hypersensitivity reaction was seen in 6 (75%) of the cases. Conclusions A foreign body or hypersensitivity reaction in the form of giant cells and lymphocytic cell infiltration is common following cochlear implantation and may be one possible cause of soft failure. PMID:18997635

  19. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans

    SciTech Connect

    Tamura, Akitoshi, E-mail: akitoshi-tamura@ds-pharma.co.jp; Miyawaki, Izuru; Yamada, Toru; Kimura, Juki; Funabashi, Hitoshi

    2013-08-15

    It is important to evaluate the potential of drug hypersensitivity as well as other adverse effects during the preclinical stage of the drug development process, but validated methods are not available yet. In the present study we examined whether it would be possible to develop a new predictive model of drug hypersensitivity using Brown Norway (BN) rats. As representative drugs with hypersensitivity potential in humans, phenytoin (PHT), carbamazepine (CBZ), amoxicillin (AMX), and sulfamethoxazole (SMX) were orally administered to BN rats for 28 days to investigate their effects on these animals by examinations including observation of clinical signs, hematology, determination of serum IgE levels, histology, and flow cytometric analysis. Skin rashes were not observed in any animals treated with these drugs. Increases in the number of circulating inflammatory cells and serum IgE level did not necessarily occur in the animals treated with these drugs. However, histological examination revealed that germinal center hyperplasia was commonly induced in secondary lymphoid organs/tissues in the animals treated with these drugs. In cytometric analysis, changes in proportions of lymphocyte subsets were noted in the spleen of the animals treated with PHT or CBZ during the early period of administration. The results indicated that the potential of drug hypersensitivity was identified in BN rat by performing histological examination of secondary lymphoid organs/tissues. Data obtained herein suggested that drugs with hypersensitivity potential in humans gained immune reactivity in BN rat, and the germinal center hyperplasia induced by administration of these drugs may serve as a predictive biomarker for drug hypersensitivity occurrence. - Highlights: • We tested Brown Norway rats as a candidate model for predicting drug hypersensitivity. • The allergic drugs did not induce skin rash, whereas D-penicillamine did so in the rats. • Some of allergic drugs increased inflammatory cells and IgE, but the others did not. • The allergic drugs commonly induced germinal center hyperplasia in lymphoid tissues. • Some of these allergic drugs transiently increased CD4{sup +}CD25{sup +} T cells in the spleen.

  20. Plasma proteome response to severe burn injury revealed by 18O-labeled "universal" reference-based quantitative proteomics.

    PubMed

    Qian, Wei-Jun; Petritis, Brianne O; Kaushal, Amit; Finnerty, Celeste C; Jeschke, Marc G; Monroe, Matthew E; Moore, Ronald J; Schepmoes, Athena A; Xiao, Wenzhong; Moldawer, Lyle L; Davis, Ronald W; Tompkins, Ronald G; Herndon, David N; Camp, David G; Smith, Richard D

    2010-09-01

    A burn injury represents one of the most severe forms of human trauma and is responsible for significant mortality worldwide. Here, we present the first quantitative proteomics investigation of the blood plasma proteome response to severe burn injury by comparing the plasma protein concentrations of 10 healthy control subjects with those of 15 severe burn patients at two time-points following the injury. The overall analytical strategy for this work integrated immunoaffinity depletion of the 12 most abundant plasma proteins with cysteinyl-peptide enrichment-based fractionation prior to LC-MS analyses of individual patient samples. Incorporation of an 18O-labeled "universal" reference among the sample sets enabled precise relative quantification across samples. In total, 313 plasma proteins confidently identified with two or more unique peptides were quantified. Following statistical analysis, 110 proteins exhibited significant abundance changes in response to the burn injury. The observed changes in protein concentrations suggest significant inflammatory and hypermetabolic response to the injury, which is supported by the fact that many of the identified proteins are associated with acute phase response signaling, the complement system, and coagulation system pathways. The regulation of approximately 35 proteins observed in this study is in agreement with previous results reported for inflammatory or burn response, but approximately 50 potentially novel proteins previously not known to be associated with burn response or inflammation are also found. Elucidating proteins involved in the response to severe burn injury may reveal novel targets for therapeutic interventions as well as potential predictive biomarkers for patient outcomes such as multiple organ failure. PMID:20698492

  1. Neural responses to visual scenes reveals inconsistencies between fMRI adaptation and multivoxel pattern analysis.

    PubMed

    Epstein, Russell A; Morgan, Lindsay K

    2012-03-01

    Human observers can recognize real-world visual scenes with great efficiency. Cortical regions such as the parahippocampal place area (PPA) and retrosplenial complex (RSC) have been implicated in scene recognition, but the specific representations supported by these regions are largely unknown. We used functional magnetic resonance imaging adaptation (fMRIa) and multi-voxel pattern analysis (MVPA) to explore this issue, focusing on whether the PPA and RSC represent scenes in terms of general categories, or as specific scenic exemplars. Subjects were scanned while viewing images drawn from 10 outdoor scene categories in two scan runs and images of 10 familiar landmarks from their home college campus in two scan runs. Analyses of multi-voxel patterns revealed that the PPA and RSC encoded both category and landmark information, with a slight advantage for landmark coding in RSC. fMRIa, on the other hand, revealed a very different picture: both PPA and RSC adapted when landmark information was repeated, but category adaptation was only observed in a small subregion of the left PPA. These inconsistencies between the MVPA and fMRIa data suggests that these two techniques interrogate different aspects of the neuronal code. We propose three hypotheses about the mechanisms that might underlie adaptation and multi-voxel signals. PMID:22001314

  2. The cortical analysis of speech-specific temporal structure revealed by responses to sound quilts.

    PubMed

    Overath, Tobias; McDermott, Josh H; Zarate, Jean Mary; Poeppel, David

    2015-06-01

    Speech contains temporal structure that the brain must analyze to enable linguistic processing. To investigate the neural basis of this analysis, we used sound quilts, stimuli constructed by shuffling segments of a natural sound, approximately preserving its properties on short timescales while disrupting them on longer scales. We generated quilts from foreign speech to eliminate language cues and manipulated the extent of natural acoustic structure by varying the segment length. Using functional magnetic resonance imaging, we identified bilateral regions of the superior temporal sulcus (STS) whose responses varied with segment length. This effect was absent in primary auditory cortex and did not occur for quilts made from other natural sounds or acoustically matched synthetic sounds, suggesting tuning to speech-specific spectrotemporal structure. When examined parametrically, the STS response increased with segment length up to ?500 ms. Our results identify a locus of speech analysis in human auditory cortex that is distinct from lexical, semantic or syntactic processes. PMID:25984889

  3. Genome Wide Binding Site Analysis Reveals Transcriptional Coactivation of Cytokinin-Responsive Genes by DELLA Proteins

    PubMed Central

    Marín-de la Rosa, Nora; Pfeiffer, Anne; Hill, Kristine; Locascio, Antonella; Bhalerao, Rishikesh P.; Miskolczi, Pal; Grřnlund, Anne L.; Wanchoo-Kohli, Aakriti; Thomas, Stephen G.; Bennett, Malcolm J.; Lohmann, Jan U.; Blázquez, Miguel A.; Alabadí, David

    2015-01-01

    The ability of plants to provide a plastic response to environmental cues relies on the connectivity between signaling pathways. DELLA proteins act as hubs that relay environmental information to the multiple transcriptional circuits that control growth and development through physical interaction with transcription factors from different families. We have analyzed the presence of one DELLA protein at the Arabidopsis genome by chromatin immunoprecipitation coupled to large-scale sequencing and we find that it binds at the promoters of multiple genes. Enrichment analysis shows a strong preference for cis elements recognized by specific transcription factor families. In particular, we demonstrate that DELLA proteins are recruited by type-B ARABIDOPSIS RESPONSE REGULATORS (ARR) to the promoters of cytokinin-regulated genes, where they act as transcriptional co-activators. The biological relevance of this mechanism is underpinned by the necessity of simultaneous presence of DELLAs and ARRs to restrict root meristem growth and to promote photomorphogenesis. PMID:26134422

  4. Genome Wide Binding Site Analysis Reveals Transcriptional Coactivation of Cytokinin-Responsive Genes by DELLA Proteins.

    PubMed

    Marín-de la Rosa, Nora; Pfeiffer, Anne; Hill, Kristine; Locascio, Antonella; Bhalerao, Rishikesh P; Miskolczi, Pal; Grřnlund, Anne L; Wanchoo-Kohli, Aakriti; Thomas, Stephen G; Bennett, Malcolm J; Lohmann, Jan U; Blázquez, Miguel A; Alabadí, David

    2015-07-01

    The ability of plants to provide a plastic response to environmental cues relies on the connectivity between signaling pathways. DELLA proteins act as hubs that relay environmental information to the multiple transcriptional circuits that control growth and development through physical interaction with transcription factors from different families. We have analyzed the presence of one DELLA protein at the Arabidopsis genome by chromatin immunoprecipitation coupled to large-scale sequencing and we find that it binds at the promoters of multiple genes. Enrichment analysis shows a strong preference for cis elements recognized by specific transcription factor families. In particular, we demonstrate that DELLA proteins are recruited by type-B ARABIDOPSIS RESPONSE REGULATORS (ARR) to the promoters of cytokinin-regulated genes, where they act as transcriptional co-activators. The biological relevance of this mechanism is underpinned by the necessity of simultaneous presence of DELLAs and ARRs to restrict root meristem growth and to promote photomorphogenesis. PMID:26134422

  5. Multivariate genetic analysis of plant responses to water deficit and high temperature revealed contrasting adaptive strategies

    PubMed Central

    Vasseur, François; Bontpart, Thibaut; Dauzat, Myriam; Granier, Christine; Vile, Denis

    2014-01-01

    How genetic factors control plant performance under stressful environmental conditions is a central question in ecology and for crop breeding. A multivariate framework was developed to examine the genetic architecture of performance-related traits in response to interacting environmental stresses. Ecophysiological and life history traits were quantified in the Arabidopsis thaliana Ler×Cvi mapping population exposed to constant soil water deficit and high air temperature. The plasticity of the genetic variance–covariance matrix (G-matrix) was examined using mixed-effects models after regression into principal components. Quantitative trait locus (QTL) analysis was performed on the predictors of genotype effects and genotype by environment interactions (G×E). Three QTLs previously identified for flowering time had antagonistic G×E effects on carbon acquisition and the other traits (phenology, growth, leaf morphology, and transpiration). This resulted in a size-dependent response of water use efficiency (WUE) to high temperature but not soil water deficit, indicating that most of the plasticity of carbon acquisition and WUE to temperature is controlled by the loci that control variation of development, size, growth, and transpiration. A fourth QTL, MSAT2.22, controlled the response of carbon acquisition to specific combinations of watering and temperature irrespective of plant size and development, growth, and transpiration rate, which resulted in size-independent plasticity of WUE. These findings highlight how the strategies to optimize plant performance may differ in response to water deficit and high temperature (or their combination), and how different G×E effects could be targeted to improve plant tolerance to these stresses. PMID:25246443

  6. Phosphoproteomic Analyses Reveal Early Signaling Events in the Osmotic Stress Response1[W][OPEN

    PubMed Central

    E. Stecker, Kelly; Minkoff, Benjamin B.; Sussman, Michael R.

    2014-01-01

    Elucidating how plants sense and respond to water loss is important for identifying genetic and chemical interventions that may help sustain crop yields in water-limiting environments. Currently, the molecular mechanisms involved in the initial perception and response to dehydration are not well understood. Modern mass spectrometric methods for quantifying changes in the phosphoproteome provide an opportunity to identify key phosphorylation events involved in this process. Here, we have used both untargeted and targeted isotope-assisted mass spectrometric methods of phosphopeptide quantitation to characterize proteins in Arabidopsis (Arabidopsis thaliana) whose degree of phosphorylation is rapidly altered by hyperosmotic treatment. Thus, protein phosphorylation events responsive to 5 min of 0.3 m mannitol treatment were first identified using 15N metabolic labeling and untargeted mass spectrometry with a high-resolution ion-trap instrument. The results from these discovery experiments were then validated using targeted Selected Reaction Monitoring mass spectrometry with a triple quadrupole. Targeted Selected Reaction Monitoring experiments were conducted with plants treated under nine different environmental perturbations to determine whether the phosphorylation changes were specific for osmosignaling or involved cross talk with other signaling pathways. The results indicate that regulatory proteins such as members of the mitogen-activated protein kinase family are specifically phosphorylated in response to osmotic stress. Proteins involved in 5? messenger RNA decapping and phosphatidylinositol 3,5-bisphosphate synthesis were also identified as targets of dehydration-induced phosphoregulation. The results of these experiments demonstrate the utility of targeted phosphoproteomic analysis in understanding protein regulation networks and provide new insight into cellular processes involved in the osmotic stress response. PMID:24808101

  7. Correlation of transcriptomic responses and metal bioaccumulation in Mytilus edulis L. reveals early indicators of stress.

    PubMed

    Poynton, Helen C; Robinson, William E; Blalock, Bonnie J; Hannigan, Robyn E

    2014-10-01

    Marine biomonitoring programs in the U.S. and Europe have historically relied on monitoring tissue concentrations of bivalves to monitor contaminant levels and ecosystem health. By integrating 'omic methods with these tissue residue approaches we can uncover mechanistic insight to link tissue concentrations to potential toxic effects. In an effort to identify novel biomarkers and better understand the molecular toxicology of metal bioaccumulation in bivalves, we exposed the blue mussel, Mytilus edulis L., to sub-lethal concentrations (0.54 ?M) of cadmium, lead, and a Cd+Pb mixture. Metal concentrations were measured in gill tissues at 1, 2, and 4 weeks, and increased linearly over the 4 week duration. In addition, there was evidence that Pb interfered with Cd uptake in the mixture treatment. Using a 3025 sequence microarray for M. edulis, we performed transcriptomic analysis, identifying 57 differentially expressed sequences. Hierarchical clustering of these sequences successfully distinguished the different treatment groups demonstrating that the expression profiles were reproducible among the treatments. Enrichment analysis of gene ontology terms identified several biological processes that were perturbed by the treatments, including nucleoside phosphate biosynthetic processes, mRNA metabolic processes, and response to stress. To identify transcripts whose expression level correlated with metal bioaccumulation, we performed Pearson correlation analysis. Several transcripts correlated with gill metal concentrations including mt10, mt20, and contig 48, an unknown transcript containing a wsc domain. In addition, three transcripts directly involved in the unfolded protein response (UPR) were induced in the metal treatments at 2 weeks and were further up-regulated at 4 weeks. Overall, correlation of tissue concentrations and gene expression responses indicates that as mussels accumulate higher concentrations of metals, initial stress responses are mobilized to protect tissues. However, given the role of UPR in apoptosis, it serves as an early indicator of stress, which once overwhelmed will result in adverse physiological effects. PMID:25016106

  8. Exposure to natural pathogens reveals costly aphid response to fungi but not bacteria

    PubMed Central

    Barribeau, Seth M; Parker, Benjamin J; Gerardo, Nicole M

    2014-01-01

    Immune responses are costly, causing trade-offs between defense and other host life history traits. Aphids present a special system to explore the costs associated with immune activation since they are missing several humoral and cellular mechanisms thought important for microbial resistance, and it is unknown whether they have alternative, novel immune responses to deal with microbial threat. Here we expose pea aphids to an array of heat-killed natural pathogens, which should stimulate immune responses without pathogen virulence, and measure changes in life-history traits. We find significant reduction in lifetime fecundity upon exposure to two fungal pathogens, but not to two bacterial pathogens. This finding complements recent genomic and immunological studies indicating that pea aphids are missing mechanisms important for bacterial resistance, which may have important implications for how aphids interact with their beneficial bacterial symbionts. In general, recent exploration of the immune systems of non-model invertebrates has called into question the generality of our current picture of insect immunity. Our data highlight that taking an ecological approach and measuring life-history traits to a broad array of pathogens provides valuable information that can complement traditional approaches. PMID:24634732

  9. The heterogeneity of human antibody responses to vaccinia virus revealed through use of focused protein arrays

    PubMed Central

    Duke-Cohan, Jonathan S.; Wollenick, Kristin; Witten, Elizabeth A.; Seaman, Michael S.; Baden, Lindsey R.; Dolin, Raphael; Reinherz, Ellis L.

    2009-01-01

    The renewed interest in strategies to combat infectious agents with epidemic potential has led to a re-examination of vaccination protocols against smallpox. To help define which antigens elucidate a human antibody response, we have targeted proteins known or predicted to be presented on the surface of the intracellular mature virion (IMV) or the extracellular enveloped virion (EEV). The predicted ectodomains were expressed in a mammalian in vitro coupled transcription/translation reaction using tRNAlys precharged with lysine-?-biotin followed by solid phase immobilization on 384 well neutravidin-coated plates. The generated array is highly specific and sensitive in a microELISA format. By comparison of binding of vaccinia-immune sera to the reticulocyte lysate-produced proteins and to secreted post-translationally-modified proteins, we demonstrate that for several proteins including the EEV proteins B5 and A33, proper recognition is dependent upon appropriate folding, with little dependence upon glycosylation per se. We further demonstrate that the humoral immune response to vaccinia among different individuals is not uniform in specificity or strength, as different IMV and EEV targets predominate within the group of immunogenic proteins. This heterogeneity likely results from the diversity of HLA Class II alleles and CD4 T helper cell epitopes stimulating B cell antibody production. Our findings have important implications both for design of new recombinant subunit vaccines as well as for methods of assaying the human antibody response utilizing recombinant proteins produced in vitro. PMID:19146908

  10. Digital Quantification of Gene Expression in Sequential Breast Cancer Biopsies Reveals Activation of an Immune Response

    PubMed Central

    Jeselsohn, Rinath M.; Werner, Lillian; Regan, Meredith M.; Fatima, Aquila; Gilmore, Lauren; Collins, Laura C.; Beck, Andrew H.; Bailey, Shannon T.; He, Housheng Hansen; Buchwalter, Gilles; Brown, Myles; Iglehart, J. Dirk; Richardson, Andrea; Come, Steven E.

    2013-01-01

    Advancements in molecular biology have unveiled multiple breast cancer promoting pathways and potential therapeutic targets. Large randomized clinical trials remain the ultimate means of validating therapeutic efficacy, but they require large cohorts of patients and are lengthy and costly. A useful approach is to conduct a window of opportunity study in which patients are exposed to a drug pre-surgically during the interval between the core needle biopsy and the definitive surgery. These are non-therapeutic studies and the end point is not clinical or pathological response but rather evaluation of molecular changes in the tumor specimens that can predict response. However, since the end points of the non-therapeutic studies are biologic, it is critical to first define the biologic changes that occur in the absence of treatment. In this study, we compared the molecular profiles of breast cancer tumors at the time of the diagnostic biopsy versus the definitive surgery in the absence of any intervention using the Nanostring nCounter platform. We found that while the majority of the transcripts did not vary between the two biopsies, there was evidence of activation of immune related genes in response to the first biopsy and further investigations of the immune changes after a biopsy in early breast cancer seem warranted. PMID:23741308

  11. A novel phototropic response to red light is revealed in microgravity.

    PubMed

    Millar, Katherine D L; Kumar, Prem; Correll, Melanie J; Mullen, Jack L; Hangarter, Roger P; Edelmann, Richard E; Kiss, John Z

    2010-05-01

    The aim of this study was to investigate phototropism in plants grown in microgravity conditions without the complications of a 1-g environment. Experiments performed on the International Space Station (ISS) were used to explore the mechanisms of both blue-light- and red-light-induced phototropism in plants. This project utilized the European Modular Cultivation System (EMCS), which has environmental controls for plant growth as well as centrifuges for gravity treatments used as a 1-g control. Images captured from video tapes were used to analyze the growth, development, and curvature of Arabidopsis thaliana plants that developed from seed in space. A novel positive phototropic response to red light was observed in hypocotyls of seedlings that developed in microgravity. This response was not apparent in seedlings grown on Earth or in the 1-g control during the space flight. In addition, blue-light-based phototropism had a greater response in microgravity compared with the 1-g control. Although flowering plants are generally thought to lack red light phototropism, our data suggest that at least some flowering plants may have retained a red light sensory system for phototropism. Thus, this discovery may have important implications for understanding the evolution of light sensory systems in plants. PMID:20298479

  12. Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells

    PubMed Central

    2011-01-01

    Background The small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGF? signaling and activation of the amino acid restriction response (AAR) have been linked to HF transcriptional control of a number of ECM components and amelioration of fibrosis and alleviation of autoimmune disease by regulation of Th17 cell differentiation, respectively. The aim of this study was to generate a global expression profile of HF targets in epithelial cells to identify potential mediators of HF function in this cell type. Results We report that HF modulation of the expression of the ECM remodeling protein Mmp13 in epithelial cells is separable from previously reported effects of HF on TGF? signal inhibition, and use microarray expression analysis to correlate this with transcriptional responses characteristic of the Integrated Stress Response (ISR). Conclusions Our findings suggest activation of the ISR may be a common mechanism underlying HF biological effects. PMID:21974968

  13. Analysis of Global Gene Expression in Brachypodium distachyon Reveals Extensive Network Plasticity in Response to Abiotic Stress

    PubMed Central

    Priest, Henry D.; Fox, Samuel E.; Rowley, Erik R.; Murray, Jessica R.; Michael, Todd P.; Mockler, Todd C.

    2014-01-01

    Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium. PMID:24489928

  14. Effects of Oxytocin and Prolactin on Stress-Induced Bladder Hypersensitivity in Female Rats

    PubMed Central

    Ness, Timothy J.; Robbins, Meredith T.

    2009-01-01

    Anecdotal evidence suggests that chronic bladder pain improves while breastfeeding. The present study sought to identify potential mechanisms for such a phenomenon by investigating the effects of the lactogenic hormones prolactin (PL) and oxytocin (OXY) in a rat model of bladder nociception. Lactating rats were less sensitive to urinary bladder distension (UBD) than controls. In investigating potential antinociceptive and anxiolytic roles for these hormones, we found exposure to a footshock paradigm (STRESS groups) produced bladder hypersensitivity in saline-treated rats, manifested as significantly higher electromyographical (EMG) responses to UBD, compared to rats exposed to a non-footshock paradigm (SHAM groups). This hypersensitivity was attenuated by the intraperitoneal administration of OXY prior to footshock in the STRESS-OXY group. The administration of PL augmented EMG responses in the SHAM-PL group but had no effect on the responses of the STRESS-PL group. In the absence of behavioral pretreatment, OXY attenuated UBD-evoked responses while PL had no effect. Moreover, OXY-treated rats spent more time in the open arm of an elevated plus maze compared to saline-treated rats suggesting anxiolysis. These studies suggest the potential for systemic OXY, but not PL, as an analgesic and anxiolytic treatment for painful bladder disorders such as interstitial cystitis. PMID:19595642

  15. Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

    PubMed Central

    Latremoliere, Alban; Woolf, Clifford J.

    2009-01-01

    Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. Perspective In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors. PMID:19712899

  16. Application of xCELLigence RTCA Biosensor Technology for Revealing the Profile and Window of Drug Responsiveness in Real Time

    PubMed Central

    Kho, Dan; MacDonald, Christa; Johnson, Rebecca; Unsworth, Charles P.; O’Carroll, Simon J.; du Mez, Elyce; Angel, Catherine E.; Graham, E. Scott

    2015-01-01

    The xCELLigence technology is a real-time cellular biosensor, which measures the net adhesion of cells to high-density gold electrode arrays printed on custom-designed E-plates. The strength of cellular adhesion is influenced by a myriad of factors that include cell type, cell viability, growth, migration, spreading and proliferation. We therefore hypothesised that xCELLigence biosensor technology would provide a valuable platform for the measurement of drug responses in a multitude of different experimental, clinical or pharmacological contexts. In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1) not only if cells respond to a particular drug, but (2) the window of drug responsiveness. The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay. In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time. PMID:25893878

  17. The combined effect of salinity and heat reveals a specific physiological, biochemical and molecular response in tomato plants.

    PubMed

    Rivero, Rosa M; Mestre, Teresa C; Mittler, Ron; Rubio, Francisco; Garcia-Sanchez, Francisco; Martinez, Vicente

    2014-05-01

    Many studies have described the response mechanisms of plants to salinity and heat applied individually; however, under field conditions some abiotic stresses often occur simultaneously. Recent studies revealed that the response of plants to a combination of two different stresses is specific and cannot be deduced from the stresses applied individually. Here, we report on the response of tomato plants to a combination of heat and salt stress. Interestingly, and in contrast to the expected negative effect of the stress combination on plant growth, our results show that the combination of heat and salinity provides a significant level of protection to tomato plants from the effects of salinity. We observed a specific response of plants to the stress combination that included accumulation of glycine betaine and trehalose. The accumulation of these compounds under the stress combination was linked to the maintenance of a high K(+) concentration and thus a lower Na(+) /K(+) ratio, with a better performance of the cell water status and photosynthesis as compared with salinity alone. Our findings unravel new and unexpected aspects of the response of plants to stress combination and provide a proposed list of enzymatic targets for improving crop tolerance to the abiotic field environment. PMID:24028172

  18. Super-resolution microscopy reveals protein spatial reorganization in early innate immune responses.

    SciTech Connect

    Carson, Bryan D.; Aaron, Jesse S.; Timlin, Jerilyn Ann

    2010-10-01

    Over the past decade optical approaches were introduced that effectively break the diffraction barrier. Of particular note were introductions of Stimulated Emission/Depletion (STED) microscopy, Photo-Activated Localization Microscopy (PALM), and the closely related Stochastic Optical Reconstruction Microscopy (STORM). STORM represents an attractive method for researchers, as it does not require highly specialized optical setups, can be implemented using commercially available dyes, and is more easily amenable to multicolor imaging. We implemented a simultaneous dual-color, direct-STORM imaging system through the use of an objective-based TIRF microscope and filter-based image splitter. This system allows for excitation and detection of two fluorophors simultaneously, via projection of each fluorophor's signal onto separate regions of a detector. We imaged the sub-resolution organization of the TLR4 receptor, a key mediator of innate immune response, after challenge with lipopolysaccharide (LPS), a bacteria-specific antigen. While distinct forms of LPS have evolved among various bacteria, only some LPS variations (such as that derived from E. coli) typically result in significant cellular immune response. Others (such as from the plague bacteria Y. pestis) do not, despite affinity to TLR4. We will show that challenge with LPS antigens produces a statistically significant increase in TLR4 receptor clusters on the cell membrane, presumably due to recruitment of receptors to lipid rafts. These changes, however, are only detectable below the diffraction limit and are not evident using conventional imaging methods. Furthermore, we will compare the spatiotemporal behavior of TLR4 receptors in response to different LPS chemotypes in order to elucidate possible routes by which pathogens such as Y. pestis are able to circumvent the innate immune system. Finally, we will exploit the dual-color STORM capabilities to simultaneously image LPS and TLR4 receptors in the cellular membrane at resolutions at or below 40nm.

  19. Vibronically-induced change in the chiral response of molecules revealed by electronic circular dichroism spectroscopy

    NASA Astrophysics Data System (ADS)

    Lin, Na; Luo, Yi; Santoro, Fabrizio; Zhao, Xian; Rizzo, Antonio

    2008-10-01

    A computational study of the vibronically resolved electronic circular dichroism (ECD) spectra of R-(+)-3-methyl-cyclopentanone, including both Franck-Condon and Herzberg-Teller contributions, shows how the latter can introduce a change of sign on the chiral response of an electronic excited state. This sign inversion within the vibronically resolved electronic band, which can be interpreted as a change of the chirality of the system, has in principle important consequences in comparisons of theoretical and experimental ECD spectra employed for the assignment of absolute configurations.

  20. Functional characterisation of wheat Pgip genes reveals their involvement in the local response to wounding.

    PubMed

    Janni, M; Bozzini, T; Moscetti, I; Volpi, C; D'Ovidio, R

    2013-11-01

    Polygalacturonase-inhibiting proteins (PGIPs) are cell wall leucine-rich repeat (LRR) proteins involved in plant defence. The hexaploid wheat (Triticum aestivum, genome AABBDD) genome contains one Pgip gene per genome. Tapgip1 (B genome) and Tapgip2 (D genome) are expressed in all tissues, whereas Tapgip3 (A genome) is inactive because of a long terminal repeat, Copia retrotransposon insertion within the coding region. To verify whether Tapgip1 and Tapgip2 encode active PGIPs and are involved in the wheat defence response, we expressed them transiently and analysed their expression under stress conditions. Neither TaPGIP1 nor TaPGIP2 showed inhibition activity in vitro against fungal polygalacturonases. Moreover, a wheat genotype (T. turgidum ssp. dicoccoides) lacking active homologues of Tapgip1 or Tapgip2 possesses PGIP activity. At transcript level, Tapgip1 and Tapgip2 were both up-regulated after fungal infection and strongly induced following wounding. This latter result has been confirmed in transgenic wheat plants expressing the ?-glucuronidase (GUS) gene under control of the 5'-flanking region of Tdpgip1, a homologue of Tapgip1 with an identical sequence. Strong and transient GUS staining was mainly restricted to the damaged tissues and was not observed in adjacent tissues. Taken together, these results suggest that Tapgips and their homologues are involved in the wheat defence response by acting at the site of the lesion caused by pathogen infection. PMID:23574379

  1. Cellular microenvironments reveal defective mechanosensing responses and elevated YAP signaling in LMNA-mutated muscle precursors.

    PubMed

    Bertrand, Anne T; Ziaei, Simindokht; Ehret, Camille; Duchemin, Hélčne; Mamchaoui, Kamel; Bigot, Anne; Mayer, Michčle; Quijano-Roy, Susana; Desguerre, Isabelle; Lainé, Jeanne; Ben Yaou, Rabah; Bonne, Gisčle; Coirault, Catherine

    2014-07-01

    The mechanisms underlying the cell response to mechanical forces are crucial for muscle development and functionality. We aim to determine whether mutations of the LMNA gene (which encodes lamin A/C) causing congenital muscular dystrophy impair the ability of muscle precursors to sense tissue stiffness and to respond to mechanical challenge. We found that LMNA-mutated myoblasts embedded in soft matrix did not align along the gel axis, whereas control myoblasts did. LMNA-mutated myoblasts were unable to tune their cytoskeletal tension to the tissue stiffness as attested by inappropriate cell-matrix adhesion sites and cytoskeletal tension in soft versus rigid substrates or after mechanical challenge. Importantly, in soft two-dimensional (2D) and/or static three-dimensional (3D) conditions, LMNA-mutated myoblasts showed enhanced activation of the yes-associated protein (YAP) signaling pathway that was paradoxically reduced after cyclic stretch. siRNA-mediated downregulation of YAP reduced adhesion and actin stress fibers in LMNA myoblasts. This is the first demonstration that human myoblasts with LMNA mutations have mechanosensing defects through a YAP-dependent pathway. In addition, our data emphasize the crucial role of biophysical attributes of cellular microenvironment to the response of mechanosensing pathways in LMNA-mutated myoblasts. PMID:24806962

  2. Hepatic gene expression profiling reveals protective responses in Atlantic salmon vaccinated against furunculosis

    PubMed Central

    Škugor, Stanko; Jřrgensen, Sven Martin; Gjerde, Bjarne; Krasnov, Aleksei

    2009-01-01

    Background Furunculosis, a disease caused with gram negative bacteria Aeromonas salmonicida produces heavy losses in aquaculture. Vaccination against furunculosis reduces mortality of Atlantic salmon but fails to eradicate infection. Factors that determine high individual variation of vaccination efficiency remain unknown. We used gene expression analyses to search for the correlates of vaccine protection against furunculosis in Atlantic salmon. Results Naďve and vaccinated fish were challenged by co-habitance. Fish with symptoms of furunculosis at the onset of mass mortality (LR - low resistance) and survivors (HR - high resistance) were sampled. Hepatic gene expression was analyzed with microarray (SFA2.0 - immunochip) and real-time qPCR. Comparison of LR and HR indicated changes associated with the protection and results obtained with naďve fish were used to find and filter the vaccine-independent responses. Genes involved in recruitment and migration of immune cells changed expression in both directions with greater magnitude in LR. Induction of the regulators of immune responses was either equal (NFkB) or greater (Jun) in LR. Expression levels of proteasome components and extracellular proteases were higher in LR while protease inhibitors were up-regulated in HR. Differences in chaperones and protein adaptors, scavengers of reactive oxygen species and genes for proteins of iron metabolism suggested cellular and oxidative stress in LR. Reduced levels of free iron and heme can be predicted in LR by gene expression profiles with no protection against pathogen. The level of complement regulation was greater in HR, which showed up-regulation of the components of membrane attack complex and the complement proteins that protect the host against the auto-immune damages. HR fish was also characterized with up-regulation of genes for proteins involved in the protection of extracellular matrix, lipid metabolism and clearance of endogenous and exogenous toxic compounds. A number of genes with marked expression difference between HR and LR can be considered as positive and negative correlates of vaccine protection against furunculosis. Conclusion Efficiency of vaccination against furunculosis depends largely on the ability of host to neutralize the negative impacts of immune responses combined with efficient clearance and prevention of tissue damages. PMID:19878563

  3. Immune response of the Caribbean sea fan, Gorgonia ventalina, exposed to an Aplanochytrium parasite as revealed by transcriptome sequencing

    PubMed Central

    Burge, Colleen A.; Mouchka, Morgan E.; Harvell, C. Drew; Roberts, Steven

    2013-01-01

    Coral reef communities are undergoing marked declines due to a variety of stressors including disease. The sea fan coral, Gorgonia ventalina, is a tractable study system to investigate mechanisms of immunity to a naturally occurring pathogen. Functional studies in Gorgonia ventalina immunity indicate that several key pathways and cellular components are involved in response to natural microbial invaders, although to date the functional and regulatory pathways remain largely un-described. This study used short-read sequencing (Illumina GAIIx) to identify genes involved in the response of G. ventalina to a naturally occurring Aplanochytrium spp. parasite. De novo assembly of the G. ventalina transcriptome yielded 90,230 contigs of which 40,142 were annotated. RNA-Seq analysis revealed 210 differentially expressed genes in sea fans exposed to the Aplanochytrium parasite. Differentially expressed genes involved in immunity include pattern recognition molecules, anti-microbial peptides, and genes involved in wound repair and reactive oxygen species formation. Gene enrichment analysis indicated eight biological processes were enriched representing 36 genes, largely involved with protein translation and energy production. This is the first report using high-throughput sequencing to characterize the host response of a coral to a natural pathogen. Furthermore, we have generated the first transcriptome for a soft (octocoral or non-scleractinian) coral species. Expression analysis revealed genes important in invertebrate innate immune pathways, as well as those whose role is previously un-described in cnidarians. This resource will be valuable in characterizing G. ventalina immune response to infection and co-infection of pathogens in the context of environmental change. PMID:23898300

  4. In Vivo Profiling Reveals a Competent Heat Shock Response in Adult Neurons: Implications for Neurodegenerative Disorders

    PubMed Central

    Carnemolla, Alisia; Lazell, Hayley; Moussaoui, Saliha; Bates, Gillian P.

    2015-01-01

    The heat shock response (HSR) is the main pathway used by cells to counteract proteotoxicity. The inability of differentiated neurons to induce an HSR has been documented in primary neuronal cultures and has been proposed to play a critical role in ageing and neurodegeneration. However, this accepted dogma has not been demonstrated in vivo. We used BAC transgenic mice generated by the Gene Expression Nervous System Atlas project to investigate the capacity of striatal medium sized spiny neurons to induce an HSR as compared to that of astrocytes and oligodendrocytes. We found that all cell populations were competent to induce an HSR upon HSP90 inhibition. We also show the presence and relative abundance of heat shock-related genes and proteins in these striatal cell populations. The identification of a competent HSR in adult neurons supports the development of therapeutics that target the HSR pathway as treatments for neurodegenerative disorders. PMID:26134141

  5. Plant root transcriptome profiling reveals a strain-dependent response during Azospirillum-rice cooperation.

    PubMed

    Drogue, Benoît; Sanguin, Hervé; Chamam, Amel; Mozar, Michael; Llauro, Christel; Panaud, Olivier; Prigent-Combaret, Claire; Picault, Nathalie; Wisniewski-Dyé, Florence

    2014-01-01

    Cooperation involving Plant Growth-Promoting Rhizobacteria results in improvements of plant growth and health. While pathogenic and symbiotic interactions are known to induce transcriptional changes for genes related to plant defense and development, little is known about the impact of phytostimulating rhizobacteria on plant gene expression. This study aims at identifying genes significantly regulated in rice roots upon Azospirillum inoculation, considering possible favored interaction between a strain and its original host cultivar. Genome-wide analyzes of Oryza sativa japonica cultivars Cigalon and Nipponbare were performed, by using microarrays, seven days post-inoculation with Azospirillum lipoferum 4B (isolated from Cigalon) or Azospirillum sp. B510 (isolated from Nipponbare) and compared to the respective non-inoculated condition. A total of 7384 genes were significantly regulated, which represent about 16% of total rice genes. A set of 34 genes is regulated by both Azospirillum strains in both cultivars, including a gene orthologous to PR10 of Brachypodium, and these could represent plant markers of Azospirillum-rice interactions. The results highlight a strain-dependent response of rice, with 83% of the differentially expressed genes being classified as combination-specific. Whatever the combination, most of the differentially expressed genes are involved in primary metabolism, transport, regulation of transcription and protein fate. When considering genes involved in response to stress and plant defense, it appears that strain B510, a strain displaying endophytic properties, leads to the repression of a wider set of genes than strain 4B. Individual genotypic variations could be the most important driving force of rice roots gene expression upon Azospirillum inoculation. Strain-dependent transcriptional changes observed for genes related to auxin and ethylene signaling highlight the complexity of hormone signaling networks in the Azospirillum-rice cooperation. PMID:25414716

  6. Use of acoustic tools to reveal otherwise cryptic responses of forest elephants to oil exploration.

    PubMed

    Wrege, Peter H; Rowland, Elizabeth D; Thompson, Bruce G; Batruch, Nikolas

    2010-12-01

    Most evaluations of the effects of human activities on wild animals have focused on estimating changes in abundance and distribution of threatened species; however, ecosystem disturbances also affect aspects of animal behavior such as short-term movement, activity budgets, and reproduction. It may take a long time for changes in behavior to manifest as changes in abundance or distribution. Therefore, it is important to have methods with which to detect short-term behavioral responses to human activity. We used continuous acoustic and seismic monitoring to evaluate the short-term effects of seismic prospecting for oil on forest elephants (Loxodonta cyclotis) in Gabon, Central Africa. We monitored changes in elephant abundance and activity as a function of the frequency and intensity of acoustic and seismic signals from dynamite detonation and human activity. Elephants did not flee the area being explored; the relative number of elephants increased in a seasonal pattern typical of elsewhere in the ecosystem. In the exploration area, however, they became more nocturnal. Neither the intensity nor the frequency of dynamite blasts affected the frequency of calling or the daily pattern of elephant activity. Nevertheless, the shift of activity to nocturnal hours became more pronounced as human activity neared each monitored area of forest. This change in activity pattern and its likely causes would not have been detected through standard monitoring methods, which are not sensitive to behavioral changes over short time scales (e.g., dung transects, point counts) or cover a limited area (e.g., camera traps). Simultaneous acoustic monitoring of animal communication, human, and environmental sounds allows the documentation of short-term behavioral changes in response to human disturbance. PMID:20666800

  7. Proteomics analysis of urine reveals acute phase response proteins as candidate diagnostic biomarkers for prostate cancer.

    PubMed

    Davalieva, Katarina; Kiprijanovska, Sanja; Komina, Selim; Petrusevska, Gordana; Zografska, Natasha Chokrevska; Polenakovic, Momir

    2015-01-01

    Despite the overall success of prostate specific antigen (PSA) in screening and detection of prostate cancer (PCa), its use has been limited due to the lack of specificity. The principal driving goal currently within PCa research is to identify non-invasive biomarker(s) for early detection of aggressive tumors with greater sensitivity and specificity than PSA. In this study, we focused on identification of non-invasive biomarkers in urine with higher specificity than PSA. We tested urine samples from PCa and benign prostatic hyperplasia (BPH) patients by 2-D DIGE coupled with MS and bioinformatics analysis. Statistically significant (p?Response Signaling pathway. Nine proteins with differential abundances were included in this pathway: AMBP, APOA1, FGA, FGG, HP, ITIH4, SERPINA1, TF and TTR. The expression pattern of 4 acute phase response proteins differed from the defined expression in the canonical pathway. The urine levels of TF, AMPB and HP were measured by immunoturbidimetry in an independent validation set. The concentration of AMPB in urine was significantly higher in PCa while levels of TF and HP were opposite (p?

  8. Serine Proteolytic Pathway Activation Reveals an Expanded Ensemble of Wound Response Genes in Drosophila

    PubMed Central

    Patterson, Rachel A.; Juarez, Michelle T.; Hermann, Anita; Sasik, Roman; Hardiman, Gary; McGinnis, William

    2013-01-01

    After injury to the animal epidermis, a variety of genes are transcriptionally activated in nearby cells to regenerate the missing cells and facilitate barrier repair. The range and types of diffusible wound signals that are produced by damaged epidermis and function to activate repair genes during epidermal regeneration remains a subject of very active study in many animals. In Drosophila embryos, we have discovered that serine protease function is locally activated around wound sites, and is also required for localized activation of epidermal repair genes. The serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier. We developed a trypsin wounding treatment as an amplification tool to more fully understand the changes in the Drosophila transcriptome that occur after epidermal injury. By comparing our array results with similar results on mammalian skin wounding we can see which evolutionarily conserved pathways are activated after epidermal wounding in very diverse animals. Our innovative serine protease-mediated wounding protocol allowed us to identify 8 additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair. Additionally, our data augments the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues. PMID:23637905

  9. Apoplast proteome reveals that extracellular matrix contributes to multistress response in poplar

    PubMed Central

    2010-01-01

    Background Riverine ecosystems, highly sensitive to climate change and human activities, are characterized by rapid environmental change to fluctuating water levels and siltation, causing stress on their biological components. We have little understanding of mechanisms by which riverine plant species have developed adaptive strategies to cope with stress in dynamic environments while maintaining growth and development. Results We report that poplar (Populus spp.) has evolved a systems level "stress proteome" in the leaf-stem-root apoplast continuum to counter biotic and abiotic factors. To obtain apoplast proteins from P. deltoides, we developed pressure-chamber and water-displacement methods for leaves and stems, respectively. Analyses of 303 proteins and corresponding transcripts coupled with controlled experiments and bioinformatics demonstrate that poplar depends on constitutive and inducible factors to deal with water, pathogen, and oxidative stress. However, each apoplast possessed a unique set of proteins, indicating that response to stress is partly compartmentalized. Apoplast proteins that are involved in glycolysis, fermentation, and catabolism of sucrose and starch appear to enable poplar to grow normally under water stress. Pathogenesis-related proteins mediating water and pathogen stress in apoplast were particularly abundant and effective in suppressing growth of the most prevalent poplar pathogen Melampsora. Unexpectedly, we found diverse peroxidases that appear to be involved in stress-induced cell wall modification in apoplast, particularly during the growing season. Poplar developed a robust antioxidative system to buffer oxidation in stem apoplast. Conclusion These findings suggest that multistress response in the apoplast constitutes an important adaptive trait for poplar to inhabit dynamic environments and is also a potential mechanism in other riverine plant species. PMID:21114852

  10. Plant root transcriptome profiling reveals a strain-dependent response during Azospirillum-rice cooperation

    PubMed Central

    Drogue, Benoît; Sanguin, Hervé; Chamam, Amel; Mozar, Michael; Llauro, Christel; Panaud, Olivier; Prigent-Combaret, Claire; Picault, Nathalie; Wisniewski-Dyé, Florence

    2014-01-01

    Cooperation involving Plant Growth-Promoting Rhizobacteria results in improvements of plant growth and health. While pathogenic and symbiotic interactions are known to induce transcriptional changes for genes related to plant defense and development, little is known about the impact of phytostimulating rhizobacteria on plant gene expression. This study aims at identifying genes significantly regulated in rice roots upon Azospirillum inoculation, considering possible favored interaction between a strain and its original host cultivar. Genome-wide analyzes of Oryza sativa japonica cultivars Cigalon and Nipponbare were performed, by using microarrays, seven days post-inoculation with Azospirillum lipoferum 4B (isolated from Cigalon) or Azospirillum sp. B510 (isolated from Nipponbare) and compared to the respective non-inoculated condition. A total of 7384 genes were significantly regulated, which represent about 16% of total rice genes. A set of 34 genes is regulated by both Azospirillum strains in both cultivars, including a gene orthologous to PR10 of Brachypodium, and these could represent plant markers of Azospirillum-rice interactions. The results highlight a strain-dependent response of rice, with 83% of the differentially expressed genes being classified as combination-specific. Whatever the combination, most of the differentially expressed genes are involved in primary metabolism, transport, regulation of transcription and protein fate. When considering genes involved in response to stress and plant defense, it appears that strain B510, a strain displaying endophytic properties, leads to the repression of a wider set of genes than strain 4B. Individual genotypic variations could be the most important driving force of rice roots gene expression upon Azospirillum inoculation. Strain-dependent transcriptional changes observed for genes related to auxin and ethylene signaling highlight the complexity of hormone signaling networks in the Azospirillum-rice cooperation. PMID:25414716

  11. Anaesthetists should be aware of delayed hypersensitivity to phenylephrine.

    PubMed

    Dewachter, P; Mouton-Faivre, C

    2007-05-01

    Delayed reactions to phenylephrine, used as a mydriatic agent during ophthalmological surgical procedures, are well known. We diagnosed a delayed hypersensitivity reaction to phenylephrine included in an ophthalmic insert in a woman presenting, 24 h after surgery, with an acute blepharoconjunctivitis associated with eyelid eczema of the operated eye. The diagnosis was supported by the recognition of clinical symptoms associated with a positive patch test to phenylephrine. Patients who present with previous contact eczema to phenylephrine may develop a generalized eczema if phenylephrine is injected intravenously. Intravenous phenylephrine is increasingly being used in the operating room to treat hypotension. This case report confirms the need for systematic allergological investigation of all drugs and substances administered during the peri-operative period in order to avoid a delayed hypersensitivity reaction occurring after the peri-operative period. Anaesthetists should be aware of the possibility of delayed hypersensitivity reactions involving phenylephrine. PMID:17430329

  12. Cross-fostering reveals an effect of spleen size and nest temperatures on immune responses in nestling European starlings.

    PubMed

    Ardia, Daniel R

    2005-09-01

    Immunocompetence may be a good measure of offspring quality, however, factors affecting variation in immune responses are not clear. Research suggests that immune function can vary due to differences in genetics, development conditions and individual quality. Here, I examined factors affecting variation in immune response among nestling European starlings through a split-nest cross-fostering brood manipulation that included two important covariates: spleen size and nest temperatures. Immunocompetence was assessed via a cell-mediated immune response to phytohaemagglutinin (PHA). This paper provides the first direct evidence that individuals with large spleens also mount strong immune responses. Exposure to PHA did not cause splenomegaly, as there was no difference in spleen size between control birds and those injected with PHA. Offspring immune function was affected by common origin and by rearing environment, though rearing environment appeared to exert its influence only through nest temperatures. A comparison of the immune performance of siblings reared in their home nest versus those reared in other nests revealed a strong effect of maternal quality. As the difference in natal clutch size increased, the magnitude of the difference in immune performance between home-reared nestlings versus out-reared nestlings increased. Overall, nestling immune function appears to be determined by the combination of genetic, maternal and environmental effects. PMID:15868164

  13. Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling? †

    PubMed Central

    Beek, Alex Ter; Keijser, Bart J. F.; Boorsma, Andre; Zakrzewska, Anna; Orij, Rick; Smits, Gertien J.; Brul, Stanley

    2008-01-01

    The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses normally seen upon nutrient limitation. This is indicated by the strong derepression of the CcpA, CodY, and Fur regulon and the induction of tricarboxylic acid cycle genes, SigL- and SigH-mediated genes, and the stringent response. Intriguingly, these conditions did not lead to the activation of sporulation, competence, or the general stress response. The fatty acid biosynthesis (fab) genes and BkdR-regulated genes are upregulated, which may indicate plasma membrane remodeling. This was further supported by the reduced sensitivity toward the fab inhibitor cerulenin upon sorbic acid stress. We are the first to present a comprehensive analysis of the transcriptional response of B. subtilis to sorbic acid stress. PMID:18156260

  14. Tomato transcriptional changes in response to Clavibacter michiganensis subsp. michiganensis reveal a role for ethylene in disease development.

    PubMed

    Balaji, Vasudevan; Mayrose, Maya; Sherf, Ofra; Jacob-Hirsch, Jasmine; Eichenlaub, Rudolf; Iraki, Naim; Manulis-Sasson, Shulamit; Rechavi, Gideon; Barash, Isaac; Sessa, Guido

    2008-04-01

    Clavibacter michiganensis subsp. michiganensis (Cmm) is a gram-positive actinomycete, causing bacterial wilt and canker disease in tomato (Solanum lycopersicum). Host responses to gram-positive bacteria and molecular mechanisms associated with the development of disease symptoms caused by Cmm in tomato are largely unexplored. To investigate plant responses activated during this compatible interaction, we used microarray analysis to monitor changes in host gene expression during disease development. This analysis was performed at 4 d postinoculation, when bacteria were actively multiplying and no wilt symptoms were yet visible; and at 8 d postinoculation, when bacterial growth approached saturation and typical wilt symptoms were observed. Of the 9,254 tomato genes represented on the array, 122 were differentially expressed in Cmm-infected plants, compared with mock-inoculated plants. Functional classification of Cmm-responsive genes revealed that Cmm activated typical basal defense responses in the host, including induction of defense-related genes, production and scavenging of free oxygen radicals, enhanced protein turnover, and hormone synthesis. Cmm infection also induced a subset of host genes involved in ethylene biosynthesis and response. After inoculation with Cmm, Never ripe (Nr) mutant plants, impaired in ethylene perception, and transgenic plants with reduced ethylene synthesis showed significant delay in the appearance of wilt symptoms, compared with wild-type plants. The retarded wilting in Nr plants was a specific effect of ethylene insensitivity, and was not due to altered expression of defense-related genes, reduced bacterial populations, or decreased ethylene synthesis. Taken together, our results indicate that host-derived ethylene plays an important role in regulation of the tomato susceptible response to Cmm. PMID:18245454

  15. Transcript profiling reveals diverse roles of auxin-responsive genes during reproductive development and abiotic stress in rice.

    PubMed

    Jain, Mukesh; Khurana, Jitendra P

    2009-06-01

    Auxin influences growth and development in plants by altering gene expression. Many auxin-responsive genes have been characterized in Arabidopsis in detail, but not in crop plants. Earlier, we reported the identification and characterization of the members of the GH3, Aux/IAA and SAUR gene families in rice. In this study, whole genome microarray analysis of auxin-responsive genes in rice was performed, with the aim of gaining some insight into the mechanism of auxin action. A comparison of expression profiles of untreated and auxin-treated rice seedlings identified 315 probe sets representing 298 (225 upregulated and 73 downregulated) unique genes as auxin-responsive. Functional categorization revealed that genes involved in various biological processes, including metabolism, transcription, signal transduction, and transport, are regulated by auxin. The expression profiles of auxin-responsive genes identified in this study and those of the members of the GH3, Aux/IAA, SAUR and ARF gene families were analyzed during various stages of vegetative and reproductive (panicle and seed) development by employing microarray analysis. Many of these genes are, indeed, expressed in a tissue-specific or developmental stage-specific manner, and the expression profiles of some of the representative genes were confirmed by real-time PCR. The differential expression of auxin-responsive genes during various stages of panicle and seed development implies their involvement in diverse developmental processes. Moreover, several auxin-responsive genes were differentially expressed under various abiotic stress conditions, indicating crosstalk between auxin and abiotic stress signaling. PMID:19490115

  16. Hapten-Induced Contact Hypersensitivity, Autoimmune Reactions, and Tumor Regression: Plausibility of Mediating Antitumor Immunity

    PubMed Central

    Erkes, Dan A.; Selvan, Senthamil R.

    2014-01-01

    Haptens are small molecule irritants that bind to proteins and elicit an immune response. Haptens have been commonly used to study allergic contact dermatitis (ACD) using animal contact hypersensitivity (CHS) models. However, extensive research into contact hypersensitivity has offered a confusing and intriguing mechanism of allergic reactions occurring in the skin. The abilities of haptens to induce such reactions have been frequently utilized to study the mechanisms of inflammatory bowel disease (IBD) to induce autoimmune-like responses such as autoimmune hemolytic anemia and to elicit viral wart and tumor regression. Hapten-induced tumor regression has been studied since the mid-1900s and relies on four major concepts: (1) ex vivo haptenation, (2) in situ haptenation, (3) epifocal hapten application, and (4) antigen-hapten conjugate injection. Each of these approaches elicits unique responses in mice and humans. The present review attempts to provide a critical appraisal of the hapten-mediated tumor treatments and offers insights for future development of the field. PMID:24949488

  17. Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone

    PubMed Central

    1996-01-01

    Mice rendered deficient in IL-1 beta by gene targeting in embryonic stem cells develop and grow normally in a protected laboratory environment. Endotoxin-stimulated peritoneal macrophages from IL-1beta- deficient mice showed normal synthesis and cellular release of IL- 1alpha after treatment with 5 mM ATP demonstrating that IL-1beta is not necessary for expression and release of the IL-1alpha isoform. Mice deficient in IL-1beta showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine. In contrast, IL- 1beta-deficient mice showed defective contact hypersensitivity responses to topically applied trinitrochlorobenzene (TNCB). This defect could be overcome either by application of very high doses of sensitizing antigen, or by local intradermal injection of recombinant IL-1beta immediately before antigen application. These data demonstrate an essential role for IL-1beta in contact hypersensitivity and suggest that IL-1beta acts early during the sensitization phase of response. They suggest an important role for IL-1beta in initiation of the host of response at the epidermal barrier. PMID:8666901

  18. Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress

    PubMed Central

    McDade, Simon S.; Patel, Daksha; Moran, Michael; Campbell, James; Fenwick, Kerry; Kozarewa, Iwanka; Orr, Nicholas J.; Lord, Christopher J.; Ashworth, Alan A.; McCance, Dennis J.

    2014-01-01

    In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome-wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53-dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveal that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair. PMID:24823795

  19. Genomic and proteomic analysis of transcription factor TFII-I reveals insight into the response to cellular stress

    PubMed Central

    Fan, Alex Xiucheng; Papadopoulos, Giorgio L.; Hossain, Mir A.; Lin, I.-Ju; Hu, Jianhong; Tang, Tommy Ming; Kilberg, Michael S.; Renne, Rolf; Strouboulis, John; Bungert, Jörg

    2014-01-01

    The ubiquitously expressed transcription factor TFII-I exerts both positive and negative effects on transcription. Using biotinylation tagging technology and high-throughput sequencing, we determined sites of chromatin interactions for TFII-I in the human erythroleukemia cell line K562. This analysis revealed that TFII-I binds upstream of the transcription start site of expressed genes, both upstream and downstream of the transcription start site of repressed genes, and downstream of RNA polymerase II peaks at the ATF3 and other stress responsive genes. At the ATF3 gene, TFII-I binds immediately downstream of a Pol II peak located 5 kb upstream of exon 1. Induction of ATF3 expression increases transcription throughout the ATF3 gene locus which requires TFII-I and correlates with increased association of Pol II and Elongin A. Pull-down assays demonstrated that TFII-I interacts with Elongin A. Partial depletion of TFII-I expression caused a reduction in the association of Elongin A with and transcription of the DNMT1 and EFR3A genes without a decrease in Pol II recruitment. The data reveal different interaction patterns of TFII-I at active, repressed, or inducible genes, identify novel TFII-I interacting proteins, implicate TFII-I in the regulation of transcription elongation and provide insight into the role of TFII-I during the response to cellular stress. PMID:24875474

  20. Systems-Scale Analysis Reveals Pathways Involved in Cellular Response to Methamphetamine

    PubMed Central

    Sun, Lijie; Li, Hong-Mei; Seufferheld, Manfredo J.; Walters, Kent R.; Margam, Venu M.; Jannasch, Amber; Diaz, Naomi; Riley, Catherine P.; Sun, Weilin; Li, Yueh-Feng; Muir, William M.; Xie, Jun; Wu, Jing; Zhang, Fan; Chen, Jake Y.; Barker, Eric L.; Adamec, Jiri; Pittendrigh, Barry R.

    2011-01-01

    Background Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced. Methodology/Results We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis/contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level. Conclusion Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions. PMID:21533132

  1. Modifying Behavioral Phenotypes in Fmr1 KO Mice: Genetic Background Differences Reveal Autistic-Like Responses

    PubMed Central

    Spencer, Corinne M.; Alekseyenko, Olga; Hamilton, Shannon M.; Thomas, Alexia M.; Serysheva, Ekaterina; Yuva-Paylor, Lisa A.; Paylor, Richard

    2010-01-01

    Scientific Abstract Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild-type mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD-1). Male Fmr1 knockout and wild-type littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic-like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic-like traits. PMID:21268289

  2. Aging Analysis Reveals Slowed Tau Turnover and Enhanced Stress Response in a Mouse Model of Tauopathy

    PubMed Central

    Dickey, Chad; Kraft, Clara; Jinwal, Umesh; Koren, John; Johnson, Amelia; Anderson, Laura; Lebson, Lori; Lee, Daniel; Dickson, Dennis; de Silva, Rohan; Binder, Lester I.; Morgan, David; Lewis, Jada

    2009-01-01

    We have extensively analyzed the biochemical and histochemical profiles of the tau protein from the rTg4510 transgenic mouse model in which the animals uniquely develop forebrain tau pathologies similar to those found in human tauopathies. Levels of several soluble phosphorylated tau species were highest at 1 month relative to later time points, suggesting that certain tau hyperphosphorylation events were insufficient to drive tangle formation in young mice. Despite a robust, pre-tangle-like accumulation of phospho-tau in 1-month-old mice, this material was cleared by 3 months, indicating that the young mouse brain either fails to facilitate tau insolubility or possesses an enhanced ability to clear tau relative to the adult. We also found that while heat shock protein expression increased with normal aging, this process was accelerated in rTg4510 mice. Moreover, by exploiting an exon 10 (?) specific antibody, we demonstrated that endogenous mouse tau turnover was slowed in response to human tau over-expression, and that this endogenous tau adopted disease-related properties. These data suggest that a younger brain fails to develop lasting tau pathology despite elevated levels of phosphorylated tau, perhaps because of reduced expression of stress-related proteins. Moreover, we show that the active production of small amounts of abnormal tau protein facilitates dysfunction and accumulation of otherwise normal tau, a significant implication for the pathogenesis of patients with Alzheimer’s disease. PMID:19074615

  3. Revealing Real-Time Emotional Responses: a Personalized Assessment based on Heartbeat Dynamics

    PubMed Central

    Valenza, Gaetano; Citi, Luca; Lanatá, Antonio; Scilingo, Enzo Pasquale; Barbieri, Riccardo

    2014-01-01

    Emotion recognition through computational modeling and analysis of physiological signals has been widely investigated in the last decade. Most of the proposed emotion recognition systems require relatively long-time series of multivariate records and do not provide accurate real-time characterizations using short-time series. To overcome these limitations, we propose a novel personalized probabilistic framework able to characterize the emotional state of a subject through the analysis of heartbeat dynamics exclusively. The study includes thirty subjects presented with a set of standardized images gathered from the international affective picture system, alternating levels of arousal and valence. Due to the intrinsic nonlinearity and nonstationarity of the RR interval series, a specific point-process model was devised for instantaneous identification considering autoregressive nonlinearities up to the third-order according to the Wiener-Volterra representation, thus tracking very fast stimulus-response changes. Features from the instantaneous spectrum and bispectrum, as well as the dominant Lyapunov exponent, were extracted and considered as input features to a support vector machine for classification. Results, estimating emotions each 10 seconds, achieve an overall accuracy in recognizing four emotional states based on the circumplex model of affect of 79.29%, with 79.15% on the valence axis, and 83.55% on the arousal axis. PMID:24845973

  4. Computational Phenotyping of Two-Person Interactions Reveals Differential Neural Response to Depth-of-Thought

    PubMed Central

    Xiang, Ting; Ray, Debajyoti; Lohrenz, Terry; Dayan, Peter; Montague, P. Read

    2012-01-01

    Reciprocating exchange with other humans requires individuals to infer the intentions of their partners. Despite the importance of this ability in healthy cognition and its impact in disease, the dimensions employed and computations involved in such inferences are not clear. We used a computational theory-of-mind model to classify styles of interaction in 195 pairs of subjects playing a multi-round economic exchange game. This classification produces an estimate of a subject's depth-of-thought in the game (low, medium, high), a parameter that governs the richness of the models they build of their partner. Subjects in each category showed distinct neural correlates of learning signals associated with different depths-of-thought. The model also detected differences in depth-of-thought between two groups of healthy subjects: one playing patients with psychiatric disease and the other playing healthy controls. The neural response categories identified by this computational characterization of theory-of-mind may yield objective biomarkers useful in the identification and characterization of pathologies that perturb the capacity to model and interact with other humans. PMID:23300423

  5. Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage

    PubMed Central

    Younger, Scott T.; Kenzelmann-Broz, Daniela; Jung, Heiyoun; Attardi, Laura D.; Rinn, John L.

    2015-01-01

    The tumor suppressor p53 has been studied extensively as a direct transcriptional activator of protein-coding genes. Recent studies, however, have shed light on novel regulatory functions of p53 within noncoding regions of the genome. Here, we use a systematic approach that integrates transcriptome-wide expression analysis, genome-wide p53 binding profiles and chromatin state maps to characterize the global regulatory roles of p53 in response to DNA damage. Notably, our approach identified conserved features of the p53 network in both human and mouse primary fibroblast models. In addition to known p53 targets, we identify many previously unappreciated mRNAs and long noncoding RNAs that are regulated by p53. Moreover, we find that p53 binding occurs predominantly within enhancers in both human and mouse model systems. The ability to modulate enhancer activity offers an additional layer of complexity to the p53 network and greatly expands the diversity of genomic elements directly regulated by p53. PMID:25883152

  6. Computational phenotyping of two-person interactions reveals differential neural response to depth-of-thought.

    PubMed

    Xiang, Ting; Ray, Debajyoti; Lohrenz, Terry; Dayan, Peter; Montague, P Read

    2012-01-01

    Reciprocating exchange with other humans requires individuals to infer the intentions of their partners. Despite the importance of this ability in healthy cognition and its impact in disease, the dimensions employed and computations involved in such inferences are not clear. We used a computational theory-of-mind model to classify styles of interaction in 195 pairs of subjects playing a multi-round economic exchange game. This classification produces an estimate of a subject's depth-of-thought in the game (low, medium, high), a parameter that governs the richness of the models they build of their partner. Subjects in each category showed distinct neural correlates of learning signals associated with different depths-of-thought. The model also detected differences in depth-of-thought between two groups of healthy subjects: one playing patients with psychiatric disease and the other playing healthy controls. The neural response categories identified by this computational characterization of theory-of-mind may yield objective biomarkers useful in the identification and characterization of pathologies that perturb the capacity to model and interact with other humans. PMID:23300423

  7. Nanotube Action between Human Mesothelial Cells Reveals Novel Aspects of Inflammatory Responses

    PubMed Central

    Abel, Marcus; Leyh, Julia; Kihm, Lars; Witkowski, Margarete; Scheurich, Peter; Zeier, Martin; Schwenger, Vedat

    2011-01-01

    A well-known role of human peritoneal mesothelial cells (HPMCs), the resident cells of the peritoneal cavity, is the generation of an immune response during peritonitis by activation of T-cells via antigen presentation. Recent findings have shown that intercellular nanotubes (NTs) mediate functional connectivity between various cell types including immune cells - such as T-cells, natural killer (NK) cells or macrophages - by facilitating a spectrum of long range cell-cell interactions. Although of medical interest, the relevance of NT-related findings for human medical conditions and treatment, e.g. in relation to inflammatory processes, remains elusive, particularly due to a lack of appropriate in vivo data. Here, we show for the first time that primary cultures of patient derived HPMCs are functionally connected via membranous nanotubes. NT formation appears to be actin cytoskeleton dependent, mediated by the action of filopodia. Importantly, significant variances in NT numbers between different donors as a consequence of pathophysiological alterations were observable. Furthermore, we show that TNF-? induces nanotube formation and demonstrate a strong correlation of NT connectivity in accordance with the cellular cholesterol level and distribution, pointing to a complex involvement of NTs in inflammatory processes with potential impact for clinical treatment. PMID:22216308

  8. Revealing Real-Time Emotional Responses: a Personalized Assessment based on Heartbeat Dynamics

    NASA Astrophysics Data System (ADS)

    Valenza, Gaetano; Citi, Luca; Lanatá, Antonio; Scilingo, Enzo Pasquale; Barbieri, Riccardo

    2014-05-01

    Emotion recognition through computational modeling and analysis of physiological signals has been widely investigated in the last decade. Most of the proposed emotion recognition systems require relatively long-time series of multivariate records and do not provide accurate real-time characterizations using short-time series. To overcome these limitations, we propose a novel personalized probabilistic framework able to characterize the emotional state of a subject through the analysis of heartbeat dynamics exclusively. The study includes thirty subjects presented with a set of standardized images gathered from the international affective picture system, alternating levels of arousal and valence. Due to the intrinsic nonlinearity and nonstationarity of the RR interval series, a specific point-process model was devised for instantaneous identification considering autoregressive nonlinearities up to the third-order according to the Wiener-Volterra representation, thus tracking very fast stimulus-response changes. Features from the instantaneous spectrum and bispectrum, as well as the dominant Lyapunov exponent, were extracted and considered as input features to a support vector machine for classification. Results, estimating emotions each 10 seconds, achieve an overall accuracy in recognizing four emotional states based on the circumplex model of affect of 79.29%, with 79.15% on the valence axis, and 83.55% on the arousal axis.

  9. Gene cluster of Pseudomonas syringae pv. "phaseolicola" controls pathogenicity of bean plants and hypersensitivity of nonhost plants.

    PubMed Central

    Lindgren, P B; Peet, R C; Panopoulos, N J

    1986-01-01

    Loss of the ability of Pseudomonas syringae pv. "phaseolicola" NPS3121 to elicit a hypersensitive response on tobacco and other nonhost plants was associated with loss of pathogenicity on the susceptible host bean. Eight independent, prototrophic transposon Tn5 insertion mutants which had lost the ability to elicit a hypersensitive response on tobacco plants were identified. Six of these mutants no longer produced disease lesions on primary leaves of the susceptible bean cultivar Red Kidney and failed to elicit a hypersensitive response on the resistant bean cultivar Red Mexican and on the nonhost plants tomato, cowpea, and soybean. The two remaining mutants had reduced pathogenicity on Red Kidney bean and elicited variable hypersensitive responses on the other plants tested. Southern blot analysis indicated that each mutant carried a single independent Tn5 insertion in one of three EcoRI fragments of about 17, 7, and 5 kilobases. Marker exchange mutagenesis further supported the conclusion that the pleiotropic mutant phenotype was not associated with multiple Tn5 insertions. A genomic library of the wild-type strain was constructed in the cosmid vector pLAFR3. A recombinant plasmid, designated pPL6, that carried P. syringae pv. "phaseolicola" genomic sequences was identified by colony hybridization. This plasmid restored the wild-type phenotype to all but one mutant, suggesting that genes affected by the insertions were clustered. Structural analysis of pPL6 and the wild-type genome indicated that the 17- and 5-kilobase EcoRI fragments were contiguous in the strain NPS3121 genome. Images PMID:3023280

  10. A mutation in a cuticle collagen causes hypersensitivity to the endocrine disrupting chemical, bisphenol A, in Caenorhabditis elegans

    Microsoft Academic Search

    Masahito Watanabe; Nanako Mitani; Naoaki Ishii; Keizaburo Miki

    2005-01-01

    A novel mutant gene, bis-1 (bisphenol A sensitive) has been isolated in the nematode, Caenorhabditis elegans, that affects the response to endocrine disrupting chemicals (EDC). The bis-1(nx3) allele is hypersensitive to bisphenol A (BPA), is allelic to a collagen gene (col-121), and is expressed in hypodermal cells. Among the collagen mutants so far studied, bis-1(nx3), dpy-2(e8), dpy-7(e88) and dpy-10(e128) showed

  11. Hypersensitivity to common tree pollens in New York City patients.

    PubMed

    Lin, Robert Y; Clauss, Allison E; Bennett, Edward S

    2002-01-01

    Testing for tree pollen hypersensitivity typically requires the use of several tree pollens. Identifying patterns of cross-sensitivity to tree pollens could reduce the number of trees used for testing. The goal of this study was to relate reported tree pollen levels to hypersensitivity patterns. Three hundred seventy-one allergy patients were tested serologically for hypersensitivity toward prevalent tree pollens in the surrounding New York area over the years 1993-2000. Specific tree pollens that were examined included oak (Quercus alba), birch (Betula verrucosa), beech (Fagus grandifolia), poplar (Populus deltoides), maple (Acer negundo), ash (Fraxinus americana), hickory (Carya pecan), and elm (Ulmus americana). Statistical analysis of the levels of hypersensitivity was performed to identify correlations and grouping factors. Pollen levels, obtained from published annual pollen and spore reports, were characterized and related to the prevalence of hypersensitivity for the various trees. The highest prevalence of hypersensitivity (score > or = class 1) was for oak (34.3%), birch (32.9%), and maple (32.8%) tree pollens. Lower prevalences were observed for beech (29.6%), hickory (27.1%), ash (26%), elm (24.6%), and poplar (20.6%) trees. Significant correlations were observed between oak, birch, and beech radioallergosorbent test scores. Factor analysis identified two independent pollen groups with oak, birch, and beech consisting of one group and the other five tree pollens constituting the other group. Peak pollen counts clearly were highest for oak, birch, and maple trees. The peak pollen counts corresponded roughly to seropositivity prevalences for the tree pollens. When elm, poplar, and beech test scores were not used to identify patients who were allergic to tree pollens, only 1 of 106 patients with any positive tree radioallergosorbent test score was missed. It is concluded that in the New York City area, hypersensitivity to tree pollens most often is manifested with allergy to oak, birch, and maple tree pollens. Identifying beech, poplar, and elm hypersensitivity adds little toward identifying patients who are allergic to tree pollens. This may relate in part to cross-reactive epitopes. These data suggest that these three trees can be eliminated from testing with only a < 1% loss of sensitivity. PMID:12221895

  12. Microseismicity and Temporal Changes in Seismic Velocity Reveal Crustal Response to Dynamic Stress

    NASA Astrophysics Data System (ADS)

    Delorey, A. A.; Johnson, P. A.; Chao, K.; Obara, K.

    2014-12-01

    Earthquake occurrence is both a driver of and the result of complexity in the stress field and elastic properties of the crust. If we understand how static and dynamic stresses perturb the crust, we can use these observations to better understand the current state of the crust. Here we focus on how the crust responds to dynamic stresses outside the region where static stresses are important. A tool to understand the current state of the crust has broad applications in seismic hazards, induced seismicity, and a general understanding of earthquake physics. As dynamic strains outside of the near field of an earthquake are small, often no more than a micro strain, we need sensitive measures to detect any resulting perturbations to the properties of the crust. Two methods we currently use are (i) measuring temporal changes in seismic velocities applying ambient noise, and (ii) measuring the spatiotemporal change in microseismic activity. A strength of using ambient noise to detect changes in seismic velocities is the ability to stack over space and time to reveal very small changes. We use microseismicity because there are many more small earthquakes than large ones, so more robust statistics can be applied to small earthquakes—applying microseismicity improves the detection of changes within the crust. A striking observation applying these methods is widespread increased seismicity and a transient increase in seismic velocities in Japan after the passage of surface waves from the 2012 M8.6 Indian Ocean earthquake. The velocity observations are obtained by stacking 113 Hinet stations and using 10-day windows. The velocity change extends to at least 5 km depth based on the spatial wavelengths employed (0.1-5 Hz). Based on our field observations and those of others, as well as our laboratory studies one may expect a decrease in the crustal velocity from wave dynamics. The observed increase in velocity could be an indirect effect such that frictional contacts stiffen under changing quasi-static stress conditions in the presence of an increase in microseismicity. Alternatively, an increase in velocity may suggest that weak motions strengthen frictional contacts within the crust, whereas those contacts are slightly destabilized under ambient conditions.

  13. Different responses to heat shock stress revealed heteromorphic adaptation strategy of Pyropia haitanensis (Bangiales, Rhodophyta).

    PubMed

    Luo, Qijun; Zhu, Zhenggang; Zhu, Zhujun; Yang, Rui; Qian, Feijian; Chen, Haimin; Yan, Xiaojun

    2014-01-01

    Pyropia has a unique heteromorphic life cycle with alternation stages between thallus and conchocelis, which lives at different water temperatures in different seasons. To better understand the different adaptation strategies for temperature stress, we tried to observe comparative biochemical changes of Pyropia haitanensis based on a short term heat shock model. The results showed that: (1) At normal temperature, free-living conchocelis contains significantly higher levels of H2O2, fatty acid-derived volatiles, the copy number of Phrboh and Phhsp70 genes,the activities of NADPH oxidase and floridoside than those in thallus. The released H2O2 and NADPH oxidase activity of conchocelis were more than 7 times higher than those of thallus. The copy number of Phrboh in conchocelis was 32 times that in thallus. (2) After experiencing heat shock at 35°C for 30 min, the H2O2 contents, the mRNA levels of Phrboh and Phhsp70, NADPH oxidase activity and the floridoside content in thallus were all significantly increased. The mRNA levels of Phrboh increased 5.78 times in 5 min, NADPH oxidase activity increased 8.45 times in 20 min. (3) Whereas, in conchocelis, the changes in fatty acids and their down-stream volatiles predominated, significantly increasing levels of saturated fatty acids and decreasing levels of polyunsaturated fatty acids occurred, and the 8-carbon volatiles were accumulated. However, the changes in H2O2 content and expression of oxidant-related genes and enzymatic activity were not obvious. Overall, these results indicate that conchocelis maintains a high level of active protective apparatus to endure its survival at high temperature, while thallus exhibit typical stress responses to heat shock. It is concluded that Pyropia haitanensis has evolved a delicate strategy for temperature adaptation for its heteromorphic life cycle. PMID:24709783

  14. Different Responses to Heat Shock Stress Revealed Heteromorphic Adaptation Strategy of Pyropia haitanensis (Bangiales, Rhodophyta)

    PubMed Central

    Zhu, Zhujun; Yang, Rui; Qian, Feijian; Chen, Haimin; Yan, Xiaojun

    2014-01-01

    Pyropia has a unique heteromorphic life cycle with alternation stages between thallus and conchocelis, which lives at different water temperatures in different seasons. To better understand the different adaptation strategies for temperature stress, we tried to observe comparative biochemical changes of Pyropia haitanensis based on a short term heat shock model. The results showed that: (1) At normal temperature, free-living conchocelis contains significantly higher levels of H2O2, fatty acid-derived volatiles, the copy number of Phrboh and Phhsp70 genes,the activities of NADPH oxidase and floridoside than those in thallus. The released H2O2 and NADPH oxidase activity of conchocelis were more than 7 times higher than those of thallus. The copy number of Phrboh in conchocelis was 32 times that in thallus. (2) After experiencing heat shock at 35°C for 30 min, the H2O2 contents, the mRNA levels of Phrboh and Phhsp70, NADPH oxidase activity and the floridoside content in thallus were all significantly increased. The mRNA levels of Phrboh increased 5.78 times in 5 min, NADPH oxidase activity increased 8.45 times in 20 min. (3) Whereas, in conchocelis, the changes in fatty acids and their down-stream volatiles predominated, significantly increasing levels of saturated fatty acids and decreasing levels of polyunsaturated fatty acids occurred, and the 8-carbon volatiles were accumulated. However, the changes in H2O2 content and expression of oxidant-related genes and enzymatic activity were not obvious. Overall, these results indicate that conchocelis maintains a high level of active protective apparatus to endure its survival at high temperature, while thallus exhibit typical stress responses to heat shock. It is concluded that Pyropia haitanensis has evolved a delicate strategy for temperature adaptation for its heteromorphic life cycle. PMID:24709783

  15. Comparative expression analysis of genes induced during development of bacterial rot and induction of hypersensitive cell death in lettuce.

    PubMed

    Kiba, Akinori; Lee, Kyon-Ye; Ohnishi, Kouhei; Hikichi, Yasufumi

    2008-11-28

    The development of bacterial rot disease caused by Pseudomonas cichorii is closely associated with programmed cell death. To investigate the molecular events occurring during the development of bacterial rot, we isolated 20 P. cichorii-responsive genes (PcRGs) in lettuce by differential display. Among these PcRGs, signal transduction-, transcription/translation- and defense/stress responses-related PcRGs were subjected to a comparative expression study. We used RNA samples isolated from lettuce leaves inoculated with P. cichorii and hypersensitive response-inducing Pseudomonas syringae pv. syringae. Expression of PcRG1-5-5 (spliceosomal protein), 2-9-2 (protein kinase) and 1-6-2 (ACC oxidase), 7-5 (alternative oxidase) and BI-I (bax inhibitor I) significantly increased in lettuce leaves inoculated with both P. cichorii and P. syringae pv. syringae. Intriguingly, PcRG 1-2-6 (protein phosphatase 2C) and 4-D-5 (protein kinase) were only up-regulated in P. cichorii-inoculated lettuce, whereas expression of PcRG1-3-2 (ribonucleoprotein) was only enhanced in P. syringae pv. syringae-inoculated lettuce. Expressions of PcRG1-3-2, 1-5-5, 1-6-2, 2-9-2, 7-5 and BI-I were induced by treatments with salicylic acid and/or methyl jasmonate. However, expression of PcRG1-2-6 and 4-D-5, which were specifically up-regulated by P. cichorii, were scarcely affected by these chemicals. Pharmacological studies suggested that ethylene and alternative oxidase were commonly related to disease development and hypersensitive responses. By contrast, there may be a different role for protein synthesis and protein kinase during disease development and in hypersensitive responses. These results suggested the overall similarity of genes expressed during disease development and in hypersensitive responses. However, there were differences not only in induction kinetics and the level of gene expression but also in the signal transduction pathway between hypersensitive responses and disease development. PMID:18171591

  16. Comprehensive transcriptional profiling of prion infection in mouse models reveals networks of responsive genes

    PubMed Central

    Sorensen, Garrett; Medina, Sarah; Parchaliuk, Debra; Phillipson, Clark; Robertson, Catherine; Booth, Stephanie A

    2008-01-01

    Background Prion infection results in progressive neurodegeneration of the central nervous system invariably resulting in death. The pathological effects of prion diseases in the brain are morphologically well defined, such as gliosis, vacuolation, and the accumulation of disease-specific protease-resistant prion protein (PrPSc). However, the underlying molecular events that lead to the death of neurons are poorly characterised. Results In this study cDNA microarrays were used to profile gene expression changes in the brains of two different strains of mice infected with three strains of mouse-adapted scrapie. Extensive data was collected and analyzed, from which we identified a core group of 349 prion-related genes (PRGs) that consistently showed altered expression in mouse models. Gene ontology analysis assigned many of the up-regulated genes to functional groups associated with one of the primary neuropathological features of prion diseases, astrocytosis and gliosis; protein synthesis, inflammation, cell proliferation and lipid metabolism. Using a computational tool, Ingenuity Pathway Analysis (IPA), we were able to build networks of interacting genes from the PRG list. The regulatory cytokine TGFB1, involved in modulating the inflammatory response, was identified as the outstanding interaction partner for many of the PRGs. The majority of genes expressed in neurons were down-regulated; a number of these were involved in regulatory pathways including synapse function, calcium signalling, long-term potentiation and ERK/MAPK signalling. Two down-regulated genes coding for the transcription regulators, EGR1 and CREB1, were also identified as central to interacting networks of genes; these factors are often used as markers of neuronal activity and their deregulation could be key to loss of neuronal function. Conclusion These data provides a comprehensive list of genes that are consistently differentially expressed in multiple scrapie infected mouse models. Building networks of interactions between these genes provides a means to understand the complex interplay in the brain during neurodegeneration. Resolving the key regulatory and signaling events that underlie prion pathogenesis will provide targets for the design of novel therapies and the elucidation of biomarkers. PMID:18315872

  17. Serotonergic and non-serotonergic targets in the pharmacotherapy of visceral hypersensitivity.

    PubMed

    Bueno, L; de Ponti, F; Fried, M; Kullak-Ublick, G A; Kwiatek, M A; Pohl, D; Quigley, E M M; Tack, J; Talley, N J

    2007-01-01

    Visceral hypersensitivity is considered a key mechanism in the pathogenesis of functional gastrointestinal (GI) disorders. Targeting visceral hypersensitivity seems an attractive approach to the development of drugs for functional GI disorders. This review summarizes current knowledge on targets for the treatment of visceral hypersensitivity, and the status of current and future drug and probiotic treatment development, and the role of pharmacogenomic factors. PMID:17280587

  18. Plasticity in intact A?- and C-fibers contributes to cold hypersensitivity in neuropathic rats

    Microsoft Academic Search

    G. Ji; S. Zhou; M. Y. Kochukov; K. N. Westlund; S. M. Carlton

    2007-01-01

    Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats

  19. Localized Changes in Peroxidase Activity Accompany Hydrogen Peroxide Generation during the Development of a Nonhost Hypersensitive Reaction in Lettuce1

    PubMed Central

    Bestwick, Charles S.; Brown, Ian R.; Mansfield, John W.

    1998-01-01

    Peroxidase activity was characterized in lettuce (Lactuca sativa L.) leaf tissue. Changes in the activity and distribution of the enzyme were examined during the development of a nonhost hypersensitive reaction (HR) induced by Pseudomonas syringae (P. s.) pv phaseolicola and in response to an hrp mutant of the bacterium. Assays of activity in tissue extracts revealed pH optima of 4.5, 6.0, 5.5 to 6.0, and 6.0 to 6.5 for the substrates tetramethylbenzidine, guaiacol, caffeic acid, and chlorogenic acid, respectively. Inoculation with water or with wild-type or hrp mutant strains of P. s. pv phaseolicola caused an initial decline in total peroxidase activity; subsequent increases depended on the hydrogen donor used in the assay. Guaiacol peroxidase recovered more rapidly in tissues undergoing the HR, whereas changes in tetramethylbenzidine peroxidase were generally similar in the two interactions. In contrast, increases in chlorogenic acid peroxidase were significantly higher in tissues inoculated with the hrp mutant. During the HR, increased levels of Mn2+/2,4-dichlorophenol-stimulated NADH and NADPH oxidase activities, characteristic of certain peroxidases, were found in intercellular fluids and closely matched the accumulation of H2O2 in the apoplast. Histochemical analysis of peroxidase distribution by electron microscopy revealed a striking, highly localized increase in activity within the endomembrane system and cell wall at the sites of bacterial attachment. However, no clear differences in peroxidase location were observed in tissue challenged by the wild-type strain or the hrp mutant. Our results highlight the significance of the subcellular control of oxidative reactions leading to the generation of reactive oxygen species, cell wall alterations, and the HR. PMID:9808752

  20. Involvement of cannabinoid receptors in inflammatory hypersensitivity to colonic distension in rats.

    PubMed

    Sanson, M; Bueno, L; Fioramonti, J

    2006-10-01

    Activation of cannabinoid CB1 and CB2 receptors is known to attenuate nociception and hyperalgesia in somatic inflammatory conditions. The aim of this study was to determine whether cannabinoids modulate colonic sensitivity in basal and inflammatory conditions. The effects of CB1 and CB2 receptor agonists and antagonists on the abdominal contractile response to colorectal distension (CRD) in basal conditions and after 2,4,6-trinitrobenzenesulphonic acid-induced colitis were investigated. As previously described, colitis triggered a hypersensitivity to CRD. In basal conditions, both CB1 (WIN 55212-2) and CB2 (JWH 015) agonists reduced the abdominal response to CRD at a dose of 1 mg kg(-1), i.p. Both compounds were active at a lower dose (0.1 mg kg(-1)) abolishing the hypersensitivity induced by colitis. Administered alone, CB1 (Rimonabant) and CB2 (SR 144528) receptor antagonists (10 mg kg(-1)) had no effect on basal sensitivity. In contrast, the CB1, but not the CB2, receptor antagonist enhanced colitis-induced hyperalgesia. It is concluded that colonic inflammation enhances the antinociceptive action of CB1 and CB2 receptor agonists, and activates an endogenous, CB1 receptor mediated, antinociceptive pathway. PMID:16961698

  1. A dose-response strategy reveals differences between normal-weight and obese men in their metabolic and inflammatory responses to a high-fat meal.

    PubMed

    Schwander, Flurina; Kopf-Bolanz, Katrin A; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G; Piya, Milan K; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergčres, Guy

    2014-10-01

    A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. PMID:24812072

  2. HLA-B*5701 screening for susceptibility to abacavir hypersensitivity

    Microsoft Academic Search

    Andrew Lucas; David Nolan; Simon Mallal

    The introduction of highly active antiretroviral therapy (also known as combination therapy) has trans- formed the nature of HIV infection from a severe and ultimately fatal disease to that of a manageable chronic condition. HIV drugs are highly efficacious, but their use comes at the cost of a range of drug- related adverse events, including severe drug hypersensitivity reactions (HSRs)

  3. Amalgam-contact hypersensitivity lesions and oral lichen planus

    Microsoft Academic Search

    Martin H. Thornhill; Michael N. Pemberton; Raymond K. Simmons; Elizabeth D. Theaker

    2003-01-01

    Objective. The purpose of this study was to investigate the relationship between amalgam restorations and oral lichen planus. Study design. Eighty-one patients with oral lichenoid lesions were characterized clinically and skin patch tested for amalgam or mercury hypersensitivity. Thirty-three of these patients had amalgam fillings in contact with oral lesions replaced and were followed to determine the outcome. Results. Clinically,

  4. The Angiogenesis Inhibitor Thrombospondin1 Inhibits Acute Cutaneous Hypersensitivity Reactions

    Microsoft Academic Search

    Paula Velasco; Rainer Huegel; Jochen Brasch; Jens M Schröder; Michael Weichenthal; Eggert Stockfleth; Thomas Schwarz; Jack Lawler; Michael Detmar; Bernhard Lange-Asschenfeldt

    2009-01-01

    There is increasing evidence that vascular remodeling and endothelial cell activation promote acute and chronic inflammation. Thrombospondin 1 (TSP-1) is a potent endogenous angiogenesis inhibitor thought to play an important role in maintaining cutaneous vascular quiescence. We first investigated TSP-1 expression in human and contact hypersensitivity (CHS) reactions and found that TSP-1 was upregulated in the inflamed skin of patients

  5. Electromagnetic Hypersensitivity: A Systematic Review of Provocation Studies

    Microsoft Academic Search

    G. JAMES RUBIN; SIMON WESSELY

    2005-01-01

    Objectives: The objectives of this study were to assess whether people who report hypersensitivity to weak electromagnetic fields (EMFs) are better at detecting EMF under blind or double-blind conditions than nonhypersensitive individuals, and to test whether they respond to the presence of EMF with increased symptom reporting. Methods: An extensive systematic search was used to identify relevant blind or double-blind

  6. Secretome analysis revealed adaptive and non-adaptive responses of the Staphylococcus carnosus femB mutant

    PubMed Central

    Nega, Mulugeta; Dube, Linda; Kull, Melanie; Ziebandt, Anne-Kathrin; Ebner, Patrick; Albrecht, Dirk; Krismer, Bernhard; Rosenstein, Ralf; Hecker, Michael; Götz, Friedrich

    2015-01-01

    FemABX peptidyl transferases are involved in non-ribosomal pentaglycine interpeptide bridge biosynthesis. Here, we characterized the phenotype of a Staphylococcus carnosus femB deletion mutant, which was affected in growth and showed pleiotropic effects such as enhanced methicillin sensitivity, lysostaphin resistance, cell clustering, and decreased peptidoglycan cross-linking. However, comparative secretome analysis revealed a most striking difference in the massive secretion or release of proteins into the culture supernatant in the femB mutant than the wild type. The secreted proteins can be categorized into typical cytosolic proteins and various murein hydrolases. As the transcription of the murein hydrolase genes was up-regulated in the mutant, they most likely represent an adaption response to the life threatening mutation. Even though the transcription of the cytosolic protein genes was unaltered, their high abundance in the supernatant of the mutant is most likely due to membrane leakage triggered by the weakened murein sacculus and enhanced autolysins. PMID:25430637

  7. Parallel in vivo and in vitro melanoma RNAi dropout screens reveal synthetic lethality between hypoxia and DNA damage response inhibition.

    PubMed

    Possik, Patricia A; Müller, Judith; Gerlach, Carmen; Kenski, Juliana C N; Huang, Xinyao; Shahrabi, Aida; Krijgsman, Oscar; Song, Ji-Ying; Smit, Marjon A; Gerritsen, Bram; Lieftink, Cor; Kemper, Kristel; Michaut, Magali; Beijersbergen, Roderick L; Wessels, Lodewyk; Schumacher, Ton N; Peeper, Daniel S

    2014-11-20

    To identify factors preferentially necessary for driving tumor expansion, we performed parallel in vitro and in vivo negative-selection short hairpin RNA (shRNA) screens. Melanoma cells harboring shRNAs targeting several DNA damage response (DDR) kinases had a greater selective disadvantage in vivo than in vitro, indicating an essential contribution of these factors during tumor expansion. In growing tumors, DDR kinases were activated following hypoxia. Correspondingly, depletion or pharmacologic inhibition of DDR kinases was toxic to melanoma cells, including those that were resistant to BRAF inhibitor, and this could be enhanced by angiogenesis blockade. These results reveal that hypoxia sensitizes melanomas to targeted inhibition of the DDR and illustrate the utility of in vivo shRNA dropout screens for the identification of pharmacologically tractable targets. PMID:25456132

  8. Comparative Genomic and Transcriptomic Analyses Reveal Habitat Differentiation and Different Transcriptional Responses during Pectin Metabolism in Alishewanella Species

    PubMed Central

    Jung, Jaejoon

    2013-01-01

    Alishewanella species are expected to have high adaptability to diverse environments because they are isolated from different natural habitats. To investigate how the evolutionary history of Alishewanella species is reflected in their genomes, we performed comparative genomic and transcriptomic analyses of A. jeotgali, A. aestuarii, and A. agri, which were isolated from fermented seafood, tidal flat sediment, and soil, respectively. Genomic islands with variable GC contents indicated that invasion of prophage and transposition events occurred in A. jeotgali and A. agri but not in A. aestuarii. Habitat differentiation of A. agri from a marine environment to a terrestrial environment was proposed because the species-specific genes of A. agri were similar to those of soil bacteria, whereas those of A. jeotgali and A. aestuarii were more closely related to marine bacteria. Comparative transcriptomic analysis with pectin as a sole carbon source revealed different transcriptional responses in Alishewanella species, especially in oxidative stress-, methylglyoxal detoxification-, membrane maintenance-, and protease/chaperone activity-related genes. Transcriptomic and experimental data demonstrated that A. agri had a higher pectin degradation rate and more resistance to oxidative stress under pectin-amended conditions than the other 2 Alishewanella species. However, expression patterns of genes in the pectin metabolic pathway and of glyoxylate bypass genes were similar among all 3 Alishewanella species. Our comparative genomic and transcriptomic data revealed that Alishewanella species have evolved through horizontal gene transfer and habitat differentiation and that pectin degradation pathways in Alishewanella species are highly conserved, although stress responses of each Alishewanella species differed under pectin culture conditions. PMID:23934491

  9. Quantification of the rat spinal microglial response to peripheral nerve injury as revealed by immunohistochemical image analysis and flow cytometry.

    PubMed

    Blackbeard, J; O'Dea, K P; Wallace, V C J; Segerdahl, A; Pheby, T; Takata, M; Field, M J; Rice, A S C

    2007-08-30

    Microgliosis is implicated in the pathophysiology of several neurological disorders, including neuropathic pain. Consequently, perturbation of microgliosis is a mechanistic and drug development target in neuropathic pain, which highlights the requirement for specific, sensitive and reproducible methods of microgliosis measurement. In this study, we used the spinal microgliosis associated with L5 spinal nerve transection and minocycline-induced attenuation thereof to: (1) evaluate novel software based semi-quantitative image analysis paradigms for the assessment of immunohistochemical images. Microgliosis was revealed by immunoreactivity to OX42. Several image analysis paradigms were assessed and compared to a previously validated subjective categorical rating scale. This comparison revealed that grey scale measurement of the proportion of a defined area of spinal cord occupied by OX42 immunoreactive cells is a robust image analysis paradigm. (2) Develop and validate a flow cytometric approach for quantification of spinal microgliosis. The flow cytometric technique reliably quantified microgliosis in spinal cord cell suspensions, using OX42 and ED9 immunoreactivity to identify microglia. The results suggest that image analysis of immunohistochemical revelation of microgliosis reliably detects the spinal microgliosis in response to peripheral nerve injury and pharmacological attenuation thereof. In addition, flow cytometry provides an alternative approach for quantitative analysis of spinal microgliosis elicited by nerve injury. PMID:17553569

  10. Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a nonforensic sample.

    PubMed

    Yoder, Keith J; Porges, Eric C; Decety, Jean

    2015-04-01

    Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a nonforensic sample are linked to amygdala response to violence, this study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self-Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. PMID:25557777

  11. Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum

    PubMed Central

    2010-01-01

    Background Cutaneous mycoses are common human infections among healthy and immunocompromised hosts, and the anthropophilic fungus Trichophyton rubrum is the most prevalent microorganism isolated from such clinical cases worldwide. The aim of this study was to determine the transcriptional profile of T. rubrum exposed to various stimuli in order to obtain insights into the responses of this pathogen to different environmental challenges. Therefore, we generated an expressed sequence tag (EST) collection by constructing one cDNA library and nine suppression subtractive hybridization libraries. Results The 1388 unigenes identified in this study were functionally classified based on the Munich Information Center for Protein Sequences (MIPS) categories. The identified proteins were involved in transcriptional regulation, cellular defense and stress, protein degradation, signaling, transport, and secretion, among other functions. Analysis of these unigenes revealed 575 T. rubrum sequences that had not been previously deposited in public databases. Conclusion In this study, we identified novel T. rubrum genes that will be useful for ORF prediction in genome sequencing and facilitating functional genome analysis. Annotation of these expressed genes revealed metabolic adaptations of T. rubrum to carbon sources, ambient pH shifts, and various antifungal drugs used in medical practice. Furthermore, challenging T. rubrum with cytotoxic drugs and ambient pH shifts extended our understanding of the molecular events possibly involved in the infectious process and resistance to antifungal drugs. PMID:20144196

  12. Systematic analysis of maize class III peroxidase gene family reveals a conserved subfamily involved in abiotic stress response.

    PubMed

    Wang, Yu; Wang, Qianqian; Zhao, Yang; Han, Guomin; Zhu, Suwen

    2015-07-15

    Class III peroxidases (PRXs) are plant-specific enzymes that play key roles in the responses to biotic and abiotic stress during plant growth and development. In this study, we identified 119 nonredundant PRX genes (designated ZmPRXs). These PRX genes were divided into 18 groups based on their phylogenetic relationships. We performed systematic bioinformatics analysis of the PRX genes, including analysis of gene structures, conserved motifs, phylogenetic relationships and gene expression profiles. The ZmPRXs are unevenly distributed on the 10 maize chromosomes. In addition, these genes have undergone 16 segmental duplication and 12 tandem duplication events, indicating that both segmental and tandem duplication were the main contributors to the expansion of the maize PRX family. Ka/Ks analysis suggested that most duplicated ZmPRXs experienced purifying selection, with limited functional divergence during the duplication events, and comparative analysis among maize, sorghum and rice revealed that there were independent duplication events besides the whole-genome duplication of the maize genome. Furthermore, microarray analysis indicated that most highly expressed genes might play significant roles in root. We examined the expression of five candidate ZmPRXs under H2O2, SA, NaCl and PEG stress conditions using quantitative real-time PCR (qRT-PCR), revealing differential expression patterns. This study provides useful information for further functional analysis of the PRX gene family in maize. PMID:25895479

  13. Transcriptomics of the rice blast fungus Magnaporthe oryzae in response to the bacterial antagonist Lysobacter enzymogenes reveals candidate fungal defense response genes.

    PubMed

    Mathioni, Sandra M; Patel, Nrupali; Riddick, Bianca; Sweigard, James A; Czymmek, Kirk J; Caplan, Jeffrey L; Kunjeti, Sridhara G; Kunjeti, Saritha; Raman, Vidhyavathi; Hillman, Bradley I; Kobayashi, Donald Y; Donofrio, Nicole M

    2013-01-01

    Plants and animals have evolved a first line of defense response to pathogens called innate or basal immunity. While basal defenses in these organisms are well studied, there is almost a complete lack of understanding of such systems in fungal species, and more specifically, how they are able to detect and mount a defense response upon pathogen attack. Hence, the goal of the present study was to understand how fungi respond to biotic stress by assessing the transcriptional profile of the rice blast pathogen, Magnaporthe oryzae, when challenged with the bacterial antagonist Lysobacter enzymogenes. Based on microscopic observations of interactions between M. oryzae and wild-type L. enzymogenes strain C3, we selected early and intermediate stages represented by time-points of 3 and 9 hours post-inoculation, respectively, to evaluate the fungal transcriptome using RNA-seq. For comparative purposes, we also challenged the fungus with L. enzymogenes mutant strain DCA, previously demonstrated to be devoid of antifungal activity. A comparison of transcriptional data from fungal interactions with the wild-type bacterial strain C3 and the mutant strain DCA revealed 463 fungal genes that were down-regulated during attack by C3; of these genes, 100 were also found to be up-regulated during the interaction with DCA. Functional categorization of genes in this suite included those with roles in carbohydrate metabolism, cellular transport and stress response. One gene in this suite belongs to the CFEM-domain class of fungal proteins. Another CFEM class protein called PTH11 has been previously characterized, and we found that a deletion in this gene caused advanced lesion development by C3 compared to its growth on the wild-type fungus. We discuss the characterization of this suite of 100 genes with respect to their role in the fungal defense response. PMID:24098512

  14. Transcriptional responses of invasive and indigenous whiteflies to different host plants reveal their disparate capacity of adaptation.

    PubMed

    Xu, Hong-Xing; Hong, Yue; Zhang, Min-Zhu; Wang, Yong-Liang; Liu, Shu-Sheng; Wang, Xiao-Wei

    2015-01-01

    The whitefly Bemisia tabaci contains more than 35 cryptic species. The higher adaptability of Middle East-Asia Minor 1 (MEAM1) cryptic species has been recognized as one important factor for its invasion and displacement of other indigenous species worldwide. Here we compared the performance of the invasive MEAM1 and the indigenous Asia II 3 whitefly species following host plant transfer from a suitable host (cotton) to an unsuitable host (tobacco) and analyzed their transcriptional responses. After transfer to tobacco for 24 h, MEAM1 performed much better than Asia II 3. Transcriptional analysis showed that the patterns of gene regulation were very different with most of the genes up-regulated in MEAM1 but down-regulated in Asia II 3. Whereas carbohydrate and energy metabolisms were repressed in Asia II 3, the gene expression and protein metabolisms were activated in MEAM1. Compared to the constitutive high expression of detoxification genes in MEAM1, most of the detoxification genes were down-regulated in Asia II 3. Enzymatic activities of P450, GST and esterase further verified that the detoxification of MEAM1 was much higher than that of Asia II 3. These results reveal obvious differences in responses of MEAM1 and Asia II 3 to host transfer. PMID:26041313

  15. Capturing Arabidopsis Root Architecture Dynamics with root-fit Reveals Diversity in Responses to Salinity1[W][OPEN

    PubMed Central

    Julkowska, Magdalena M.; Hoefsloot, Huub C.J.; Mol, Selena; Feron, Richard; de Boer, Gert-Jan; Haring, Michel A.; Testerink, Christa

    2014-01-01

    The plant root is the first organ to encounter salinity stress, but the effect of salinity on root system architecture (RSA) remains elusive. Both the reduction in main root (MR) elongation and the redistribution of the root mass between MRs and lateral roots (LRs) are likely to play crucial roles in water extraction efficiency and ion exclusion. To establish which RSA parameters are responsive to salt stress, we performed a detailed time course experiment in which Arabidopsis (Arabidopsis thaliana) seedlings were grown on agar plates under different salt stress conditions. We captured RSA dynamics with quadratic growth functions (root-fit) and summarized the salt-induced differences in RSA dynamics in three growth parameters: MR elongation, average LR elongation, and increase in number of LRs. In the ecotype Columbia-0 accession of Arabidopsis, salt stress affected MR elongation more severely than LR elongation and an increase in LRs, leading to a significantly altered RSA. By quantifying RSA dynamics of 31 different Arabidopsis accessions in control and mild salt stress conditions, different strategies for regulation of MR and LR meristems and root branching were revealed. Different RSA strategies partially correlated with natural variation in abscisic acid sensitivity and different Na+/K+ ratios in shoots of seedlings grown under mild salt stress. Applying root-fit to describe the dynamics of RSA allowed us to uncover the natural diversity in root morphology and cluster it into four response types that otherwise would have been overlooked. PMID:25271266

  16. Transcriptional responses of invasive and indigenous whiteflies to different host plants reveal their disparate capacity of adaptation

    PubMed Central

    Xu, Hong-Xing; Hong, Yue; Zhang, Min-Zhu; Wang, Yong-Liang; Liu, Shu-Sheng; Wang, Xiao-Wei

    2015-01-01

    The whitefly Bemisia tabaci contains more than 35 cryptic species. The higher adaptability of Middle East-Asia Minor 1 (MEAM1) cryptic species has been recognized as one important factor for its invasion and displacement of other indigenous species worldwide. Here we compared the performance of the invasive MEAM1 and the indigenous Asia II 3 whitefly species following host plant transfer from a suitable host (cotton) to an unsuitable host (tobacco) and analyzed their transcriptional responses. After transfer to tobacco for 24 h, MEAM1 performed much better than Asia II 3. Transcriptional analysis showed that the patterns of gene regulation were very different with most of the genes up-regulated in MEAM1 but down-regulated in Asia II 3. Whereas carbohydrate and energy metabolisms were repressed in Asia II 3, the gene expression and protein metabolisms were activated in MEAM1. Compared to the constitutive high expression of detoxification genes in MEAM1, most of the detoxification genes were down-regulated in Asia II 3. Enzymatic activities of P450, GST and esterase further verified that the detoxification of MEAM1 was much higher than that of Asia II 3. These results reveal obvious differences in responses of MEAM1 and Asia II 3 to host transfer. PMID:26041313

  17. A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis

    PubMed Central

    Lissina, Elena; Young, Brian; Urbanus, Malene L.; Guan, Xue Li; Lowenson, Jonathan; Hoon, Shawn; Baryshnikova, Anastasia; Riezman, Isabelle; Michaut, Magali; Riezman, Howard; Cowen, Leah E.; Wenk, Markus R.; Clarke, Steven G.; Giaever, Guri; Nislow, Corey

    2011-01-01

    Using small molecule probes to understand gene function is an attractive approach that allows functional characterization of genes that are dispensable in standard laboratory conditions and provides insight into the mode of action of these compounds. Using chemogenomic assays we previously identified yeast Crg1, an uncharacterized SAM-dependent methyltransferase, as a novel interactor of the protein phosphatase inhibitor cantharidin. In this study we used a combinatorial approach that exploits contemporary high-throughput techniques available in Saccharomyces cerevisiae combined with rigorous biological follow-up to characterize the interaction of Crg1 with cantharidin. Biochemical analysis of this enzyme followed by a systematic analysis of the interactome and lipidome of CRG1 mutants revealed that Crg1, a stress-responsive SAM-dependent methyltransferase, methylates cantharidin in vitro. Chemogenomic assays uncovered that lipid-related processes are essential for cantharidin resistance in cells sensitized by deletion of the CRG1 gene. Lipidome-wide analysis of mutants further showed that cantharidin induces alterations in glycerophospholipid and sphingolipid abundance in a Crg1-dependent manner. We propose that Crg1 is a small molecule methyltransferase important for maintaining lipid homeostasis in response to drug perturbation. This approach demonstrates the value of combining chemical genomics with other systems-based methods for characterizing proteins and elucidating previously unknown mechanisms of action of small molecule inhibitors. PMID:22028670

  18. Comparative proteomic and physiological analyses reveal the protective effect of exogenous calcium on the germinating soybean response to salt stress.

    PubMed

    Yin, Yongqi; Yang, Runqiang; Han, Yongbin; Gu, Zhenxin

    2015-01-15

    Calcium enhances salt stress tolerance of soybeans. Nevertheless, the molecular mechanism of calcium's involvement in resistance to salt stress is unclear. A comparative proteomic approach was used to investigate protein profiles in germinating soybeans under NaCl-CaCl2 and NaCl-LaCl3 treatments. A total of 80 proteins affected by calcium in 4-day-old germinating soybean cotyledons and 71 in embryos were confidently identified. The clustering analysis showed proteins were subdivided into 5 and 6 clusters in cotyledon and embryo, respectively. Among them, proteins involved in signal transduction and energy pathways, in transportation, and in protein biosynthesis were largely enriched while those involved in proteolysis were decreased. Abundance of nucleoside diphosphate kinase and three antioxidant enzymes were visibly increased by calcium. Accumulation of gamma-aminobutyric acid and polyamines was also detected after application of exogenous calcium. This was consistent with proteomic results, which showed that proteins involved in the glutamate and methionine metabolism were mediated by calcium. Calcium could increase the salt stress tolerance of germinating soybeans via enriching signal transduction, energy pathway and transportation, promoting protein biosynthesis, inhibiting proteolysis, redistributing storage proteins, regulating protein processing in endoplasmic reticulum, enriching antioxidant enzymes and activating their activities, accumulating secondary metabolites and osmolytes, and other adaptive responses. Biological significance Soybean (Glycine max L.), as a traditional edible legume, is being targeted for designing functional foods. During soybean germination under stressful conditions especially salt stress, newly discovered functional components such as gamma-aminobutyric acid (GABA) are rapidly accumulated. However, soybean plants are relatively salt-sensitive and the growth, development and biomass of germinating soybeans are significantly suppressed under salt stress condition. According to previous studies, exogenous calcium counters the harmful effect of salt stress and increases the biomass and GABA content of germinating soybeans. Nevertheless, the precise molecular mechanism underlying the role of calcium in resistance to salt stress is still unknown. This paper is the first study employing comparative proteomic and physiological analyses to reveal the protective effect of exogenous calcium in the germinating soybean response to salt stress. Our study links the biological events with proteomic information and provides detailed peptide information on all identified proteins. The functions of those significantly changed proteins are also analyzed. The physiological and comparative proteomic analyses revealed the putative molecular mechanism of exogenous calcium treatment induced salt stress responses. The findings from this paper are beneficial to high GABA-rich germinating soybean biomass. Additionally, these findings also might be applicable to the genetic engineering of soybean plants to improve stress tolerance. PMID:25284050

  19. Brain Transcriptional Responses to High-Fat Diet in Acads-Deficient Mice Reveal Energy Sensing Pathways

    PubMed Central

    Kruger, Claudia; Kumar, K. Ganesh; Mynatt, Randall L.; Volaufova, Julia; Richards, Brenda K.

    2012-01-01

    Background How signals from fatty acid metabolism are translated into changes in food intake remains unclear. Previously we reported that mice with a genetic inactivation of Acads (acyl-coenzyme A dehydrogenase, short-chain), the enzyme responsible for mitochondrial beta-oxidation of C4–C6 short-chain fatty acids (SCFAs), shift consumption away from fat and toward carbohydrate when offered a choice between diets. In the current study, we sought to indentify candidate genes and pathways underlying the effects of SCFA oxidation deficiency on food intake in Acads?/? mice. Methodology/Principal Findings We performed a transcriptional analysis of gene expression in brain tissue of Acads?/? and Acads+/+ mice fed either a high-fat (HF) or low-fat (LF) diet for 2 d. Ingenuity Pathway Analysis revealed three top-scoring pathways significantly modified by genotype or diet: oxidative phosphorylation, mitochondrial dysfunction, and CREB signaling in neurons. A comparison of statistically significant responses in HF Acads?/? vs. HF Acads+/+ (3917) and Acads+/+ HF vs. LF Acads+/+ (3879) revealed 2551 genes or approximately 65% in common between the two experimental comparisons. All but one of these genes were expressed in opposite direction with similar magnitude, demonstrating that HF-fed Acads-deficient mice display transcriptional responses that strongly resemble those of Acads+/+ mice fed LF diet. Intriguingly, genes involved in both AMP-kinase regulation and the neural control of food intake followed this pattern. Quantitative RT-PCR in hypothalamus confirmed the dysregulation of genes in these pathways. Western blotting showed an increase in hypothalamic AMP-kinase in Acads?/? mice and HF diet increased, a key protein in an energy-sensing cascade that responds to depletion of ATP. Conclusions Our results suggest that the decreased beta-oxidation of short-chain fatty acids in Acads-deficient mice fed HF diet produces a state of energy deficiency in the brain and that AMP-kinase may be the cellular energy-sensing mechanism linking fatty acid oxidation to feeding behavior in this model. PMID:22936979

  20. Multiscale Distribution and Bioaccumulation Analysis of Clofazimine Reveals a Massive Immune System-Mediated Xenobiotic Sequestration Response

    PubMed Central

    Baik, Jason; Stringer, Kathleen A.; Mane, Gerta

    2013-01-01

    Chronic exposure to some well-absorbed but slowly eliminated xenobiotics can lead to their bioaccumulation in living organisms. Here, we studied the bioaccumulation and distribution of clofazimine, a riminophenazine antibiotic used to treat mycobacterial infection. Using mice as a model organism, we performed a multiscale, quantitative analysis to reveal the sites of clofazimine bioaccumulation during chronic, long-term exposure. Remarkably, between 3 and 8 weeks of dietary administration, clofazimine massively redistributed from adipose tissue to liver and spleen. During this time, clofazimine concentration in fat and serum significantly decreased, while the mass of clofazimine in spleen and liver increased by >10-fold. These changes were paralleled by the accumulation of clofazimine in the resident macrophages of the lymphatic organs, with as much as 90% of the clofazimine mass in spleen sequestered in intracellular crystal-like drug inclusions (CLDIs). The amount of clofazimine associated with CLDIs of liver and spleen macrophages disproportionately increased and ultimately accounted for a major fraction of the total clofazimine in the host. After treatment was discontinued, clofazimine was retained in spleen while its concentrations decreased in blood and other organs. Immunologically, clofazimine bioaccumulation induced a local, monocyte-specific upregulation of various chemokines and receptors. However, interleukin-1 receptor antagonist was also upregulated, and the acute-phase response pathways and oxidant capacity decreased or remained unchanged, marking a concomitant activation of an anti-inflammatory response. These experiments indicate an inducible, immune system-dependent, xenobiotic sequestration response affecting the atypical pharmacokinetics of a small molecule chemotherapeutic agent. PMID:23263006

  1. In vivo electrophysiological recordings in amygdala subnuclei reveal selective and distinct responses to a behaviorally identified predator odor.

    PubMed

    Govic, Antonina; Paolini, Antonio G

    2015-03-01

    Chemosensory cues signaling predators reliably stimulate innate defensive responses in rodents. Despite the well-documented role of the amygdala in predator odor-induced fear, evidence for the relative contribution of the specific nuclei that comprise this structurally heterogeneous structure is conflicting. In an effort to clarify this we examined neural activity, via electrophysiological recordings, in amygdala subnuclei to controlled and repeated presentations of a predator odor: cat urine. Defensive behaviors, characterized by avoidance, decreased exploration, and increased risk assessment, were observed in adult male hooded Wistar rats (n = 11) exposed to a cloth impregnated with cat urine. Electrophysiological recordings of the amygdala (777 multiunit clusters) were subsequently obtained in freely breathing anesthetized rats exposed to cat urine, distilled water, and eugenol via an air-dilution olfactometer. Recorded units selectively responded to cat urine, and frequencies of responses were distributed differently across amygdala nuclei; medial amygdala (MeA) demonstrated the greatest frequency of responses to cat urine (51.7%), followed by the basolateral and basomedial nuclei (18.8%) and finally the central amygdala (3.0%). Temporally, information transduction occurred primarily from the cortical amygdala and MeA (ventral divisions) to other amygdala nuclei. Interestingly, MeA subnuclei exhibited distinct firing patterns to predator urine, potentially revealing aspects of the underlying neurocircuitry of predator odor processing and defensiveness. These findings highlight the critical involvement of the MeA in processing olfactory cues signaling predator threat and converge with previous studies to indicate that amygdala regulation of predator odor-induced fear is restricted to a particular set of subnuclei that primarily include the MeA, particularly the ventral divisions. PMID:25475347

  2. Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression.

    PubMed

    Klüver, Nils; Yang, Lixin; Busch, Wibke; Scheffler, Katja; Renner, Patrick; Strähle, Uwe; Scholz, Stefan

    2011-01-01

    Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe) mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds. PMID:22205996

  3. T lymphocyte lines induce autoimmune encephalomyelitis, delayed hypersensitivity and bystander encephalitis or arthritis.

    PubMed

    Holoshitz, J; Naparstek, Y; Ben-Nun, A; Marquardt, P; Cohen, I R

    1984-08-01

    Lines of rat T lymphocytes responsive to the basic protein of myelin (BP) or to the purified protein derivative of Mycobacterium tuberculosis (PPD) were inoculated i.v. into recipient rats. As reported previously, the anti-BP line cells, but not the anti-PPD line cells spontaneously accumulated in the central nervous system and caused encephalomyelitis. However, the anti-PPD line cells could be induced to enter the brain and cause bystander encephalitis by intracerebral inoculation of PPD. Anti-PPD or anti-BP line cells could mediate delayed-type hypersensitivity skin reactions or bystander arthritis elicited by specific antigen. The lines did not cause specific cytolysis in vitro. Susceptibility to delayed-type hypersensitivity or bystander disease was long lasting in rats inoculated with anti-PPD line cells, while rats inoculated with anti-BP line cells were susceptible for only a few days. Thus, lines of T lymphocytes can mediate a variety of pathological reactions directed by the presence of specific antigen, self or foreign. PMID:6205882

  4. An Arabidopsis mutant hypersensitive to red and far-red light signals.

    PubMed Central

    Genoud, T; Millar, A J; Nishizawa, N; Kay, S A; Schäfer, E; Nagatani, A; Chua, N H

    1998-01-01

    A new mutant called psi2 (for phytochrome signaling) was isolated by screening for elevated activity of a chlorophyll a/b binding protein-luciferase (CAB2-LUC) transgene in Arabidopsis. This mutant exhibited hypersensitive induction of CAB1, CAB2, and the small subunit of ribulose-1,5-bisphosphate carboxylase (RBCS) promoters in the very low fluence range of red light and a hypersensitive response in hypocotyl growth in continuous red light of higher fluences. In addition, at high- but not low-light fluence rates, the mutant showed light-dependent superinduction of the pathogen-related protein gene PR-1a and developed spontaneous necrotic lesions in the absence of any pathogen. Expression of genes responding to various hormone and environmental stress pathways in the mutant was not significantly different from that of the wild type. Analysis of double mutants demonstrated that the effects of the psi2 mutation are dependent on both phytochromes phyA and phyB. The mutation is recessive and maps to the bottom of chromosome 5. Together, our results suggest that PSI2 specifically and negatively regulates both phyA and phyB phototransduction pathways. The induction of cell death by deregulated signaling pathways observed in psi2 is reminiscent of retinal degenerative diseases in animals and humans. PMID:9634578

  5. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management

    PubMed Central

    Rampton, David; Folkersen, Joergen; Fishbane, Steven; Hedenus, Michael; Howaldt, Stefanie; Locatelli, Francesco; Patni, Shalini; Szebeni, Janos; Weiss, Guenter

    2014-01-01

    Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases. Early pregnancy is a contraindication to iron infusions, while old age and serious co-morbidity may worsen the impact of acute reactions if they occur. Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. PMID:25420283

  6. Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles

    PubMed Central

    2012-01-01

    Background Astatine-211 (211At) is an alpha particle emitting halogen with almost optimal linear energy transfer for creating DNA double-strand breaks and is thus proposed for radionuclide therapy when bound to tumor-seeking agents. Unbound 211At accumulates in the thyroid gland, and the concept of basal radiation-induced biological effects in the thyroid tissue is, to a high degree, unknown and is most valuable. Methods Female BALB/c nude mice were intravenously injected with 0.064 to 42 kBq of 211At, resulting in absorbed doses of 0.05 to 32 Gy in the thyroid gland. Thyroids were removed 24 h after injection; total RNA was extracted from pooled thyroids and processed in triplicate using Illumina MouseRef-8 Whole-Genome Expression Beadchips. Results Thyroids exposed to 211At revealed distinctive gene expression profiles compared to non-irradiated controls. A larger number of genes were affected at low absorbed doses (0.05 and 0.5 Gy) compared to intermediate (1.4 Gy) and higher absorbed doses (11 and 32 Gy). The proportion of dose-specific genes increased with decreased absorbed dose. Additionally, 1.4 Gy often exerted opposite regulation on gene expression compared to the other absorbed doses. Using Gene Ontology data, an immunological effect was detected at 0.05 and 11 Gy. Effects on cellular response to external stress and cell cycle regulation and proliferation were detected at 1.4 and 11 Gy. Conclusions Conclusively, the cellular response to ionizing radiation is complex and differs with absorbed dose. The response acquired at high absorbed doses cannot be extrapolated down to low absorbed doses or vice versa. We also demonstrated that the thyroid - already at absorbed doses similar to those obtained in radionuclide therapy - responds with expression of a high number of genes. Due to the increased heterogeneous irradiation at low absorbed doses, we suggest that this response partly originates from non-irradiated cells in the tissue, i.e., bystander cells. PMID:22697397

  7. Analysis of the Organic Hydroperoxide Response of Chromobacterium violaceum Reveals That OhrR Is a Cys-Based Redox Sensor Regulated by Thioredoxin

    PubMed Central

    da Silva Neto, José F.; Negretto, Caroline C.; Netto, Luis E. S.

    2012-01-01

    Organic hydroperoxides are oxidants generated during bacterial-host interactions. Here, we demonstrate that the peroxidase OhrA and its negative regulator OhrR comprise a major pathway for sensing and detoxifying organic hydroperoxides in the opportunistic pathogen Chromobacterium violaceum. Initially, we found that an ohrA mutant was hypersensitive to organic hydroperoxides and that it displayed a low efficiency for decomposing these molecules. Expression of ohrA and ohrR was specifically induced by organic hydroperoxides. These genes were expressed as monocistronic transcripts and also as a bicistronic ohrR-ohrA mRNA, generating the abundantly detected ohrA mRNA and the barely detected ohrR transcript. The bicistronic transcript appears to be processed. OhrR repressed both the ohrA and ohrR genes by binding directly to inverted repeat sequences within their promoters in a redox-dependent manner. Site-directed mutagenesis of each of the four OhrR cysteine residues indicated that the conserved Cys21 is critical to organic hydroperoxide sensing, whereas Cys126 is required for disulfide bond formation. Taken together, these phenotypic, genetic and biochemical data indicate that the response of C. violaceum to organic hydroperoxides is mediated by OhrA and OhrR. Finally, we demonstrated that oxidized OhrR, inactivated by intermolecular disulfide bond formation, is specifically regenerated via thiol-disulfide exchange by thioredoxin (but not other thiol reducing agents such as glutaredoxin, glutathione and lipoamide), providing a physiological reducing system for this thiol-based redox switch. PMID:23071722

  8. [Effect of the cholinesterase reactivator dipyroxime in various models of delayed hypersensitivity during acute intoxication by acrylonitrile].

    PubMed

    Zabrodski?, P F; Kirichuk, V F; Romashchenko, S A; Germanchuk, V G

    2000-01-01

    Delayed type hypersensitivity (DTH) response with respect to sheep erythrocytes was studied on various models in CBA mice against the background of acute intoxication with nitrile acrylic acid (NAA). The effect of dipiroxime on the DTH response under these conditions was determined and the relationship of these reactions with the activity of alpha-naphthylbutyratesterase in splenic cells and popliteal lymph nodes was assessed. Dipiroxime partly recovered DTH in various experimental series (except for the reaction of suppressor cell transfer) by restoring the alpha-naphthylbutyratesterase activity in cells of the lymphoid organs studied. PMID:11109527

  9. Spinal D-amino acid oxidase contributes to mechanical pain hypersensitivity induced by sleep deprivation in the rat.

    PubMed

    Wei, Hong; Gong, Nian; Huang, Jin-Lu; Fan, Hui; Ma, Ai-Niu; Li, Xin-Yan; Wang, Yong-Xiang; Pertovaara, Antti

    2013-10-01

    We studied the hypothesis that spinal d-amino acid oxidase (DAAO) that is expressed in astrocytes and that has been reported to promote tonic pain in various pathophysiological conditions plays a role in 'physiological' pain hypersensitivity induced by rapid eye movement sleep deprivation (REMSD). The experiments were performed in healthy rats with a chronic intrathecal (i.t.) catheter. Pain behavior was assessed by determining limb withdrawal response to repetitive stimulation of the hind paw with a calibrated series of monofilaments. REMSD of 48 h duration produced a significant mechanical hypersensitivity. At 48 h of REMSD, the animals were treated i.t. with a DAAO inhibitor or vehicle. Three structurally different DAAO inhibitors were tested in this study: 6-chlorobenzo[d]isoxazol-3-ol (CBIO), sodium benzoate, and 5-methylpyrazole-3-carboxylic acid (AS-057278). CBIO (1-3 ?g), sodium benzoate (30-100 ?g) and AS-057278 (3-10 ?g) produced dose-related antihypersensitivity effects in sleep-deprived animals. In control animals (with no sleep deprivation), the currently used doses of DAAO inhibitors failed to produce significant changes in mechanically evoked pain behavior. The results indicate that among spinal pain facilitatory mechanisms that contribute to the sleep deprivation-induced mechanical pain hypersensitivity is DAAO, presumably due to production of reactive oxygen species, such as hydrogen peroxide, an endogenous agonist of the pronociceptive TRPA1 ion channel. PMID:23958579

  10. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK.

    PubMed

    Wang, Shao-Jun; Yang, Hao-Yan; Xu, Guo-Shuang

    2012-01-01

    Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD) tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36) and Shangjuxu (ST37) in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture. PMID:23097675

  11. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK

    PubMed Central

    Wang, Shao-Jun; Yang, Hao-Yan; Xu, Guo-Shuang

    2012-01-01

    Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD) tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36) and Shangjuxu (ST37) in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture. PMID:23097675

  12. Transfection of normal human and Chinese hamster DNA corrects diepoxybutane-induced chromosomal hypersensitivity of Fanconi anemia fibroblasts

    SciTech Connect

    Shaham, M.; Adler, B.; Ganguly, S.; Chaganti, R.S.K.

    1987-08-01

    Cultured cells from individuals affected with Fanconi anemia (FA) exhibit spontaneous chromosome breakage and hypersensitivity to the cell killing and clastogenic effects of the difunctional alkylating agent diepoxybutane (DEB). The authors report here the correction of both of these DEB-hypersensitivity phenotypes of FA cells achieved by cotransfection of normal placental of Chinese hamster lung cell DNA and the plasmid pSV2-neo-SVgpt. Transfectants were selected for clonogenic survival after treatment with DEB at a dose of 5 ..mu..gml. At this dose of DEB, the clonogenicity of normal fibroblasts was reduced to 50% and that of FA fibroblasts was reduced to zero. DEB-resistant (DEB/sup r/) colonies selected in this system exhibited a normal response to DEB-induced chromosome breakage and resistance to repeated DEB treatment. The neo and gpt sequences were detected by Southern blot analysis of DNA from one of four DEB/sup r/ colonies independently derived from transfection of human DNA and one of three DEB/sup r/ colonies independently derived from transfection of Chinese hamster DNA. The results demonstrate that DNA sequences that complement the two hallmark cellular phenotypes (cellular and chromosomal hypersensitivity to alkylating agents) of FA are present in human as well as Chinese hamster DNA. The cloning of these genes using transfection strategies can be expected to enable molecular characterization of FA

  13. [Application of basophil activation test in diagnosing aspirin hypersensitivity].

    PubMed

    Gawinowska, Marika; Specjalski, Krzysztof; Che?mi?ska, Marta; ?ata, Jakub; Zieli?ski, Maciej

    2015-01-01

    In the face of increasing prevalence of hypersensitivity reactions, introduction of effective, reliable and safe methods plays a crucial role in their diagnosing. Among the currently available laboratory (in vitro) methods is basophil activation test (BAT). It is a flow- cytometry based assay that allows to identificate in the blood sample basophils and additionally to asses the degree of cell activation after exposure to an antigen. The most common superficial identification markers are CD63 and CD203c, which increase in number after activation. Basophil actvation test can be applied to confirm diagnosis of allergy to Hymenoptera venoms, food, pollens and hypersensitivity to drugs. The aim of present paper is to present theoretical methods of this test as well as its pros and cons. We focus also on presentation of clinical case where BAT seemed to be a necessary addition to a routine diagnostic pathway. We present a case of identification of the culprit drug which caused an anaphylactic reaction. PMID:25577537

  14. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    PubMed

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-04-01

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories. PMID:24707159

  15. Hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji).

    PubMed

    Akizuki, N; Inase, N; Ishiwata, N; Jin, Y; Atarashi, K; Ichioka, M; Yoshizawa, Y; Marumo, F

    1999-01-01

    We report five cases of hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji). After having worked for 5 to 20 years, they began to notice symptoms of cough, sputum, and dyspnea. They were diagnosed as having a hypersensitivity pneumonitis based on clinical features, bronchoalveolar lavage and transbronchial lung biopsy. By the double immunodiffusion test, precipitating lines between shimeji spore antigen and sera were observed in all of the patients. By enzyme-linked immunosorbent assay, the antibody activities against shimeji and three species of fungi (Cladosporium sphaerospermum, Penicillium frequentans, and Scopulariopsis species) were significantly higher in the sera of the patients than in those of normal subjects who were cultivating shimeji. Although it is not clear what causes this disease, these findings may be helpful in determining the specific antigen. PMID:10364747

  16. The Hypersensitivity of Horses to Culicoides Bites in British Columbia

    PubMed Central

    Anderson, Gail S.; Belton, Peter; Kleider, Nicholas

    1988-01-01

    Culicoides hypersensitivity is a chronic, recurrent, seasonal dermatitis of horses that has a worldwide distribution, but has only recently been reported in Canada. It is characterized by intense pruritus resulting in lesions associated with self-induced trauma. A survey of veterinarians and horse-owners in British Columbia showed no differences in susceptibility due to the sex, color, breed, or height of the horses. The prevalence of the disease in the 209 horses surveyed was 26%. Horses sharing the same pasture could be unaffected. The disease was reported primarily from southwestern British Columbia; it occurred between April and October and usually affected the ventral midline, mane, and tail. Horses were generally less than nine years old when the clinical signs first appeared ([unk]=5.9 yr). Culicoides hypersensitivity was common in the lineage of several affected horses, possibly indicating a genetic susceptibility. Most cases were severe enough to require veterinary attention and some horses were euthanized. PMID:17423117

  17. Diagnosis and Management of Immediate Hypersensitivity Reactions to Cephalosporins

    PubMed Central

    Kim, Min-Hye

    2014-01-01

    Cephalosporins can cause a range of hypersensitivity reactions, including IgE-mediated, immediate reactions. Cephalosporin allergy has been reported with use of a specific cephalosporin, as a cross-reaction between different cephalosporins or as a cross-reaction to other ?-lactam antibiotics. Unlike penicillins, the exact allergenic determinants of cephalosporins are less well understood and thus, standardized diagnostic skin testing is not available. Nevertheless, skin testing with diluted solutions of cephalosporins can be valuable in confirming IgE-mediated hypersensitivity reactions. In vitro tests are in development using recent technological advances and can be used as complementary tests. However, they are not commonly used because of their reduced sensitivity and limited availability. In selected cases of inconclusive results in both skin tests and IgE assays, a graded challenge or induction of drug tolerance with the implicated cephalosporin should be performed. PMID:25374747

  18. Delayed hypersensitivity reaction from black henna tattoo manifesting as severe facial swelling.

    PubMed

    Shavit, Itai; Hoffmann, Yoav; Shachor-Meyouhas, Yael; Knaani-Levinz, Hadas

    2008-05-01

    We report on a 14-year-old boy who was presented to the emergency department with an acute swelling of the face and scalp 3 days after using a new hair dye. The patient had applied a black henna tattoo 1 year earlier. Patch testing revealed an allergy to the potent skin sensitizer paraphenylenediamine, a common ingredient of hair dyes and also found in black henna tattoo. It is important for emergency physicians to be aware of the possibility of a delayed type-IV hypersensitivity reaction from black henna tattoos manifesting as an acute contact dermatitis. These patients may have gross facial swelling but should not be treated for angioedema. PMID:18410830

  19. Alopecia in Rhesus macaques correlates with immunophenotypic alterations in dermal inflammatory infiltrates consistent with hypersensitivity etiology

    PubMed Central

    Kramer, Joshua; Fahey, Michele; Santos, Rosemary; Carville, Angela; Wachtman, Lynn; Mansfield, Keith

    2010-01-01

    Background Although alopecia is a commonly recognized problem affecting many captive Rhesus macaque colonies, there is no consensus as to the underlying etiology or appropriate course of management. Methods and Results We performed skin biopsies on a group of Rhesus macaques and demonstrate that alopecia is associated with superficial dermal perivascular mononuclear cell infiltrates and skin pathology consistent with chronic hypersensitivity dermatitis. Immunohistochemistry demonstrated that the inflammation is primarily composed of CD4+ cells admixed with histiocytes and mast cells. Inflammation is correlated with degree of alopecia. Further analysis in different groups of macaques revealed that animals born outdoors or infected with lung mites had reduced dermal inflammatory cell infiltrates and a lower incidence of alopecia. Conclusions These findings support a hypothesis that an altered housing status resulting in decreased pathogen burden in Rhesus macaque colonies may contribute to dermal immunophenotypic alterations and subsequent development of dermatitis with resultant alopecia. PMID:20102458

  20. Type IV hypersensitivity reaction to a temporary tattoo.

    PubMed

    Sonnen, Gregory

    2007-01-01

    A 6-year-old boy developed a skin eruption 10 days after application of a temporary tattoo advertised as a "natural black henna tattoo." The eruption was a delayed hypersensitivity reaction to the tattoo ink. The textile dye paraphenylenediamine (PPD) is a common industrial allergen and can be found in some temporary tattoo inks. This case describes the reaction and reviews the international literature pertaining to PPD and temporary tattoos. PMID:17256041

  1. Adrenergic hypersensitivity after beta-blocker withdrawal in hypertrophic cardiomyopathy.

    PubMed

    Gilligan, D M; Chan, W L; Stewart, R; Oakley, C M

    1991-09-15

    Withdrawal of beta-blocker therapy has been associated with the development of adrenergic hypersensitivity and adverse clinical effects in patients with coronary artery disease and hypertension. The aim of this study was to establish the occurrence and clinical significance of adrenergic hypersensitivity after abrupt withdrawal of long-term beta blockade in hypertrophic cardiomyopathy. Beta-adrenergic sensitivity was measured using the isoprenaline chronotropic dose25. Symptom assessment chronotropic dose25 calculation, bicycle exercise, echocardiography and Holter monitoring were performed while the patient received beta-blocker therapy and repeated on days 2, 4, 6, 8 (acute withdrawal period) and on day 21 after abrupt withdrawal. The study was terminated after 7 patients had been studied because all patients experienced a marked deterioration in symptoms and several clinical events had occurred. The chronotropic dose25 (mean +/- standard deviation) demonstrated beta 1-adrenergic hypersensitivity with a minimal value of 1.6 +/- 0.8 micrograms during the acute withdrawal period compared with 3.8 +/- 1.7 micrograms on day 21 (p = 0.003). Heart rates during rest and exercise showed an overshoot increase during the acute withdrawal period. The maximal 24-hour ventricular ectopic count was higher during the acute withdrawal period than during day 21 (p = 0.04). Of 3 patients with inducible outflow tract gradients, 2 developed resting gradients greater than 30 mm Hg during the acute withdrawal period. There was an increase in peak late filling velocity of mitral inflow after beta-blocker withdrawal. In conclusion, transient beta-adrenergic hypersensitivity occurs after beta-blocker withdrawal in hypertrophic cardiomyopathy and is associated with significant physiologic changes and adverse clinical consequences. PMID:1892084

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

    PubMed Central

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

    2013-01-01

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

  3. Pyrosequencing-Based Transcriptome Analysis of the Asian Rice Gall Midge Reveals Differential Response during Compatible and Incompatible Interaction

    PubMed Central

    Sinha, Deepak Kumar; Nagaraju, Javaregowda; Tomar, Archana; Bentur, Jagadish S.; Nair, Suresh

    2012-01-01

    The Asian rice gall midge (Orseolia oryzae) is a major pest responsible for immense loss in rice productivity. Currently, very little knowledge exists with regard to this insect at the molecular level. The present study was initiated with the aim of developing molecular resources as well as identifying alterations at the transcriptome level in the gall midge maggots that are in a compatible (SH) or in an incompatible interaction (RH) with their rice host. Roche 454 pyrosequencing strategy was used to develop both transcriptomics and genomics resources that led to the identification of 79,028 and 85,395 EST sequences from gall midge biotype 4 (GMB4) maggots feeding on a susceptible and resistant rice variety, TN1 (SH) and Suraksha (RH), respectively. Comparative transcriptome analysis of the maggots in SH and RH revealed over-representation of transcripts from proteolysis and protein phosphorylation in maggots from RH. In contrast, over-representation of transcripts for translation, regulation of transcription and transcripts involved in electron transport chain were observed in maggots from SH. This investigation, besides unveiling various mechanisms underlying insect-plant interactions, will also lead to a better understanding of strategies adopted by insects in general, and the Asian rice gall midge in particular, to overcome host defense. PMID:23202939

  4. Phenotypic and transcriptional profiling in Entamoeba histolytica reveal costs to fitness and adaptive responses associated with metronidazole resistance

    PubMed Central

    Penuliar, Gil M.; Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2015-01-01

    Antimicrobial chemotherapy is critical in the fight against infectious diseases caused by Entamoeba histolytica. Among the drugs available for the treatment of amebiasis, metronidazole (MTZ) is considered the drug of choice. Recently, in vitro studies have described MTZ resistance and the potential mechanisms involved. Costs to fitness and adaptive responses associated with resistance, however, have not been investigated. In this study we generated an HM-1 derived strain resistant to 12 ?M MTZ (MTZR). We examined its phenotypic and transcriptional profile to determine the consequences and mRNA level changes associated with MTZ resistance. Our results indicated increased cell size and granularity, and decreased rates in cell division, adhesion, phagocytosis, cytopathogenicity, and glucose consumption. Transcriptome analysis revealed 142 differentially expressed genes in MTZR. In contrast to other MTZ resistant parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but showed increased expression of genes for a hypothetical protein (HP1) and several iron-sulfur flavoproteins, and downregulation of genes for leucine-rich proteins. Fisher's exact test showed 24 significantly enriched GO terms in MTZR, and a 3-way comparison of modulated genes in MTZR against those of MTZR cultured without MTZ and HM-1 cultured with MTZ, showed that 88 genes were specific to MTZR. Overall, our findings suggested that MTZ resistance is associated with specific transcriptional changes and decreased parasite virulence. PMID:25999919

  5. Online Nanoflow RP-RP-MS Reveals Dynamics of Multi-component Ku Complex in Response to DNA Damage

    PubMed Central

    Zhou, Feng; Cardoza, Job D.; Ficarro, Scott B.; Adelmant, Guillaume O.; Lazaro, Jean-Bernard; Marto, Jarrod A.

    2010-01-01

    Tandem affinity purification (TAP) coupled with mass spectrometry has become the technique of choice for characterization of multi-component protein complexes. While current TAP protocols routinely provide high yield and specificity for proteins expressed under physiologically relevant conditions, analytical figures of merit required for efficient and in-depth LC-MS analysis remain unresolved. Here we implement a multidimensional chromatography platform, based on two stages of reversed-phase separation operated at high and low pH, respectively. We compare performance metrics for RP-RP and SCX-RP for the analysis of complex peptide mixtures derived from cell lysate, as well as protein complexes purified via TAP. Our data reveal that RP-RP fractionation outperforms SCX-RP primarily due to increased peak capacity in the first dimension separation. We integrate this system with miniaturized LC assemblies to achieve true online fractionation at low (?5nL/min) effluent flow rates. Stable isotope labeling is used to monitor the dynamics of the multi-component Ku protein complex in response to DNA damage induced by gamma radiation. PMID:20873769

  6. Structural ensembles reveal intrinsic disorder for the multi-stimuli responsive bio-mimetic protein Rec1-resilin.

    PubMed

    Balu, Rajkamal; Knott, Robert; Cowieson, Nathan P; Elvin, Christopher M; Hill, Anita J; Choudhury, Namita R; Dutta, Naba K

    2015-01-01

    Rec1-resilin is the first recombinant resilin-mimetic protein polymer, synthesized from exon-1 of the Drosophila melanogaster gene CG15920 that has demonstrated unusual multi-stimuli responsiveness in aqueous solution. Crosslinked hydrogels of Rec1-resilin have also displayed remarkable mechanical properties including near-perfect rubber-like elasticity. The structural basis of these extraordinary properties is not clearly understood. Here we combine a computational and experimental investigation to examine structural ensembles of Rec1-resilin in aqueous solution. The structure of Rec1-resilin in aqueous solutions is investigated experimentally using circular dichroism (CD) spectroscopy and small angle X-ray scattering (SAXS). Both bench-top and synchrotron SAXS are employed to extract structural data sets of Rec1-resilin and to confirm their validity. Computational approaches have been applied to these experimental data sets in order to extract quantitative information about structural ensembles including radius of gyration, pair-distance distribution function, and the fractal dimension. The present work confirms that Rec1-resilin is an intrinsically disordered protein (IDP) that displays equilibrium structural qualities between those of a structured globular protein and a denatured protein. The ensemble optimization method (EOM) analysis reveals a single conformational population with partial compactness. This work provides new insight into the structural ensembles of Rec1-resilin in solution. PMID:26042819

  7. Spatial organization of embryonic stem cell responsiveness to autocrine gp130 ligands reveals an autoregulatory stem cell niche.

    PubMed

    Davey, Ryan E; Zandstra, Peter W

    2006-11-01

    Highly ordered aggregates of cells, or niches, regulate stem cell fate. Specific tissue location need not be an obligatory requirement for a stem cell niche, particularly during embryogenesis, where cells exist in a dynamic environment. We investigated autoregulatory fixed-location-independent processes controlling cell fate by analyzing the spatial organization of embryonic stem cells (ESCs) using quantitative single-cell immunocytochemistry and a computational approach involving Delaunay triangulation. ESC colonies demonstrated radial organization of phosphorylated signal transducer and activator of transcription 3, Nanog, and Oct4 (among others) in the presence and absence of exogenous leukemia inhibitory factor (LIF). Endogenous self-renewal signaling resulted from autocrine non-LIF gp130 ligands, which buffered cells against differentiation upon exogenous LIF deprivation. Together with a radial organization of differential responsiveness to gp130 ligands within colonies, autocrine signaling produced a radial organization of self-renewal, generating a fixed-location-independent autoregulatory niche. These findings reveal fundamental properties of niches and elucidate mechanisms colonies of cells use to transition between fates during morphogenesis. PMID:16825607

  8. High-Density PhyloChip profiling of stimulated aquifer microbial communities reveals a complex response to acetate amendment

    SciTech Connect

    Handley, Kim M.; Wrighton, Kelly C.; Piceno, Y. M.; Andersen, Gary L.; DeSantis, Todd; Williams, Kenneth H.; Wilkins, Michael J.; N'Guessan, A. Lucie; Peacock, Aaron D.; Bargar, John; Long, Philip E.; Banfield, Jillian F.

    2012-04-13

    There is increasing interest in harnessing the functional capacities of indigenous microbial communities to transform and remediate a wide range of environmental contaminants. Information about which community members respond to stimulation can guide the interpretation and development of remediation approaches. To comprehensively determine community membership and abundance patterns among a suite of samples associated with uranium bioremediation experiments we employed a high?density microarray (PhyloChip). Samples were unstimulated, naturally reducing, or collected during Fe(III) (early) and sulfate reduction (late biostimulation) from an acetate re?amended/amended aquifer in Rifle, Colorado, and from laboratory experiments using field?collected materials. Deep community sampling with PhyloChip identified hundreds?to?thousands of operational taxonomic units (OTUs) present during amendment, and revealed close similarity among highly enriched taxa from drill?core and groundwater well?deployed column sediment. Overall, phylogenetic data suggested stimulated community membership was most affected by a carryover effect between annual stimulation events. Nevertheless, OTUs within the Fe(III)? and sulfate?reducing lineages, Desulfuromonadales and Desulfobacterales, were repeatedly stimulated. Less consistent, co?enriched taxa represented additional lineages associated with Fe(III) and sulfate reduction (for example, Desulfovibrionales; Syntrophobacterales; Peptococcaceae) and autotrophic sulfur oxidation (Sulfurovum; Campylobacterales). These data imply complex membership among highly stimulated taxa, and by inference biogeochemical responses to acetate, a non?fermentable substrate.

  9. Structural ensembles reveal intrinsic disorder for the multi-stimuli responsive bio-mimetic protein Rec1-resilin

    PubMed Central

    Balu, Rajkamal; Knott, Robert; Cowieson, Nathan P.; Elvin, Christopher M.; Hill, Anita J.; Choudhury, Namita R.; Dutta, Naba K.

    2015-01-01

    Rec1-resilin is the first recombinant resilin-mimetic protein polymer, synthesized from exon-1 of the Drosophila melanogaster gene CG15920 that has demonstrated unusual multi-stimuli responsiveness in aqueous solution. Crosslinked hydrogels of Rec1-resilin have also displayed remarkable mechanical properties including near-perfect rubber-like elasticity. The structural basis of these extraordinary properties is not clearly understood. Here we combine a computational and experimental investigation to examine structural ensembles of Rec1-resilin in aqueous solution. The structure of Rec1-resilin in aqueous solutions is investigated experimentally using circular dichroism (CD) spectroscopy and small angle X-ray scattering (SAXS). Both bench-top and synchrotron SAXS are employed to extract structural data sets of Rec1-resilin and to confirm their validity. Computational approaches have been applied to these experimental data sets in order to extract quantitative information about structural ensembles including radius of gyration, pair-distance distribution function, and the fractal dimension. The present work confirms that Rec1-resilin is an intrinsically disordered protein (IDP) that displays equilibrium structural qualities between those of a structured globular protein and a denatured protein. The ensemble optimization method (EOM) analysis reveals a single conformational population with partial compactness. This work provides new insight into the structural ensembles of Rec1-resilin in solution. PMID:26042819

  10. Adrenergic hypersensitivity after beta-blocker withdrawal.

    PubMed

    Ross, P J; Lewis, M J; Sheridan, D J; Henderson, A H

    1981-06-01

    We investigated the possibility of a rebound increase in sympathetic response after stopping beta-blocker treatment by measuring heart rate under conditions of increased sympathetic drive, as provided by standing with vasodilatation, or the Valsalva manoeuvure. Significant rebound increases in heart rate were observed after stopping propranolol given for one or more weeks but not when given for only four days. The amplitude of the rebound heart rate relative to the control heart rate off beta-blockers was similar after propranolol, atenolol, oxprenolol, or acebutolol, and in hyperthyroid subjects. PMID:6114739

  11. Differential modulation of contact hypersensitivity and delayed hypersensitivity reactions by topical application of 12-O-tetradecanoylphorbol-13-acetate.

    PubMed

    Kodari, E; Pavone, A; Reiners, J J

    1993-11-01

    Ear/footpad swelling following sensitization and challenge with 2,4-dinitrofluorobenzene (DNFB)/allogenic splenocytes (AS) were used to monitor the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on contact hypersensitivity (CHS) and delayed hypersensitivity (DHS) reactions, respectively. Topical treatment of dorsal or ventral SENCAR mouse skin 4x with 2 micrograms of TPA prior to sensitization of dorsal skin with DNFB suppressed attempts to induce CHS by subsequent challenge with DNFB. The adoptive transfer of splenocytes isolated from mice pretreated on the dorsum with TPA prior to dorsal sensitization with DNFB inhibited the development of CHS to DNFB in recipient mice. Conversely, topical treatment with TPA prior to s.c. sensitization with AS neither suppressed subsequent attempts to induce DHS, nor resulted in the generation of a splenocyte population capable of suppressing DHS reactions in adoptive transfer studies. Thus, promoting doses of topically applied TPA has differential effects on CHS and DHS reactions. PMID:8301022

  12. Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response

    PubMed Central

    2013-01-01

    Background Traumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24?h post-injury. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and naďve (control) brain tissue were used for microarray analysis. Ingenuity Pathway Analysis (IPA) software was used to identify molecular pathways and networks that were associated with the altered gene expression in brain tissues following TBI. Results Inspection of the top fifteen biological functions in IPA associated with TBI in the ipsilateral tissues revealed that all had an inflammatory component. IPA analysis also indicated that inflammatory genes were altered on the contralateral side, but many of the genes were inversely expressed compared to the ipsilateral side. The contralateral gene expression pattern suggests a remote anti-inflammatory molecular response. We created a network of the inversely expressed common (i.e., same gene changed on both sides of the brain) inflammatory response (IR) genes and those IR genes included in pathways and networks identified by IPA that changed on only one side. We ranked the genes by the number of direct connections each had in the network, creating a gene interaction hierarchy (GIH). Two well characterized signaling pathways, toll-like receptor/NF-kappaB signaling and JAK/STAT signaling, were prominent in our GIH. Conclusions Bioinformatic analysis of microarray data following TBI identified key molecular pathways and networks associated with neural injury following TBI. The GIH created here provides a starting point for investigating therapeutic targets in a ranked order that is somewhat different than what has been presented previously. In addition to being a vehicle for identifying potential targets for post-TBI therapeutic strategies, our findings can also provide a context for evaluating the potential of therapeutic agents currently in development. PMID:23617241

  13. Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity

    PubMed Central

    Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J.; Kerr, Simon R. J.; Parry, Steve W.

    2015-01-01

    Background Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Methods Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Results Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Conclusions Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity. PMID:26057525

  14. Expression analysis of global gene response to chronic heat exposure in broiler chickens (Gallus gallus) reveals new reactive genes.

    PubMed

    Li, C; Wang, X; Wang, G; Li, N; Wu, C

    2011-05-01

    The process of heat regulation is complex and the exact molecular mechanism is not fully understood. To investigate the global gene response to chronic heat exposure, a breast muscle cDNA library and a liver tissue cDNA library from Silkie fowl were constructed and analyzed in bioinformatics. A total of 8,935 nonredundant EST were identified from and used for gene expression analysis. Microarray assay revealed that in breast muscle of broiler chickens (Gallus gallus), 110 genes changed expression levels after 3 wk of cycling heat stress. Ubiquitin B (UBB); ubiquitin C (UBC); tumor necrosis factor receptor-associated factor 3-interacting Jun amino-terminal kinase activating modulator (TRAF3IP3); eukaryotic translation initiation factor 3, subunit 6 (EIF3S6); poly(A) binding protein, cytoplasmic 1 (PABPC1); and F-box only protein 11 (FBXO11) were the only genes that have been reported to be involved in heat regulation; the majority of the other genes were shown to be related for the first time. The finding of new heat-reactive genes [mitogen-activated protein kinase activating protein PM20/PM21; suppressors of cytokine signaling (SOCS) box-containing protein 2 (ASB2); ubiquitin-specific proteinase 45 (USP45); and TRK-fused gene (TFG)] suggests that the mitogen-activated protein kinase pathways as well as the ubiquitin-proteasome pathways and the nuclear factor ?B pathways play important roles in heat regulation. This study provides new information on the regulation of heat stress, though the mechanism is far from being understood. Further in-depth research on the newly discovered heat-reactive genes is required to fully understand their molecular functions in thermoregulation. PMID:21489951

  15. High-density PhyloChip profiling of stimulated aquifer microbial communities reveals a complex response to acetate amendment

    SciTech Connect

    Handley, Kim M.; Wrighton, Kelly E.; Piceno, Y. M.; Anderson, Gary L.; DeSantis, Todd; Williams, Kenneth H.; Wilkins, Michael J.; N'Guessan, A. L.; Peacock, Aaron; Bargar, John R.; Long, Philip E.; Banfield, Jillian F.

    2012-06-13

    There is increasing interest in harnessing the functional diversity of indigenous microbial communities to transform and remediate a wide range of environmental contaminants. Understanding the response of communities to stimulation, including flanking taxa, presents important opportunities for optimizing remediation approaches. We used high-density PhyloChip microarray analysis to comprehensively determine community membership and abundance patterns amongst a suite of samples from U(VI) bioremediation experiments. Samples were unstimulated or collected during Fe(III) and sulfate reduction from an acetate-augmented aquifer in Rifle, Colorado, and from laboratory experiments using field-collected materials. Results showed the greatest diversity in abundant SRB lineages was present in naturally-reduced sediment. Desulfuromonadales and Desulfobacterales were consistently identified as the dominant Fe(III)- and sulfate-reducing bacteria (IRB and SRB) throughout acetate amendment experiments. Stimulated communities also exhibited a high degree of functional redundancy amongst enriched flanking members. Not surprisingly, competition for both sulfate and iron was evident amongst abundant taxa, but the distribution and abundance of these ancillary SRB (Peptococcaceae, Desulfovibrionales and Syntrophobacterales), and lineages containing IRB (excluding Desulfobacteraceae) was heterogeneous amongst sample types. Interesting, amongst the most abundant taxa, particularly during sulfate reduction, were Epsilonproteobacteria that perform microaerobic or nitrate-dependant sulfur oxidation, and a number of bacteria other than Geobacteraceae that may enzymatically reduce U(VI). Finally, in depth community probing with PhyloChip determined the efficacy of experimental approaches, notably revealing striking similarity amongst stimulated sediment (from drill cores and in-situ columns) and groundwater communities, and demonstrating that sediment-packed in-situ (down-well) columns served as an ideal method for subsurface biostimulation.

  16. Lipidomic Profiling of Saccharomyces cerevisiae and Zygosaccharomyces bailii Reveals Critical Changes in Lipid Composition in Response to Acetic Acid Stress

    PubMed Central

    Riezman, Howard; Olsson, Lisbeth; Bettiga, Maurizio

    2013-01-01

    When using microorganisms as cell factories in the production of bio-based fuels or chemicals from lignocellulosic hydrolysate, inhibitory concentrations of acetic acid, released from the biomass, reduce the production rate. The undissociated form of acetic acid enters the cell by passive diffusion across the lipid bilayer, mediating toxic effects inside the cell. In order to elucidate a possible link between lipid composition and acetic acid stress, the present study presents detailed lipidomic profiling of the major lipid species found in the plasma membrane, including glycerophospholipids, sphingolipids and sterols, in Saccharomyces cerevisiae (CEN.PK 113_7D) and Zygosaccharomyces bailii (CBS7555) cultured with acetic acid. Detailed physiological characterization of the response of the two yeasts to acetic acid has also been performed in aerobic batch cultivations using bioreactors. Physiological characterization revealed, as expected, that Z. bailii is more tolerant to acetic acid than S. cerevisiae. Z. bailii grew at acetic acid concentrations above 24 g L?1, while limited growth of S. cerevisiae was observed after 11 h when cultured with only 12 g L?1 acetic acid. Detailed lipidomic profiling using electrospray ionization, multiple-reaction-monitoring mass spectrometry (ESI-MRM-MS) showed remarkable changes in the glycerophospholipid composition of Z. bailii, including an increase in saturated glycerophospholipids and considerable increases in complex sphingolipids in both S. cerevisiae (IPC 6.2×, MIPC 9.1×, M(IP)2C 2.2×) and Z. bailii (IPC 4.9×, MIPC 2.7×, M(IP)2C 2.7×), when cultured with acetic acid. In addition, the basal level of complex sphingolipids was significantly higher in Z. bailii than in S. cerevisiae, further emphasizing the proposed link between lipid saturation, high sphingolipid levels and acetic acid tolerance. The results also suggest that acetic acid tolerance is associated with the ability of a given strain to generate large rearrangements in its lipid profile. PMID:24023914

  17. Langerhans cell function dictates induction of contact hypersensitivity or unresponsiveness to DNFB in Syrian hamsters

    SciTech Connect

    Streilein, J.W.; Bergstresser, P.R.

    1981-09-01

    The relationship between distribution and function of Langerhans cells within the epidermis and the capacity of cutaneous surfaces to promote the induction of contact hypersensitivity to DNFB have been examined in inbred Syrian hamsters. In a manner very similar to previous findings in mice, the results indicate that hamster cutaneous surfaces deficient in normally functioning Langerhans cells, naturally (cheek pouch epithelium) or artificially (after perturbation with ultraviolet light), are inefficient at promoting DNFB sensitization. Instead, DNFB applied to these regions of skin results in the induction of a state of specific unresponsiveness. Viable lymphoid cells from unresponsive hamsters can transfer the unresponsiveness to naive hamsters suggesting that active suppression is at least partly responsible, probably mediated by T lymphocytes.

  18. Hypersensitivity of human testis-tumour cell lines to chemotherapeutic drugs.

    PubMed

    Masters, J R; Osborne, E J; Walker, M C; Parris, C N

    1993-01-21

    Metastatic testis tumours, in contrast to most other types of cancer, can be cured by drugs. To investigate which classes of chemotherapeutic drug are differentially toxic to testis-tumour cells, we compared the in vitro dose-response curves of 5 human testis and 5 bladder-cancer cell lines to 12 compounds. The testis cells were hypersensitive to drugs that interact directly with DNA (m-amsa, bleomycin, cisplatin, doxorubicin, methylnitrosourea, mitozolomide, etoposide, mitomycin-C), but little or no difference between the 2 cell types was seen following exposure to drugs whose mechanisms of action do not involve direct interaction with DNA (methotrexate, 5-fluorouracil, colchicine, vinblastine). We conclude that testis tumour cells are either less tolerant of, or have a reduced capacity to repair, DNA damage. PMID:8425772

  19. HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review

    PubMed Central

    Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

    2014-01-01

    T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity. PMID:24901010

  20. Sensitization of Cutaneous, Neuronal Purinergic Receptors Contributes to Endothelin-1-Induced Mechanical Hypersensitivity

    PubMed Central

    Barr, Travis P.; Hrnjic, Alen; Khodorova, Alla; Sprague, Jared M.; Strichartz, Gary R.

    2014-01-01

    Endothelin (ET-1), an endogenous peptide with a prominent role in cutaneous pain, causes mechanical hypersensitivity in the rat hind paw, partly through mechanisms involving local release of algogenic molecules in the skin. The present study investigated involvement of cutaneous ATP, which contributes to pain in numerous animal models. Pre-exposure of ND7/104 immortalized sensory neurons to ET-1 (30 nM) for 10 min increased the proportion of cells responding to ATP (2 ?M) with an increase in intracellular calcium, an effect prevented by the ETA receptor-selective antagonist BQ-123. ET-1 (3 nM) pre-exposure also increased the proportion of isolated mouse DRG neurons responding to ATP (0.2-0.4 ?M). Blocking ET-1-evoked increases in intracellular calcium with the IP3 receptor antagonist 2-APB did not inhibit sensitization to ATP, indicating a mechanism independent of ET-1-mediated intracellular calcium increases. ET-1-sensitized ATP calcium responses were largely abolished in the absence of extracellular calcium, implicating ionotropic P2X receptors. Experiments using qPCR and receptor-selective ligands in ND7/104 showed that ET-1-induced sensitization most likely involves the P2X4 receptor subtype. ET-1-sensitized calcium responses to ATP were strongly inhibited by broad spectrum (TNP-ATP) and P2X4-selective (5-BDBD) antagonists, but not antagonists for other P2X subtypes. TNP-ATP and 5-BDBD also significantly inhibited ET-1-induced mechanical sensitization in the rat hind paw, supporting a role for purinergic receptor sensitization in vivo. These data provide evidence that mechanical hypersensitivity caused by cutaneous ET-1 involves an increase in the neuronal sensitivity to ATP in the skin, possibly due to sensitization of P2X4 receptors. PMID:24569146

  1. ATHB17 is a positive regulator of abscisic acid response during early seedling growth.

    PubMed

    Park, Min Young; Kim, Sung-Ah; Lee, Sun-Ji; Kim, Soo Young

    2013-02-01

    We performed activation tagging screen to isolate abscisic acid (ABA) response mutants. One of the mutants, designated ahs10 (ABA-hypersensitive 10), exhibited ABA-hypersensitive phenotypes. TAIL-PCR analysis of the mutant revealed that T-DNA was inserted in the promoter region of the Arabidopsis gene, At2g01430, which encodes a homeodomain-leucine zipper protein ATHB17. Subsequent expression analysis indicated that ATHB17 was activated in ahs10. To recapitulate the mutant phenotypes, we prepared ATHB17 OX lines and investigated their phenotypes. The results showed that ATHB17 confers ABA-hypersensitivity and drought tolerance. On the contrary, ATHB17 knockout lines were ABA-insensitive and drought-sensitive, further demonstrating that ATHB17 is involved in ABA and water-stress responses. Interestingly, the ATHB17 effect on seedling growth in the presence of ABA was observed only during the postgermination seedling establishment stage, suggesting that it functions during a narrow developmental window of early seedling growth. PMID:23456334

  2. Intensities of hypersensitive transitions in garnet crystals doped with Er3+ ions

    NASA Astrophysics Data System (ADS)

    Bol'Shakova, E. V.; Malov, A. V.; Ryabochkina, P. A.; Ushakov, S. N.; Nishchev, K. N.

    2011-06-01

    We examine the oscillator strengths and the intensity parameters ? t ( t = 2, 4, 6) of yttrium-aluminum, scandium-containing, and gallium garnet crystals doped with Er3+ ions. A comparative analysis of the oscillator strengths and the intensity parameters ? t ( t = 2, 4, 6) of garnets with different contents of Al3+ and Sc3+ ions (Gd2.4Er0.5Sc1.8Al3.3O12, Gd2.4Er0.5Sc1.9Al3.2O12, Gd2.4Er0.5Sc2.0Al3.1O12) is performed, as a result of which the oscillator strengths and the intensity parameters ? t ( t = 2, 4, 6) of these crystals are shown to have close values. We find that Ca3(NbGa)5O12 crystals doped with Er3+ ions are characterized by highest values of the oscillator strengths for hypersensitive transitions and of the intensity parameter ?2 of Er3+ ions compared to the values of these quantities in the examined garnet crystals, which is determined by the fact that the symmetry of the local environment of Er3+ ions in these crystals is C 1, C 2, or C 2?. We reveal that, as the concentration of Er3+ ions in these crystals increases from 1 to 39 at %, both the oscillator strength of the hypersensitive transition 4 I 15/2 ? 2 H 11/2 of Er3+ ions and their intensity parameter ?2 tend to decrease, which can be related to an increase in the relative fraction of Er3+ ions with higher symmetry of the local environment.

  3. A mutation in a cuticle collagen causes hypersensitivity to the endocrine disrupting chemical, bisphenol A, in Caenorhabditis elegans.

    PubMed

    Watanabe, Masahito; Mitani, Nanako; Ishii, Naoaki; Miki, Keizaburo

    2005-02-15

    A novel mutant gene, bis-1 (bisphenol A sensitive) has been isolated in the nematode, Caenorhabditis elegans, that affects the response to endocrine disrupting chemicals (EDC). The bis-1(nx3) allele is hypersensitive to bisphenol A (BPA), is allelic to a collagen gene (col-121), and is expressed in hypodermal cells. Among the collagen mutants so far studied, bis-1(nx3), dpy-2(e8), dpy-7(e88) and dpy-10(e128) showed BPA sensitivity. The isolated mutant may work as a useful tool for the assay of EDC toxicity since the physiological effect of the collagen mutation (glycine substitution) indicates an increased sensitivity to BPA. PMID:15680404

  4. Effects of electroacupuncture on corticotropin-releasing hormone in rats with chronic visceral hypersensitivity

    PubMed Central

    Liu, Hui-Rong; Fang, Xiao-Yi; Wu, Huan-Gan; Wu, Lu-Yi; Li, Jing; Weng, Zhi-Jun; Guo, Xin-Xin; Li, Yu-Guang

    2015-01-01

    AIM: To investigate the effect of electroacupuncture on corticotropin-releasing hormone (CRH) in the colon, spinal cord, and hypothalamus of rats with chronic visceral hypersensitivity. METHODS: A rat model of chronic visceral hypersensitivity was generated according to the internationally accepted method of colorectal balloon dilatation. In the 7th week after the procedure, rats were randomly divided into a model group (MG), electroacupuncture group (EA), and sham electroacupuncture group (S-EA). After treatment, the abdominal withdrawal reflex (AWR) score was used to assess the behavioral response of visceral hyperalgesia. Immunohistochemistry (EnVision method), ELISA, and fluorescence quantitative PCR methods were applied to detect the expression of CRH protein and mRNA in the colon, spinal cord, and hypothalamus. RESULTS: The sensitivity of the rats to the colorectal distension stimulus applied at different strengths (20-80 mmHg) increased with increasing stimulus strength, resulting in increasing AWR scores in each group. Compared with NG, the AWR score of MG was significantly increased (P < 0.01). After conducting EA, the AWR scores of the rats were decreased compared with MG rats. The relative expression of CRH mRNA in the colon, spinal cord, and hypothalamus of MG rats was significantly increased compared with NG rats (P < 0.01). CRH mRNA in the colon and spinal cord of EA and S-EA rats was decreased to varying degrees (P > 0.05) compared with normal rats (NG). However, the decrease in EA compared with MG rats was statistically significant (P < 0.01). The average optical density of CRH expression in the colon of the MG rats was significantly enhanced compared with NG (P < 0.05), while the average optical density of CRH expression in the EA and S-EA rats was significantly decreased compared with MG rats (P < 0.01, P < 0.05, respectively). Compared with MG rats, the CRH concentration in the spinal cord of EA rats was significantly reduced (P < 0.01), but there was no significant change in S-EA rats (P > 0.05). CONCLUSION: Electroacupuncture at the Shangjuxu acupoint was able to significantly reduce the visceral hypersensitivity in rats, and regulated the expression of CRH protein and mRNA in the colon, spinal cord and hypothalamus at different levels, playing a therapeutic role in this model of irritable bowel syndrome.

  5. Hypersensitive transition spectrum of f-element and coordination structure

    NASA Astrophysics Data System (ADS)

    Xuan, Cao; Chongli, Song; Yongjun, Zhu

    1992-10-01

    Some f-f transitions of Ln(An) metallic ions have particular super-sensitivity to the change of coordination environments. This is called super-sensitive transitions. Based on the irreducible tensor operator method, a computation model and corresponding computer program for calculating the hypersensitive transition spectrum of f-element were developed. By comparing the theoretical spectra of all possible coordination structures with the experimental one, the possible coordination structures of complex can be determined. The coordination structures of Nd(3+), Er(3+) hydrate, and their extraction complex with H(DEHP) were successfully determined by this method, and the experimental spectra were also assigned.

  6. Electromagnetic hypersensitivity: The opinion of an observer neurologist

    NASA Astrophysics Data System (ADS)

    Marc-Vergnes, Jean-Pierre

    2010-11-01

    Electromagnetic hypersensitivity (EHS) is a recent, uncertain and somehow confusing concept. It is now widely agreed that people claiming to be EHS really experience symptoms. However, no evidence for a causal link between the symptoms and electromagnetic fields (EMF) has been reported. Thus, we have to wonder whether EHS constitutes truly a relevant entity. Most of the previous studies suffer from methodological flaws. Owing to the quantification of symptoms, the interdisciplinary assessment of patients, and the use of personal exposimeters, the recent studies are of better quality. A set of convergent associated signs suggests that individual neuropsychic factors take a prominent, but maybe not unique, part in this condition.

  7. Spinal transient receptor potential ankyrin 1 channel induces mechanical hypersensitivity, increases cutaneous blood flow, and mediates the pronociceptive action of dynorphin A.

    PubMed

    Wei, H; Saarnilehto, M; Falck, L; Viisanen, H; Lasierra, M; Koivisto, A; Pertovaara, A

    2013-06-01

    We characterized pain behavior and cutaneous blood flow response induced by activation of the spinal transient receptor potential ankyrin 1 (TRPA1) channel using intrathecal drug administrations in the rat. Additionally, we assessed whether the pronociceptive actions induced by intrathecally administered dynorphin A, cholecystokinin or prostaglandin F(2?) are mediated by the spinal TRPA1 channel. Cinnamaldehyde, a TRPA1 agonist, produced a dose-related (3-10 ?g) cutaneous blood flow increase and mechanical hypersensitivity effect. These effects at the currently used doses were of short duration and attenuated, although not completely, by pretreatment with A-967079, a TRPA1 antagonist. The cinnamaldehyde-induced hypersensitivity was also reduced by pretreatment with minocycline (an inhibitor of microglial activation), but not by carbenoxolone (a gap junction decoupler). In vitro study, however, indicated that minocycline only poorly blocks the TRPA1 channel. The mechanical hypersensitivity effect induced by dynorphin A, but not that by cholecystokinin or prostaglandin F(2?), was attenuated by a TRPA1 antagonist Chembridge-5861528 as well as A-967079. The cinnamaldehyde-induced cutaneous blood flow increase was not suppressed by MK-801, an NMDA receptor antagonist, or bicuculline, a GABA(A) receptor antagonist. The results indicate that spinal TRPA1 channels promote mechanical pain hypersensitivity and due to antidromic activation of nociceptive nerve fibers increase cutaneous blood flow. The attenuation of the cinnamaldehyde-induced hypersensitivity effect by minocycline may be explained by action other than block of the TRPA1 channel. Moreover, the spinal TRPA1 channel is involved in mediating the pronociceptive action of dynorphin A, but not that of the spinal cholecystokinin or prostaglandin F(2?). PMID:23959730

  8. Growth advantage of chronic myeloid leukemia CFU-GM in vitro: survival to growth factor deprivation, possibly related to autocrine stimulation, is a more common feature than hypersensitivity to GM-CSF\\/IL3 and is efficiently counteracted by retinoids ± ?-interferon

    Microsoft Academic Search

    D Ferrero; C Foli; F Giaretta; C Argentino; C Rus; A Pileri

    2001-01-01

    Bcr\\/abl fusion gene, in experimental models, induces survival to growth factor deprivation and hypersensitivity to IL3. However, conflicting data were reported about chronic myeloid leukemia (CML) progenitors. We investigated the responsiveness of purified CML CFU-GM to GM-CSF\\/IL3 and their survival to growth factor deprivation. CFU-GM hypersensitivity to IL3 and\\/or GM-CSF was found in 3\\/11 CML cases only. CML CFU-GM survived

  9. In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses, Revealing Rapid Loss of Virus Reactive CD4+ T Cells in Acute HIV-1 Infection

    PubMed Central

    Lubong Sabado, Rachel; Kavanagh, Daniel G.; Kaufmann, Daniel E.; Fru, Karlhans; Babcock, Ethan; Rosenberg, Eric; Walker, Bruce; Lifson, Jeffrey; Bhardwaj, Nina; Larsson, Marie

    2009-01-01

    Background The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission. Methodology The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited. Findings Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naďve T cells. Responses included several CD4+ and CD8+ T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4+ T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4+ T cell depletion which renders the newly activated HIV-specific CD4+ T cells prime targets for elimination. Conclusion Our studies highlight the ability of DCs to efficiently prime naďve T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo. PMID:19165342

  10. Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation

    PubMed Central

    1989-01-01

    This study was conducted to explore the involvement of DNA damage in the suppression of contact hypersensitivity (CHS) by UV irradiation. The opossum, Monodelphis domestica, was used because cells of these marsupials have an enzyme that is activated by visible light (photoreactivating enzyme) and repairs ultraviolet radiation (UVR)- induced pyrimidine dimers in DNA. A single dose of 1,500 J/m2 of UVB (280-320 nm) radiation, representing 2 minimal erythema doses, was administered to the dorsal skin of opossums. This treatment prevented the opossums from developing a CHS response to dinitrofluorobenze (DNFB) applied either at the site of irradiation or an unirradiated site. In addition, this dose of UVR decreased the number of ATPase+ epidermal Langerhans cells in the dorsal epidermis to approximately 3% of that in unirradiated skin at the time of DNFB application. Treatment of the animals with wavelengths that activate the repair enzyme (320- 500 nm, photoreactivating light, PRL) for 120 min immediately after UV irradiation inhibited the UVR-induced suppression of CHS almost completely. Exposure to PRL before UVR did not prevent UVR-induced suppression of CHS. PRL treatment after UV irradiation also prevented the decrease in the number of ATPase+ Langerhans cells. Measurements of lesions in DNA indicated that PRL treatment removed around 85% of the UVR-induced pyrimidine dimers. These data provide direct evidence that DNA, and most likely, the pyrimidine dimer, is the primary molecular target for the UVB-induced suppression of contact hypersensitivity to haptens applied to irradiated or unexposed skin. PMID:2529340

  11. Transcriptome analysis reveals response regulator SO2426-mediated gene expression in Shewanella oneidensis MR1 under chromate challenge

    Microsoft Academic Search

    Karuna Chourey; Wei Wei; Xiu-Feng Wan; Dorothea K Thompson

    2008-01-01

    BACKGROUND: Shewanella oneidensis MR-1 exhibits diverse metal ion-reducing capabilities and thus is of potential utility as a bioremediation agent. Knowledge of the molecular components and regulatory mechanisms dictating cellular responses to heavy metal stress, however, remains incomplete. In a previous work, the S. oneidensis so2426 gene, annotated as a DNA-binding response regulator, was demonstrated to be specifically responsive at both

  12. Delayed Hypersensitivity to Propionibacterium acnes in Patients with Severe Nodular Acne and Acne fulminans

    Microsoft Academic Search

    S. L. Karvonen; L. Räsänen; W. J. Cunliffe; K. T. Holland; J. Karvonen; T. Reunala

    1994-01-01

    Background: Increased hypersensitivity reactions to Propionibacterium acnes may be involved in the pathogenesis of severe acne. Objective: To study delayed and immediate hypersensitivity reactions to P. acnes in patients with severe nodular acne (SNA) and acne fulminans (AF). Methods: We performed lymphocyte stimulation and skin tests for P. acnes antigens on 11 patients with SNA and 7 patients with AF.

  13. Laboratory confirmed polymethyl-methacrylate (Palacos)-hypersensitivity after cranioplasty.

    PubMed

    Gautschi, Oliver P; Schlett, Christopher L; Fournier, Jean-Yves; Cadosch, Dieter

    2010-12-01

    Polymethyl-methacrylate (PMMA) as part of bone cement is a widely used material in the context of orthopaedic implants and also in cranioplasty. Although PMMA is characterised by excellent biocompatibility with low intrinsic toxicity and inflammatory activation, a minor portion of patients develop allergic reactions. We present the case of a 39-year-old woman with an increasing headache and a corresponding erythema over the parieto-occipital cranioplasty, which was performed 42 days prior using a PMMA compound. A patch test specific for bone cement components confirmed the diagnosis of a PMMA delayed-type hypersensitivity reaction. The prevalence of allergic reactions to bone cement components are known to vary from between 0.6% and 1.6%, however no adequate, pre-interventional diagnostic tool is currently available. Therefore, physicians are required to consider this differential diagnosis even after an extremely delayed onset of symptoms. This case describes the first ever-reported case in the literature of hypersensitivity to bone cement cranioplasty. PMID:20719430

  14. Clinical evaluation of desensitizing treatments for cervical dentin hypersensitivity.

    PubMed

    Aranha, Ana Cecilia Corręa; Pimenta, Luiz André Freire; Marchi, Giselle Maria

    2009-01-01

    The aim of this study was to compare different treatments for dentin hypersensitivity in a 6-month follow-up. One hundred and one teeth exhibiting non carious cervical lesions were selected. The assessment method used to quantify sensitivity was the cold air syringe, recorded by the visual analogue scale (VAS), prior to treatment (baseline), immediately after topical treatment, after 1 week, 1, 3 and 6 months. Teeth were randomly assigned to five groups (n = 20): G1: Gluma Desensitizer (GD); G2: Seal& (SP); G3: Oxa-gel (OG); G4: Fluoride (F); G5: Low intensity laser-LILT (660 nm/3.8 J/cm(2)/15 mW). Analysis was based on the non-parametric Kruskal-Wallis test that demonstrated statistical differences immediately after the treatment (p = 0.0165). To observe the individual effects of each treatment, data was submitted to Friedman test. It was observed that GD and SP showed immediate effect after application. Reduction in the pain level throughout the six-month follow-up was also observed. In contrast, LILT presented a gradual reduction of hypersensitivity. OG and F showed effects as of the first and third month respectively. It can be concluded that, after the 6-month clinical evaluation, all therapies showed lower VAS sensitivity values compared with baseline, independently of their different modes of action. PMID:19893971

  15. Tomato Transcriptional Changes in Response to Clavibacter michiganensis subsp. michiganensis Reveal a Role for Ethylene in Disease Development1(W)

    Microsoft Academic Search

    Vasudevan Balaji; Maya Mayrose; Ofra Sherf; Jasmine Jacob-Hirsch; Rudolf Eichenlaub; Naim Iraki; Shulamit Manulis-Sasson; Gideon Rechavi; Isaac Barash; Guido Sessa

    Clavibacter michiganensis subsp. michiganensis (Cmm) is a gram-positive actinomycete, causing bacterial wilt and canker disease in tomato (Solanum lycopersicum). Host responses to gram-positive bacteria and molecular mechanisms associated with the development of disease symptoms caused by Cmm in tomato are largely unexplored. To investigate plant responses activated during this compatible interaction, we used microarray analysis to monitor changes in host

  16. Peripheral N-methyl-D-aspartate receptors contribute to mechanical hypersensitivity in a rat model of inflammatory temporomandibular joint pain

    PubMed Central

    Ivanusic, JJ; Beaini, D; Hatch, RJ; Staikopoulos, V; Sessle, BJ; Jennings, EA

    2010-01-01

    The aim of this study was to determine whether peripheral N-methyl-D-aspartate (NMDA) receptors are involved in inflammation-induced mechanical hypersensitivity of the temporomandibular joint (TMJ) region. We developed a rat model of mechanical sensitivity to Complete Freund’s Adjuvant (CFA; 2?l containing 1?g Mycobacterium tuberculosis)-induced inflammation of the TMJ and examined changes in sensitivity following injection of NMDA receptor antagonists (DL-2-amino-5-phosphonovaleric acid (AP5) or Ifenprodil) with CFA. CFA injected into the TMJ resulted in an increase in mechanical sensitivity relative to pre-injection that peaked at day 1 and lasted for up to 3 days (n=8, P<0.05). There was no change in mechanical sensitivity in vehicle-injected rats at any time-point (n=9). At day 1, there was a significant increase in mechanical sensitivity in animals injected with CFA+vehicle (n=7) relative to those injected with vehicle alone (n=7; P<0.05), and co-injection of AP5 (n=6) or Ifenprodil (n=7) with CFA blocked this hypersensitivity. Subcutaneous injection of AP5 (n=7) and Ifenprodil (n=5) instead of into the TMJ had no significant effect on CFA-induced hypersensitivity of the TMJ region. Western blot analysis revealed constitutive expression of the NR1 and NR2B subunits in trigeminal ganglion lysates. Immunohistochemical studies showed that 99% and 28% of trigeminal ganglion neurons that innervated the TMJ contained the NR1 and NR2B subunits respectively. Our findings suggest a role for peripheral NMDA receptors in inflammation-induced pain of the TMJ region. Targeting peripheral NMDA receptors with peripheral application of NMDA receptor antagonists could provide therapeutic benefit and avoid side effects associated with blockade of NMDA receptors in the central nervous system. PMID:20675160

  17. Subjective Welfare, Well-Being, and Self-Reported Food Hypersensitivity in Four European Countries: Implications for European Policy

    ERIC Educational Resources Information Center

    Voordouw, Jantine; Antonides, Gerrit; Fox, Margaret; Cerecedo, Inmaculada; Zamora, Javier; de la Hoz Caballer, Belen; Rokicka, Ewa; Cornelisse-Vermaat, Judith; Jewczak, Maciej; Starosta, Pawel; Kowalska, Marek L.; Jedrzejczak-Czechowicz, Monika; Vazquez-Cortes, Sonia; Escudero, Cano; de Blok, Bertine Flokstra; Dubois, Anthony; Mugford, Miranda; Frewer, Lynn J.

    2012-01-01

    This study estimates the effects of food hypersensitivity on individuals' perceived welfare and well-being compared to non-food hypersensitive individuals. Study respondents were recruited in the Netherlands, Poland, Spain and UK. The difference in welfare between food hypersensitive respondents and those asymptomatic to foods was estimated using…

  18. Delayed Hypersensitivity to Toxoplasma and Unrelated Antigens in Toxoplasma-Infected Mice: Induction and Elicitation of Delayed-Type Hypersensitivity by Antigen-Pulsed Macrophages

    PubMed Central

    Handman, Emanuela; Chester, Patrice M.; Remington, Jack S.

    1980-01-01

    Delayed-type hypersensitivity (DTH) to Toxoplasma and unrelated antigens in Toxoplasma-infected BALB/c mice was investigated by the radioisotopic uptake method of Vadas et al. (Int. Arch. Allergy Appl. Immunol. 49: 670-692, 1975). DTH became positive on day 30 of infection and remained positive during chronic infection. The expression of DTH in mice infected with the relatively avirulent C37 strain of the parasite paralleled the Toxoplasma antibody response as detected by the Sabin-Feldman dye test. Mice sensitized with Toxoplasma, keyhole limpet hemocyanin, or sheep erythrocytes during the acute or chronic phase of Toxoplasma infection showed a DTH reaction similar to that of uninfected sensitized controls. No parasite antigens could be detected by immunofluorescence techniques on the surface of Toxoplasma-infected cells. When killed organisms were added to the cell cultures, specks of fluorescence appeared on cells containing intracellular parasites as well as on cells without intracellular organisms. That the antigens may be present in or on macrophages in a form readily recognizable by T cells is suggested by experiments in which we demonstrated that injection of uninfected normal macrophages pulsed with Toxoplasma-soluble antigens into the ears of chronically infected mice elicited a DTH reaction comparable to that observed when 106 Formalin-fixed tachyzoites were used as the test antigen. When macrophages pulsed with Toxoplasma antigen were used in attempts to induce DTH in naive uninfected mice, the intensity of the reaction was similar to that observed in infected mice. PMID:7399673

  19. Global transcriptional profiling of a cold-tolerant rice variety under moderate cold stress reveals different cold stress response mechanisms.

    PubMed

    Zhao, Junliang; Zhang, Shaohong; Yang, Tifeng; Zeng, Zichong; Huang, Zhanghui; Liu, Qing; Wang, Xiaofei; Leach, Jan; Leung, Hei; Liu, Bin

    2015-07-01

    Gene expression profiling under severe cold stress (4°C) has been conducted in plants including rice. However, rice seedlings are frequently exposed to milder cold stresses under natural environments. To understand the responses of rice to milder cold stress, a moderately low temperature (8°C) was used for cold treatment prior to genome-wide profiling of gene expression in a cold-tolerant japonica variety, Lijiangxintuanheigu (LTH). A total of 5557 differentially expressed genes (DEGs) were found at four time points during moderate cold stress. Both the DEGs and differentially expressed transcription factor genes were clustered into two groups based on their expression, suggesting a two-phase response to cold stress and a determinative role of transcription factors in the regulation of stress response. The induction of OsDREB2A under cold stress is reported for the first time in this study. Among the anti-oxidant enzyme genes, glutathione peroxidase (GPX) and glutathione S-transferase (GST) were upregulated, suggesting that the glutathione system may serve as the main reactive oxygen species (ROS) scavenger in LTH. Changes in expression of genes in signal transduction pathways for auxin, abscisic acid (ABA) and salicylic acid (SA) imply their involvement in cold stress responses. The induction of ABA response genes and detection of enriched cis-elements in DEGs suggest that ABA signaling pathway plays a dominant role in the cold stress response. Our results suggest that rice responses to cold stress vary with the specific temperature imposed and the rice genotype. PMID:25263631

  20. Protein carbonylation and heat shock response in Ruditapes decussatus following p,p'-dichlorodiphenyldichloroethylene (DDE) exposure: a proteomic approach reveals that DDE causes oxidative stress.

    PubMed

    Dowling, Vera; Hoarau, Pascal C; Romeo, Michčle; O'Halloran, John; van Pelt, Frank; O'Brien, Nora; Sheehan, David

    2006-04-20

    Protein carbonylation and levels of heat shock proteins (hsp; 60, 70 and 90 kDa) were measured in gill, mantle and digestive gland of Ruditapes decussatus following exposure to p,p'-dichlorodiphenyldichloroethylene (DDE). Heat shock response was measured by immunoblotting using antibodies specific to heat shock proteins (hsps). Densitometry analysis of individual bands revealed no difference between control and treated samples except appearance of hsp90 in DDE-treated mantle. Carbonylated protein content was determined following 2,4-dinitrophenylhydrazine derivatization and two-dimensional electrophoresis coupled with western blotting. Immunoblotting with dinitrophenol-specific antibody revealed extensive differences in both extent and number of carbonylated proteins in mantle and digestive gland in response to DDE while gill was unaffected. These results demonstrate for the first time that DDE causes tissue-specific formation of reactive oxygen species in clams. PMID:16318879

  1. Retinal pigment epithelium disorder in Vogt-Koyanagi-Harada disease revealed by hyperosmolarity response of ocular standing potential.

    PubMed

    Madachi-Yamamoto, S; Kawasaki, K; Yonemura, D

    1984-01-01

    The hyperosmolarity response of the ocular standing potential was examined in 14 eyes of 7 cases of Harada's disease between 8 and 1,341 days after the onset of the disease. The hyperosmolarity response remained normal at the initial stage of the disease when choroiditis, retinal detachment and iridocyclitis were the main manifestations. The hyperosmolarity response was suppressed when depigmentation of the fundus progressed to the stage of the "sunset glow" appearance. The present study suggests that a sensitivity reduction to osmotic stress takes place in the retinal pigment epithelium concomitantly with the transition from the stage of depigmentation to the stage of "sunset glow". This dysfunction can be disclosed by the hyperosmolarity response, but not by the conventional examination of the light peak/dark trough ratio of the ocular standing potential. PMID:6530837

  2. The Phytoalexin Resveratrol Regulates the Initiation of Hypersensitive Cell Death in Vitis Cell

    PubMed Central

    Chang, Xiaoli; Heene, Ernst; Qiao, Fei; Nick, Peter

    2011-01-01

    Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR), while susceptible European Vitis vinifera cv. ‘Pinot Noir’ does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy) transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. ‘Pinot Noir’ accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative ?-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5) transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death. PMID:22053190

  3. Atypical radiation response of SCID cells

    NASA Astrophysics Data System (ADS)

    Chawapun, Nisa

    Murine SCID (severe combined immune deficiency) cells are well known for their defect in DNA double-strand break repair and in variable(diversity)joining [V(D)J] recombination due to a mutation in a catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). As a consequence, scid cells are hypersensitive to ionizing radiation. The present study showed that asynchronous populations of scid cells were about two-fold more sensitive than Balb/c with respect to cell killing and the defect in scid cells was corrected by complementation with human chromosome 8. Analysis of the survival of synchronized populations as a function of the cell cycle revealed that while scid cells were hypersensitive in all cell cycle phases compared to wild-type cells, this hypersensitivity is even more pronounced in G1 phase. The hypersensitivity reduced as the cells progressed into S phase suggested that homologous recombination repair plays a role. The results imply that there are at least two pathways for the repair of DSB DNA, consistent with a model previously proposed by others. The scid cells were also more sensitive to UVC light (254 nm) killing as compared to wild type cells by clonogenic survival. Using a host cell reactivation (HCR) assay to study the nucleotide excision repair (NER) which is the major repair pathway for UV-photoproducts, the results showed that NER in scid cells was not as efficient as CB- 17. This suggests that DNA-PK is involved in NER as well as non-homologous end-joining (NHEJ) DSB repair which is responsible for ionizing radiation sensitivity in scid cells. Repair in scid cells was not totally absent as shown by low dose rate sparing of cell killing after exposure to 137Cs ?-rays at dose rate of 0.6 cGy/h, 1.36 cGy/h, 6 cGy/h as compared to high dose rate at 171 cGy/min, although this phenomenon could be explained partly by proliferation. However, for radiation induced transformation, no significant dose rate effect was seen. A plot of transformation versus survival revealed that the transformation induction was inversely proportional to radiation dose rate. Lower dose rates were more effective in inducing transformation in scid cells. This finding could lead to the influence of cancer risk estimation in an irradiated population consisting of a subpopulation(s) with genetic disorders predisposing those individuals to cancer.

  4. Intraspecific comparisons reveal differences in the pattern of ultraviolet radiation responses in four maize (Zea mays L.) varieties.

    PubMed

    Cartwright, H N; Baucom, C; Singh, P; Smith, K L; Stapleton, A E

    2001-09-01

    Four maize (Zea mays L.) varieties were examined for ultraviolet radiation-induced changes in leaf rolling, biomass, fluctuating leaf asymmetry and DNA damage. Short-term dose-response curves for each response were constructed and responses in each line compared. The four varieties each exhibited a different pattern of tolerance and reactivity, ranging from B73, which was tolerant in all four measures, to TS1, which was affected in DNA damage levels and leaf rolling but unaffected in biomass accumulation and fluctuating leaf asymmetry. The pattern of ultraviolet radiation responses allows us to narrow the possibilities for the source of the defect in reactive varieties. The four varieties tested include inbred parents that have been used to construct recombinant inbred lines and a variety that is found in the background of the engineered RescueMu transposon mutagenesis lines. These dose-response curves and variety comparisons provide the foundation for genetic dissection of the mechanisms of ultraviolet radiation responses in maize. PMID:11693370

  5. Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B

    PubMed Central

    Kim, Jeong Tae; Jeong, Hye Won; Choi, Ki Hwa; Yoon, Tae Young; Sung, Nohyun; Choi, Young Ki; Kim, Eun Ha; Chae, Hee Bok

    2014-01-01

    Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment. PMID:25400481

  6. Heat Hyperalgesia and Mechanical Hypersensitivity Induced by Calcitonin Gene-Related Peptide in a Mouse Model of Neurofibromatosis

    PubMed Central

    White, Stephanie; Marquez de Prado, Blanca; Russo, Andrew F.; Hammond, Donna L.

    2014-01-01

    This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/? mice (B6.129S6 Nf1/J) and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/? mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/? and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/? and wild type mice. Female Nf1+/? mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/? mice of both genders compared to wild type mice. Male Nf1+/? mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/? mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients. PMID:25184332

  7. De novo sequencing of root transcriptome reveals complex cadmium-responsive regulatory networks in radish (Raphanus sativus L.).

    PubMed

    Xu, Liang; Wang, Yan; Liu, Wei; Wang, Jin; Zhu, Xianwen; Zhang, Keyun; Yu, Rugang; Wang, Ronghua; Xie, Yang; Zhang, Wei; Gong, Yiqin; Liu, Liwang

    2015-07-01

    Cadmium (Cd) is a nonessential metallic trace element that poses potential chronic toxicity to living organisms. To date, little is known about the Cd-responsive regulatory network in root vegetable crops including radish. In this study, 31,015 unigenes representing 66,552 assembled unique transcripts were isolated from radish root under Cd stress based on de novo transcriptome assembly. In all, 1496 differentially expressed genes (DEGs) consisted of 3579 transcripts were identified from Cd-free (CK) and Cd-treated (Cd200) libraries. Gene Ontology and pathway enrichment analysis indicated that the up- and down-regulated DEGs were predominately involved in glucosinolate biosynthesis as well as cysteine and methionine-related pathways, respectively. RT-qPCR showed that the expression profiles of DEGs were in consistent with results from RNA-Seq analysis. Several candidate genes encoding phytochelatin synthase (PCS), metallothioneins (MTs), glutathione (GSH), zinc iron permease (ZIPs) and ABC transporter were responsible for Cd uptake, accumulation, translocation and detoxification in radish. The schematic model of DEGs and microRNAs-involved in Cd-responsive regulatory network was proposed. This study represents a first comprehensive transcriptome-based characterization of Cd-responsive DEGs in radish. These results could provide fundamental insight into complex Cd-responsive regulatory networks and facilitate further genetic manipulation of Cd accumulation in root vegetable crops. PMID:26025544

  8. Quantitative trait loci mapping and transcriptome analysis reveal candidate genes regulating the response to ozone in Arabidopsis thaliana.

    PubMed

    Xu, Enjun; Vaahtera, Lauri; Hőrak, Hanna; Hincha, Dirk K; Heyer, Arnd G; Brosché, Mikael

    2015-07-01

    As multifaceted molecules, reactive oxygen species (ROS) are known to accumulate in response to various stresses. Ozone (O3 ) is an air pollutant with detrimental effect on plants and O3 can also be used as a tool to study the role of ROS in signalling. Genetic variation of O3 sensitivity in different Arabidopsis accessions highlights the complex genetic architecture of plant responses to ROS. To investigate the genetic basis of O3 sensitivity, a recombinant inbred line (RIL) population between two Arabidopsis accessions with distinct O3 sensitivity, C24 (O3 tolerant) and Te (O3 sensitive) was used for quantitative trait loci (QTL) mapping. Through analysis of QTL mapping combined with transcriptome changes in response to O3 , we identified three causal QTLs and several potential candidate genes regulating the response to O3 . Based on gene expression data, water loss and stomatal conductance measurement, we found that a combination of relatively low stomatal conductance and constitutive activation of salicylic acid (SA)-mediated defence signalling were responsible for the O3 tolerance in C24. Application of exogenous SA prior to O3 exposure can mimic the constitutive SA signalling in C24 and could attenuate O3 -induced leaf damage in the sensitive Arabidopsis accessions Te and Cvi-0. PMID:25496229

  9. Delayed Hypersensitivity: Indicator of Acquired Failure of Host Defenses in Sepsis and Trauma

    PubMed Central

    Meakins, Jonathan L.; Pietsch, John B.; Bubenick, Oldrich; Kelly, Ralph; Rode, Harold; Gordon, Julius; MacLean, Lloyd D.

    1977-01-01

    Primary failure of host defense mechanisms has been associated with increased infection and mortality. Anergy, the failure of delayed hypersensitivity response, has been shown to identify surgical patients at increased risk for sepsis and related mortality. The anergic and relatively anergic patients whose skin tests failed to improve had a mortality rate of 74.4%, whereas those who improved their responses had a mortality rate of 5.1% (P < 0.001). This study documents abnormalities of neutrophil chemotaxis, T-lymphocyte rosetting in anergic patients and the effect of autologous serum. These abnormalities may account for the increased infection and mortality rates in anergic patients. Skin testing with five standard antigens has identified 110 anergic (A) or relatively anergic (RA) patients in whom neutrophil chemotaxis (CTX) and bactericidal function (NBF), T-lymphocyte rosettes, mixed lymphocyte culture (MLC), cell-mediated lympholysis (CML), and blastogenic factor (BF) were studied. The MLC, CML and BF were normal in the patients studied, and were not clinically helpful. Neutrophil CTX in 19 controls was 117.5 ± 1.6 u whereas in 40 A patients, neutrophils migrated 81.7 ± 2.3 u and in 15 RA patients 97.2 ± 3.8 u (P < 0.01). In 14 patients whose skin tests converted to normal, neutrophil migration improved from 78.2 ± 5.4 u to 107.2 ± 4.0 u (P < 0.01). Incubation of A or control neutrophils in A serum reduced migration in A patients from 93 ± 3.7 u to 86.2 ± 3.5 u (P < 0.01) and in normals from 121.2 ± 1.6 u to 103.6 ± 2.6 u (P < 0.001). The per cent rosette forming cells in 66 A patients was 42.5 ± 3.1 compared to 53.6 ± 2.8 in normal responders (P < 0.02). Incubation of normal lymphocytes in anergic serum further reduced rosetting by 30%. Restoration of delayed hypersensitivity responses and concurrent improvement in cellular and serum components of host defense were correlated with maintenance of adequate nutrition and aggressive surgical drainage. PMID:142452

  10. An Arabidopsis soluble chloroplast proteomic analysis reveals the participation of the Executer pathway in response to increased light conditions.

    PubMed

    Uberegui, Estefanía; Hall, Michael; Lorenzo, Óscar; Schröder, Wolfgang P; Balsera, Mónica

    2015-04-01

    The Executer1 and Executer2 proteins have a fundamental role in the signalling pathway mediated by singlet oxygen in chloroplast; nonetheless, not much is known yet about their specific activity and features. Herein, we have followed a differential-expression proteomics approach to analyse the impact of Executer on the soluble chloroplast protein abundance in Arabidopsis. Because singlet oxygen plays a significant role in signalling the oxidative response of plants to light, our analysis also included the soluble chloroplast proteome of plants exposed to a moderate light intensity in the time frame of hours. A number of light- and genotype-responsive proteins were detected, and mass-spectrometry identification showed changes in abundance of several photosynthesis- and carbon metabolism-related proteins as well as proteins involved in plastid mRNA processing. Our results support the participation of the Executer proteins in signalling and control of chloroplast metabolism, and in the regulation of plant response to environmental changes. PMID:25740923

  11. [Radiation-induced "bystander effect" revealed by means of adaptive response in cocultured lymphocytes from humans of different genders].

    PubMed

    Kolesnikova, I S; Vorobtsova, I E

    2011-01-01

    The "bystander effect" was investigated in mixed cultures of lymphocytes from humans of opposite genders. Development of the adaptive response (AR) in non-irradiated female/male cells was estimated after adaptive pretreatment of opposite gender lymphocytes, chromosome aberrations being evaluated. Experiments were performed using two schedules of adaptive (0.05 Gy) and challenging (1 Gy) irradiations: G0-G1 and G1-G1. The results obtained indicate the development of a mediated adaptive response ("bystander effect") in the lymphocytes neighboring pre-irradiated cells, as well as the influence of a time scheme of adapting and challenging irradiations on the amount of induced chromosome aberrations in mixed cultures and a possible dependence of the adaptive response intensity on the donor gender. PMID:22279767

  12. An Arabidopsis soluble chloroplast proteomic analysis reveals the participation of the Executer pathway in response to increased light conditions

    PubMed Central

    Uberegui, Estefanía; Hall, Michael; Lorenzo, Óscar; Schröder, Wolfgang P.; Balsera, Mónica

    2015-01-01

    The Executer1 and Executer2 proteins have a fundamental role in the signalling pathway mediated by singlet oxygen in chloroplast; nonetheless, not much is known yet about their specific activity and features. Herein, we have followed a differential-expression proteomics approach to analyse the impact of Executer on the soluble chloroplast protein abundance in Arabidopsis. Because singlet oxygen plays a significant role in signalling the oxidative response of plants to light, our analysis also included the soluble chloroplast proteome of plants exposed to a moderate light intensity in the time frame of hours. A number of light- and genotype-responsive proteins were detected, and mass-spectrometry identification showed changes in abundance of several photosynthesis- and carbon metabolism-related proteins as well as proteins involved in plastid mRNA processing. Our results support the participation of the Executer proteins in signalling and control of chloroplast metabolism, and in the regulation of plant response to environmental changes. PMID:25740923

  13. Delayed hypersensitivity reaction related to the use of pegfilgrastim.

    PubMed

    Dadla, Aliakbar; Tannenbaum, Susan; Yates, Breton; Holle, Lisa

    2014-07-01

    Filgrastim and pegfilgrastim are granulocyte colony-stimulating factor products, which have been part of the supportive treatment of cancer patients for years to increase the white blood cell count and absolute neutrophil count with the objective of preventing neutropenic fever in patients at risk because of chemotherapy. Pegfilgrastim is a glycosylated form of filgrastim with a prolonged duration of effect, a reduced renal clearance, and relatively fewer side effects. We present a patient with early breast cancer who developed a rash more than a week after the use of pegfilgrastim. Clinicians must be aware of the possibility of a delayed hypersensitivity reaction as the application of this drug is increasing and an adverse event can result in delay of chemotherapy treatment. PMID:24993705

  14. Astrometry of comets using hypersensitized type 2415 film

    NASA Technical Reports Server (NTRS)

    Everhart, E.

    1984-01-01

    Kodak Technical Pan Film 2415 should be known to those doing cometary astrometry. It has exceedingly fine resolution (320 lines/mm) and, when properly hypersensitized, it is almost as fast as treated IIIa-J plates and reaches fainter stars. Reciprocity failure with the treated film is practically zero, and the shelf life of treated film sheets is about a month at 2 C stored in a nitrogen atmosphere. This film is readily available in 4 by 5-inch sheets and is inexpensive. The film base is Estar, a plastic chosen for its stability. Over 120 astrometric measures of negatives on this film have shown a median residual error in comet positions of 1.1 seconds, a value that compares favorably with those of most observatories reporting positions.

  15. Hypersensitivity reaction to the ingestion of mango flesh.

    PubMed

    Thoo, Caroline H F; Freeman, Susi

    2008-05-01

    A 42-year-old woman presented with a hypersensitivity reaction after the ingestion of a small amount of fresh mango gelato. She developed itchy palpable purpuric lesions over her arms, legs, neck and abdomen 4 days after ingestion. The lesions persisted for 5 weeks despite treatment with betamethasone-17 valerate 0.05% ointment and avoidance of mango. Resolution of these lesions was eventually achieved with continuing treatment. The patient denied any prior contact with mango skin but had experienced previous sensitizing reactions to mango flesh. Patch testing was strongly positive to mango skin and mango flesh. Skin-prick testing was negative. This case describes a systemic contact dermatitis to mango flesh, an entity less common than allergic contact dermatitis. PMID:18412816

  16. Transcriptomic and proteomic analysis of a compatible tomato-aphid interaction reveals a predominant salicylic acid-dependent plant response

    PubMed Central

    2013-01-01

    Background Aphids are among the most destructive pests in temperate climates, causing significant damage on several crops including tomato. We carried out a transcriptomic and proteomic study to get insights into the molecular mechanisms and dynamics of the tomato response to the Macrosyphum euphorbiae aphid. Results The time course analysis of aphid infestation indicated a complex, dynamic pattern of gene expression. Several biological functions were affected and genes related to the stress and defence response were the most represented. The Gene Ontology categories of the differentially expressed genes (899) and identified proteins (57) indicated that the tomato response is characterized by an increased oxidative stress accompanied by the production of proteins involved in the detoxification of oxygen radicals. Aphids elicit a defense reaction based on the cross-communication of different hormone-related signaling pathways such as those related to the salicylic acid (SA), jasmonic acid (JA), ethylene and brassinosteroids. Among them, the SA-signaling pathway and stress-responsive SA-dependent genes play a dominant role. Furthermore, tomato response is characterized by a reduced accumulation of photosynthetic proteins and a modification of the expression of various cell wall related genes. Conclusions Our work allowed a more comprehensive understanding of the signaling events and the defense dynamics of the tomato response to aphids in a compatible interaction and, based on experimental data, a model of the tomato–aphid molecular interaction was proposed. Considering the rapid advancement of tomato genomics, this information will be important for the development of new protection strategies. PMID:23895395

  17. Mutation of Arabidopsis HY1 causes UV-C hypersensitivity by impairing carotenoid and flavonoid biosynthesis and the down-regulation of antioxidant defence

    PubMed Central

    Xie, Yanjie; Xu, Daokun; Cui, Weiti; Shen, Wenbiao

    2012-01-01

    Previous pharmacological results confirmed that haem oxygenase-1 (HO-1) is involved in protection of cells against ultraviolet (UV)-induced oxidative damage in soybean [Glycine max (L.) Merr.] seedlings, but there remains a lack of genetic evidence. In this study, the link between Arabidopsis thaliana HO-1 (HY1) and UV-C tolerance was investigated at the genetic and molecular levels. The maximum inducible expression of HY1 in wild-type Arabidopsis was observed following UV-C irradiation. UV-C sensitivity was not observed in ho2, ho3, and ho4 single and double mutants. However, the HY1 mutant exhibited UV-C hypersensitivity, consistent with the observed decreases in chlorophyll content, and carotenoid and flavonoid metabolism, as well as the down-regulation of antioxidant defences, thereby resulting in severe oxidative damage. The addition of the carbon monoxide donor carbon monoxide-releasing molecule-2 (CORM-2), in particular, and bilirubin (BR), two catalytic by-products of HY1, partially rescued the UV-C hypersensitivity, and other responses appeared in the hy1 mutant. Transcription factors involved in the synthesis of flavonoid or UV responses were induced by UV-C, but reduced in the hy1 mutant. Overall, the findings showed that mutation of HY1 triggered UV-C hypersensitivity, by impairing carotenoid and flavonoid synthesis and antioxidant defences. PMID:22419743

  18. Polynomial algebra reveals diverging roles of the unfolded protein response in endothelial cells during ischemia-reperfusion injury.

    PubMed

    Le Pape, Sylvain; Dimitrova, Elena; Hannaert, Patrick; Konovalov, Alexander; Volmer, Romain; Ron, David; Thuillier, Raphaël; Hauet, Thierry

    2014-08-25

    The unfolded protein response (UPR)--the endoplasmic reticulum stress response--is found in various pathologies including ischemia-reperfusion injury (IRI). However, its role during IRI is still unclear. Here, by combining two different bioinformatical methods--a method based on ordinary differential equations (Time Series Network Inference) and an algebraic method (probabilistic polynomial dynamical systems)--we identified the IRE1?-XBP1 and the ATF6 pathways as the main UPR effectors involved in cell's adaptation to IRI. We validated these findings experimentally by assessing the impact of their knock-out and knock-down on cell survival during IRI. PMID:24945730

  19. A comparative study of ethylene growth response kinetics in eudicots and monocots reveals a role for gibberellin in growth inhibition and recovery.

    PubMed

    Kim, Joonyup; Wilson, Rebecca L; Case, J Brett; Binder, Brad M

    2012-11-01

    Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa 'Nipponbare') seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics. PMID:22977279

  20. Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.

    PubMed

    Cobb, J; Cule, E; Moncrieffe, H; Hinks, A; Ursu, S; Patrick, F; Kassoumeri, L; Flynn, E; Bulatovi?, M; Wulffraat, N; van Zelst, B; de Jonge, R; Bohm, M; Dolezalova, P; Hirani, S; Newman, S; Whitworth, P; Southwood, T R; De Iorio, M; Wedderburn, L R; Thomson, W

    2014-08-01

    Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA. PMID:24709693

  1. RNAseq reveals weed-induced PIF3-like as a candidate target to manipulate weed stress response in soybean.

    PubMed

    Horvath, David P; Hansen, Stephanie A; Moriles-Miller, Janet P; Pierik, Ronald; Yan, Changhui; Clay, David E; Scheffler, Brian; Clay, Sharon A

    2015-07-01

    Weeds reduce yield in soybeans (Glycine max) through incompletely defined mechanisms. The effects of weeds on the soybean transcriptome were evaluated in field conditions during four separate growing seasons. RNASeq data were collected from six biological samples of soybeans growing with or without weeds. Weed species and the methods to maintain weed-free controls varied between years to mitigate treatment effects, and to allow detection of general soybean weed responses. Soybean plants were not visibly nutrient- or water-stressed. We identified 55 consistently downregulated genes in weedy plots. Many of the downregulated genes were heat shock genes. Fourteen genes were consistently upregulated. Several transcription factors including a PHYTOCHROME INTERACTING FACTOR 3-like gene (PIF3) were included among the upregulated genes. Gene set enrichment analysis indicated roles for increased oxidative stress and jasmonic acid signaling responses during weed stress. The relationship of this weed-induced PIF3 gene to genes involved in shade avoidance responses in Arabidopsis provide evidence that this gene may be important in the response of soybean to weeds. These results suggest that the weed-induced PIF3 gene will be a target for manipulating weed tolerance in soybean. PMID:25711503

  2. Genome-wide investigation reveals pathogen-specific and shared signatures in the response of C. elegans to infection

    E-print Network

    Paris-Sud XI, Université de

    and adaptive. Innate immune mechanisms represent front-line protection against pathogens and instruct the subsequent adaptive response. One of the principal attributes of the adaptive immune system is its remarkable of T- and B-cell receptors and antibodies. While such adaptive immunity is restricted to jawed

  3. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors

    PubMed Central

    Metcalf, Talibah U; Cubas, Rafael A; Ghneim, Khader; Cartwright, Michael J; Grevenynghe, Julien Van; Richner, Justin M; Olagnier, David P; Wilkinson, Peter A; Cameron, Mark J; Park, Byung S; Hiscott, John B; Diamond, Michael S; Wertheimer, Anne M; Nikolich-Zugich, Janko; Haddad, Elias K

    2015-01-01

    Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (? 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (? 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNF?, IL-6, IL-1?, IFN?, IFN?, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections. PMID:25728020

  4. Escherichia coli enterobactin synthesis and uptake mutants are hypersensitive to an antimicrobial peptide that limits the availability of iron in addition to blocking Holliday junction resolution

    PubMed Central

    Orchard, Samantha S.; Rostron, Jason E.

    2012-01-01

    The peptide wrwycr inhibits Holliday junction resolution and is a potent antimicrobial. To study the physiological effects of wrwycr treatment on Escherichia coli cells, we partially screened the Keio collection of knockout mutants for those with increased sensitivity to wrwycr. Strains lacking part of the ferric-enterobactin (iron-bound siderophore) uptake and utilization system, parts of the enterobactin synthesis pathway, TolC (an outer-membrane channel protein) or Fur (an iron-responsive regulator) were hypersensitive to wrwycr. We provide evidence that the ?tolC mutant was hypersensitive to wrwycr due to its reduced ability to efflux wrwycr from the cell rather than due to its export of newly synthesized enterobactin. Deleting ryhB, which encodes a small RNA involved in iron regulation, mostly relieved the wrwycr hypersensitivity of the fur and ferric-enterobactin uptake mutants, indicating that the altered regulation of a RyhB-controlled gene was at least partly responsible for the hypersensitivity of these strains. Chelatable iron in the cell, measured by electron paramagnetic resonance spectroscopy, increased dramatically following wrwycr treatment, as did expression of Fur-repressed genes and, to some extent, mutation frequency. These incongruous results suggest that while wrwycr treatment caused accumulation of chelatable iron in the cell, iron was not available to bind to Fur. This is corroborated by the observed induction of the suf system, which assembles iron–sulfur clusters in low-iron conditions. Disruption of iron metabolism by wrwycr, in addition to its effects on DNA repair, may make it a particularly effective antimicrobial in the context of the low-iron environment of a mammalian host. PMID:22096151

  5. Gait Analysis at Multiple Speeds Reveals Differential Functional and Structural Outcomes in Response to Graded Spinal Cord Injury

    PubMed Central

    Krizsan-Agbas, Dora; Winter, Michelle K.; Eggimann, Linda S.; Meriwether, Judith; Berman, Nancy E.; McCarson, Kenneth E.

    2014-01-01

    Abstract Open-field behavioral scoring is widely used to assess spinal cord injury (SCI) outcomes, but has limited usefulness in describing subtle changes important for posture and locomotion. Additional quantitative methods are needed to increase the resolution of locomotor outcome assessment. This study used gait analysis at multiple speeds (GAMS) across a range of mild-to-severe intensities of thoracic SCI in the rat. Overall, Basso, Beattie, and Bresnahan (BBB) scores and subscores were assessed, and detailed automated gait analysis was performed at three fixed walking speeds (3.5, 6.0, and 8.5?cm/sec). Variability in hindpaw brake, propel, and stance times were analyzed further by integrating across the stance phase of stepping cycles. Myelin staining of spinal cord sections was used to quantify white matter loss at the injury site. Varied SCI intensity produced graded deficits in BBB score, BBB subscores, and spinal cord white matter and total volume loss. GAMS measures of posture revealed decreased paw area, increased limb extension, altered stance width, and decreased values for integrated brake, propel, and stance. Measures of coordination revealed increased stride frequency concomitant with decreased stride length, resulting in deviation from consistent forelimb/hindlimb coordination. Alterations in posture and coordination were correlated to impact severity. GAMS results correlated highly with functional and histological measures and revealed differential relationships between sets of GAMS dynamics and cord total volume loss versus epicenter myelin loss. Automated gait analysis at multiple speeds is therefore a useful tool for quantifying nuanced changes in gait as an extension of histological and observational methods in assessing SCI outcomes. PMID:24405378

  6. [Aspirin and other nonsteroidal anti-inflammatory drugs hypersensitivity--mechanisms, diagnostics and treatment].

    PubMed

    Kupczyk, Maciej; Kuna, Piotr

    2008-01-01

    Aspirin hypersensitivity syndrome includes several symptoms from the respiratory tract, skin and digestive system triggered by ingestion of aspirin or other nonsteroidal anti-inflammatory drugs. Asthmatic attacks precipitated by aspirin or other nonsteroidal anti-inflammatory drugs occur in about 10% of all asthmatic patients. In subjects with aspirin hypersensitivity disruption of synthesis of prostaglandin E2 (PGE2) and overproduction of cysteinyl leukotrienes (Cys-LT) seem to be crucial in the pathogenesis of bronchial symptoms. Double blind, placebo controlled challenges are regarded as a gold standard in the diagnosis of aspirin hypersensitivity. PMID:19003768

  7. Transcriptional profiling of an Fd-GOGAT1/GLU1 mutant in Arabidopsis thaliana reveals a multiple stress response and extensive reprogramming of the transcriptome

    PubMed Central

    2010-01-01

    Background Glutamate plays a central position in the synthesis of a variety of organic molecules in plants and is synthesised from nitrate through a series of enzymatic reactions. Glutamate synthases catalyse the last step in this pathway and two types are present in plants: NADH- or ferredoxin-dependent. Here we report a genome wide microarray analysis of the transcriptional reprogramming that occurs in leaves and roots of the A. thaliana mutant glu1-2 knocked-down in the expression of Fd-GOGAT1 (GLU1; At5g04140), one of the two genes of A. thaliana encoding ferredoxin-dependent glutamate synthase. Results Transcriptional profiling of glu1-2 revealed extensive changes with the expression of more than 5500 genes significantly affected in leaves and nearly 700 in roots. Both genes involved in glutamate biosynthesis and transformation are affected, leading to changes in amino acid compositions as revealed by NMR metabolome analysis. An elevated glutamine level in the glu1-2 mutant was the most prominent of these changes. An unbiased analysis of the gene expression datasets allowed us to identify the pathways that constitute the secondary response of an FdGOGAT1/GLU1 knock-down. Among the most significantly affected pathways, photosynthesis, photorespiratory cycle and chlorophyll biosynthesis show an overall downregulation in glu1-2 leaves. This is in accordance with their slight chlorotic phenotype. Another characteristic of the glu1-2 transcriptional profile is the activation of multiple stress responses, mimicking cold, heat, drought and oxidative stress. The change in expression of genes involved in flavonoid biosynthesis is also revealed. The expression of a substantial number of genes encoding stress-related transcription factors, cytochrome P450 monooxygenases, glutathione S-transferases and UDP-glycosyltransferases is affected in the glu1-2 mutant. This may indicate an induction of the detoxification of secondary metabolites in the mutant. Conclusions Analysis of the glu1-2 transcriptome reveals extensive changes in gene expression profiles revealing the importance of Fd-GOGAT1, and indirectly the central role of glutamate, in plant development. Besides the effect on genes involved in glutamate synthesis and transformation, the glu1-2 mutant transcriptome was characterised by an extensive secondary response including the downregulation of photosynthesis-related pathways and the induction of genes and pathways involved in the plant response to a multitude of stresses. PMID:20307264

  8. Neutrophils are required for both the sensitization and elicitation phase of contact hypersensitivity

    PubMed Central

    Weber, Felix C.; Németh, Tamás; Csepregi, Janka Z.; Dudeck, Anne; Roers, Axel; Ozsvári, Béla; Oswald, Eva; Puskás, László G.; Jakob, Thilo

    2015-01-01

    Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell–mediated inflammatory skin diseases induced by contact allergens. Though numerous cellular and molecular players are known, the mechanism of chemical-induced sensitization remains poorly understood. Here, we identify neutrophils as crucial players in the sensitization phase of CHS. Genetic deficiency of neutrophils caused by myeloid-specific deletion of Mcl-1 or antibody-mediated depletion of neutrophils before sensitization abrogated the CHS response. Neutrophil deficiency reduced contact allergen-induced cytokine production, gelatinase release, and reactive oxygen species production in naive mice. Mast cell deficiency inhibited neutrophil accumulation at the site of sensitization. In turn, neutrophils were required for contact allergen-induced release of further neutrophil-attracting chemokines, migration of DCs to the draining lymph nodes, and priming of allergen-specific T cells. Lymph node cells from mice sensitized in the absence of neutrophils failed to transfer sensitization to naive recipients. Furthermore, no CHS response could be induced when neutrophils were depleted before elicitation or when normally sensitized lymph node cells were transferred to neutrophil-deficient recipients, indicating an additional role for neutrophils in the elicitation phase. Collectively, our data identify neutrophils to be critically involved in both the sensitization and elicitation phase of CHS. PMID:25512469

  9. Neutrophils are required for both the sensitization and elicitation phase of contact hypersensitivity.

    PubMed

    Weber, Felix C; Németh, Tamás; Csepregi, Janka Z; Dudeck, Anne; Roers, Axel; Ozsvári, Béla; Oswald, Eva; Puskás, László G; Jakob, Thilo; Mócsai, Attila; Martin, Stefan F

    2015-01-12

    Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell-mediated inflammatory skin diseases induced by contact allergens. Though numerous cellular and molecular players are known, the mechanism of chemical-induced sensitization remains poorly understood. Here, we identify neutrophils as crucial players in the sensitization phase of CHS. Genetic deficiency of neutrophils caused by myeloid-specific deletion of Mcl-1 or antibody-mediated depletion of neutrophils before sensitization abrogated the CHS response. Neutrophil deficiency reduced contact allergen-induced cytokine production, gelatinase release, and reactive oxygen species production in naive mice. Mast cell deficiency inhibited neutrophil accumulation at the site of sensitization. In turn, neutrophils were required for contact allergen-induced release of further neutrophil-attracting chemokines, migration of DCs to the draining lymph nodes, and priming of allergen-specific T cells. Lymph node cells from mice sensitized in the absence of neutrophils failed to transfer sensitization to naive recipients. Furthermore, no CHS response could be induced when neutrophils were depleted before elicitation or when normally sensitized lymph node cells were transferred to neutrophil-deficient recipients, indicating an additional role for neutrophils in the elicitation phase. Collectively, our data identify neutrophils to be critically involved in both the sensitization and elicitation phase of CHS. PMID:25512469

  10. Transcriptome analysis reveals response regulator SO2426-mediated gene expression in Shewanella oneidensis MR-1 under chromate challenge

    PubMed Central

    Chourey, Karuna; Wei, Wei; Wan, Xiu-Feng; Thompson, Dorothea K

    2008-01-01

    Background Shewanella oneidensis MR-1 exhibits diverse metal ion-reducing capabilities and thus is of potential utility as a bioremediation agent. Knowledge of the molecular components and regulatory mechanisms dictating cellular responses to heavy metal stress, however, remains incomplete. In a previous work, the S. oneidensis so2426 gene, annotated as a DNA-binding response regulator, was demonstrated to be specifically responsive at both the transcript and protein levels to acute chromate [Cr(VI)] challenge. To delineate the cellular function of SO2426 and its contribution to metal stress response, we integrated genetic and physiological approaches with a genome-wide screen for target gene candidates comprising the SO2426 regulon. Results Inactivation of so2426 by an in-frame deletion resulted in enhanced chromate sensitivity and a reduced capacity to remove extracellular Cr(VI) relative to the parental strain. Time-resolved microarray analysis was used to compare transcriptomic profiles of wild-type and SO2426-deficient mutant S. oneidensis under conditions of chromate exposure. In total, 841 genes (18% of the arrayed genome) were up- or downregulated at least twofold in the ?so2426 mutant for at least one of six time-point conditions. Hierarchical cluster analysis of temporal transcriptional profiles identified a distinct cluster (n = 46) comprised of co-ordinately regulated genes exhibiting significant downregulated expression (p < 0.05) over time. Thirteen of these genes encoded proteins associated with transport and binding functions, particularly those involved in Fe transport and homeostasis (e.g., siderophore biosynthetic enzymes, TonB-dependent receptors, and the iron-storage protein ferritin). A conserved hypothetical operon (so1188-so1189-so1190), previously identified as a potential target of Fur-mediated repression, as well as a putative bicyclomycin resistance gene (so2280) and cation efflux family protein gene (so2045) also were repressed in the so2426 deletion mutant. Furthermore, the temporal expression profiles of four regulatory genes including a cpxR homolog were perturbed in the chromate-challenged mutant. Conclusion Our findings suggest a previously unrecognized functional role for the response regulator SO2426 in the activation of genes required for siderophore-mediated Fe acquisition, Fe storage, and other cation transport mechanisms. SO2426 regulatory function is involved at a fundamental molecular level in the linkage between Fe homeostasis and the cellular response to chromate-induced stress in S. oneidensis. PMID:18718017

  11. Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction

    PubMed Central

    Guarnieri, Douglas J.; Brayton, Catherine E.; Richards, Sarah M.; Maldonado-Aviles, Jaime; Trinko, Joseph R.; Nelson, Jessica; Taylor, Jane R.; Gourley, Shannon L.; DiLeone, Ralph J.

    2011-01-01

    Background Food restriction is known to enhance learning and motivation. The neural mechanisms underlying these responses likely involve alterations in gene expression in brain regions mediating the motivation to feed. Methods Analysis of gene expression profiles in male C57BL6/J mice using whole-genome microarrays was completed in the medial prefrontal cortex, nucleus accumbens, ventral tegmental area, and the hypothalamus following a five day food restriction. Quantitative PCR was used to validate these findings and determine the time-course of expression changes. Plasma levels of the stress hormone corticosterone (CORT) were measured by ELISA. Expression changes were measured in adrenalectomized animals that underwent food restriction, as well as in animals receiving daily injections of CORT. Progressive ratio responding for food, a measure of motivated behavior, was assessed after CORT treatment in restricted and fed animals. Results Brief food restriction results in an upregulation of peripheral stress responsive genes in the mammalian brain. Time-course analysis demonstrated rapid and persistent expression changes in all four brain regions under study. Administration of CORT to non-restricted animals was sufficient to induce a subset of the genes, and alterations in gene expression after food restriction were dependent on intact adrenal glands. CORT can increase the motivation to work for food only in the restricted state. Conclusions These data demonstrate a central role for CORT in mediating both molecular and behavioral responses to food restriction. The stress hormone-induced alterations in gene expression described here may be relevant for both adaptive and pathological responses to stress. PMID:21855858

  12. Multimodal microvascular imaging reveals that selective inhibition of class I PI3K is sufficient to induce an antivascular response.

    PubMed

    Sampath, Deepak; Oeh, Jason; Wyatt, Shelby K; Cao, Tim C; Koeppen, Hartmut; Eastham-Anderson, Jeffrey; Robillard, Liliane; Ho, Calvin C K; Ross, Jed; Zhuang, Guanglei; Reslan, Hani Bou; Vitorino, Philip; Barck, Kai H; Ungersma, Sharon E; Vernes, Jean Michel; Caunt, Maresa; Van Bruggen, Nick; Ye, Weilan; Vijapurkar, Ulka; Meng, Yu-Ju Gloria; Ferrara, Napoleone; Friedman, Lori S; Carano, Richard A D

    2013-07-01

    The phosphatidylinositol 3-kinase (PI3K) pathway is a central mediator of vascular endothelial growth factor (VEGF)-driven angiogenesis. The discovery of small molecule inhibitors that selectively target PI3K or PI3K and mammalian target of rapamycin (mTOR) provides an opportunity to pharmacologically determine the contribution of these key signaling nodes in VEGF-A-driven tumor angiogenesis in vivo. This study used an array of micro-vascular imaging techniques to monitor the antivascular effects of selective class I PI3K, mTOR, or dual PI3K/mTOR inhibitors in colorectal and prostate cancer xenograft models. Micro-computed tomography (micro-CT) angiography, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), vessel size index (VSI) MRI, and DCE ultrasound (DCE-U/S) were employed to quantitatively evaluate the vascular (structural and physiological) response to these inhibitors. GDC-0980, a dual PI3K/mTOR inhibitor, was found to reduce micro-CT angiography vascular density, while VSI MRI demonstrated a significant reduction in vessel density and an increase in mean vessel size, consistent with a loss of small functional vessels and a substantial antivascular response. DCE-MRI showed that GDC-0980 produces a strong functional response by decreasing the vascular permeability/perfusion-related parameter, K (trans). Interestingly, comparable antivascular effects were observed for both GDC-980 and GNE-490 (a selective class I PI3K inhibitor). In addition, mTOR-selective inhibitors did not affect vascular density, suggesting that PI3K inhibition is sufficient to generate structural changes, characteristic of a robust antivascular response. This study supports the use of noninvasive microvascular imaging techniques (DCE-MRI, VSI MRI, DCE-U/S) as pharmacodynamic assays to quantitatively measure the activity of PI3K and dual PI3K/mTOR inhibitors in vivo. PMID:23814482

  13. Cross-species transcriptional network analysis reveals conservation and variation in response to metal stress in cyanobacteria

    PubMed Central

    2013-01-01

    Background As one of the most dominant bacterial groups on Earth, cyanobacteria play a pivotal role in the global carbon cycling and the Earth atmosphere composition. Understanding their molecular responses to environmental perturbations has important scientific and environmental values. Since important biological processes or networks are often evolutionarily conserved, the cross-species transcriptional network analysis offers a useful strategy to decipher conserved and species-specific transcriptional mechanisms that cells utilize to deal with various biotic and abiotic disturbances, and it will eventually lead to a better understanding of associated adaptation and regulatory networks. Results In this study, the Weighted Gene Co-expression Network Analysis (WGCNA) approach was used to establish transcriptional networks for four important cyanobacteria species under metal stress, including iron depletion and high copper conditions. Cross-species network comparison led to discovery of several core response modules and genes possibly essential to metal stress, as well as species-specific hub genes for metal stresses in different cyanobacteria species, shedding light on survival strategies of cyanobacteria responding to different environmental perturbations. Conclusions The WGCNA analysis demonstrated that the application of cross-species transcriptional network analysis will lead to novel insights to molecular response to environmental changes which will otherwise not be achieved by analyzing data from a single species. PMID:23421563

  14. Aequorin-based luminescence imaging reveals differential calcium signalling responses to salt and reactive oxygen species in rice roots.

    PubMed

    Zhang, Yanyan; Wang, Yifeng; Taylor, Jemma L; Jiang, Zhonghao; Zhang, Shu; Mei, Fengling; Wu, Yunrong; Wu, Ping; Ni, Jun

    2015-05-01

    It is well established that both salt and reactive oxygen species (ROS) stresses are able to increase the concentration of cytosolic free Ca(2+) ([Ca(2+)]i), which is caused by the flux of calcium (Ca(2+)). However, the differences between these two processes are largely unknown. Here, we introduced recombinant aequorin into rice (Oryza sativa) and examined the change in [Ca(2+)]i in response to salt and ROS stresses. The transgenic rice harbouring aequorin showed strong luminescence in roots when treated with exogenous Ca(2+). Considering the histological differences in roots between rice and Arabidopsis, we reappraised the discharging solution, and suggested that the percentage of ethanol should be 25%. Different concentrations of NaCl induced immediate [Ca(2+)]i spikes with the same durations and phases. In contrast, H2O2 induced delayed [Ca(2+)]i spikes with different peaks according to the concentrations of H2O2. According to the Ca(2+) inhibitor research, we also showed that the sources of Ca(2+) induced by NaCl and H2O2 are different. Furthermore, we evaluated the contribution of [Ca(2+)]i responses in the NaCl- and H2O2-induced gene expressions respectively, and present a Ca(2+)- and H2O2-mediated molecular signalling model for the initial response to NaCl in rice. PMID:25754405

  15. Meta-analysis reveals complex marine biological responses to the interactive effects of ocean acidification and warming

    PubMed Central

    Harvey, Ben P; Gwynn-Jones, Dylan; Moore, Pippa J

    2013-01-01

    Ocean acidification and warming are considered two of the greatest threats to marine biodiversity, yet the combined effect of these stressors on marine organisms remains largely unclear. Using a meta-analytical approach, we assessed the biological responses of marine organisms to the effects of ocean acidification and warming in isolation and combination. As expected biological responses varied across taxonomic groups, life-history stages, and trophic levels, but importantly, combining stressors generally exhibited a stronger biological (either positive or negative) effect. Using a subset of orthogonal studies, we show that four of five of the biological responses measured (calcification, photosynthesis, reproduction, and survival, but not growth) interacted synergistically when warming and acidification were combined. The observed synergisms between interacting stressors suggest that care must be made in making inferences from single-stressor studies. Our findings clearly have implications for the development of adaptive management strategies particularly given that the frequency of stressors interacting in marine systems will be likely to intensify in the future. There is now an urgent need to move toward more robust, holistic, and ecologically realistic climate change experiments that incorporate interactions. Without them accurate predictions about the likely deleterious impacts to marine biodiversity and ecosystem functioning over the next century will not be possible. PMID:23610641

  16. High-Resolution Metabolomics with Acyl-CoA Profiling Reveals Widespread Remodeling in Response to Diet.

    PubMed

    Liu, Xiaojing; Sadhukhan, Sushabhan; Sun, Shengyi; Wagner, Gregory R; Hirschey, Matthew D; Qi, Ling; Lin, Hening; Locasale, Jason W

    2015-06-01

    The availability of acyl-Coenzyme A (acyl-CoA) thioester compounds affects numerous cellular functions including autophagy, lipid oxidation and synthesis, and post-translational modifications. Consequently, the acyl-CoA level changes tend to be associated with other metabolic alterations that regulate these critical cellular functions. Despite their biological importance, this class of metabolites remains difficult to detect and quantify using current analytical methods. Here we show a universal method for metabolomics that allows for the detection of an expansive set of acyl-CoA compounds and hundreds of other cellular metabolites. We apply this method to profile the dynamics of acyl-CoA compounds and corresponding alterations in metabolism across the metabolic network in response to high fat feeding in mice. We identified targeted metabolites (>50) and untargeted features (>1000) with significant changes (FDR < 0.05) in response to diet. A substantial extent of this metabolic remodeling exhibited correlated changes in acyl-CoA metabolism with acyl-carnitine metabolism and other features of the metabolic network that together can lead to the discovery of biomarkers of acyl-CoA metabolism. These findings show a robust acyl-CoA profiling method and identify coordinated changes of acyl-CoA metabolism in response to nutritional stress. PMID:25795660

  17. Medicago truncatula Root Nodule Proteome Analysis Reveals Differential Plant and Bacteroid Responses to Drought Stress12[W][OA

    PubMed Central

    Larrainzar, Estíbaliz; Wienkoop, Stefanie; Weckwerth, Wolfram; Ladrera, Rubén; Arrese-Igor, Cesar; González, Esther M.

    2007-01-01

    Drought is one of the environmental factors most affecting crop production. Under drought, symbiotic nitrogen fixation is one of the physiological processes to first show stress responses in nodulated legumes. This inhibition process involves a number of factors whose interactions are not yet understood. This work aims to further understand changes occurring in nodules under drought stress from a proteomic perspective. Drought was imposed on Medicago truncatula ‘Jemalong A17’ plants grown in symbiosis with Sinorhizobium meliloti strain 2011. Changes at the protein level were analyzed using a nongel approach based on liquid chromatography coupled to tandem mass spectrometry. Due to the complexity of nodule tissue, the separation of plant and bacteroid fractions in M. truncatula root nodules was first checked with the aim of minimizing cross contamination between the fractions. Second, the protein plant fraction of M. truncatula nodules was profiled, leading to the identification of 377 plant proteins, the largest description of the plant nodule proteome so far. Third, both symbiotic partners were independently analyzed for quantitative differences at the protein level during drought stress. Multivariate data mining allowed for the classification of proteins sets that were involved in drought stress responses. The isolation of the nodule plant and bacteroid protein fractions enabled the independent analysis of the response of both counterparts, gaining further understanding of how each symbiotic member is distinctly affected at the protein level under a water-deficit situation. PMID:17545507

  18. Protein Profiles Reveal Diverse Responsive Signaling Pathways in Kernels of Two Maize Inbred Lines with Contrasting Drought Sensitivity

    PubMed Central

    Yang, Liming; Jiang, Tingbo; Fountain, Jake C.; Scully, Brian T.; Lee, Robert D.; Kemerait, Robert C.; Chen, Sixue; Guo, Baozhu

    2014-01-01

    Drought stress is a major factor that contributes to disease susceptibility and yield loss in agricultural crops. To identify drought responsive proteins and explore metabolic pathways involved in maize tolerance to drought stress, two maize lines (B73 and Lo964) with contrasting drought sensitivity were examined. The treatments of drought and well water were applied at 14 days after pollination (DAP), and protein profiles were investigated in developing kernels (35 DAP) using iTRAQ (isobaric tags for relative and absolute quantitation). Proteomic analysis showed that 70 and 36 proteins were significantly altered in their expression under drought treatments in B73 and Lo964, respectively. The numbers and levels of differentially expressed proteins were generally higher in the sensitive genotype, B73, implying an increased sensitivity to drought given the function of the observed differentially expressed proteins, such as redox homeostasis, cell rescue/defense, hormone regulation and protein biosynthesis and degradation. Lo964 possessed a more stable status with fewer differentially expressed proteins. However, B73 seems to rapidly initiate signaling pathways in response to drought through adjusting diverse defense pathways. These changes in protein expression allow for the production of a drought stress-responsive network in maize kernels. PMID:25334062

  19. A meta-analysis of responses of canopy photosynthetic conversion efficiency to environmental factors reveals major causes of yield gap.

    PubMed

    Slattery, Rebecca A; Ainsworth, Elizabeth A; Ort, Donald R

    2013-09-01

    Improving plant energy conversion efficiency (?c) is crucial for increasing food and bioenergy crop production and yields. Using a meta-analysis, the effects of greenhouse gases, weather-related stresses projected to intensify due to climate change, and management practices including inputs, shading, and intercropping on ?c were statistically quantified from 140 published studies to identify where improvements would have the largest impact on closing yield gaps. Variation in the response of ?c to treatment type and dosage, plant characteristics, and growth conditions were also examined. Significant mean increases in ?c were caused by elevated [CO2] (20%), shade (18%), and intercropping (15%). ?c increased curvilinearly up to 55% with nitrogen additions whereas phosphorus application was most beneficial at low levels. Significant decreases in ?c of -8.4% due to elevated [O3], -16.8% due to water stress, and -6.5% due to foliar damage were found. A non-significant decrease in ?c of -17.3% was caused by temperature stress. These results identify the need to engineer greater stress tolerance and enhanced responses to positive factors such as [CO2] and nitrogen to improve average yields and yield potential. Optimizing management strategies will also enhance the benefits possible with intercropping, shade, and pest resilience. To determine optimal practices for ?c improvement, further studies should be conducted in the field since several responses were exaggerated by non-field experimental conditions. PMID:23873996

  20. Anoctamin 1 contributes to inflammatory and nerve-injury induced hypersensitivity

    PubMed Central

    2014-01-01

    Background Various pathological conditions such as inflammation or injury can evoke pain hypersensitivity. That represents the response to innocuous stimuli or exaggerated response to noxious stimuli. The molecular mechanism based on the pain hypersensitivity is associated with changes in many of ion channels in dorsal-root ganglion (DRG) neurons. Anoctamin 1 (ANO1/TMEM16A), a Ca2+ activated chloride channel is highly visible in small DRG neurons and responds to heat. Mice with an abolished function of ANO1 in DRG neurons demonstrated attenuated pain-like behaviors when exposed to noxious heat, suggesting a role in acute thermal nociception. In this study, we further examined the function of ANO1 in mediating inflammation- or injury-induced hyperalgesia or allodynia. Results Using Advillin/Ano1 fl/fl (Adv/Ano1 fl/fl ) mice that have a functional ablation of Ano1 mainly in DRG neurons, we were able to determine its role in mediating thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury. The thermal hyperalgesia and mechanical allodynia induced by carrageenan injection and spared-nerve injury were significantly reduced in Adv/Ano1 fl/fl mice. In addition, flinching or licking behavior after bradykinin or formalin injection was also significantly reduced in Adv/Ano1 fl/fl mice. Since pathological conditions augment nociceptive behaviors, we expected ANO1?s contribution to the excitability of DRG neurons. Indeed, the application of inflammatory mediators reduced the threshold for action potential (rheobase) or time for induction of the first action potential in DRG neurons isolated from control (Ano1 fl/fl ) mice. These parameters for neuronal excitability induced by inflammatory mediators were not changed in Adv/Ano1 fl/fl mice, suggesting an active contribution of ANO1 in augmenting the neuronal excitability. Conclusions In addition to ANO1's role in mediating acute thermal pain as a heat sensor, ANO1 is also capable of augmenting the excitability of DRG neurons under inflammatory or neuropathic conditions and thereby aggravates inflammation- or tissue injury-induced pathological pain. PMID:24450308

  1. Proteomic analysis of anatoxin-a acute toxicity in zebrafish reveals gender specific responses and additional mechanisms of cell stress.

    PubMed

    Carneiro, Mariana; Gutiérrez-Praena, Daniel; Osório, Hugo; Vasconcelos, Vítor; Carvalho, António Paulo; Campos, Alexandre

    2015-10-01

    Anatoxin-a is a potent neurotoxin produced by several genera of cyanobacteria. Deaths of wild and domestic animals due to anatoxin-a exposure have been reported following a toxic response that is driven by the inhibition of the acetylcholine receptors at neuromuscular junctions. The consequent neuron depolarization results in an overstimulation of the muscle cells. In order to unravel further molecular events implicated in the toxicity of anatoxin-a, a proteomic investigation was conducted. Applying two-dimensional gel electrophoresis (2DE) and MALDI-TOF mass spectrometry, we report early proteome changes in brain and muscle of zebrafish (Danio rerio) caused by acute exposure to anatoxin-a. In this regard, the test group of male and female zebrafish received an intraperitoneal (i.p.) injection of an anatoxin-a dose of 0.8µgg(-1) of fish body weight (bw) in phosphate buffered saline solution (PBS), while the control received an i.p. injection of PBS only. Five minutes after i.p. injection, brain and muscle tissues were collected, processed and analyzed with 2DE. Qualitative and quantitative analyzes of protein abundance allowed the detection of differences in the proteome of control and exposed fish groups, and between male and female fish (gender specific responses). The altered proteins play functions in carbohydrate metabolism and energy production, ATP synthesis, cell structure maintenance, cellular transport, protein folding, stress response, detoxification and protease inhibition. These changes provide additional insights relative to the toxicity of anatoxin-a in fish. Taking into account the short time of response considered (5min of response to the toxin), the changes in the proteome observed in this work are more likely to derive from fast occurring reactions in the cells. These could occur by protein activity regulation through degradation (proteolysis) and/or post-translational modifications, than from a differential regulation of gene expression, which may require more time for proteins to be synthesized and to produce changes at the proteomic level. PMID:26046835

  2. Survey of Transcript Expression in Rainbow Trout Leukocytes Reveals a Major Contribution of Interferon-Responsive Genes in the Early Response to a Rhabdovirus Infection

    Microsoft Academic Search

    Caroline O'Farrell; Nikta Vaghefi; Monique Cantonnet; Benedicte Buteau; Pierre Boudinot; Abdenour Benmansour

    2002-01-01

    Virus infections induce changes in the expression of host cell genes. A global knowledge of these modifica- tions should help to better understand the virus\\/host cell interactions. To obtain a more comprehensive view of the rainbow trout response to a viral infection, we used the subtractive suppressive hybridization method- ology in the viral hemorrhagic septicemia model of infection. We infected

  3. Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara.

    PubMed

    Sharpe, Sally; Hanke, Tomás; Tinsley-Bown, Anne; Dennis, Mike; Dowall, Stuart; McMichael, Andrew; Cranage, Martin

    2003-08-15

    Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 microm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01(+) rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals. PMID:12951017

  4. B-lymphocytes from a population of children with autism spectrum disorder and their unaffected siblings exhibit hypersensitivity to thimerosal.

    PubMed

    Sharpe, Martyn A; Gist, Taylor L; Baskin, David S

    2013-01-01

    The role of thimerosal containing vaccines in the development of autism spectrum disorder (ASD) has been an area of intense debate, as has the presence of mercury dental amalgams and fish ingestion by pregnant mothers. We studied the effects of thimerosal on cell proliferation and mitochondrial function from B-lymphocytes taken from individuals with autism, their nonautistic twins, and their nontwin siblings. Eleven families were examined and compared to matched controls. B-cells were grown with increasing levels of thimerosal, and various assays (LDH, XTT, DCFH, etc.) were performed to examine the effects on cellular proliferation and mitochondrial function. A subpopulation of eight individuals (4 ASD, 2 twins, and 2 siblings) from four of the families showed thimerosal hypersensitivity, whereas none of the control individuals displayed this response. The thimerosal concentration required to inhibit cell proliferation in these individuals was only 40% of controls. Cells hypersensitive to thimerosal also had higher levels of oxidative stress markers, protein carbonyls, and oxidant generation. This suggests certain individuals with a mild mitochondrial defect may be highly susceptible to mitochondrial specific toxins like the vaccine preservative thimerosal. PMID:23843785

  5. Immune function in sarcoidosis. Studies on delayed hypersensitivity, B and T lymphocytes, serum immunoglobulins and serum complement components.

    PubMed Central

    Tannenbaum, H; Rocklin, R E; Schur, P H; Sheffer, A L

    1976-01-01

    An assessment of immune function was performed in twenty-four patients with recently diagnosed active sarcoidosis. Four patients manifested skin anergy to four antigens. All subjects except one were capable of generating a positive skin response to a croton oil patch test. The incorporation of [3H]thymidine by lymphocytes in vitro in response to the nonspecific mitogens--phytohaemagglutinin, pokeweed mitogen and Con A did not differ between anergic and non-anergic thymidine incorporation in vitro when stimulated by the specific antigens, streptokinase/streptodornase or Candida albicans. Lymphocytes obtained from nine of eleven patients having positive delayed hypersensitivity skin reactions demonstrated MIF production in vitro upon specific antigen challenge. Quantities of circulating B and T lymphocytes did not differ between anergic and absolute numbers of circulating B and T lymphocytes, as well as hypercomplementaemia and hypergammaglobulinaemia when compared to the control group. PMID:795577

  6. A Computational Framework for Evaluating the Efficiency of Arabidopsis Accessions in Response to Nitrogen Stress Reveals Important Metabolic Mechanisms

    PubMed Central

    Kleessen, Sabrina; Fernie, Alisdair R.; Nikoloski, Zoran

    2012-01-01

    High-throughput phenotyping technologies in combination with genetic variability for the plant model species Arabidopsis thaliana (Arabidopsis) offer an excellent experimental platform to reveal the effects of different gene combinations on phenotypes. These developments have been coupled with computational approaches to extract information not only from the multidimensional data, capturing various levels of biochemical organization, but also from various morphological and growth-related traits. Nevertheless, the existing methods usually focus on data aggregation which may neglect accession-specific effects. Here we argue that revealing the molecular mechanisms governing a desired set of output traits can be performed by ranking of accessions based on their efficiencies relative to all other analyzed accessions. To this end, we propose a framework for evaluating accessions via their relative efficiencies which establish a relationship between multidimensional system’s inputs and outputs from different environmental conditions. The framework combines data envelopment analysis (DEA) with a novel valency index characterizing the difference in congruence between the efficiency rankings of accessions under various conditions. We illustrate the advantages of the proposed approach for analyzing genetic variability on a publicly available data set comprising quantitative data on metabolic and morphological traits for 23 Arabidopsis accessions under three conditions of nitrogen availability. In addition, we extend the proposed framework to identify the set of traits displaying the highest influence on ranking based on the relative efficiencies of the considered accessions. As an outlook, we discuss how the proposed framework can be combined with well-established statistical techniques to further dissect the relationship between natural variability and metabolism. PMID:23056002

  7. The Transcriptome of the Nosocomial Pathogen Enterococcus faecalis V583 Reveals Adaptive Responses to Growth in Blood

    PubMed Central

    Vebř, Heidi C.; Snipen, Lars; Nes, Ingolf F.; Brede, Dag A.

    2009-01-01

    Background Enterococcus faecalis plays a dual role in human ecology, predominantly existing as a commensal in the alimentary canal, but also as an opportunistic pathogen that frequently causes nosocomial infections like bacteremia. A number of virulence factors that contribute to the pathogenic potential of E. faecalis have been established. However, the process in which E. faecalis gains access to the bloodstream and establishes a persistent infection is not well understood. Methodology/Principal Findings To enhance our understanding of how this commensal bacterium adapts during a bloodstream infection and to examine the interplay between genes we designed an in vitro experiment using genome-wide microarrays to investigate what effects the presence of and growth in blood have on the transcriptome of E. faecalis strain V583. We showed that growth in both 2xYT supplemented with 10% blood and in 100% blood had a great impact on the transcription of many genes in the V583 genome. We identified several immediate changes signifying cellular processes that might contribute to adaptation and growth in blood. These include modulation of membrane fatty acid composition, oxidative and lytic stress protection, acquisition of new available substrates, transport functions including heme/iron transporters and genes associated with virulence in E. faecalis. Conclusions/Significance The results presented here reveal that cultivation of E. faecalis in blood in vitro has a profound impact on its transcriptome, which includes a number of virulence traits. Observed regulation of genes and pathways revealed new insight into physiological features and metabolic capacities which enable E. faecalis to adapt and grow in blood. A number of the regulated genes might potentially be useful candidates for development of new therapeutic approaches for treatment of E. faecalis infections. PMID:19888459

  8. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    PubMed Central

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-01-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28?d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice. PMID:26066376

  9. [Treatment of dentin hypersensitivity: a retrospective and comparative study of two therapeutic approaches].

    PubMed

    Landry, R G; Voyer, R

    1990-11-01

    Stimulation on exposed dentine at the enamo-dentinal junction is often painful and uncomfortable for the affected patient. Two hundred and forty-four subjects suffering from dentinal sensitivity, aged from 18 to 48 years old, were treated with two types of desensitizing agent. In this study, we used sodium fluoride (Duraflor) and calcium hydroxide (Dycal catalyst). The desensitizing agent is first applied on the exposed dentine and then burnished, without local anaesthesia, until all sensitivity has disappeared. After the first session, 100% of the subjects were desensitized. All subjects were seen 1, 2, 3, 6, 13 and 26 weeks after the first application. After 6 months, 94% of the subjects treated with calcium hydroxide (Dycal) and 87% of those treated with sodium fluoride (Duraflor) were still desensitized. This difference is statistically significant at alpha = 0.01 (Anova test). In conclusion, our study reveals that both calcium hydroxide (Dycal) and sodium fluoride (Duraflor) are effective in the treatment of dentinal hypersensitivity. A slight significant advantage in using calcium hydroxide is also noted. PMID:2261591

  10. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice.

    PubMed

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-01-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28?d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice. PMID:26066376

  11. Plant defense responses in opium poppy cell cultures revealed by liquid chromatography-tandem mass spectrometry proteomics.

    PubMed

    Zulak, Katherine G; Khan, Morgan F; Alcantara, Joenel; Schriemer, David C; Facchini, Peter J

    2009-01-01

    Opium poppy (Papaver somniferum) produces a diverse array of bioactive benzylisoquinoline alkaloids, including the narcotic analgesic morphine and the antimicrobial agent sanguinarine. In contrast to the plant, cell cultures of opium poppy do not accumulate alkaloids constitutively but produce sanguinarine in response to treatment with certain fungal-derived elicitors. The induction of sanguinarine biosynthesis provides a model platform to characterize the regulation of benzylisoquinoline alkaloid pathways and other defense responses. Proteome analysis of elicitor-treated opium poppy cell cultures by two-dimensional denaturing-polyacrylamide gel electrophoresis coupled with liquid chromatography-tandem mass spectrometry facilitated the identification of 219 of 340 protein spots based on peptide fragment fingerprint searches of a combination of databases. Of the 219 hits, 129 were identified through pre-existing plant proteome databases, 63 were identified by matching predicted translation products in opium poppy-expressed sequence tag databases, and the remainder shared evidence from both databases. Metabolic enzymes represented the largest category of proteins and included S-adenosylmethionine synthetase, several glycolytic, and a nearly complete set of tricarboxylic acid cycle enzymes, one alkaloid, and several other secondary metabolic enzymes. The abundance of chaperones, heat shock proteins, protein degradation factors, and pathogenesis-related proteins provided a comprehensive proteomics view on the coordination of plant defense responses. Qualitative comparison of protein abundance in control and elicitor-treated cell cultures allowed the separation of induced and constitutive or suppressed proteins. DNA microarrays were used to corroborate increases in protein abundance with a corresponding induction in cognate transcript levels. PMID:18682378

  12. Anterograde transneuronal viral tract tracing reveals central sensory circuits from brown fat and sensory denervation alters its thermogenic responses

    PubMed Central

    Vaughan, Cheryl H.

    2012-01-01

    Brown adipose tissue (BAT) thermogenic activity and growth are controlled by its sympathetic nervous system (SNS) innervation, but nerve fibers containing sensory-associated neuropeptides [substance P, calcitonin gene-related peptide (CGRP)] also suggest sensory innervation. The central nervous system (CNS) projections of BAT afferents are unknown. Therefore, we used the H129 strain of the herpes simplex virus-1 (HSV-1), an anterograde transneuronal viral tract tracer used to delineate sensory nerve circuits, to define these projections. HSV-1 was injected into interscapular BAT (IBAT) of Siberian hamsters and HSV-1 immunoreactivity (ir) was assessed 24, 48, 72, 96, and 114 h postinjection. The 96- and 114-h groups had the most HSV-1-ir neurons with marked infections in the hypothalamic paraventricular nucleus, periaqueductal gray, olivary areas, parabrachial nuclei, raphe nuclei, and reticular areas. These sites also are involved in sympathetic outflow to BAT suggesting possible BAT sensory-SNS thermogenesis feedback circuits. We tested the functional contribution of IBAT sensory innervation on thermogenic responses to an acute (24 h) cold exposure test by injecting the specific sensory nerve toxin capsaicin directly into IBAT pads and then measuring core (Tc) and IBAT (TIBAT) temperature responses. CGRP content was significantly decreased in capsaicin-treated IBAT demonstrating successful sensory nerve destruction. TIBAT and Tc were significantly decreased in capsaicin-treated hamsters compared with the saline controls at 2 h of cold exposure. Thus the central sensory circuits from IBAT have been delineated for the first time, and impairment of sensory feedback from BAT appears necessary for the appropriate, initial thermogenic response to acute cold exposure. PMID:22378771

  13. The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.

    PubMed

    Kanaan, Nicholas M; Collier, Timothy J; Cole-Strauss, Allyson; Grabinski, Tessa; Mattingly, Zachary R; Winn, Mary E; Steece-Collier, Kathy; Sortwell, Caryl E; Manfredsson, Fredric P; Lipton, Jack W

    2015-01-01

    We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in the substantia nigra (SN) after intrastriatal 6-OHDA in the Sprague-Dawley rat (rattus norvegicus) would identify cellular responses during the degenerative process that could be axoprotective. Specifically, we hypothesized that genes expressed within the SN that followed a profile of being highly upregulated early after the lesion (during active axonal degeneration) and then progressively declined to baseline over 16 weeks as DA neurons died are indicative of potential protective responses to the striatal 6-OHDA insult. Utilizing a ?-means cluster analysis strategy, we demonstrated that one such cluster followed this hypothesized expression pattern over time, and that this cluster contained several interrelated transcripts that are classified as regeneration-associated genes (RAGs) including Atf3, Sprr1a, Ecel1, Gadd45a, Gpnmb, Sox11, Mmp19, Srgap1, Rab15,Lifr, Trib3, Tgfb1, and Sema3c. All exemplar transcripts tested from this cluster (Sprr1a, Ecel1, Gadd45a, Atf3 and Sox11) were validated by qPCR and a smaller subset (Sprr1a, Gadd45a and Sox11) were shown to be exclusively localized to SN DA neurons using a dual label approach with RNAScope in situ hybridization and immunohistochemistry. Upregulation of RAGs is typically associated with the response to axonal injury in the peripheral nerves and was not previously reported as part of the axodegenerative process for DA neurons of the SN. Interestingly, as part of this cluster, other transcripts were identified based on their expression pattern but without a RAG provenance in the literature. These "RAG-like" transcripts need further characterization to determine if they possess similar functions to or interact with known RAG transcripts. Ultimately, it is hoped that some of the newly identified axodegeneration-reactive transcripts could be exploited as axoprotective therapies in PD and other neurodegenerative diseases. PMID:25992874

  14. Systematic analysis of phloem-feeding insect-induced transcriptional reprogramming in Arabidopsis highlights common features and reveals distinct responses to specialist and generalist insects.

    PubMed

    Foyer, Christine H; Verrall, Susan R; Hancock, Robert D

    2015-02-01

    Phloem-feeding insects (PFIs), of which aphids are the largest group, are major agricultural pests causing extensive damage to crop plants. In contrast to chewing insects, the nature of the plant response to PFIs remains poorly characterized. Scrutiny of the literature concerning transcriptional responses of model and crop plant species to PFIs reveals surprisingly little consensus with respect to the transcripts showing altered abundance following infestation. Nevertheless, core features of the transcriptional response to PFIs can be defined in Arabidopsis thaliana. This comparison of the PFI-associated transcriptional response observed in A. thaliana infested by the generalists Myzus persicae and Bemisia tabaci with the specialist Brevicoryne brassicae highlights the importance of calcium-dependent and receptor kinase-associated signalling. We discuss these findings within the context of the complex cross-talk between the different hormones regulating basal immune response mechanisms in plants. We identify PFI-responsive genes, highlighting the importance of cell wall-associated kinases in plant-PFI interactions, as well as the significant role of kinases containing the domain of unknown function 26. A common feature of plant-PFI interaction is enhanced abundance of transcripts encoding WRKY transcription factors. However, significant divergence was observed with respect to secondary metabolism dependent upon the insect attacker. Transcripts encoding enzymes and proteins associated with glucosinolate metabolism were decreased following attack by the generalist M. persicae but not by the specialist B. brassicae. This analysis provides a comprehensive overview of the molecular patterns associated with the plant response to PFIs and suggests that plants recognize and respond to perturbations in the cell wall occurring during PFI infestation. PMID:25540442

  15. Reciprocal Analysis of Francisella novicida Infections of a Drosophila melanogaster Model Reveal Host-Pathogen Conflicts Mediated by Reactive Oxygen and imd-Regulated Innate Immune Response

    PubMed Central

    Moule, Madeleine G.; Monack, Denise M.; Schneider, David S.

    2010-01-01

    The survival of a bacterial pathogen within a host depends upon its ability to outmaneuver the host immune response. Thus, mutant pathogens provide a useful tool for dissecting host-pathogen relationships, as the strategies the microbe has evolved to counteract immunity reveal a host's immune mechanisms. In this study, we examined the pathogen Francisella novicida and identified new bacterial virulence factors that interact with different parts of the Drosophila melanogaster innate immune system. We performed a genome-wide screen to identify F. novicida genes required for growth and survival within the fly and identified a set of 149 negatively selected mutants. Among these, we identified a class of genes including the transcription factor oxyR, and the DNA repair proteins uvrB, recB, and ruvC that help F. novicida resist oxidative stress. We determined that these bacterial genes are virulence factors that allow F. novicida to counteract the fly melanization immune response. We then performed a second in vivo screen to identify an additional subset of bacterial genes that interact specifically with the imd signaling pathway. Most of these mutants have decreased resistance to the antimicrobial peptide polymyxin B. Characterization of a mutation in the putative transglutaminase FTN_0869 produced a curious result that could not easily be explained using known Drosophila immune responses. By using an unbiased genetic screen, these studies provide a new view of the Drosophila immune response from the perspective of a pathogen. We show that two branches of the fly's immunity are important for fighting F. novicida infections in a model host: melanization and an imd-regulated immune response, and identify bacterial genes that specifically counteract these host responses. Our work suggests that there may be more to learn about the fly immune system, as not all of the phenotypes we observe can be readily explained by its interactions with known immune responses. PMID:20865166

  16. A world allergy organization international survey on diagnostic procedures and therapies in drug allergy/hypersensitivity

    E-print Network

    Thong, Bernard YH; Mirakian, Rita; Castells, Mariana; Pichler, Werner; Romano, Antonino; Bonadonna, Patrizia; Diana, Deleanu; Kowalski, Marek; Yanez, Anahi; Lleonart, Ramon; Sanchez-Borges, Mario; Demoly, Pascal

    2011-12-15

    Abstract Objective To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). Methods A questionnaire comprising 39 questions was circulated electronically to member...

  17. Role of specific delayed-type hypersensitivity in Pseudomonas aeruginosa-infected mice.

    PubMed Central

    Colizzi, V; Garzelli, C; Campa, M; Toca, L; Falcone, G

    1982-01-01

    The role of specific cell-mediated immunity was studied in mice injected in the hind footpad with viable Pseudomonas aeruginosa cells. The results reported here show that a state of specific delayed-type hypersensitivity, evaluated both as footpad swelling and as weight increase of popliteal lymph node, occurs in P. aeruginosa-infected mice. Furthermore, a T-cell-enriched spleen population from infected animals was able to transfer delayed hypersensitivity to normal recipients. However, identity at the major histocompatibility complex to transfer delayed hypersensitivity was required. Acquired cellular resistance was not transferred to normal recipients by immune T lymphocytes. On the contrary, mice receiving immune T cells showed an increase in the severity of the lesion caused by a viable challenge. The dichotomy between acquired cellular resistance and delayed hypersensitivity, and the possibility that T-cell reactivity to P. aeruginosa may be actively controlled, is discussed. PMID:6811422

  18. Hypersensitivity reactions to vaccine constituents: a case series and review of the literature.

    PubMed

    Leventhal, Jonathan S; Berger, Emily M; Brauer, Jeremy A; Cohen, David E

    2012-01-01

    Vaccines are composed of immunogens, preservatives, adjuvants, antibiotics, and manufacturing by-products. Components of vaccines may rarely elicit adverse reactions in susceptible individuals, thus raising concerns regarding vaccine safety. In this report, we add to the medical literature 3 cases of cutaneous delayed-type hypersensitivity to the vaccine preservative aluminum. We provide a review of major constituents in vaccines that have elicited immediate-type or delayed-type hypersensitivity reactions and describe their clinical manifestations. We include a table of the Food and Drug Administration-approved vaccines, which lists the quantities of major components including ovalbumin (egg protein), gelatin, aluminum, neomycin, 2-phenoxyethanol, thimerosal, and formaldehyde. Our goals were to inform physicians on the variety of hypersensitivity reactions to common vaccines and to provide information on the choice of vaccines in patients with suspected hypersensitivity. PMID:22653170

  19. Electroacupuncture at He-Mu points reduces P2X4 receptor expression in visceral hypersensitivity

    PubMed Central

    Guo, Xinxin; Chen, Jifei; Lu, Yuan; Wu, Luyi; Weng, Zhijun; Yang, Ling; Xin, Yuhu; Lin, Xianming; Liang, Yi; Fang, Jianqiao

    2013-01-01

    Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats. Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome. Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X4 receptor immureactivity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X4 receptor immunoreactivity in the colon and spinal cord. PMID:25206515

  20. Electroacupuncture at He-Mu points reduces P2X4 receptor expression in visceral hypersensitivity.

    PubMed

    Guo, Xinxin; Chen, Jifei; Lu, Yuan; Wu, Luyi; Weng, Zhijun; Yang, Ling; Xin, Yuhu; Lin, Xianming; Liang, Yi; Fang, Jianqiao

    2013-08-01

    Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats. Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome. Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X4 receptor immureactivity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X4 receptor immunoreactivity in the colon and spinal cord. PMID:25206515

  1. Neonatal Maternal Deprivation Response and Developmental Changes in Gene Expression Revealed by Hypothalamic Gene Expression Profiling in Mice

    PubMed Central

    Ding, Feng; Li, Hong Hua; Li, Jun; Myers, Richard M.; Francke, Uta

    2010-01-01

    Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS). Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period. PMID:20195375

  2. Gene expression signatures in motor neurone disease fibroblasts reveal dysregulation of metabolism, hypoxia-response and RNA processing functions

    PubMed Central

    Raman, R; Allen, S P; Goodall, E F; Kramer, S; Ponger, L-L; Heath, P R; Milo, M; Hollinger, H C; Walsh, T; Highley, J R; Olpin, S; McDermott, C J; Shaw, P J; Kirby, J

    2015-01-01

    Aims Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are two syndromic variants within the motor neurone disease spectrum. As PLS and most ALS cases are sporadic (SALS), this limits the availability of cellular models for investigating pathogenic mechanisms and therapeutic targets. The aim of this study was to use gene expression profiling to evaluate fibroblasts as cellular models for SALS and PLS, to establish whether dysregulated biological processes recapitulate those seen in the central nervous system and to elucidate pathways that distinguish the clinically defined variants of SALS and PLS. Methods Microarray analysis was performed on fibroblast RNA and differentially expressed genes identified. Genes in enriched biological pathways were validated by quantitative PCR and functional assays performed to establish the effect of altered RNA levels on the cellular processes. Results Gene expression profiling demonstrated that whilst there were many differentially expressed genes in common between SALS and PLS fibroblasts, there were many more expressed specifically in the SALS fibroblasts, including those involved in RNA processing and the stress response. Functional analysis of the fibroblasts confirmed a significant decrease in miRNA production and a reduced response to hypoxia in SALS fibroblasts. Furthermore, metabolic gene changes seen in SALS, many of which were also evident in PLS fibroblasts, resulted in dysfunctional cellular respiration. Conclusions The data demonstrate that fibroblasts can act as cellular models for ALS and PLS, by establishing the transcriptional changes in known pathogenic pathways that confer subsequent functional effects and potentially highlight targets for therapeutic intervention. PMID:24750211

  3. Differential adaptive responses to 1- or 2-day fasting in various mouse tissues revealed by quantitative PCR analysis

    PubMed Central

    Yamamoto, Junya; Kamata, Shotaro; Miura, Asumi; Nagata, Tomoko; Kainuma, Ryo; Ishii, Isao

    2015-01-01

    Dietary or caloric restriction confers various clinical benefits. Short-term fasting of mice is a common experimental procedure that may involve systemic metabolic remodeling, which may significantly affect experimental outputs. This study evaluated adaptive cellular responses after 1- or 2-day fasting in 13 mouse tissues by quantitative PCR using 15 marker primer sets for the activation of ubiquitin–proteasome (Atrogin-1 and MuRF1), autophagy–lysosome (LC3b, p62 and Lamp2), amino acid response (Asns, Trib3, Herpud1, xCT, and Chop), Nrf2-mediated antioxidant (HO-1 and Gsta1), and amino acid transport (Slc38a2, Slc7a5, and Slc7a1) systems. Differential activation profiles obtained in seven highly (thymus, liver, spleen, and small intestine) or mildly (stomach, kidney, and colon) atrophied tissues as well as in six non-atrophied tissues (brain, eye, lung, heart, skeletal muscle, and testis) suggested tissue-specific active metabolic remodeling. PMID:25973363

  4. Dissecting the heat stress response in Chlamydomonas by pharmaceutical and RNAi approaches reveals conserved and novel aspects.

    PubMed

    Schmollinger, Stefan; Schulz-Raffelt, Miriam; Strenkert, Daniela; Veyel, Daniel; Vallon, Olivier; Schroda, Michael

    2013-11-01

    To study how conserved fundamental concepts of the heat stress response (HSR) are in photosynthetic eukaryotes, we applied pharmaceutical and antisense/amiRNA approaches to the unicellular green alga Chlamydomonas reinhardtii. The Chlamydomonas HSR appears to be triggered by the accumulation of unfolded proteins, as it was induced at ambient temperatures by feeding cells with the arginine analog canavanine. The protein kinase inhibitor staurosporine strongly retarded the HSR, demonstrating the importance of phosphorylation during activation of the HSR also in Chlamydomonas. While the removal of extracellular calcium by the application of EGTA and BAPTA inhibited the HSR in moss and higher plants, only the addition of BAPTA, but not of EGTA, retarded the HSR and impaired thermotolerance in Chlamydomonas. The addition of cycloheximide, an inhibitor of cytosolic protein synthesis, abolished the attenuation of the HSR, indicating that protein synthesis is necessary to restore proteostasis. HSP90 inhibitors induced a stress response when added at ambient conditions and retarded attenuation of the HSR at elevated temperatures. In addition, we detected a direct physical interaction between cytosolic HSP90A/HSP70A and heat shock factor 1, but surprisingly this interaction persisted after the onset of stress. Finally, the expression of antisense constructs targeting chloroplast HSP70B resulted in a delay of the cell's entire HSR, thus suggesting the existence of a retrograde stress signaling cascade that is desensitized in HSP70B-antisense strains. PMID:23713078

  5. Discovery of the surface polarity gradient on iridescent Morpho butterfly scales reveals a mechanism of their selective vapor response

    PubMed Central

    Potyrailo, Radislav A.; Starkey, Timothy A.; Vukusic, Peter; Ghiradella, Helen; Vasudev, Milana; Bunning, Timothy; Naik, Rajesh R.; Tang, Zhexiong; Larsen, Michael; Deng, Tao; Zhong, Sheng; Palacios, Manuel; Grande, James C.; Zorn, Gilad; Goddard, Gregory; Zalubovsky, Sergey

    2013-01-01

    For almost a century, the iridescence of tropical Morpho butterfly scales has been known to originate from 3D vertical ridge structures of stacked periodic layers of cuticle separated by air gaps. Here we describe a biological pattern of surface functionality that we have found in these photonic structures. This pattern is a gradient of surface polarity of the ridge structures that runs from their polar tops to their less-polar bottoms. This finding shows a biological pattern design that could stimulate numerous technological applications ranging from photonic security tags to self-cleaning surfaces, gas separators, protective clothing, sensors, and many others. As an important first step, this biomaterial property and our knowledge of its basis has allowed us to unveil a general mechanism of selective vapor response observed in the photonic Morpho nanostructures. This mechanism of selective vapor response brings a multivariable perspective for sensing, where selectivity is achieved within a single chemically graded nanostructured sensing unit, rather than from an array of separate sensors. PMID:24019497

  6. Evaluation of the effect of closed areas on a unique and shallow water coral reef fish assemblage reveals complex responses

    NASA Astrophysics Data System (ADS)

    Shedrawi, G.; Harvey, E. S.; McLean, D. L.; Prince, J.; Bellchambers, L. M.; Newman, S. J.

    2014-09-01

    Areas closed to fishing are advocated as both fisheries management and biodiversity conservation tools. However, few studies investigate the responses of suites of both target and non-target fish species within an assemblage, which is an important consideration for ecosystem-based fisheries management approaches. Diver-operated stereo-video was used to assess the abundance and length of coral reef fish across multiple areas both open and closed to fishing at the Houtman Abrolhos Islands, Western Australia. After taking into consideration spatial differences in benthic habitat, the composition of fish assemblages was found to differ between open and closed areas. The target species, Plectropomus leopardus, was approximately two times more abundant in closed areas. Furthermore, 51 % of P. leopardus were larger than the minimum legal length (MLL) for retention in closed areas compared with only 1.8 % in areas open to fishing. Another target species, Choerodon rubescens was surveyed in greater abundance at sizes larger than the MLL in closed areas (64 % >400 mm) in comparison with areas open to fishing (36 %). A number of non-target species were also larger in closed areas (e.g., Kyphosus cornelii, Scarus schlegeli). In contrast, several non-targeted prey species were more abundant in open areas (e.g., Pomacentrus milleri was six times more abundant in open areas). Our results document complex responses of target and non-target species in closed areas at the Houtman Abrolhos Islands.

  7. Hydrological response to earthquakes in the Haibara well, central Japan - I. Groundwater level changes revealed using state space decomposition of atmospheric pressure, rainfall and tidal responses

    USGS Publications Warehouse

    Matsumoto, N.; Kitagawa, G.; Roeloffs, E.A.

    2003-01-01

    For the groundwater level observed at the Haibara well, Shizuoka Prefecture, central Japan, time series analysis using state-space modelling is applied to extract hydrological anomalies related to eart