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1

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

PubMed

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

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

2012-09-01

2

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

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

Orlowska, Elzbieta; Llorente, Briardo

2012-01-01

3

Lipid Profiling of the Arabidopsis Hypersensitive Response Reveals Specific Lipid Peroxidation and Fragmentation Processes: Biogenesis of Pimelic and Azelaic Acid1[C][W  

PubMed Central

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

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

2012-01-01

4

Programmed cell death, mitochondria and the plant hypersensitive response  

Microsoft Academic Search

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

Eric Lam; Naohiro Kato; Michael Lawton

2001-01-01

5

Progressively Increased M50 Responses to Repeated Sounds in Autism Spectrum Disorder with Auditory Hypersensitivity: A Magnetoencephalographic Study  

PubMed Central

The aim of this study was to investigate the differential time-course responses of the auditory cortex to repeated auditory stimuli in children with autism spectrum disorder (ASD) showing auditory hypersensitivity. Auditory-evoked field values were obtained from 21 boys with ASD (12 with and 9 without auditory hypersensitivity) and 15 age-matched typically developing controls. M50 dipole moments were significantly increased during the time-course study only in the ASD with auditory hypersensitivity compared with those for the other two groups. The boys having ASD with auditory hypersensitivity also showed more prolonged response duration than those in the other two groups. The response duration was significantly related to the severity of auditory hypersensitivity. We propose that auditory hypersensitivity is associated with decreased inhibitory processing, possibly resulting from an abnormal sensory gating system or dysfunction of inhibitory interneurons. PMID:25054201

Matsuzaki, Junko; Kagitani-Shimono, Kuriko; Sugata, Hisato; Hirata, Masayuki; Hanaie, Ryuzo; Nagatani, Fumiyo; Tachibana, Masaya; Tominaga, Koji; Mohri, Ikuko; Taniike, Masako

2014-01-01

6

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...

7

Th2Biased Immune Responses Are Important in a Murine Model of Chronic Hypersensitivity Pneumonitis  

Microsoft Academic Search

Background: Chronic hypersensitivity pneumonitis (HP) can lead to irreversible pulmonary fibrosis. A good animal model is essential to elucidate the mechanisms of this disease. We previously reported that a Th2 predominance may play an important role in the fibrogenesis in chronic HP patients. A study was undertaken to evaluate whether Th2-biased immune responses were crucial during the processes of lung

Keiko Mitaka; Yasunari Miyazaki; Makito Yasui; Masashi Furuie; Shuji Miyake; Naohiko Inase; Yasuyuki Yoshizawa

2011-01-01

8

Involvement of cathepsin B in the plant disease resistance hypersensitive response  

Microsoft Academic Search

Summary A diverse range of plant proteases are implicated in pathogen perception and in subsequent signalling and execution of disease resistance. We demonstrate, using protease inhibitors and virus-induced gene silencing (VIGS), that the plant papain cysteine protease cathepsin B is required for the disease resistance hypersensitive response (HR). VIGS of cathepsin B prevented programmed cell death (PCD) and compromised disease

Eleanor M. Gilroy; Ingo Hein; Renier van der Hoorn; Petra C. Boevink; Eduard Venter; Hazel McLellan; Florian Kaffarnik; Katarina Hrubikova; Jane Shaw; Maria Holeva; Eduardo C. Lopez; Orlando Borras-Hidalgo; Leighton Pritchard; Gary J. Loake; Christophe Lacomme; Paul R. J. Birch

2007-01-01

9

System-wide hypersensitive response-associated transcriptome and metabolome reprogramming in tomato.  

PubMed

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

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

2013-07-01

10

Inhibition by Agrobacterium tumefaciens and Pseudomonas savastanoi of development of the hypersensitive response elicited by Pseudomonas syringae pv. phaseolicola.  

PubMed Central

Injection into tobacco leaves of biotype 1 Agrobacterium tumefaciens or of Pseudomonas savastanoi inhibited the development of a visible hypersensitive response to the subsequent injection at the same site of Pseudomonas syringae pv. phaseolicola. This interference with the hypersensitive response was not seen with injection of bacterial growth medium or Escherichia coli cells. Live A. tumefaciens cells were required for the inhibitory effect. Various mutants and strains of A. tumefaciens were examined to determine the genes involved. Known chromosomal mutations generally had no effect on the ability of A. tumefaciens to inhibit the hypersensitive response, except for chvB mutants which showed a reduced (but still significant) inhibition of the hypersensitive response. Ti plasmid genes appeared to be required for the inhibition of the hypersensitive response. The bacteria did not need to be virulent in order to inhibit the hypersensitive response. Deletion of the vir region from pTi had no effect on the inhibition. However, the T region of the Ti plasmid was required for inhibition. Studies of transposon mutants suggested that the tms but not tmr or ocs genes were required. These genes were not acting after transfer to plant cells since they were effective in strains lacking vir genes and thus unable to transfer DNA to plant cells. The results suggest that the expression of the tms genes in the bacteria may inhibit the development of the hypersensitive response by the plant. An examination of the genes required in P. savastanoi for the inhibition of the hypersensitive response suggested that bacterial production of auxin was also required for the inhibition of the hypersensitive response by these bacteria. Images PMID:2211508

Robinette, D; Matthysse, A G

1990-01-01

11

Inhibition by Agrobacterium tumefaciens and Pseudomonas savastanoi of development of the hypersensitive response elicited by Pseudomonas syringae pv. phaseolicola.  

PubMed

Injection into tobacco leaves of biotype 1 Agrobacterium tumefaciens or of Pseudomonas savastanoi inhibited the development of a visible hypersensitive response to the subsequent injection at the same site of Pseudomonas syringae pv. phaseolicola. This interference with the hypersensitive response was not seen with injection of bacterial growth medium or Escherichia coli cells. Live A. tumefaciens cells were required for the inhibitory effect. Various mutants and strains of A. tumefaciens were examined to determine the genes involved. Known chromosomal mutations generally had no effect on the ability of A. tumefaciens to inhibit the hypersensitive response, except for chvB mutants which showed a reduced (but still significant) inhibition of the hypersensitive response. Ti plasmid genes appeared to be required for the inhibition of the hypersensitive response. The bacteria did not need to be virulent in order to inhibit the hypersensitive response. Deletion of the vir region from pTi had no effect on the inhibition. However, the T region of the Ti plasmid was required for inhibition. Studies of transposon mutants suggested that the tms but not tmr or ocs genes were required. These genes were not acting after transfer to plant cells since they were effective in strains lacking vir genes and thus unable to transfer DNA to plant cells. The results suggest that the expression of the tms genes in the bacteria may inhibit the development of the hypersensitive response by the plant. An examination of the genes required in P. savastanoi for the inhibition of the hypersensitive response suggested that bacterial production of auxin was also required for the inhibition of the hypersensitive response by these bacteria. PMID:2211508

Robinette, D; Matthysse, A G

1990-10-01

12

Hypersensitivity Vasculitis  

MedlinePLUS

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

13

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

NSDL National Science Digital Library

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.

Evangelia Charmandari (University of Athens Medical School; REV)

2012-10-02

14

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

Microsoft Academic Search

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

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

1992-01-01

15

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

Microsoft Academic Search

Summary Resistance to Turnip Crinkle Virus (TCV) in Arabidopsis ecotype Dijon (Di)-17 is conferred by the resistance gene HRT and a recessive locus rrt. In Di-17, TCV elicits a hypersensitive response (HR), which is accompanied by increased expression of pathogenesis-related (PR) genes and high levels of salicylic acid (SA). We have previously shown that HRT-mediated resistance to TCV is dependent

A. C. Chandra-Shekara; Manisha Gupte; Duroy Navarre; Surabhi Raina; Ramesh Raina; Daniel Klessig; Pradeep Kachroo

2006-01-01

16

DWD HYPERSENSITIVE TO UV-B 1 is negatively involved in UV-B mediated cellular responses in Arabidopsis.  

PubMed

Among T-DNA insertion mutants of various cullin4-RING ubiquitin E3 ligase (CRL4) substrate receptors, one mutant that exhibits enhanced sensitivity in response to ultraviolet-B (UV-B) illumination has been isolated and its corresponding gene has been named DWD HYPERSENSITIVE TO UV-B 1 (DHU1) in Arabidopsis. dhu1 lines showed much shorter hypocotyls than those in wild type under low doses of UV-B. Other light did not alter hypocotyl growth patterns in dhu1, indicating the hypersensitivity of dhu1 is restricted to UV-B. DHU1 was upregulated by more than two times in response to UV-B application of 1.5 ?mol m(-2) s(-1), implying its possible involvement in UV-B signaling. DHU1 is able to bind to DDB1, an adaptor of CRL4; accordingly, DHU1 is thought to act as a substrate receptor of CRL4. Microarray data generated from wild-type and dhu1 under low doses of UV-B revealed that 209 or 124 genes were upregulated or downregulated by more than two times in dhu1 relative to wild type, respectively. About 23.4 % of the total upregulated genes in dhu1 were upregulated by more than five times in response to UV-B based on the AtGenExpress Visualization Tool data, while only about 1.4 % were downregulated to the same degree by UV-B, indicating that loss of DHU1 led to the overall enhancement of the upregulation of UV-B inducible genes. dhu1 also showed altered responsiveness under high doses of UV-B. Taken together, these findings indicate that DHU1 is a potent CRL4 substrate receptor that may function as a negative regulator of UV-B response in Arabidopsis. PMID:25193399

Kim, Sang-Hoon; Kim, Hani; Seo, Kyoung-In; Kim, Soon-Hee; Chung, Sunglan; Huang, Xi; Yang, Panyu; Deng, Xing Wang; Lee, Jae-Hoon

2014-12-01

17

Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity.  

PubMed

Horses are affected by a wide variety of arthropod ectoparasites, ranging from lice which spend their entire life on the host, through ticks which feed over a period of days, to numerous biting insects that only transiently visit the host to feed. The presence of ectoparasites elicits a number of host responses including innate inflammatory responses, adaptive immune reactions and altered behaviour; all of which can reduce the severity of the parasite burden. All of these different responses are linked through immune mechanisms mediated by mast cells and IgE antibodies which have an important role in host resistance to ectoparasites, yet immune responses also cause severe pathological reactions. One of the best described examples of such pathological sequelae is insect bite hypersensitivity (IBH) of horses; an IgE-mediated type 1 hypersensitivity to the salivary proteins of Culicoides spp. associated with T-helper-2 production of IL4 and IL13. Importantly, all horses exposed to Culicoides have an expanded population of Culicoides antigen-specific T cells with this pattern of cytokine production, but in those which remain healthy, the inflammatory reaction is tempered by the presence of FoxP3+ CD4+ regulatory T cells that express IL10 and TGF-beta, which suppresses the IL4 production by Culicoides antigen-activated T cells. PMID:25180696

Wilson, A D

2014-11-01

18

Novel study on the elicitation of hypersensitive response by polyunsaturated fatty acids in potato tuber.  

PubMed

A GC-MS procedure was carried out for the simultaneous and unequivocal quantitation of both potato phytoalexin (rishitin and lubimin) accumulation and the rate of disappearance of polyunsaturated fatty acids (PUFA) and some of their esters tested as possible elicitors. Potato 5-lipoxygenase and lipolytic acyl hydrolase play a key role in hypersensitive response (HR) induction. As expected, arachidonic acid, its hydrolysable esters, and eicosapentaenoic acid elicited much higher HR than the other PUFA tested, although the latter were equally affected by potato 5-lipoxygenase. Hydroxyl radicals appear to be actively involved in the browning process. The polyaminoacid poly-L-lysine did not show any eliciting activity. PMID:1344908

Fanelli, C; Castoria, R; Fabbri, A A; Passi, S

1992-01-01

19

Delayed-type hypersensitivity to Phlebotomus papatasi sand fly bite: An adaptive response induced by the fly?  

Microsoft Academic Search

The saliva of bloodsucking arthropods contains a large array of pharmacologically active compounds that assist hematophagy. Arthropod saliva is also responsible for causing uncomfortable allergic responses in its vertebrate hosts. In this article, we investigate whether the sand fly Phlebotomus papatasi, known to produce a strong delayed-type hypersensitivity (DTH) in humans, could benefit from, and possibly adaptively induce, this response

Yasmine Belkaid; Jesus G. Valenzuela; Shaden Kamhawi; Edgar Rowton; David L. Sacks; José M. C. Ribeiro

2000-01-01

20

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

PubMed

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 anti-canine IgE, before and after a single oral administration of PEA at doses of 3, 10 and 30 mg/kg. A significant reduction in wheal area induced by both antigen and anti-canine IgE challenge was observed after PEA administration. No significant differences were observed between the two higher doses studied, suggesting that the 10 mg/kg dose had exerted the maximum inhibitory effect. When blood levels of PEA were compared with the effects at different times, an evident correlation was obtained. However, the anti-inflammatory effects of PEA were more long-lasting than their plasma concentrations. The intradermal injection of substance P did not reveal any skin reaction (wheal or erythema formation) at any of the concentrations tested. In conclusion, PEA might constitute a new therapeutic strategy for the treatment of allergic inflammatory skin diseases in companion animals. PMID:21601500

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

2012-03-01

21

Retrospective study of clinical observations on insect hypersensitivity and response to immunotherapy in allergic dogs.  

PubMed

A retrospective study was conducted to evaluate the importance of insect hypersensitivity in atopic dogs in the northeastern United States. Fifty (63%) of 79 dogs tested with 7 insect allergens, other than flea, had positive reactions to one or more insects. No dog had positive reactions to insects only. Forty-four dogs underwent immunotherapy. Thirty-one had insect antigens in their prescription mixture and 13 had only conventional environmental allergens. There was no statistical difference in the response rate between the 2 groups. Thus, testing with insect allergens did not decrease the number of dogs with negative skin tests, and including insect allergens in immunotherapy mixtures did not improve the response rate. PMID:11360857

Rothstein, E; Miller, W H; Scott, D W; Mohammed, H O

2001-05-01

22

Variation in plant defense against invasive herbivores: evidence for a hypersensitive response in eastern hemlocks (Tsuga canadensis).  

PubMed

Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces a defensive hypersensitive response, a defense mechanism consisting of elevated H(2)O(2) levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae ('HWA') and elongate hemlock scale Fiorinia externa ('EHS') feed on eastern hemlocks; although both are sessile sap feeders, HWA causes more damage than EHS. The rapid rate of tree death following HWA infestation has led to the suggestion that feeding induces a hypersensitive response in hemlock trees. We assessed the potential for an herbivore-induced hypersensitive response in eastern hemlocks by measuring H(2)O(2) levels in foliage from HWA-infested, EHS-infested, and uninfested trees. Needles with settled HWA or EHS had higher H(2)O(2) levels than control needles, suggesting a localized hypersensitive plant response. Needles with no direct contact to settled HWA also had high H(2)O(2) levels, suggesting that HWA infestation may induce a systemic defense response in eastern hemlocks. There was no similar systemic defensive response in the EHS treatment. Our results showed that two herbivores in the same feeding guild had dramatically different outcomes on the health of their shared host. PMID:21573865

Radville, Laura; Chaves, Arielle; Preisser, Evan L

2011-06-01

23

PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity  

SciTech Connect

Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.

Nelson, T.A.; Holmes, S.; Alekseyenko, A.V.; Shenoy, M.; DeSantis, T.; Wu, C.H.; Andersen, G.L.; Winston, J.; Sonnenburg, J.; Pasricha, P.J.; Spormann, A.

2010-12-01

24

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

PubMed

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

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

2014-05-01

25

IL1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response  

Microsoft Academic Search

IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1a and IL-1b, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by Th2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response

Susumu Nakae; Yutaka Komiyama; Hiroshi Yokoyama; Aya Nambu; Masaomi Umeda; Michiko Iwase; Ikuo Homma; Katsuko Sudo; Reiko Horai; Masahide Asano; Yoichiro Iwakura

2003-01-01

26

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

PubMed

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

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

2009-01-01

27

Response heterogeneity of 5-HT3 receptor antagonists in a rat visceral hypersensitivity model.  

PubMed

Subcutaneous administration of granisetron (BRL 43694, endo-1-methyl-N-(9-methyl-9-azabicyclo[3.3.1.]non-3-yl-1 H-indazole-3-carboxamide) and zacopride (4-amino-N-(1-azabicyclo[2.2.2.]oct-3-yl)-5-chloro-2-methoxybenzamide), two 5-HT3 receptor antagonists, at doses ranging from 3 to 1000 micrograms/kg, inhibited abdominal contractions induced by distension (30 mmHg, 10 min) of irritated colon (0.6% acetic acid) in conscious rats with a bell-shaped dose-response curve. The ED50 of granisetron and zacopride were 17.6 and 8.2 micrograms/kg, respectively. In contrast, both tropisetron (ICS 205-930, (3-a-tropanyl)t-indole-3-carboxylic ester) and ondansetron (GR38032F, 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1 H-imidazol-1-yl)methyl]-4 H-carbazol-4-one hydrocloride dihydrate) were inactive in this model. These data further support the concept of a heterogeneity in the potency of 5-HT3 receptor antagonists in modulating visceral hypersensitivity in conscious rats. This finding is in agreement with a reported efficacy of granisetron but not of ondansetron in patients with irritable bowel syndrome. PMID:9007525

Langlois, A; Pascaud, X; Junien, J L; Dahl, S G; Rivière, P J

1996-12-27

28

Influence of Maternal Murine Immunization with Dermatophagoides pteronyssinus Extract on the Type I Hypersensitivity Response in Offspring  

Microsoft Academic Search

Background: Maternal exposure to environmental ubiquitous allergens could exert an influence on the newborn’s immune repertoire and the later development of allergy. The aim of this study was to investigate the effects of maternal immunization with Dermatophagoides pteronyssinus (Dp) on the hypersensitivity response and IgG subclass production in offspring using a murine model. Methods: A\\/Sn mice were immunized with Dp

A. E. Fusaro; M. Maciel; J. R. Victor; C. R. Oliveira; A. J. S. Duarte; M. N. Sato

2002-01-01

29

Variation in Plant Defense against Invasive Herbivores: Evidence for a Hypersensitive Response in Eastern Hemlocks ( Tsuga canadensis )  

Microsoft Academic Search

Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces\\u000a a defensive hypersensitive response, a defense mechanism consisting of elevated H2O2 levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae (‘HWA’) and elongate hemlock scale Fiorinia externa (‘EHS’) feed on eastern hemlocks;

Laura Radville; Arielle Chaves; Evan L. Preisser

2011-01-01

30

Glutathione and tryptophan metabolism are required for Arabidopsis immunity during the hypersensitive response to hemibiotrophs.  

PubMed

The hypersensitive response (HR) is a type of strong immune response found in plants that is accompanied by localized cell death. However, it is unclear how HR can block a broad range of pathogens with different infective modes. In this study, we report that ?-glutamylcysteine synthetase GSH1, which is critical for glutathione biosynthesis, and tryptophan (Trp) metabolism contribute to HR and block development of fungal pathogens with hemibiotrophic infective modes. We found that GSH1 is involved in the penetration2 (PEN2)-based entry control of the nonadapted hemibiotroph Colletotrichum gloeosporioides. However, Arabidopsis mutants specifically defective in entry control terminated further growth of the pathogen in the presence of HR cell death, whereas gsh1 mutants supported pathogen invasive growth in planta, demonstrating the requirement of GSH1 for postinvasive nonhost resistance. Remarkably, on the basis of the phenotypic and metabolic analysis of Arabidopsis mutants defective in Trp metabolism, we showed that biosynthesis of Trp-derived phytochemicals is also essential for resistance to C. gloeosporioides during postinvasive HR. By contrast, GSH1 and these metabolites are likely to be dispensable for the induction of cell death during postinvasive HR. Furthermore, the resistance to Ralstonia solanacearum 1/resistance to Pseudomonas syringae 4 dual Resistance gene-dependent immunity of Arabidopsis to the adapted hemibiotroph shared GSH1 and cytochromes P450 CYP79B2/CYP79B3 with postinvasive nonhost resistance, whereas resistance to P. syringae pv. maculicola 1 and resistance to P. syringae 2-based Resistance gene resistance against bacterial pathogens did not. These data suggest that the synthesis of glutathione and Trp-derived metabolites during HR play crucial roles in terminating the invasive growth of both nonadapted and adapted hemibiotrophs. PMID:23696664

Hiruma, Kei; Fukunaga, Satoshi; Bednarek, Pawel; Pislewska-Bednarek, Mariola; Watanabe, Satoshi; Narusaka, Yoshihiro; Shirasu, Ken; Takano, Yoshitaka

2013-06-01

31

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

SciTech Connect

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.

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

1988-03-01

32

Prevention of the induction of allospecific cytotoxic T lymphocyte and delayed-type hypersensitivity responses by ultraviolet irradiation of corneal allografts  

SciTech Connect

The effect of ultraviolet radiation (UVR) on the immunogenicity of corneal allografts was examined in a mouse model. Corneal allografts differing from the host at the entire MHC and multiple minor H loci were subjected to 200 mJ/cm2 of UVB irradiation immediately prior to heterotropic transplantation. Analysis of cytotoxic T lymphocyte and delayed-type hypersensitivity responses revealed that UVR treated corneal grafts failed to induce either CTL or DTH responses in C57BL/6 recipients. UVB treatment abolished the immunogenicity of highly immunogenic corneal grafts containing either resident or infiltrating donor-specific Langerhans cells. Sequential grafting experiments demonstrated that UVB-treated grafts rendered the hosts anergic to subsequent immunization with highly immunogenic corneal limbus grafts that contained dense concentrations of Ia+ Langerhans cells of donor origin. The results indicate that UV treatment not only reduces the immunogenicity of the corneal allograft but may also render it tolerogenic.

Niederkorn, J.Y.; Callanan, D.; Ross, J.R. (Univ. of Texas Southwestern Medical Center, Dallas (USA))

1990-08-01

33

Hypersensitivity pneumonitis  

MedlinePLUS

Rose CS, Lara AR. Hypersensitivity pneumonia. In: Mason RJ, Broaddus VC, Martin TR, et al., eds. Murray and Nadel's Textbook of Respiratory Medicine . 5th ed. Philadelphia, Pa: Elsevier Saunders; 2010:chap ...

34

Trends in hypersensitivity drug reactions: more drugs, more response patterns, more heterogeneity.  

PubMed

Hypersensitivity drug reactions (HDRs) vary over time in frequency, drugs involved, and clinical entities. Specific reactions are mediated by IgE, other antibody isotypes (IgG or IgM), and T cells. Nonspecific HDRs include those caused by nonsteroidal anti-inflammatory drugs (NSAIDs). beta-Lactams--the most important of which are amoxicillin and clavulanic acid--are involved in specific immunological mechanisms. Fluoroquinolones (mainly moxifloxacin, followed by ciprofloxacin and levofloxacin) can also induce HDRs mediated by IgE and T cells. In the case of radio contrast media, immediate reactions have decreased, while nonimmediate reactions, mediated by T cells, have increased. There has been a substantial rise in hypersensitivity reactions to antibiotics and latex in perioperative allergic reactions to anesthetics. NSAIDs are the most frequent drugs involved in HDRs. Five well-defined clinical entities, the most common of which is NSAID-induced urticaria/angioedema, have been proposed in a new consensus classification. Biological agents are proteins including antibodies that have been humanized in order to avoid adverse reactions. Reactions can be mediated by IgE or T cells or they may be due to an immunological imbalance. Chimeric antibodies are still in use and may have epitopes that are recognized by the immune system, resulting in allergic reactions. PMID:25011351

Doña, I; Barrionuevo, E; Blanca-Lopez, N; Torres, M J; Fernandez, T D; Mayorga, C; Canto, G; Blanca, M

2014-01-01

35

Capsaicin-sensitive cough receptors in lower airway are responsible for cough hypersensitivity in patients with upper airway cough syndrome  

PubMed Central

Background Cough hypersensitivity may be related to the pathogenesis of upper airway cough syndrome (UACS). The purpose of the study was to investigate the role of capsaicin-sensitive cough receptors on the laryngopharynx and lower airway in the cough hypersensitivity of patients with UACS. Material/Methods 59 patients with UACS, 33 patients with rhinitis/sinusitis without cough, and 39 healthy volunteers were recruited for the study. Cough threshold C5, defined as the lowest concentration of capsaicin required for the induction of ?5 coughs upon esposure to capsaicin, were determined at baseline and after laryngopharngeal anesthesia with lidocaine in all the subjects. After induced sputum cytology, the concentrations of histamine, prostaglandin E2 (PGE2), and calcitonin-gene-related peptide (CGPR) in the induced sputum were measured by ELISA. In 15 patients with UACS, sputum cytology and measurement of the above mediators were repeated after successful therapy. Results C5 response to capsaicin was significantly lower in the UACS group than in the rhinitis/sinusitis group and healthy control groups [3.9 (0.98, 7.8) ?mol/L vs. 7.8 (3.9, 93.75) ?mol/L vs. 31.2 (15.6, 62.5) ?mol/L, H=40.12, P=0.000]. Laryngopharngeal anesthesia with lidocaine dramatically increased C5 to capsaicin in the subjects of all 3 groups by a similar degree, but the increase in the UACS group was still the lowest, with an increased level of histamine, PGE2, and CGRP in the induced sputum. When cough resolved with the treatment of cetirizine alone or in combination with erythromycin, the levels of CGRP and histamine in the induced sputum decreased significantly in 15 patients with UACS, with no obvious change in cell differential or concentration of PGE2 in the induced sputum. Conclusions Laryngeal TRPV1 plays an important role in cough sensitivity, but sensitization of capsaicin-sensitive cough receptors in the lower airway may be more responsible for the cough hypersensitivity in patients with UACS. PMID:24296694

Yu, Li; Xu, Xianghuai; Wang, Lan; Yang, Zhongmin; Lü, Hanjing; Qiu, Zhongmin

2013-01-01

36

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

PubMed Central

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

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

2009-01-01

37

Role of Calcium in Signal Transduction during the Hypersensitive Response Caused by Basidiospore-Derived Infection of the Cowpea Rust Fungus  

Microsoft Academic Search

The hypersensitive response (HR) of disease-resistant plant cells to fungal invasion is a rapid cell death that has some features in common with programmed cell death (apoptosis) in animals. We investigated the role of cytosolic free cal- cium ((Ca 2 1 ) i ) in the HR of cowpea to the cowpea rust fungus. By using confocal laser scanning microscopy

Haixin Xu; Michèle C. Heath

1998-01-01

38

Gender differences in delayed-type hypersensitivity response: effects of stress and coping in first-year law students.  

PubMed

Law students show significant deficits in emotional and physical well-being compared with groups of students in other areas of higher education. Furthermore, evidence suggests that these effects may be worse for women than for men. The use of active coping can positively affect immunity under stress, but this may be most true for men in the context of law school. The current study examined the delayed-type hypersensitivity (DTH) skin responses of first-year law students (n=121) and a comparison group (n=30). Students' health behaviors, self-evaluative emotions, and coping strategies were also reported. Male law students had larger DTH responses than females, but this gender effect was not present in the comparison group. Endorsement of perseverance under stress (n=19), an active coping strategy, moderated the gender effect on immunity. Perseverance associated with larger DTH responses and more positive self-evaluative emotion, but only among men. These results indicate that active coping may be less efficacious for women than for men in law school, which in turn may limit women's opportunities to attenuate negative effects of law school. PMID:19162169

Flynn, Sarah McQueary; Schipper, Lindsey J; Roach, Abbey R; Segerstrom, Suzanne C

2009-07-01

39

Gender Differences in Delayed-Type Hypersensitivity Response: Effects of Stress and Coping in First Year Law Students  

PubMed Central

Law students show significant deficits in emotional and physical well-being compared with groups of students in other areas of higher education. Furthermore, evidence suggests that these effects may be worse for women than for men. The use of active coping can positively affect immunity under stress, but this may be most true for men in the context of law school. The current study examined the delayed-type hypersensitivity (DTH) skin responses of first year law students (n=121) and a comparison group (n=30). Students' health behaviors, self-evaluative emotions, and coping strategies were also reported. Male law students had larger DTH responses than females, but this gender effect was not present in the comparison group. Endorsement of perseverance under stress (n = 19), an active coping strategy, moderated the gender effect on immunity. Perseverance associated with larger DTH responses and more positive self-evaluative emotion, but only among men. These results indicate that active coping may be less efficacious for women than for men in law school, which in turn may limit women's opportunities to attenuate negative effects of law school. PMID:19162169

Flynn, Sarah McQueary; Schipper, Lindsey J.; Roach, Abbey R.; Segerstrom, Suzanne C.

2009-01-01

40

Decrease in sensitisation rate and intestinal anaphylactic response after nitric oxide synthase inhibition in a food hypersensitivity model.  

PubMed Central

BACKGROUND--Although nitric oxide (NO) has been found to have a role in gut inflammation and to modulate immunoglobulin production, little is known about its part in food hypersensitivities. AIM--This study aimed to evaluate the role of NO through the inhibition of constitutive and inducible NO synthase (cNOS and iNOS respectively) on the sensitisation process (antibody titres) and on intestinal anaphylactic responses (colonic hypersecretion upon antigen challenge). ANIMALS AND METHODS--Guinea pigs sensitised to cow's milk proteins were treated either during the sensitisation period or before antigen challenge by N-nitro-L-arginine methyl ester (L-NAME) (inhibiting both cNOS and iNOS) or amino-guanidine (selective iNOS inhibitor). RESULTS--Chronic treatment by L-NAME or aminoguanidine reduced antibody titres and the secretory response to antigen challenge. In contrast, only L-NAME administered before challenge was able to antagonise the hypersecretion induced by the challenge. CONCLUSIONS--NO generated by iNOS has a role in the sensitisation process: iNOS inhibition results in lower rates of antibodies leading to a reduced secretory response upon challenge. In contrast, blockade of colonic hypersecretion by L-NAME but not by aminoguanidine suggests that NO via cNOS is a key mediator in intestinal anaphylactic reactions. PMID:8707095

Fargeas, M J; Theodorou, V; Weirich, B; Fioramonti, J; Bueno, L

1996-01-01

41

A Connected Set of Genes Associated with Programmed Cell Death Implicated in Controlling the Hypersensitive Response in Maize  

PubMed Central

Rp1-D21 is a maize auto-active resistance gene conferring a spontaneous hypersensitive response (HR) of variable severity depending on genetic background. We report an association mapping strategy based on the Mutant Assisted Gene Identification and Characterization approach to identify naturally occurring allelic variants associated with phenotypic variation in HR. Each member of a collection of 231 diverse inbred lines of maize constituting a high-resolution association mapping panel were crossed to a parental stock heterozygous for Rp1-D21, and the segregating F1 generation testcrosses were evaluated for phenotypes associated with lesion severity for 2 years at two locations. A genome-wide scan for associations with HR was conducted with 47,445 SNPs using a linear mixed model that controlled for spurious associations due to population structure. Since the ability to identify candidate genes and the resolution of association mapping are highly influenced by linkage disequilibrium (LD), we examined the extent of genome-wide LD. On average, marker pairs separated by >10 kbp had an r2 value of <0.1. Genomic regions surrounding SNPs significantly associated with HR traits were locally saturated with additional SNP markers to establish local LD structure and precisely identify candidate genes. Six significantly associated SNPs at five loci were detected. At each locus, the associated SNP was located within or immediately adjacent to candidate causative genes predicted to play significant roles in the control of programmed cell death and especially in ubiquitin pathway-related processes. PMID:23222653

Olukolu, Bode A.; Negeri, Adisu; Dhawan, Rahul; Venkata, Bala P.; Sharma, Pankaj; Garg, Anshu; Gachomo, Emma; Marla, Sandeep; Chu, Kevin; Hasan, Anna; Ji, Jiabing; Chintamanani, Satya; Green, Jason; Shyu, Chi-Ren; Wisser, Randall; Holland, James; Johal, Guri; Balint-Kurti, Peter

2013-01-01

42

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

PubMed

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 (MØ) 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 MØ, whereas MIF inhibited MØ 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

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

2007-01-01

43

Bean dwarf mosaic virus BV1 protein is a determinant of the hypersensitive response and avirulence in Phaseolus vulgaris.  

PubMed

The capacities of the begomoviruses Bean dwarf mosaic virus (BDMV) and Bean golden yellow mosaic virus (BGYMV) to differeBean dwarf mosaic viru certain common bean (Phaseolus vulgaris) cultivars were used to identify viral determinants of the hypersensitive response (HR) and avirulence (avr) in BDMV. A series of hybrid DNA-B components, containing BDMV and BGYMV sequences, was constructed and coinoculated with BDMV DNA-A (BDMV-A) or BDMVA-green florescent protein into seedlings of cv. Topcrop (susceptible to BDMV and BGYMV) and the BDMV-resistant cvs. Othello and Black Turtle Soup T-39 (BTS). The BDMV avr determinant, in bean hypocotyl tissue, was mapped to the BDMV BV1 open reading frame and, most likely, to the BV1 protein. The BV1 also was identified as the determinant of the HR in Othello. However, the HR was not required for resistance in Othello nor was it associated with BDMV resistance in BTS. BDMV BV1, a nuclear shuttle protein that mediates viral DNA export from the nucleus, represents a new class of viral avr determinant. These results are discussed in terms of the relationship between the HR and resistance. PMID:11059485

Garrido-Ramirez, E R; Sudarshana, M R; Lucas, W J; Gilbertson, R L

2000-11-01

44

Genetics of resistance to the geminivirus, Bean dwarf mosaic virus, and the role of the hypersensitive response in common bean.  

PubMed

Bean dwarf mosaic virus (BDMV) is a single-stranded DNA virus (genus: Begomovirus, family: Geminiviridae) that infects common bean ( Phaseolus vulgaris L.) and causes stunted plant growth, and mosaic and mottle symptoms in leaves. BDMV shows differential pathogenicity in common bean, infecting germplasm of the Andean gene pool (e.g., the snap bean cultivar Topcrop), but not that of the Middle American gene pool (e.g., the pinto bean cultivar Othello). Resistance to BDMV in Othello is associated with development of a hypersensitive response (HR) in vascular (phloem) tissues. In this study, Middle American germplasm representing the four recognized races (i.e., Durango, Guatemala, Jalisco, and Mesoamerica) and the parents of Othello were inoculated with BDMV and a BDMV-green fluorescent protein (GFP) reporter. All genotypes showed partial or complete resistance to BDMV and BDMV-GFP, indicating the widespread distribution of resistance in the Middle American gene pool. A number of BDMV-resistant germplasm did not show the HR, indicating it is not correlated with resistance. In the F(1), F(2), and F(3) of reciprocal crosses between Othello and Topcrop, a single dominant allele, Bdm, conferred BDMV resistance. PMID:14625673

Seo, Y-S; Gepts, P; Gilbertson, R L

2004-03-01

45

Corneal Allografts Induce Cyrotoxic T Cell but nor Delayed Hypersensitivity Responses in Mice  

Microsoft Academic Search

alloantigens (footpad swelling assay) were negative (P> 0.05) in 83% of the animals tested. The absence of DTH responsiveness to corneal allografts was not a result of the small graft size or antigenic load. Either two or six circular skin allografts (3-mm diam) of BALB\\/c origin induced both strong CTL and DTH responses (P < 0.001) in C57BL\\/6 recipients, while

John Peeler; Jerry Niederkorn

1985-01-01

46

A genome-wide association study of the maize hypersensitive defense response identifies genes that cluster in related pathways.  

PubMed

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

Olukolu, Bode A; Wang, Guan-Feng; Vontimitta, Vijay; 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

2014-08-01

47

The Pseudomonas syringae pv. tomato HrpW Protein Has Domains Similar to Harpins and Pectate Lyases and Can Elicit the Plant Hypersensitive Response and Bind to Pectate  

Microsoft Academic Search

The host-specific plant pathogen Pseudomonas syringae elicits the hypersensitive response (HR) in nonhost plants and secretes the HrpZ harpin in culture via the Hrp (type III) secretion system. Previous genetic evidence suggested the existence of another harpin gene in the P. syringae genome. hrpW was found in a region adjacent to the hrp cluster in P. syringae pv. tomato DC3000.

AMY O. CHARKOWSKI; JAMES R. ALFANO; GAIL PRESTON; JING YUAN; SHENG YANG HE; ALAN COLLMER

48

Engagement of CD47 inhibits the contact hypersensitivity response via the suppression of motility and B7 expression by Langerhans cells.  

PubMed

CD47 is a membrane-associated glycoprotein that suppresses the function of immune cells. We previously reported that Langerhans cells (LCs) express Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1), a ligand for CD47, which plays an important role in the regulation of their motility. In this study, we show that LCs also express CD47, and that ligation of CD47 with SHPS-1-Fc fusion protein in vivo diminishes the development of the contact hypersensitivity response. We further demonstrate that CD47 engagement affects immune functions of LCs. CD47 engagement in vivo significantly inhibits the emigration of LCs from the epidermis into draining lymph nodes following treatment with haptens and tumor necrosis factor-alpha. The emigration of dendritic cells from skin explants into the medium and the chemotaxis of murine XS52 dendritic cells were significantly reduced by treatment with SHPS-1-Fc or an anti-CD47 mAb. Under explant culture system, SHPS-1-Fc treatment suppressed the expression of CD80 and CD86 of LCs. These effects on LCs and contact hypersensitivity response of CD47 ligation were reversed by treatment with pertussis toxin. These results suggest that the ligation of CD47 inhibits the migration of LCs and the expression of B7 costimulatory molecules, which results in inhibition of the contact hypersensitivity response. PMID:16456531

Yu, Xijun; Fukunaga, Atsushi; Nagai, Hiroshi; Oniki, Shuntaro; Honma, Nakayuki; Ichihashi, Masamitsu; Matozaki, Takashi; Nishigori, Chikako; Horikawa, Tatsuya

2006-04-01

49

Suppression of the hypersensitive response in potato by acetyl salicylic acid.  

PubMed

Increased salicylic acid has been correlated with systemic acquired resistance in several plants. Inoculation of potato plants with the pathogen Phytophthora Infestans or inducers from the fungus, arachidonic acid and eicosapentaenoic acid also induce systemic acquired resistance in the plant. We now report that treatment of potato tuber slices with acetyl salicylic acid markedly reduces the resistant response of these tissues. PMID:8670201

Lee, M; Currier, W W

1996-05-15

50

A Plant Caspase-Like Protease Activated during the Hypersensitive Response  

Microsoft Academic Search

To test the hypothesis that caspase-like proteases exist and are critically involved in the implementation of programmed cell death (PCD) in plants, a search was undertaken for plant caspases activated during the N gene-mediated hypersensi- tive response (HR; a form of pathogen-induced PCD in plants) in tobacco plants infected with Tobacco mosaic virus (TMV). For detection, characterization, and partial purification

Nina V. Chichkova; Sang Hyon Kim; Elena S. Titova; Markus Kalkum; Vasiliy S. Morozov; Yuri P. Rubtsov; Natalia O. Kalinina; Michael E. Taliansky; Andrey B. Vartapetian

2004-01-01

51

PS3, a semisynthetic beta-1,3-glucan sulfate, diminishes contact hypersensitivity responses through inhibition of L- and P-selectin functions.  

PubMed

Leukocyte extravasation is initiated by an interaction of selectin adhesion molecules and appropriate carbohydrate ligands. Targeting those interactions seems a promising approach to treat chronic inflammation. We developed a beta-1, 3-glucan sulfate (PS3) with inhibitory activity toward L and P-selectins under static conditions. Here, detailed investigation showed inhibition of P- and L-selectins, but not E-selectin under flow conditions (relative reduction of interaction with appropriate ligands to 34.4+/-16.6, 8.5+/-3.6, or 99.5+/-9.9%, respectively, by PS3 for P-, L- or E-selectin). Intravital microscopy revealed reduction of leukocyte rolling in skin microvasculature from 22.7+/-5.0 to 12.6+/-4.0% after injection of PS3. In the next experiments, mice were sensitized with 2,4,-dinitrofluorobenzene (DNFB), and lymphocytes were transferred into syngeneic recipients, which were challenged by DNFB. Inflammatory responses were reduced when immunity was generated in mice treated with PS3 or in L-selectin-deficient mice. No effect was observed when L-selectin-deficient donor mice were treated with PS3, further suggesting that PS3 acted primarily through inhibition of L-selectin. Elicitation of a contact hypersensitivity response was reduced in P-selectin-deficient and in PS3-treated mice. Again, PS3 had no effect in P-selectin-deficient mice. PS3 is a potent P- and L-selectin inhibitor that may add to the therapy of inflammatory diseases. PMID:19052560

Alban, Susanne; Ludwig, Ralf J; Bendas, Gerd; Schön, Michael P; Oostingh, Gertie J; Radeke, Heinfried H; Fritzsche, Juliane; Pfeilschifter, Josef; Kaufmann, Roland; Boehncke, Wolf-Henning

2009-05-01

52

Modulation of in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. I. Inhibition by RP-3 treatment of the priming and effector phases of delayed type hypersensitivity to sheep red blood cells in rats.  

PubMed

Recent studies on neutrophils have revealed that these cells produce various cytokines, and may be involved in regulation of the immune response. We examined whether neutrophils are involved in delayed type hypersensitivity (DTH) to SRBC in rats by selective depletion of in vivo neutrophils using a mAb designated RP-3. When the rats had been treated with RP-3 at the time of priming with SRBC, DTH to these cells was inhibited. Furthermore, RP-3 treatment was effective in inhibiting the effector phase of the DTH response to SRBC. When spleen cells from rats that had been treated with RP-3 at the time of immunization were used for local transfer of DTH, footpad swelling was significantly less than that induced by spleen cells from the RP-3-untreated immune rats. PMID:8473729

Kudo, C; Yamashita, T; Araki, A; Terashita, M; Watanabe, T; Atsumi, M; Tamura, M; Sendo, F

1993-05-01

53

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

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

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

2014-12-01

54

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

PubMed Central

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

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

2011-01-01

55

Stress responses to polycyclic aromatic hydrocarbons in Arabidopsis include growth inhibition and hypersensitive response-like symptoms  

Microsoft Academic Search

Polycyclic aromatic hydrocarbons (PAHs) are of global environmental concern because they cause many health problems including cancer and inflammation of tissue in humans. Plants are important in removing PAHs from the atmosphere; yet, information on the physiology, cell and molecular biology, and biochemis- try of PAH stress responses in plants is lacking. The PAH stress response was studied in Arabidopsis

Merianne Alkio; Tomoko M. Tabuchi; Xuchen Wang; Adan Colon-Carmona

2010-01-01

56

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

PubMed Central

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

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

2012-01-01

57

Genomic analysis of severe hypersensitivity to hygromycin B reveals linkage to vacuolar defects and new vacuolar gene functions in Saccharomyces cerevisiae  

Microsoft Academic Search

The vacuole of Saccharomyces cerevisiae has been a seminal model for studies of lysosomal trafficking, biogenesis, and function. Several yeast mutants defective\\u000a in such vacuolar events have been unable to grow at low levels of hygromycin B, an aminoglycoside antibiotic. We hypothesized\\u000a that such severe hypersensitivity to hygromycin B (hhy) is linked to vacuolar defects and performed a genomic screen

M. G. Banuelos; D. E. Moreno; D. K. Olson; Q. Nguyen; F. Ricarte; C. R. Aguilera-Sandoval; Editte Gharakhanian

2010-01-01

58

The Pseudomonas syringae pv. syringae 61 hrpH product, an envelope protein required for elicitation of the hypersensitive response in plants.  

PubMed Central

Pseudomonas syringae pv. syringae 61 contains a 25-kb cluster of hrp genes that are required for elicitation of the hypersensitive response (HR) in tobacco. TnphoA mutagenesis of cosmid pHIR11, which contains the hrp cluster, revealed two genes encoding exported or inner-membrane-spanning proteins (H.-C. Huang, S. W. Hutcheson, and A. Collmer, Mol. Plant-Microbe Interact. 4:469-476, 1991). The gene in complementation group X, designated hrpH, was subcloned on a 3.1-kb SalI fragment into pCPP30, a broad-host-range, mobilizable vector. The subclone restored the ability of hrpH mutant P. syringae pv. syringae 61-2089 to elicit the HR in tobacco. DNA sequence analysis of the 3.1-kb SalI fragment revealed a single open reading frame encoding an 81,956-Da preprotein with a typical amino-terminal signal peptide and no likely inner-membrane-spanning hydrophobic regions. hrpH was expressed in the presence of [35S]methionine by using the T7 RNA polymerase-promoter system and vector pT7-3 in Escherichia coli and was shown to encode a protein with an apparent molecular weight of 83,000 on sodium dodecyl sulfate-polyacrylamide gels. The HrpH protein in E. coli was located in the membrane fraction and was absent from the periplasm and cytoplasm. The HrpH protein possessed similarity with several outer membrane proteins that are known to be involved in protein or phage secretion, including the Klebsiella oxytoca PulD protein, the Yersinia enterocolitica YscC protein, and the pIV protein of filamentous coliphages. All of these proteins possess a possible secretion motif, GG(X)12VP(L/F)LXXIPXIGXL(F/L), near the carboxyl terminus, and they lack a carboxyl-terminal phenylalanine, in contrast to other outer membrane proteins with no known secretion function. These results suggest that the P. syringae pv. syringae HrpH protein is involved in the secretion of a proteinaceous HR elicitor. Images PMID:1400238

Huang, H C; He, S Y; Bauer, D W; Collmer, A

1992-01-01

59

Arachidonic acid-related elicitors of the hypersensitive response in potato and enhancement of their activities by glucans from Phytophthora infestans (Mont.) deBary.  

PubMed

The dose response for elicitation of the hypersensitive reaction in potato tuber discs by arachidonic acid (AA) suggested saturation at higher concentrations. Glucans from Phytophthora infestans, inactive themselves as elicitors of the hypersensitive reaction, enhanced sesquiterpene accumulation and hypersensitive browning elicited by AA. Significant activity (seven times control values) was observed with 33 pmol AA/3.0-cm potato disc in the presence of glucans. Glucans did not affect accumulation of steroid glycoalkaloids, influence the timing or relative amounts of sesquiterpenes which accumulate, or affect recovery of AA added to potato discs. Glucans enhanced activity whether added to potato discs 18 h prior to AA, at the same time as AA, or 18 h after AA. Elicitor activity in the presence of glucans was evident with 20-carbon unsaturated fatty acids that had little or no elicitor activity in the absence of glucans. The position of double bonds had considerable influence on the specific activity of unsaturated fatty acids. The most active had a minimum of three double bonds in a methylene-interrupted series beginning with delta 5, e.g., delta 5,8,11. A delta 5 double bond conferred significant activity even if it was not part of a methylene-interrupted series. The 20-carbon chain length appeared optimal for elicitor activity. The 22-carbon chain acids had low activity, and 16- and 18-carbon acids were inactive. A free carboxyl group or easily transesterified group appeared necessary for activity. Arachidonyl alcohol had very low activity and arachidonyl cyanide was inactive. AA-containing phosphatidylcholine, lysophosphatidylcholine and monoacylglycerol were at least as active as free AA, AA-containing diacylglycerols were slightly less active than free AA, and triarachidonyl glycerol was inactive. PMID:3966802

Preisig, C L; Ku?, J A

1985-01-01

60

Immunological Principles of Drug Hypersensitivity  

Microsoft Academic Search

Drug Hypersensitivity Reactions account for about one of six of all adverse drug reactions. T lymphocytes were shown to play\\u000a a central role in mediating drug allergy and are involved in all types of immune response to the drugs. Upon antigen-specific\\u000a stimulation T cells secrete various cytokines and can orchestrate different effector mechanisms of immune response including\\u000a immediate, IgE mediated

Anna Zawodniak; Werner J. Pichler

61

Hydroxyurea Induces a Hypersensitive Apoptotic Response in Mouse Embryonic Stem Cells Through p38-Dependent Acetylation of p53.  

PubMed

While hydroxyurea (HU) is well known to deplete dNTP pools and lead to replication fork arrest in the cell, the mechanisms by which it exerts a cell response are poorly understood. Here, our results suggest that mouse embryonic stem cells (mESCs), unlike terminally differentiated cells such as mouse embryonic fibroblasts (MEFs), rapidly respond to low concentrations of HU by p53 acetylation, leading to activation of the caspase-dependent apoptotic pathway. We show that HU treatment induces the production of nitric oxide (NO), which plays a central role in the rapid induction of apoptosis in mESCs. By contrast, reactive oxygen species, which are expressed at significantly higher levels in mESCs compared with MEFs, are not related to the HU response. Furthermore, on exposure to HU, the p38 signaling pathway becomes activated in a dose-dependent manner, and chemical inhibition of the p38 pathway attenuates HU-dependent apoptosis in mESCs. Our data reveal that acetylation of p53 as a result of HU-dependent NO production plays a key role in the induction of the apoptotic response in mESCs. Finally, p38 signaling appears to be the main pathway underlying the activation of apoptosis in mESCs in response to HU exposure. PMID:24836177

Heo, Sun-Hee; Cha, Young; Park, Kyung-Soon

2014-10-15

62

Cloning and expression pattern of a novel microspore-specific gene encoding hypersensitive-induced response protein (LjHIR1) from the model legume, Lotus japonicus.  

PubMed

In order to understand the microspore and pollen development, recently, we have isolated a number of anther-specific genes in the model legume, Lotus japonicus. From these anther-specific genes, we identified one novel microspore-specific gene, LjImfb-c82. In order to determine the molecular characterization of LjImfb-c82, full-length cDNA clone was first isolated and sequenced. It encoded a protein of 286 amino acids (LjHIR1), which had sequence similarity to Hypersensitive-Induced Response like protein. LjHIR1 was specifically expressed in microspore on the in situ hybridization experiment. From the sequence similarity to prohibitin-domain protein, the LjHIR1 might be related to ion channel regulation in microspore development. PMID:15599061

Hakozaki, Hirokazu; Endo, Makoto; Masuko, Hiromi; Park, Jong-In; Ito, Hitoshi; Uchida, Masanori; Kamada, Motoshi; Takahashi, Hideyuki; Higashitani, Atsushi; Watanabe, Masao

2004-10-01

63

Wheat hypersensitive-induced reaction genes TaHIR1 and TaHIR3 are involved in response to stripe rust fungus infection and abiotic stresses.  

PubMed

KEY MESSAGE : TaHIR1 and TaHIR3 play positive roles in resistance to the stripe rust fungus via inducing HR and regulating defense-related genes, but are negatively regulated by various abiotic stimuli. Plant hypersensitive-induced reaction (HIR) genes are known to be associated with the hypersensitive response and disease defense. In wheat, two HIR genes, TaHIR1 and TaHIR3, have been identified and found to be up-regulated after infection with the stripe rust fungus. Here, we further determined their roles in defense against abiotic stresses and the stripe rust pathogen, Puccinia striiformis f. sp. tritici. TaHIR1 and TaHIR3 proteins were localized in the plasma membrane of tobacco cells. The expression of TaHIR1 and TaHIR3 was reduced by the environmental stimuli, including low temperature, drought, and high salinity stresses. In addition, the expression of TaHIR1 and TaHIR3 was down-regulated by exogenously applied ethrel and abscisic acid, whereas expression was not affected by treatments with salicylic acid and methyl jasmonate. Furthermore, barley stripe mosaic virus-induced gene silencing of TaHIR1 and TaHIR3 reduced resistance in wheat cultivar Suwon11 against an avirulent stripe rust pathotype CYR23 and area of necrotic cells neighboring the infection sites, and altered the expression levels of defense-related genes. These results suggest that TaHIR1 and TaHIR3 function positively in the incompatible interaction of wheat-stripe rust fungus, but exhibit negative transcriptional response to abiotic stresses. PMID:23111787

Duan, Yinghui; Guo, Jun; Shi, Xuexia; Guan, Xiangnan; Liu, Furong; Bai, Pengfei; Huang, Lili; Kang, Zhensheng

2013-02-01

64

Role of the penetration-resistance genes PEN1, PEN2 and PEN3 in the hypersensitive response and race-specific resistance in Arabidopsis thaliana.  

PubMed

Plants are highly capable of recognizing and defending themselves against invading microbes. Adapted plant pathogens secrete effector molecules to suppress the host's immune system. These molecules may be recognized by host-encoded resistance proteins, which then trigger defense in the form of the hypersensitive response (HR) leading to programmed cell death of the host tissue at the infection site. The three proteins PEN1, PEN2 and PEN3 have been found to act as central components in cell wall-based defense against the non-adapted powdery mildew Blumeria graminis fsp. hordei (Bgh). We found that loss of function mutations in any of the three PEN genes cause decreased hypersensitive cell death triggered by recognition of effectors from oomycete and bacterial pathogens in Arabidopsis. There were considerable additive effects of the mutations. The HR induced by recognition of AvrRpm1 was almost completely abolished in the pen2 pen3 and pen1 pen3 double mutants and the loss of cell death could be linked to indole glucosinolate breakdown products. However, the loss of the HR in pen double mutants did not affect the plants' ability to restrict bacterial growth, whereas resistance to avirulent isolates of the oomycete Hyaloperonospora arabidopsidis was strongly compromised. In contrast, the double and triple mutants demonstrated varying degrees of run-away cell death in response to Bgh. Taken together, our results indicate that the three genes PEN1, PEN2 and PEN3 extend in functionality beyond their previously recognized functions in cell wall-based defense against non-host pathogens. PMID:24889055

Johansson, Oskar N; Fantozzi, Elena; Fahlberg, Per; Nilsson, Anders K; Buhot, Nathalie; Tör, Mahmut; Andersson, Mats X

2014-08-01

65

Chronic cough hypersensitivity syndrome  

PubMed Central

Chronic cough has been suggested to be due to three conditions, asthma, post nasal drip, and reflux disease. A different paradigm has evolved in which cough is viewed as the primary condition characterised by afferent neuronal hypersensitivity and different aspects of this syndrome are manifest in the different phenotypes of cough. There are several advantages to viewing cough hypersensitivity as the unifying diagnosis; Communication with patients is aided, aetiology is not restricted and therapeutic avenues opened. Cough Hypersensitivity Syndrome is a more applicable label to embrace the clinical manifestations of this disabling disease. PMID:23668427

2013-01-01

66

Immunomodulation of delayed-type hypersensitivity responses by mesenchymal stem cells is associated with bystander T cell apoptosis in the draining lymph node.  

PubMed

Disease amelioration by mesenchymal stem cells (MSCs) has been shown to be closely related to their immunomodulatory functions on the host immune system in many disease models. However, the underlying mechanisms of how these cells affect the immune cells in vivo are not fully understood. In this study, we report findings that a small but significant number of MSCs accumulate in the secondary lymphoid organs and attenuate delayed-type hypersensitivity (DTH) response by inducing apoptotic cell death of surrounding immune cells in the draining lymph node (LN). In the migration study, i.v. infused GFP-MSCs preferentially accumulated at the boundary between the paracortical area and the germinal center in the LNs, in close proximity to various types of immune cells including T, B, and dendritic cells in a dose-dependent manner. As a result, accumulated MSCs markedly attenuated DTH response in proportion to the number of MSCs infused. During the DTH response, the infiltration of T cells in the challenged site was significantly decreased, whereas a number of apoptotic T cells were remarkably increased in the draining LN. Apoptosis was significantly induced in activated T cells (CD3(+) and BrdU(+)), but not in the resting T cells (CD3(+) and BrdU(-)). NO was associated with these apoptotic events. Taken together, we conclude that significant numbers of i.v. infused MSCs preferentially localize in the draining LN, where they induce apoptosis of the activated T cells by producing NO and thus attenuate the DTH response. PMID:20802154

Lim, Jong-Hyung; Kim, Jung-Sik; Yoon, Il-Hee; Shin, Jun-Seop; Nam, Hye-Young; Yang, Seung-Ha; Kim, Sang-Joon; Park, Chung-Gyu

2010-10-01

67

Oral Hypersensitivity Reactions  

MedlinePLUS

... a hypersensitivity reaction in the mouth? A: A large number of substances. The most common causes are food, ... What is the “Latex-Fruit Syndrome”? A: A large number of individuals who are allergic to latex products ...

68

DNaseI Hypersensitivity and Ultraconservation Reveal Novel, Interdependent Long-Range Enhancers at the Complex Pax6 Cis-Regulatory Region  

PubMed Central

The PAX6 gene plays a crucial role in development of the eye, brain, olfactory system and endocrine pancreas. Consistent with its pleiotropic role the gene exhibits a complex developmental expression pattern which is subject to strict spatial, temporal and quantitative regulation. Control of expression depends on a large array of cis-elements residing in an extended genomic domain around the coding region of the gene. The minimal essential region required for proper regulation of this complex locus has been defined through analysis of human aniridia-associated breakpoints and YAC transgenic rescue studies of the mouse smalleye mutant. We have carried out a systematic DNase I hypersensitive site (HS) analysis across 200 kb of this critical region of mouse chromosome 2E3 to identify putative regulatory elements. Mapping the identified HSs onto a percent identity plot (PIP) shows many HSs correspond to recognisable genomic features such as evolutionarily conserved sequences, CpG islands and retrotransposon derived repeats. We then focussed on a region previously shown to contain essential long range cis-regulatory information, the Pax6 downstream regulatory region (DRR), allowing comparison of mouse HS data with previous human HS data for this region. Reporter transgenic mice for two of the HS sites, HS5 and HS6, show that they function as tissue specific regulatory elements. In addition we have characterised enhancer activity of an ultra-conserved cis-regulatory region located near Pax6, termed E60. All three cis-elements exhibit multiple spatio-temporal activities in the embryo that overlap between themselves and other elements in the locus. Using a deletion set of YAC reporter transgenic mice we demonstrate functional interdependence of the elements. Finally, we use the HS6 enhancer as a marker for the migration of precerebellar neuro-epithelium cells to the hindbrain precerebellar nuclei along the posterior and anterior extramural streams allowing visualisation of migratory defects in both pathways in Pax6Sey/Sey mice. PMID:22220192

McBride, David J.; Buckle, Adam; van Heyningen, Veronica; Kleinjan, Dirk A.

2011-01-01

69

TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHAEL (IT) EXPOSURES  

EPA Science Inventory

ABSTRACT for 2001 DMS213 TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHEAL (IT) EXPOSURES. E Boykin, M Ward, MJ Selgrade, and D Sailstad. NHEERL, ORD, US EPA, RTP, NC, USA. TMA causes respiratory hypersensitivity (RH) responses. W...

70

Localized Changes in Peroxidase Activity Accompany Hydrogen Peroxide Generation during the Development of a Nonhost Hypersensitive Reaction in Lettuce  

Microsoft Academic Search

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. )p vphase- olicola and in response to an hrp mutant of the bacterium. Assays of activity in tissue extracts revealed pH optima of

Charles S. Bestwick; Ian R. Brown; John W. Mansfield

1998-01-01

71

Maternal and postnatal dietary probiotic supplementation enhances splenic regulatory T helper cell population and reduces ovalbumin allergen-induced hypersensitivity responses in mice.  

PubMed

Neonatal to early childhood is the critical period for establishing a balance of T helper 1 (Th1) versus T helper 2 (Th2) cellular immunity within the gut, which is strongly influenced by the source and establishment of gut microflora. Probiotic administration has been shown to attenuate Th2-biased cellular immunity and predisposition to food allergies. To test this hypothesis we provided ad libitum a probiotic-supplemented (Primalac 454 Feed Grade Microbials) or control diet to lactating dams with suckling pups and weaned pups until 10 weeks of age. Weaned mice were sensitized/challenged with egg allergen ovalbumin, saline or adjuvant at 6, 8 and 10 weeks of age. At 3, 6, 8 and 10 weeks, fecal samples were collected for microbial analysis, while blood samples were analyzed for ovalbumin-IgE and total plasma IgE levels. At termination, splenic T helper cell lymphocyte population subtypes were determined using FACS analysis and Th1/Th2/Th17 gene expression by PCR array. At 21 days of age, pups suckled by lactating dams fed the probiotic supplemented diet had significantly enhanced Lactobacillus acidophilus fecal counts compared to controls. Moreover, mice fed the probiotic supplemented diet had enhanced splenic naturally occurring and induced regulatory T cell populations, enhanced TGF? gene expression and reduced expression of allergic mediator IL13 compared to controls. These results provide evidence that early probiotic supplementation may provide host protection from hypersensitivity reactions to food allergens by attenuating food allergen inflammatory responses. PMID:24612822

Toomer, Ondulla T; Ferguson, Martine; Pereira, Marion; Do, Andrew; Bigley, Elmer; Gaines, Dennis; Williams, Kristina

2014-05-01

72

Hypersensitivity pneumonitis from ordinary residential exposures.  

PubMed Central

A previously healthy woman developed hypersensitivity pneumonitis of such severity that she required chronic systemic corticosteroid therapy for symptom control. Detailed investigation of her workplace and home environments revealed fungi in her typical suburban home, to which she had specific serum precipitating antibodies. Efforts to remove mold from the home were unsuccessful in relieving symptoms, and moving to another residence was the only intervention that allowed her to be withdrawn from corticosteroid therapy. Hypersensitivity pneumonitis is commonly associated with occupational or avocational exposures, such as moldy hay in farmers or bird antigen in bird breeders. We propose that hypersensitivity pneumonitis may occur in North America, as it does in Japan, from domestic exposures alone. PMID:11673130

Apostolakos, M J; Rossmoore, H; Beckett, W S

2001-01-01

73

Lichenoid tattoo hypersensitivity  

Microsoft Academic Search

Four patients are described who developed granulomatous reactions in the red portions of their tattoos. Histopathological and immunofluorescence studies showed features of lichen planus. Mercury was identified in only one patient's lesion, and hypersensitivity to mercury was shown by patch testing in one other patient. Tattooing may provide a localised antigenic challenge resulting in spontaneously occurring lichen planus.

A Taaffe; A G Knight; R Marks

1978-01-01

74

Isolation of Listeria monocytogenes antigens responsible for the induction of delayed hypersensitivity and MIF production in Balb/c mice  

E-print Network

facultative intracellular organisms necessitated a procedure for identifying lymphocyte subsets. The location of the theta isoantigen on thymus-derived lymphocytes proved to be an excellent indicator of T lymphocyte cell populations (149). Using antisera... determinant (45, 172, 199, 202). The idea of MHC restriction of immune responses was first suggested involving T cell/B cell cooperation. Through the early studies of Kindred and Shreffler (87), it was demonstrated that thymus cell transfers into nude mice...

Ruff, Rose Longoria

2012-06-07

75

Cognitive and physiological responses in humans exposed to a TETRA base station signal in relation to perceived electromagnetic hypersensitivity.  

PubMed

Terrestrial Trunked Radio (TETRA) technology ("Airwave") has led to public concern because of its potential interference with electrical activity in the brain. The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses. Participants were exposed to a 420?MHz TETRA signal at a power flux density of 10?mW/m(2) as well as sham (no signal) under double-blind conditions. Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study. Forty-eight sensitive and 132 control participants completed all three sessions. Measures of short-term memory, working memory, and attention were administered while physiological responses (blood volume pulse, heart rate, skin conductance) were monitored. After applying exclusion criteria based on task performance for each aforementioned cognitive measure, data were analyzed for 36, 43, and 48 sensitive participants for these respective tasks and, likewise, 107,125, and 129 controls. We observed no differences in cognitive performance between sham and TETRA exposure in either group; physiological response also did not differ between the exposure conditions. These findings are similar to previous double-blind studies with other mobile phone signals (900-2100?MHz), which could not establish any clear evidence that mobile phone signals affect health or cognitive function. PMID:21647932

Wallace, Denise; Eltiti, Stacy; Ridgewell, Anna; Garner, Kelly; Russo, Riccardo; Sepulveda, Francisco; Walker, Stuart; Quinlan, Terence; Dudley, Sandra; Maung, Sithu; Deeble, Roger; Fox, Elaine

2012-01-01

76

Two phenotypically distinct T cells are involved in ultraviolet-irradiated urocanic acid-induced suppression of the efferent delayed-type hypersensitivity response to herpes simplex virus, type 1 in vivo  

SciTech Connect

When UVB-irradiated urocanic acid, the putative photoreceptor/mediator for UVB suppression, is administered to mice it induces a dose-dependent suppression of the delayed-type hypersensitivity response to herpes simplex virus, type 1 (HSV-1), of similar magnitude to that induced by UV irradiation of mice. In this study, the efferent suppression of delayed-type hypersensitivity by UV-irradiated urocanic acid is demonstrated to be due to 2 phenotypically distinct T cells, (Thy1+, L3T4-, Ly2+) and (Thy1+, L3T4+, Ly2-). The suppression is specific for HSV-1. This situation parallels the generation of 2 distinct T-suppressor cells for HSV-1 by UV irradiation of mice and provides further evidence for the involvement of urocanic acid in the generation of UVB suppression.

Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.

1987-09-01

77

A ChIP–chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response  

PubMed Central

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP–chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response. PMID:19129219

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-01-01

78

Affinity of Avr2 for tomato cysteine protease Rcr3 correlates with the Avr2-triggered Cf-2-mediated hypersensitive response.  

PubMed

The Cladosporium fulvum Avr2 effector is a novel type of cysteine protease inhibitor with eight cysteine residues that are all involved in disulphide bonds. We have produced wild-type Avr2 protein in Pichia pastoris and determined its disulphide bond pattern. By site-directed mutagenesis of all eight cysteine residues, we show that three of the four disulphide bonds are required for Avr2 stability. The six C-terminal amino acid residues of Avr2 contain one disulphide bond that is not embedded in its overall structure. Avr2 is not processed by the tomato cysteine protease Rcr3 and is an uncompetitive inhibitor of Rcr3. We also produced mutant Avr2 proteins in which selected amino acid residues were individually replaced by alanine, and, in one mutant, all six C-terminal amino acid residues were deleted. We determined the inhibitory constant (K(i) ) of these mutants for Rcr3 and their ability to trigger a Cf-2-mediated hypersensitive response (HR) in tomato. We found that the two C-terminal cysteine residues and the six amino acid C-terminal tail of Avr2 are required for both Rcr3 inhibitory activity and the ability to trigger a Cf-2-mediated HR. Individual replacement of the lysine-17, lysine-20 or tyrosine-21 residue by alanine did not affect significantly the biological activity of Avr2. Overall, our data suggest that the affinity of the Avr2 mutants for Rcr3 correlates with their ability to trigger a Cf-2-mediated HR. PMID:21118346

Van't Klooster, John W; Van der Kamp, Marc W; Vervoort, Jacques; Beekwilder, Jules; Boeren, Sjef; Joosten, Matthieu H A J; Thomma, Bart P H J; De Wit, Pierre J G M

2011-01-01

79

Hypersensitivity to Suture Anchors  

PubMed Central

Hypersensitivity to suture anchor is extremely rare. Herein, we present a case in which hypersensitivity to suture anchor was strongly suspected. The right rotator cuff of a 50-year-old woman was repaired with a metal suture anchor. Three weeks after the surgery, she developed erythema around her face, trunk, and hands, accompanied by itching. Infection was unlikely because no abnormalities were detected by blood testing or by medical examination. Suspicious of a metallic allergy, a dermatologist performed a patch testing 6 months after the first surgery. The patient had negative reactions to tests for titanium, aluminum, and vanadium, which were the principal components of the suture anchor. The anchor was removed 7 months after the first surgery, and the erythema disappeared immediately. When allergic symptoms occur and persist after the use of a metal anchor, removal should be considered as a treatment option even if the patch test result is negative. PMID:23956902

Goto, Masafumi; Gotoh, Masafumi; Mitsui, Yasuhiro; Tanesue, Ryo; Okawa, Takahiro; Higuchi, Fujio; Shiba, Naoto

2013-01-01

80

Responses of C-fiber low threshold mechanoreceptors and nociceptors to cold were facilitated in rats persistently inflamed and hypersensitive to cold  

Microsoft Academic Search

Cold allodynia is an annoying symptom in conditions of chronic inflammation such as rheumatoid arthritis. To examine whether primary afferent nerve activities are changed in association with hypersensitivity to cold, we recorded single nerve activities from the sural nerve in persistently inflamed rats in vivo. Inflammation was induced by an injection of complete Freund’s adjuvant (CFA) solution into the tibio-tarsal

Ken Takahashi; Jun Sato; Kazue Mizumura

2003-01-01

81

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

PubMed Central

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

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

2014-01-01

82

Monkey Steering Responses Reveal Rapid Visual-Motor Feedback  

PubMed Central

The neural mechanisms underlying primate locomotion are largely unknown. While behavioral and theoretical work has provided a number of ideas of how navigation is controlled, progress will require direct physiolgical tests of the underlying mechanisms. In turn, this will require development of appropriate animal models. We trained three monkeys to track a moving visual target in a simple virtual environment, using a joystick to control their direction. The monkeys learned to quickly and accurately turn to the target, and their steering behavior was quite stereotyped and reliable. Monkeys typically responded to abrupt steps of target direction with a biphasic steering movement, exhibiting modest but transient overshoot. Response latencies averaged approximately 300 ms, and monkeys were typically back on target after about 1 s. We also exploited the variability of responses about the mean to explore the time-course of correlation between target direction and steering response. This analysis revealed a broad peak of correlation spanning approximately 400 ms in the recent past, during which steering errors provoke a compensatory response. This suggests a continuous, visual-motor loop controls steering behavior, even during the epoch surrounding transient inputs. Many results from the human literature also suggest that steering is controlled by such a closed loop. The similarity of our results to those in humans suggests the monkey is a very good animal model for human visually guided steering. PMID:20694144

Egger, Seth W.; Engelhardt, Heidi R.; Britten, Kenneth H.

2010-01-01

83

Immediate-type hypersensitivity drug reactions.  

PubMed

Hypersensitivity reactions including anaphylaxis have been reported for nearly all classes of therapeutic reagents and these reactions can occur within minutes to hours of exposure. These reactions are unpredictable, not directly related to dose or the pharmacological action of the drug and have a relatively high mortality risk. This review will focus on the clinical presentation, immune mechanisms, diagnosis and prevention of the most serious form of immediate onset drug hypersensitivity reaction, anaphylaxis. The incidence of drug-induced anaphylaxis deaths appears to be increasing and our understanding of the multiple and complex reasons for the unpredictable nature of anaphylaxis to drugs is also expanding. This review highlights the importance of enhancing our understanding of the biology of the patient (i.e. immune response, genetics) as well as the pharmacology and chemistry of the drug when investigating, diagnosing and treating drug hypersensitivity. Misdiagnosis of drug hypersensitivity leads to substantial patient risk and cost. Although oral provocation is often considered the gold standard of diagnosis, it can pose a potential risk to the patient. There is an urgent need to improve and standardize diagnostic testing and desensitization protocols as other diagnostic tests currently available for assessment of immediate drug allergy are not highly predictive. PMID:24286446

Stone, Shelley F; Phillips, Elizabeth J; Wiese, Michael D; Heddle, Robert J; Brown, Simon G A

2014-07-01

84

Phenological sequences reveal aggregate life history response to climatic warming.  

PubMed

Climatic warming is associated with organisms breeding earlier in the season than is typical for their species. In some species, however, response to warming is more complex than a simple advance in the timing of all life history events preceding reproduction. Disparities in the extent to which different components of the reproductive phenology of organisms vary with climatic warming indicate that not all life history events are equally responsive to environmental variation. Here, we propose that our understanding of phenological response to climate change can be improved by considering entire sequences of events comprising the aggregate life histories of organisms preceding reproduction. We present results of a two-year warming experiment conducted on 33 individuals of three plant species inhabiting a low-arctic site. Analysis of phenological sequences of three key events for each species revealed how the aggregate life histories preceding reproduction responded to warming, and which individual events exerted the greatest influence on aggregate life history variation. For alpine chickweed (Cerastium alpinum), warming elicited a shortening of the duration of the emergence stage by 2.5 days on average, but the aggregate life history did not differ between warmed and ambient plots. For gray willow (Salix glauca), however, all phenological events monitored occurred earlier on warmed than on ambient plots, and warming reduced the aggregate life history of this species by 22 days on average. Similarly, in dwarf birch (Betula nana), warming advanced flower bud set, blooming, and fruit set and reduced the aggregate life history by 27 days on average. Our approach provides important insight into life history responses of many organisms to climate change and other forms of environmental variation. Such insight may be compromised by considering changes in individual phenological events in isolation. PMID:18409426

Post, Eric S; Pedersen, Christian; Wilmers, Christopher C; Forchhammer, Mads C

2008-02-01

85

Metabolic phenotyping reveals a lipid mediator response to ionizing radiation.  

PubMed

Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to ? radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to ? radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine. PMID:25126707

Laiakis, Evagelia C; Strassburg, Katrin; Bogumil, Ralf; Lai, Steven; Vreeken, Rob J; Hankemeier, Thomas; Langridge, James; Plumb, Robert S; Fornace, Albert J; Astarita, Giuseppe

2014-09-01

86

Expression of the Pseudomonas syringae Avirulence Pmtein AvrB in Plant Cells Alleviates Its Dependence on the Hypersensitive Response and Pathogenicity (Hrp) Secretion System in Eliciting Genotype-Specif ic Hypersensitive Cell Death  

Microsoft Academic Search

The nonpathogenic bacteria Pseudomonas fluorescens and Escherichia coli can elicit a genotype-specific hypersensi- tive response (HR) in plants if they express both the HR and pathogenesis (Hrp) protein secretion system and the HrpZ harpin from I? syringae pv syringae 61 and a c! syringae avirulence (avr) gene whose presence is recognized by a corre- sponding disease resistance gene in the

Suresh Gopalan; David W. Bauer; James R. Alfano; Amy O. Loniello; Sheng Yang; Alan Collmerbi

1996-01-01

87

The cough hypersensitivity syndrome: a novel paradigm for understanding cough.  

PubMed

For many years patients with chronic cough have been investigated in an attempt to diagnose the cause of the cough. Here I suggest that the overwhelming majority of patients with chronic cough have a single diagnosis: cough hypersensitivity syndrome. This is demonstrated by the homogeneous nature of the clinical history and investigational results of patients attending cough clinics. The hypersensitivity facet of the syndrome is demonstrated by objective testing with capsaicin and other protussive agents. Within the cough hypersensitivity syndrome there are different phenotypes. Those patients with a predominantly Th2-type immune response will develop eosinophilic inflammation and either cough-variant asthma or eosinophilic bronchitis. Those with predominantly heartburn symptoms will have a phenotype that reflects GERD and cough. However, the similarities between the different phenotypes far outweigh differences in a unifying diagnosis of the cough hypersensitivity syndrome, providing a more rational understanding of chronic cough. PMID:19809853

Morice, Alyn H

2010-01-01

88

Bacterial evolution of antibiotic hypersensitivity  

PubMed Central

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

Lazar, Viktoria; Pal Singh, Gajinder; Spohn, Reka; Nagy, Istvan; Horvath, Balazs; Hrtyan, Monika; Busa-Fekete, Robert; Bogos, Balazs; Mehi, Orsolya; Csorgo, Balint; Posfai, Gyorgy; Fekete, Gergely; Szappanos, Balazs; Kegl, Balazs; Papp, Balazs; Pal, Csaba

2013-01-01

89

Tomato Transcriptional Changes in Response to Clavibacter michiganensis subsp. michiganensis Reveal  

E-print Network

Tomato Transcriptional Changes in Response to Clavibacter michiganensis subsp. michiganensis Reveal, causing bacterial wilt and canker disease in tomato (Solanum lycopersicum). Host responses to gram in tomato are largely unexplored. To investigate plant responses activated during this compatible

Sessa, Guido

90

A chemical screen for suppressors of the avrRpm1-RPM1-dependent hypersensitive cell death response in Arabidopsis thaliana.  

PubMed

Arabidopsis thaliana RPM1 encodes an intracellular immune sensor that conditions disease resistance to Pseudomonas syringae expressing the type III effector protein AvrRpm1. Conditional expression of this type III effector in a transgenic line carrying avrRpm1 under the control of a steroid-inducible promoter results in RPM1-dependent cell death that resembles the cell death response of the incompatible RPM1-avrRpm1 plant-bacterium interaction. This line was previously used in a genetic screen, which revealed two genes that likely function in the folding of pre-activation RPM1. We established a chemical screen for small molecules that suppress steroid-inducible and RPM1-avrRpm1-dependent cell death in Arabidopsis seedlings. Screening of a library comprising 6,800 compounds of natural origin identified two trichothecene-type mycotoxins, 4,15-diacetoxyscirpenol (DAS) and neosolaniol (NEO), which are synthesized by Fusarium and other fungal species. However, protein blot analysis revealed that DAS and NEO inhibit AvrRpm1 synthesis rather than suppress RPM1-mediated responses. This inhibition of translational activity likely explains the survival of the seedlings under screening conditions. Likewise, flg22-induced defense responses are also impaired at the translational, but not the transcriptional, level by DAS or NEO. Unexpectedly, both compounds not only prevented AvrRpm1 synthesis, but rather caused an apparent hyper-accumulation of RPM1 and HSP70. The hyper-accumulation phenotype is likely unrelated to the ribotoxic function of DAS and NEO and could be due to an inhibitory activity on the proteolytic machinery of Arabidopsis or elicitor-like activities of type A trichothecenes. PMID:20140739

Serrano, Mario; Hubert, David A; Dangl, Jeffery L; Schulze-Lefert, Paul; Kombrink, Erich

2010-04-01

91

The effect of decomplementation on delayed-type hypersensitive reactions to a conjugated antigen in rats  

PubMed Central

A method has been described for quantitative measurement of the intensity of cutaneous delayed hypersensitive reactions in rats. This method is based on the measurement of the weight of skin infiltration at the site of cutaneous reaction. In vivo decomplementation of rats with antigen—antibody complexes or aggregated ?-globulin is accompanied by a decrease in delayed hypersensitivity responsiveness. When the level of serum complement is reduced by 90 per cent delayed hypersensitive reactions are completely suppressed. The results presented, although suggestive, do not provide a definite proof of the role of complement in the development of delayed hypersensitive reactions in the skin. PMID:4158582

Neveu, Thérèse; Biozzi, G.

1965-01-01

92

PHENOLOGICAL SEQUENCES REVEAL AGGREGATE LIFE HISTORY RESPONSE TO CLIMATIC WARMING  

Microsoft Academic Search

Climatic warming is associated with organisms breeding earlier in the season than is typical for their species. In some species, however, response to warming is more complex than a simple advance in the timing of all life history events preceding reproduction. Disparities in the extent to which different components of the reproductive phenology of organisms vary with climatic warming indicate

Eric S. Post; Christian Pedersen; Christopher C. Wilmers; Mads C. Forchhammer

2008-01-01

93

Divergent responses of Pygoscelis penguins reveal a common environmental driver.  

PubMed

The responses of predators to environmental variability in the Antarctic Peninsula region have exhibited divergent patterns owing to variation in the geographic settings of colonies and predator life-history strategies. Five breeding colonies of Pygoscelis penguins from King George Island and Livingston Island, South Shetland Islands, Antarctica, were examined to (1) compare the responses of sympatric congeners to recent changes in their Antarctic ecosystem and (2) assess underlying causes for such responses. We used linear regression and correlation analyses to compare indices of abundance, recruitment, and summer breeding performance of the Adélie (P. adeliae), gentoo (P. papua), and chinstrap penguins (P. antarctica). Breeding colonies of Adélie and chinstrap penguins have declined by roughly 50% since the mid-1970s, and recruitment indices of Adélie penguins have declined by roughly 80%, but no such patterns are evident for gentoo penguins. Fledging success, however, has remained stable at all breeding colonies. The different trends in abundance and recruitment indices for each species, despite generally similar indices of summer performance, suggest that winter conditions contribute to the divergent responses among the penguins. In particular, strong correlations between indices of penguin and krill recruitment suggest that penguins in the South Shetland Islands may live under an increasingly krill-limited system that has disproportionate effects on the survival of juvenile birds. PMID:17566778

Hinke, Jefferson T; Salwicka, Kasia; Trivelpiece, Susan G; Watters, George M; Trivelpiece, Wayne Z

2007-10-01

94

Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1\\/CCR3 blockade  

Microsoft Academic Search

The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co- stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva

Dai Miyazaki; Takao Nakamura; Masaharu Ohbayashi; Chuan Hui Kuo; Naoki Komatsu; Keiko Yakura; Takeshi Tominaga; Yoshitsugu Inoue; Hidemitsu Higashi; Meguru Murata; Shuzo Takeda; Atsuki Fukushima; Fu-Tong Liu; Marc E. Rothenberg; Santa Jeremy Ono

2009-01-01

95

TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER MULTIPLE INTRATRACHAEL (IT) EXPOSURE  

EPA Science Inventory

SOT 2001 DMS214 TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER MULTIPLE INTRATRACHEAL (IT) EXPOSURES. D Sailstad, E Boykin, M Ward, and MJ Selgrade. NHEERL, ORD, US EPA, RTP, NC, USA. TMA causes Th2 related respiratory hypersensitivity (RH) responses. W...

96

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

PubMed Central

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

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

2013-01-01

97

Membrane properties revealed by spatiotemporal response to a local inhomogeneity.  

PubMed

We study theoretically the spatiotemporal response of a lipid membrane submitted to a local chemical change of its environment, taking into account the time-dependent profile of the reagent concentration due to diffusion in the solution above the membrane. We show that the effect of the evolution of the reagent concentration profile becomes negligible after some time. It then becomes possible to extract interesting properties of the membrane response to the chemical modification. We find that a local density asymmetry between the two monolayers relaxes by spreading diffusively in the whole membrane. This behavior is driven by intermonolayer friction. Moreover, we show how the ratio of the spontaneous curvature change to the equilibrium density change induced by the chemical modification can be extracted from the dynamics of the local membrane deformation. Such information cannot be obtained by analyzing the equilibrium vesicle shapes that exist in different membrane environments in light of the area-difference elasticity model. PMID:23201541

Bitbol, Anne-Florence; Fournier, Jean-Baptiste

2013-04-01

98

Bmp Indicator Mice Reveal Dynamic Regulation of Transcriptional Response  

PubMed Central

Cellular responses to Bmp ligands are regulated at multiple levels, both extracellularly and intracellularly. Therefore, the presence of these growth factors is not an accurate indicator of Bmp signaling activity. While a common approach to detect Bmp signaling activity is to determine the presence of phosphorylated forms of Smad1, 5 and 8 by immunostaining, this approach is time consuming and not quantitative. In order to provide a simpler readout system to examine the presence of Bmp signaling in developing animals, we developed BRE-gal mouse embryonic stem cells and a transgenic mouse line that specifically respond to Bmp ligand stimulation. Our reporter identifies specific transcriptional responses that are mediated by Smad1 and Smad4 with the Schnurri transcription factor complex binding to a conserved Bmp-Responsive Element (BRE), originally identified among Drosophila, Xenopus and human Bmp targets. Our BRE-gal mES cells specifically respond to Bmp ligands at concentrations as low as 5 ng/ml; and BRE-gal reporter mice, derived from the BRE-gal mES cells, show dynamic activity in many cellular sites, including extraembryonic structures and mammary glands, thereby making this a useful scientific tool. PMID:22984405

Javier, Anna L.; Doan, Linda T.; Luong, Mui; Reyes de Mochel, N. Soledad; Sun, Aixu; Monuki, Edwin S.; Cho, Ken W. Y.

2012-01-01

99

Causes, prevention, and treatment of dentin hypersensitivity.  

PubMed

This article presents an overview of dentin hypersensitivity, including its causes, prevention, and treatment. The author provides information on hypersensitivity associated with exposed cervical dentin, tooth-whitening procedures, and direct and indirect restorations. PMID:15645869

Swift, Edward J

2004-02-01

100

Antibody and delayed-type hypersensitivity responses to Ochrobactrum anthropi cytosolic and outer membrane antigens in infections by smooth and rough Brucella spp.  

PubMed Central

Immunological cross-reactions between Brucella spp. and Ochrobactrum anthropi were investigated in animals and humans naturally infected by Brucella spp. and in experimentally infected rams (Brucella ovis infected), rabbits (Brucella melitensis infected), and mice (B. melitensis and Brucella abortus infected). In the animals tested, O. anthropi cytosolic proteins evoked a delayed-type hypersensitivity reaction of a frequency and intensity similar to that observed with B. melitensis brucellin. O. anthropi cytosolic proteins also reacted in gel precipitation tests with antibodies in sera from Brucella natural hosts with a frequency similar to that observed with B. melitensis proteins, and absorption experiments and immunoblotting showed antibodies to both Brucella-specific proteins and proteins common to Brucella and O. anthropi. No antibodies to O. anthropi cytosolic proteins were detected in the sera of Brucella-free hosts. Immunoblotting with sera of Brucella-infected sheep and goats showed immunoglobulin G (IgG) to Brucella group 3 outer membrane proteins and to O. anthropi proteins of similar molecular weight. No IgG to the O-specific polysaccharide of O. anthropi lipopolysaccharide was detected in the sera of Brucella-infected hosts. The sera of sheep, goats, and rabbits infected with B. melitensis contained IgG to O. anthropi rough lipopolysaccharide and lipid A, and B. ovis and O. anthropi rough lipopolysaccharides showed equal reactivities with IgG in the sera of B. ovis-infected rams. The findings show that the immunoresponse of Brucella-infected hosts to protein antigens is not necessarily specific for brucellae and suggest that the presence of O. anthropi or some related bacteria explains the previously described reactivities to Brucella rough lipopolysaccharide and outer membrane proteins in healthy animals. PMID:9144364

Velasco, J; Díaz, R; Grilló, M J; Barberán, M; Marín, C; Blasco, J M; Moriyón, I

1997-01-01

101

Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast  

PubMed Central

Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms. DOI: http://dx.doi.org/10.7554/eLife.03023.001 PMID:25073701

Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara; Dodgson, Stacie E; Gygi, Steven P; Amon, Angelika; Torres, Eduardo M

2014-01-01

102

Hypersensitivity to thrombin of platelets from hypercholesterolemic rats  

SciTech Connect

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.

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

1986-03-01

103

Management of hypersensitivity reactions to anti-D immunoglobulin preparations.  

PubMed

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

Rutkowski, K; Nasser, S M

2014-11-01

104

Lymphocyte transformation studies in drug hypersensitivity  

PubMed Central

In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents. Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects. For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test. It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs. PMID:445303

Warrington, R.J.; Tse, K.S.

1979-01-01

105

The P25 pathogenicity factor of Beet necrotic yellow vein virus targets the sugar beet 26S proteasome involved in the induction of a hypersensitive resistance response via interaction with an F-box protein.  

PubMed

P25, a Beet necrotic yellow vein virus (BNYVV) pathogenicity factor, interacts with a sugar beet protein with high homology to Arabidopsis thaliana kelch repeat containing F-box family proteins (FBK) of unknown function in yeast. FBK are members of the Skp1-Cullin-F-box (SCF) complex that mediate protein degradation. Here, we confirm this sugar beet FBK-P25 interaction in vivo and in vitro and provide evidence for in planta interaction and similar subcellular distribution in Nicotiana tabacum leaf cells. P25 even interacts with an FBK from A. thaliana, a BNYVV nonhost. FBK functional classification was possible by demonstrating the interaction with A. thaliana orthologs of Skp1-like (ASK) genes, a member of the SCF E3 ligase. By means of a yeast two-hybrid bridging assay, a direct effect of P25 on SCF-complex formation involving ASK1 protein was demonstrated. FBK transient Agrobacterium tumefaciens-mediated expression in N. benthamiana leaves induced a hypersensitive response. The full-length F-box protein consists of one F-box domain followed by two kelch repeats, which alone were unable to interact with P25 in yeast and did not lead to cell-death induction. The results support the idea that P25 is involved in virus pathogenicity in sugar beet and suggest suppression of resistance response. PMID:22512382

Thiel, Heike; Hleibieh, Kamal; Gilmer, David; Varrelmann, Mark

2012-08-01

106

Carotid sinus “irritability” rather than hypersensitivity: a new name for an old syndrome?  

Microsoft Academic Search

Carotid sinus hypersensitivity (CSH) is a well-described cause of syncope, resulting in bradycardia and\\/or hypotension in\\u000a response to neck pressure. The authors hypothesized that (CSH) represents an inappropriate response of the baroreflex system\\u000a to a nonphysiologic stimulus, rather than a truly hypersensitive carotid carotid sinus (ie, excessive vagotonia and sympathoinhibition\\u000a in response to arterial hypertension). To test their hypothesis, the

Christopher R. Cole; Julie Zuckerman; Benjamin D. Levine

2001-01-01

107

Occupational asthma due to esparto hypersensitivity in a building worker.  

PubMed

Esparto is a gramineous plant that has multiple applications in today's industry. Several cases of hypersensitivity pneumonitis (HP) caused by esparto inhalation have been reported, but only one case of asthma caused by Aspergillus fumigatus contaminating esparto has been communicated. We report a case of asthma induced by esparto inhalation in a 58-year-old man, who is a building industry worker, with subclinical sensitization to grass pollen. The relation between clinical symptoms and work activities was supported by peak expiratory flow (PEF) monitorization; PEF values decreased by 20% the days he handled esparto. Prick test with esparto was positive. Immunoblot analysis revealed several allergens in the esparto extract, some of them present in Lolium and A. fumigatus extracts. IgE immunoblot inhibition revealed a complete inhibition of lolium and A. fumigatus IgE reactive bands by esparto proteins. The patient then avoided the exposure to esparto at work and has remained asymptomatic for the last 2 years. In conclusion, this is a case of occupational asthma caused by esparto dust mediated by IgE antibodies. Proteins of A. fumigatus as well as proteins from this gramineous plant, which cross-reacted with esparto allergens, were responsible for the disease. PMID:18034977

Ruiz-Hornillos, Francisco Javier; De Barrio Fernández, Manuel; Molina, Pilar Tornero; Marcén, Itziar Sánchez; Fernandez, Galicia Davila; Sotés, María Rubio; de Ocariz, María Luisa Baeza Ochoa

2007-01-01

108

Clinical efficacy of the Er:YAG laser treatment on hypersensitive dentin.  

PubMed

Dentin hypersensitivity is a common symptomatic condition that causes discomfort and sometimes severe pain. The purpose of this study was to evaluate the clinical efficacy of the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser treatment on cervically exposed hypersensitive dentin. Twenty patients with dentin hypersensitivity of caries-free teeth were selected. A visual analog scale (VAS) was used to measure dentin sensitivity in response to air stimulus. A 2-minute Er:YAG laser (energy level: 60 mJ/pulse; repetition rate: 2 Hz) was applied to cervically exposed hypersensitive dentin. After 4 weeks, the hypersensitive teeth were examined again, and the VAS score was measured again and recorded. No complications such as detrimental pulpal effects were observed. Eighteen participants reported significantly reduced dentin hypersensitivity 4 weeks after the laser desensitization treatment. The VAS scores measured 4 weeks after the Er:YAG laser desensitization treatment were significantly decreased as compared with those measured at the baseline (p < 0.05). In conclusion, the Er:YAG laser desensitization treatment can effectively reduce hypersensitivity of cervically exposed hypersensitive dentin. PMID:23602018

Yu, Chuan-Hang; Chang, Yu-Chao

2014-06-01

109

Drug Hypersensitivity Reactions Involving Skin  

Microsoft Academic Search

Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside\\u000a immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions\\u000a appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely\\u000a skin involvement to fulminant systemic diseases which may

Oliver Hausmann; Benno Schnyder; Werner J. Pichler

110

Genotyping for severe drug hypersensitivity.  

PubMed

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

Karlin, Eric; Phillips, Elizabeth

2014-03-01

111

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

E-print Network

The Arabidopsis hrl1 mutation reveals novel overlapping roles for salicylic acid, jasmonic acid molecules: salicylic acid (SA), jasmonic acid (JA) and ethylene (ET). The hrl1 (hypersensitive response defence. Salicylic acid (SA) is both essential and suf®cient to induce SAR because transgenic expression

Raina, Ramesh

112

Hypersensitivity pneumonitis from Pezizia domiciliana. A case of El Niño lung.  

PubMed

A previously healthy woman developed severe dyspnea and was found to have restrictive lung disease and evidence of alveolitis. Open lung biopsy revealed extrinsic allergic alveolitis (hypersensitivity pneumonitis). The etiology was not initially apparent, but a home inspection showed an unusual mushroom growing in the patient's basement. Air sampling and serum precipitins against the fungal antigens confirmed that Pezizia domiciliana was the cause of the patient's hypersensitivity pneumonitis. This is the first described case of hypersensitivity pneumonitis cause by P. domiciliana. We speculate that unprecedented rainfall and flooding of the patient's basement as a result of El Niño rains produced ideal factors for the growth of this fungus. PMID:10556152

Wright, R S; Dyer, Z; Liebhaber, M I; Kell, D L; Harber, P

1999-11-01

113

Jasmonic Acid Signaling Modulates Ozone-Induced Hypersensitive Cell Death  

Microsoft Academic Search

Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent sig- naling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O 3 ) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling

Mulpuri V. Rao; Hyung-il Lee; Robert A. Creelman; John E. Mullet; Keith R. Davis

2000-01-01

114

The tomato gene Pti1 encodes a serine\\/threonine kinase that is phosphorylated by Pto and is involved in the hypersensitive response  

Microsoft Academic Search

The Pto gene encodes a serine\\/threonine kinase that confers resistance to bacterial speck disease in tomato. Using the yeast two-hybrid system, we identified a second serine\\/threonine kinase, Pto-interacting 1 (Pti1), that physically interacts with Pto. Crossphosphorylation assays revealed that Pto specifically phosphorylates Ptil and that Ptil does not phosphorylate Pto. Fen, another serine\\/threonine kinase from tomato that is closely related

Jianmin Zhou; Ying-Tsu Loh; Ray A. Bressan; Gregory B. Martin

1995-01-01

115

Anticonvulsant hypersensitivity syndrome closely mimicking Kawasaki disease  

PubMed Central

Anticonvulsant hypersensitivity syndrome (AHS) is an acute, life-threatening, idiosyncratic drug reaction seen within 1–8 weeks after administration of an aromatic antiepileptic drug. The authors present the case of a 16-month-old boy who developed prolonged fever, a generalised pruritic rash and eosinophilia within 4 weeks after starting treatment with phenobarbital for complicated febrile seizures. He gradually fulfilled the diagnostic criteria for classical Kawasaki disease (KD), although the rash and the subsequent desquamation were atypical, he did not defervesce quickly with administration of corticosteroids and intravenous ?-globulin, and he had only two suggestive cardiac features of KD—that is, perivascular echogenicity of the coronary arteries and a small pericardial effusion. Other conditions considered in the differential diagnosis were excluded by appropriate extensive serological and microbiological studies. He recovered fully. This report shows that drugs such as phenobarbital may be responsible for febrile exanthematous illnesses that closely mimic KD. PMID:21686467

Mantadakis, Elpis; Tsalkidis, Aggelos; Paraskakis, Emmanouel; Papadopoulou-Legbelou, Kyriaki; Varlamis, George; Evangeliou, Athanassios; Chatzimichael, Athanassios

2009-01-01

116

Cordycepin-hypersensitive growth links elevated polyphosphate levels to inhibition of poly(A) polymerase in Saccharomyces cerevisiae.  

PubMed

To identify genes involved in poly(A) metabolism, we screened the yeast gene deletion collection for growth defects in the presence of cordycepin (3'-deoxyadenosine), a precursor to the RNA chain terminating ATP analog cordycepin triphosphate. Deltapho80 and Deltapho85 strains, which have a constitutively active phosphate-response pathway, were identified as cordycepin hypersensitive. We show that inorganic polyphosphate (poly P) accumulated in these strains and that poly P is a potent inhibitor of poly(A) polymerase activity in vitro. Binding analyses of poly P and yeast Pap1p revealed an interaction with a k(D) in the low nanomolar range. Poly P also bound mammalian poly(A) polymerase, however, with a 10-fold higher k(D) compared to yeast Pap1p. Genetic tests with double mutants of Deltapho80 and other genes involved in phosphate homeostasis and poly P accumulation suggest that poly P contributed to cordycepin hypersensitivity. Synergistic inhibition of mRNA synthesis through poly P-mediated inhibition of Pap1p and through cordycepin-mediated RNA chain termination may thus account for hypersensitive growth of Deltapho80 and Deltapho85 strains in the presence of the chain terminator. Consistent with this, a mutation in the 3'-end formation component rna14 was synthetic lethal in combination with Deltapho80. Based on these observations, we suggest that binding of poly P to poly(A) polymerase negatively regulates its activity. PMID:18033801

Holbein, Sandra; Freimoser, Florian M; Werner, Thomas P; Wengi, Agnieszka; Dichtl, Bernhard

2008-02-01

117

Cordycepin-hypersensitive growth links elevated polyphosphate levels to inhibition of poly(A) polymerase in Saccharomyces cerevisiae  

PubMed Central

To identify genes involved in poly(A) metabolism, we screened the yeast gene deletion collection for growth defects in the presence of cordycepin (3?-deoxyadenosine), a precursor to the RNA chain terminating ATP analog cordycepin triphosphate. ?pho80 and ?pho85 strains, which have a constitutively active phosphate-response pathway, were identified as cordycepin hypersensitive. We show that inorganic polyphosphate (poly P) accumulated in these strains and that poly P is a potent inhibitor of poly(A) polymerase activity in vitro. Binding analyses of poly P and yeast Pap1p revealed an interaction with a kD in the low nanomolar range. Poly P also bound mammalian poly(A) polymerase, however, with a 10-fold higher kD compared to yeast Pap1p. Genetic tests with double mutants of ?pho80 and other genes involved in phosphate homeostasis and poly P accumulation suggest that poly P contributed to cordycepin hypersensitivity. Synergistic inhibition of mRNA synthesis through poly P-mediated inhibition of Pap1p and through cordycepin-mediated RNA chain termination may thus account for hypersensitive growth of ?pho80 and ?pho85 strains in the presence of the chain terminator. Consistent with this, a mutation in the 3?-end formation component rna14 was synthetic lethal in combination with ?pho80. Based on these observations, we suggest that binding of poly P to poly(A) polymerase negatively regulates its activity. PMID:18033801

Holbein, Sandra; Freimoser, Florian M.; Werner, Thomas P.; Wengi, Agnieszka; Dichtl, Bernhard

2008-01-01

118

Cyclosporine immunomodulation in a rabbit model of chronic hypersensitivity pneumonitis.  

PubMed

Rabbit models of chronic experimental hypersensitivity pneumonitis and desensitization were used to evaluate the effects of systemic cyclosporine. When administered 12 to 18 h before each inhalational challenge with aerosolized antigen and the adjuvant muramyl dipeptide, cyclosporine suppressed the development of disease as well as the anamnestic antibody response, particularly in bronchoalveolar lavage fluids. When administered at the time of sensitization only, cyclosporine suppressed the primary antibody response but not the anamnestic antibody response or the disease. Antigen- and mitogen-induced blastogenesis was inhibited by cyclosporine in vitro, but antigen-specific blastogenesis was not abrogated by cyclosporine previously administered in vivo. These results indicate that cyclosporine caused profound immunomodulation in this model, which can be at least partially explained by transient suppressive effects on T cells, particularly the helper/inducer and delayed hypersensitivity subset(s). PMID:4062034

Kopp, W C; Dierks, S E; Butler, J E; Upadrashta, B S; Richerson, H B

1985-11-01

119

Anticonvulsant hypersensitivity syndrome treated with intravenous immunoglobulin.  

PubMed

Anticonvulsant hypersensitivity syndrome is a severe, potentially life-threatening, reaction to the aromatic anticonvulsant medications. Reported here is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and intravenous immunoglobulin. The literature regarding treatment of this syndrome is reviewed. PMID:20682208

Dredge, David C; Parsons, Elizabeth C; Carter, Lindsay P; Staley, Kevin J

2010-07-01

120

Prasugrel-induced hypersensitivity skin reaction.  

PubMed

We report a case of hypersensitivity skin reaction to prasugrel. The patient exhibited a generalized skin rash after treatment with prasugrel, which was resolved after discontinuation of prasugrel and substitution to clopidogrel. Clopidogrel was successfully administered as an alternative to prasugrel without any signs of further hypersensitivity. PMID:25278991

Kim, Soo-Han; Park, Sang-Don; Baek, Yong-Soo; Lee, Seon-Young; Shin, Sung-Hee; Woo, Sung-Il; Kim, Dae-Hyeok; Kwan, Jun

2014-09-01

121

Prasugrel-Induced Hypersensitivity Skin Reaction  

PubMed Central

We report a case of hypersensitivity skin reaction to prasugrel. The patient exhibited a generalized skin rash after treatment with prasugrel, which was resolved after discontinuation of prasugrel and substitution to clopidogrel. Clopidogrel was successfully administered as an alternative to prasugrel without any signs of further hypersensitivity.

Park, Sang-Don; Baek, Yong-Soo; Lee, Seon-Young; Shin, Sung-Hee; Woo, Sung-Il; Kim, Dae-Hyeok; Kwan, Jun

2014-01-01

122

Severe type IV hypersensitivity to ‘black henna’ tattoo  

PubMed Central

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

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

2010-01-01

123

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

E-print Network

Spatial Organization of Embryonic Stem Cell Responsiveness to Autocrine Gp130 Ligands Reveals, Ontario, Canada Key Words. Autocrine signaling · Embryonic stem cell · Niche · Self-renewal · Stem cell-location-independent processes control- ling cell fate by analyzing the spatial organization of embryonic stem cells (ESCs) using

Zandstra, Peter W.

124

Environmental Hypersensitivity Disorder, Total Allergy and 20th Century Disease  

PubMed Central

Environmental hypersensitivity disorder is reputed to cause multiple allergic responses in susceptible people after exposure to common substances in the environment. The seriously afflicted, who believe themselves to be unable to live in the modern world, often become severely disabled. After a careful search of the literature, I am unable to find any scientific evidence for the validity of the theories, testing methods, or treatments given to these patients by clinical ecologists. This paper critically examines the concepts of environmental hypersensitivity and reviews scientific studies on this subject. It concludes that these patients are a heterogeneous group, and that many of them suffer from treatable psychiatric disorders. Guidelines are given for their management. PMID:21263833

Stewart, D.E.

1987-01-01

125

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine.  

PubMed

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

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

126

CUTANEOUS DRUG HYPERSENSITIVITY: IMMUNOLOGICAL AND GENETIC PERSPECTIVE  

PubMed Central

Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of “hapten concept” in immune sensitization has recently been contested by the “pharmacological interaction” hypothesis. After completion of the “human genome project” and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity. PMID:21716938

Ghosh, Kisalay; Banerjee, Gautam; Ghosal, Asok Kumar; Nandi, Jayoti

2011-01-01

127

Oxazolone-Induced Contact Hypersensitivity Reduces Lymphatic Drainage but Enhances the Induction of Adaptive Immunity  

PubMed Central

Contact hypersensitivity (CHS) induced by topical application of haptens is a commonly used model to study dermal inflammatory responses in mice. Several recent studies have indicated that CHS-induced skin inflammation triggers lymphangiogenesis but may negatively impact the immune-function of lymphatic vessels, namely fluid drainage and dendritic cell (DC) migration to draining lymph nodes (dLNs). On the other hand, haptens have been shown to exert immune-stimulatory activity by inducing DC maturation. In this study we investigated how the presence of pre-established CHS-induced skin inflammation affects the induction of adaptive immunity in dLNs. Using a mouse model of oxazolone-induced skin inflammation we observed that lymphatic drainage was reduced and DC migration from skin to dLNs was partially compromised. At the same time, a significantly stronger adaptive immune response towards ovalbumin (OVA) was induced when immunization had occurred in CHS-inflamed skin as compared to uninflamed control skin. In fact, immunization with sterile OVA in CHS-inflamed skin evoked a delayed-type hypersensitivity (DTH) response comparable to the one induced by conventional immunization with OVA and adjuvant in uninflamed skin. Striking phenotypic and functional differences were observed when comparing DCs from LNs draining uninflamed or CHS-inflamed skin. DCs from LNs draining CHS-inflamed skin expressed higher levels of co-stimulatory molecules and MHC molecules, produced higher levels of the interleukin-12/23 p40 subunit (IL-12/23-p40) and more potently induced T cell activation in vitro. Immunization experiments revealed that blockade of IL-12/23-p40 during the priming phase partially reverted the CHS-induced enhancement of the adaptive immune response. Collectively, our findings indicate that CHS-induced skin inflammation generates an overall immune-stimulatory milieu, which outweighs the potentially suppressive effect of reduced lymphatic vessel function. PMID:24911791

Aebischer, David; Willrodt, Ann-Helen; Halin, Cornelia

2014-01-01

128

Stipatosis or hypersensitivity pneumonitis caused by esparto (Stipa tenacissima) fibers.  

PubMed

Hypersensitivity pneumonitis or extrinsic allergic alveolitis may be defined as an immunological pulmonary disease caused by a variety of antigens reaching the lungs through inhaled organic and inorganic dusts derived from different sources, although they are usually occupational. Farmer's lung and pigeon breeder's lung are probably the most well-known types of hypersensitivity pneumonitis worldwide. Esparto grass (Stipa tenacissima), which is a grammineous plant which is commonly found in the Mediterranean countries, has a wide variety of uses. Esparto fiber is used for the manufacturing of ropes, hemp sandals, rush mats and parkets; for decorative stucco plates, used on walls and ceilings. Esparto supports a large industry in Spain. The first reports referring to esparto dust as a cause of respiratory disease did not appear until the 1960s, and it was first described as a byssinosis-like disorder. The first cases reported, in which immunologic and challenge tests were used to confirm this association, were described 14 years ago and referred as hypersensitivity pneumonitis nominated as stipatosis. Later, a large number of cases of esparto dust-induced hypersensitivity pneumonitis were reported by different authors, so that esparto may be nowadays considered as the main substance causing extrinsic allergic alveolitis in Spain. Afumigatus has been revealed to be the main inducing cause of stipatosis but probably is not the only one since other microorganisms could be implicated. On the other hand esparto fibers may also cause occupational asthma. In this article the prominent clinical findings of this disease as well as the results of serologic, bronchoalveolar lavage (BAL) and specific inhalation tests are shown. A complete historical review of esparto-induced allergic respiratory disease is also described. PMID:11642575

Hinojosa, M

2001-01-01

129

Sympathoinhibition and hypotension in carotid sinus hypersensitivity  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

130

Drug Induced Hypersensitivity and the HLA Complex  

PubMed Central

Drug-induced hypersensitivity reactions are of major concern and present a burden for national healthcare systems due to their often severe nature, high rate of hospital admissions and high mortality. They manifest with a wide range of symptoms and signs, and can be initiated by a wide range of structurally diverse chemical compounds. The pathophysiological mechanisms underlying hypersensitivity reactions are not well understood, but it is thought that they are immune mediated. MHC region on Chromosome 6 contains many genes with immune function. Classical MHC molecules are highly polymorphic cell surface glycoproteins whose function is to present peptide antigens to T cells. In addition to conferring protection from some diseases, HLA alleles are also associated with an increased risk of other diseases, including drug-induced hypersensitivity. Pharmacogenetic approach to predict the risk of drug-induced hypersensitivity has been established for several drugs. We will discuss the progress of hypersensitivity pharmacogenetics over the last few years and focus on current efforts of the international community to develop consortia which aim to standardize disease phenotypes and to identify affected individuals through international collaborations. In addition, we will discuss the clinical utility of HLA typing as predictive or diagnostic testing for drug-induced hypersensitivity.

Alfirevic, Ana; Pirmohamed, Munir

2011-01-01

131

Contribution of Afferent Pathways to Nerve-injury Induced Spontaneous Pain and Evoked Hypersensitivity  

PubMed Central

A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as “burning”. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of experimental neuropathic pain model were explored. Desensitization of TRPV1 positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. Following nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large diameter fibers and inactivation of the brainstem target of these fibers in the n. gracilis prevents tactile, but not thermal, hypersensitivity. Blockade of NPY signaling within the n. gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into n. gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1 positive fibers and spinal NK-1 positive ascending projections. In contrast, the large diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. As inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the n. gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect “allodynia”. PMID:21620567

King, Tamara; Qu, Chaoling; Okun, Alec; Mercado, Ramon; Ren, Jiyang; Brion, Triza; Lai, Josephine; Porreca, Frank

2011-01-01

132

A double blind controlled trial comparing three treatment modalities for dentin hypersensitivity  

PubMed Central

Aim: This randomized, double blind, split mouth study was aimed to compare three dentin desensitizing treatment modalities. Methods: Two hundred sixty teeth of 25 patients; each having at least 2 hypersensitive teeth in each quadrant, were included. Teeth were randomized to 4 groups: Group A treated with 2% NaF solution, Group B received GLUMA®; an aqueous solution of Hydroxy-Ethyl-Methacrylate and Glutarldehyde, (HEMA-G), Group C received iontophoresis with distilled water (placebo) and Group D was treated with NaF-iontophoresis. Pain response was evaluated on a visual analogue scale (VAS), by using tactile, air blast and cold-water stimuli at 0-day, 15-day, 1-month and 3-months interval. Results: All treatments were effective in reducing dentinal hypersensitivity significantly, Group D and Group B were more effective than Group A and Group C at all time intervals. Group D and Group B were equally effective in reducing dentinal hypersensitivity at 15-day and 1-month interval but Group D was more effective at 3-months. Conclusion: All treatment modalities were more effective in reducing hypersensitivity than placebo. 2% NaF-iontophoresis and HEMA-G were more effective than 2% NaF local application at all time intervals. But at 3-months, 2% NaF-iontophoresis was more effective than HEMA-G, while placebo produced no significant effect in reduction of hypersensitivity. Key words:Hypersensitivity, desensitisation, iontophoresis, dentin adhesive, sodium fluoride. PMID:22143734

Bhavsar, Neeta; Sahayata, Vishal; Acharya, Aneesha; Kshatriya, Payal

2012-01-01

133

Subacute hypersensitivity pneumonitis in an HIV infected patient receiving antiretroviral therapy  

PubMed Central

Abnormal pulmonary immune response to various antigens can lead to hypersensitivity pneumonitis. This disease has not previously been reported in HIV infected patients. This case report describes an HIV infected woman who developed subacute hypersensitivity pneumonitis in response to bird exposure. The disease manifested itself only after the patient experienced an improvement in her CD4 positive T lymphocyte count secondary to antiretroviral therapy. This case emphasises the need to consider non-HIV associated diseases in patients with HIV and suggests that diseases in which host immune response plays an essential role in pathogenesis may become more prevalent in HIV infected patients receiving effective antiretroviral therapy.?? PMID:10856327

Morris, A.; Nishimura, S.; Huang, L.

2000-01-01

134

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most commonly involved in hypersensitivity drug reactions. Such reactions can be due to the release of inflammatory mediators in the absence of specific immunologic recognition, or immunoglobulin E (IgE)- or T-cell-selective responses. The former include upper and lower airway symptoms in patients with chronic underlying respiratory disease, the exacerbation of chronic spontaneous urticaria, and the induction of cutaneous symptoms. The latter include selective responses to a single NSAID with good tolerance to strong cyclooxygenase-1 inhibitors, with a putative IgE or T-cell mechanism proposed. These reactions can be acute or delayed. PMID:25017675

Torres, Maria Jose; Barrionuevo, Esther; Kowalski, Marek; Blanca, Miguel

2014-08-01

135

[Overdose or hypersensitivity to vitamin D?].  

PubMed

Vitamin D intoxication with severe hypercalcemia is rare in the neonatal and infancy period. Through nine cases of hypercalcemia, secondary to taking 600,000 units of vitamin D (Sterogyl(®)), a review of vitamin D requirements and possible mechanisms of toxicity including hypersensitivity to this vitamin will be discussed. We report nine cases of babies admitted to our department between the ages of 25 and 105 days for treatment of severe dehydration. The pregnancies were normal, with no incidents at delivery. Clinical signs were dominated by weight loss, vomiting, and fever. Examination on admission revealed dehydration whose degree ranged from 8 to 15% with preserved diuresis and loss weight between 100 and 1100 g. Laboratory tests objectified hypercalcemia between 113 and 235mg/L, hypercalciuria (urinary calcium/creatinine mmol/mmol >0.5), and a low-level of parathyroid hormone. The vitamin D values in nine patients were toxic (344-749 nmol/L; normal >50 nmol/L; toxicity if >250 nmol/L). Abdominal ultrasound objectified renal nephrocalcinosis in seven patients. The DNA study, performed in eight patients, did not reveal a mutation of the vitamin D 24-hydroxylase gene (CYP24A1). The treatment consisted of intravenous rehydration with treatment of hypercalcemia (diuretics and corticosteroids). Serum calcium returned to the normal range within 4-50 days, with weight gain progressively over the following weeks. The follow-up (2 years for the oldest case) showed the persistence of images of nephrocalcinosis. Genetic susceptibility and metabolic differences appear to modulate the threshold of vitamin D toxicity. However, respect for recommended doses, recognized as safe in a large study population, reduces the risk of toxicity. PMID:25129320

Hmami, F; Oulmaati, A; Amarti, A; Kottler, M-L; Bouharrou, A

2014-10-01

136

Targeted protein destabilization reveals an estrogen-mediated ER stress response.  

PubMed

Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells leads to an unfolded protein response (UPR) that either restores homeostasis or commits the cells to apoptosis. Tools traditionally used to study the UPR are proapoptotic and thus confound analysis of long-term cellular responses to ER stress. Here, we describe an ER-localized HaloTag (ERHT) protein that can be conditionally destabilized using a small-molecule hydrophobic tag (HyT36). Treatment of ERHT-expressing cells with HyT36 induces acute, resolvable ER stress that results in transient UPR activation without induction of apoptosis. Transcriptome analysis of late-stage responses to this UPR stimulus reveals a link between UPR activity and estrogen signaling. PMID:25242550

Raina, Kanak; Noblin, Devin J; Serebrenik, Yevgeniy V; Adams, Alison; Zhao, Connie; Crews, Craig M

2014-11-01

137

Yeast translational response to high salinity: Global analysis reveals regulation at multiple levels  

PubMed Central

Genome-wide studies of steady-state mRNA levels revealed common principles underlying transcriptional changes in response to external stimuli. To uncover principles that govern other stages of the gene-expression response, we analyzed the translational response and its coordination with transcriptome changes following exposure to severe stress. Yeast cells were grown for 1 h in medium containing 1 M NaCl, which elicits a maximal but transient translation inhibition, and nonpolysomal or polysomal mRNA pools were subjected to DNA-microarray analyses. We observed a strong repression in polysomal association for most mRNAs, with no simple correlation with the changes in transcript levels. This led to an apparent accumulation of many mRNAs as a nontranslating pool, presumably waiting for recovery from the stress. However, some mRNAs demonstrated a correlated change in their polysomal association and their transcript levels (i.e., potentiation). This group was enriched with targets of the transcription factors Msn2/Msn4, and the translational induction of several tested mRNAs was diminished in an Msn2/Msn4 deletion strain. Genome-wide analysis of a strain lacking the high salinity response kinase Hog1p revealed that the group of translationally affected genes is significantly enriched with motifs that were shown to be associated with the ARE-binding protein Pub1. Since a relatively small number of genes was affected by Hog1p deletion, additional signaling pathways are likely to be involved in coordinating the translational response to severe salinity stress. PMID:18495938

Melamed, Daniel; Pnueli, Lilach; Arava, Yoav

2008-01-01

138

Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.  

PubMed

Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes. PMID:22530030

Zhang, Lingling; Hou, Rui; Su, Hailin; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

2012-01-01

139

PERSISTENT SUPPRESSION OF CONTACT HYPERSENSITIVITY, AND ALTERED T-CELL PARAMETERS IN F344 RATS EXPOSED PERINATALLY TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)  

EPA Science Inventory

Abstract The outcome of perinatal low-level TCDD exposure on the T cell-mediated contact hypersensitivity response (CHS) in adult F344 rats was investigated. Suppression of the 2,4- dinitrofluorobenzene (DNFB)-specific contact hypersensitivity reponse occurred in mature off...

140

Unusual formaldehyde-induced hypersensitivity in two schoolgirls  

SciTech Connect

Two schoolgirls developed a syndrome resembling Henoch-Schonlein purpura while attending a recently opened school insulated with urea-formaldehyde foam (UFFI). Skin rashes and swellings were accompanied by bizarre, blue-green discoloration of the skin. Subsequent investigations by county, state and federal authorities, and low measured concentrations of formaldehyde, prompted initial conclusions that in-school formaldehyde exposures were not responsible for the girls' problems. Subsequent controlled exposures to UFFI and formaldehyde while in hospital elicited the whole cascade of symptoms. The chronology of the onset and amplification of systems make it probable that the formaldehyde exposures precipitating the girls' hypersensitivity, occurred in the school. 3 refs.

Gammage, R.B. (Oak Ridge National Lab., TN (USA)); Hanna, W.T.; Painter, P.B. (Tennessee Univ., Knoxville, TN (USA))

1990-01-01

141

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

PubMed Central

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 3rd 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

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

2014-01-01

142

Global Analysis of Neutrophil Responses to Neisseria gonorrhoeae Reveals a Self-Propagating Inflammatory Program.  

PubMed

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

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

143

Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots.  

PubMed

Plant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1-g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation-related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella-located PIN3 were stronger than in those deprived of the epidermis and cortex cell-specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up-regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis. PMID:24373012

Aubry-Hivet, D; Nziengui, H; Rapp, K; Oliveira, O; Paponov, I A; Li, Y; Hauslage, J; Vagt, N; Braun, M; Ditengou, F A; Dovzhenko, A; Palme, K

2014-01-01

144

[Subacute hypersensitivity pneumonitis after occupational mold exposure].  

PubMed

Mold-induced hypersensitivity pneumonitis is a rare and usually slowly progressing disorder. Therefore, the diagnosis and etiological investigations may be challenging and may often cause delay, despite the fact that early diagnosis and avoidance of the disease inducing agent are essential for the management of the disease. When appropriately treated, hypersensitivity pneumonitis is usually a relatively benign disorder. Irreversible pulmonary fibrosis may develop in cases of prolonged exposure. The disorder is considered as an occupational disease if the sufficient exposure occurs at workplace. PMID:23786111

Eerikäinen, Johanna; Nynäs, Pia; Uitti, Jukka

2013-01-01

145

Metabolite profiling and network analysis reveal coordinated changes in grapevine water stress response  

PubMed Central

Background Grapevine metabolism in response to water deficit was studied in two cultivars, Shiraz and Cabernet Sauvignon, which were shown to have different hydraulic behaviors (Hochberg et al. Physiol. Plant. 147:443–453, 2012). Results Progressive water deficit was found to effect changes in leaf water potentials accompanied by metabolic changes. In both cultivars, but more intensively in Shiraz than Cabernet Sauvignon, water deficit caused a shift to higher osmolality and lower C/N ratios, the latter of which was also reflected in marked increases in amino acids, e.g., Pro, Val, Leu, Thr and Trp, reductions of most organic acids, and changes in the phenylpropanoid pathway. PCA analysis showed that changes in primary metabolism were mostly associated with water stress, while diversification of specialized metabolism was mostly linked to the cultivars. In the phloem sap, drought was characterized by higher ABA concentration and major changes in benzoate levels coinciding with lower stomatal conductance and suberinization of vascular bundles. Enhanced suberin biosynthesis in Shiraz was reflected by the higher abundance of sap hydroxybenzoate derivatives. Correlation-based network analysis revealed that compared to Cabernet Sauvignon, Shiraz had considerably larger and highly coordinated stress-related changes, reflected in its increased metabolic network connectivity under stress. Network analysis also highlighted the structural role of major stress related metabolites, e.g., Pro, quercetin and ascorbate, which drastically altered their connectedness in the Shiraz network under water deficit. Conclusions Taken together, the results showed that Vitis vinifera cultivars possess a common metabolic response to water deficit. Central metabolism, and specifically N metabolism, plays a significant role in stress response in vine. At the cultivar level, Cabernet Sauvignon was characterized by milder metabolic perturbations, likely due to a tighter regulation of stomata upon stress induction. Network analysis was successfully implemented to characterize plant stress molecular response and to identify metabolites with a significant structural and biological role in vine stress response. PMID:24256338

2013-01-01

146

Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata.  

PubMed

Proper protein folding in the endoplasmic reticulum (ER) is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR), is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata ?ire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata. PMID:23382685

Miyazaki, Taiga; Nakayama, Hironobu; Nagayoshi, Yohsuke; Kakeya, Hiroshi; Kohno, Shigeru

2013-01-01

147

Proteomic Research Reveals the Stress Response and Detoxification of Yeast to Combined Inhibitors  

PubMed Central

The tolerant mechanism of yeast to the combination of three inhibitors (furfural, phenol and acetic acid) was investigated using 2-DE combined with MALDI-TOF/TOF-MS. The stress response and detoxification related proteins (e.g., Ahp1p, Hsp26p) were expressed higher in the tolerant yeast than in the parental yeast. The expressions of most nitrogen metabolism related proteins (e.g. Gdh1p, Met1p) were higher in the parental yeast, indicating that the tolerant yeast decreases its nitrogen metabolism rate to reserve energy, and possesses high resistance to the stress of combined inhibitors. Furthermore, upon exposure to the inhibitors, the proteins related to protein folding, degradation and translation (e.g., Ssc1p, Ubp14p, Efb1p) were all significantly affected, and the oxidative stress related proteins (e.g., Ahp1p, Grx1p) were increased. Knockdown of genes related to the oxidative stress and unfolded protein response (Grx1, Gre2, Asc1) significantly decreased the tolerance of yeast to inhibitors, which further suggested that yeast responded to the inhibitors mainly by inducing unfolded protein response. This study reveals that increasing the detoxification and tolerating oxidative stress, and/or decreasing the nitrogen metabolism would be promising strategies in developing more tolerant strains to the multiple inhibitors in lignocellulose hydrolysates. PMID:22952687

Ding, Ming-Zhu; Wang, Xin; Liu, Wei; Cheng, Jing-Sheng; Yang, Yang; Yuan, Ying-Jin

2012-01-01

148

The Transcriptome and Proteome of the Diatom Thalassiosira pseudonana Reveal a Diverse Phosphorus Stress Response  

PubMed Central

Phosphorus (P) is a critical driver of phytoplankton growth and ecosystem function in the ocean. Diatoms are an abundant class of marine phytoplankton that are responsible for significant amounts of primary production. With the control they exert on the oceanic carbon cycle, there have been a number of studies focused on how diatoms respond to limiting macro and micronutrients such as iron and nitrogen. However, diatom physiological responses to P deficiency are poorly understood. Here, we couple deep sequencing of transcript tags and quantitative proteomics to analyze the diatom Thalassiosira pseudonana grown under P-replete and P-deficient conditions. A total of 318 transcripts were differentially regulated with a false discovery rate of <0.05, and a total of 136 proteins were differentially abundant (p<0.05). Significant changes in the abundance of transcripts and proteins were observed and coordinated for multiple biochemical pathways, including glycolysis and translation. Patterns in transcript and protein abundance were also linked to physiological changes in cellular P distributions, and enzyme activities. These data demonstrate that diatom P deficiency results in changes in cellular P allocation through polyphosphate production, increased P transport, a switch to utilization of dissolved organic P through increased production of metalloenzymes, and a remodeling of the cell surface through production of sulfolipids. Together, these findings reveal that T. pseudonana has evolved a sophisticated response to P deficiency involving multiple biochemical strategies that are likely critical to its ability to respond to variations in environmental P availability. PMID:22479440

Dyhrman, Sonya T.; Mercier, Melissa L.; Alexander, Harriet; Whitney, LeAnn P.; Drzewianowski, Andrea; Bulygin, Vladimir V.; Bertrand, Erin M.; Wu, Zhijin; Benitez-Nelson, Claudia; Heithoff, Abigail

2012-01-01

149

BCL-2 family genetic profiling reveals microenvironment-specific determinants of chemotherapeutic response  

PubMed Central

The Bcl-2 family encompasses a diverse set of apoptotic regulators that are dynamically activated in response various cell intrinsic and extrinsic stimuli. An extensive variety of cell culture experiments have identified effects of growth factors, cytokines and drugs on BCL-2 family functions, but in vivo studies have tended to focus on role of one or two particular members in development and organ homeostasis. Thus, the ability of physiologically relevant contexts to modulate canonical dependencies that are likely to be more complex has yet to be investigated systematically. In this study, we report findings derived from a pool-based shRNA assay that systematically and comprehensively interrogated the functional dependence of leukemia and lymphoma cells upon various BCL-2 family members across many diverse in vitro and in vivo settings. This approach permitted us to report the first in vivo loss of function screen for modifiers of the response to a frontline chemotherapeutic agent. Notably, our results reveal an unexpected role for the extrinsic death pathway as a tissue-specific modifier of therapeutic response. In particular, our findings demonstrate that particular tissue sites of tumor dissemination play critical roles in demarcating the nature and extent of cancer cell vulnerabilities and mechanisms of chemoresistance. PMID:21784872

Pritchard, Justin R.; Gilbert, Luke A.; Meacham, Corbin E.; Ricks, Jennifer L.; Jiang, Hai; Lauffenburger, Douglas A.; Hemann, Michael T.

2011-01-01

150

Response of Arabidopsis to Iron Deficiency Stress as Revealed by Microarray Analysis1  

PubMed Central

Gene expression in response to Fe deficiency was analyzed in Arabidopsis roots and shoots through the use of a cDNA collection representing at least 6,000 individual gene sequences. Arabidopsis seedlings were grown 1, 3, and 7 d in the absence of Fe, and gene expression in roots and shoots was investigated. Following confirmation of data and normalization methods, expression of several sequences encoding enzymes known to be affected by Fe deficiency was investigated by microarray analysis. Confirmation of literature reports, particularly for changes in enzyme activity, was not always possible, but changes in gene expression could be confirmed. An expression analysis of genes in glycolysis, the tricarboxylic acid cycle, and oxidative pentose phosphate pathway revealed an induction of several enzymes within 3 d of Fe-deficient growth, indicating an increase in respiration in response to Fe deficiency. In roots, transcription of sequences corresponding to enzymes of anaerobic respiration was also induced, whereas in shoots, the induction of several genes in gluconeogenesis, starch degradation, and phloem loading was observed. Thus, it seemed likely that the energy demand in roots required for the Fe deficiency response exceeded the capacity of oxidative phosphorylation, and an increase in carbon import and anaerobic respiration were required to maintain metabolism. PMID:11706184

Thimm, Oliver; Essigmann, Bernd; Kloska, Sebastian; Altmann, Thomas; Buckhout, Thomas J.

2001-01-01

151

A Case of Chlorpheniramine Maleate-Induced Hypersensitivity With Aspirin Intolerance  

PubMed Central

Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines. PMID:21217928

Kim, Min-Hye; Lee, Sang-Min; Lee, So-Hee; Kwon, Hyouk-Soo; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young

2011-01-01

152

Tissue glucocorticoid resistance\\/hypersensitivity syndromes  

Microsoft Academic Search

Glucocorticoids have a broad array of life-sustaining functions and play an important role in the therapy of many diseases. Thus, changes of tissue sensitivity to glucocorticoids may be associated with and influence the course and treatment of many pathologic states. Such tissue sensitivity changes may present on either side of an optimal range, respectively as glucocorticoid resistance or hypersensitivity, and

Tomoshige Kino; Massimo U De Martino; Evangelia Charmandari; Marco Mirani; George P Chrousos

2003-01-01

153

Dentine hypersensitivity in dental bleaching: case report.  

PubMed

Hydrogen and carbamide peroxides used for in-office and at-home whitening treatments are potentially harmful to pulp causing various alterations. Also characteristic and quite frequent is the presence of dental sensitivity. The aim of this paper is to review the appearance of post-whitening tooth hypersensitivity in clinical cases treated with different techniques. A study of patients (N = 56) with 5 different dental whitening techniques was managed: in-office light activated, with 35% hydrogen peroxide (N1 = 10); in-office chemical activated, also with 35% hydrogen peroxide (N2 = 10); in-office with custom-formed trays using 35% carbamide peroxide (N3 = 10); at-home with custom-formed trays (N4 = 16, 8 with 10% carbamide peroxide and 8 with 3.5% hydrogen peroxide); and at-home with a 6% carbamide peroxide varnish (N5 = 10). For the set of cases, sensitivity was 55% and varied between slight and intense. All whitening procedures can cause hypersensitivity, although it does not always occur. When present (31-55% of all the patients treated), hypersensitivity is not usually very intense and affects only a few teeth in each patient. Greater sensitivity was observed with in-office chemical activated (70%) and light-activated (100%) whitening techniques. So, after dental whitening treatment, dental hypersensitivity is to be expected, independently of technique and product used, in at least one out of two patients. PMID:19369923

Amengual, J; Forner, L

2009-04-01

154

Granulomatous hypersensitivity induced by sensory peripheral nerve  

Microsoft Academic Search

THE nature of granulomas remains uncertain. In sarcoidosis and Crohn's disease of the ileum, the aetiology is unknown. Even where a causative organism has been identified, as in tuberculosis and non-lepromatous leprosy, the role the mycobacteria play in the development of the granuloma is obscure1. There is no animal model available for the study of granulomatous hypersensitivity. But in susceptible

C. L. Crawford; P. M. D. Hardwicke; D. H. L. Evans; E. M. Evans

1977-01-01

155

Modulation of in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. II. Inhibition by RP-3 treatment of mononuclear leukocyte recruitment in delayed-type hypersensitivity to sheep red blood cells in rats.  

PubMed

We demonstrated in our previous paper that treatment of rats with RP-3, a mAb that depletes in vivo neutrophils selectively, resulted in inhibition of both the priming and effector phases of delayed type hypersensitivity (DTH) to SRBC. In order to clarify the mechanisms of this phenomenon, we examined the effect of RP-3 treatment on mononuclear leukocyte (MNL) recruitment in DTH. When rats had been treated with RP-3 at the time of Ag priming, MNL migration, which accompanies DTH, was inhibited. The prior infiltration of neutrophils was also partially required for MNL recruitment because migration was inhibited when the immune rats were treated with RP-3 at the time of DTH elicitation. PMID:8473730

Kudo, C; Yamashita, T; Terashita, M; Sendo, F

1993-05-01

156

Combined magnetic resonance and fluorescence imaging of the living mouse brain reveals glioma response to chemotherapy  

PubMed Central

Fluorescent molecular tomographic (FMT) imaging can noninvasively monitor molecular function in living animals using specific fluorescent probes. However, macroscopic imaging methods such as FMT generally exhibit low anatomical details. To overcome this, we report a quantitative technique to image both structure and function by combining FMT and magnetic resonance (MR) imaging. We show that FMT-MR imaging can produce three-dimensional, multimodal images of living mouse brains allowing for serial monitoring of tumor morphology and protease activity. Combined FMT-MR tumor imaging provides a unique in vivo diagnostic parameter, protease activity concentration (PAC), which reflects histological changes in tumors and is significantly altered by systemic chemotherapy. Alterations in this diagnostic parameter are detectable early after chemotherapy and correlate with subsequent tumor growth, predicting tumor response to chemotherapy. Our results reveal that combined FMT-MR imaging of fluorescent molecular probes could be valuable for brain tumor drug development and other neurological and somatic imaging applications. PMID:19154791

McCann, Corey M.; Waterman, Peter; Figueiredo, Jose-Luiz; Aikawa, Elena; Weissleder, Ralph; Chen, John W.

2009-01-01

157

Transcriptome signatures of class I and III stress response deregulation in Lactobacillus plantarum reveal pleiotropic adaptation  

PubMed Central

Background To cope with environmental challenges bacteria possess sophisticated defense mechanisms that involve stress-induced adaptive responses. The canonical stress regulators CtsR and HrcA play a central role in the adaptations to a plethora of stresses in a variety of organisms. Here, we determined the CtsR and HrcA regulons of the lactic acid bacterium Lactobacillus plantarum WCFS1 grown under reference (28°C) and elevated (40°C) temperatures, using ctsR, hrcA, and ctsR-hrcA deletion mutants. Results While the maximum specific growth rates of the mutants and the parental strain were similar at both temperatures (0.33?±?0.02 h-1 and 0.34?±?0.03 h-1, respectively), DNA microarray analyses revealed that the CtsR or HrcA deficient strains displayed altered transcription patterns of genes encoding functions involved in transport and binding of sugars and other compounds, primary metabolism, transcription regulation, capsular polysaccharide biosynthesis, as well as fatty acid metabolism. These transcriptional signatures enabled the refinement of the gene repertoire that is directly or indirectly controlled by CtsR and HrcA of L. plantarum. Deletion of both regulators, elicited transcriptional changes of a large variety of additional genes in a temperature-dependent manner, including genes encoding functions involved in cell-envelope remodeling. Moreover, phenotypic assays revealed that both transcription regulators contribute to regulation of resistance to hydrogen peroxide stress. The integration of these results allowed the reconstruction of CtsR and HrcA regulatory networks in L. plantarum, highlighting the significant intertwinement of class I and III stress regulons. Conclusions Taken together, our results enabled the refinement of the CtsR and HrcA regulatory networks in L. plantarum, illustrating the complex nature of adaptive stress responses in this bacterium. PMID:24238744

2013-01-01

158

Short Communication Artificial light at night alters delayed-type hypersensitivity reaction in  

E-print Network

Short Communication Artificial light at night alters delayed-type hypersensitivity reaction increased the DTH reaction in dark nights, but exposure to nighttime light pre- vented this response in revised form 20 May 2013 Accepted 26 May 2013 Available online 4 June 2013 Keywords: Light pollution

Nelson, Randy J.

159

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

Microsoft Academic Search

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

María Elena Alvarez

2000-01-01

160

Microarray analysis of Pseudomonas aeruginosa reveals induction of pyocin genes in response to hydrogen peroxide  

PubMed Central

Background Pseudomonas aeruginosa, a pathogen infecting those with cystic fibrosis, encounters toxicity from phagocyte-derived reactive oxidants including hydrogen peroxide during active infection. P. aeruginosa responds with adaptive and protective strategies against these toxic species to effectively infect humans. Despite advances in our understanding of the responses to oxidative stress in many specific cases, the connectivity between targeted protective genes and the rest of cell metabolism remains obscure. Results Herein, we performed a genome-wide transcriptome analysis of the cellular responses to hydrogen peroxide in order to determine a more complete picture of how oxidative stress-induced genes are related and regulated. Our data reinforce the previous conclusion that DNA repair proteins and catalases may be among the most vital antioxidant defense systems of P. aeruginosa. Our results also suggest that sublethal oxidative damage reduces active and/or facilitated transport and that intracellular iron might be a key factor for a relationship between oxidative stress and iron regulation. Perhaps most intriguingly, we revealed that the transcription of all F-, R-, and S-type pyocins was upregulated by oxidative stress and at the same time, a cell immunity protein (pyocin S2 immunity protein) was downregulated, possibly leading to self-killing activity. Conclusion This finding proposes that pyocin production might be another novel defensive scheme against oxidative attack by host cells. PMID:16150148

Chang, Wook; Small, David A; Toghrol, Freshteh; Bentley, William E

2005-01-01

161

Optically Trapped Bacteria Pairs Reveal Discrete Motile Response to Control Aggregation upon Cell-Cell Approach.  

PubMed

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell-cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 ?m. Moreover, the motile response displays spatial sensitivity with greater cell-cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation. PMID:24965235

Dienerowitz, Maria; Cowan, Laura V; Gibson, Graham M; Hay, Rebecca; Padgett, Miles J; Phoenix, Vernon R

2014-11-01

162

Capturing Arabidopsis Root Architecture Dynamics with root-fit Reveals Diversity in Responses to Salinity.  

PubMed

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

Julkowska, Magdalena M; Hoefsloot, Huub C J; Mol, Selena; Feron, Richard; de Boer, Gert-Jan; Haring, Michel A; Testerink, Christa

2014-11-01

163

Quantitative Proteomics Reveal ATM Kinase-dependent Exchange in DNA Damage Response Complexes  

PubMed Central

ATM is a protein kinase that initiates a well-characterized signaling cascade in cells exposed to ionizing radiation (IR). However, the role for ATM in coordinating critical protein interactions and subsequent exchanges within DNA damage response (DDR) complexes is unknown. We combined SILAC-based tandem mass spectrometry and a subcellular fractionation protocol to interrogate the proteome of irradiated cells treated with or without the ATM kinase inhibitor KU55933. We developed an integrative network analysis to identify and prioritize proteins that were responsive to KU55933, specifically in chromatin, and that were also enriched for physical interactions with known DNA repair proteins. This analysis identified 53BP1 and annexin A1 (ANXA1) as strong candidates. Using fluorescence recovery after photobleaching, we found that the exchange of GFP-53BP1 in DDR complexes decreased with KU55933. Further, we found that ANXA1 knockdown sensitized cells to IR via a mechanism that was not potentiated by KU55933. Our study reveals a role for ATM kinase activity in the dynamic exchange of proteins in DDR complexes and identifies a role for ANXA1 in cellular radioprotection. PMID:22909323

Choi, Serah; Srivas, Rohith; Fu, Katherine Y.; Hood, Brian L.; Dost, Banu; Gibson, Gregory A.; Watkins, Simon C.; Van Houten, Bennett; Bandeira, Nuno; Conrads, Thomas P.; Ideker, Trey; Bakkenist, Christopher J.

2012-01-01

164

Children processing music: electric brain responses reveal musical competence and gender differences.  

PubMed

Numerous studies investigated physiological correlates of the processing of musical information in adults. How these correlates develop during childhood is poorly understood. In the present study, we measured event-related electric brain potentials elicited in 5- and 9-year-old children while they listened to (major-minor tonal) music. Stimuli were chord sequences, infrequently containing harmonically inappropriate chords. Our results demonstrate that the degree of (in)appropriateness of the chords modified the brain responses in both groups according to music-theoretical principles. This suggests that already 5-year-old children process music according to a well-established cognitive representation of the major-minor tonal system and according to music-syntactic regularities. Moreover, we show that, in contrast to adults, an early negative brain response was left predominant in boys, whereas it was bilateral in girls, indicating a gender difference in children processing music, and revealing that children process music with a hemispheric weighting different from that of adults. Because children process, in contrast to adults, music in the same hemispheres as they process language, results indicate that children process music and language more similarly than adults. This finding might support the notion of a common origin of music and language in the human brain, and concurs with findings that demonstrate the importance of musical features of speech for the acquisition of language. PMID:12965042

Koelsch, Stefan; Grossmann, Tobias; Gunter, Thomas C; Hahne, Anja; Schröger, Erich; Friederici, Angela D

2003-07-01

165

Hypersensitivity Reactions to Vaccine Components  

Microsoft Academic Search

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

Noushin Heidary; David E. Cohen

2005-01-01

166

Microbiome of prebiotic treated mice reveals novel targets involved in host-response during obesity  

PubMed Central

The gut microbiota is involved in metabolic and immune disorders associated with obesity and type 2 diabetes. We previously demonstrated that prebiotic treatment may significantly improve host health by modulating bacterial species related to the improvement of gut endocrine, barrier and immune functions. An analysis of gut metagenome is needed to determine which bacterial functions and taxa are responsible for beneficial microbiota-host interactions upon nutritional intervention. We subjected mice to prebiotic (Pre) treatment under physiological (control diet: CT) and pathological conditions (high-fat diet: HFD) for 8 weeks and investigated the production of intestinal antimicrobial peptides and the gut microbiome. HFD feeding significantly decreased the expression of regenerating islet-derived 3-gamma (Reg3g) and phospholipase A2 group-II (PLA2g2) in the jejunum. Prebiotic treatment increased Reg3g expression (by approximately 50-fold) and improved intestinal homeostasis as suggested by the increase in the expression of intectin, a key protein involved in intestinal epithelial cell turnover. Deep metagenomic sequencing analysis revealed that HFD and prebiotic treatment significantly affected the gut microbiome at different taxonomic levels. Functional analyses based on the occurrence of clusters of orthologous groups of proteins (COGs) also revealed distinct profiles for the HFD, Pre, HFD-Pre and CT groups. Finally, the gut microbiota modulations induced by prebiotics counteracted HFD-induced inflammation and related metabolic disorders. Thus, we identified novel putative taxa and metabolic functions that may contribute to the development of or protection against the metabolic alterations observed during HFD feeding and HFD-Pre feeding. PMID:24694712

Gaia, Nadia; Johansson, Maria; Stahlman, Marcus; Backhed, Fredrik; Delzenne, Nathalie M.; Schrenzel, Jacques; Francois, Patrice; Cani, Patrice D.

2014-01-01

167

Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity.  

PubMed

The gut microbiota is involved in metabolic and immune disorders associated with obesity and type 2 diabetes. We previously demonstrated that prebiotic treatment may significantly improve host health by modulating bacterial species related to the improvement of gut endocrine, barrier and immune functions. An analysis of the gut metagenome is needed to determine which bacterial functions and taxa are responsible for beneficial microbiota-host interactions upon nutritional intervention. We subjected mice to prebiotic (Pre) treatment under physiological (control diet: CT) and pathological conditions (high-fat diet: HFD) for 8 weeks and investigated the production of intestinal antimicrobial peptides and the gut microbiome. HFD feeding significantly decreased the expression of regenerating islet-derived 3-gamma (Reg3g) and phospholipase A2 group-II (PLA2g2) in the jejunum. Prebiotic treatment increased Reg3g expression (by ?50-fold) and improved intestinal homeostasis as suggested by the increase in the expression of intectin, a key protein involved in intestinal epithelial cell turnover. Deep metagenomic sequencing analysis revealed that HFD and prebiotic treatment significantly affected the gut microbiome at different taxonomic levels. Functional analyses based on the occurrence of clusters of orthologous groups (COGs) of proteins also revealed distinct profiles for the HFD, Pre, HFD-Pre and CT groups. Finally, the gut microbiota modulations induced by prebiotics counteracted HFD-induced inflammation and related metabolic disorders. Thus, we identified novel putative taxa and metabolic functions that may contribute to the development of or protection against the metabolic alterations observed during HFD feeding and HFD-Pre feeding. PMID:24694712

Everard, Amandine; Lazarevic, Vladimir; Gaïa, Nadia; Johansson, Maria; Ståhlman, Marcus; Backhed, Fredrik; Delzenne, Nathalie M; Schrenzel, Jacques; François, Patrice; Cani, Patrice D

2014-10-01

168

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

PubMed Central

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

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

169

Comparison of Inflammatory Events during Developing Immunoglobulin E-Mediated Late-Phase Reactions and Delayed-Hypersensitivity Reactions  

Microsoft Academic Search

To compare cellular and mediator responses in early developing late-phase skin reactions (LPR) and delayed-hypersensitivity (DH) reactions in the same subjects, responses in skin chambers overlying sites of challenge with pollen antigen and Candida albicans antigens were compared in six humans with demonstrated prominent LPR and DH responses. Histamine levels in overlying chamber fluids at 1 h were much higher

BURTON ZWEIMAN; ANNE R. MOSKOVITZ; CAROLYN VON ALLMEN

1998-01-01

170

Probabilistic independent component analysis for laser speckle contrast images reveals in vivo multi - component vascular responses to forepaw stimulation  

Microsoft Academic Search

Brain's functional response can be studied by observing the spatiotemporal dynamics of functional and structural changes in cerebral vasculature. However, very few studies explore detailed changes at the level of individual microvessels while revealing the simultaneous wide field view of microcirculation responses to functional stimulation. Here we use a high spatiotemporal resolution laser speckle contrast imaging method, in combination with

Nan Li; Galit Pelled; Nitish V. Thakor

2010-01-01

171

Barcoded Pyrosequencing Reveals That Consumption of Galactooligosaccharides Results in a Highly Specific Bifidogenic Response in Humans  

PubMed Central

Prebiotics are selectively fermented ingredients that allow specific changes in the gastrointestinal microbiota that confer health benefits to the host. However, the effects of prebiotics on the human gut microbiota are incomplete as most studies have relied on methods that fail to cover the breadth of the bacterial community. The goal of this research was to use high throughput multiplex community sequencing of 16S rDNA tags to gain a community wide perspective of the impact of prebiotic galactooligosaccharide (GOS) on the fecal microbiota of healthy human subjects. Fecal samples from eighteen healthy adults were previously obtained during a feeding trial in which each subject consumed a GOS-containing product for twelve weeks, with four increasing dosages (0, 2.5, 5, and 10 gram) of GOS. Multiplex sequencing of the 16S rDNA tags revealed that GOS induced significant compositional alterations in the fecal microbiota, principally by increasing the abundance of organisms within the Actinobacteria. Specifically, several distinct lineages of Bifidobacterium were enriched. Consumption of GOS led to five- to ten-fold increases in bifidobacteria in half of the subjects. Increases in Firmicutes were also observed, however, these changes were detectable in only a few individuals. The enrichment of bifidobacteria was generally at the expense of one group of bacteria, the Bacteroides. The responses to GOS and the magnitude of the response varied between individuals, were reversible, and were in accordance with dosage. The bifidobacteria were the only bacteria that were consistently and significantly enriched by GOS, although this substrate supported the growth of diverse colonic bacteria in mono-culture experiments. These results suggest that GOS can be used to enrich bifidobacteria in the human gastrointestinal tract with remarkable specificity, and that the bifidogenic properties of GOS that occur in vivo are caused by selective fermentation as well as by competitive interactions within the intestinal environment. PMID:21966454

Davis, Lauren M. G.; Martinez, Ines; Walter, Jens; Goin, Caitlin; Hutkins, Robert W.

2011-01-01

172

Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria  

PubMed Central

A previously healthy man working as a machine operator in an automotive factory developed respiratory symptoms. Medical evaluation showed abnormal pulmonary function tests, a lung biopsy showed hypersensitivity pneumonitis, and his illness was traced to his work environment. His physician asked the employer to remove him from exposure to metalworking fluids. Symptoms reoccurred when he was later reexposed to metalworking fluids, and further permanent decrement in his lung function occurred. Investigation of his workplace showed that five of six large reservoirs of metalworking fluids (cutting oils) grew Mycobacterium chelonae (or Mycobacterium immunogenum), an organism previously associated with outbreaks of hypersensitivity pneumonitis in automaking factories. His lung function remained stable after complete removal from exposure. The employer, metalworking fluid supplier, union, and the National Institute for Occupational Safety and Health were notified of this sentinel health event. No further cases have been documented in this workplace. PMID:15929902

Beckett, William; Kallay, Michael; Sood, Akshay; Zuo, Zhengfa; Milton, Donald

2005-01-01

173

Responses of a bursting pacemaker to excitation reveal spatial segregation between bursting and spiking mechanisms  

PubMed Central

Central pattern generators (CPGs) frequently include bursting neurons that serve as pacemakers for rhythm generation. Phase resetting curves (PRCs) can provide insight into mechanisms underlying phase locking in such circuits. PRCs were constructed for a pacemaker bursting complex in the pyloric circuit in the stomatogastric ganglion of the lobster and crab. This complex is comprised of the Anterior Burster (AB) neuron and two Pyloric Dilator (PD) neurons that are all electrically coupled. Artificial excitatory synaptic conductance pulses of different strengths and durations were injected into one of the AB or PD somata using the Dynamic Clamp. Previously, we characterized the inhibitory PRCs by assuming a single slow process that enabled synaptic inputs to trigger switches between an up state in which spiking occurs and a down state in which it does not. Excitation produced five different PRC shapes, which could not be explained with such a simple model. A separate dendritic compartment was required to separate the mechanism that generates the up and down phases of the bursting envelope (1) from synaptic inputs applied at the soma, (2) from axonal spike generation and (3) from a slow process with a slower time scale than burst generation. This study reveals that due to the nonlinear properties and compartmentalization of ionic channels, the response to excitation is more complex than inhibition. PMID:21360137

Maran, Selva K; Sieling, Fred H; Demla, Kavita; Prinz, Astrid A; Canavier, Carmen C

2011-01-01

174

Optical tweezers reveal a dynamic mechanical response of cationic peptide-DNA complexes  

NASA Astrophysics Data System (ADS)

Nonviral carriers have been developed to deliver nucleic acids by forming nanoscale complexes; however, there has been limited success in achieving high transfection efficiency. Our hypothesis is that a factor affecting gene delivery efficiency is the mechanical response of the condensed complex. To begin to test this hypothesis, we directly measured the mechanical properties of DNA-carrier complexes using optical tweezers. Histidine-lysine (HK) polymer, Asparagine-lysine (NK) polymer and poly-L-lysine were used to form complexes with a single DNA molecule. As carriers were introduced, a sudden decrease in DNA extension occurrs at a force level which is defined as critical force (Fc). Fc is carrier and concentration dependent. Pulling revealed reduction in DNA extension length for HK-DNA complexes. The characteristics of force profiles vary by agent and can be dynamically manipulated by changes in environmental conditions such as ionic strength of the buffer as well as pH. Heparin can remove cationic reagents which are otherwise irreversibly bound to DNA. The implications for optimizing molecular interactions to enhance transfection efficiency will be discussed.

Lee, Amy; Zheng, Tai; Sucayan, Sarah; Chou, Szu-Ting; Tricoli, Lucas; Hustedt, Jason; Kahn, Jason; Mixson, A. James; Seog, Joonil

2013-03-01

175

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

PubMed Central

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

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

2009-01-01

176

Transcriptomics Reveal Several Gene Expression Patterns in the Piezophile Desulfovibrio hydrothermalis in Response to Hydrostatic Pressure  

PubMed Central

RNA-seq was used to study the response of Desulfovibrio hydrothermalis, isolated from a deep-sea hydrothermal chimney on the East-Pacific Rise at a depth of 2,600 m, to various hydrostatic pressure growth conditions. The transcriptomic datasets obtained after growth at 26, 10 and 0.1 MPa identified only 65 differentially expressed genes that were distributed among four main categories: aromatic amino acid and glutamate metabolisms, energy metabolism, signal transduction, and unknown function. The gene expression patterns suggest that D. hydrothermalis uses at least three different adaptation mechanisms, according to a hydrostatic pressure threshold (HPt) that was estimated to be above 10 MPa. Both glutamate and energy metabolism were found to play crucial roles in these mechanisms. Quantitation of the glutamate levels in cells revealed its accumulation at high hydrostatic pressure, suggesting its role as a piezolyte. ATP measurements showed that the energy metabolism of this bacterium is optimized for deep-sea life conditions. This study provides new insights into the molecular mechanisms linked to hydrostatic pressure adaptation in sulfate-reducing bacteria. PMID:25215865

Amrani, Amira; Bergon, Aurelie; Holota, Helene; Tamburini, Christian; Garel, Marc; Ollivier, Bernard; Imbert, Jean; Dolla, Alain; Pradel, Nathalie

2014-01-01

177

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

PubMed Central

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

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

2014-01-01

178

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

PubMed Central

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 (Nb/Na) increased significantly despite sevenfold reduction of Na. 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

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

2014-01-01

179

Immunologic Evaluation of Immediate Hypersensitivity to Cefaclor  

PubMed Central

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

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

2014-01-01

180

Genetic Markers for Differentiating Aspirin-Hypersensitivity  

Microsoft Academic Search

The ingestion of acetylsalicylic acid (ASA) can induce allergic reactions such as ASA-intolerant asthma (AIA), ASA-induced\\u000a acute or chronic urticaria\\/angioedema (AIAU or AICU), anaphylaxis, and, in rare cases, hypersensitivity pneumonitis [1, 2].\\u000a Among these, AIA and AIU are most prevalent. Although the pathogenic mechanism of AIA is not completely understood, a chronic\\u000a overproduction of cysteinyl leukotrienes (Cys-LTs) derived from cyclooxygenase

Hae-Sim Park; Seung-Hyun Kim; Young-Min Ye; Gyu-Young Hur

181

Alleviating pain hypersensitivity through activation of type 4 metabotropic glutamate receptor.  

PubMed

Hyperactivity of the glutamatergic system is involved in the development of central sensitization in the pain neuraxis, associated with allodynia and hyperalgesia observed in patients with chronic pain. Herein we study the ability of type 4 metabotropic glutamate receptors (mGlu4) to regulate spinal glutamate signaling and alleviate chronic pain. We show that mGlu4 are located both on unmyelinated C-fibers and spinal neurons terminals in the inner lamina II of the spinal cord where they inhibit glutamatergic transmission through coupling to Cav2.2 channels. Genetic deletion of mGlu4 in mice alters sensitivity to strong noxious mechanical compression and accelerates the onset of the nociceptive behavior in the inflammatory phase of the formalin test. However, responses to punctate mechanical stimulation and nocifensive responses to thermal noxious stimuli are not modified. Accordingly, pharmacological activation of mGlu4 inhibits mechanical hypersensitivity in animal models of inflammatory or neuropathic pain while leaving acute mechanical perception unchanged in naive animals. Together, these results reveal that mGlu4 is a promising new target for the treatment of chronic pain. PMID:24285900

Vilar, Bruno; Busserolles, Jérôme; Ling, Bing; Laffray, Sophie; Ulmann, Lauriane; Malhaire, Fanny; Chapuy, Eric; Aissouni, Youssef; Etienne, Monique; Bourinet, Emmanuel; Acher, Francine; Pin, Jean-Philippe; Eschalier, Alain; Goudet, Cyril

2013-11-27

182

Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor ?-3 in colorectal afferents.  

PubMed

Irritable bowel syndrome is characterized by colorectal hypersensitivity and contributed to by sensitized mechanosensitive primary afferents and recruitment of mechanoinsensitive (silent) afferents. Neurotrophic factors are well known to orchestrate dynamic changes in the properties of sensory neurons. Although pain modulation by proteins in the glial cell line-derived neurotrophic factor (GDNF) family has been documented in various pathophysiological states, their role in colorectal hypersensitivity remains unexplored. Therefore, we investigated the involvement of the GDNF family receptor ?-3 (GFR?3) signaling in visceral hypersensitivity by quantifying visceromotor responses (VMR) to colorectal distension before and after intracolonic treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baseline responses to colorectal distension did not differ between C57BL/6 and GFR?3 knockout (KO) mice. Relative to intracolonic saline treatment, TNBS significantly enhanced the VMR to colorectal distension in C57BL/6 mice 2, 7, 10, and 14 days posttreatment, whereas TNBS-induced visceral hypersensitivity was significantly suppressed in GFR?3 KO mice. The proportion of GFR?3 immunopositive thoracolumbar and lumbosacral colorectal dorsal root ganglion neurons was significantly elevated 2 days after TNBS treatment. In single fiber recordings, responses to circumferential stretch of colorectal afferent endings in C57BL/6 mice were significantly increased (sensitized) after exposure to an inflammatory soup, whereas responses to stretch did not sensitize in GFR?3 KO mice. These findings suggest that enhanced GFR?3 signaling in visceral afferents may contribute to development of colorectal hypersensitivity. PMID:21193524

Tanaka, T; Shinoda, M; Feng, B; Albers, K M; Gebhart, G F

2011-03-01

183

Symptom hypersensitivity to acid infusion is associated with hypersensitivity of esophageal contractility.  

PubMed

Several investigators have observed that repeated acid infusions induce stronger symptoms (symptom hypersensitivity). The goal of our study was to determine whether symptom hypersensitivity is associated with esophageal contractile hypersensitivity. Subjects with chronic heartburn symptoms underwent simultaneous pressure and ultrasound imaging of esophagus. Normal saline and 0.1 N HCl were sequentially infused into the esophagus, and subjects scored heartburn symptoms on a 1-10 scale. Saline and HCl infusions were repeated in 10 subjects with a positive Bernstein test. Esophageal contraction amplitude and duration and muscularis propria thickness were measured using a computerized method during recording. Acid infusion induced heartburn. Esophageal contractions had higher amplitudes (pressure 114.2 +/- 7.0%) and longer duration (116.8 +/- 4.4%) during acid infusion compared with saline infusion. Average muscle thickness was greater during acid infusion than saline infusion (107.0 +/- 2.0%). Sustained esophageal contractions (SECs) were identified during acid infusion. A second acid infusion (acid-2) induced heartburn with shorter latency (93.0 +/- 15.0 vs. 317.0 +/- 43.0 s) and stronger severity (8.5 +/- 0.5 vs. 5.3 +/- 0.8) than the first acid infusion (acid-1). Contraction amplitudes (140.2 +/- 13.0%), average muscle thickness (118.0 +/- 3.3%), and contraction duration (148.5 +/- 5.6 vs. 116.8 +/- 4.4%) were higher during acid-2 than acid-1. Also, numbers of SECs were greater during acid-2 than acid-1 (31 in 8 subjects vs. 11 in 6 subjects). Our data show that acid infusion into esophagus induces esophageal hypersensitivity and that a close temporal correlation exists between symptom hypersensitivity and contractility hypersensitivity. PMID:14977636

Bhalla, Vikas; Liu, Jianmin; Puckett, James L; Mittal, Ravinder K

2004-07-01

184

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

USGS Publications Warehouse

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.

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

185

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) induced by isocyanates  

Microsoft Academic Search

Background: Chemical-induced hypersensitivity pneumonitis has been so far rarely described. The purpose of this study was to find out whether hypersensitivity pneumonitis is a common disorder in isocyanate workers. Methods: Company physicians' case histories of 1780 isocyanate workers were evaluated. In 16 subjects suspected of having isocyanate-induced hypersensitivity pneumonitis, chest x-ray films were made; levels of IgE and IgG antibodies

Xaver Baur

1995-01-01

186

Basement shower hypersensitivity pneumonitis secondary to Epicoccum nigrum.  

PubMed

Two children developed hypersensitivity pneumonitis after extensive exposure to an unventilated basement shower. Commercial precipitin panels were negative. After home inspection, individual mold species were isolated from the household and extracted. Precipitating antibodies to Epicoccum nigrum were found in both children. Resolution of the hypersensitivity pneumonitis occurred with avoidance and glucocorticosteroid therapy. E nigrum is a newly identified etiologic agent for hypersensitivity pneumonitis found in a mold-contaminated home. PMID:8797443

Hogan, M B; Patterson, R; Pore, R S; Corder, W T; Wilson, N W

1996-09-01

187

Probabilistic independent component analysis for laser speckle contrast images reveals in vivo multi - component vascular responses to forepaw stimulation.  

PubMed

Brain's functional response can be studied by observing the spatiotemporal dynamics of functional and structural changes in cerebral vasculature. However, very few studies explore detailed changes at the level of individual microvessels while revealing the simultaneous wide field view of microcirculation responses to functional stimulation. Here we use a high spatiotemporal resolution laser speckle contrast imaging method, in combination with probabilistic independent component analysis to reveal the changes of cerebral blood flow pattern in response to electrical forepaw stimulation in an anesthetized rat model. The proposed method is able to pick up the response of a single vessel down to approximately 20 microm diameter in a 4mm × 4mm field of view, and automatically extract response from multiple vascular components. Two main vascular components, arteriolar and capillary responses respectively, show significantly different temporal dynamics. Overall, the experimental results from five rats reveal that the specific arteriole branch proximal to the activation sites dilate prior consistently to the increase of blood flow in the capillaries with a latency time 0.91 ± 0.05s. The presented results provide novel microscopic scale evidence of the contribution of different vascular compartments in the hemodynamic response to neuronal activation. PMID:21096788

Li, Nan; Pelled, Galit; Thakor, Nitish V

2010-01-01

188

Cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma after dapsone-induced hypersensitivity syndrome.  

PubMed

A 36-year-old woman presented with erythematous confluent macules on her whole body with fever and chills associated with jaundice after 8 months of dapsone therapy. Her symptoms had developed progressively, and a physical examination revealed bilateral cervical lymphadenopathy and splenomegaly. Excisional biopsy of a cervical lymph node showed effacement of the normal architecture with atypical lymphoid hyperplasia and proliferation of high endothelial venules compatible with angioimmunoblastic T-cell lymphoma. However, it was assumed that the cervical lymphadenopathy was a clinical manifestation of a systemic hypersensitivity reaction because her clinical course was reminiscent of dapsone-induced hypersensitivity syndrome. A liver biopsy revealed drug-induced hepatitis with no evidence of lymphomatous involvement. Intravenous glucocorticoid was immediately initiated and her symptoms and clinical disease dramatically improved. The authors present an unusual case of cervical lymphadenopathy mimicking angioimmunoblastic T-cell lymphoma as an adverse reaction to dapsone. PMID:23323115

Rim, Min Young; Hong, Junshik; Yo, Inku; Park, Hyeonsu; Chung, Dong Hae; Ahn, Jeong Yeal; Park, Sanghui; Park, Jinny; Kim, Yun Soo; Lee, Jae Hoon

2012-12-01

189

LLLT in treating dentinary hypersensitivity: new concepts  

NASA Astrophysics Data System (ADS)

Dental hypersensitivity has been studied for several years and it is reported as a strikingly painful condition originating from the exposition of dentinal tubuli . The exposed area is subjected to several kinds of stimuli, resulting in a rapid sharp acute pain. LLLT has been shown to have antiinflammatory, analgesic and cellular effects in both hyperemia and inflammation of the dental pulp. Our previous histological study showed that irradiated animals presented an increased production of dentine and shutting of dentinal tubuli. On the other hand, non-irradiated subjects still showed signals of intense inflammatory reaction and even necrosis at the same experimental times. Irradiated teeth did not show cell degeneration. The LLLT was shown to be efficient in the stimulation of odontoblast cells, producing reparative dentin and closing dentin tubuli. Our clinical studies with 660nm, 790nm and 830nm diode laser, and the total dose per tooth of 4J/cm was shown effective in treating dentinal hypersensitivity as it quickly reduces pain and maintains a prolonged painless status in 91.27 % to 97% of the cases. In a recent study our team observed that significant levels of dentinal desensitization were only found in patients belonging to the 25-35 age group. In conclusion, the results demonstrated indeed that LLLT, when based on the use of correct irradiations parameters is effective in treating hypersensitivity, but the age of patients is one of the factors that may alter the success of treatment due to dentinal sclerosis, which makes the penetration of light more difficult.

Brugnera, Aldo, Jr.; Zanin, Fatima; Ladalardo, Thereza C.; Pinheiro, Antonio; Pecora, Jesus D.

2006-02-01

190

Glycerol Hypersensitivity in a Drosophila Model for Glycerol Kinase Deficiency Is Affected by Mutations in Eye Pigmentation Genes  

PubMed Central

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

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

2012-01-01

191

Trypanosomes lacking uracil-DNA glycosylase are hypersensitive to antifolates and present a mutator phenotype.  

PubMed

Cells contain low amounts of uracil in DNA which can be the result of dUTP misincorporation during replication or cytosine deamination. Elimination of uracil in the base excision repair pathway yields an abasic site, which is potentially mutagenic unless repaired. The Trypanosoma brucei genome presents a single uracil-DNA glycosylase responsible for removal of uracil from DNA. Here we establish that no excision activity is detected on U:G, U:A pairs or single-strand uracil-containing DNA in uracil-DNA glycosylase null mutant cell extracts, indicating the absence of back-up uracil excision activities. While procyclic forms can survive with moderate amounts of uracil in DNA, an analysis of the mutation rate and spectra in mutant cells revealed a hypermutator phenotype where the predominant events were GC to AT transitions and insertions. Defective elimination of uracil via the base excision repair pathway gives rise to hypersensitivity to antifolates and oxidative stress and an increased number of DNA strand breaks, suggesting the activation of alternative DNA repair pathways. Finally, we show that uracil-DNA glycosylase defective cells exhibit reduced infectivity in vivo demonstrating that efficient uracil elimination is important for survival within the mammalian host. PMID:22728162

Castillo-Acosta, Víctor M; Aguilar-Pereyra, Fernando; Vidal, Antonio E; Navarro, Miguel; Ruiz-Pérez, Luis M; González-Pacanowska, Dolores

2012-09-01

192

Pain and the defense response: structural equation modeling reveals a coordinated psychophysiological response to increasing painful stimulation.  

PubMed

The defense response theory implies that individuals should respond to increasing levels of painful stimulation with correlated increases in affectively mediated psychophysiological responses. This paper employs structural equation modeling to infer the latent processes responsible for correlated growth in the pain report, evoked potential amplitudes, pupil dilation, and skin conductance of 92 normal volunteers who experienced 144 trials of three levels of increasingly painful electrical stimulation. The analysis assumed a two-level model of latent growth as a function of stimulus level. The first level of analysis formulated a nonlinear growth model for each response measure, and allowed intercorrelations among the parameters of these models across individuals. The second level of analysis posited latent process factors to account for these intercorrelations. The best-fitting parsimonious model suggests that two latent processes account for the correlations. One of these latent factors, the activation threshold, determines the initial threshold response, while the other, the response gradient, indicates the magnitude of the coherent increase in response with stimulus level. Collectively, these two second-order factors define the defense response, a broad construct comprising both subjective pain evaluation and physiological mechanisms. PMID:12620601

Donaldson, Gary W; Chapman, C Richard; Nakamura, Yoshi; Bradshaw, David H; Jacobson, Robert C; Chapman, Christopher N

2003-03-01

193

Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity  

PubMed Central

Bioactivation of sulphamethoxazole (SMX) to chemically-reactive metabolites and subsequent protein conjugation is thought to be involved in SMX hypersensitivity. We have therefore examined the cellular metabolism, disposition and conjugation of SMX and its metabolites in vitro. Flow cytometry revealed binding of N-hydroxy (SMX-NHOH) and nitroso (SMX-NO) metabolites of SMX, but not of SMX itself, to the surface of viable white blood cells. Cellular haptenation by SMX-NO was reduced by exogenous glutathione (GSH). SMX-NHOH and SMX-NO were rapidly reduced back to the parent compound by cysteine (CYS), GSH, human peripheral blood cells and plasma, suggesting that this is an important and ubiquitous bioinactivation mechanism. Fluorescence HPLC showed that SMX-NHOH and SMX-NO depleted CYS and GSH in buffer, and to a lesser extent, in cells and plasma. Neutrophil apoptosis and inhibition of neutrophil function were induced at lower concentrations of SMX-NHOH and SMX-NO than those inducing loss of membrane viability, with SMX having no effect. Lymphocytes were significantly (P<0.05) more sensitive to the direct cytotoxic effects of SMX-NO than neutrophils. Partitioning of SMX-NHOH into red blood cells was significantly (P<0.05) lower than with the hydroxylamine of dapsone. Our results suggest that the balance between oxidation of SMX to its toxic metabolites and their reduction is an important protective cellular mechanism. If an imbalance exists, haptenation of the toxic metabolites to bodily proteins including the surface of viable cells can occur, and may result in drug hypersensitivity. PMID:10217534

Naisbitt, Dean J; Hough, Sally J; Gill, Helen J; Pirmohamed, Munir; Kitteringham, Neil R; Park, B Kevin

1999-01-01

194

Does an Insect's Unconditioned Response to Sucrose Reveal Expectations of Reward?  

E-print Network

to Sucrose Reveal Expectations of Reward?. PLoS ONE 3(7): e2810. doi:10.1371/journal.pone.0002810 Editor of reward. Further experiments will aim to elucidate the neural substrates underlying reward anticipation

Menzel, Randolf - Institut für Biologie

195

Delayed hypersensitivity to one low-molecular-weight heparin with tolerance of other low-molecular-weight heparins.  

PubMed

We report a patient who developed infiltrated plaques at the sites of subcutaneous injection of a low-molecular-weight heparin. Skin tests and a lymphocyte transformation test revealed hypersensitivity to sandoparin and heparin sodium. The low-molecular-weight heparins nadroparin and dalteparin were subsequently tolerated without adverse effects. Possible risk factors for sensitization are discussed. PMID:7718467

Bircher, A J; Itin, P H; Tsakiris, D A; Surber, C

1995-03-01

196

The Pupillary Light Response Reveals the Focus of Covert Visual Attention  

PubMed Central

The pupillary light response is often assumed to be a reflex that is not susceptible to cognitive influences. In line with recent converging evidence, we show that this reflexive view is incomplete, and that the pupillary light response is modulated by covert visual attention: Covertly attending to a bright area causes a pupillary constriction, relative to attending to a dark area under identical visual input. This attention-related modulation of the pupillary light response predicts cuing effects in behavior, and can be used as an index of how strongly participants attend to a particular location. Therefore, we suggest that pupil size may offer a new way to continuously track the focus of covert visual attention, without requiring a manual response from the participant. The theoretical implication of this finding is that the pupillary light response is neither fully reflexive, nor under complete voluntary control, but is instead best characterized as a stereotyped response to a voluntarily selected target. In this sense, the pupillary light response is similar to saccadic and smooth pursuit eye movements. Together, eye movements and the pupillary light response maximize visual acuity, stabilize visual input, and selectively filter visual information as it enters the eye. PMID:24205144

Mathot, Sebastiaan; van der Linden, Lotje; Grainger, Jonathan; Vitu, Francoise

2013-01-01

197

Journal of Insect Physiology 54 (2008) 645655 Metabolomics reveals unique and shared metabolic changes in response  

E-print Network

changes in response to heat shock, freezing and desiccation in the Antarctic midge, Belgica antarctica M The midge, Belgica antarctica Jacobs, is subjected to numerous environmental stressors during its 2-year overview of changes in energy metabolism, amino acids, and polyols in response to three of the midge

Lee Jr., Richard E.

198

Pharmacogenetics of antiepileptic drug-induced hypersensitivity.  

PubMed

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

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

2014-04-01

199

Fasting mitigates immediate hypersensitivity: a pivotal role of endogenous D-beta-hydroxybutyrate  

PubMed Central

Background Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Methods Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca2+]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Results Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24 hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca2+]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. Conclusions The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in suppression of hypersensitivity reaction.

2014-01-01

200

Influence of PUVA and UVB radiation on delayed hypersensitivity in the guinea pig  

SciTech Connect

Exposure of guinea pigs to UVA (320--400 nm) radiation following administration of 8-methoxypsoralen by gavage (referred to by the acronym, PUVA) or exposure to UVB (290--320 nm) radiation, produced suppression of the cutaneous delayed hypersensitivity reaction at the site of exposure to radiation and at distant nonexposed sites. In these experiments, the animals were immunized by injection of dinitrophenyl-bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant and delayed hypersensitivity responses were provoked by intradermal injections of DNP-BGG, DNP and BGG on the flanks. Exposure to erythemogenic doses of either PUVA or UVB radiation for 7 days prior to immunization and for the 7 days between immunization and challenge (total period of radiation: 14 days) produced inhibiton of responses to each of the test substances. In addition, treatment with erythemogenic doses of PUVA either for 7 days prior to immunization or during the interval between immunization and challenge with DNP-BGG, inhibited the delayed hypersensitivity responses at the site of irradiation and at a nonexposed site. These findings suggest that in vivo exposure to nonionizing radiation leads to both local and systemic alteration of certain immune responses.

Morison, W.L.; Parrish, J.A.; Woehler, M.E.; Krugler, J.I.; Bloch, K.J.

1981-06-01

201

Evaluation of hypersensitivity to microencapsulated ampicillin in guinea pigs  

Microsoft Academic Search

The purpose of this study was to determine if the sustained release of ampicillin from a biodegradable drug-delivery system (microencapsulated ampicillin anhydrate (MEAA)) will increase or decrease the intensity of a hypersensitivity reaction compared with that observed with free drug. Ovalbumin, which is known to elicit a marked hypersensitivity reaction in guinea pigs, and microencapsulated ovalbumin (MOVA) were tested in

I. S. Barsoum; K. M. Kopydlowski; P. Cuenin; J. A. Setterstrom

1997-01-01

202

Immune complex glomerulopathy in a child with food hypersensitivity  

Microsoft Academic Search

Immune complex glomerulopathy in a child with food hypersensitivity. This report describes the occurrence of immune complex glomerulonephritis in a patient with eosinophilic gastroenteritis and food hypersensitivity. A coincident allergen injection may have been a contributing factor in the sudden development ofthe nephrotic syndrome. Markedly elevated levels of circulating immune complexes (greater than 6400 mg\\/dl) were found containing kappa–casein and

Wallace W McCrory; Carl G Becker; Renate F Klein; Janet Mouradian; Lewis Reisman

1986-01-01

203

[Type IV of hypersensitivity and its subtypes].  

PubMed

Type IV of hypersensitivity reaction is usually manifested in the skin in different clinical pattern. According to traditional Gell and Coombs classification, the mechanism of IV type of allergic reaction has been associated with contact allergy with the activity of lymphocytes Th1 secreting interferon gamma. Now, this vision seems to be too simplified. In the last years there were publications, which can throw a new light on these complicated mechanisms leading to the development of the type IV of allergy, especially to drugs, nickel and other haptens and also can explain the differentiation of clinical pattern in respective patients. The skin symptoms in type IV of hypersensitivity are triggered by activation of specific T-cell CD4+ and CD8+. Immunohistochemical and functional analysis of reactive T-cell has shown that the delayed hypersensitivity reaction depends on the secreted cytokines. For example maculo-papular exanthema may be either triggered by Th1 or Th2 in nature and cytokines interferon gamma, tumor necrosis factor alfa or interleukin-4, 5 and 13. Bullous reactions (i.e. Stevens-Johnsons Syndrome or toxic epidermal necrolysis) are characterized by widespread keratinocyte apoptosis, a consequence of high CD8+ T-cell involvement and the molecular cytotoxicity of Fas, perforin and granzyme B. Pustular exanthema reactions are stimulated via the T-cell release of 11-8 and granulocyte-monocyte colony-stimulatig factor (GM-CSF). For the better understanding of these inflammatory cascades deleted type IV of hypersensitivity reactions have been re-classified into four main subtypes: 1. IVa with Th1 and monocyte directed and cytokines: IFNgamma, IL-1, IL-2, 2. IVb with Th2 and eosinophils directed and cytokines: L-5, IL-4, IL-13, 3. IVc with T CD8+ directed and cytokines: perforin, granzyme B, Fas Ligand, 4. IVd with T CD4+, CD8+ and neutrophil directed and cytokines: IL8, GM-CSF. Clinically delayed hypersensitivity eruptions are often an overlap of cytokine pathways, with one preferential reaction dominating the final picture. Type IVa and IVc play a role inthe mechanism of contact dermatitis, however type IV b in chronic asthma, chronic allergic rhinitis and maculo-papular exanthema with eosinophilia, type IV c in bullous reactions (i.e. Stevens-Johnsons Syndrome or toxic epidermal necrolysis), so type IV d in pustular exanthema reactions (i.g. AGEP - Acute Generalized Exanthematosus Pustule, Behcet disease). This different clinical pattern of allergic disease mainly including drug allergy to nickel and other haptens as well as chronic asthma and allergic rhinitis may be explained by above mechanisms. The study of different mechanisms of four subtypes of type IVof allergic reaction may be helpful in the differential diagnostics and in the treatment of allergic diseases. PMID:18409354

Czarnobilska, Ewa; Obtu?owicz, Krystyna; Wso?ek, Katarzyna

2007-01-01

204

Global transcription profiling reveals differential responses to chronic nitrogen stress and putative nitrogen regulatory components in Arabidopsis  

PubMed Central

Background A large quantity of nitrogen (N) fertilizer is used for crop production to achieve high yields at a significant economic and environmental cost. Efforts have been directed to understanding the molecular basis of plant responses to N and identifying N-responsive genes in order to manipulate their expression, thus enabling plants to use N more efficiently. No studies have yet delineated these responses at the transcriptional level when plants are grown under chronic N stress and the understanding of regulatory elements involved in N response is very limited. Results To further our understanding of the response of plants to varying N levels, a growth system was developed where N was the growth-limiting factor. An Arabidopsis whole genome microarray was used to evaluate global gene expression under different N conditions. Differentially expressed genes under mild or severe chronic N stress were identified. Mild N stress triggered only a small set of genes significantly different at the transcriptional level, which are largely involved in various stress responses. Plant responses were much more pronounced under severe N stress, involving a large number of genes in many different biological processes. Differentially expressed genes were also identified in response to short- and long-term N availability increases. Putative N regulatory elements were determined along with several previously known motifs involved in the responses to N and carbon availability as well as plant stress. Conclusion Differentially expressed genes identified provide additional insights into the coordination of the complex N responses of plants and the components of the N response mechanism. Putative N regulatory elements were identified to reveal possible new components of the regulatory network for plant N responses. A better understanding of the complex regulatory network for plant N responses will help lead to strategies to improve N use efficiency. PMID:17705847

Bi, Yong-Mei; Wang, Rong-Lin; Zhu, Tong; Rothstein, Steven J

2007-01-01

205

Distinct roles of the pepper hypersensitive induced reaction protein gene CaHIR1 in disease and osmotic stress, as determined by comparative transcriptome and proteome analyses  

Microsoft Academic Search

A Capsicum \\u000a annuum hypersensitive induced reaction protein1 (CaHIR1) was recently proposed as a positive regulator of hypersensitive cell death\\u000a in plants. Overexpression of CaHIR1 in transgenic Arabidopsis plants conferred enhanced resistance against the hemi-biotrophic Pseudomonas syringae pv. tomato (Pst) and the biotrophic Hyaloperonospora parasitica. Infection by avirulent Pseudomonas strains carrying avrRpm1 or avrRpt2 caused enhanced resistance responses in transgenic plants,

Ho Won Jung; Chae Woo Lim; Sung Chul Lee; Hyong Woo Choi; Cheol Ho Hwang; Byung Kook Hwang

2008-01-01

206

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

Microsoft Academic Search

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

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

207

Selective visual responses to expansion and rotation in the human MT complex revealed by functional magnetic  

E-print Network

sensitivity to optic flow in the human occipital cortex using an event-related functional magnetic resonance, a technique has recently been developed that allows the disentanglement of responses from functi

Royal Holloway, University of London

208

Common garden experiments reveal uncommon responses across temperatures, locations, and species of ants  

E-print Network

of ants Shannon L. Pelini1,2 , Sarah E. Diamond3 , Heidi MacLean4 , Aaron M. Ellison1 , Nicholas J and spatial variation in responses to warming. Such experiments are useful for deter- mining if geographically

Sanders, Nathan J.

209

ResponseNet: revealing signaling and regulatory networks linking genetic and transcriptomic screening data  

E-print Network

Cellular response to stimuli is typically complex and involves both regulatory and metabolic processes. Large-scale experimental efforts to identify components of these processes often comprise of genetic screening and ...

Lan, Alex

210

ResponseNet: revealing signaling and regulatory networks linking genetic transcriptomic screening data  

E-print Network

Cellular response to stimuli is typically complex and involves both regulatory and metabolic processes. Large-scale experimental efforts to identify components of these processes often comprise of genetic screening and ...

Lan, Alex

211

BCL-2 family genetic profiling reveals microenvironment-specific determinants of chemotherapeutic response  

E-print Network

The Bcl-2 family encompasses a diverse set of apoptotic regulators that are dynamically activated in response to various cell-intrinsic and -extrinsic stimuli. An extensive variety of cell culture experiments have identified ...

Pritchard, Justin Robert

212

Ultraviolet-Irradiated Urocanic Acid Suppresses Delayed-Type Hypersensitivity to Herpes Simplex Virus in Mice  

Microsoft Academic Search

Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting

James A. Ross; Sarah E. M. Howie; Mary Norval; Jean Maingay; Thomas J. Simpson

1986-01-01

213

[Stress-induced changes of hypothalamic structure cell responses to antigen injection (LPS) (revealed by c-Fos protein expression)].  

PubMed

Stress stimuli are known to influence the intensity if immune response. To elucidate the role of central regulating structures in this changes, analysis of activation level of hypothalamic neurons (revealed by quantity of c-Fos-positive cells) was carried out in rats within 2 hours after intravenous LPS injection and after this--impact associated with electric pain stimulation (EPS). The investigation was carried out in 52 male Wistar rats, 200-250 g. The c-Fos protein expression was analyzed with immunohistochemical method. The increase of c-Fos-positive cells number in 2 hours after LPS injection was observed in AFTN, PVH, LHA, VMH, DMH and PH. After electrical pain stimulation, the quantity of c-Fos-positive cells increased in the same structures. Combined application of electric pain stimulation and LPS injection results in diminished activation level in AHN, PVH, LHA and VMH as compared with typical response to single LPS injection without EPS. The EPS suppresses intensity of the immune response induced by injection of LPS (revealed by local hemolysis method with calculation of antibody-forming cells quantity (%) in the rat spleen). Thus the activation level changes of hypothalamic structures (AHN, PVH, LHA, PH) correlate with development of stress-induced immunosuppression, i. e. morphofunctional description of hypothalamic structures activation as revealed by pattern of activated cell alterations in hypothalamic structures during realization of stress-induced changes of immune system responses to antigen injection. PMID:17385422

Gavrilov, Iu V; Perekrest, S V; Novikova, N S; Korneva, E A

2006-11-01

214

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

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

215

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

PubMed Central

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

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

2013-01-01

216

Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes.  

PubMed

A differential response to sound frequency is a fundamental property of auditory neurons. Frequency analysis in the cochlea gives rise to V-shaped tuning functions in auditory nerve fibres, but by the level of the inferior colliculus (IC), the midbrain nucleus of the auditory pathway, neuronal receptive fields display diverse shapes that reflect the interplay of excitation and inhibition. The origin and nature of these frequency receptive field types is still open to question. One proposed hypothesis is that the frequency response class of any given neuron in the IC is predominantly inherited from one of three major afferent pathways projecting to the IC, giving rise to three distinct receptive field classes. Here, we applied subjective classification, principal component analysis, cluster analysis, and other objective statistical measures, to a large population (2826) of frequency response areas from single neurons recorded in the IC of the anaesthetised guinea pig. Subjectively, we recognised seven frequency response classes (V-shaped, non-monotonic Vs, narrow, closed, tilt down, tilt up and double-peaked), that were represented at all frequencies. We could identify similar classes using our objective classification tools. Importantly, however, many neurons exhibited properties intermediate between these classes, and none of the objective methods used here showed evidence of discrete response classes. Thus receptive field shapes in the IC form continua rather than discrete classes, a finding consistent with the integration of afferent inputs in the generation of frequency response areas. The frequency disposition of inhibition in the response areas of some neurons suggests that across-frequency inputs originating at or below the level of the IC are involved in their generation. PMID:23753527

Palmer, Alan R; Shackleton, Trevor M; Sumner, Christian J; Zobay, Oliver; Rees, Adrian

2013-08-15

217

Stem transcriptome reveals mechanisms to reduce the energetic cost of shade-avoidance responses in tomato.  

PubMed

While the most conspicuous response to low red/far-red ratios (R:FR) of shade light perceived by phytochrome is the promotion of stem growth, additional, less obvious effects may be discovered by studying changes in the stem transcriptome. Here, we report rapid and reversible stem transcriptome responses to R:FR in tomato (Solanum lycopersicum). As expected, low R:FR promoted the expression of growth-related genes, including those involved in the metabolism of cell wall carbohydrates and in auxin responses. In addition, genes involved in flavonoid synthesis, isoprenoid metabolism, and photosynthesis (dark reactions) were overrepresented in clusters showing reduced expression in the stem of low R:FR-treated plants. Consistent with these responses, low R:FR decreased the levels of flavonoids (anthocyanin, quercetin, kaempferol) and selected isoprenoid derivatives (chlorophyll, carotenoids) in the stem and severely reduced the photosynthetic capacity of this organ. However, lignin contents were unaffected. Low R:FR reduced the stem levels of jasmonate, which is a known inducer of flavonoid synthesis. The rate of stem respiration was also reduced in low R:FR-treated plants, indicating that by downsizing the stem photosynthetic apparatus and the levels of photoprotective pigments under low R:FR, tomato plants reduce the energetic cost of shade-avoidance responses. PMID:22872775

Cagnola, Juan Ignacio; Ploschuk, Edmundo; Benech-Arnold, Tomás; Finlayson, Scott A; Casal, Jorge José

2012-10-01

218

Experimental stroke-induced changes in the bone marrow reveal complex regulation of leukocyte responses.  

PubMed

Stroke induces a systemic response that involves rapid activation of inflammatory cascades, followed later by immunodepression. Experimental stroke-induced responses in the bone marrow, which is the primary source of circulating monocytes and granulocytes, have not been investigated previously. We show that cerebral ischaemia induced early (4 ?hours) release of CXCR2-positive granulocytes from the bone marrow, which was associated with rapid systemic upregulation of CXCL1 (a ligand for CXCR2) and granulocyte-colony-stimulating factor, a key cytokine involved in the mobilisation of bone marrow leukocytes. This process involves rapid activation of nuclear factor-?B and p38 mitogen-activated protein kinase in bone marrow myeloid cells. T-cell numbers in the bone marrow increased after stroke, and bone marrow cells did not show suppressed cytokine response to bacterial endotoxin stimulation in vitro. Stroke-induced laterality observed in the brain stem and in the bone marrow indicates direct involvement of the autonomic nervous system in stroke-induced cell mobilisation. We also show that systemic inflammatory changes and leukocyte responses in the bone marrow are profoundly affected by both anaesthetic and surgical stress. We conclude that stroke influences leukocyte responses in the bone marrow through multiple mechanisms and suggest that preclinical studies should take into consideration the effect of surgical manipulation in experimental models of stroke. PMID:21045863

Denes, Adam; McColl, Barry W; Leow-Dyke, Sophie F; Chapman, Katie Z; Humphreys, Neil E; Grencis, Richard K; Allan, Stuart M; Rothwell, Nancy J

2011-04-01

219

A novel single-cell screening platform reveals proteome plasticity during yeast stress responses  

PubMed Central

Uncovering the mechanisms underlying robust responses of cells to stress is crucial for our understanding of cellular physiology. Indeed, vast amounts of data have been collected on transcriptional responses in Saccharomyces cerevisiae. However, only a handful of pioneering studies describe the dynamics of proteins in response to external stimuli, despite the fact that regulation of protein levels and localization is an essential part of such responses. Here we characterized unprecedented proteome plasticity by systematically tracking the localization and abundance of 5,330 yeast proteins at single-cell resolution under three different stress conditions (DTT, H2O2, and nitrogen starvation) using the GFP-tagged yeast library. We uncovered a unique “fingerprint” of changes for each stress and elucidated a new response arsenal for adapting to radical environments. These include bet-hedging strategies, organelle rearrangement, and redistribution of protein localizations. All data are available for download through our online database, LOQATE (localization and quantitation atlas of yeast proteome). PMID:23509072

Breker, Michal; Gymrek, Melissa

2013-01-01

220

Development and transfer of immediate cutaneous hypersensitivity in mice exposed to aerosolized antigen.  

PubMed Central

We previously showed that BALB/c mice sensitized to ovalbumin (OVA) by brief daily inhalations of antigen over 10 consecutive days exhibit elevated antigen-specific serum IgE antibody levels and increased airways responsiveness. For the first time, we now show that animals sensitized in this fashion to either OVA or ragweed (RGW) develop immediate hypersensitivity skin test reactions when challenged 2 d after completion of the sensitization protocol. Skin testing, performed by direct assessment of wheal formation after intradermal injection of allergen, was sensitive and specific, since animals exposed to RGW by inhalation only responded to RGW, and OVA-sensitized animals responded only to OVA. Positive reactions were associated with mast cell degranulation, whereas control injections were not. Since only sensitized IgE high responder BALB/c mice but neither nonsensitized BALB/c mice nor OVA-sensitized IgE low responder SJL/J mice exhibited wheal responses, induction of OVA-specific IgE appeared to be essential for the mediation of OVA-specific immediate hypersensitivity reactions of the skin in this model. Passive cutaneous anaphylaxis (PCA) testing confirmed the presence of antigen-specific IgE in the serum. Mice that developed IgG (predominantly IgG2b) anti-OVA antibodies did not respond to OVA injection, indicating that OVA-specific IgG was not involved in this system. Further support for the role of IgE in the immediate hypersensitivity response included the wheal response to intradermal injection of anti-IgE antibody that occurred in OVA- and RGW-sensitized mice at 10-fold lower concentrations than in nonsensitized BALB/c mice and not in sensitized SJL/J mice. After transfer of mononuclear cells from peribronchial lymph nodes of OVA- or RGW-sensitized BALB/c mice, naive, syngeneic recipients developed antigen-specific IgE and specific immediate hypersensitivity responses, indicating that the local lymphoid tissue at the site of sensitization can transfer responsiveness to these allergens. These results demonstrate for the first time the ability to elicit and study IgE-mediated immediate skin hypersensitivity responses in the mouse and illustrate the association of increased antigen-specific and total serum IgE levels, airways hyperresponsiveness, and antigen-specific immediate cutaneous reactivity after sensitization to allergen via the airways. Images PMID:8423213

Saloga, J; Renz, H; Lack, G; Bradley, K L; Greenstein, J L; Larsen, G; Gelfand, E W

1993-01-01

221

Metabolomics Reveals Amino Acids Contribute to Variation in Response to Simvastatin Treatment  

PubMed Central

Statins are widely prescribed for reducing LDL-cholesterol (C) and risk for cardiovascular disease (CVD), but there is considerable variation in therapeutic response. We used a gas chromatography-time-of-flight mass-spectrometry-based metabolomics platform to evaluate global effects of simvastatin on intermediary metabolism. Analyses were conducted in 148 participants in the Cholesterol and Pharmacogenetics study who were profiled pre and six weeks post treatment with 40 mg/day simvastatin: 100 randomly selected from the full range of the LDL-C response distribution and 24 each from the top and bottom 10% of this distribution (“good” and “poor” responders, respectively). The metabolic signature of drug exposure in the full range of responders included essential amino acids, lauric acid (p<0.0055, q<0.055), and alpha-tocopherol (p<0.0003, q<0.017). Using the HumanCyc database and pathway enrichment analysis, we observed that the metabolites of drug exposure were enriched for the pathway class amino acid degradation (p<0.0032). Metabolites whose change correlated with LDL-C lowering response to simvastatin in the full range responders included cystine, urea cycle intermediates, and the dibasic amino acids ornithine, citrulline and lysine. These dibasic amino acids share plasma membrane transporters with arginine, the rate-limiting substrate for nitric oxide synthase (NOS), a critical mediator of cardiovascular health. Baseline metabolic profiles of the good and poor responders were analyzed by orthogonal partial least square discriminant analysis so as to determine the metabolites that best separated the two response groups and could be predictive of LDL-C response. Among these were xanthine, 2-hydroxyvaleric acid, succinic acid, stearic acid, and fructose. Together, the findings from this study indicate that clusters of metabolites involved in multiple pathways not directly connected with cholesterol metabolism may play a role in modulating the response to simvastatin treatment. Trial Registration ClinicalTrials.gov NCT00451828 PMID:22808006

Wikoff, William R.; Baillie, Rebecca A.; Zeng, Zhao-Bang; Karp, Peter D.; Fiehn, Oliver; Krauss, Ronald M.; Kaddurah-Daouk, Rima

2012-01-01

222

Ion Irradiation as a Tool to Reveal the Spatiotemporal Dynamics of DNA Damage Response Processes  

Microsoft Academic Search

In response to genotoxic exposure, mammalian cells have developed efficient DNA\\u000a repair and cell-cycle checkpoint mechanisms that allow coping with both endogenous\\u000a and exogenous sources of DNA damage. Imaging approaches to visualize the dynamics of\\u000a repair-related proteins at locally restricted regions of DNA damage have\\u000a substantially contributed to the understanding of the biochemical processes involved\\u000a in these damage response pathways.

Gisela Taucher-Scholz; Burkhard Jakob

223

Dynamics of cellular response to hypotonic stimulation revealed by quantitative phase microscopy and multi-fractal detrended fluctuation analysis  

NASA Astrophysics Data System (ADS)

Hypotonic stimulation is known to cause morphological changes in cells and also leads to modulation of cellular physiology. In order to evaluate the dynamics of cellular response to hypotonic stimulation, we utilized digital holographic microscopy for quantitative phase microscopy, achieved by a common-path interferometry geometry based on extraction of reference beam by spatial-filtering. Results from live cell investigations demonstrate the capability of this method for dynamic quantitative phase imaging. Further, wavelet and multi-fractal detrended fluctuation analysis revealed that the dynamic phase changes, in response to hypotonic stimulation, are multifractal in nature.

Cardenas, Nelson; Kumar, Satish; Mohanty, Samarendra

2012-11-01

224

Pain hypersensitivity mechanisms at a glance  

PubMed Central

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

Gangadharan, Vijayan; Kuner, Rohini

2013-01-01

225

Current Understanding of Delayed Anticonvulsant Hypersensitivity Reactions  

PubMed Central

Hypersensitivity syndrome (HSS) reactions are one of the most feared idiosyncratic drug reactions and are most common with exposure to antiepileptic drugs (AEDs), sulfonamides, nonsteroidal antiinflammatory drugs, corticosteroids, and allopurinol. HSS is associated with chemotoxic and T-cell–mediated inflammatory injuries in barrier tissue systems that contain cytochrome oxidases (e.g., skin, mucosa, liver, and lungs) and can be seen as a derangement in the defense system against xenobiotics—bioactive foreign molecules. The mechanisms for anticonvulsant HSS are incompletely understood but involve genetic susceptibility, with accumulation of AEDs and oxidized metabolites causing major histocompatibility complex (MHC) and non–MHC–dependent clonal activation of T cells and subsequent cytokine/chemokine production in T cells, keratinocytes, and other target cells. This review discusses the classification and possible mechanisms for anticonvulsant HSS. PMID:16604195

Krauss, Gregory

2006-01-01

226

Microarray analysis of Pseudomonas aeruginosa reveals induction of pyocin genes in response to hydrogen peroxide  

Microsoft Academic Search

BACKGROUND: Pseudomonas aeruginosa, a pathogen infecting those with cystic fibrosis, encounters toxicity from phagocyte-derived reactive oxidants including hydrogen peroxide during active infection. P. aeruginosa responds with adaptive and protective strategies against these toxic species to effectively infect humans. Despite advances in our understanding of the responses to oxidative stress in many specific cases, the connectivity between targeted protective genes and

Wook Chang; David A Small; Freshteh Toghrol; William E Bentley

2005-01-01

227

Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response.  

PubMed

Arginine phosphorylation is an emerging protein modification implicated in the general stress response of Gram-positive bacteria. The modification is mediated by the arginine kinase McsB, which phosphorylates and inactivates the heat shock repressor CtsR. In this study, we developed a mass spectrometric approach accounting for the peculiar chemical properties of phosphoarginine. The improved methodology was used to analyze the dynamic changes in the Bacillus subtilis arginine phosphoproteome in response to different stress situations. Quantitative analysis showed that a B. subtilis mutant lacking the YwlE arginine phosphatase accumulated a strikingly large number of arginine phosphorylations (217 sites in 134 proteins), however only a minor fraction of these sites was increasingly modified during heat shock or oxidative stress. The main targets of McsB-mediated arginine phosphorylation comprise central factors of the stress response system including the CtsR and HrcA heat shock repressors, as well as major components of the protein quality control system such as the ClpCP protease and the GroEL chaperonine. These findings highlight the impact of arginine phosphorylation in orchestrating the bacterial stress response. PMID:24263382

Schmidt, Andreas; Trentini, Débora Broch; Spiess, Silvia; Fuhrmann, Jakob; Ammerer, Gustav; Mechtler, Karl; Clausen, Tim

2014-02-01

228

Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses  

Microsoft Academic Search

The fate of cells exposed to ionizing radiation (IR) may depend greatly on changes in gene expression, so that an improved view of gene induction profiles is important for understanding mechanisms of checkpoint control, repair and cell death following such exposures. We have used a quantitative fluorescent cDNA microarray hybridization approach to identify genes regulated in response to ?-irradiation in

Sally A Amundson; Mike Bittner; Yidong Chen; Jeffrey Trent; Paul Meltzer; Albert J Fornace

1999-01-01

229

Pharmacological Stimulation of Locus Coeruleus Reveals a New Antipsychotic-Responsive Pathway for Deficient Sensorimotor Gating  

Microsoft Academic Search

Surprisingly little is known about the modulation of core endophenotypes of psychiatric disease by discrete noradrenergic (NE) circuits. Prepulse inhibition (PPI), the diminution of startle responses when weak prestimuli precede the startling event, is a widely validated translational paradigm for information-processing deficits observed in several mental disorders including schizophrenia, Tourette's syndrome, and post-traumatic stress disorder (PTSD). Despite putative NE disturbances

Karen M Alsene; Vaishali P Bakshi

2011-01-01

230

How We Know It Hurts: Item Analysis of Written Narratives Reveals Distinct Neural Responses to Others'  

E-print Network

of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United of the ``Shared Pain network'' identified using a separate data set, responses to others' physical pain, or even who just read this brief verbal description of the event, respond to two distinct (though related

Saxe, Rebecca

231

Dissecting a Role for Melanopsin in Behavioural Light Aversion Reveals a Response Independent of Conventional Photoreception  

Microsoft Academic Search

Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA) is a well-documented but poorly understood phenomenon during which animals

Ma'ayan Semo; Carlos Gias; Ahmad Ahmado; Eriko Sugano; Annette E. Allen; Jean M. Lawrence; Hiroshi Tomita; Peter J. Coffey; Anthony A. Vugler; Steven Barnes

2010-01-01

232

Effect of a single UVB or PUVA exposure on immediate and delayed skin hypersensitivity reactions in humans  

Microsoft Academic Search

A single UVB or PUVA exposure given 4 days prior to skin testing affected skin responses both to contact allergens and to histamine and the histamine liberator, compound 48\\/80. The delayed contact hypersensitivity reactions were attenuated by UVB in 75% and by PUVA in 79% of the tests. The immediate skin reactions to histamine and compound 48\\/80 were diminished by

K. Kalimo; L. Koulu; C. T. Jansén

1983-01-01

233

An Unbiased Genetic Screen Reveals the Polygenic Nature of the Influenza Virus Anti-Interferon Response  

PubMed Central

ABSTRACT Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space. IMPORTANCE In natural virus infections, the production of interferons leads to an antiviral state in cells that effectively limits virus replication. The interferon response places considerable selection pressure on viruses, and they have evolved a variety of ways to evade it. Although the influenza virus NS1 protein is a powerful interferon antagonist, the contributions of other viral genes to interferon evasion have not been well characterized. Here, we examined the effects of alleviating the selection pressure exerted by interferon by serially passaging influenza viruses in cells unable to respond to interferon. Viruses that grew to high titers had mutations at many normally conserved positions in nearly all genes and were not restricted to the NS1 gene. Our results demonstrate that influenza viruses have fine-tuned their entire genomes to evade the interferon response, and by removing interferon-mediated constraints, viruses can mutate at genome positions normally restricted by the interferon response. PMID:24574395

Perez-Cidoncha, Maite; Killip, Marian J.; Oliveros, Juan C.; Asensio, Victor J.; Fernandez, Yolanda; Bengoechea, Jose A.; Randall, Richard E.

2014-01-01

234

Temporal dynamics reveal atypical brain response to social exclusion in autism  

PubMed Central

Despite significant social difficulties, children with autism spectrum disorder (ASD) are vulnerable to the effects of social exclusion. We recorded EEG while children with ASD and typical peers played a computerized game involving peer rejection. Children with ASD reported ostracism-related distress comparable to typically developing children. Event-related potentials (ERPs) indicated a distinct pattern of temporal processing of rejection events in children with ASD. While typically developing children showed enhanced response to rejection at a late slow wave indexing emotional arousal and regulation, those with autism showed attenuation at an early component, suggesting reduced engagement of attentional resources in the aversive social context. Results emphasize the importance of studying the time course of social information processing in ASD; they suggest distinct mechanisms subserving similar overt behavior and yield insights relevant to development and implementation of targeted treatment approaches and objective measures of response to treatment. PMID:21731598

McPartland, James C.; Crowley, Michael J.; Perszyk, Danielle R.; Naples, Adam; Mukerji, Cora E.; Wu, Jia; Molfese, Peter; Bolling, Danielle Z.; Pelphrey, Kevin A.; Mayes, Linda C.

2011-01-01

235

Temporal dynamics reveal atypical brain response to social exclusion in autism.  

PubMed

Despite significant social difficulties, children with autism spectrum disorder (ASD) are vulnerable to the effects of social exclusion. We recorded EEG while children with ASD and typical peers played a computerized game involving peer rejection. Children with ASD reported ostracism-related distress comparable to typically developing children. Event-related potentials (ERPs) indicated a distinct pattern of temporal processing of rejection events in children with ASD. While typically developing children showed enhanced response to rejection at a late slow wave indexing emotional arousal and regulation, those with autism showed attenuation at an early component, suggesting reduced engagement of attentional resources in the aversive social context. Results emphasize the importance of studying the time course of social information processing in ASD; they suggest distinct mechanisms subserving similar overt behavior and yield insights relevant to development and implementation of targeted treatment approaches and objective measures of response to treatment. PMID:21731598

McPartland, James C; Crowley, Michael J; Perszyk, Danielle R; Naples, Adam; Mukerji, Cora E; Wu, Jia; Molfese, Peter; Bolling, Danielle Z; Pelphrey, Kevin A; Mayes, Linda C

2011-07-01

236

Perturbation-response scanning reveals ligand entry-exit mechanisms of ferric binding protein.  

PubMed

We study apo and holo forms of the bacterial ferric binding protein (FBP) which exhibits the so-called ferric transport dilemma: it uptakes iron from the host with remarkable affinity, yet releases it with ease in the cytoplasm for subsequent use. The observations fit the "conformational selection" model whereby the existence of a weakly populated, higher energy conformation that is stabilized in the presence of the ligand is proposed. We introduce a new tool that we term perturbation-response scanning (PRS) for the analysis of remote control strategies utilized. The approach relies on the systematic use of computational perturbation/response techniques based on linear response theory, by sequentially applying directed forces on single-residues along the chain and recording the resulting relative changes in the residue coordinates. We further obtain closed-form expressions for the magnitude and the directionality of the response. Using PRS, we study the ligand release mechanisms of FBP and support the findings by molecular dynamics simulations. We find that the residue-by-residue displacements between the apo and the holo forms, as determined from the X-ray structures, are faithfully reproduced by perturbations applied on the majority of the residues of the apo form. However, once the stabilizing ligand (Fe) is integrated to the system in holo FBP, perturbing only a few select residues successfully reproduces the experimental displacements. Thus, iron uptake by FBP is a favored process in the fluctuating environment of the protein, whereas iron release is controlled by mechanisms including chelation and allostery. The directional analysis that we implement in the PRS methodology implicates the latter mechanism by leading to a few distant, charged, and exposed loop residues. Upon perturbing these, irrespective of the direction of the operating forces, we find that the cap residues involved in iron release are made to operate coherently, facilitating release of the ion. PMID:19851447

Atilgan, Canan; Atilgan, Ali Rana

2009-10-01

237

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

PubMed

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

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

2014-12-01

238

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates  

PubMed Central

Vertebrate innate immunity is the first line of defense against an invading pathogen and has long been assumed to be largely unspecific with respect to parasite/pathogen species. However, recent phenotypic evidence suggests that immunogenetic variation, i.e. allelic variability in genes associated with the immune system, results in host-parasite genotype-by-genotype interactions and thus specific innate immune responses. Immunogenetic variation is common in all vertebrate taxa and this reflects an effective immunological function in complex environments. However, the underlying variability in host gene expression patterns as response of innate immunity to within-species genetic diversity of macroparasites in vertebrates is unknown. We hypothesized that intra-specific variation among parasite genotypes must be reflected in host gene expression patterns. Here we used high-throughput RNA-sequencing to examine the effect of parasite genotypes on gene expression patterns of a vertebrate host, the three-spined stickleback (Gasterosteus aculeatus). By infecting naïve fish with distinct trematode genotypes of the species Diplostomum pseudospathaceum we show that gene activity of innate immunity in three-spined sticklebacks depended on the identity of an infecting macroparasite genotype. In addition to a suite of genes indicative for a general response against the trematode we also find parasite-strain specific gene expression, in particular in the complement system genes, despite similar infection rates of single clone treatments. The observed discrepancy between infection rates and gene expression indicates the presence of alternative pathways which execute similar functions. This suggests that the innate immune system can induce redundant responses specific to parasite genotypes. PMID:25254967

Haase, David; Rieger, Jennifer K.; Witten, Anika; Stoll, Monika; Bornberg-Bauer, Erich; Kalbe, Martin; Reusch, Thorsten B. H.

2014-01-01

239

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

PubMed Central

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

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

2014-01-01

240

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

PubMed Central

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

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

241

Continuous functional magnetic resonance imaging reveals dynamic nonlinearities of "dose-response" curves for finger opposition.  

PubMed

Linear experimental designs have dominated the field of functional neuroimaging, but although successful at mapping regions of relative brain activation, the technique assumes that both cognition and brain activation are linear processes. To test these assumptions, we performed a continuous functional magnetic resonance imaging (MRI) experiment of finger opposition. Subjects performed a visually paced bimanual finger-tapping task. The frequency of finger tapping was continuously varied between 1 and 5 Hz, without any rest blocks. After continuous acquisition of fMRI images, the task-related brain regions were identified with independent components analysis (ICA). When the time courses of the task-related components were plotted against tapping frequency, nonlinear "dose- response" curves were obtained for most subjects. Nonlinearities appeared in both the static and dynamic sense, with hysteresis being prominent in several subjects. The ICA decomposition also demonstrated the spatial dynamics with different components active at different times. These results suggest that the brain response to tapping frequency does not scale linearly, and that it is history-dependent even after accounting for the hemodynamic response function. This implies that finger tapping, as measured with fMRI, is a nonstationary process. When analyzed with a conventional general linear model, a strong correlation to tapping frequency was identified, but the spatiotemporal dynamics were not apparent. PMID:10407059

Berns, G S; Song, A W; Mao, H

1999-07-15

242

Spectrotemporal resolution tradeoff in auditory processing as revealed by human auditory brainstem responses and psychophysical indices.  

PubMed

Auditory filter theory dictates a physiological compromise between frequency and temporal resolution of cochlear signal processing. We examined neurophysiological correlates of these spectrotemporal tradeoffs in the human auditory system using auditory evoked brain potentials and psychophysical responses. Temporal resolution was assessed using scalp-recorded auditory brainstem responses (ABRs) elicited by paired clicks. The inter-click interval (ICI) between successive pulses was parameterized from 0.7 to 25 ms to map ABR amplitude recovery as a function of stimulus spacing. Behavioral frequency difference limens (FDLs) and auditory filter selectivity (Q10 of psychophysical tuning curves) were obtained to assess relations between behavioral spectral acuity and electrophysiological estimates of temporal resolvability. Neural responses increased monotonically in amplitude with increasing ICI, ranging from total suppression (0.7 ms) to full recovery (25 ms) with a temporal resolution of ?3-4 ms. ABR temporal thresholds were correlated with behavioral Q10 (frequency selectivity) but not FDLs (frequency discrimination); no correspondence was observed between Q10 and FDLs. Results suggest that finer frequency selectivity, but not discrimination, is associated with poorer temporal resolution. The inverse relation between ABR recovery and perceptual frequency tuning demonstrates a time-frequency tradeoff between the temporal and spectral resolving power of the human auditory system. PMID:24793771

Bidelman, Gavin M; Syed Khaja, Ameenuddin

2014-06-20

243

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

PubMed

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

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

2014-02-01

244

Insights into the metabolic response to traumatic brain injury as revealed by 13C NMR spectroscopy  

PubMed Central

The present review highlights critical issues related to cerebral metabolism following traumatic brain injury (TBI) and the use of 13C labeled substrates and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First we address some pathophysiologic factors contributing to metabolic dysfunction following TBI. We then examine how 13C NMR spectroscopy strategies have been used to investigate energy metabolism, neurotransmission, the intracellular redox state, and neuroglial compartmentation following injury. 13C NMR spectroscopy studies of brain extracts from animal models of TBI have revealed enhanced glycolytic production of lactate, evidence of pentose phosphate pathway (PPP) activation, and alterations in neuronal and astrocyte oxidative metabolism that are dependent on injury severity. Differential incorporation of label into glutamate and glutamine from 13C labeled glucose or acetate also suggest TBI-induced adaptations to the glutamate-glutamine cycle. PMID:24109452

Bartnik-Olson, Brenda L.; Harris, Neil G.; Shijo, Katsunori; Sutton, Richard L.

2013-01-01

245

Quantised transistor response to ion channels revealed by nonstationary noise analysis  

NASA Astrophysics Data System (ADS)

We report on the quantised response of a field-effect transistor to molecular ion channels in a biomembrane. HEK293-type cells overexpressing the Shaker B potassium channel were cultured on a silicon chip. An enhanced noise of the transistor is observed when the ion channels are activated. The analysis of the fluctuations in terms of binomial statistics identifies voltage quanta of about 1 ?V on the gate. They are attributed to the channel currents that affect the gate voltage according to the Green's function of the cell-chip junction.

Becker-Freyseng, C.; Fromherz, P.

2011-11-01

246

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire  

PubMed Central

Idiosyncratic adverse drug reactions are unpredictable, dose-independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkages between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function; however, the mechanism by which abacavir induces this pathologic T-cell response remains unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional compounds with suspected HLA-linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA-linked hypersensitivities, and guide the development of safer drugs. PMID:22645359

Ostrov, David A.; Grant, Barry J.; Pompeu, Yuri A.; Sidney, John; Harndahl, Mikkel; Southwood, Scott; Oseroff, Carla; Lu, Shun; Jakoncic, Jean; de Oliveira, Cesar Augusto F.; Yang, Lun; Mei, Hu; Shi, Leming; Shabanowitz, Jeffrey; English, A. Michelle; Wriston, Amanda; Lucas, Andrew; Phillips, Elizabeth; Mallal, Simon; Grey, Howard M.; Sette, Alessandro; Hunt, Donald F.; Buus, Soren; Peters, Bjoern

2012-01-01

247

Equine insect bite hypersensitivity: what do we know?  

PubMed

Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin and with stimulated peripheral blood mononuclear cells. Various studies have shown IBH to be associated with IgE-mediated reactions against salivary antigens from Culicoides spp. However, until recently, the causative allergens had not been characterized at the molecular level. A major advance has now been made, as 11 Culicoides salivary gland proteins have been identified as relevant allergens for IBH. Currently, there is no satisfactory treatment of IBH. Characterization of the main allergens for IBH and understanding what mechanisms induce a healthy or allergic immune response towards these allergens may help to develop new treatment strategies, such as immunotherapy. PMID:22575371

Schaffartzik, A; Hamza, E; Janda, J; Crameri, R; Marti, E; Rhyner, C

2012-06-30

248

Gene Expression Profiling in Tibial Muscular Dystrophy Reveals Unfolded Protein Response and Altered Autophagy  

PubMed Central

Tibial muscular dystrophy (TMD) is a late onset, autosomal dominant distal myopathy that results from mutations in the two last domains of titin. The cascade of molecular events leading from the causative Titin mutations to the preterm death of muscle cells in TMD is largely unknown. In this study we examined the mRNA and protein changes associated with the myopathology of TMD. To identify these components we performed gene expression profiling using muscle biopsies from TMD patients and healthy controls. The profiling results were confirmed through quantitative real-time PCR and protein level analysis. One of the pathways identified was activation of endoplasmic reticulum (ER) stress response. ER stress activates the unfolded protein response (UPR) pathway. UPR activation was supported by elevation of the marker genes HSPA5, ERN1 and the UPR specific XBP1 splice form. However, UPR activation appears to be insufficient to correct the protein abnormalities causing its activation because degenerative TMD muscle fibres show an increase in ubiquitinated protein inclusions. Abnormalities of VCP-associated degradation pathways are also suggested by the presence of proteolytic VCP fragments in western blotting, and VCP's accumulation within rimmed vacuoles in TMD muscle fibres together with p62 and LC3B positive autophagosomes. Thus, pathways controlling turnover and degradation, including autophagy, are distorted and lead to degeneration and loss of muscle fibres. PMID:24618559

Screen, Mark; Raheem, Olayinka; Holmlund-Hampf, Jeanette; Jonson, Per Harald; Huovinen, Sanna; Hackman, Peter; Udd, Bjarne

2014-01-01

249

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

PubMed

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

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

2013-11-01

250

Meta-analysis of high-throughput datasets reveals cellular responses following hemorrhagic fever virus infection.  

PubMed

The continuing use of high-throughput assays to investigate cellular responses to infection is providing a large repository of information. Due to the large number of differentially expressed transcripts, often running into the thousands, the majority of these data have not been thoroughly investigated. Advances in techniques for the downstream analysis of high-throughput datasets are providing additional methods for the generation of additional hypotheses for further investigation. The large number of experimental observations, combined with databases that correlate particular genes and proteins with canonical pathways, functions and diseases, allows for the bioinformatic exploration of functional networks that may be implicated in replication or pathogenesis. Herein, we provide an example of how analysis of published high-throughput datasets of cellular responses to hemorrhagic fever virus infection can generate additional functional data. We describe enrichment of genes involved in metabolism, post-translational modification and cardiac damage; potential roles for specific transcription factors and a conserved involvement of a pathway based around cyclooxygenase-2. We believe that these types of analyses can provide virologists with additional hypotheses for continued investigation. PMID:21994748

Bowick, Gavin C; McAuley, Alexander J

2011-05-01

251

Direct measurement of transcription rates reveals multiple mechanisms for configuration of the Arabidopsis ambient temperature response  

PubMed Central

Background Sensing and responding to ambient temperature is important for controlling growth and development of many organisms, in part by regulating mRNA levels. mRNA abundance can change with temperature, but it is unclear whether this results from changes in transcription or decay rates, and whether passive or active temperature regulation is involved. Results Using a base analog labelling method, we directly measured the temperature coefficient, Q10, of mRNA synthesis and degradation rates of the Arabidopsis transcriptome. We show that for most genes, transcript levels are buffered against passive increases in transcription rates by balancing passive increases in the rate of decay. Strikingly, for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay and not vice versa, suggesting a global transcriptional process exists that controls mRNA abundance by temperature. This is partly accounted for by gene body H2A.Z which is associated with low transcription rate Q10, but is also influenced by other marks and transcription factor activities. Conclusions Our data show that less frequent chromatin states can produce temperature responses simply by virtue of their rarity and the difference between their thermal properties and those of the most common states, and underline the advantages of directly measuring transcription rate changes in dynamic systems, rather than inferring rates from changes in mRNA abundance. PMID:24580780

2014-01-01

252

Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways.  

PubMed

The fission yeast Schizosaccharomyces pombe has more metazoan-like features than the budding yeast Saccharomyces cerevisiae, yet it has similarly facile genetics. We present a large-scale verified binary protein-protein interactome network, "StressNet," based on high-throughput yeast two-hybrid screens of interacting proteins classified as part of stress response and signal transduction pathways in S. pombe. We performed systematic, cross-species interactome mapping using StressNet and a protein interactome network of orthologous proteins in S. cerevisiae. With cross-species comparative network studies, we detected a previously unidentified component (Snr1) of the S. pombe mitogen-activated protein kinase Sty1 pathway. Coimmunoprecipitation experiments showed that Snr1 interacted with Sty1 and that deletion of snr1 increased the sensitivity of S. pombe cells to stress. Comparison of StressNet with the interactome network of orthologous proteins in S. cerevisiae showed that most of the interactions among these stress response and signaling proteins are not conserved between species but are "rewired"; orthologous proteins have different binding partners in both species. In particular, transient interactions connecting proteins in different functional modules were more likely to be rewired than conserved. By directly testing interactions between proteins in one yeast species and their corresponding binding partners in the other yeast species with yeast two-hybrid assays, we found that about half of the interactions that are traditionally considered "conserved" form modified interaction interfaces that may potentially accommodate novel functions. PMID:23695164

Das, Jishnu; Vo, Tommy V; Wei, Xiaomu; Mellor, Joseph C; Tong, Virginia; Degatano, Andrew G; Wang, Xiujuan; Wang, Lihua; Cordero, Nicolas A; Kruer-Zerhusen, Nathan; Matsuyama, Akihisa; Pleiss, Jeffrey A; Lipkin, Steven M; Yoshida, Minoru; Roth, Frederick P; Yu, Haiyuan

2013-05-21

253

Analysis of Natural Variation in Bermudagrass (Cynodon dactylon) Reveals Physiological Responses Underlying Drought Tolerance  

PubMed Central

Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass and one of the most drought tolerant species. Dissecting the natural variation in drought tolerance and physiological responses will bring us powerful basis and novel insight for plant breeding. In the present study, we evaluated the natural variation of drought tolerance among nine bermudagrass varieties by measuring physiological responses after drought stress treatment through withholding water. Three groups differing in drought tolerance were identified, including two tolerant, five moderately tolerant and two susceptible varieties. Under drought stress condition, drought sensitive variety (Yukon) showed relative higher water loss, more severe cell membrane damage (EL), and more accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA), while drought tolerant variety (Tifgreen) exhibited significantly higher antioxidant enzymes activities. Further results indicated that drought induced cell injury in different varieties (Yukon, SR9554 and Tifgreen) exhibited liner correlation with leaf water content (LWC), H2O2 content, MDA content and antioxidant enzyme activities. Additionally, Tifgreen plants had significantly higher levels of osmolytes (proline level and soluble sugars) when compared with Yukon and SR9554 under drought stress condition. Taken together, our results indicated that natural variation of drought stress tolerance in bermudagrass varieties might be largely related to the induced changes of water status, osmolyte accumulation and antioxidant defense system. PMID:23285294

Cheng, Zhangmin; Ye, Tiantian; Chan, Zhulong

2012-01-01

254

Analysis of natural variation in bermudagrass (Cynodon dactylon) reveals physiological responses underlying drought tolerance.  

PubMed

Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass and one of the most drought tolerant species. Dissecting the natural variation in drought tolerance and physiological responses will bring us powerful basis and novel insight for plant breeding. In the present study, we evaluated the natural variation of drought tolerance among nine bermudagrass varieties by measuring physiological responses after drought stress treatment through withholding water. Three groups differing in drought tolerance were identified, including two tolerant, five moderately tolerant and two susceptible varieties. Under drought stress condition, drought sensitive variety (Yukon) showed relative higher water loss, more severe cell membrane damage (EL), and more accumulation of hydrogen peroxide (H?O?) and malondialdehyde (MDA), while drought tolerant variety (Tifgreen) exhibited significantly higher antioxidant enzymes activities. Further results indicated that drought induced cell injury in different varieties (Yukon, SR9554 and Tifgreen) exhibited liner correlation with leaf water content (LWC), H?O? content, MDA content and antioxidant enzyme activities. Additionally, Tifgreen plants had significantly higher levels of osmolytes (proline level and soluble sugars) when compared with Yukon and SR9554 under drought stress condition. Taken together, our results indicated that natural variation of drought stress tolerance in bermudagrass varieties might be largely related to the induced changes of water status, osmolyte accumulation and antioxidant defense system. PMID:23285294

Shi, Haitao; Wang, Yanping; Cheng, Zhangmin; Ye, Tiantian; Chan, Zhulong

2012-01-01

255

Yacht-maker's lung: A case of hypersensitivity pneumonitis in yacht manufacturing.  

PubMed

We present a case of hypersensitivity pneumonitis in a 46-year-old female working at a yacht manufacturing company. She reported a 2-month history of progressive dyspnea, chest tightness, and daytime, nocturnal, and exertional cough in temporal relationship to work where she was exposed to chemicals involved in the manufacture of yachts. Treatment with systemic antibiotic therapy, inhaled bronchodilators, and inhaled corticosteroids provided minimal relief of symptoms. Spirometry revealed a restrictive defect and a chest x-ray demonstrated a diffuse interstitial pattern. She improved on oral corticosteroids and with avoidance of her work environment had resolution of her symptoms and normalization of her spirometry. Among the various chemicals the patient was exposed to, the most likely causative agents for her symptoms were dimethyl phthalate and styrene. Although the specific chemical or antigen could not be determined, the history and objective findings are consistent with occupational hypersensitivity pneumonitis. This represents a case of hypersensitivity pneumonitis related to the manufacture of yachts. PMID:17163087

Volkman, Kristen K; Merrick, James G; Zacharisen, Michael C

2006-10-01

256

RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus  

PubMed Central

Background In a context of climate change, phenotypic plasticity provides long-lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. Results Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by-treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. Conclusions For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance of biomass growth during the dry season. Its strategy may involve a decrease of photosynthetic activity during the dry season associated with resources reallocation through major changes in the expression of primary metabolism associated genes. Further efforts will be needed to assess the adaptive nature of the genes highlighted in this study. PMID:22047139

2011-01-01

257

Biomarker responses reveal that food quality affects cadmium exposure in the soil collembolan Folsomia candida.  

PubMed

Food quality affects the food consumption rate, flux through the gut, and exposure to contaminants in animals. This study evaluated the effects of food quality on cadmium exposure in the soil collembolan Folsomia candida. Animals were exposed to constant concentrations of cadmium for 38 h via artificial food consisting of an agar medium with various concentrations of sugar (glucose), total nutrients (baker's yeast), or fungal odour (1-octen-3-ol). The expression of the gene encoding a deduced metallothionein-like motif containing protein was used as a biomarker of cadmium exposure. Glucose concentrations of 2% or higher reduced the expression levels of the biomarker. Within the range of 0.1-8% yeast, medium concentrations led to higher biomarker levels. At high concentrations of 1-octen-3-ol (2000 mg/l), feeding and the biomarker response were reduced. These results suggest that even at equivalent cadmium concentrations, food quality affects cadmium exposure by altering food consumption rates. PMID:23421985

Nakamori, Taizo; Kaneko, Nobuhiro

2013-05-01

258

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

PubMed

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

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

259

Phylogenetically Driven Sequencing of Extremely Halophilic Archaea Reveals Strategies for Static and Dynamic Osmo-response.  

PubMed

Organisms across the tree of life use a variety of mechanisms to respond to stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms and phenotypes associated with osmoadaptation also play important roles in bacterial virulence, human health, agricultural production and many other biological systems. To improve understanding of osmoadaptive strategies, we have generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade whose members thrive in hypersaline environments and routinely experience drastic changes in environmental salinity) and analyzed these new genomes in combination with those from 21 previously sequenced haloarchaeal isolates. We propose a generalized model for haloarchaeal management of cytoplasmic osmolarity in response to osmotic shifts, where potassium accumulation and sodium expulsion during osmotic upshock are accomplished via secondary transport using the proton gradient as an energy source, and potassium loss during downshock is via a combination of secondary transport and non-specific ion loss through mechanosensitive channels. We also propose new mechanisms for magnesium and chloride accumulation. We describe the expansion and differentiation of haloarchaeal general transcription factor families, including two novel expansions of the TATA-binding protein family, and discuss their potential for enabling rapid adaptation to environmental fluxes. We challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. The combination of broad (17 genera) and deep (?5 species in four genera) sampling of a phenotypically unified clade has enabled us to uncover both highly conserved and specialized features of osmoadaptation. Finally, we demonstrate the broad utility of such datasets, for metagenomics, improvements to automated gene annotation and investigations of evolutionary processes. PMID:25393412

Becker, Erin A; Seitzer, Phillip M; Tritt, Andrew; Larsen, David; Krusor, Megan; Yao, Andrew I; Wu, Dongying; Madern, Dominique; Eisen, Jonathan A; Darling, Aaron E; Facciotti, Marc T

2014-11-01

260

Laser capture microdissection reveals dose-response of gene expression in situ consequent to asbestos exposure  

PubMed Central

The genes that mediate fibroproliferative lung disease remain to be defined. Prior studies from our laboratory showed by in situ hybridization and immunohistochemistry that the genes coding for tumour necrosis factor alpha, transforming growth factor beta, the platelet-derived growth factor A and B isoforms, and alpha-1 pro-collagen are expressed in fibroproliferative lesions that develop quickly after asbestos inhalation. These five genes, along with matrix metalloproteinase 9, a collagenase found to be increased in several lung diseases, are known to control matrix production and cell proliferation in humans and animals. Here we show by laser capture microdissection that (i) The six genes are expressed at significantly higher levels in the asbestos-exposed mice when comparing the same anatomic regions ‘captured’ in unexposed mice. (ii) The bronchiolar-alveolar duct (BAD) junctions, where the greatest number of fibres initially deposit, were always significantly higher than the other anatomic regions for each gene. The first alveolar duct bifurcation (ADB) generally was higher than the second ADB, the ADBs were always significantly higher than the airway walls and pleura, and the airway walls and pleura were generally higher than the unexposed tissues. (iii) Animals exposed for 3 days always exhibited significantly higher levels of gene expression at the BAD junctions and ADBs than animals exposed for 2 days. To our knowledge, this is the first demonstration of a dose–response to a toxic particle in situ, and this response appears to be dependent on the number of fibres that deposits at the individual anatomic site. PMID:18039278

Yin, Qi; Brody, Arnold R; Sullivan, Deborah E

2007-01-01

261

Phylogenetically Driven Sequencing of Extremely Halophilic Archaea Reveals Strategies for Static and Dynamic Osmo-response  

PubMed Central

Organisms across the tree of life use a variety of mechanisms to respond to stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms and phenotypes associated with osmoadaptation also play important roles in bacterial virulence, human health, agricultural production and many other biological systems. To improve understanding of osmoadaptive strategies, we have generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade whose members thrive in hypersaline environments and routinely experience drastic changes in environmental salinity) and analyzed these new genomes in combination with those from 21 previously sequenced haloarchaeal isolates. We propose a generalized model for haloarchaeal management of cytoplasmic osmolarity in response to osmotic shifts, where potassium accumulation and sodium expulsion during osmotic upshock are accomplished via secondary transport using the proton gradient as an energy source, and potassium loss during downshock is via a combination of secondary transport and non-specific ion loss through mechanosensitive channels. We also propose new mechanisms for magnesium and chloride accumulation. We describe the expansion and differentiation of haloarchaeal general transcription factor families, including two novel expansions of the TATA-binding protein family, and discuss their potential for enabling rapid adaptation to environmental fluxes. We challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. The combination of broad (17 genera) and deep (?5 species in four genera) sampling of a phenotypically unified clade has enabled us to uncover both highly conserved and specialized features of osmoadaptation. Finally, we demonstrate the broad utility of such datasets, for metagenomics, improvements to automated gene annotation and investigations of evolutionary processes. PMID:25393412

Tritt, Andrew; Larsen, David; Krusor, Megan; Yao, Andrew I.; Wu, Dongying; Madern, Dominique; Eisen, Jonathan A.; Darling, Aaron E.; Facciotti, Marc T.

2014-01-01

262

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

PubMed Central

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

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

2014-01-01

263

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

PubMed Central

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

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

2014-01-01

264

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2011 CFR

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5500 Hypersensitivity pneumonitis immunological test...

2011-04-01

265

Comparative transcriptome analysis reveals novel roles of the Ras and cyclic AMP signaling pathways in environmental stress response and antifungal drug sensitivity in Cryptococcus neoformans.  

PubMed

The cyclic AMP (cAMP) pathway plays a central role in the growth, differentiation, and virulence of pathogenic fungi, including Cryptococcus neoformans. Three upstream signaling regulators of adenylyl cyclase (Cac1), Ras, Aca1, and Gpa1, have been demonstrated to control the cAMP pathway in C. neoformans, but their functional relationship remains elusive. We performed a genome-wide transcriptome analysis with a DNA microarray using the ras1Delta, gpa1Delta, cac1Delta, aca1Delta, and pka1Delta pka2Delta mutants. The aca1Delta, gpa1Delta, cac1Delta, and pka1Delta pka2Delta mutants displayed similar transcriptome patterns, whereas the ras1Delta mutant exhibited transcriptome patterns distinct from those of the wild type and the cAMP mutants. Interestingly, a number of environmental stress response genes are modulated differentially in the ras1Delta and cAMP mutants. In fact, the Ras signaling pathway was found to be involved in osmotic and genotoxic stress responses and the maintenance of cell wall integrity via the Cdc24-dependent signaling pathway. Notably, the Ras and cAMP mutants exhibited hypersensitivity to a polyene drug, amphotericin B, without showing effects on ergosterol biosynthesis, which suggested a novel method of antifungal combination therapy. Among the cAMP-dependent gene products that we characterized, two small heat shock proteins, Hsp12 and Hsp122, were found to be involved in the polyene antifungal drug susceptibility of C. neoformans. PMID:20097740

Maeng, Shinae; Ko, Young-Joon; Kim, Gyu-Bum; Jung, Kwang-Woo; Floyd, Anna; Heitman, Joseph; Bahn, Yong-Sun

2010-03-01

266

Functional analysis of rice HOMEOBOX4 (Oshox4) gene reveals a negative function in gibberellin responses.  

PubMed

The homeodomain-leucine zipper (HD-Zip) putative transcription factor genes are divided into 4 families. In this work, we studied the function of a rice HD-Zip I gene, H OME O BO X4 (Oshox4). Oshox4 transcripts were detected in leaf and floral organ primordia but excluded from the shoot apical meristem and the protein was nuclear localized. Over-expression of Oshox4 in rice induced a semi-dwarf phenotype that could not be complemented by applied GA3. The over-expression plants accumulated elevated levels of bioactive GA, while the GA catabolic gene GA2ox3 was upregulated in the transgenic plants. In addition, over-expression of Oshox4 blocked GA-dependent alpha-amylase production. However, down-regulation of Oshox4 in RNAi transgenic plants induced no phenotypic alteration. Interestingly, the expression of YAB1 that is involved in the negative feedback regulation of the GA biosynthesis was upregulated in the Oshox4 over-expressing plants. One-hybrid assays showed that Oshox4 could interact with YAB1 promoter in yeast. In addition, Oshox4 expression was upregulated by GA. These data together suggest that Oshox4 may be involved in the negative regulation of GA signalling and may play a role to fine tune GA responses in rice. PMID:18049796

Dai, Mingqiu; Hu, Yongfeng; Ma, Qian; Zhao, Yu; Zhou, Dao-Xiu

2008-02-01

267

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

NASA Astrophysics Data System (ADS)

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.

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

2014-05-01

268

Robust dynamic classes revealed by measuring the response function of a social system  

PubMed Central

We study the relaxation response of a social system after endogenous and exogenous bursts of activity using the time series of daily views for nearly 5 million videos on YouTube. We find that most activity can be described accurately as a Poisson process. However, we also find hundreds of thousands of examples in which a burst of activity is followed by an ubiquitous power-law relaxation governing the timing of views. We find that these relaxation exponents cluster into three distinct classes and allow for the classification of collective human dynamics. This is consistent with an epidemic model on a social network containing two ingredients: a power-law distribution of waiting times between cause and action and an epidemic cascade of actions becoming the cause of future actions. This model is a conceptual extension of the fluctuation-dissipation theorem to social systems [Ruelle, D (2004) Phys Today 57:48–53] and [Roehner BM, et al., (2004) Int J Mod Phys C 15:809–834], and provides a unique framework for the investigation of timing in complex systems. PMID:18824681

Crane, Riley; Sornette, Didier

2008-01-01

269

Revealing real-time emotional responses: a personalized assessment based on heartbeat dynamics.  

PubMed

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

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

2014-01-01

270

Amygdala responses to Valence and its interaction by arousal revealed by MEG.  

PubMed

It is widely accepted that the amygdala plays a crucial role in the processing of emotions. The precise nature of its involvement is however unclear. We hypothesized that ambivalent findings from neuroimaging studies that report amygdala's activity in emotions, are due to distinct functional specificity of amygdala's sub-divisions and specifically to differential reactivity to arousal and valence. The goal of the present study is to characterize the amygdala response to affective stimuli by disentangling the contributions of arousal and valence. Our hypothesis was prompted by recent reports claiming anatomical sub-divisions of amygdala based on cytoarchitecture and the functional maps obtained from diverse behavioral, emotional, and physiological stimulation. We measured magnetoencephalography (MEG) recordings from 12 healthy individuals passively exposed to affective stimuli from the International Affective Picture System (IAPS) collection using a 2 (Valence levels)× 2 (Arousal levels) design. Source power was estimated using a beamformer technique with the activations referring to the amygdala sub-divisions defined through probabilistic cytoarchitectonic maps. Right laterobasal amygdala activity was found to mediate negative valence (elicited by unpleasant stimuli) while left centromedial activity was characterized by an interaction of valence by arousal (arousing pleasant stimuli). We did not find a main effect for amygdala activations in any of its sub-divisions for arousal modulation. To the best of our knowledge, our findings from non-invasive MEG data indicate for the first time, a distinct functional specificity of amygdala anatomical sub-divisions in the emotional processing. PMID:23688672

Styliadis, Charalampos; Ioannides, Andreas A; Bamidis, Panagiotis D; Papadelis, Christos

2014-07-01

271

Hypersensitivity reactions associated with exposure to naproxen and ibuprofen  

Microsoft Academic Search

The aim of the study was to evaluate the risks of hospitalisation and death due to hypersensitivity reactions associated with the NSAIDs naproxen and ibuprofen, using a record-linkage database for Tayside, Scotland (population 400,000). Cohorts of patients exposed to naproxen (n=54,038) and ibuprofen (n=79,513) were assembled. There were no deaths due to hypersensitivity. There was an increased risk of unvalidated

Alex D McMahon; Josie M. M Evans; Thomas M MacDonald

2001-01-01

272

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

PubMed

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

Luo, Qijun; Zhu, Zhenggang; Zhu, Zhujun; Yang, Rui; Qian, Feijian; Chen, Haimin; Yan, Xiaojun

2014-01-01

273

Spectral reconstruction of phase response curves reveals the synchronization properties of mouse globus pallidus neurons.  

PubMed

The propensity of a neuron to synchronize is captured by its infinitesimal phase response curve (iPRC). Determining whether an iPRC is biphasic, meaning that small depolarizing perturbations can actually delay the next spike, if delivered at appropriate phases, is a daunting experimental task because negative lobes in the iPRC (unlike positive ones) tend to be small and may be occluded by the normal discharge variability of a neuron. To circumvent this problem, iPRCs are commonly derived from numerical models of neurons. Here, we propose a novel and natural method to estimate the iPRC by direct estimation of its spectral modes. First, we show analytically that the spectral modes of the iPRC of an arbitrary oscillator are readily measured by applying weak harmonic perturbations. Next, applying this methodology to biophysical neuronal models, we show that a low-dimensional spectral reconstruction is sufficient to capture the structure of the iPRC. This structure was preserved reasonably well even with added physiological scale jitter in the neuronal models. To validate the methodology empirically, we applied it first to a low-noise electronic oscillator with a known design and then to cortical pyramidal neurons, recorded in whole cell configuration, that are known to possess a monophasic iPRC. Finally, using the methodology in conjunction with perforated-patch recordings from pallidal neurons, we show, in contrast to recent modeling studies, that these neurons have biphasic somatic iPRCs. Biphasic iPRCs would cause lateral somatically targeted pallidal inhibition to desynchronize pallidal neurons, providing a plausible explanation for their lack of synchrony in vivo. PMID:23966679

Goldberg, Joshua A; Atherton, Jeremy F; Surmeier, D James

2013-11-01

274

Different Responses to Heat Shock Stress Revealed Heteromorphic Adaptation Strategy of Pyropia haitanensis (Bangiales, Rhodophyta)  

PubMed Central

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

Zhu, Zhujun; Yang, Rui; Qian, Feijian; Chen, Haimin; Yan, Xiaojun

2014-01-01

275

Hypersensitivity associated with sugammadex administration: a systematic review.  

PubMed

Sugammadex is a drug used to reverse neuromuscular blockade induced by rocuronium or vecuronium. It has not yet been approved by the Food and Drug Administration in the USA due to concerns regarding hypersensitivity. The objective of this review was to identify similarities in the presentation of hypersensitivity reactions to sugammadex. A comprehensive search was performed in PubMed, Scopus and Web of Science for cases reporting hypersensitivity reactions to sugammadex. In addition, we contacted regulatory agencies and the company marketing the drug for unpublished reports. Reports were included if they were in English, primary investigations, lacked an alternative probable explanation for the reaction and included a comprehensive description of the hypersensitivity. We identified 15 cases of hypersensitivity following sugammadex administration. All cases that reported exact timing (14/15) occurred in 4 min or less. Most of the patients (11/15; 73%) met World Anaphylaxis Organization criteria for anaphylaxis. Awareness must be raised for the possibility of drug-induced hypersensitivity during the critical 5-min period immediately following sugammadex administration. PMID:24848211

Tsur, A; Kalansky, A

2014-11-01

276

Hypersensitivities for Acetaldehyde and Other Agents among Cancer Cells Null for Clinically Relevant Fanconi Anemia Genes  

PubMed Central

Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and ?-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. PMID:24200853

Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R.; Rago, Carlo; Bhunia, Anil K.; Hossain, M. Zulfiquer; Paun, Bogdan C.; Ren, Yunzhao R.; Iacobuzio-Donahue, Christine A.; Azad, Nilofer A.; Kern, Scott E.

2014-01-01

277

Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity  

PubMed Central

Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive. PMID:18400801

Audicana, M. Teresa; Kennedy, Malcolm W.

2008-01-01

278

Severe dapsone hypersensitivity syndrome in a child  

PubMed Central

Dapsone (4,4'-diaminodiphenylsulfone, DDS), a potent anti-inflammatory agent, is widely used in the treatment of leprosy and several chronic inflammatory skin diseases. Dapsone therapy rarely results in development of dapsone hypersensitivity syndrome, which is characterized by fever, hepatitis, generalized exfoliative dermatitis, and lymphadenopathy. Here, we describe the case of an 11-year-old Korean boy who initially presented with high fever, a morbilliform skin rash, generalized lymphadenopathy, hepatosplenomegaly, and leukopenia after 6 weeks of dapsone intake. Subsequently, he exhibited cholecystitis, gingivitis, colitis, sepsis, aseptic meningitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, pneumonia, pleural effusions, peritonitis, bronchiectatic changes, exfoliative dermatitis, and acute renal failure. After 2 months of supportive therapy, and prednisolone and antibiotic administration, most of the systemic symptoms resolved, with the exception of exfoliative dermatitis and erythema, which ameliorated over the following 4 months. Agranulocytosis, atypical lymphocytosis, aseptic meningitis, and bronchiectatic changes along with prolonged systemic symptoms with exfoliative dermatitis were the most peculiar features of the present case. PMID:23807893

Choi, So Yoon; Hwang, Ho Yeon; Lee, Jung Hyun; Jang, Min Soo

2013-01-01

279

In Vivo Physiological and Transcriptional Profiling Reveals Host Responses to Clostridium difficile Toxin A and Toxin B  

PubMed Central

Toxin A (TcdA) and toxin B (TcdB) of Clostridium difficile cause gross pathological changes (e.g., inflammation, secretion, and diarrhea) in the infected host, yet the molecular and cellular pathways leading to observed host responses are poorly understood. To address this gap, we evaluated the effects of single doses of TcdA and/or TcdB injected into the ceca of mice, and several endpoints were analyzed, including tissue pathology, neutrophil infiltration, epithelial-layer gene expression, chemokine levels, and blood cell counts, 2, 6, and 16 h after injection. In addition to confirming TcdA's gross pathological effects, we found that both TcdA and TcdB resulted in neutrophil infiltration. Bioinformatics analyses identified altered expression of genes associated with the metabolism of lipids, fatty acids, and detoxification; small GTPase activity; and immune function and inflammation. Further analysis revealed transient expression of several chemokines (e.g., Cxcl1 and Cxcl2). Antibody neutralization of CXCL1 and CXCL2 did not affect TcdA-induced local pathology or neutrophil infiltration, but it did decrease the peripheral blood neutrophil count. Additionally, low serum levels of CXCL1 and CXCL2 corresponded with greater survival. Although TcdA induced more pronounced transcriptional changes than TcdB and the upregulated chemokine expression was unique to TcdA, the overall transcriptional responses to TcdA and TcdB were strongly correlated, supporting differences primarily in timing and potency rather than differences in the type of intracellular host response. In addition, the transcriptional data revealed novel toxin effects (e.g., altered expression of GTPase-associated and metabolic genes) underlying observed physiological responses to C. difficile toxins. PMID:23897615

D'Auria, Kevin M.; Kolling, Glynis L.; Donato, Gina M.; Warren, Cirle A.; Gray, Mary C.

2013-01-01

280

Modulation of hypersensitivity reaction by lipids given orally.  

PubMed

The effect of lipids administration by gavage (0.4% body weight) given daily during four weeks on the hypersensitivity reaction in trachea, upper and lower bronchi, liver, kidney, mesentery, and pancreas was investigated in male rats. The plasma exudation was assessed by using Evans blue (EB) dye extravasation method. There was a significant difference in the permeability of the organs in nonimmunized rats. The immunization increased the vascular permeability and the response with the organs varied greatly. The effect of lipids on anaphylactic reaction was compared to those of untreated rats (control group). The EB extravasation was significantly increased in the trachea obtained from rats treated with cocoa butter and soybean oil. In the upper bronchi of rats treated with soybean oil, the EB extravasation was increased. However, in the lower bronchi, none of the treatments with lipids changed the extravasation of EB. The same was observed in the liver and kidney. The animals treated with lipids by gavage did not present differences in EB extravasation in the mesentery. However, in the pancreas and duodenum, the treatment with fish and soybean oils and cocoa butter markedly lowered EB extravasation. PMID:10382863

Miyasaka, C K; Mendonça, J R; Silva, Z L; de Sousa, J A; Tavares de Lima, W; Curi, R

1999-05-01

281

Tomato Transcriptional Changes in Response to Clavibacter michiganensis subsp. michiganensis Reveal a Role for Ethylene in Disease Development1[W  

PubMed Central

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

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

2008-01-01

282

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

PubMed

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

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

283

Effect of hypersensitivity on protein uptake across the air-blood barrier of isolated rabbit lungs.  

PubMed

In previous studies with isolated perfused rabbit lungs, we observed that human serum albumin (HSA) and ovalbumin, introduced into the isolated lungs as an aerosol, entered the pulmonary circulation antigenically intact. The "inhaled" proteins were also broken down in the lung. When lungs from animals immunized with one protein inhaled the two proteins simultaneously, absorption of intact antigen was specifically reduced, and there was a nonspecific increase in the appearance of metabolites of both proteins in the blood. In the present study, we investigated the antigen-specific and nonspecific effects of two types of hypersensitivity responses on protein absorption across the air-blood barrier of isolated rabbit lungs. In one group of lungs, an acute hypersensitivity response was induced by introducing HSA into the blood perfusing lungs from HSA-immunized rabbits. In another, the rabbits had been previously exposed to chronic HSA aerosol until their lungs exhibited a chronic immunologic inflammatory response. Lungs from both groups were insufflated simultaneously with HSA, and a nonspecific protein, ovalbumin. Lungs in which the acute anaphylactic response was induced showed no alteration in the absorption of either intact protein compared with HSA-immunized controls, but absorbed a somewhat larger quantity of breakdown products of the specific antigen. Lungs undergoing the chronic alveolar inflammation were more permeable to nonspecific protein than were noninflamed lungs. Despite the increased permeability to nonspecific protein, the absorption of antigen was blocked as effectively as in immune but noninflamed controls. In these chronically inflamed lungs, the absorption of antigen breakdown products was enhanced. The results indicate that both immunologic and inflammatory mechanisms may control the amounts of inhaled soluble proteins that reach the blood via the alveolocapillary barrier. Alterations in the absorption of inhaled proteins and their metabolites across the air-blood barrier during certain types of hypersensitivity responses may be of immunologic and pathologic significance. PMID:447837

Braley, J F; Peterson, L B; Dawson, C A; Moore, V L

1979-06-01

284

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

PubMed Central

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

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, Jorg

2014-01-01

285

International Congress on Hormonal Steroids and Hormones and Cancer Adaptive hypersensitivity to estrogen: mechanism for superiority of aromatase inhibitors over selective estrogen receptor modulators for breast cancer treatment and prevention  

Microsoft Academic Search

Clinical observations suggest that human breast tumors can adapt to endocrine therapy by developing hypersensitivity to estradiol (E2). To understand the mechanisms responsible, we examined estrogenic stimulation of cell proliferation in a model system and provided in vitro and in vivo evidence that long-term E2 deprivation (LTED) causes 'adaptive hypersensitivity'. The enhanced responses to E2 do not involve mechanisms acting

R J Santen; R X Song; Z Zhang; R Kumar; M-H Jeng; S Masamura; W Yue; L Berstein

286

Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats  

SciTech Connect

Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY by using /sup 32/P-labeled quiescent platelets. In unstimulated cells, both the rate and extent of /sup 32/P incorporation into individual inositol-containing phospholipids and phosphatidic acid were identical in SHR and WKY. This finding suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced phosphoinositide metabolism, when monitored as changes in (/sup 32/P)phosphatidic acid, was significantly higher in SHR than in WKY. For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more (/sup 32/P)phosphatidic acid in SHR than in WKY. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced (/sup 32/P)phosphatidic acid formation in SHR. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. Following thrombin stimulation, (/sup 32/P)phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR.

Koutouzov, S.; Remmal, A.; Marche, P.; Meyer, P.

1987-11-01

287

Exposure to Low-Dose Ultraviolet Radiation Suppresses Delayed-Type Hypersensitivity to Herpes Simplex Virus in Mice  

Microsoft Academic Search

Ultraviolet B (UVB) radiation is reported to induce a defect in epidermal antigen presentation which leads to specific suppression of the delayed-type hypersensitivity (DTH) response to trinitrochlorobenzene. We have used a similar system to examine the murine DTH response to herpes simplex virus type 1 (HSV-1). Mice irradiated with 96 mJ\\/cm2 UVB on shaved dorsal skin 3 days before s.c.

Sarah Howie; Mary Norval; Jean Maingay

1986-01-01

288

Inducible Ablation of Melanopsin-Expressing Retinal Ganglion Cells Reveals Their Central Role in Non-Image Forming Visual Responses  

PubMed Central

Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diphtheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals. PMID:18545654

Hatori, Megumi; Le, Hiep; Vollmers, Christopher; Keding, Sheena Racheal; Tanaka, Nobushige; Schmedt, Christian; Jegla, Timothy; Panda, Satchidananda

2008-01-01

289

Voltage-sensitive dye imaging reveals improved topographic activation of cortex in response to manipulation of thalamic microstimulation parameters  

NASA Astrophysics Data System (ADS)

Voltage-sensitive dye imaging was used to quantify in vivo, network level spatiotemporal cortical activation in response to electrical microstimulation of the thalamus in the rat vibrissa pathway. Thalamic microstimulation evoked a distinctly different cortical response than natural sensory stimulation, with response to microstimulation spreading over a larger area of cortex and being topographically misaligned with the cortical column to which the stimulated thalamic region projects. Electrical stimulation with cathode-leading asymmetric waveforms reduced this topographic misalignment while simultaneously increasing the spatial specificity of the cortical activation. Systematically increasing the asymmetry of the microstimulation pulses revealed a continuum between symmetric and asymmetric stimulation that gradually reduced the topographic bias. These data strongly support the hypothesis that manipulation of the electrical stimulation waveform can be used to selectively activate specific neural elements. Specifically, our results are consistent with the prediction that cathode-leading asymmetric waveforms preferentially stimulate cell bodies over axons, while symmetric waveforms preferentially activate axons over cell bodies. The findings here provide some initial steps toward the design and optimization of microstimulation of neural circuitry, and open the door to more sophisticated engineering tools, such as nonlinear system identification techniques, to develop technologies for more effective control of activity in the nervous system.

Wang, Qi; Millard, Daniel C.; Zheng, He J. V.; Stanley, Garrett B.

2012-04-01

290

Novel TRPM8 antagonist attenuates cold hypersensitivity after peripheral nerve injury in rats.  

PubMed

Abnormal cold sensitivity is a common feature of a range of neuropathies. In the murine somatosensory system, multiple aspects of cold sensitivity are dependent on TRPM8, both short term and in response to peripheral nerve injury. The specialized nature of cold-sensitive afferents and the restricted expression of TRPM8 render it an attractive target for the treatment of cold hypersensitivity. This current study examines the effect of a novel TRPM8 antagonist (M8-An) in naive and spinal nerve-ligated rats through behavioral and in vivo electrophysiological approaches. In vitro, M8-An inhibited icilin-evoked Ca(2+) currents in HEK293 cells stably expressing human TRPM8 with an IC(50) of 10.9 nM. In vivo, systemic M8-An transiently decreased core body temperature. Deep dorsal horn recordings were made in vivo from neurons innervating the hind paw. M8-An inhibited neuronal responses to innocuous and noxious cooling of the receptive field in spinal nerve-ligated rats but not in naive rats. No effect on neuronal responses to mechanical and heat stimulation was observed. In addition, M8-An also attenuated behavioral responses to cold but not mechanical stimulation after nerve ligation without affecting the uninjured contralateral response. The data presented here support a contribution of TRPM8 to the pathophysiology of cold hypersensitivity in this model and highlight the potential of the pharmacological block of TRPM8 in alleviating the associated symptoms. PMID:24472724

Patel, Ryan; Gonçalves, Leonor; Newman, Robert; Jiang, Feng Li; Goldby, Anne; Reeve, Jennifer; Hendrick, Alan; Teall, Martin; Hannah, Duncan; Almond, Sarah; Brice, Nicola; Dickenson, Anthony H

2014-04-01

291

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

PubMed Central

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

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

2014-01-01

292

Sleep Fragmentation Exacerbates Mechanical Hypersensitivity and Alters Subsequent Sleep-Wake Behavior in a Mouse Model of Musculoskeletal Sensitization  

PubMed Central

Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization. Conclusions: Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved. Citation: Sutton BC; Opp MR. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization. SLEEP 2014;37(3):515-524. PMID:24587574

Sutton, Blair C.; Opp, Mark R.

2014-01-01

293

Integrative analysis of large scale expression profiles reveals core transcriptional response and coordination between multiple cellular processes in a cyanobacterium  

PubMed Central

Background Cyanobacteria are the only known prokaryotes capable of oxygenic photosynthesis. They play significant roles in global biogeochemical cycles and carbon sequestration, and have recently been recognized as potential vehicles for production of renewable biofuels. Synechocystis sp. PCC 6803 has been extensively used as a model organism for cyanobacterial studies. DNA microarray studies in Synechocystis have shown varying degrees of transcriptome reprogramming under altered environmental conditions. However, it is not clear from published work how transcriptome reprogramming affects pre-existing networks of fine-tuned cellular processes. Results We have integrated 163 transcriptome data sets generated in response to numerous environmental and genetic perturbations in Synechocystis. Our analyses show that a large number of genes, defined as the core transcriptional response (CTR), are commonly regulated under most perturbations. The CTR contains nearly 12% of Synechocystis genes found on its chromosome. The majority of genes in the CTR are involved in photosynthesis, translation, energy metabolism and stress protection. Our results indicate that a large number of differentially regulated genes identified in most reported studies in Synechocystis under different perturbations are associated with the general stress response. We also find that a majority of genes in the CTR are coregulated with 25 regulatory genes. Some of these regulatory genes have been implicated in cellular responses to oxidative stress, suggesting that reactive oxygen species are involved in the regulation of the CTR. A Bayesian network, based on the regulation of various KEGG pathways determined from the expression patterns of their associated genes, has revealed new insights into the coordination between different cellular processes. Conclusion We provide here the first integrative analysis of transcriptome data sets generated in a cyanobacterium. This compilation of data sets is a valuable resource to researchers for all cyanobacterial gene expression related queries. Importantly, our analysis provides a global description of transcriptional reprogramming under different perturbations and a basic framework to understand the strategies of cellular adaptations in Synechocystis. PMID:20678200

2010-01-01

294

A mathematical model of the unfolded protein stress response reveals the decision mechanism for recovery, adaptation and apoptosis  

PubMed Central

Background The unfolded protein response (UPR) is a major signalling cascade acting in the quality control of protein folding in the endoplasmic reticulum (ER). The cascade is known to play an accessory role in a range of genetic and environmental disorders including neurodegenerative and cardiovascular diseases, diabetes and kidney diseases. The three major receptors of the ER stress involved with the UPR, i.e. IRE1 ?, PERK and ATF6, signal through a complex web of pathways to convey an appropriate response. The emerging behaviour ranges from adaptive to maladaptive depending on the severity of unfolded protein accumulation in the ER; however, the decision mechanism for the switch and its timing have so far been poorly understood. Results Here, we propose a mechanism by which the UPR outcome switches between survival and death. We compose a mathematical model integrating the three signalling branches, and perform a comprehensive bifurcation analysis to investigate possible responses to stimuli. The analysis reveals three distinct states of behaviour, low, high and intermediate activity, associated with stress adaptation, tolerance, and the initiation of apoptosis. The decision to adapt or destruct can, therefore, be understood as a dynamic process where the balance between the stress and the folding capacity of the ER plays a pivotal role in managing the delivery of the most appropriate response. The model demonstrates for the first time that the UPR is capable of generating oscillations in translation attenuation and the apoptotic signals, and this is supplemented with a Bayesian sensitivity analysis identifying a set of parameters controlling this behaviour. Conclusions This work contributes largely to the understanding of one of the most ubiquitous signalling pathways involved in protein folding quality control in the metazoan ER. The insights gained have direct consequences on the management of many UPR-related diseases, revealing, in addition, an extended list of candidate disease modifiers. Demonstration of stress adaptation sheds light to how preconditioning might be beneficial in manifesting the UPR outcome to prevent untimely apoptosis, and paves the way to novel approaches for the treatment of many UPR-related conditions. PMID:23433609

2013-01-01

295

Comparative Genomic and Transcriptomic Analyses Reveal Habitat Differentiation and Different Transcriptional Responses during Pectin Metabolism in Alishewanella Species  

PubMed Central

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

Jung, Jaejoon

2013-01-01

296

Resistance to oomycetes: a general role for the hypersensitive response?  

Microsoft Academic Search

Oomycete plant pathogens, such as Phytophthora, downy mildews and Pythium, have devastating disease effects on numerous crop and ornamental plants. Various types of genetic resistance to oomycetes occur in plants, and can be determined at the subspecific or varietal level (race or cultivar-specific resistance), or at the species or genus level (nonhost resistance). In addition, resistance might be a quantitative

Sophien Kamoun; Edgar Huitema; Vivianne G. A. A. Vleeshouwers

1999-01-01

297

A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis  

PubMed Central

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

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

298

Mos1 Mutagenesis Reveals a Diversity of Mechanisms Affecting Response of Caenorhabditis elegans to the Bacterial Pathogen Microbacterium nematophilum  

PubMed Central

A specific host–pathogen interaction exists between Caenorhabditis elegans and the gram-positive bacterium Microbacterium nematophilum. This bacterium is able to colonize the rectum of susceptible worms and induces a defensive tail-swelling response in the host. Previous mutant screens have identified multiple loci that affect this interaction. Some of these loci correspond to known genes, but many bus genes [those with a bacterially unswollen (Bus) mutant phenotype] have yet to be cloned. We employed Mos1 transposon mutagenesis as a means of more rapidly cloning bus genes and identifying new mutants with altered pathogen response. This approach revealed new infection-related roles for two well-characterized and much-studied genes, egl-8 and tax-4. It also allowed the cloning of a known bus gene, bus-17, which encodes a predicted galactosyltransferase, and of a new bus gene, bus-19, which encodes a novel, albeit ancient, protein. The results illustrate advantages and disadvantages of Mos1 transposon mutagenesis in this system. PMID:17151260

Yook, Karen; Hodgkin, Jonathan

2007-01-01

299

Environmental proteomics reveals early microbial community responses to biostimulation at a uranium- and nitrate-contaminated site.  

PubMed

High-performance MS instrumentation coupled with improved protein extraction techniques enables metaproteomics to identify active members of soil and groundwater microbial communities. Metaproteomics workflows were applied to study the initial responses (i.e. 4 days post treatment) of the indigenous aquifer microbiota to biostimulation with emulsified vegetable oil (EVO) at a uranium-contaminated site. Members of the Betaproteobacteria (i.e. Dechloromonas, Ralstonia, Rhodoferax, Polaromonas, Delftia, Chromobacterium) and the Firmicutes dominated the biostimulated aquifer community. Proteome characterization revealed distinct differences between the microbial biomass collected from groundwater influenced by biostimulation and groundwater collected upgradient of the EVO injection points. In particular, proteins involved in ammonium assimilation, EVO degradation, and polyhydroxybutyrate granule formation were prominent following biostimulation. Interestingly, the atypical NosZ of Dechloromonas spp. was highly abundant, suggesting active nitrous oxide (N2 O) respiration. c-Type cytochromes were barely detected, as was citrate synthase, a biomarker for hexavalent uranium reduction activity, suggesting that uranium reduction has not commenced 4 days post EVO amendment. Environmental metaproteomics identified microbial community responses to biostimulation and elucidated active pathways demonstrating the value of this technique as a monitoring tool and for complementing nucleic acid-based approaches. PMID:23894087

Chourey, Karuna; Nissen, Silke; Vishnivetskaya, Tatiana; Shah, Manesh; Pfiffner, Susan; Hettich, Robert L; Löffler, Frank E

2013-10-01

300

Capturing Arabidopsis Root Architecture Dynamics with root-fit Reveals Diversity in Responses to Salinity1[W][OPEN  

PubMed Central

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

Julkowska, Magdalena M.; Hoefsloot, Huub C.J.; Mol, Selena; Feron, Richard; de Boer, Gert-Jan; Haring, Michel A.; Testerink, Christa

2014-01-01

301

Imaging reveals the focal area of spreading depolarizations and a variety of hemodynamic responses in a rat microembolic stroke model.  

PubMed

Spreading depolarizations (SDs) occur in stroke, but the spatial association between SDs and the corresponding hemodynamic changes is incompletely understood. We applied multimodal imaging to visualize the focal area of selected SDs, and hemodynamic responses with SDs propagating over the ischemic cortex. The intracarotid infusion of polyethylene microspheres (d=45 to 53??m) produced multifocal ischemia in anesthetized rats (n=7). Synchronous image sequences captured through a cranial window above the frontoparietal cortex revealed: Changes in membrane potential (voltage-sensitive (VS) dye method); cerebral blood flow (CBF; laser speckle contrast (LSC) imaging); and hemoglobin (Hb) deoxygenation (red intrinsic optical signal (IOS) at 620 to 640?nm). A total of 31 SD events were identified. The foci of five SDs were seen in the cranial window, originating where CBF was the lowest (56.9±9%), but without evident signs of infarcts. The hyperemic CBF responses to propagating SDs were coupled with three types of Hb saturation kinetics. More accentuated Hb desaturation was related to a larger decrease in CBF shortly after ischemia induction. Microsphere-induced embolization triggers SDs in the rat brain, relevant for small embolic infarcts in patients. The SD occurrence during the early phase of ischemia is not tightly associated with immediate infarct evolution. Various kinetics of Hb saturation may determine the metabolic consequences of individual SDs. PMID:25074743

Bere, Zsófia; Obrenovitch, Tihomir P; Kozák, Gábor; Bari, Ferenc; Farkas, Eszter

2014-10-01

302

Expression profiling reveals functionally redundant multiple-copy genes related to zinc, iron and cadmium responses in Brassica rapa.  

PubMed

Genes underlying environmental adaptability tend to be over-retained in polyploid plant species. Zinc deficiency (ZnD) and iron deficiency (FeD), excess Zn (ZnE) and cadmium exposure (CdE) are major environmental problems for crop cultivation, but little is known about the differential expression of duplicated genes upon these stress conditions. Applying Tag-Seq technology to leaves of Brassica rapa grown under FeD, ZnD, ZnE or CdE conditions, with normal conditions as a control, we examined global gene expression changes and compared the expression patterns of multiple paralogs. We identified 812, 543, 331 and 447 differentially expressed genes under FeD, ZnD, ZnE and CdE conditions, respectively, in B. rapa leaves. Genes involved in regulatory networks centered on the transcription factors bHLH038 or bHLH100 were differentially expressed under (ZnE-induced) FeD. Further analysis revealed that genes associated with Zn, Fe and Cd responses tended to be over-retained in the B. rapa genome. Most of these multiple-copy genes showed the same direction of expression change under stress conditions. We conclude that the duplicated genes involved in trace element responses in B. rapa are functionally redundant, making the regulatory network more complex in B. rapa than in Arabidopsis thaliana. PMID:24738937

Li, Jimeng; Liu, Bo; Cheng, Feng; Wang, Xiaowu; Aarts, Mark G M; Wu, Jian

2014-07-01

303

Asthma and chemical hypersensitivity: prevalence, etiology, and age of onset.  

PubMed

This study investigates asthma's national prevalence and potential overlap with chemical hypersensitivity. It also examines asthma's etiology, age of onset, and demographic characteristics. Data were collected from a geographically weighted random sample of the continental U.S. (1058 cases), in four seasonal cohorts (2005-2006). The study found that 12.9% of the sample report asthma, 11.6% report chemical hypersensitivity, and 31.4% of those with asthma report chemical hypersensitivity. Among asthmatics, 38% report irritation from scented products, 37.2% report health problems from air fresheners, and 13.6% report their asthma was caused by toxic exposure. Asthma cases affected each racial/ethic group in roughly the same proportion, with nearly 50% classified as childhood onset. PMID:19318506

Caress, S M; Steinemann, A C

2009-02-01

304

The generalization of an olfactory-based conditioned response reveals unique but overlapping odour representations in the moth Manduca sexta.  

PubMed

Most highly derived olfactory systems, such as the insect antennal lobe, discriminate among a wide array of monomolecular odourants and blends of odourants. Given the relatively limited number of neurons used to code these odours, this ability implies that neural representations for odours overlap in a cross-fiber coding scheme. Here we use the generalization of a conditioned feeding response in the sphinx moth, Manduca sexta, to quantify three geometry-based dimensions of odour space in which monomolecular odours may be assessed. In a series of experiments we show that generalization of a conditioned response from one monomolecular odour to another is a function of differences in length and shape of the carbon chain as well as the functional group on the molecule. When moths were conditioned to 2-hexanone or 1-decanol and tested with a number of alcohols and ketones, we found that the generalization of the conditioned response decreased as a function of the chain length and functional group. In contrast, when conditioned to 1-hexanol, moths failed to distinguish alcohols from ketones of the same chain length. In all of these cases, chain length did not interact with functional group, thus indicating the independence of these dimensions. Differential conditioning of alcohols and of alcohols and ketones revealed interaction of excitatory and inhibitory generalization gradients within an odour 'dimension'. When odourants were sufficiently distinct, the peak of the generalization gradient was shifted away from the conditioning odour and in an opposite direction from the unreinforced odour. Altogether, these data substantiate the claim that these molecular characteristics are relevant coding dimensions in the moth olfactory system. These data are consistent with a cross-fiber coding scheme in which odours are coded by spatio-temporally overlapping sets of neurons, both in the periphery and in the antennal lobes. PMID:11551996

Daly, K C; Chandra, S; Durtschi, M L; Smith, B H

2001-09-01

305

Expression Profiling during Arabidopsis/Downy Mildew Interaction Reveals a Highly-Expressed Effector That Attenuates Responses to Salicylic Acid  

PubMed Central

Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome. PMID:25329884

Asai, Shuta; Caillaud, Marie-Cecile; Furzer, Oliver J.; Ishaque, Naveed; Wirthmueller, Lennart; Fabro, Georgina; Shirasu, Ken; Jones, Jonathan D. G.

2014-01-01

306

Hypersensitivity to common tree pollens in New York City patients.  

PubMed

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

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

2002-01-01

307

Neuropathy-Induced Spinal GAP-43 Expression Is Not a Main Player in the Onset of Mechanical Pain Hypersensitivity  

PubMed Central

Abstract Structural plasticity within the spinal nociceptive network may be fundamental to the chronic nature of neuropathic pain. In the present study, the spatiotemporal expression of growth-associated protein-43 (GAP-43), a protein which has been traditionally implicated in nerve fiber growth and sprouting, was investigated in relation to mechanical pain hypersensitivity. An L5 spinal nerve transection model was validated by the presence of mechanical pain hypersensitivity and an increase in the early neuronal activation marker cFos within the superficial spinal dorsal horn upon innocuous hindpaw stimulation. Spinal GAP-43 was found to be upregulated in the superficial L5 dorsal horn from 5 up to 10 days after injury. GAP-43 was co-localized with calcitonin-gene related peptide (CGRP), but not vesicular glutamate transporter-1 (VGLUT-1), IB4, or protein kinase-? (PKC-?), suggesting the regulation of GAP-43 in peptidergic nociceptive afferents. These GAP-43/CGRP fibers may be indicative of sprouting peptidergic fibers. Fiber sprouting largely depends on growth factors, which are typically associated with neuro-inflammatory processes. The putative role of neuropathy-induced GAP-43 expression in the development of mechanical pain hypersensitivity was investigated using the immune modulator propentofylline. Propentofylline treatment strongly attenuated the development of mechanical pain hypersensitivity and glial responses to nerve injury as measured by microglial and astroglial markers, but did not affect neuropathy-induced levels of spinal GAP-43 or GAP-43 regulation in CGRP fibers. We conclude that nerve injury induces structural plasticity in fibers expressing CGRP, which is regarded as a main player in central sensitization. Our data do not, however, support a major role of these structural changes in the onset of mechanical pain hypersensitivity. PMID:21671799

Jaken, Robby J.; van Gorp, Sebastiaan; Joosten, Elbert A.; Losen, Mario; Martinez-Martinez, Pilar; De Baets, Marc; Marcus, Marco A.

2011-01-01

308

Contact hypersensitivity to oxazolone provokes vulvar mechanical hyperalgesia in mice.  

PubMed

The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone. Female mice were sensitized with topical oxazolone on their flanks and challenged 1-3 times on the labia. We then measured mechanical sensitivity of the vulvar region with an electronic pressure meter and evaluated expression of inflammatory genes, leukocyte influx and levels of innervation in the labiar tissue. Oxazolone-sensitized mice developed vulvar mechanical hyperalgesia after a single labiar oxazolone challenge. Hyperalgesia lasted up to 24 hours along with local influx of neutrophils, upregulation of inflammatory cytokine gene expression, and increased density of cutaneous labiar nerve fibers. Three daily oxazolone challenges produced vulvar mechanical hyperalgesic responses and increases in nerve density that were detectable up to 5 days post-challenge even after overt inflammation resolved. This persistent vulvar hyperalgesia is resonant with vulvodynia, an understudied chronic pain condition that is remarkably prevalent in 18-60 year-old women. An elevated risk for vulvodynia has been associated with a history of environmental allergies. Our pre-clinical model can be readily adapted to regimens of chronic exposures and long-term assessment of vulvar pain with and without concurrent inflammation to improve our understanding of mechanisms underlying subsets of vulvodynia and to develop new therapeutics for this condition. PMID:24205293

Martinov, Tijana; Glenn-Finer, Rose; Burley, Sarah; Tonc, Elena; Balsells, Evelyn; Ashbaugh, Alyssa; Swanson, Linnea; Daughters, Randy S; Chatterjea, Devavani

2013-01-01

309

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

PubMed Central

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

Erkes, Dan A.; Selvan, Senthamil R.

2014-01-01

310

Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles  

PubMed Central

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

2012-01-01

311

De Novo Transcriptome and Small RNA Analysis of Two Chinese Willow Cultivars Reveals Stress Response Genes in Salix matsudana  

PubMed Central

Salix matsudana Koidz. is a deciduous, rapidly growing, and drought resistant tree and is one of the most widely distributed and commonly cultivated willow species in China. Currently little transcriptomic and small RNAomic data are available to reveal the genes involve in the stress resistant in S. matsudana. Here, we report the RNA-seq analysis results of both transcriptome and small RNAome data using Illumina deep sequencing of shoot tips from two willow variants(Salix. matsudana and Salix matsudana Koidz. cultivar ‘Tortuosa’). De novo gene assembly was used to generate the consensus transcriptome and small RNAome, which contained 106,403 unique transcripts with an average length of 944 bp and a total length of 100.45 MB, and 166 known miRNAs representing 35 miRNA families. Comparison of transcriptomes and small RNAomes combined with quantitative real-time PCR from the two Salix libraries revealed a total of 292 different expressed genes(DEGs) and 36 different expressed miRNAs (DEMs). Among the DEGs and DEMs, 196 genes and 24 miRNAs were up regulated, 96 genes and 12 miRNA were down regulated in S. matsudana. Functional analysis of DEGs and miRNA targets showed that many genes were involved in stress resistance in S. matsudana. Our global gene expression profiling presents a comprehensive view of the transcriptome and small RNAome which provide valuable information and sequence resources for uncovering the stress response genes in S. matsudana. Moreover the transcriptome and small RNAome data provide a basis for future study of genetic resistance in Salix. PMID:25275458

Zeng, Yanfei; He, Caiyun; Duan, Aiguo; Zhang, Jianguo

2014-01-01

312

De novo transcriptome and small RNA analysis of two Chinese willow cultivars reveals stress response genes in Salix matsudana.  

PubMed

Salix matsudana Koidz. is a deciduous, rapidly growing, and drought resistant tree and is one of the most widely distributed and commonly cultivated willow species in China. Currently little transcriptomic and small RNAomic data are available to reveal the genes involve in the stress resistant in S. matsudana. Here, we report the RNA-seq analysis results of both transcriptome and small RNAome data using Illumina deep sequencing of shoot tips from two willow variants(Salix. matsudana and Salix matsudana Koidz. cultivar 'Tortuosa'). De novo gene assembly was used to generate the consensus transcriptome and small RNAome, which contained 106,403 unique transcripts with an average length of 944 bp and a total length of 100.45 MB, and 166 known miRNAs representing 35 miRNA families. Comparison of transcriptomes and small RNAomes combined with quantitative real-time PCR from the two Salix libraries revealed a total of 292 different expressed genes(DEGs) and 36 different expressed miRNAs (DEMs). Among the DEGs and DEMs, 196 genes and 24 miRNAs were up regulated, 96 genes and 12 miRNA were down regulated in S. matsudana. Functional analysis of DEGs and miRNA targets showed that many genes were involved in stress resistance in S. matsudana. Our global gene expression profiling presents a comprehensive view of the transcriptome and small RNAome which provide valuable information and sequence resources for uncovering the stress response genes in S. matsudana. Moreover the transcriptome and small RNAome data provide a basis for future study of genetic resistance in Salix. PMID:25275458

Rao, Guodong; Sui, Jinkai; Zeng, Yanfei; He, Caiyun; Duan, Aiguo; Zhang, Jianguo

2014-01-01

313

Suppression of Delayed-Type Hypersensitivity in Mice Pretreated With Diethylstilbesterol: Involvement of Sex Hormones in Immunomodulation  

Microsoft Academic Search

Delayed-type hypersensitivity (DTH) responses were suppressed in female mice treated with diethylstilbesterol (DES), a synthetic nonsteroidal compound possessing estro- genic activity, but not in male mice. Upon analysis of this DTH-suppression in DES- treated female mice by use of the macrophage migration inhibition (Ml) assay, an in vitro correlate of DTH, suppressor adherent cells (i.e., macrophages) in the peritoneal cavity

Kazuyuki Kato; Yu Chen; Akio Nakane; Tomonori Minagawa; Kenji Fujieda; Takuro Kimura; Ken-ichi Yamamoto

314

Cordycepin-hypersensitive growth links elevated polyphosphate levels to inhibition of poly(A) polymerase in Saccharomyces cerevisiae  

Microsoft Academic Search

To identify genes involved in poly(A) metabolism, we screened the yeast gene deletion collection for growth defects in the presence of cordycepin (3'-deoxyadenosine), a precursor to the RNA chain terminating ATP analog cordycepin triphosphate. Dpho80 and Dpho85 strains, which have a constitu- tively active phosphate-response pathway, were identified as cordycepin hypersensitive. We show that inorganic polyphosphate (poly P) accumulated in

Sandra Holbein; Florian M. Freimoser; Thomas P. Werner; Agnieszka Wengi; Bernhard Dichtl

2007-01-01

315

Spinal Glial Activation Contributes to Postoperative Mechanical Hypersensitivity in the Rat  

Microsoft Academic Search

The activation of spinal cord microglia and astrocytes after peripheral nerve injury or inflammation contributes to behavioral hypersensitivity. The contribution of spinal cord glia to mechanical hypersensitivity after hind paw incision has not been investigated previously. Male Sprague-Dawley rats underwent a unilateral plantar hind paw incision, and the development of mechanical hypersensitivity was assessed by using von Frey filaments. The

Hideaki Obata; James C. Eisenach; Hesham Hussain; Tanishua Bynum; Michelle Vincler

2006-01-01

316

Fluorescence spectroscopy of soluble E. coli SPase I ?2-75 reveals conformational changes in response to ligand binding.  

PubMed

The bacterial Sec pathway is responsible for the translocation of secretory preproteins. During the later stages of transport, the membrane-embedded signal peptidase I (SPase I) cleaves the signal peptide from a preprotein. We used tryptophan fluorescence spectroscopy of a soluble, catalytically active E. coli SPase I ?2-75 enzyme to study its dynamic conformational changes while in solution and when interacting with lipids and signal peptides. We generated four single Trp SPase I ?2-75 mutants, W261, W284, W300, and W310. Based on fluorescence quenching experiments, W300 and W310 were found to be more solvent accessible than W261 and W284 in the absence of ligands. W300 and W310 inserted into lipids, consistent with their location at the enzyme's proposed membrane-interface region, while the solvent accessibilities of W261, W284, and W300 were modified in the presence of signal peptide, suggesting propagation of structural changes beyond the active site in response to peptide binding. The signal peptide binding affinity for the enzyme was measured via FRET experiments and the Kd determined to be 4.4 ?M. The location of the peptide with respect to the enzyme was also established; this positioning is crucial for the peptide to gain access to the enzyme active site as it emerges from the translocon into the membrane bilayer. These studies reveal enzymatic structural changes required for preprotein proteolysis as it interacts with its two key partners, the signal peptide and membrane phospholipids. PMID:24115229

Bhanu, Meera K; Kendall, Debra A

2014-04-01

317

Community-wide response of the gut microbiota to enteropathogenic Citrobacter rodentium infection revealed by deep sequencing.  

PubMed

We investigated the spatial and temporal response of the murine gut microbiome to infection with Citrobacter rodentium, an attaching-and-effacing bacterium that provokes innate and adaptive immune responses, resulting in transient bacterial colitis. Previous studies have suggested that C. rodentium-induced inflammation is associated with an increased abundance of Enterobacteriaceae. We report here a deeper analysis of this model using DNA bar coding and 454 pyrosequencing to characterize 101,894 partial 16S rRNA gene sequences from 85 microbial samples from tissue-adhered and luminal bacteria of the cecum, proximal colon, and distal colon, which allowed us to identify previously unappreciated spatial and kinetic changes in multiple bacterial lineages. The deep sequencing data revealed that C. rodentium was most abundantly associated with the cecal mucosa at day 9 postinfection and then diminished in abundance, providing the first reported use of deep sequencing to track a pathogen in vivo through the course of infection. Notable changes were associated with both the mucosally adhered and luminal microbiota at both day 9 and day 14 postinfection. Alterations in abundance were seen for Proteobacteria, Deferribacteres, Clostridia, and others; however, changes in Enterobacteriaceae could be accounted for by the presence of C. rodentium itself, which is a member of this family. The Lactobacillus group decreased in abundance during infection, which may be important for pathogenesis because members of this lineage modulate the composition of the gut microbiota and are used as probiotics. Thus, deep sequencing provides previously inaccessible information on how Citrobacter infection and clearance reshapes the gut microbial community in space and time. PMID:19635824

Hoffmann, Christian; Hill, David A; Minkah, Nana; Kirn, Thomas; Troy, Amy; Artis, David; Bushman, Frederic

2009-10-01

318

Short- and long-latency somatosensory neuronal responses reveal selective brain injury and effect of hypothermia in global hypoxic ischemia  

PubMed Central

Evoked potentials recorded from the somatosensory cortex have been shown to be an electrophysiological marker of brain injury in global hypoxic ischemia (HI). The evoked responses in somatosensory neurons carry information pertaining to signal from the ascending pathway in both the subcortical and cortical areas. In this study, origins of the subcortical and cortical signals are explored by decomposing the evoked neuronal activities into short- and long-latency responses (SLR and LLR), respectively. We evaluated the effect of therapeutic hypothermia on SLR and LLR during early recovery from cardiac arrest (CA)-induced HI in a rodent model. Twelve rats were subjected to CA, after which half of them were treated with hypothermia (32–34°C) and the rest were kept at normal temperature (36–37°C). Evoked neuronal activities from the primary somatosensory cortex, including multiunit activity (MUA) and local field potential (LFP), were continuously recorded during injury and early recovery. Results showed that upon initiation of injury, LLR disappeared first, followed by the disappearance of SLR, and after a period of isoelectric silence SLR reappeared prior to LLR. This suggests that cortical activity, which primarily underlies the LLR, may be more vulnerable to ischemic injury than SLR, which relates to subcortical activity. Hypothermia potentiated the SLR but suppressed the LLR by delaying its recovery after CA (hypothermia: 38.83 ± 5.86 min, normothermia: 23.33 ± 1.15 min; P < 0.05) and attenuating its amplitude, suggesting that hypothermia may selectively downregulate cortical activity as an approach to preserve the cerebral cortex. In summary, our study reveals the vulnerability of the somatosensory neural structures to global HI and the differential effects of hypothermia on these structures. PMID:22157111

Wu, Dan; Xiong, Wei; Jia, Xiaofeng; Geocadin, Romergryko G.

2012-01-01

319

Analysis of the Organic Hydroperoxide Response of Chromobacterium violaceum Reveals That OhrR Is a Cys-Based Redox Sensor Regulated by Thioredoxin  

PubMed Central

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

da Silva Neto, José F.; Negretto, Caroline C.; Netto, Luis E. S.

2012-01-01

320

Assessment of immediate and delayed hypersensitivity skin tests with Schistosoma mansoni adult worm antigen in a rural Egyptian population.  

PubMed

Immediate and delayed hypersensitivity responses to schistosome adult worm skin test antigen were assessed in 418 farmers in Dakahlia Governorate, Egypt. All were from a population frame being epidemiologically evaluated for bilharzial urinary bladder cancer and thus were all 20 years old or older. A control, group of 108 adult urban dwellers without antecedent or current history of schistosomiasis were also tested. Ninety eight percent (411/418) of farmers and 35% (38/108) of controls showed reaginic hypersensitivity to 20 micrograms protein antigen. While 43% (180/418) of farmers and 4.6% (5/108) of controls showed positive delayed responses. Schistosoma haematobium eggs were found in 6% on urine cytology smears (Papanicolaou) and in 5% by Nuclepore filtration. A subsample of 97 individuals showed 21% to have S. haematobium eggs in urine by a traditional sedimentation technique. Immediate skin tests were equally positive in egg positive or egg negative farmers but delayed responses were 55% positive in the former and 26% in the latter. It is suggested that the delayed hypersensitivity skin test may be more specific and useful in epidemiologic surveys. The changing prevalence of S. haematobium infections in the Nile Delta is briefly discussed. PMID:7210159

Higashi, G I; El-Asfahani, A M; El-Bolkainy, M N; Chu, E W; Raafat, M

1980-09-01

321

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

PubMed Central

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

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

2013-01-01

322

Transcriptomic analysis of responses to exudates reveal genes required for rhizosphere competence of the endophyte Azoarcus sp. strain BH72.  

PubMed

Endophytic colonization is a very complex process which is not yet completely understood. Molecules exuded by the plants may act as signals which influence the ability of the microbe to colonize the host or survive in the rhizosphere. Here we used the whole genome microarray approach to investigate the response of the diazotrophic model endophyte, Azoarcus sp. strain BH72, to exudates of O. sativa cv. Nipponbare in order to identify differentially regulated genes. On exposure to exudates, an overall expression of 4.4% of the 3992 protein coding genes of Azoarcus sp. strain BH72 was altered, out of which 2.4% was upregulated and 2.0% was downregulated. Genes with modulated expression included a few whose involvement in plant-microbe interaction had already been established, whereas a large fraction comprised of genes encoding proteins with putative or unknown functions. Mutational analysis of several differentially regulated genes like those encoding a minor pilin PilX, signal transduction proteins containing GGDEF domains and a serine-threonine kinase as a putative component of the type IV secretion system (T6SS), revealed their role in host colonization. Our data suggest that strain BH72 may be primed for the endophytic lifestyle by exudates, as the expression of bacterial genes relevant for endophytic colonization of roots is induced by root exudates. PMID:22616609

Shidore, Teja; Dinse, Theresa; Öhrlein, Johannes; Becker, Anke; Reinhold-Hurek, Barbara

2012-10-01

323

Drosophila cryb mutation reveals two circadian clocks that drive locomotor rhythm and have different responsiveness to light.  

PubMed

Cryptochrome (CRY) is a blue-light-absorbing protein involved in the photic entrainment of the circadian clock in Drosophila melanogaster. We have investigated the locomotor activity rhythms of flies carrying cryb mutant and revealed that they have two separate circadian oscillators with different responsiveness to light. When kept in constant light conditions, wild-type flies became arrhythmic, while cryb mutant flies exhibited free-running rhythms with two rhythmic components, one with a shorter and the other with a longer free-running period. The rhythm dissociation was dependent on the light intensities: the higher the light intensities, the greater the proportion of animals exhibiting the two oscillations. External photoreceptors including the compound eyes and the ocelli are the likely photoreceptors for the rhythm dissociation, since rhythm dissociation was prevented in so1;cryb and norpAP41;cryb double mutant flies. Immunohistochemical analysis demonstrated that the PERIOD expression rhythms in ventrally located lateral neurons (LNvs) occurred synchronously with the shorter period component, while those in the dorsally located per-expressing neurons showed PER expression most likely related to the longer period component, in addition to that synchronized to the LNvs. These results suggest that the Drosophila locomotor rhythms are driven by two separate per-dependent clocks, responding differentially to constant light. PMID:15183277

Yoshii, Taishi; Funada, Yuriko; Ibuki-Ishibashi, Tadashi; Matsumoto, Akira; Tanimura, Teiichi; Tomioka, Kenji

2004-06-01

324

High-Density PhyloChip profiling of stimulated aquifer microbial communities reveals a complex response to acetate amendment  

SciTech Connect

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.

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

325

Spatial-temporal analysis of zinc homeostasis reveals the response mechanisms to acute zinc deficiency in Sorghum bicolor.  

PubMed

Zinc (Zn) is an essential micronutrient in plants. The activity of copper/zinc superoxide dismutase (CSD) and carbonic anhydrase (CA) correlate with differences in Zn efficiency in plants; therefore, it is reasonable to hypothesize the existence of a Zn economy model that saves Zn for these essential Zn proteins during Zn deficiency. However, up to this point, direct evidence for the idea that CSD and/or CA might be priorities for Zn delivery has been lacking. Here, we investigated the spatial-temporal effects of acute Zn depletion and resupply by integrating physiological studies and molecular analyses using hydroponically grown Sorghum. The elevated expression of miR398 repressed CSD expression in roots, whereas the reduced expression of miR528 resulted in a relatively stable level of CSD expression in Sorghum leaves under Zn depletion. Spatial-temporal analysis after Zn resupply to previously depleted plants revealed that the expression and activity of CA were the first to recover after Zn addition, whereas the recovery of the activities of CSD and alcohol dehydrogenase (ADH) was delayed, suggesting that CA receives priority in Zn delivery over CSD and ADH. Our results also indicate that microRNAs (miRNAs) are important regulators of the response of Zn deficiency in plants. PMID:23915383

Li, Yulong; Zhang, Yuan; Shi, Dongqing; Liu, Xiaojing; Qin, Jun; Ge, Qing; Xu, Longhua; Pan, Xiangliang; Li, Wei; Zhu, Yiyong; Xu, Jin

2013-12-01

326

Auditory Hypersensitivity in Children with Autism Spectrum Disorders  

ERIC Educational Resources Information Center

A review of records was completed to determine whether children with auditory hypersensitivities have difficulty tolerating loud sounds due to auditory-system factors or some other factors not directly involving the auditory system. Records of 150 children identified as not meeting autism spectrum disorders (ASD) criteria and another 50 meeting…

Lucker, Jay R.

2013-01-01

327

Cryptococcal culture filtrate antigen for detection of delayed-type hypersensitivity in cryptococcosis.  

PubMed Central

Previous studies on a cryptococcal culture filtrate (CneF) antigen have shown that the antigen is useful in detecting delayed-type hypersensitivity and that it is specific for Cryptococcus. This study further defined one more parameter of specificity, showing that the CneF antigen does not elicit delayed-type hypersensitivity responses in Cryptococcus albidus-sensitized guinea pigs. When the crude CneF antigen was subjected to ultrafiltration fractionation, the skin test active components were found to be in the 50,000 or greater molecular weight range fraction. The concentrated retentates of the XM50 ultrafiltration membrane were more sensitive antigens than the crude CneF antigens. Further fractionation of the XM50 retentate using 3% acrylamide gel electrophoresis separated the antigen into two bands. One band, the P fraction, migrated only a short distance into the gel; the fraction was carbohydrate-like and did not elicit significant skin test responses in sensitized guinea pigs. The other band, G fraction, appeared with the tracking dye, was glycoprotein-like, and elicited significantly positive skin tests in sensitized guinea pigs. G fractions prepared using three different serotypes of Cryptococcus neoformans elicited similar size indurations when used in skin testing guinea pigs sensitized with either the homologous serotype isolated of C. neoformans or the heterologous serotype isolate. Images PMID:383616

Murphy, J W; Pahlavan, N

1979-01-01

328

The differential spatial distribution of secondary metabolites in Arabidopsis leaves reacting hypersensitively to Pseudomonas syringae pv. tomato is dependent on the oxidative burst.  

PubMed

Secondary metabolites (SMs) play key roles in pathogen responses, although knowledge of their precise functions is limited by insufficient characterization of their spatial response. The present study addressed this issue in Arabidopsis leaves by non-targeted and targeted metabolite profiling of Pseudomonas syringae pv. tomato (Pst-AvrRpm1) infected and adjacent uninfected leaf tissues. While overlap was observed between infected and uninfected areas, the non-targeted metabolite profiles of these regions differed quantitatively and clustering analysis underscores a differential distribution of SMs within distinct metabolic pathways. Targeted metabolite profiling revealed that infected tissues accumulate more salicylic acid and the characteristic phytoalexin of Arabidopsis, camalexin, than uninfected adjacent areas. On the contrary, the antioxidant coumarin derivative, scopoletin, was induced in infected tissues while its glucoside scopolin predominated in adjacent tissues. To elucidate the still unclear relationship between the accumulation of SMs and reactive oxygen species (ROS) accumulation and signalling, a catalase-deficient line (cat2) in which ROS signalling is up-regulated, was used. Metabolic analysis of cat2 suggests that some SMs have important interactions with ROS in redox homeostasis during the hypersensitive response to Pst-AvrRpm1. Overall, the study demonstrates that ROS availability influences both the amount and the pattern of infection-induced SM accumulation. PMID:20530195

Simon, Clara; Langlois-Meurinne, Mathilde; Bellvert, Floriant; Garmier, Marie; Didierlaurent, Laure; Massoud, Kamal; Chaouch, Sejir; Marie, Arul; Bodo, Bernard; Kauffmann, Serge; Noctor, Graham; Saindrenan, Patrick

2010-07-01

329

Role of interferons in LPS hypersensitivity  

Microsoft Academic Search

The innate immune response to Gram-negative bacteria depends mainly on the ability of the host to respond to the LPS component. Consequently, the state of LPS sensitivity at the time of infection and the numbers of invading bacteria (i.e. the amounts of LPS) are primary factors determining the innate responses provoked by Gram-negative pathogens. LPS sensitivity increases following treatment of

Marina A. Freudenberg; Christoph Kalis; Yolande Chvatchko; Thomas Merlin; Marina Gumenscheimer; Chris Galanos

2003-01-01

330

Directional responses following recombinant cytokine stimulation of rainbow trout (Oncorhynchus mykiss) RTS11 macrophage cells as revealed by transcriptome profiling  

Microsoft Academic Search

BACKGROUND: The early stages of the immune response are regulated by key cytokines including both interleukin 1? (IL-1?) and interferon-? (IFN-?) which stimulate panels of responsive genes via conserved signal transduction pathways. To further our understanding of the transcriptional response to these cytokines in lower vertebrates we have utilized microarray analysis to characterize the transcriptional response to recombinant rainbow trout

Samuel AM Martin; Jun Zou; Dominic F Houlihan; Christopher J Secombes

2007-01-01

331

Comparative Genome-Wide Transcriptional Analysis of Al-Responsive Genes Reveals Novel Al Tolerance Mechanisms in Rice  

PubMed Central

Rice (Oryza sativa) is the most aluminum (Al)-tolerant crop among small-grain cereals, but the mechanism underlying its high Al resistance is still not well understood. To understand the mechanisms underlying high Al-tolerance, we performed a comparative genome-wide transcriptional analysis by comparing expression profiling between the Al-tolerance cultivar (Koshihikari) and an Al-sensitive mutant star1 (SENSITIVE TO AL RHIZOTOXICITY 1) in both the root tips and the basal roots. Exposure to 20 µM AlCl3 for 6 h resulted in up-regulation (higher than 3-fold) of 213 and 2015 genes including 185 common genes in the root tips of wild-type and the mutant, respectively. On the other hand, in the basal root, genes up-regulated by Al were 126 and 2419 including 76 common genes in the wild-type and the mutant, respectively. These results indicate that Al-response genes are not only restricted to the root tips, but also in the basal root region. Analysis with genes up- or down-regulated only in the wild-type reveals that there are other mechanisms for Al-tolerance except for a known transcription factor ART1-regulated one in rice. These mechanisms are related to nitrogen assimilation, secondary metabolite synthesis, cell-wall synthesis and ethylene synthesis. Although the exact roles of these putative tolerance genes remain to be examined, our data provide a platform for further work on Al-tolerance in rice. PMID:23110212

Tsutsui, Tomokazu; Yamaji, Naoki; Huang, Chao Feng; Motoyama, Ritsuko; Nagamura, Yoshiaki; Ma, Jian Feng

2012-01-01

332

Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome  

PubMed Central

AIM: To investigate the role of epidermal growth factor (EGF) in visceral hypersensitivity and its effect on the serotonin transporter (SERT). METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson’s correlation analysis. SERT function was examined by tritiated serotonin (5-HT) uptake experiments. Rat intestinal epithelial cells (IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor (EGFR). RESULTS: EGF levels were significantly lower in the rats with visceral hypersensitivity as measured in plasma (2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, P < 0.01) and in colonic tissue (3.244 ± 0.135 ng/100 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P < 0.01) compared with controls. Moreover, the EGF levels were positively correlated with SERT levels (r = 0.820, P < 0.01). EGF displayed dose- and time-dependent increased SERT gene expressions in IEC-6 cells. An EGFR kinase inhibitor inhibited the effect of EGF on SERT gene upregulation. SERT activity was enhanced following treatment with EGF (592.908 ± 31.515 fmol/min per milligram vs 316.789 ± 85.652 fmol/min per milligram protein, P < 0.05) and blocked by the EGFR kinase inhibitor in IEC-6 cells (590.274 ± 25.954 fmol/min per milligram vs 367.834 ± 120.307 fmol/min per milligram protein, P < 0.05). CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes. PMID:25309082

Cui, Xiu-Fang; Zhou, Wei-Mei; Yang, Yan; Zhou, Jun; Li, Xue-Liang; Lin, Lin; Zhang, Hong-Jie

2014-01-01

333

Seasonal differences in cytokine expression in the skin of Shetland ponies suffering from insect bite hypersensitivity.  

PubMed

Insect bite hypersensitivity (IBH) in horses is a seasonal, IgE-mediated, pruritic skin disorder primarily caused by Culicoides spp. We hypothesize that a mixed Th2/Th1-type immune status, off season, alters into Th2-dominated immune reactivity in the skin of IBH-affected ponies in the IBH season. To study these immune response patterns Culicoides-specific IgE levels, skin histopathology and cytokine and transcription factor mRNA expression (IL4, IL10, IL13, IFN?, FoxP3 and CD3(?)) in lesional and non-lesional skin of ponies affected by IBH in the IBH season were compared with those of the same animals off season and those in skin of healthy ponies in both seasons. The present study revealed a significantly higher histopathology score in lesional skin of affected ponies than in non-lesional skin and skin of healthy ponies in the IBH season. Culicoides obsoletus-specific IgE serum levels of ponies with IBH were significantly higher than those in healthy ponies in both seasons. Interestingly, C. obsoletus-specific IgE serum levels within each group were the same in the IBH season and off season. The expression of IL4, IL13 and IFN? mRNA in skin biopsies in the IBH season showed a significant increase compared to off season in both skin derived from healthy control ponies (n=14) as well as in lesional and in non-lesional skin from IBH-affected animals (n=17). This apparently general up-regulation of cytokine expression during the IBH season directly correlated with an increased CD3(?) mRNA expression in the skin, indicating an overall increased T cell influx during the summer months. The only significant difference observed between lesional skin from IBH-affected animals as compared to skin from healthy control animals in the IBH season was a lower expression of IL13/CD3(?) in the affected animals. FoxP3 and IL10 levels were unaffected, except for a lower expression of FoxP3 in healthy control skin in the IBH season as compared to off season, In addition, the increased level of C. obsoletus-specific IgE did not correlate with higher histological scores in LE skin. In summary, our data indicate a general immune activation in the skin of both healthy and IBH-affected ponies during the IBH season that potentially obscures the Culicoides-specific immune reaction pattern, even in lesional skin of IBH-affected animals. PMID:23219157

Meulenbroeks, C; van der Meide, N M A; Zaiss, D M W; van Oldruitenborgh-Oosterbaan, M M Sloet; van der Lugt, J J; Smak, J; Rutten, V P M G; Willemse, T

2013-01-15

334

The pepper RNA-binding protein CaRBP1 functions in hypersensitive cell death and defense signaling in the cytoplasm.  

PubMed

The regulation of gene expression via post-transcriptional modification by RNA-binding proteins is crucial for plant disease and innate immunity. Here, we report the identification of the pepper (Capsicum annuum) RNA-binding protein1 gene (CaRBP1) as essential for hypersensitive cell death and defense signaling in the cytoplasm. CaRBP1 contains an RNA recognition motif and is rapidly and strongly induced in pepper by avirulent Xanthomonas campestris pv. vesicatoria (Xcv) infection. CaRBP1 displays in vitro RNA- and DNA-binding activity and in planta nucleocytoplasmic localization. Transient expression of CaRBP1 in pepper leaves triggers cell-death and defense responses. Notably, cytoplasmic localization of CaRBP1, mediated by the N-terminal region of CaRBP1, is essential for the hypersensitive cell-death response. Silencing of CaRBP1 in pepper plants significantly enhances susceptibility to avirulent Xcv infection. This is accompanied by compromised hypersensitive cell death, production of reactive oxygen species in oxidative bursts, expression of defense marker genes and accumulation of endogenous salicylic acid and jasmonic acid. Over-expression of CaRBP1 in Arabidopsis confers reduced susceptibility to infection by the biotrophic oomycete Hyaloperonospora arabidopsidis. Together, these results suggest that cytoplasmic localization of CaRBP1 is required for plant signaling of hypersensitive cell-death and defense responses. PMID:22640562

Lee, Dong Hyuk; Kim, Dae Sung; Hwang, Byung Kook

2012-10-01

335

The edible brown seaweed Ecklonia cava reduces hypersensitivity in postoperative and neuropathic pain models in rats.  

PubMed

The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI) rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05). Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats. PMID:24918539

Kim, Jae Goo; Lim, Dong Wook; Cho, Suengmok; Han, Daeseok; Kim, Yun Tai

2014-01-01

336

Insulin Hypersensitivity Induced by Hepatic PTEN Gene Ablation Protects from Murine Endotoxemia  

PubMed Central

Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, intensive insulin treatment has proven to be effective in the reduction of disease related complications in critically ill patients. Insulin effectively reduces glucose levels and thereby contributes to protection. On the other hand insulin is a potent signaling pathway activator. One of those is the PI3K signaling axis. Activation of PI3K is known to limit pro-inflammatory gene expression. Here we can show that in a mouse model of insulin hypersensitivity induced by the deletion of the PI3K antagonist PTEN, specifically in hepatic tissue, significant protection is conferred in murine models of lethal endotoxemia and sepsis. Acute inflammatory responses are diminished, glucose metabolism normalized and vascular activation is reduced. Furthermore we investigated the hepatic gene expression profile of relevant anti-inflammatory genes in PTEN deficient mice and found marked upregulation of PPAR? and HO-1. We conclude from our data that insulin hypersensitivity via sustained activation of the PI3K signaling pathway exerts protective effects in acute inflammatory processes. PMID:23825606

Guenzl, Philipp M.; Raim, Roman; Kral, Julia; Brunner, Julia; Sahin, Emine; Schabbauer, Gernot

2013-01-01

337

Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management  

PubMed Central

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.

Rampton, David; Folkersen, Joergen; Fishbane, Steven; Hedenus, Michael; Howaldt, Stefanie; Locatelli, Francesco; Patni, Shalini; Szebeni, Janos; Weiss, Guenter

2014-01-01

338

Peripheral metabotropic glutamate receptor 5 mediates mechanical hypersensitivity in craniofacial muscle via protein kinase C dependent mechanisms.  

PubMed

We previously demonstrated that peripherally located N-methyl-D-aspartic acid (NMDA) receptors contribute to acute muscle nociception and the development of chronic muscular hyperalgesia. In the present study, we investigated the potential role of peripheral group I metabotropic glutamate receptors (mGluRs 1/5) in the development of muscular hypersensitivity to mechanical stimulation, and attempted to elucidate intracellular signaling mechanisms associated with the mGluR activation in male Sprague-Dawley rats. First, our Western blot analyses revealed that mGluR 5 protein, but not mGluR 1 protein, is reliably detected in trigeminal ganglia and the masseter nerve. Subsequent behavioral studies demonstrated that the group I mGluR agonist, R,S-3,5-dihydroxyphenylglycol (DHPG), significantly decreased the mechanical threshold to noxious stimulation of the masseter, and that the DHPG-induced mechanical hypersensitivity can be effectively prevented by pretreatment of the masseter with 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), a selective mGluR 5 antagonist, but not by 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), a selective mGluR 1 antagonist. Moreover, the DHPG-induced mechanical hypersensitivity was significantly blocked by inhibiting either the alpha or epsilon isoform of protein kinase C (PKC). Collectively, these data provide evidence that peripherally located mGluR 5 may play an important role in the development of masseter hypersensitivity, and that PKC activation is required for the modulatory effect of peripheral mGluR 5 in the craniofacial muscle tissue. Thus, selective targeting of peripheral mGluR 5 and PKCalpha, as well as PKCepsilon, might serve as an effective therapeutic strategy in the management of chronic muscle pain conditions, such as temporomandibular disorders. PMID:17306466

Lee, J-S; Ro, J Y

2007-04-25

339

Involvement of hsr203J like gene homologue, protease and protease inhibitors in triggering differential defense response against Alternaria blight in Brassica  

Microsoft Academic Search

Transcript profiling of hsr203J, a known marker gene for Hypersensitive response (HR), was performed to delineate its role in differential defense against\\u000a Alternaria brassicae in tolerant and susceptible genotypes of Brassica juncea. Reverse transcriptase (RT) PCR approach was utilized to investigate the correlation between expression of hsr203J like gene(s) and pathogenesis in stage dependent manner. It was revealed that the

Arpita Mishra; Dinesh Pandey; Manoj Singh; Anil Kumar

340

Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice  

SciTech Connect

Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells.

Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.; Simpson, T.J.

1986-11-01

341

Diagnosis of hypersensitivity pneumonitis by measurement of antibodies against environmental antigens  

SciTech Connect

Hypersensitivity pneumonitis (HP), an immunologically mediated chronic pulmonary disease, is the result of an inflammatory response of the lung initiated by the inhalation of environmental organic dusts. These organic dusts usually contain substances (antigens) capable of eliciting immune responses in humans. The symptoms of HP generally present as recurrent flu-like episodes which makes it difficult to establish the proper diagnosis. However, detection in patients' sera of high-titer antibodies against the environmental antigens could be of great help in identifying those materials causing the disease and which must be avoided. A highly specific and sensitive serodiagnostic test, a radioimmuno assay (RIA), was developed for measurement of antibodies against antigens relevant to Farmer's Lung Disease (FLD), a type of HP affecting farmers.

Dewair, M. (Univ. Clinic, Grosshadern, Munich (Germany, F.R.))

1989-01-01

342

Diagnosis and management of immediate hypersensitivity reactions to cephalosporins.  

PubMed

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

Kim, Min-Hye; Lee, Jong-Myung

2014-11-01

343

Diagnosis and Management of Immediate Hypersensitivity Reactions to Cephalosporins  

PubMed Central

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

Kim, Min-Hye

2014-01-01

344

Allopurinol hypersensitivity reactions: desensitization strategies and new therapeutic alternative molecules.  

PubMed

Allopurinol, an analog of hypoxanthine has been worldwide used for the treatment of hyperuricemia and gout for over 40 years. Unfortunately some patients assuming this medication have developed hypersensitivity reactions ranging from mild cutaneous eruption to more severe clinical manifestations such as allopurinol hypersensitivity syndrome or Steven-Johnson syndrome and lethal toxic epidermal necrolysis. Various strategies of slow desensitization have been elaborated to reintroduce allopurinol in a part of these patients, mainly patients affected by mild skin reactions as fixed drug eruption or exanthema. However, several new uricosuric therapies have been recently introduced. Actually drugs as recombinant urate oxidase and febuxostat are under post-marketing surveillance to control potential adverse effects related to their immunogenicity even. PMID:23092365

Calogiuri, Gianfranco; Nettis, Eustachio; Di Leo, Elisabetta; Foti, Caterina; Ferrannini, Antonio; Butani, Lavjay

2013-02-01

345

Hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji).  

PubMed

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

Akizuki, N; Inase, N; Ishiwata, N; Jin, Y; Atarashi, K; Ichioka, M; Yoshizawa, Y; Marumo, F

1999-01-01

346

Hypersensitivity pneumonitis due to molds in a saxophone player.  

PubMed

This 48-year-old patient was evaluated for an interstitial pneumonia. An open-lung biopsy showed a pattern of nonspecific interstitial pneumonia. The CT scan appearance, showing mosaic ground-glass opacities in the ventilated parts of the lung, the centrolobular predominance of inflammation on the lung sections, and the presence of a lymphocytic alveolitis at BAL suggested a hypersensitivity pneumonitis. The patient was a white-collar worker and had no contact with pets, birds, drugs, or molds at home. He used to play the saxophone as a hobby. Two molds, Ulocladium botrytis and Phoma sp, were detected in the saxophone. Precipitating antibodies to these molds were present in his serum. An additional study confirmed the frequent colonization of saxophones with potentially pathogenic molds, such as Fusarium sp, Penicillium sp, and Cladosporium sp. Respiratory physicians should be aware of the risk of hypersensitivity pneumonitis in saxophone or perhaps other wind instrument players. PMID:20822994

Metzger, Flora; Haccuria, Amaryllis; Reboux, Gabriel; Nolard, Nicole; Dalphin, Jean-Charles; De Vuyst, Paul

2010-09-01

347

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity  

PubMed Central

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

Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

2014-01-01

348

Genetic basis of ultraviolet-B effects on contact hypersensitivity  

Microsoft Academic Search

The genetic basis of the effects of ultraviolet B(UVB) radiation on the induction of contact hypersensitivity (CH) to dinitrofluorobenzene (DNFB) has been explored in genetically defined mice. It was found that acute, low-dose UVB radiation produced profound depletion of epidermal Langerhans cells (LC) at UVB-treated sites in all strains of mice tested. However, when DNFB was applied to UVB radiation

J. Wayne Streilein; Paul R. Bergstresser

1988-01-01

349

Occupational hypersensitivity pneumonitis in a smelter exposed to zinc fumes  

SciTech Connect

A smelter exposed to zinc fumes reported severe recurrent episodes of cough, dyspnea and fever. Bronchoalveolar lavage showed a marked increase in lymphocytes count with predominance of CD8 T-lymphocytes. Presence of zinc in alveolar macrophages was assessed by analytic transmission electron microscopy. This is the first case of recurrent bronchoalveolitis related to zinc exposure in which the clinical picture and BAL results indicate a probable hypersensitivity pneumonitis.

Ameille, J.; Brechot, J.M.; Brochard, P.; Capron, F.; Dore, M.F. (Consultation de Pathologie Professionnelle, Hopital Raymond Poincare, Garches, (France))

1992-03-01

350

IN VITRO STUDIES OF GRANULOMATOUS HYPERSENSITIVITY TO BERYLLIUM  

Microsoft Academic Search

Lymphocytes were obtained from normal subjects and subjects with granulomatous hypersensitivity to beryllium. Lymphocytes from sensitive persons underwent typical blastogenic transformation when exposed to BeO or BeSO4in vitro. Transformation was maximal between the fifth and sixth days of exposure and was dependent upon the concentration of beryllium.Monocytes from beryllium sensitive subjects matured into macrophages in vitro more rapidly than cells

Jon M. Hanifin; William L. Epstein; Martin J. Cline

1970-01-01

351

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization  

PubMed Central

The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

2013-01-01

352

Anticonvulsant hypersensitivity syndrome associated with carbamazepine administration: Case series  

PubMed Central

Hypersensitivity reactions are common adverse drug reactions (ADRs) associated with antiepileptics. Carbamazepine is one of the routinely prescribed drugs for the treatment of epilepsy and neuropathic pain. ADRs due to carbamazepine range from mild maculopapular rash to severe anticonvulsant hypersensitivity syndrome (AHS). AHS is the triad of fever, rash, and internal organ involvement occurring 1-8 weeks after exposure to an anticonvulsant (1 in 1,000 to 10,000 exposures). Spontaneously reported three cases of AHS-drug hypersensitivity reactions induced by carbamazepine are discussed here. Seven to ten days after starting therapy, patients developed maculopapular skin rashes, fever and liver or kidney involvement. The causal relationship between drug and ADR was found to be ‘certain’ in one case and ‘probable’ in other two cases with both WHO-UMC and Naranjo causality assessment scale. All the three cases show category 4a according to Hartwig's severity scale as ADR was the cause for hospital admission. On assessing preventability of ADRs by modified Schumock and Thorntons’ scale, one case was falling into category of ‘definitely preventable’ and other two were ‘not preventable’. AHS is rare but serious reaction with carbamazepine which requires vigilant monitoring by physicians to avoid major consequences. PMID:24554914

Mehta, Maulin; Shah, Jay; Khakhkhar, Tejas; Shah, Rima; Hemavathi, K. G.

2014-01-01

353

A Case of Hypersensitivity Syndrome to Both Vancomycin and Teicoplanin  

PubMed Central

Drug hypersensitivity syndrome to both vancomycin and teicoplanin has not been previously reported. We describe here a 50-yr-old male patient with vertebral osteomyelitis and epidural abscess who developed hypersensitivity syndrome to both vancomycin and teicoplanin. Skin rash, fever, eosinophilia, interstitial pneumonitis, and interstitial nephritis developed following the administration of each drug, and resolved after withdrawing the drugs and treating with high dose corticosteroids. The vertebral osteomyelitis was successfully treated with 6-week course of linezolid without further complications. Skin patch tests for vancomycin and teicoplanin was done 2 months after the recovery; a weak positive result for vancomycin (10% aq.,+at D2 and +at D4 with erythema and vesicles; ICDRG scale), and a doubtful result for teicoplanin (4% aq.-at D2 and±at D4 with macular erythema; ICDRG scale). We present this case to alert clinicians to the hypersensitivity syndrome that can result from vancomycin and teicoplanin, with possible cross-reactivity, which could potentially be life-threatening. PMID:17179696

Kwon, Hyouk-Soo; Chang, Yoon-Seok; Jeong, Yi-Yeong; Lee, Sang-Min; Song, Woo-Jung; Kim, Hong-Bin; Kim, Yoon-Keun; Cho, Sang-Heon; Kim, You-Young

2006-01-01

354

A novel ethanol-hypersensitive mutant of Arabidopsis.  

PubMed

A novel ethanol-hypersensitive mutant, geko1 (gek1), was isolated from Arabidopsis thaliana. The gek1 mutant displays an enhanced sensitivity (10-100 times greater than the wild type) to ethanol in growth medium, while it grows normally in the absence of ethanol, and responds normally to other alcohols and to environmental stresses such as heat shock and high salinity. The ethanol-hypersensitive phenotype of gek1 requires alcohol dehydrogenase activity, indicating that gek1 is sensitive not to ethanol itself but to the metabolites of ethanol. Consistent with this, gek1 shows enhanced sensitivity to acetaldehyde in the medium. The endogenous acetaldehyde levels were not different between gek1-2 and wild-type seedlings treated with ethanol. These results indicate that the ethanol hypersensitivity of gek1 is due to an enhanced sensitivity to acetaldehyde toxicity, instead of abnormally elevated accumulation of toxic acetaldehyde, which has been thought to be the major cause of ethanol toxicity in mammal cells. PMID:15215505

Hirayama, Takashi; Fujishige, Naoko; Kunii, Takanori; Nishimura, Noriyuki; Iuchi, Satoshi; Shinozaki, Kazuo

2004-06-01

355

Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk.  

PubMed Central

Arene oxide metabolites of aromatic anticonvulsants (phenytoin, phenobarbital, and carbamazepine) may be involved in the pathogenesis of hypersensitivity reactions. We investigated 53 patients with clinical sensitivity to anticonvulsants by exposing their lymphocytes in vitro to drug metabolites generated by a murine hepatic microsomal system. The diagnosis of a hypersensitivity reaction was corroborated by in vitro rechallenge for each drug (phenytoin, n = 34; phenobarbital, n = 22; carbamazepine, n = 25) when cytotoxicity (% dead cells) exceeded 3 SD above the mean result for controls. Cross-reactivity among the drugs was noted. 7 out of 10 patients who had received all three anticonvulsants had adverse reactions to each. 40 out of 50 patients tested to all three drugs in vitro were positive to each. Adverse reactions were indistinguishable among anti-convulsants. Skin rash (87%), fever (94%), hepatitis (51%), and hematologic abnormalities (51%) were common clinical features of each drug. 62% of reactions involved more than two organs. Cells from patients' parents exhibited in vitro toxicity that was intermediate between values for controls and patients. In vitro testing can help diagnose hypersensitivity to anticonvulsants. Cells from patients may also be used for prospective individualization of therapy to decrease risk of adverse reaction. Cross-reactivity among the major anticonvulsants is common and should be considered before deciding on alternative therapy. Images PMID:3198757

Shear, N H; Spielberg, S P

1988-01-01

356

Delayed hypersensitivity reaction from black henna tattoo manifesting as severe facial swelling.  

PubMed

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

Shavit, Itai; Hoffmann, Yoav; Shachor-Meyouhas, Yael; Knaani-Levinz, Hadas

2008-05-01

357

Identification of genes required for Cf-dependent hypersensitive cell death by combined proteomic and RNA interfering analyses  

PubMed Central

Identification of hypersensitive cell death (HCD) regulators is essential to dissect the molecular mechanisms underlying plant disease resistance. In this study, combined proteomic and RNA interfering (RNAi) analyses were employed to identify genes required for the HCD conferred by the tomato resistance gene Cf-4 and the Cladosporium fulvum avirulence gene Avr4. Forty-nine proteins differentially expressed in the tomato seedlings mounting and those not mounting Cf-4/Avr4-dependent HCD were identified through proteomic analysis. Among them were a variety of defence-related proteins including a cysteine protease, Pip1, an operative target of another C. fulvum effector, Avr2. Additionally, glutathione-mediated antioxidation is a major response to Cf-4/Avr4-dependent HCD. Functional analysis through tobacco rattle virus-induced gene silencing and transient RNAi assays of the chosen 16 differentially expressed proteins revealed that seven genes, which encode Pip1 homologue NbPip1, a SIPK type MAP kinase Nbf4, an asparagine synthetase NbAsn, a trypsin inhibitor LeMir-like protein NbMir, a small GTP-binding protein, a late embryogenesis-like protein, and an ASR4-like protein, were required for Cf-4/Avr4-dependent HCD. Furthermore, the former four genes were essential for Cf-9/Avr9-dependent HCD; NbPip1, NbAsn, and NbMir, but not Nbf4, affected a nonadaptive bacterial pathogen Xanthomonas oryzae pv. oryzae-induced HCD in Nicotiana benthamiana. These data demonstrate that Pip1 and LeMir may play a general role in HCD and plant immunity and that the application of combined proteomic and RNA interfering analyses is an efficient strategy to identify genes required for HCD, disease resistance, and probably other biological processes in plants. PMID:22275387

Xu, Qiu-Fang; Cheng, Wei-Shun; Zhang, Zhi-Xin; Xu, You-Ping; Zhou, Xue-Ping; Cai, Xin-Zhong

2012-01-01

358

Functional and Genomic Analyses Reveal an Essential Coordination between the Unfolded Protein Response and ER-Associated Degradation  

Microsoft Academic Search

The unfolded protein response (UPR) regulates gene expression in response to stress in the endoplasmic reticulum (ER). We determined the transcriptional scope of the UPR using DNA microarrays. Rather than regulating only ER-resident chaperones and phospholipid biosynthesis, as anticipated from earlier work, the UPR affects multiple ER and secretory pathway functions. Studies of UPR targets engaged in ER-associated protein degradation

Kevin J. Travers; Christopher K. Patil; Lisa Wodicka; David J. Lockhart; Jonathan S. Weissman; Peter Walter

2000-01-01

359

GLOBAL TRANSCRIPTION PROFILING REVEALS DIFFERENTIAL RESPONSES TO CHRONIC NITROGEN STRESS AND PUTATIVE NITROGEN REGULATORY COMPONENTS IN ARABIDOPSIS  

EPA Science Inventory

Background: A large quantity of nitrogen (N) fertilizer is used for crop production to achieve high yields at a significant economic and environmental cost. Efforts have been directed to understanding the molecular basis of plant responses to N and to identifying N-responsive gen...

360

Flavohaemoglobin HmpX from Erwinia chrysanthemi confers nitrosative stress tolerance and affects the plant hypersensitive reaction by intercepting nitric oxide produced by the host.  

PubMed

Host cells respond to infection by generating nitric oxide (NO) as a cytotoxic weapon to facilitate killing of invading microbes. Bacterial flavohaemoglobins are well-known scavengers of NO and play a crucial role in protecting animal pathogens from nitrosative stress during infection. Erwinia chrysanthemi, which causes macerating diseases in a wide variety of plants, possesses a flavohaemoglobin (HmpX) whose function in plant pathogens has remained unclear. Here we show that HmpX consumes NO and prevents inhibition by NO of cell respiration, indicating a role in protection from nitrosative stress. Furthermore, infection of Saintpaulia ionantha plants with an HmpX-deficient mutant of E. chrysanthemi revealed that the lack of NO scavenging activity causes the accumulation of unusually high levels of NO in host tissue and triggers hypersensitive cell death. Introduction of the wild-type hmpX gene in an incompatible strain of Pseudomonas syringae had a dramatic effect on the hypersensitive cell death in soya bean cell suspensions, and markedly reduced the development of macroscopic symptoms in Arabidopsis thaliana plants. These observations indicate that HmpX not only protects against nitrosative stress but also attenuates host hypersensitive reaction during infection by intercepting NO produced by the plant for the execution of the hypersensitive cell death programme. PMID:15998309

Boccara, Martine; Mills, Catherine E; Zeier, Jürgen; Anzi, Chiara; Lamb, Chris; Poole, Robert K; Delledonne, Massimo

2005-07-01

361

Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination.  

PubMed

Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females. PMID:24367114

Furman, David; Hejblum, Boris P; Simon, Noah; Jojic, Vladimir; Dekker, Cornelia L; Thiébaut, Rodolphe; Tibshirani, Robert J; Davis, Mark M

2014-01-14

362

Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination  

PubMed Central

Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females. PMID:24367114

Furman, David; Hejblum, Boris P.; Simon, Noah; Jojic, Vladimir; Dekker, Cornelia L.; Thiebaut, Rodolphe; Tibshirani, Robert J.; Davis, Mark M.

2014-01-01

363

Mycobacterial glycolipid trehalose 6,6?-dimycolate-induced hypersensitive granulomas: contribution of CD4+ lymphocytes  

PubMed Central

The granulomatous response is a characteristic histological feature of Mycobacterium tuberculosis infection responsible for organism containment. The development of cell-mediated immunity is essential for protection against disease, as well as being required for maintenance of the sequestering granulomatous response. Trehalose 6,6?-dimycolate (TDM; cord factor), a glycolipid associated with the cell wall of mycobacteria, is implicated as a key immunogenic component in M. tuberculosis infection. Models of TDM-induced hypersensitive granulomatous response have similar pathologies to that of active tuberculosis infection. Prior immunization (sensitization) of mice with TDM results in exacerbated histological damage, inflammation and lymphocytic infiltration upon subsequent TDM challenge. Adoptive transfer experiments were performed to ascertain the cell phenotype governing this response; CD4+cells were identified as critical for development of related pathology. Mice receiving CD4+ cells from donor TDM-immunized mice demonstrated significantly increased production of Th1-type cytokines IFN-? and IL-12 within the lung upon subsequent TDM challenge. Control groups receiving naïve CD4+ cells, or CD8+ or CD19+ cells isolated from TDM-immunized donors, did not exhibit an exacerbated response. The identified CD4+ cells isolated from TDM-immunized mice produced significant amounts of IFN-? and IL-2 when exposed to TDM-pulsed macrophages in vitro. These experiments provide further evidence for involvement of a cell-mediated response in TDM-induced granuloma formation, which mimics pathological damage elicited during M. tuberculosis infection. PMID:17906135

Guidry, Tera V.; Hunter, Robert L.; Actor, Jeffrey K.

2008-01-01

364

Inducible Ablation of Melanopsin-Expressing Retinal Ganglion Cells Reveals Their Central Role in NonImage Forming Visual Responses  

Microsoft Academic Search

Rod\\/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and

Megumi Hatori; Hiep Le; Christopher Vollmers; Sheena Racheal Keding; Nobushige Tanaka; Christian Schmedt; Timothy Jegla; Satchidananda Panda; Michael Hendricks

2008-01-01

365

HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review  

PubMed Central

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

Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

2014-01-01

366

Langerhans cell function dictates induction of contact hypersensitivity or unresponsiveness to DNFB in Syrian hamsters  

SciTech Connect

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.

Streilein, J.W.; Bergstresser, P.R.

1981-09-01

367

Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin  

PubMed Central

The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the ?1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable. PMID:22479203

Floquet, Celia; Hatin, Isabelle; Rousset, Jean-Pierre; Bidou, Laure

2012-01-01

368

Microarray Analysis of Tomato's Early and Late Wound Response Reveals New Regulatory Targets for Leucine Aminopeptidase A  

PubMed Central

Wounding due to mechanical injury or insect feeding causes a wide array of damage to plant cells including cell disruption, desiccation, metabolite oxidation, and disruption of primary metabolism. In response, plants regulate a variety of genes and metabolic pathways to cope with injury. Tomato (Solanum lycopersicum) is a model for wound signaling but few studies have examined the comprehensive gene expression profiles in response to injury. A cross-species microarray approach using the TIGR potato 10-K cDNA array was analyzed for large-scale temporal (early and late) and spatial (locally and systemically) responses to mechanical wounding in tomato leaves. These analyses demonstrated that tomato regulates many primary and secondary metabolic pathways and this regulation is dependent on both timing and location. To determine if LAP-A, a known modulator of wound signaling, influences gene expression beyond the core of late wound-response genes, changes in RNAs from healthy and wounded Leucine aminopeptidase A-silenced (LapA-SI) and wild-type (WT) leaves were examined. While most of the changes in gene expression after wounding in LapA-SI leaves were similar to WT, overall responses were delayed in the LapA-SI leaves. Moreover, two pathogenesis-related 1 (PR-1c and PR-1a2) and two dehydrin (TAS14 and Dhn3) genes were negatively regulated by LAP-A. Collectively, this study has shown that tomato wound responses are complex and that LAP-A’s role in modulation of wound responses extends beyond the well described late-wound gene core. PMID:24205013

Scranton, Melissa A.; Fowler, Jonathan H.; Girke, Thomas; Walling, Linda L.

2013-01-01

369

Towards the Identification of New Genes Involved in ABA-Dependent Abiotic Stresses Using Arabidopsis Suppressor Mutants of abh1 Hypersensitivity to ABA during Seed Germination  

PubMed Central

Abscisic acid plays a pivotal role in the abiotic stress response in plants. Although great progress has been achieved explaining the complexity of the stress and ABA signaling cascade, there are still many questions to answer. Mutants are a valuable tool in the identification of new genes or new alleles of already known genes and in elucidating their role in signaling pathways. We applied a suppressor mutation approach in order to find new components of ABA and abiotic stress signaling in Arabidopsis. Using the abh1 (ABA hypersensitive 1) insertional mutant as a parental line for EMS mutagenesis, we selected several mutants with suppressed hypersensitivity to ABA during seed germination. Here, we present the response to ABA and a wide range of abiotic stresses during the seed germination and young seedling development of two suppressor mutants—soa2 (suppressor of abh1 hypersensitivity to ABA 2) and soa3 (suppressor of abh1 hypersensitivity to ABA 3). Generally, both mutants displayed a suppression of the hypersensitivity of abh1 to ABA, NaCl and mannitol during germination. Both mutants showed a higher level of tolerance than Columbia-0 (Col-0—the parental line of abh1) in high concentrations of glucose. Additionally, soa2 exhibited better root growth than Col-0 in the presence of high ABA concentrations. soa2 and soa3 were drought tolerant and both had about 50% fewer stomata per mm2 than the wild-type but the same number as their parental line—abh1. Taking into account that suppressor mutants had the same genetic background as their parental line—abh1, it was necessary to backcross abh1 with Landsberg erecta four times for the map-based cloning approach. Mapping populations, derived from the cross of abh1 in the Landsberg erecta background with each suppressor mutant, were created. Map based cloning in order to identify the suppressor genes is in progress. PMID:23807502

Daszkowska-Golec, Agata; Chorazy, Edyta; Maluszynski, Miroslaw; Szarejko, Iwona

2013-01-01

370

Pairwise Agonist Scanning of human platelets reveals the high-dimensional calcium response to combinatorial mediators of thrombosis  

PubMed Central

Patient-specific prediction of cellular response to multiple stimuli is central to evaluating clinical risk, disease progression, and response to therapy. We deployed Pairwise Agonist Scanning (PAS) to measure calcium signaling of human platelets in EDTA-treated plasma exposed to 6 different agonists (at 0.1, 1, and 10×EC50) used individually or in 135 pairwise combinations. With 154 traces, we trained a neural network (NN) model to accurately predict the entire 6-dimensional response to ADP, convulxin, U46619, SFLLRN, AYPGKF, and PGE2. The NN successfully predicted calcium responses to sequential agonist additions, all ternary combinations of [ADP]+[convulxin]+[SFLLRN] (R=0.88), and 45 different combinations of 4 to 6 agonists (R=0.88). Furthermore, PAS provided 135 pairwise synergy values that allowed a unique phenotypic scoring and differentiation of 10 donors. Training of NNs with pairs of stimuli across the dose-response regime represents a highly efficient approach to predict integration of multiple, complex signals in a patient-specific disease milieu. PMID:20562863

Chatterjee, Manash S.; Purvis, Jeremy E.; Brass, Lawrence F.; Diamond, Scott L.

2010-01-01

371

Changes in BiP availability reveal hypersensitivity to acute endoplasmic reticulum stress in cells expressing  

E-print Network

, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA *Author 2011. Published by The Company of Biologists Ltd doi: 10.1242/jcs.087510 Summary Huntington's disease). Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that results from the expansion

Snapp, Erik Lee

372

Sensitization of cutaneous neuronal purinergic receptors contributes to endothelin-1-induced mechanical hypersensitivity.  

PubMed

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 (30nM) for 10min 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 (3nM) pre-exposure also increased the proportion of isolated mouse dorsal root ganglion 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 quantitative polymerase chain reaction 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

Barr, Travis P; Hrnjic, Alen; Khodorova, Alla; Sprague, Jared M; Strichartz, Gary R

2014-06-01

373

Studies of Physcomitrella patens reveal that ethylene-mediated submergence responses arose relatively early in land-plant evolution.  

PubMed

Colonization of the land by multicellular green plants was a fundamental step in the evolution of life on earth. Land plants evolved from fresh-water aquatic algae, and the transition to a terrestrial environment required the acquisition of developmental plasticity appropriate to the conditions of water availability, ranging from drought to flood. Here we show that extant bryophytes exhibit submergence-induced developmental plasticity, suggesting that submergence responses evolved relatively early in the evolution of land plants. We also show that a major component of the bryophyte submergence response is controlled by the phytohormone ethylene, using a perception mechanism that has subsequently been conserved throughout the evolution of land plants. Thus a plant environmental response mechanism with major ecological and agricultural importance probably had its origins in the very earliest stages of the colonization of the land. PMID:23046428

Yasumura, Yuki; Pierik, Ronald; Fricker, Mark D; Voesenek, Laurentius A C J; Harberd, Nicholas P

2012-10-10

374

Taxon-specific responses of Southern Ocean diatoms to Fe enrichment revealed by synchrotron radiation FTIR microspectroscopy  

NASA Astrophysics Data System (ADS)

Photosynthesis by marine diatoms contributes substantially to global biogeochemical cycling and ecosystem productivity. It is widely accepted that diatoms are extremely sensitive to changes in Fe availability, with numerous in situ experiments demonstrating rapid growth and increased export of elements (e.g. C, Si and Fe) from surface waters as a result of Fe addition. Less is known about the effects of Fe enrichment on the phenotypes of diatoms, such as associated changes in nutritional value, furthermore data on taxon-specific responses is almost non-existent. Enhanced supply of nutrient-rich waters along the coast of the subantarctic Kerguelen Island provide a valuable opportunity to examine the responses of phytoplankton to natural Fe enrichment. Here we demonstrate the use of synchrotron radiation Fourier Transform Infrared (SR-FTIR) microspectroscopy to analyse changes in the macromolecular composition of diatoms collected along the coast and plateau of Kerguelen Island, Southern Ocean. SR-FTIR microspectroscopy enabled the analysis of individual diatom cells from mixed communities of field-collected samples, thereby providing insight into in situ taxon-specific responses in relation to changes in Fe availability. Phenotypic responses were taxon-specific in terms of intraspecific variability and changes in proteins, amino acids, phosphorylated molecules, silicate and carbohydrates. In contrast to some previous studies, silicate levels increased under Fe enrichment, in conjunction with increases in carbohydrate stores. The highly abundant taxon Fragilariopsis kerguelensis displayed a higher level of phenotypic plasticity than Pseudo-nitzschia spp., while analysis of the data pooled across all measured taxa showed different patterns in macromolecular composition compared to those for individual taxon. This study demonstrates that taxon-specific responses to Fe enrichment may not always be accurately reflected by bulk community measurements, highlighting the need for further research into taxon-specific phenotypic responses of phytoplankton to environmental change.

Sackett, O.; Armand, L.; Beardall, J.; Hill, R.; Doblin, M.; Connelly, C.; Howes, J.; Stuart, B.; Ralph, P.; Heraud, P.

2014-05-01

375

Transcriptomic and proteomic analysis of a compatible tomato-aphid interaction reveals a predominant salicylic acid-dependent plant response  

PubMed Central

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

2013-01-01

376

Taxon-specific responses of Southern Ocean diatoms to Fe enrichment revealed by synchrotron radiation FTIR microspectroscopy  

NASA Astrophysics Data System (ADS)

Photosynthesis by marine diatoms contributes substantially to global biogeochemical cycling and ecosystem productivity. It is widely accepted that diatoms are extremely sensitive to changes in Fe availability, with numerous in situ experiments demonstrating rapid growth and increased export of elements (e.g. C, Si and Fe) from surface waters as a result of Fe addition. Less is known about the effects of Fe enrichment on the phenotypes of diatoms, such as associated changes in nutritional value - furthermore, data on taxon-specific responses are almost non-existent. Enhanced supply of nutrient-rich waters along the coast of the subantarctic Kerguelen Island provide a valuable opportunity to examine the responses of phytoplankton to natural Fe enrichment. Here we demonstrate the use of synchrotron radiation Fourier Transform Infrared (SR-FTIR) microspectroscopy to analyse changes in the macromolecular composition of diatoms collected along the coast and plateau of Kerguelen Island, Southern Ocean. SR-FTIR microspectroscopy enabled the analysis of individual diatom cells from mixed communities of field-collected samples, thereby providing insight into in situ taxon-specific responses in relation to changes in Fe availability. Phenotypic responses were taxon-specific in terms of intraspecific variability and changes in proteins, amino acids, phosphorylated molecules, silicate/silicic acid and carbohydrates. In contrast to some previous studies, silicate/silicic acid levels increased under Fe enrichment, in conjunction with increases in carbohydrate stores. The highly abundant taxon Fragilariopsis kerguelensis displayed a higher level of phenotypic plasticity than Pseudo-nitzschia spp., while analysis of the data pooled across all measured taxa showed different patterns in macromolecular composition compared to those for individual taxon. This study demonstrates that taxon-specific responses to Fe enrichment may not always be accurately reflected by bulk community measurements, highlighting the need for further research into taxon-specific phenotypic responses of phytoplankton to environmental change.

Sackett, O.; Armand, L.; Beardall, J.; Hill, R.; Doblin, M.; Connelly, C.; Howes, J.; Stuart, B.; Ralph, P.; Heraud, P.

2014-10-01

377

Polynomial algebra reveals diverging roles of the unfolded protein response in endothelial cells during ischemia-reperfusion injury.  

PubMed

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

Le Pape, Sylvain; Dimitrova, Elena; Hannaert, Patrick; Konovalov, Alexander; Volmer, Romain; Ron, David; Thuillier, Raphaël; Hauet, Thierry

2014-08-25

378

Focal Inflammation Causes Carbenoxolone-Sensitive Tactile Hypersensitivity in Mice  

PubMed Central

A focal and transitory inflammation induced by injection of complete Freund's adjuvant (CFA) in the submandibular skin of mice elicits pain behavior that persists for several weeks after the initial inflammation has resolved. Chronic pain, assessed as tactile hypersensitivity to stimulation with von Frey filaments, was evident from 1–7 weeks following CFA injection, although inflammation at the injection site was resolved by 3–4 weeks. In contrast, there were no changes in tactile sensitivity in the paw (un-injected site for comparison), no alterations in open field behavior and no differences in a functional observation battery evident in CFA-treated mice compared to controls (saline-injected) or to baseline (before CFA injection). Neither strain (Balb/c vs. C57BL/6) nor sex differences in baseline tactile threshold were significant in the submandibular skin. CFA-induced tactile hypersensitivity was also not a function of strain or sex. A single intraperitoneal injection of the gap junction blocker carbenoxolone (CBX) restored normal tactile thresholds in CFA-treated mice when administered at the peak of inflammation (1 week), after significant resolution of inflammation (3 weeks) or after total resolution of inflammation (4 and 5 weeks) without altering the tactile threshold of control subjects, tactile threshold in the paw or open field behavior. Thus, in this novel model of post-inflammatory pain, transitory inflammation induced persistent sex- and strain-independent behavioral hypersensitivity that was reversed by the gap junction blocker CBX, suggesting neuronal and/or glial plasticity as a major component of the chronic pain. PMID:21151805

Hanstein, Regina; Zhao, Julie B.; Basak, Rajshekhar; Smith, David N.; Zuckerman, Yonatan Y.; Hanani, Menachem; Spray, David C.; Gulinello, Maria

2010-01-01

379

Transcriptome response to heavy metal stress in Drosophila reveals a new zinc transporter that confers resistance to zinc  

PubMed Central

All organisms are confronted with external variations in trace element abundance. To elucidate the mechanisms that maintain metal homeostasis and protect against heavy metal stress, we have determined the transcriptome responses in Drosophila to sublethal doses of cadmium, zinc, copper, as well as to copper depletion. Furthermore, we analyzed the transcriptome of a metal-responsive transcription factor (MTF-1) null mutant. The gene family encoding metallothioneins, and the ABC transporter CG10505 that encodes a homolog of ‘yeast cadmium factor’ were induced by all three metals. Zinc and cadmium responses have similar features: genes upregulated by both metals include those for glutathione S-transferases GstD2 and GstD5, and for zinc transporter-like proteins designated ZnT35C and ZnT63C. Several of the metal-induced genes that emerged in our study are regulated by the transcription factor MTF-1. mRNA studies in MTF-1 overexpressing or null mutant flies and in silico search for metal response elements (binding sites for MTF-1) confirmed novel MTF-1 regulated genes such as ferritins, the ABC transporter CG10505 and the zinc transporter ZnT35C. The latter was analyzed in most detail; biochemical and genetic approaches, including targeted mutation, indicate that ZnT35C is involved in cellular and organismal zinc efflux and plays a major role in zinc detoxification. PMID:16973896

Yepiskoposyan, Hasmik; Egli, Dieter; Fergestad, Tim; Selvaraj, Anand; Treiber, Carina; Multhaup, Gerd; Georgiev, Oleg; Schaffner, Walter

2006-01-01

380

Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum  

Microsoft Academic Search

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

Nalu TA Peres; Pablo R Sanches; Juliana P Falcão; Henrique CS Silveira; Fernanda G Paião; Fernanda CA Maranhão; Diana E Gras; Fernando Segato; Rodrigo A Cazzaniga; Mendelson Mazucato; Jeny R Cursino-Santos; Roseli Aquino-Ferreira; Antonio Rossi; Nilce M Martinez-Rossi

2010-01-01

381

Transcript profiling of Zea mays roots reveals gene responses to phosphate deficiency at the plant- and species-specific levels  

Microsoft Academic Search

Maize (Zea mays) is the most widely cultivated crop around the world; however, it is commonly affected by phosphate (Pi) deficiency in many regions, particularly in acid and alkaline soils of developing countries. To cope with Pi deficiency, plants have evol