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1

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

PubMed

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

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

2012-12-01

2

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

3

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

Or?owska, El?bieta; Llorente, Briardo

2012-01-01

4

Quantitative phosphoproteomics of tomato mounting a hypersensitive response reveals a swift suppression of photosynthetic activity and a differential role for hsp90 isoforms.  

PubMed

An important mechanism by which plants defend themselves against pathogens is the rapid execution of a hypersensitive response (HR). Tomato plants containing the Cf-4 resistance gene mount an HR that relies on the activation of phosphorylation cascades, when challenged with the Avr4 elicitor secreted by the pathogenic fungus Cladosporium fulvum. Phosphopeptides were isolated from tomato seedlings expressing both Cf-4 and Avr4 using titanium dioxide columns and LC-MS/MS analysis led to the identification of 50 phosphoproteins, most of which have not been described in tomato before. Phosphopeptides were quantified using a label-free approach based on the MS peak areas. We identified 12 phosphopeptides for which the abundance changed upon HR initiation, as compared to control seedlings. Our results suggest that photosynthetic activity is specifically suppressed in a phosphorylation-dependent way during the very early stages of HR development. In addition, phosphopeptides originating from four Hsp90 isoforms exhibited altered abundances in Cf-4/Avr4 seedlings compared to control seedlings, suggesting that the isoforms of this chaperone protein have a different function in defense signaling. We show that label-free relative quantification of the phosphoproteome of complex samples is feasible, allowing extension of our knowledge on the general physiology and defense signaling of plants mounting the HR. PMID:19178300

Stulemeijer, Iris J E; Joosten, Matthieu H A J; Jensen, Ole N

2009-03-01

5

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

6

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

7

Nadroparine inhibits the hypersensitivity response in the conjunctiva  

Microsoft Academic Search

This study sought to investigate the effects of nadroparine on an in vivo experimental model of type I hypersensitivity response in the rat conjunctiva. Following drug application onto the eye, either before or after challenge with the mast cell degranulator, basic polyamine compound 48\\/80, the conjunctival histamine content and the nitrite levels in the conjunctival lavage fluid were quantified fluorometrically

Vassiliki Giannoulaki; Miltiades Papathanassiou; Nikolaos M. Sitaras; Ekaterini Tiligada

2003-01-01

8

Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli  

PubMed Central

[Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000?Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli. PMID:25140103

Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

2014-01-01

9

Clavibacter michiganensis subsp. Sepedonicus Elicits a Hypersensitive Response in Tobacco and Secretes Hypersensitive Response-Inducing Protein(s).  

PubMed

ABSTRACT Strains of Clavibacter michiganensis subsp. sepedonicus, causal agent of bacterial ring rot of potato, showed marked differences in virulence on host plants. When infiltrated into tobacco leaves, virulent strains caused a rapid localized necrotic response (within 24 to 48 h) characteristic of the hypersensitive response (HR), whereas nonpathogenic strains did not. Concentrated cell-free culture supernatants (CCS) from virulent strains caused a necrotic reaction on tobacco, whereas CCS from nonpathogenic strains did not. The necrosis-inducing activity was heat stable and protease sensitive. Inhibitors of eukaryotic metabolism suppressed the necrotic reaction of tobacco to CCS. No necrotic response was observed when host plants were infiltrated with either cells or CCS from virulent strains. HR-inducing protein(s) from a virulent strain separated from the majority of other proteins on DEAE cellulose at 250 to 300 mM NaCl. Ammonium sulfate-precipitated proteins from a virulent strain produced a necrotic reaction at a total protein concentration of 18 mug/ml, whereas those from a nonpathogenic strain did not, even at a concentration of 180 mug/ml. We conclude that virulent strains of C. michiganensis subsp. sepedonicus elicit a typical HR in tobacco and secrete proteinaceous elicitor(s) of the nonhost HR. PMID:18945088

Nissinen, R; Lai, F M; Laine, M J; Bauer, P J; Reilley, A A; Li, X; De Boer, S H; Ishimaru, C A; Metzler, M C

1997-07-01

10

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...

11

Tissue-specific expression of a soybean hypersensitive-induced response (HIR) protein gene promoter.  

PubMed

A Glycine max gene encoding a putative protein similar to hypersensitive-induced response proteins (HIR) was identified as a gene with preferred expressions in flowers and developing seeds by whole transcriptome gene expression profiling. Its promoter gm-hir1 was cloned and revealed to strongly express a fluorescence reporter gene primarily in integuments, anther tapetum, and seed coat with unique tissue-specificity. Expression in the inner integument was apparent prior to pollination, while expression in the outer integument started to develop from the micropylar end outward as the embryo matured. A 5'-deletion study showed that the promoter can be truncated to 600 bp long relative to the translation start site without affecting expression. A positive regulatory element was identified between 600 and 481 bp that controls expression in the inner integument, with no noticeable effect on expression in the outer integument or tapetum. Additionally, removal of the 5'UTR intron had no effect on levels or location of gm-hir1 expression while truncation to 370 bp resulted in a complete loss of expression suggesting that elements controlling both the outer integument and tapetum expression are located within the 481-370 bp region. PMID:25501569

Koellhoffer, Jessica P; Xing, Aiqiu; Moon, Bryan P; Li, Zhongsen

2015-02-01

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

The role of hypersensitivity and the immune response in influencing susceptibility to metal toxicity.  

PubMed Central

The immune status of the individual is an additional variable which has to be taken into account in any consideration of factors which influence the metabolism and toxicity of metals. The commonly occurring phenomena are described resulting from increased cellular reactivity to platinum, mercury, gold, nickel, chromium, and beryllium, and an attempt has attempt has been made to classify these into the four types of immune response. The clinical effects can be very varied, giving rise to conjunctivitis, rhinitis, asthma, urticaria, contact dermatitis, proteinuria, nephrotic syndrome or blood dyscrasia. Of these effects, cutaneous hypersensitivity is the most common, affecting both industrial and general population groups. Metal compounds used in therapeutics and metals used in prostheses have also been responsible for hypersensitive reactions. PMID:720296

Kazantzis, G

1978-01-01

14

Plant amphipathic proteins delay the hypersensitive response caused by harpin Pssand Pseudomonas syringae pv. syringae  

Microsoft Academic Search

HarpinPssfrom the plant pathogenPseudomonas syringaepv.syringaeis a proteinaceous elicitor that induces a hypersensitive response (HR) in non-host plants. The plant products which recognize harpinPssin the triggering of the HR are not yet known. According to the elicitor-receptor model, we hypothesize that an exogenous cell membrane receptor infiltrated into the intercellular space will interfere with the interaction between harpinPssand the putative receptor.

H.-J. Lin; H.-Y. Cheng; C.-H. Chen; H.-C. Huang; T.-Y. Feng

1997-01-01

15

Transcriptome analysis of a bacterially induced basal and hypersensitive response of Medicago truncatula  

Microsoft Academic Search

Research using the well-studied model legume Medicago truncatula has largely focused on rhizobium symbiosis, while little information is currently available for this species on pathogen-induced\\u000a transcriptome changes. We have performed a transcriptome analysis of this species with the objective of studying the basal\\u000a (BR, no visible symptoms) and hypersensitive response (HR, plant cell death) in its leaves at 6 and

Zoltán Bozsó; Nicolas Maunoury; Agnes Szatmari; Peter Mergaert; Péter G. Ott; László R. Zsíros; Erika Szabó; Éva Kondorosi; Zoltán Klement

2009-01-01

16

An amphipathic protein from sweet pepper can dissociate harpin Pssmultimeric forms and intensify the harpin Pss-mediated hypersensitive response  

Microsoft Academic Search

HarpinPss, a proteinaceous elicitor fromPseudomonas syringaepv.syringae(Pss), can induce a hypersensitive response (HR) in certain plants (e.g. tobacco and tomato). In this report, we show that an amphipathic hypersensitive response assisting protein (HRAP), purified from sweet pepper intensified the harpinPss-mediated HR in sweet pepper, a plant normally not strongly affected by harpinPss. The molecular weight of HRAP was approximately 29 kDa,

C.-H. Chen; H.-J. Lin; T.-Y. Feng

1998-01-01

17

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

PubMed

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

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

2014-04-01

18

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

PubMed Central

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

Reuben, C; Phondke, G P

1979-01-01

19

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

PubMed

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

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

2009-05-01

20

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

21

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

22

Hypersensitivity Pneumonitis  

Microsoft Academic Search

\\u000a Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, encompasses a group of pulmonary disorders\\u000a characterized by immune response to a variety of antigens derived from medications, chemicals, microorganisms, and plant and\\u000a animal proteins. The first cases of HP were described in occupational or hobbyist settings, but HP secondary to home exposures\\u000a is becoming more common. The clinical presentation has

Tracy Prematta; Jennifer Toth; Timothy Craig

23

Transcriptomic analysis of Prunus domestica undergoing hypersensitive response to plum pox virus infection.  

PubMed

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

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

2014-01-01

24

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

PubMed Central

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

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

2014-01-01

25

Identification of a Maize Locus that Modulates the Hypersensitive Defense Response, Using Mutant-Assisted Gene Identification and Characterization (MAGIC)  

Technology Transfer Automated Retrieval System (TEKTRAN)

The hypersensitive response (HR) is the most visible and arguably the most important defense response in plants, although the details of how it is controlled and executed remain patchy. In this paper a novel genetic technique called MAGIC (Mutant-Assisted Gene Identification and Characterization) i...

26

Androgen responsiveness of the murine beta-glucuronidase gene is associated with nuclease hypersensitivity, protein binding, and haplotype-specific sequence diversity within intron 9.  

PubMed Central

The tissue specificity and genetic variability of the murine beta-glucuronidase (GUS) response to androgen provide useful markers for identifying elements which underlie this responsiveness. While GUS is expressed constitutively in all examined cell types, kidney epithelial cells uniquely exhibit a manyfold yet slow rise in GUS mRNA and enzyme levels when stimulated by androgens. Three major phenotypes of this androgen response have been described among inbred strains of mice: (i) a strong response in strains of the Gusa haplotype, (ii) a reduced response in strains of the Gusb and Gush haplotypes, and (iii) no response, as observed in Gusor mice. These response variants define a cis-active element(s) which is tightly linked to the GUS structural gene. Nuclease hypersensitivity scans of kidney chromatin within and surrounding the structural gene revealed an androgen-inducible hypersensitive site in intron 9 of the gene in Gusa but not in Gusor mice. When a radiolabeled fragment of Gusa DNA containing this hypersensitive site was incubated with kidney nuclear extracts and then subjected to gel electrophoresis, two shifted bands were observed whose levels were dramatically higher in extracts of androgen-treated than in those of untreated Gusa mice. The shifted bands reflect binding of a kidney-specific factor(s) to a 57-bp region of complex dyad symmetry in Gusa and Gusor mice which is partially deleted in Gusb and Gush mice. This binding site is located approximately 130 bp downstream of a glucocorticoid response element sequence motif which is totally deleted in [Gus]or mice. Taken together, our results suggest that the androgen responsiveness of GUS in murine kidney epithelial cells is controlled by elements within the proximal end of intron 9 of the GUS structural gene. Images PMID:1922055

Lund, S D; Gallagher, P M; Wang, B; Porter, S C; Ganschow, R E

1991-01-01

27

A UVB-hypersensitive mutant in Arabidopsis thaliana is defective in the DNA damage response.  

PubMed

To investigate UVB DNA damage response in higher plants, we used a genetic screen to isolate Arabidopsis thaliana mutants that are hypersensitive to UVB irradiation, and isolated a UVB-sensitive mutant, termed suv2 (for sensitive to UV 2) that also displayed hypersensitivity to gamma-radiation and hydroxyurea. This phenotype is reminiscent of the Arabidopsis DNA damage-response mutant atr. The suv2 mutation was mapped to the bottom of chromosome 5, and contains an insertion in an unknown gene annotated as MRA19.1. RT-PCR analysis with specific primers to MRA19.1 detected a transcript consisting of 12 exons. The transcript is predicted to encode a 646 amino acid protein that contains a coiled-coil domain and two instances of predicted PIKK target sequences within the N-terminal region. Fusion proteins consisting of the predicted MRA19.1 and DNA-binding or activation domain of yeast transcription factor GAL4 interacted with each other in a yeast two-hybrid system, suggesting that the proteins form a homodimer. Expression of CYCB1;1:GUS gene, which encodes a labile cyclin:GUS fusion protein to monitor mitotic activity by GUS activity, was weaker in the suv2 plant after gamma-irradiation than in the wild-type plants and was similar to that in the atr plants, suggesting that the suv2 mutant is defective in cell-cycle arrest in response to DNA damage. Overall, these results suggest that the gene disrupted in the suv2 mutant encodes an Arabidopsis homologue of the ATR-interacting protein ATRIP. PMID:19619159

Sakamoto, Ayako N; Lan, Vo Thi Thuong; Puripunyavanich, Vichai; Hase, Yoshihiro; Yokota, Yuichiro; Shikazono, Naoya; Nakagawa, Mayu; Narumi, Issay; Tanaka, Atsushi

2009-11-01

28

Interleukin-12 reverses the inhibitory impact of photodynamic therapy (PDT) on the murine contact hypersensitivity response  

NASA Astrophysics Data System (ADS)

Treatment of mice with certain photosensitizers combined with exposure to visible light limits the development of the immunologically-mediated contact hypersensitivity (CHS) response against topically-applied chemical haptens. Understanding of the inhibitory action of photosensitizers upon the CHS response is incomplete. Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin), a photosensitizer with immunomodulatory activity, strongly depressed CHS responses to the hapten dinitrofluorobenzene (DNFB). However, if mice were administered 1 (mu) g of a recombinant preparation of the pro- inflammatory cytokine interleukin-12 (rIL-12), full-fledged CHS responses to DNFB ensued in animals treated with BPD-MA and light. In contrast, when rIL-12 was given in combination with an anti-IL-12 antibody the restorative effect of rIL-12 on the CHS response of PDT-treated mice was blocked. Evaluation of the cytokine status of spleen and draining lymph node cells showed for DNFB painted animals, that the release of the immunosuppressive cytokine IL-10 was increased by PDT and rIL-12 counter-acted the increase in IL-10 liberation associated with PDT. These studies indicate that IL-10 formation is upregulated and the availability of IL-12 may be limited in mice treated with PDT. These features may contribute to deficient CHS responses observed with PDT.

Simkin, Guillermo O.; Levy, Julia G.; Hunt, David W. C.

1998-05-01

29

Diclofenac Hypersensitivity: Antibody Responses to the Parent Drug and Relevant Metabolites  

Microsoft Academic Search

BackgroundHypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs) like diclofenac (DF) can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug- and\\/or metabolite-specific antibodies in selective DF hypersensitivity.Methodology\\/Principal FindingsDF, an organochemically synthesized

Andrea Harrer; Roland Lang; Robert Grims; Michaela Braitsch; Thomas Hawranek; Werner Aberer; Lothar Vogel; Walther Schmid; Fatima Ferreira; Martin Himly; Derya Unutmaz

2010-01-01

30

The Diamine Oxidase Gene Is Associated with Hypersensitivity Response to Non-Steroidal Anti-Inflammatory Drugs  

PubMed Central

Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR ?=?1.7 (95% CI ?=?1.3–2.1; Pc ?=?0.0003) with a gene-dose effect (P?=?0.0001). The association was replicated in two populations from different geographic areas (Pc ?=?0.008 and Pc ?=?0.004, respectively). Conclusions and implications The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response. PMID:23152756

Agúndez, José A. G.; Ayuso, Pedro; Cornejo-García, José A.; Blanca, Miguel; Torres, María J.; Doña, Inmaculada; Salas, María; Blanca-López, Natalia; Canto, Gabriela; Rondon, Carmen; Campo, Paloma; Laguna, José J.; Fernández, Javier; Martínez, Carmen; García-Martín, Elena

2012-01-01

31

Histamine involvement in UVB- and cis-urocanic acid-induced systemic suppression of contact hypersensitivity responses.  

PubMed Central

Studies in experimental models have implicated histamine and prostanoids in ultra-violet B (UVB)- and cis-urocanic acid (UCA)-induced systemic immunosuppression. This study examined the hypothesis that UVB irradiation and cis-UCA suppressed contact hypersensitivity responses to hapten by induction of histamine, which in turn evoked a prostanoid-dependent component of immunosuppression. BALB/c mice were administered with a cis-UCA monoclonal antibody, a combination of histamine types 1 and 2 receptor antagonists, or indomethacin. Mice were sensitized to 2,4,6-trinitrochlorobenzene (TNCB) on their ventral surface 5 days after UVB irradiation, or cis-UCA or histamine administration. Ears were challenged with TNCB 5 days later. Cis-UCA antibody inhibited the suppressive effects of UVB by approximately 60% and confirmed that suppression of contact hypersensitivity responses by UVB was due, at least in part, to mechanisms involving cis-UCA. Histamine suppressed contact hypersensitivity responses and the effects of cis-UCA and histamine were not cumulative, suggesting that cis-UCA and histamine signal largely through the same pathway. The immunosuppressive effects of histamine were not affected by the cis-UCA antibody, consistent with the model that histamine acts downstream of cis-UCA. Administration of histamine receptor antagonists and indomethacin each approximately halved the UVB- and cis-UCA-induced systemic suppression of contact hypersensitivity responses. The effects of the reagents that inhibited the action of histamine and prevented prostanoid production were not cumulative, and suggested involvement in the same pathway. These results support the involvement of cis-UCA, histamine and prostanoids, in a sequence, in UVB-induced systemic suppression of contact hypersensitivity responses. PMID:9378501

Hart, P H; Jaksic, A; Swift, G; Norval, M; el-Ghorr, A A; Finlay-Jones, J J

1997-01-01

32

Hypersensitivity pneumonitis  

MedlinePLUS

... Mushroom picker's disease; Humidifier or air-conditioner lung; Bird breeder's or bird fancier's lung ... to hypersensitivity pneumonitis. Examples of hypersensitivity pneumonitis include: Bird fancier's lung: This is the most common type ...

33

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

34

Participation of the phosphoinositide metabolism in the hypersensitive response of Citrus limon against Alternaria alternata.  

PubMed

Lemon seedlings inoculated with Alternaria alternata develop a hypersensitive response (HR) that includes the induction of Phenylalanine ammonia-lyase (PAL, E. C. 4.3.1.5) and the synthesis of scoparone. The signal transduction pathway involved in the development of this response is unknown. We used several inhibitors of the Phosphoinositide (PI) animal system to study a possible role of Inositol-1,4,5-triphosphate (IP3) in the transduction of the fungal conidia signal in Citrus limon. The HR was only partially inhibited by EGTA, suggesting that not only external but internal calcium as well are necessary for a complete development of the HR. In this plant system, Alternaria alternata induced an early accumulation of the second messenger IP3. When lemon seedlings were watered long term with LiCl, an inhibitor of the phosphoinositide cycle, the IP3 production was reduced, and the LiCl-watered plants could neither induce PAL nor synthesize scoparone in response to fungal conidia. Furthermore, neomycin, a Phospholipase C (PLC, E. C. 3.1.4.3) inhibitor, also inhibited PAL induction and scoparone synthesis in response to A. alternata. These results suggest that IP3 could be involved in the signal transduction pathway for the development of the HR of Citrus limon against A. alternata. PMID:11471522

Ortega, X; Pérez, L M

2001-01-01

35

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

PubMed Central

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.; Peter van Esse, H.; de Vos, Ric C.H.; Bouwmeester, Harro J.; Joosten, Matthieu H.A.J.

2013-01-01

36

Pathogen-induced elicitin production in transgenic tobacco generates a hypersensitive response and nonspecific disease resistance.  

PubMed Central

The rapid and effective activation of disease resistance responses is essential for plant defense against pathogen attack. These responses are initiated when pathogen-derived molecules (elicitors) are recognized by the host. We have developed a strategy for creating novel disease resistance traits whereby transgenic plants respond to infection by a virulent pathogen with the production of an elicitor. To this end, we generated transgenic tobacco plants harboring a fusion between the pathogen-inducible tobacco hsr 203J gene promoter and a Phytophthora cryptogea gene encoding the highly active elicitor cryptogein. Under noninduced conditions, the transgene was silent, and no cryptogein could be detected in the transgenic plants. In contrast, infection by the virulent fungus P. parasitica var nicotianae stimulated cryptogein production that coincided with the fast induction of several defense genes at and around the infection sites. Induced elicitor production resulted in a localized necrosis that resembled a P. cryptogea-induced hypersensitive response and that restricted further growth of the pathogen. The transgenic plants displayed enhanced resistance to fungal pathogens that were unrelated to Phytophthora species, such as Thielaviopsis basicola, Erysiphe cichoracearum, and Botrytis cinerea. Thus, broad-spectrum disease resistance of a plant can be generated without the constitutive synthesis of a transgene product. PMID:9927640

Keller, H; Pamboukdjian, N; Ponchet, M; Poupet, A; Delon, R; Verrier, J L; Roby, D; Ricci, P

1999-01-01

37

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

PubMed

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

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

2013-08-01

38

A Rifampin-Hypersensitive Mutant Reveals Differences between Strains of Mycobacterium smegmatis and Presence of a Novel Transposon, IS1623  

PubMed Central

Rifampin is a front-line antibiotic for the treatment of tuberculosis. Infections caused by rifampin- and multidrug-resistant Mycobacterium tuberculosis strains are difficult to treat and contribute to a poor clinical outcome. Rifampin resistance most often results from mutations in rpoB. However, some drug-resistant strains have rpoB alleles that encode the phenotype for susceptibility. Similarly, non-M. tuberculosis mycobacteria exhibit higher levels of baseline resistance to rifampin, despite the presence of rpoB alleles that encode the phenotype for susceptibility. To identify other genes involved in rifampin resistance, we generated a library of Mycobacterium smegmatis mc2155 transposon insertion mutants. Upon screening this library, we identified one mutant that was hypersensitive to rifampin. The transposon insertion was localized to the arr gene, which encodes rifampin ADP ribosyltransferase, an enzyme able to inactivate rifampin. Sequence analysis revealed differences in the arr alleles of M. smegmatis strain mc2155 and previously described strain DSM 43756. The arr region of strain mc2155 contains a second, partial copy of the arr gene plus a novel insertion sequence, IS1623. PMID:14506032

Alexander, David C.; Jones, Joses R. W.; Liu, Jun

2003-01-01

39

Structural basis of metal hypersensitivity.  

PubMed

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

Wang, Yang; Dai, Shaodong

2013-03-01

40

The role of SA in the hypersensitive response and systemic acquired resistance induced by elicitor PB90 from Phytophthora boehmeriae  

Microsoft Academic Search

We examined the role of salicylic acid (SA) accumulation in the tobacco hypersensitive response (HR) and systemic acquired resistance (SAR) induced by PB90, a 90kDa protein elicitor that is secreted by Phytophthora boehmeriae. The elicitor induced HR of a consistent shape and size on tobacco plants expressing the bacterial gene nahG. Salicylate hydroxylase is encodec by nahG and inactivates SA

Zheng-Guang Zhang; Yuan-Chao Wang; Jun li; Rui Ji; Gui Shen; Shu-Cai Wang; Xie Zhou; Xiao-Bo Zheng

2004-01-01

41

Lazarus1, a DUF300 Protein, Contributes to Programmed Cell Death Associated with Arabidopsis acd11 and the Hypersensitive Response  

Microsoft Academic Search

BackgroundProgrammed cell death (PCD) is a necessary part of the life of multi-cellular organisms. A type of plant PCD is the defensive hypersensitive response (HR) elicited via recognition of a pathogen by host resistance (R) proteins. The lethal, recessive accelerated cell death 11 (acd11) mutant exhibits HR-like accelerated cell death, and cell death execution in acd11 shares genetic requirements for

Frederikke G. Malinovsky; Peter Brodersen; Berthe Katrine Fiil; Lea Vig McKinney; Stephan Thorgrimsen; Martina Beck; H. Bjørn Nielsen; Stefano Pietra; Cyril Zipfel; Silke Robatzek; Morten Petersen; Daniel Hofius; John Mundy; Mohammed Bendahmane

2010-01-01

42

Protein kinase D1 is essential for the pro-inflammatory response induced by hypersensitivity pneumonitis-causing thermophilic actinomycetes Saccharopolyspora rectivirgula  

PubMed Central

Hypersensitivity pneumonitis is an interstitial lung disease that results from repeated pulmonary exposure to various organic antigens, including Saccharopolyspora rectivirgula (SR, the causative agent of farmer's lung disease). Although the contributions of pro-inflammatory mediators to the disease pathogenesis are relatively well documented, the mechanism(s) involved in initiation of pro-inflammatory responses against the causative microorganisms, and the contribution of signaling molecules involved in host immune defense have not been fully elucidated. In the present study, we found that SR induces activation of protein kinase D1 (PKD1) in lung cells in vitro and in vivo. Activation of PKD1 by SR was dependent on MyD88. Inhibition of PKD by pharmacological PKD inhibitor Gö6976, and silencing of PKD1 expression by siRNA, revealed that PKD1 is indispensable for SR-mediated activation of MAPKs and NF-?B and expression of various pro-inflammatory cytokines and chemokines. In addition, compared to controls, mice pretreated with Gö6976 showed significantly suppressed alveolitis and neutrophil influx in bronchial alveolar lavage fluid and interstitial lung tissue, and substantially decreased myeloperoxidase activity in the lung after pulmonary exposure to SR. These results demonstrate that PKD1 is essential for SR-mediated pro-inflammatory immune responses and neutrophil influx in the lung. Our findings also imply the possibility that PKD1 might be one of the critical factors that play a regulatory role in development of hypersensitivity pneumonitis caused by microbial antigens, and that inhibition of PKD1 activation could be an effective way to control microbial antigen-induced hypersensitivity pneumonitis. PMID:20142359

Kim, Young-In; Park, Jeoung-Eun; Brand, David D.; Fitzpatrick, Elizabeth A.; Yi, Ae-Kyung

2010-01-01

43

Hypersensitive Response-Like Reaction Is Associated with Hybrid Necrosis in Interspecific Crosses between Tetraploid Wheat and Aegilops tauschii Coss  

PubMed Central

Background Hybrid speciation is classified into homoploid and polyploid based on ploidy level. Common wheat is an allohexaploid species that originated from a naturally occurring interploidy cross between tetraploid wheat and diploid wild wheat Aegilops tauschii Coss. Aegilops tauschii provides wide naturally occurring genetic variation. Sometimes its triploid hybrids with tetraploid wheat show the following four types of hybrid growth abnormalities: types II and III hybrid necrosis, hybrid chlorosis, and severe growth abortion. The growth abnormalities in the triploid hybrids could act as postzygotic hybridization barriers to prevent formation of hexaploid wheat. Methodology/Principal Findings Here, we report on the geographical and phylogenetic distribution of Ae. tauschii accessions inducing the hybrid growth abnormalities and showed that they are widely distributed across growth habitats in Ae. tauschii. Molecular and cytological characterization of the type III necrosis phenotype was performed. The hybrid abnormality causing accessions were widely distributed across growth habitats in Ae. tauschii. Transcriptome analysis showed that a number of defense-related genes such as pathogenesis-related genes were highly up-regulated in the type III necrosis lines. Transmission electron microscope observation revealed that cell death occurred accompanied by generation of reactive oxygen species in leaves undergoing type III necrosis. The reduction of photosynthetic activity occurred prior to the appearance of necrotic symptoms on the leaves exhibiting hybrid necrosis. Conclusions/Significance Taking these results together strongly suggests that an autoimmune response might be triggered by intergenomic incompatibility between the tetraploid wheat and Ae. tauschii genomes in type III necrosis, and that genetically programmed cell death could be regarded as a hypersensitive response-like cell death similar to that observed in Arabidopsis intraspecific and Nicotiana interspecific hybrids. Only Ae. tauschii accessions without such inhibiting factors could be candidates for the D-genome donor for the present hexaploid wheat. PMID:20593003

Mizuno, Nobuyuki; Hosogi, Naoki; Park, Pyoyun; Takumi, Shigeo

2010-01-01

44

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

45

Context of action of Proline Dehydrogenase (ProDH) in the Hypersensitive Response of Arabidopsis  

PubMed Central

Background Proline (Pro) dehydrogenase (ProDH) potentiates the oxidative burst and cell death of the plant Hypersensitive Response (HR) by mechanisms not yet elucidated. ProDH converts Pro into ?1 pyrroline-5-carboxylate (P5C) and can act together with P5C dehydrogenase (P5CDH) to produce Glu, or with P5C reductase (P5CR) to regenerate Pro and thus stimulate the Pro/P5C cycle. To better understand the effects of ProDH in HR, we studied the enzyme at three stages of the defense response differing in their ROS and cell death levels. In addition, we tested if ProDH requires P5CDH to potentiate HR. Results Control and infected leaves of wild type and p5cdh plants were used to monitor ProDH activity, in vivo Pro catabolism, amino acid content, and gene expression. Wild type plants activated ProDH at all HR stages. They did not consume Pro during maximal ROS accumulation, and maintained almost basal P5C levels at all conditions. p5cdh mutants activated ProDH as wild type plants. They achieved maximum oxidative burst and cell death levels producing normal HR lesions, but evidenced premature defense activation. Conclusion ProDH activation has different effects on HR. Before the oxidative burst it leads to Pro consumption involving the action of P5CDH. During the oxidative burst, ProDH becomes functionally uncoupled to P5CDH and apparently works with P5CR. The absence of P5CDH does not reduce ROS, cell death, or pathogen resistance, indicating this enzyme is not accompanying ProDH in the potentiation of these defense responses. In contrast, p5cdh infected plants displayed increased ROS burst and earlier initiation of HR cell death. In turn, our results suggest that ProDH may sustain HR by participating in the Pro/P5C cycle, whose action on HR must be formally evaluated in a future. PMID:24410747

2014-01-01

46

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

PubMed Central

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

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

2013-01-01

47

[Analysis of contact hypersensitivity response in human monocyte chemoattractant protein (MCP)-1 transgenic mice].  

PubMed

Epidermal Langerhans cells (LC) belong to the dendritic cell lineage and represent the major antigen-presenting cells (APC) within the skin. The molecular mechanisms responsible for LC migration to the skin have not fully been defined. MCP-1 is a cytokine of C-C chemokine subfamily that is chemotactic in vitro for monocytes, memory T cells and dendritic cells. In the present study, to examine the roles of LC and MCP-1 in hapten-induced contact hypersensitivity response (CHR), we utilized human MCP-1 transgenic mice (hMCP-1 Tgm) that produce constitutively high levels of hMCP-1 in the sera. Following DNFB sensitization, enhancement of CHR was demonstrated in Tgm as compared with CHR in non-Tgm at the entire period examined. Anti-hMCP-1 antibody significantly inhibited the DNFB-included CHR in Tgm. For analysis of the mechanisms underlying the enhanced CHR, migration and activation of LC were examined in Tgm and non-Tgm. The number of LC in the Tgm skin was within a normal range. However, the Tgm showed an accumulation of NLDC-145+ cells in the draining lymph nodes (DLN) 24 h after DNFB sensitization. When Tgm and non-Tgm were treated with FITC, the number of FITC+NLDC-145+ cells was larger in Tgm DLN than that in non-Tgm DLN 24 h after FITC application. Moreover, administration of recombinant hMCP-1 to BALB/c mice led to an increase of FITC+NLDC-145+ cells in the DLN. In addition, 12 h after application of FITC, LC in the epidermal sheets of Tgm increased in size and expressed high levels of I-Ad as compared with those of non-Tgm. Expression of B7-1 in 24h-cultured LC of BA LB/c mice was augmented by addition of recombinant hMCP-1 in a dose-dependent manner. These findings suggest that MCP-1 accelerates LC migration from epidermis into the DLN and up-regulates I-Ad and B7-1 expressions on the LC, which eventually enhances CHR. PMID:10422564

Mizumoto, N

1999-05-01

48

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

PubMed Central

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

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

2011-01-01

49

Capsicum annuum WRKY transcription factor d (CaWRKYd) regulates hypersensitive response and defense response upon Tobacco mosaic virus infection.  

PubMed

WRKY transcription factors regulate biotic, abiotic, and developmental processes. In terms of plant defense, WRKY factors have important roles as positive and negative regulators via transcriptional regulation or protein-protein interaction. Here, we report the characterization of the gene encoding Capsicum annuum WRKY transcription factor d (CaWRKYd) isolated from microarray analysis in the Tobacco mosaic virus (TMV)-P(0)-inoculated hot pepper plants. CaWRKYd belongs to the WRKY IIa group, a very small clade in the WRKY subfamily, and WRKY IIa group has positive/negative regulatory roles in Arabidopsis and rice. CaWRKYd transcripts were induced by various plant defense-related hormone treatments and TMV-P(0) inoculation. Silencing of CaWRKYd affected TMV-P(0)-mediated hypersensitive response (HR) cell death and accumulation of TMV-P(0) coat protein in local and systemic leaves. Furthermore, expression of some pathogenesis-related (PR) genes and HR-related genes was reduced in the CaWRKYd-silenced plants compared with TRV2 vector control plants upon TMV-P(0) inoculation. CaWRKYd was confirmed to bind to the W-box. Thus CaWRKYd is a newly identified Capsicum annuum WRKY transcription factor that appears to be involved in TMV-P(0)-mediated HR cell death by regulating downstream gene expression. PMID:23116671

Huh, Sung Un; Choi, La Mee; Lee, Gil-Je; Kim, Young Jin; Paek, Kyung-Hee

2012-12-01

50

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

PubMed Central

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

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

2012-01-01

51

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

PubMed

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

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

1998-04-01

52

Hypersensitivity pneumonitis  

PubMed Central

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the subject has been previously sensitized. The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 30:100,000 and HP accounted for less than 2% of these cases. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence respectively, using simple diagnostic criteria. Chest X-rays may be normal in active HP; High Resolution Computed Tomography is sensitive but not specific for the diagnosis of HP. The primary use of pulmonary function tests is to determine the physiologic abnormalities and the associated impairment. Despite the pitfalls of false positive and false negatives, antigen-specific IgG antibodies analysis can be useful as supportive evidence for HP. Bronchoalveolar lavage plays an important role in the investigation of patients suspected of having HP. A normal number of lymphocytes rules out all but residual disease. Surgical lung biopsy should be reserved for rare cases with puzzling clinical presentation or for verification the clinical diagnosis when the clinical course or response to therapy is unusual. Being an immune reaction in the lung, the most obvious treatment of HP is avoidance of contact with the offending antigen. Systemic corticosteroids represent the only reliable pharmacologic treatment of HP but do not alter the long-term outcome. The use of inhaled steroids is anecdotal. Treatment of chronic or residual disease is supportive. PMID:16817954

Lacasse, Yves; Cormier, Yvon

2006-01-01

53

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

54

Cell-Mediated Immunity in Humans During Viral Infection I. Effect of Rubella on Dermal Hypersensitivity, Phytohemagglutinin Response, and T Lymphocyte Numbers  

PubMed Central

Phytohemagglutinin-induced lymphocyte deoxyribonucleic acid synthesis, dermal hypersensitivity, and peripheral blood thymus-derived lymphocyte numbers were assessed in nine men with experimentally induced rubella infection. Five of these men and two additional volunteers received treatment with tilorone dihydrochloride, an antiviral drug. Response to phytohemagglutinin was not changed during rubella; T lymphocyte numbers in peripheral blood were not influenced by the viral illness. However, dermal hypersensitivity was markedly impaired in all volunteers during the height of the illness. Tilorone alone, or with rubella, had no effect on any of the parameters studied. PMID:4546284

Kauffman, Carol A.; Phair, John P.; Linnemann, Calvin C.; Schiff, Gilbert M.

1974-01-01

55

Use of Mutant-Assisted Gene Identification and Characterization (MAGIC) to identify novel genetic loci that modify the maize hypersensitive response  

Technology Transfer Automated Retrieval System (TEKTRAN)

The partially-dominant, autoactive maize disease resistance gene Rp1-D21 causes hypersensitive response (HR) lesions to form spontaneously on the leaves and stem in the absence of pathogen recognition. The maize nested association mapping (NAM) population consists of 25 200-line subpopulations each...

56

Dentine hypersensitivity.  

PubMed

Dentine hypersensitivity is a common oral pain condition affecting many individuals. The aetiology is multifactorial; however, over recent years the importance of erosion has become more evident. For dentine hypersensitivity to occur, the lesion must first be localised on the tooth surface and then initiated to exposed dentine tubules which are patent to the pulp. The short, sharp pain symptom is thought to be derived from the hydrodynamic pain theory and, although transient, is arresting, affecting quality of life. This episodic pain condition is likely to become a more frequent dental complaint in the future due to the increase in longevity of the dentition and the rise in tooth wear, particularly amongst young adults. Many efficacious treatment regimens are now available, in particular a number of over-the-counter home use products. The basic principles of treatment are altering fluid flow in the dentinal tubules with tubule occlusion or modifying or chemically blocking the pulpal nerve. PMID:24993261

West, Nicola; Seong, Joon; Davies, Maria

2014-01-01

57

Hypersensitivity pneumonitis  

Microsoft Academic Search

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the subject has been previously sensitized. The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 30:100,000 and HP accounted for less than 2% of these cases. The diagnosis of

Yves Lacasse; Yvon Cormier

2006-01-01

58

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; Buéno, L

1996-01-01

59

Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome.  

PubMed

The use of drug eluting stents constitutes a major breakthrough in current interventional cardiology because it is more than halves the need of repeat interventions. It is incontrovertible that coronary stents, in general, have been beneficial for the vast majority of patients. A small increase in thrombosis, following DES implantation, is offset by a diminished risk of complications associated with repeat vascularization. However, late and, especially, very late stent thrombosis is a much feared complication because it is associated with myocardial infarction with increased mortality. Despite that stent thrombosis is thought to be multifactorial, so far clinical reports and reported pathology findings in patients died from coronary stent thrombosis as well as animal studies and experiments, point toward a hypersensitivity inflammation. The stented and thrombotic areas are infiltrated by interacting, via bidirectional stimuli inflammatory cells including eosinophils, macrophages, T-cells and mast cells. Stented regions constitute an ideal surrounding for endothelial damage and dysfunction, together with hemorheologic changes and turbulence as well as platelet dysfunction, coagulation and fibrinolytic disturbances. Drug eluting stent components include the metal strut which contains nickel, chromium, manganese, titanium, molybdenum, the polymer coating and the impregnated drugs which for the first generation stents are: the antimicrotubule antineoplastic agent paclitaxel and the anti-inflammatory, immunosuppressive and antiproliferative agent sirolimus. The newer stents which are called cobalt-chromiun stents and elute the sirolimus analogs everolimus and zotarolimus both contain nickel and other metals. All these components constitute an antigenic complex inside the coronary arteries which apply chronic, continuous, repetitive and persistent inflammatory action capable to induced Kounis syndrome and stent thrombosis. Allergic inflammation goes through three phases, the early phase, the late phase and the chronic phase and these three phases correspond temporally with early (acute and sub acute), late and very late stent thrombosis. Bioabsorbable allergy free poly lactic acid self expanding stents, nickel free stainless steel materials, stent coverage with nitric oxide donors and antibodies with endothelial progenitor cell capturing abilities as well as stents eluting anti-inflammatory and anti-allergic agents might be the solution of this so feared and devastating stent complication. PMID:21700348

Kounis, Nicholas G; Giannopoulos, Sotiris; Tsigkas, Grigorios G; Goudevenos, John

2012-04-19

60

Copper hypersensitivity.  

PubMed

The world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions. PMID:25098945

Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

2014-10-01

61

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

PubMed

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

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

2013-03-01

62

Glutathione Deficiency of the Arabidopsis Mutant pad2-1 Affects Oxidative Stress-Related Events, Defense Gene Expression, and the Hypersensitive Response1[C][W][OA  

PubMed Central

The Arabidopsis (Arabidopsis thaliana) phytoalexin-deficient mutant pad2-1 displays enhanced susceptibility to a broad range of pathogens and herbivorous insects that correlates with deficiencies in the production of camalexin, indole glucosinolates, and salicylic acid (SA). The pad2-1 mutation is localized in the GLUTAMATE-CYSTEINE LIGASE (GCL) gene encoding the first enzyme of glutathione biosynthesis. While pad2-1 glutathione deficiency is not caused by a decrease in GCL transcripts, analysis of GCL protein level revealed that pad2-1 plants contained only 48% of the wild-type protein amount. In contrast to the wild type, the oxidized form of GCL was dominant in pad2-1, suggesting a distinct redox environment. This finding was corroborated by the expression of GRX1-roGFP2, showing that the cytosolic glutathione redox potential was significantly less negative in pad2-1. Analysis of oxidative stress-related gene expression showed a higher transcript accumulation in pad2-1 of GLUTATHIONE REDUCTASE, GLUTATHIONE-S-TRANSFERASE, and RESPIRATORY BURST OXIDASE HOMOLOG D in response to the oomycete Phytophthora brassicae. Interestingly, oligogalacturonide elicitation in pad2-1 revealed a lower plasma membrane depolarization that was found to act upstream of an impaired hydrogen peroxide production. This impaired hydrogen peroxide production was also observed during pathogen infection and correlated with a reduced hypersensitive response in pad2-1. In addition, a lack of pathogen-triggered expression of the ISOCHORISMATE SYNTHASE1 gene, coding for the SA-biosynthetic enzyme isochorismate synthase, was identified as the cause of the SA deficiency in pad2-1. Together, our results indicate that the pad2-1 mutation is related to a decrease in GCL protein and that the resulting glutathione deficiency negatively affects important processes of disease resistance. PMID:22007023

Dubreuil-Maurizi, Carole; Vitecek, Jan; Marty, Laurent; Branciard, Lorelise; Frettinger, Patrick; Wendehenne, David; Meyer, Andreas J.; Mauch, Felix; Poinssot, Benoît

2011-01-01

63

Characterization of the draining lymph node response in the mouse drug allergy model: A model for drug hypersensitivity reactions.  

PubMed

Abstract The mouse drug allergy model (MDAM) was developed as a tool to predict the potential of systemically administered drugs to produce hypersensitivity reactions (HR). Drugs associated with HR in the clinic produce a marked increase in the cellularity of the draining lymph nodes (DLN) in the MDAM. The objective of this study was to characterize the changes in the DLN following exposure to drugs associated with HR and to investigate whether lymphocyte migration and/or proliferation play a role in the response. These endpoints were also investigated in the local lymph node assay (LLNA) to determine whether responses between the two assays occur via similar mechanisms. Results demonstrated that total numbers of T- and B-cells were proportionally increased in the DLN of mice treated with positive control drugs (i.e. abacavir, amoxicillin, ofloxacin, and sulfamethoxazole) compared to animals administered the vehicle or negative control drugs (metformin and cimetidine). In contrast, a significant increase in the B-cell population of the DLN was observed for 2,4-dinitrofluorobenzene (DNFB) following the LLNA protocol. Down-regulation of CD62L and up-regulation of CCR7 were observed for T-cells from the DLN of the positive control treated mice in the MDAM, but not with DNFB in the LLNA. A mild increase in T-cell proliferation was observed in the MDAM with positive control drugs, while DNFB in the LLNA induced proliferation within the B-cell population only. Anti-CD40L antibody administration inhibited MDAM responses to positive control drugs, but did not affect DNFB-induced increases in total cell number in the LLNA. These results suggest that the increased cellularity of the DLN in the MDAM may be the result of drug-induced alterations in lymphocyte migration and/or effects on lymphocyte proliferation. Moreover, it appears that different mechanisms may be involved in driving the MDAM and LLNA responses. PMID:25469456

Zhu, Xu; Cole, Susan H; Kawabata, Thomas T; Whritenour, Jessica

2014-12-01

64

An S-type anion channel SLAC1 is involved in cryptogein-induced ion fluxes and modulates hypersensitive responses in tobacco BY-2 cells.  

PubMed

Pharmacological evidence suggests that anion channel-mediated plasma membrane anion effluxes are crucial in early defense signaling to induce immune responses and hypersensitive cell death in plants. However, their molecular bases and regulation remain largely unknown. We overexpressed Arabidopsis SLAC1, an S-type anion channel involved in stomatal closure, in cultured tobacco BY-2 cells and analyzed the effect on cryptogein-induced defense responses including fluxes of Cl(-) and other ions, production of reactive oxygen species (ROS), gene expression and hypersensitive responses. The SLAC1-GFP fusion protein was localized at the plasma membrane in BY-2 cells. Overexpression of SLAC1 enhanced cryptogein-induced Cl(-) efflux and extracellular alkalinization as well as rapid/transient and slow/prolonged phases of NADPH oxidase-mediated ROS production, which was suppressed by an anion channel inhibitor, DIDS. The overexpressor also showed enhanced sensitivity to cryptogein to induce downstream immune responses, including the induction of defense marker genes and the hypersensitive cell death. These results suggest that SLAC1 expressed in BY-2 cells mediates cryptogein-induced plasma membrane Cl(-) efflux to positively modulate the elicitor-triggered activation of other ion fluxes, ROS as well as a wide range of defense signaling pathways. These findings shed light on the possible involvement of the SLAC/SLAH family anion channels in cryptogein signaling to trigger the plasma membrane ion channel cascade in the plant defense signal transduction network. PMID:23950973

Kurusu, Takamitsu; Saito, Katsunori; Horikoshi, Sonoko; Hanamata, Shigeru; Negi, Juntaro; Yagi, Chikako; Kitahata, Nobutaka; Iba, Koh; Kuchitsu, Kazuyuki

2013-01-01

65

Hypersensitive response and acyl?homoserine lactone production of the fire blight antagonists Erwinia tasmaniensis and Erwinia billingiae  

PubMed Central

Summary Fire blight caused by the Gram?negative bacterium Erwinia amylovora can be controlled by antagonistic microorganisms. We characterized epiphytic bacteria isolated from healthy apple and pear trees in Australia, named Erwinia tasmaniensis, and the epiphytic bacterium Erwinia billingiae from England for physiological properties, interaction with plants and interference with growth of E. amylovora. They reduced symptom formation by the fire blight pathogen on immature pears and the colonization of apple flowers. In contrast to E. billingiae, E. tasmaniensis strains induced a hypersensitive response in tobacco leaves and synthesized levan in the presence of sucrose. With consensus primers deduced from lsc as well as hrpL, hrcC and hrcR of the hrp region of E. amylovora and of related bacteria, these genes were successfully amplified from E. tasmaniensis DNA and alignment of the encoded proteins to other Erwinia species supported a role for environmental fitness of the epiphytic bacterium. Unlike E. tasmaniensis, the epiphytic bacterium E. billingiae produced an acyl?homoserine lactone for bacterial cell?to?cell communication. Their competition with the growth of E. amylovora may be involved in controlling fire blight. PMID:21261861

Jakovljevic, Vladimir; Jock, Susanne; Du, Zhiqiang; Geider, Klaus

2008-01-01

66

Dentinal hypersensitivity: a review.  

PubMed

Dentinal hypersensitivity is generally reported by the patient after experiencing a sharp pain caused by one of several different stimuli. The pain response varies substantially from one person to another. The condition generally involves the facial surfaces of teeth near the cervical aspect and is very common in premolars and canines. The most widely accepted theory of how the pain occurs is Brannstrom's hydrodynamic theory, fluid movement within the dentinal tubules. The dental professional, using a variety of diagnostic techniques, will discern the condition from other conditions that may cause sensitive teeth. Treatment of the condition can be invasive or non-invasive in nature. The most inexpensive and efficacious first line of treatment for most patients is a dentifrice containing a desensitizing active ingredient such as potassium nitrate and/or stannous fluoride. This review will address the prevalence, diagnosis, and treatment of dentinal hypersensitivity. In addition the home care recommendations will focus on desensitizing dentifrices. PMID:15915210

Walters, Patricia A

2005-05-15

67

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

PubMed Central

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

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

2014-01-01

68

The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans.  

PubMed

Like all physiological systems, the human immune system exhibits dose-response relationships in its reactions. The strength of sensitization is related to the potency of the immunogen and the dose that reaches the immune system. In skin, as sensitizing dose per unit area (mug cm(-2)) is increased on a log scale, there is a sigmoid dose-response curve for subsequent reactivity. Similarly, the response to elicitation shows a classical sigmoid response to increasing challenge dose, with the dose per unit area again being the determinant. There is a clear inverse correlation between the strength of sensitization and the subsequent dose of antigen to which an individual will respond. This is reflected in the different challenge systems used to diagnose the existence of allergic contact sensitization to a given allergen. The occluded patch test aims to use the highest concentration possible to detect the weakest degrees of allergy, whereas the repeated open application test uses much lower concentrations similar to those encountered in real life, applied repeatedly but without occlusion, to assess clinical relevance. Many authors have attempted to use the lowest concentrations to which rare, highly sensitized individuals can react to define the concentrations which might be free of risk in terms of inducing allergic sensitization. However, it is clear that the dose-response relationships for induction of sensitivity by repeated low-dose exposures must be carefully defined in future studies. This article reviews the dose-response relationships of human contact sensitization. PMID:17854376

Friedmann, P S

2007-12-01

69

Domain Swapping and Gene Shuffling Identify Sequences Required for Induction of an Avr-Dependent Hypersensitive Response by the Tomato Cf4 and Cf9 Proteins  

Microsoft Academic Search

The tomato Cf-4 and Cf-9 genes confer resistance to infection by the biotrophic leaf mold pathogen Cladosporium. Their protein products induce a hypersensitive response (HR) upon recognition of the fungus-encoded Avr4 and Avr9 peptides. Cf-4 and Cf-9 share . 91% sequence identity and are distinguished by sequences in their N-terminal domains A and B, their N-terminal leucine-rich repeats (LRRs) in

Brande B. H. Wulff; Colwyn M. Thomas; Matthew Smoker; Murray Grant; Jonathan D. G. Jones

2001-01-01

70

Role of autophagy in disease resistance and hypersensitive response-associated cell death  

Microsoft Academic Search

Ancient autophagy pathways are emerging as key defense modules in host eukaryotic cells against microbial pathogens. Apart from actively eliminating intracellular intruders, autophagy is also responsible for cell survival, for example by reducing the deleterious effects of endoplasmic reticulum stress. At the same time, autophagy can contribute to cellular suicide. The concurrent engagement of autophagy in these processes during infection

D Hofius; D Munch; S Bressendorff; J Mundy; M Petersen

2011-01-01

71

2,4-Dinitrofluorobenzene-induced contact hypersensitivity response in NC/Nga mice fed fructo-oligosaccharide.  

PubMed

Strategies to manipulate gut microbiota in infancy have been considered to prevent the development of allergic diseases later in life. We previously demonstrated that maternal dietary supplementation with fructo-oligosaccharide (FOS) during pregnancy and lactation modulated the composition of gut microbiota and diminished the severity of spontaneously developing atopic dermatitis-like skin lesions in the offspring of NC/Nga mice. The present study tested whether dietary FOS affects contact hypersensitivity (CHS), another model for allergic skin disease, in NC/Nga mice. In experiment 1, 5-wk-old female NC/Nga mice were fed diets either with or without FOS supplementation for 3 wk and then received 2,4-dinitrofluorobenzene (DNFB) on the ear auricle 5 times at 7-d intervals. FOS supplementation reduced CHS response as demonstrated by ear swelling. Quantitative RT-PCR analysis showed that mRNA levels for interleukin (IL)-10, IL-12p40, and IL-17 in the lesional ear skin were significantly lower in mice fed FOS. In experiment 2, female NC/Nga mice were fed diets either with or without FOS during pregnancy and lactation. After weaning, offspring were fed the diets supplemented with or without FOS. Three weeks after weaning, offspring received DNFB on the ear auricle 4 times at 7-d intervals. Although FOS supplementation after weaning reduced ear swelling, maternal FOS consumption was ineffective in offspring. The present data suggest that dietary FOS reduces CHS while maternal FOS consumption is ineffective in offspring of DNFB-treated NC/Nga mice. PMID:20924149

Fujiwara, Reiko; Sasajima, Naho; Takemura, Naoki; Ozawa, Keisuke; Nagasaka, Yuki; Okubo, Takuma; Sahasakul, Yuraporn; Watanabe, Jun; Sonoyama, Kei

2010-01-01

72

Signal transduction in lemon seedlings in the hypersensitive response against Alternaria alternata: participation of calmodulin, G-protein and protein kinases.  

PubMed

The development of an effective hypersensitive response (HR) in any plant system relies, not only in their gene composition and expression, but also on an effective and rapid signal transduction system. Lemon seedlings induce the phenylpropanoid pathway, which results in the de novo biosynthesis of the phytoalexin scoparone, as part of the hypersensitive response against Alternaria alternata. In order to elucidate some of the signaling elements that participate in the development of HR in lemon seedlings, we used several compounds that are known as activators or inhibitors of signal transduction elements in plants or in animal cells. Lemon seedlings treated either with cholera toxin or with phorbol 12-myristate 13-acetate (PMA), in the absence of A. alternata induced phenylalanine ammonia-lyase (PAL, E. C. 4.3.1.5) and the synthesis of scoparone, suggesting the participation of a G-protein and of a serine/threonine kinase, respectively, in signal transduction. The use of trifluoperazine (TFP), W-7, staurosporine, lavendustin A or 2,5-dihydroximethyl cinnamate (DHMC) prevented PAL induction as well as scoparone biosynthesis in response to the fungal inoculation, thus allowing us to infer the participation of Calmodulin (CaM), of serine/threonine and of tyrosine protein kinases (TPK) for signal transduction in Citrus limon in response to A. alternata. PMID:12462990

Ortega, Ximena; Polanco, Rubén; Castañeda, Patricia; Perez, Luz M

2002-01-01

73

A simple method for screening of plant NBS-LRR genes that confer a hypersensitive response to plant viruses and its application for screening candidate pepper genes against Pepper mottle virus.  

PubMed

Plant NBS-LRR genes are abundant and have been increasingly cloned from plant genomes. In this study, a method based on agroinfiltration and virus inoculation was developed for the simple and inexpensive screening of candidate R genes that confer a hypersensitive response to plant viruses. The well-characterized resistance genes Rx and N, which confer resistance to Potato virus X (PVX) and tobamovirus, respectively, were used to optimize a transient expression assay for detection of hypersensitive response in Nicotiana benthamiana. Infectious sap of PVX and Tobacco mosaic virus were used to induce hypersensitive response in Rx- and N-infiltrated leaves, respectively. The transient expression of the N gene induced local hypersensitive response upon infection of another tobamovirus, Pepper mild mottle virus, through both sap and transcript inoculation. When this method was used to screen 99 candidate R genes from pepper, an R gene that confers hypersensitive response to the potyvirus Pepper mottle virus was identified. The method will be useful for the identification of plant R genes that confer resistance to viruses. PMID:24552951

Tran, Phu-Tri; Choi, Hoseong; Kim, Saet-Byul; Lee, Hyun-Ah; Choi, Doil; Kim, Kook-Hyung

2014-06-01

74

Mutational analysis of the Verticillium dahliae protein elicitor PevD1 identifies distinctive regions responsible for hypersensitive response and systemic acquired resistance in tobacco.  

PubMed

In our previous study, PevD1 was characterized as a novel protein elicitor produced by Verticillium dahliae inducing hypersensitive response (HR) and systemic acquired resistance (SAR) in tobacco plants; however, the detailed mechanisms of PevD1's elicitor activity remain unclear. In this study, five mutant fragments of PevD1 were generated by polymerase chain reaction-based mutagenesis and the truncated proteins expressed in Escherichia coli were used to test their elicitor activities. Biological activity analysis showed that the N-terminal and C-terminal of PevD1 had distinct influence on HR and SAR elicitation. Fragment PevD1?N98, which spans the C-terminal 57 amino acids of PevD1, was critical for the induction of HR in tobacco plants. In contrast, fragment PevD1?C57, the N-terminal of 98 amino acids of PevD1, retained the ability to induce SAR against tobacco mosaic virus (TMV) but not induction of HR, suggesting that the induction of HR is not essential for SAR mediated by PevD1. Our results indicated that fragment PevD1?C57 could be a candidate peptide for plant protection against pathogens without causing negative effects. PMID:24080193

Liu, Wenxian; Zeng, Hongmei; Liu, Zhipeng; Yang, Xiufen; Guo, Lihua; Qiu, Dewen

2014-01-01

75

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

PubMed

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

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

2003-09-01

76

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

PubMed Central

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

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

2012-01-01

77

Impaired delayed-type hypersensitivity response in mutant mice secreting soluble CD4 without expression of membrane-bound CD4  

PubMed Central

Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell-mediated immunity. We examined the DTH response to methylated bovine serum albumin of a novel mutant strain of mice that have soluble CD4 (sCD4) in their circulation without expression of CD4 on the cell surface. The DTH response of the mutant mice was severely impaired, although the response of CD4 knockout (KO) mice, generated by homologous recombination, was comparable to that of wild-type mice. The response of the mutant mice was restored by the neutralization of sCD4 with anti-CD4, and that of CD4KO mice was markedly reduced by the implantation of a diffusion chamber containing sCD4 cDNA transfectant cells. The restored DTH response of the mutant mice treated with anti-CD4 was abolished by treatment with anti-interferon-? (IFN-?). IFN-? production by CD4 mutant and CD4KO mice was consistent with their DTH response and inversely related to the presence of sCD4 in their circulation, indicating that sCD4 impairs the DTH response by blocking the production of IFN-? in our mutant mice. These results raise the possibility that sCD4 could impair cell-mediated immunity. Our mutant mice would provide a useful tool with which to analyse the mechanisms of the DTH reaction. PMID:10929052

Wang, C-R; Hino, A; Yoshimoto, T; Nagase, H; Kato, T; Hirokawa, K; Matsuzawa, A; Nariuchi, H

2000-01-01

78

An Induced Hypersensitive-Like Response Limits Expression of Foreign Peptides via a Recombinant TMV-Based Vector in a Susceptible Tobacco  

PubMed Central

Background By using tobacco mosaic virus (TMV)-based vectors, foreign epitopes of the VP1 protein from food-and-month disease virus (FMDV) could be fused near to the C-terminus of the TMV coat protein (CP) and expressed at high levels in susceptible tobacco plants. Previously, we have shown that the recombinant TMV vaccines displaying FMDV VP1 epitopes could generate protection in guinea pigs and swine against the FMDV challenge. Recently, some recombinant TMV, such as TMVFN20 that contains an epitope FN20 from the FMDV VP1, were found to induce local necrotic lesions (LNL) on the inoculated leaves of a susceptible tobacco, Nicotiana tabacum Samsun nn. This hypersensitive-like response (HLR) blocked amplification of recombinant TMVFN20 in tobacco and limited the utility of recombinant TMV vaccines against FMDV. Methodology/Principal Findings Here we investigate the molecular mechanism of the HLR in the susceptible Samsun nn. Histochemical staining analyses show that these LNL are similar to those induced in a resistant tobacco Samsun NN inoculated with wild type (wt) TMV. The recombinant CP subunits are specifically related to the HLR. Interestingly, this HLR in Samsun nn (lacking the N/N?-gene) was able to be induced by the recombinant TMV at both 25°C and 33°C, whereas the hypersensitive response (HR) in the resistant tobacco plants induced by wt TMV through the N/N?-gene pathways only at a permissive temperature (below 30°C). Furthermore, we reported for the first time that some of defense response (DR)-related genes in tobacco were transcriptionally upregulated during HLR. Conclusions Unlike HR, HLR is induced in the susceptible tobacco through N/N?-gene independent pathways. Induction of the HLR is associated with the expression of the recombinant CP subunits and upregulation of the DR-related genes. PMID:21124743

Li, Mangmang; Li, Ping; Song, Rentao; Xu, Zhengkai

2010-01-01

79

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

PubMed Central

The vacuole of Saccharomyces cerevisiae has been a seminal model for studies of lysosomal trafficking, biogenesis, and function. Several yeast mutants defective in such vacuolar events have been unable to grow at low levels of hygromycin B, an aminoglycoside antibiotic. We hypothesized that such severe hypersensitivity to hygromycin B (hhy) is linked to vacuolar defects and performed a genomic screen for the phenotype using a haploid deletion strain library of non-essential genes. Fourteen HHY genes were initially identified and were subjected to bioinformatics analyses. The uncovered hhy mutants were experimentally characterized with respect to vesicular trafficking, vacuole morphology, and growth under various stress and drug conditions. The combination of bioinformatics analyses and phenotypic characterizations implicate defects in vesicular trafficking, vacuole fusion/fission, or vacuole function in all hhy mutants. The collection was enriched for sensitivity to monensin, indicative of vacuolar trafficking defects. Additionally, all hhy mutants showed severe sensitivities to rapamycin and caffeine, suggestive of TOR kinase pathway defects. Our experimental results also establish a new role in vacuolar and vesicular functions for two genes: PAF1, encoding a RNAP II-associated protein required for expression of cell cycle-regulated genes, and TPD3, encoding the regulatory subunit of protein phosphatase 2A. Thus, our results support linkage between severe hypersensitivity to hygromycin B and vacuolar defects. PMID:20043226

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

2010-01-01

80

Treating dentin hypersensitivity  

PubMed Central

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

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

2011-01-01

81

Abrogation of the capacity of delayed-type hypersensitivity responses to alloantigens by intravenous injection of neuraminidase-treated allogeneic cells  

SciTech Connect

BALB/c or C3H/He mice were inoculated i.v. with allogeneic spleen cells untreated or treated with neuraminidase. Appreciable or potent anti-allo-delayed-type hypersensitivity (DTH) responses were observed when mice were inoculated i.v. with untreated allogeneic cells or inoculated i.v. with those cells followed by s.c. immunization with untreated allogeneic cells. In contrast, i.v. inoculation of neuraminidase-treated allogeneic cells (presensitization) not only failed to induce any significant anti-allo-DTH responses but also abolished the capability of the animals to develop DTH responses after s.c. immunization, indicating the tolerance induction. This tolerance was alloantigen-specific, and rapidly inducible and long lasting. The induction of suppressor cell activity was demonstrated in tolerant mice. When spleen cells from such tolerant mice were transferred i.v. into 600 R x-irradiated syngeneic recipient mice alone or together with normal syngeneic spleen cells, these tolerant spleen cells themselves failed to induce DTH responses but did not exhibit suppressive effect on the generation of DTH responses induced by normal spleen cells cotransferred. These results indicate that i.v. administration of neuraminidase-treated allogeneic cells results in the induction of alloantigen-specific tolerance which is not always associated with the induction of suppressor cell activity but rather with the elimination or functional impairment of alloantigen-specific clones.

Sano, S.; Suda, T.; Qian, J.H.; Sato, S.; Ikegami, R.; Hamaoka, T.; Fujiwara, H.

1987-12-01

82

Delayed-type hypersensitivity response to crude and fractionated antigens from Fonsecaea pedrosoi CMMI 1 grown in different culture media.  

PubMed

Chromoblastomycosis is a subcutaneous fungal disease caused by dematiaceous fungi, especially by Fonsecaea pedrosoi, regarded as its major causative agent in Brazil. In recent years there has been a decline in the use of skin testing for delayed-type hypersensitivity (DTH) in epidemiological surveys of fungal infections, mainly because of the unpredictability of positive reactions and lack of specificity of the antigens used. The aim of the present study was to assess delayed-type skin tests in guinea pigs experimentally infected with F. pedrosoi using exoantigens prepared from two culture filtrates. Sixteen adult male guinea pigs were inoculated intratesticularly with fungal cells and submitted to sensitivity assays 4 weeks after inoculation. They received an intradermal injection with crude and fractionated antigens from Alviano's and Smith's cultures, and were assessed 24 and 48 h thereafter. Except for one animal, all of them had positive indurations after 48 h. There were no statistical differences between the measurements at 24 and 48 h for each exoantigen used, neither among the induration measurements at 48 h when different preparations were compared. Our results suggest that a delayed-type skin test using antigens produced in synthetic media may be useful for the assessment of primary exposure to chromoblastomycosis. PMID:16830192

Corbellini, Valeriano Antonio; Scroferneker, Maria Lúcia; Carissimi, Mariana; Santolin, Luciane Domingues

2006-07-01

83

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

PubMed

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

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

2006-10-01

84

Anandamide Attenuates Th-17 Cell-Mediated Delayed-Type Hypersensitivity Response by Triggering IL-10 Production and Consequent microRNA Induction  

PubMed Central

Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions. However, their role in the regulation of Th17 cells has not been studied previously. In the current study, we used methylated Bovine Serum Albumin [mBSA]-induced delayed type hypersensitivity [DTH] response in C57BL/6 mice, mediated by Th17 cells, as a model to test the anti-inflammatory effects of endocannabinoids. Administration of anandamide [AEA], a member of the endocannabinoid family, into mice resulted in significant mitigation of mBSA-induced inflammation, including foot pad swelling, cell infiltration, and cell proliferation in the draining lymph nodes [LN]. AEA treatment significantly reduced IL-17 and IFN-? production, as well as decreased ROR?t expression while causing significant induction of IL-10 in the draining LNs. IL-10 was critical for the AEA-induced mitigation of DTH response inasmuch as neutralization of IL-10 reversed the effects of AEA. We next analyzed miRNA from the LN cells and found that 100 out of 609 miRNA species were differentially regulated in AEA-treated mice when compared to controls. Several of these miRNAs targeted proinflammatory mediators. Interestingly, many of these miRNA were also upregulated upon in vitro treatment of LN cells with IL-10. Together, the current study demonstrates that AEA may suppress Th-17 cell–mediated DTH response by inducing IL-10 which in turn triggers miRNA that target proinflammatory pathways. PMID:24699635

Jackson, Austin R.; Nagarkatti, Prakash; Nagarkatti, Mitzi

2014-01-01

85

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

PubMed Central

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

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

1995-01-01

86

Oral Hypersensitivity Reactions  

MedlinePLUS

... Million NIDCR/NIH Grant 2015 AAOM Call for Abstract Submissions Upcoming Events 2015 Annual Conference Registration is Now Open 2016 Annual Meeting in Atlanta - Save the Date! Oral Hypersensitivity Reactions ...

87

Elicitin-like proteins Oli-D1 and Oli-D2 from Pythium oligandrum trigger hypersensitive response in Nicotiana benthamiana and induce resistance against Botrytis cinerea in tomato.  

PubMed

The biocontrol agent Pythium oligandrum and its elicitin-like proteins oligandrins have been shown to induce disease resistance in a range of plants. In the present study, the ability of two oligandrins, Oli-D1 and Oli-D2, to induce an immune response and the possible molecular mechanism regulating the defence responses in Nicotiana benthamiana and tomato were investigated. Infiltration of recombinant Oli-D1 and Oli-D2 proteins induced a typical immune response in N.?benthamiana including the induction of a hypersensitive response (HR), accumulation of reactive oxygen species and production of autofluorescence. Agrobacterium-mediated transient expression assays revealed that full-length Oli-D1 and Oli-D2 were required for full HR-inducing activity in N.?benthamiana, and virus-induced gene silencing-mediated knockdown of some of the signalling regulatory genes demonstrated that NbSGT1 and NbNPR1 were required for Oli-D1 and Oli-D2 to induce HR in N.?benthamiana. Subcellular localization analyses indicated that both Oli-D1 and Oli-D2 were targeted to the plasma membrane of N.?benthamiana. When infiltrated or transiently expressed in leaves, Oli-D1 and Oli-D2 induced resistance against Botrytis cinerea in tomato and activated the expression of a set of genes involved in the jasmonic acid/ethylene (JA/ET)-mediated signalling pathway. Our results demonstrate that Oli-D1 and Oli-D2 are effective elicitors capable of inducing immune responses in plants, probably through the JA/ET-mediated signalling pathway, and that both Oli-D1 and Oli-D2 have potential for the development of bioactive formulae for crop disease control in practice. PMID:25047132

Ouyang, Zhigang; Li, Xiaohui; Huang, Lei; Hong, Yongbo; Zhang, Yafen; Zhang, Huijuan; Li, Dayong; Song, Fengming

2014-07-22

88

Protein-DNA interactions in the human beta-globin locus control region hypersensitive site-2 as revealed by four nitrogen mustards.  

PubMed Central

Four nitrogen mustards have been used in this study to examine protein-DNA interactions in intact human cells, specifically at the locus control region hypersensitive site-2 (LCR HS-2) of the human beta-globin locus. Three of these nitrogen mustards are DNA-targeted by attachment of an acridine or amsacrine intercalating chromophore, while the fourth (chlorambucil) is a non-targeted mustard. The ligation-mediated PCR technique was used to determine the sites of damage at base pair resolution on DNA sequencing gels. A densitometric comparison was made between DNA damaged in intact erythroid K562 cells and in purified DNA. The intensity of DNA damage sites in the LCR HS-2 were found to differ significantly between intact K562 cells and purified DNA. At the NF-E2/AP-1 motif, pronounced damage protection was observed in DNA derived from drug treated cells. The nuclear factor- erythroid 2 (NF-E2) protein factor is thought to bind at this NF-E2/AP-1 motif in K562 cells. Other sites of protection and enhancement that corresponded to known transcription factor binding sites were also detected. These nitrogen mustards are therefore very effective compounds for detection of transcription factor binding to DNA in intact cells and are superior to other commonly used agents. The sequence selectivity of the compounds was determined using plasmid DNA and compared to that found in intact cells. The acridine-based nitrogen mustard had a preference for forming adducts at guanine bases, while the two amsacrine-based nitrogen mustards and chlorambucil formed adducts at both guanine and adenine bases. PMID:9241238

Temple, M D; Cairns, M J; Denny, W A; Murray, V

1997-01-01

89

Role of calcium in signal transduction during the hypersensitive response caused by basidiospore-derived infection of the cowpea rust fungus  

PubMed Central

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 calcium ([Ca2+]i) in the HR of cowpea to the cowpea rust fungus. By using confocal laser scanning microscopy in conjunction with a calcium reporter dye, we found a slow, prolonged elevation of [Ca2+]i in epidermal cells of resistant but not susceptible plants as the fungus grew through the cell wall. [Ca2+]i levels declined to normal levels as the fungus entered and grew within the cell lumen. This elevation was related to the stage of fungal growth and not to the speed of initiation of subsequent cell death. Elevated [Ca2+]i levels also represent the first sign of the HR detectable in this cowpea-cowpea rust fungus system. The increase in [Ca2+]i was prevented by calcium channnel inhibitors. This effect was consistent with pharmacological tests in which these inhibitors delayed the HR. The data suggest that elevation of [Ca2+]i is involved in signal transduction leading to the HR during rust fungal infection. PMID:9548984

Xu, H; Heath, MC

1998-01-01

90

Capsicum annuum basic transcription factor 3 (CaBtf3) regulates transcription of pathogenesis-related genes during hypersensitive response upon Tobacco mosaic virus infection.  

PubMed

Hypersensitive response (HR) cell death upon plant virus infection is an excellent plant strategy for inhibiting viral movement and obtaining systemic acquired resistance (SAR) against further infection. Various host factors are involved in these HR processes, either directly as viral resistance proteins or indirectly. We characterized a gene encoding the CaBtf3 [?-nascent polypeptide-associated complex (NAC) subunit] of NAC from the hot pepper plant. NAC contacts nascent polypeptides to prevent aggregation and degradation of newly synthesized proteins by controlling cotranslational protein folding. CaBtf3 protein fused to green fluorescent protein predominantly localized to the nucleus. Silencing phenotype of CaBtf3 upon the Tobacco mosaic virus (TMV)-P(0) inoculation exhibited reduced HR cell death and decreased expression of some HR-associated genes, but increased TMV coat protein levels compared with TRV2 control plants. Furthermore, silencing of NbBtf3, a highly homologous gene of CaBtf3, also led to the reduced Bax- and Pto-mediated cell death. The results indicate that CaBtf3 might be involved in HR cell death and could function as a transcription factor in the nucleus by transcriptional regulation of HR-related gene expression. PMID:22209846

Huh, Sung Un; Kim, Ki-Jeong; Paek, Kyung-Hee

2012-01-13

91

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

PubMed Central

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

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

2014-01-01

92

Hypersensitivity Pneumonitis Caused by Trichoderma viride  

Microsoft Academic Search

Hypersensitivity pneumonitis (HP) can be induced by exposure to indoor molds contaminating humidifiers and heating or ventilation systems. A 54-year-old woman with dyspnea, cough, chest pain, and fever was seen in the emergency room. A chest radiograph revealed interstitial infiltrates and blood tests showed leukocytosis with neutrophilia and severe hypoxemia. A diagnosis of HP was made by a combination of

Alicia Enríquez-Matas; Santiago Quirce; Noelia Cubero; Joaquín Sastre; Rosario Melchor

2009-01-01

93

IL1-induced tumor necrosis factor-a elicits inflammatory cell infiltration in the skin by inducing IFN-g-inducible protein 10 in the elicitation phase of the contact hypersensitivity response  

Microsoft Academic Search

Contact hypersensitivity (CHS) is a typical inflammatory response against contact allergens. Inflammatory cytokines, including IL-1 and tumor necrosis factor (TNF)-a, are implicated in the reaction, although the precise roles of each cytokine have not been completely elucidated. In this report, we dissected the functional roles of IL-1 and TNF-a during CHS. CHS induced by 2,4,6- trinitorochlorobenzene as well as oxazolone

Susumu Nakae; Yutaka Komiyama; Shosaku Narumi; Katsuko Sudo; Reiko Horai; Yoh-ichi Tagawa; Kenji Sekikawa; Koji Matsushima; Masahide Asano; Yoichiro Iwakura

94

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

Microsoft Academic Search

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

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

2002-01-01

95

High dose dietary pyridoxine induces T-helper type 1 polarization and decreases contact hypersensitivity response to fluorescein isothiocyanate in mice.  

PubMed

Pyridoxine (vitamin B(6)) is commonly used as a dietary supplement and beneficial effects of it are expected. However, excess ingestion of pyridoxine has been shown to cause a severe sensory neuropathy in humans and experimental animals. We have been studying the linkage between the nervous and immune systems using a fluorescein isothiocyanate (FITC)-induced contact hypersensitivity (CHS) mouse model. We have found that activation of transient receptor potential ankyrin 1 (TRPA1), which is expressed on sensory neurons, enhances skin sensitization to FITC. Another feature of FITC-induced CHS is its dependence on T helper 2 (Th2) type responses. We hypothesized that the excess intake of pyridoxine may affect sensitization to FITC and influence helper T-cell polarization. We examined FITC-induced CHS in BALB/c mice fed a diet containing excess pyridoxine (120 mg/kg diet) for 3 weeks. We found that mice fed on the excess-pyridoxine diet exhibited a lower response as to FITC-induced CHS compared with ones fed on a diet with a standard pyridoxine content (6.0 mg/kg diet). Moreover, the interferon (IFN)-?/interleukin (IL)-4 ratio produced by draining lymph node cells was significantly higher with the excess-pyridoxine diet. This suggested that the cytokine balance was shifted toward Th1 with the excess-pyridoxine diet. Consistently, Th1-dependent oxazolone-induced CHS was enhanced with the excess-pyridoxine diet. These results suggested that an excess pyridoxine intake actively influences the immune system by altering helper T cell polarization. PMID:22466557

Kobayashi, Chie; Kurohane, Kohta; Imai, Yasuyuki

2012-01-01

96

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

97

Classification of Hypersensitivity Pneumonitis  

Microsoft Academic Search

Background: Regardless of the causative antigen, hypersensitivity pneumonitis (HP) is usually classified as ‘acute’, ‘subacute’ or ‘chronic’. Considerable confusion still surrounds this classification because there are no widely accepted criteria to distinguish the various stages. The objective of this study wasto determine whether the current classification of HP truly reflects categories of patients with distinct clinical features. Methods: Data obtained

Yves Lacasse; Moises Selman; Ulrich Costabel; Jean-Charles Dalphin; Ferran Morell; Riitta Erkinjuntti-Pekkanen; Nestor L. Mueller; Thomas V. Colby; Mark Schuyler; Valérie Jomphe; Yvon Cormier

2009-01-01

98

Planarian Phototactic Assay Reveals Differential Behavioral Responses Based on Wavelength  

PubMed Central

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

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

2014-01-01

99

A suppressor of the menadione-hypersensitive phenotype of a Xanthomonas campestris pv. phaseoli oxyR mutant reveals a novel mechanism of toxicity and the protective role of alkyl hydroperoxide reductase.  

PubMed

We isolated menadione-resistant mutants of Xanthomonas campestris pv. phaseoli oxyR (oxyR(Xp)). The oxyRR2(Xp) mutant was hyperresistant to the superoxide generators menadione and plumbagin and was moderately resistant to H(2)O(2) and tert-butyl hydroperoxide. Analysis of enzymes involved in oxidative-stress protection in the oxyRR2(Xp) mutant revealed a >10-fold increase in AhpC and AhpF levels, while the levels of superoxide dismutase (SOD), catalase, and the organic hydroperoxide resistance protein (Ohr) were not significantly altered. Inactivation of ahpC in the oxyRR2(Xp) mutant resulted in increased sensitivity to menadione killing. Moreover, high levels of expression of cloned ahpC and ahpF in the oxyR(Xp) mutant complemented the menadione hypersensitivity phenotype. High levels of other oxidant-scavenging enzymes such as catalase and SOD did not protect the cells from menadione toxicity. These data strongly suggest that the toxicity of superoxide generators could be mediated via organic peroxide production and that alkyl hydroperoxide reductase has an important novel function in the protection against the toxicity of these compounds in X. campestris. PMID:12591894

Vattanaviboon, Paiboon; Whangsuk, Wirongrong; Mongkolsuk, Skorn

2003-03-01

100

Hypersensitivity to suture anchors.  

PubMed

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

101

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.; González, Virginia; Parisi, Gustavo; Cauerhff, Ana; Barrios, Ivana; Blanch, Luis Bruno; Fossati, Carlos A.

2014-01-01

102

Hypersensitivity reactions to vaccine components.  

PubMed

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

Heidary, Noushin; Cohen, David E

2005-09-01

103

Purification and immunocytolocalization of a novel Phytophthora boehmeriae protein inducing the hypersensitive response and systemic acquired resistance in tobacco and Chinese cabbage  

Microsoft Academic Search

A 90 kDa protein elicitor, PB90, was purified from the culture filtrate of Phytophthora boehmeriae. Procedures including hydrophobic interaction and ion-exchange chromatography were used to purify the protein. PB90 induced hypersensitive reaction in tobacco leaves at a concentration as low as 200pM and induced systemic acquired resistance (SAR) to TMV, Alternaria alternata, P. parasitica and Ralstonia solanacearum. In addition, it

Y. C. Wang; D. W. Hu; Z. G. Zhang; Z. C. Ma; X. B. Zheng; D. B. Li

2003-01-01

104

Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota  

PubMed Central

Animals have developed the means for supporting complex and dynamic consortia of microorganisms during their life cycle. A transcendent view of vertebrate biology therefore requires an understanding of the contributions of these indigenous microbial communities to host development and adult physiology. These contributions are most obvious in the gut, where studies of gnotobiotic mice have disclosed that the microbiota affects a wide range of biological processes, including nutrient processing and absorption, development of the mucosal immune system, angiogenesis, and epithelial renewal. The zebrafish (Danio rerio) provides an opportunity to investigate the molecular mechanisms underlying these interactions through genetic and chemical screens that take advantage of its transparency during larval and juvenile stages. Therefore, we developed methods for producing and rearing germ-free zebrafish through late juvenile stages. DNA microarray comparisons of gene expression in the digestive tracts of 6 days post fertilization germ-free, conventionalized, and conventionally raised zebrafish revealed 212 genes regulated by the microbiota, and 59 responses that are conserved in the mouse intestine, including those involved in stimulation of epithelial proliferation, promotion of nutrient metabolism, and innate immune responses. The microbial ecology of the digestive tracts of conventionally raised and conventionalized zebrafish was characterized by sequencing libraries of bacterial 16S rDNA amplicons. Colonization of germ-free zebrafish with individual members of its microbiota revealed the bacterial species specificity of selected host responses. Together, these studies establish gnotobiotic zebrafish as a useful model for dissecting the molecular foundations of host-microbial interactions in the vertebrate digestive tract. PMID:15070763

Rawls, John F.; Samuel, Buck S.; Gordon, Jeffrey I.

2004-01-01

105

Quantification of the stapedial reflex reveals delayed responses in autism.  

PubMed

Autism is a developmental disorder characterized, in part, by sensory abnormalities. It is well established that most if not all patients with autism have problems with auditory processing, ranging from deafness to hyperacusis, and physiological testing of auditory function (i.e. auditory brain stem responses) implicates brain stem dysfunction in autism. Additionally, previous research from this lab has revealed significantly fewer auditory brain stem neurons in autistic subjects as young as 2 years of age. These observations have led us to hypothesize that objective, noninvasive measures of auditory function can be used as an early screening tool to identify neonates with an elevated risk of carrying a diagnosis of autism. Here, we provide a detailed quantitative investigation of the acoustic stapedial reflex (ASR), a three- or four-neuron brain stem circuit, in young autistic subjects and normal developing controls. Indeed, we find significantly lower thresholds, responses occurring at significantly longer latency and right-left asymmetry in autistic subjects. The results from this investigation support deficits in auditory function as a cardinal feature of autism and suggest that individuals with autism can be identified by their ASR responses. PMID:23825093

Lukose, Richard; Brown, Kevin; Barber, Carol M; Kulesza, Randy Joseph

2013-10-01

106

Hypersensitivity to antihistamines.  

PubMed

Antihistamines are the cornerstone of allergy therapy and are not expected to cause hypersensitivity reactions. We describe two cases, one had urticaria to multiple anti-H1-preparations and the other had anaphylaxis to hydroxyzine. We also provide a review of the English literature on reported reactions regarding causative preparations and manifestations. The latter showed a wide range; most commonly urticaria/angioedema, contact dermatitis, anaphylaxis, and fixed drug eruption (FDE). Most reported cases were young to middle age adults, with apparent predilection to female subjects. The onset of reactions varied from a few minutes for anaphylaxis and urticaria/angioedema, several hours for maculopapular rashes, or longer for contact dermatitis and FDE. Almost all antihistamines have been reported as causing reactions; cetirizine was the most common oral preparation followed by its parent drug, hydroxyzine. Doxepin cream was the most commonly implicated topical preparation in causing contact dermatitis. A causal relationship is often difficult to recognize because the reaction may be similar to the disease being treated with that antihistamine preparation. Reactions to one preparation are likely to occur, but not always, to other members of the same class. Diagnosis is based on clinical suspicion and may be verified by challenge testing. Except for patch testing in contact dermatitis or fixed eruption, other tests have not shown optimal reliability. In most cases, challenge testing with multiple preparations would identify one or more preparations that can be tolerated. Although hypersensitivity to antihistamines seems to be very rare, awareness of the problem would reduce its misdiagnosis. PMID:24169055

Shakouri, Alireza A; Bahna, Sami L

2013-01-01

107

Subacute hypersensitivity pneumonitis in an HIV infected patient receiving antiretroviral therapy  

Microsoft Academic Search

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

Alison M Morris; Stephen Nishimura; Laurence Huang

2000-01-01

108

The prevalence of dentin hypersensitivity in general dental practices in the northwest United States  

PubMed Central

Background The prevalence of dentin hypersensitivity is uncertain, yet appropriate diagnosis and treatment of dentin hypersensitivity require accurate knowledge regarding its prevalence. The authors conducted a study to estimate the prevalence of dentin hypersensitivity in general dental practices and to investigate associated risk factors. Methods The authors conducted a cross-sectional survey of 787 adult patients from 37 general dental practices within Northwest Practice-based Research Collaborative in Evidence-based DENTistry (PRECEDENT). Dentin hypersensitivity was diagnosed by means of participants’ responses to a question regarding pain in their teeth and gingivae, and practitioner-investigators conducted a clinical examination to rule out alternative causes of pain. Participants recorded their pain level on a visual analog scale and the Seattle Scales in response to a one-second air blast. The authors used generalized estimating equation log-linear models to estimate the prevalence and the prevalence ratios. Results The prevalence of dentin hypersensitivity was 12.3 percent; patients with hypersensitivity had, on average, 3.5 hypersensitive teeth. The prevalence of dentin hypersensitivity was higher among 18- to 44-year olds than among participants 65 years or older; it also was higher in women than in men, in participants with gingival recession than in those without gingival recession and in participants who underwent at-home tooth whitening than in those who did not. Hypersensitivity was not associated with obvious occlusal trauma, noncarious cervical lesions or aggressive toothbrushing habits. Conclusions One in eight participants from general practices had dentin hypersensitivity, which was a chronic condition causing intermittent, low-level pain. Patients with hypersensitivity were more likely to be younger, to be female and to have a high prevalence of gingival recession and at-home tooth whitening. Practical Implications Given dentin hypersensitivity’s prevalence, clinicians should diagnose it only after investigating all other possible sources of pain. PMID:23449905

Cunha-Cruz, Joana; Wataha, John C.; Heaton, Lisa J.; Rothen, Marilynn; Sobieraj, Martin; Scott, JoAnna; Berg, Joel

2013-01-01

109

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

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

2013-01-01

110

Central and peripheral hypersensitivity in the irritable bowel syndrome  

PubMed Central

Previous investigations of somatic hypersensitivity in IBS patients have typically involved only a single stimulus modality, and little information exists regarding whether patterns of somatic pain perception vary across stimulus modalities within a group of patients with IBS. Therefore, the current study was designed to characterize differences in perceptual responses to a battery of noxious somatic stimuli in IBS patients compared to controls. A total of 78 diarrhea-predominant and 57 controls participated in the study. We evaluated pain threshold and tolerance and sensory and affective ratings of contact thermal, mechanical pressure, ischemic stimuli, and cold pressor stimuli. In addition to assessing perceptual responses, we also evaluated differences in neuroendocrine and cardiovascular responses to these experimental somatic pain stimuli. A subset of IBS patients demonstrated the presence of somatic hypersensitivity to thermal, ischemic, and cold pressor nociceptive stimuli. The somatic hypersensitivity in IBS patients was somatotopically organized in that the lower extremities that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. There were also changes in ACTH, cortisol, and systolic blood pressure in response to the ischemic pain testing in IBS patients when compared to controls. The results of this study suggest that a more widespread alteration in central pain processing in a subset of IBS patients may be present as they display hypersensitivity to heat, ischemic, and cold pressor stimuli. PMID:20074857

Zhou, QiQi; Fillingim, Roger B.; Riley, Joseph L.; Malarkey, William B.; Verne, G. Nicholas

2010-01-01

111

Pepper Suppressor of the G2 Allele of skp1 Interacts with the Receptor-Like Cytoplasmic Kinase1 and Type III Effector AvrBsT and Promotes the Hypersensitive Cell Death Response in a Phosphorylation-Dependent Manner1[C][W][OPEN  

PubMed Central

Xanthomonas campestris pv vesicatoria type III effector protein, AvrBsT, triggers hypersensitive cell death in pepper (Capsicum annuum). Here, we have identified the pepper SGT1 (for suppressor of the G2 allele of skp1) as a host interactor of AvrBsT and also the pepper PIK1 (for receptor-like cytoplasmic kinase1). PIK1 specifically phosphorylates SGT1 and AvrBsT in vitro. AvrBsT specifically binds to the CHORD-containing protein and SGT1 domain of SGT1, resulting in the inhibition of PIK1-mediated SGT1 phosphorylation and subsequent nuclear transport of the SGT1-PIK1 complex. Liquid chromatography-tandem mass spectrometry of the proteolytic peptides of SGT1 identified the residues serine-98 and serine-279 of SGT1 as the major PIK1-mediated phosphorylation sites. Site-directed mutagenesis of SGT1 revealed that the identified SGT1 phosphorylation sites are responsible for the activation of AvrBsT-triggered cell death in planta. SGT1 forms a heterotrimeric complex with both AvrBsT and PIK1 exclusively in the cytoplasm. Agrobacterium tumefaciens-mediated coexpression of SGT1 and PIK1 with avrBsT promotes avrBsT-triggered cell death in Nicotiana benthamiana, dependent on PIK1. Virus-induced silencing of SGT1 and/or PIK1 compromises avrBsT-triggered cell death, hydrogen peroxide production, defense gene induction, and salicylic acid accumulation, leading to the enhanced bacterial pathogen growth in pepper. Together, these results suggest that SGT1 interacts with PIK1 and the bacterial effector protein AvrBsT and promotes the hypersensitive cell death associated with PIK1-mediated phosphorylation in plants. PMID:24686111

Kim, Nak Hyun; Kim, Dae Sung; Chung, Eui Hwan; Hwang, Byung Kook

2014-01-01

112

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

PubMed

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

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

2013-11-01

113

Vitamin D Deficiency Promotes Skeletal Muscle Hypersensitivity and Sensory Hyperinnervation  

PubMed Central

Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin D deficient. Previous findings demonstrated that putative nociceptors (“pain-sensing” nerves) express vitamin D receptors (VDRs), suggesting responsiveness to 1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient diets for 2– 4 weeks showed mechanical deep muscle hypersensitivity, but not cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance deficits and occurred before onset of overt muscle or bone pathology. Hypersensitivity was not due to hypocalcemia and was actually accelerated by increased dietary calcium. Morphometry of skeletal muscle innervation showed increased numbers of presumptive nociceptor axons (peripherin-positive axons containing calcitonin gene-related peptide), without changes in sympathetic or skeletal muscle motor innervation. Similarly, there was no change in epidermal innervation. In culture, sensory neurons displayed enriched VDR expression in growth cones, and sprouting was regulated by VDR-mediated rapid response signaling pathways, while sympathetic outgrowth was not affected by different concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D deficiency can lead to selective alterations in target innervation, resulting in presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is likely to contribute to muscular hypersensitivity and pain. PMID:21957236

Tague, Sarah E.; Clarke, Gwenaëlle L.; Winter, Michelle K.; McCarson, Kenneth E.; Wright, Douglas E.; Smith, Peter G.

2012-01-01

114

THE "DELAYED HYPERSENSITIVITY" INDUCED BY ANTIGEN-ANTIBODY COMPLEXES  

PubMed Central

The "delayed hypersensitive" reactivity induced by antigen-antibody complexes has been studied from the standpoints of the role of such complexes in establishing this state, and the relationship of this state to classical delayed hypersensitivity. It has been shown that the reactivity established by antigen-antibody complexes appears early after injection, disappears within a few days, and is characterized by several properties which make it appear similar to true delayed hypersensitivity, including its appearance, its relative persistence for 48 hours, and its occurrence in the absence of antibodies. By the same tokens, it may be distinguished from hypersensitive reactions of the immediate type. It is referred to here as reactivity of the Jones-Mote type. Antigen alone stimulates exactly the same kind of early reactive state, but with larger doses of antigen this is later replaced by other immunologic responses including circulating antibodies and Arthus reactivity. If sufficiently small doses of antigen are employed, however, the "monophasic" reaction which follows antigen-antibody complexes consisting of the Jones-Mote type of skin responsiveness may be seen. The dermal reactivity under discussion is unlike classical delayed hypersensitivity chiefly in its evanescent character; it is present only during a few days early after antigen administration. It is suggested that this kind of reactivity, which may perhaps require a category of its own, may be related to the "tissue immunity" to tumor transplants which has been observed in mice. PMID:13598815

Raffel, Sidney; Newel, J. Michael

1958-01-01

115

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

116

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

117

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

PubMed

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

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

2003-08-01

118

Pharmacometabolomics Reveals That Serotonin Is Implicated in Aspirin Response Variability  

PubMed Central

While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81?mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72?±?8 vs. 61?±?11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9?×?10?4, N = 12). These results suggest that serotonin is implicated in aspirin response variability. PMID:25029353

Ellero-Simatos, S; Lewis, J P; Georgiades, A; Yerges-Armstrong, L M; Beitelshees, A L; Horenstein, R B; Dane, A; Harms, A C; Ramaker, R; Vreeken, R J; Perry, C G; Zhu, H; Sànchez, C L; Kuhn, C; Ortel, T L; Shuldiner, A R; Hankemeier, T; Kaddurah-Daouk, R

2014-01-01

119

What boxing-related stimuli reveal about response behaviour.  

PubMed

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

Ottoboni, Giovanni; Russo, Gabriele; Tessari, Alessia

2014-11-11

120

Development of a flow cytometry assay for the identification and differentiation of chemicals with the potential to elicit irritation, IgE-mediated, or T cell-mediated hypersensitivity responses.  

PubMed

These studies were conducted to investigate the potential use of a flow cytometric analysis method for the identification and differentiation of chemicals with the capacity to induce irritation, IgE- or T cell-mediated hypersensitivity responses. An initial study investigated the ability of equally sensitizing concentrations (determined by local lymph node assay) of IgE-mediated (Toluene Diisocyanate-TDI) and T cell-mediated (Dinitrofluorobenzene-DNFB) allergens to differentially modulate the IgE+B220+ population in the lymph nodes draining the dermal exposure site. Sodium lauryl sulfate (SLS) was also tested as a nonsensitizing irritant control. Female B6C3F1 mice were dermally exposed once daily for 4 consecutive days, with the optimum time point for analysis determined by examining the IgE+B220+ population 8, 10, and 12 days post-initial chemical exposure. At the peak time point, day 10, the IgE+B220+ population was significantly elevated in TDI (41%), while moderately elevated in DNFB (18%) exposed animals when compared to the vehicle (0.8%), and remained unchanged in SLS (2.2%) exposed animals when compared to the ethanol control (2.5%). Experiments in our laboratory and others have demonstrated that the draining lymph node B220+ population becomes significantly elevated following exposure to allergens (IgE- and T cell-mediated), not irritants, allowing for their differentiation. An existing mouse ear swelling assay was used to identify chemical irritants. Therefore, using the endpoints of percent ear swelling, percent B220+ cells, and percent IgE+B220+ cells, a combined irritancy/phenotypic analysis assay was developed and tested with tetradecane (irritant), toluene diisocyanate, trimellitic anhydride (IgE-mediated allergens), benzalkonium chloride, dinitrofluorobenzene, oxazolone, and dinitrochlorobenzene (T cell-mediated allergens) over a range of concentrations. Based upon the pattern of response observed, a paradigm was developed for continued evaluation: Irritant exposure will result in significant ear swelling without altering the B220+ or IgE+B220+ populations. Exposure to sensitizers (IgE-mediated or T cell-mediated) will increase the B220+ population and the percent ear swelling will remain unchanged or will significantly increase, depending on the irritancy capacity of the chemical. Both the IgE+B220+ and B220+ populations will become elevated at the same test concentration following exposure to IgE-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will be equal to the percent of B220+ cells. The B220+ population will increase at a lower test concentration than the IgE+B220+ population, following exposure to T cell-mediated, hypersensitivity inducing allergens. At its peak, the percent of IgE+B220+ cells will reach less than half that of the percent of B220+ cells. The irritancy/phenotypic analysis method may represent a single murine assay able to identify and differentiate chemicals with the capacity to induce irritation, or IgE-mediated or T cell-mediated responses. PMID:10353312

Manetz, T S; Meade, B J

1999-04-01

121

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

122

Network deconstruction reveals network structure in responsive microgels.  

PubMed

Detailed characterization of hydrogel particle erosion revealed critical physicochemical differences between spheres, where network decomposition was informative of network structure. Real-time, in situ monitoring of the triggered erosion of colloidal hydrogels (microgels) was performed via multiangle light scattering. The solution-average molar mass and root-mean-square radii of eroding particles were measured as a function of time for microgels prepared from N-isopropylacrylamide (NIPAm) or N-isopropylmethacrylamide (NIPMAm), copolymerized with a chemically labile cross-linker (1,2-dihydroxylethylene)bisacrylamide (DHEA). Precipitation polymerization was employed to yield particles of comparable dimensions but with distinct topological features. Heterogeneous cross-linker incorporation resulted in a heterogeneous network structure for pNIPAm microgels. During the erosion reaction, mass loss proceeded from the exterior toward the interior of the polymer. In contrast, pNIPMAm microgels had a more homogeneous network structure, which resulted in a more uniform mass loss throughout the particle during erosion. Although both particle types degraded into low molar mass products, pNIPAm microgels were incapable of complete dissolution due to the presence of nondegradable cross-links arising from chain transfer and branching during particle synthesis. The observations described herein provide insight into key design parameters associated with the synthesis of degradable hydrogel particles, which may be of use in various biotechnological applications. PMID:21425815

Smith, Michael H; Herman, Emily S; Lyon, L Andrew

2011-04-14

123

Molecular Analysis of Plant Defense Responses to Plant Pathogens  

PubMed Central

A number of inducible plant responses are believed to contribute to disease resistance. These responses include the hypersensitive reaction, phytoalexin synthesis, and the production of chitinase, glucanase, and hydroxyproline-rich glycoproteins. Because of the coordinate induction of these responses, it has been difficult to determine whether they are functional defense responses, and if they are, how they specifically contribute to disease resistance. Recent developments in molecular biology have provided experimental techniques that will reveal the specific contribution of each response to disease resistance. In this paper, we describe a strategy to determine if the hypersensitive reaction is a functional plant defense mechanism. PMID:19283005

Lindgren, P. B.; Jakobek, J. L.; Smith, J. A.

1992-01-01

124

Transcript and protein profiling analysis of OTA-induced cell death reveals the regulation of the toxicity response process in Arabidopsis thaliana  

PubMed Central

Ochratoxin A (OTA) is a toxic isocoumarin derivative produced by various species of mould which mainly grow on grain, coffee, and nuts. Recent studies have suggested that OTA induces cell death in plants. To investigate possible mechanisms of OTA phytotoxicity, both digital gene expression (DGE) transcriptomic and two-dimensional electrophoresis proteomic analyses were used, through which 3118 genes and 23 proteins were identified as being up- or down-regulated at least 2-fold in Arabidopsis leaf in response to OTA treatment. First, exposure of excised Arabidopsis thaliana leaves to OTA rapidly causes the hypersensitive reponse, significantly accelerates the increase of reactive oxygen species and malondialdehyde, and enhances antioxidant enzyme defence responses and xenobiotic detoxification. Secondly, OTA stimulation causes dynamic changes in transcription factors and activates the membrane transport system dramatically. Thirdly, a concomitant persistence of compromised photosynthesis and photorespiration is indicative of a metabolic shift from a highly active to a weak state. Finally, the data revealed that ethylene, salicylic acid, jasmonic acid, and mitogen-activated protein kinase signalling molecules mediate the process of toxicity caused by OTA. Profiling analyses on Arabidopsis in response to OTA will provide new insights into signalling transduction that modulates the OTA phytotoxicity mechanism, facilitate mapping of regulatory networks, and extend the ability to improve OTA tolerance in Arabidopsis. PMID:22207617

Wang, Yan; Peng, Xiaoli; Xu, Wentao; Luo, YunBo; Zhao, Weiwei; Hao, Junran; Liang, Zhihong; Zhang, Yu; Huang, Kunlun

2012-01-01

125

Hypersensitivity reactions to beta-lactams.  

PubMed

Beta-lactam antibiotics (BLs) are the most frequent cause of hypersensitivity reactions mediated by specific immunological mechanisms, with two main types, IgE reactions or T-cell-dependent responses. From a practical point of view, these reactions can be classified into immediate, for those appearing within 1 h after drug intake, and non-immediate, for those appearing at least 1 h after and usually within 24 h of BL administration. The clinical symptoms differ according to this classification. Urticaria and anaphylaxis are the most frequently recorded symptoms in immediate reactions and maculopapular exanthema and delayed urticaria in non-immediate reactions. Although the exact diagnostic approach differs depending on the underlying mechanism, it is based on the performance of skin testing, laboratory tests, and drug provocation tests.T cells are a key factor in all types of hypersensitivity reactions to BLs, regulating both IgE production or acting as effector cells, with a different profile of cytokine production. A Th1 pattern is observed in both CD4(+) and CD8(+) peripheral T cells in non-immediate reactions, whereas a Th2 pattern is expressed in CD4(+) T cells in immediate reactions. PMID:24214624

Torres, Maria J; Mayorga, Cristobalina; Blanca-López, Natalia; Blanca, Miguel

2014-01-01

126

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

127

Rituximab-Induced Hypersensitivity Pneumonitis  

Microsoft Academic Search

Rituximab is a chimeric anti-CD20 monoclonal antibody used to treat CD20+ non-Hodgkin’s lymphoma. Although pulmonary adverse reactions such as cough, rhinitis, bronchospasm, dyspnea and sinusitis are relatively common, other respiratory conditions like cryptogenic organizing pneumonia, interstitial pneumonitis and diffuse alveolar hemorrhage have rarely been reported. Only 2 possible cases of rituximab-associated hypersensitivity pneumonitis have been described to date. We present

Adriano R. Tonelli; Richard Lottenberg; Robert W. Allan; P. S. Sriram

2009-01-01

128

Dapsone hypersensitivity syndrome causing disseminated intravascular coagulation  

PubMed Central

Dapsone hypersensitivity syndrome is an idiosyncratic reaction to this drug and can present with different clinical manifestations of varying severity. We describe a patient with disseminated intravascular coagulation (DIC) as an adverse reaction to dapsone. To the best of our knowledge, this is the first time it has been described in the literature. She presented with fever, rash and abdominal pain; she also had marked eosinophilia and features suggestive of oxidative haemolysis. Her course was complicated by DIC, splenic infarction and gastrointestinal bleeding. Extensive investigations did not reveal any alternative aetiology. She was initially treated with supportive measures and folic acid; steroids were administered later, following clinical deterioration. There was gradual improvement and the steroids were tapered. The patient recovered fully and remains well; her underlying chronic dermatologic condition is under satisfactory control with other medications. PMID:21829418

Figtree, Melanie Clare; Miyakis, Spiros; Tanaka, Kumiko; Martin, Linda; Konecny, Pam; Krilis, Steven

2009-01-01

129

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

130

The IgE and IgG antibody responses to aerosols of Nephrops norvegicus (prawn) antigens: the association with clinical hypersensitivity and with cigarette smoking.  

PubMed Central

Raised levels of serum IgE antibodies to prawn antigens were found in 15 of 26 seafood factory process workers with respiratory symptoms and in one of 26 case-matched asymptomatic controls (P < 0.001). Raised IgG antibody titres against the same antigens were found in 18 subjects in each symptom grouping, and the median titres of this antibody did not differ significantly between the groups. The prawn-specific IgE antibody response was significantly associated with atopy (IgE antibody response to common allergens) and with a history of cigarette smoking, confirmed by level of serum cotinine, a major nicotine metabolite. Non-atopic non-smokers were unlikely to become sensitized. The titre of the prawn-specific IgE antibody correlated with the duration of exposure and with the duration of symptoms. Discriminant analysis of the serological profile (anti-prawn IgE, total IgE and cotinine) was sufficient to assign individuals correctly into symptomatic or asymptomatic categories in 77% of subjects. The titres of the IgE and IgG antibody responses to prawn antigens did not correlate, and the main factor which seemed to determine the antibody isotype response to these inhaled antigens was cigarette smoking. IgE antibody was produced mainly by smokers, whereas IgG antibody was the predominant isotype produced by non-smokers. PMID:8082306

McSharry, C; Anderson, K; McKay, I C; Colloff, M J; Feyerabend, C; Wilson, R B; Wilkinson, P C

1994-01-01

131

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

Microsoft Academic Search

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

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

132

Common and unique components of response inhibition revealed by fMRI  

E-print Network

among tasks were low, for both brain activity and performance. We suggest that common interferenceCommon and unique components of response inhibition revealed by fMRI Tor D. Wager(a,T Ching-Yune C evidence for a common set of frontal and parietal regions engaged in response inhibition across three tasks

Jonides, John

133

ORIGINAL PAPER Zircon response to high-grade metamorphism as revealed  

E-print Network

ORIGINAL PAPER Zircon response to high-grade metamorphism as revealed by U- grade metamorphic terrains poses a major challenge because of the differential response of the U­Pb system to metamorphism, and many aspects like pressure­tempera- ture conditions, metamorphic mineral

Siebel, Wolfgang

134

Angioneurotic edema: a rare case of hypersensitivity to metoclopramide  

PubMed Central

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

Zakrzewski, Aleksander; Matuszewski, Tomasz; Kruszewski, Jerzy

2013-01-01

135

Severe type IV hypersensitivity to ‘black henna’ tattoo  

Microsoft Academic Search

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

Vasileios Vasilakis; Bernice Knight; Satnam Lidder; Sarah Frankton

2010-01-01

136

Regulatory T cells in cutaneous immune responses  

Microsoft Academic Search

Regulatory T cells (Treg) are a subset of T cells with strong immunosuppressive activity. In the skin, it has recently been revealed that Treg play important roles not only in the maintenance of skin homeostasis but also in the regulation of the immune responses, such as contact hypersensitivity and atopic dermatitis. Furthermore, the skin plays important roles in the induction

Tetsuya Honda; Yoshiki Miyachi; Kenji Kabashima

2011-01-01

137

IL-1-induced tumor necrosis factor-alpha elicits inflammatory cell infiltration in the skin by inducing IFN-gamma-inducible protein 10 in the elicitation phase of the contact hypersensitivity response.  

PubMed

Contact hypersensitivity (CHS) is a typical inflammatory response against contact allergens. Inflammatory cytokines, including IL-1 and tumor necrosis factor (TNF)-alpha, are implicated in the reaction, although the precise roles of each cytokine have not been completely elucidated. In this report, we dissected the functional roles of IL-1 and TNF-alpha during CHS. CHS induced by 2,4,6-trinitorochlorobenzene as well as oxazolone was suppressed in both IL-1alpha/beta(-/-) and TNF-alpha(-/-) mice. Hapten-specific T cell activation, as examined by T cell proliferation, OX40 expression and IL-17 production, was reduced in IL-1alpha/beta(-/-) mice, but not in TNF-alpha(-/-) mice, suggesting that IL-1 but not TNF-alpha is required for hapten-specific T cell priming in the sensitization phase. On the other hand, TNF-alpha, induced by IL-1, was necessary for the induction of local inflammation during the elicitation phase. We also found that the expression of IFN-gamma-inducible protein 10 (IP-10) was augmented at the inflammatory site. Although IP-10 mRNA expression was abrogated in TNF-alpha(-/-) mice, both CHS development and TNF-alpha mRNA expression occurred normally in IFN-gamma(-/-) mice, indicating that the induction of IP-10 during CHS was primarily controlled by TNF-alpha. Interestingly, CHS was suppressed by treatment with anti-IP-10 mAb, suggesting a critical role for IP-10 in CHS. Reduced CHS in TNF-alpha(-/-) mice was reversed by IP-10 injection during the elicitation phase. Thus, it was shown that the roles for IL-1 and TNF-alpha are different, although both cytokines are crucial for the development of CHS. PMID:12578855

Nakae, Susumu; Komiyama, Yutaka; Narumi, Shosaku; Sudo, Katsuko; Horai, Reiko; Tagawa, Yoh-Ichi; Sekikawa, Kenji; Matsushima, Koji; Asano, Masahide; Iwakura, Yoichiro

2003-02-01

138

Development and validation of the Newcastle laryngeal hypersensitivity questionnaire  

PubMed Central

Background Laryngeal hypersensitivity may be an important component of the common disorders of laryngeal motor dysfunction including chronic refractory cough, pdoxical vocal fold movement (vocal cord dysfunction), muscle tension dysphonia, and globus pharyngeus. Patients with these conditions frequently report sensory disturbances, and an emerging concept of the ‘irritable larynx’ suggests common features of a sensory neuropathic dysfunction as a part of these disorders. The aim of this study was to develop a Laryngeal Hypersensitivity Questionnaire for patients with laryngeal dysfunction syndromes in order to measure the laryngeal sensory disturbance occurring in these conditions. Methods The 97 participants included 82 patients referred to speech pathology for behavioural management of laryngeal dysfunction and 15 healthy controls. The participants completed a 21 item self administered questionnaire regarding symptoms of abnormal laryngeal sensation. Factor analysis was conducted to examine correlations between items. Discriminant analysis and responsiveness to change were evaluated. Results The final questionnaire comprised 14 items across three domains: obstruction, pain/thermal, and irritation. The questionnaire demonstrated significant discriminant validity with a mean difference between the patients with laryngeal disorders and healthy controls of 5.5. The clinical groups with laryngeal hypersensitivity had similar abnormal scores. Furthermore the Newcastle Laryngeal Hypersensitivity Questionnaire (LHQ) showed improvement following behavioural speech pathology intervention with a mean reduction in LHQ score of 2.3. Conclusion The Newcastle Laryngeal Hypersensitivity Questionnaire is a simple, non-invasive tool to measure laryngeal pesthesia in patients with laryngeal conditions such as chronic cough, pdoxical vocal fold movement (vocal cord dysfunction), muscle tension dysphonia, and globus pharyngeus. It can successfully differentiate patients from healthy controls and measure change following intervention. It is a promising tool for use in clinical research and practice. PMID:24552215

2014-01-01

139

Pentoxifylline Suppresses Irritant and Contact Hypersensitivity Reactions  

Microsoft Academic Search

Pharmacologic suppression of the effector phase ot contact hypersensitivity appears to have major relevance with regard to treatment of type IV reactions like contact dermatitis. Recently, tumor necrosis factor ? has been shown to be a critical mediator in hapten-induced irritant and contact hypersensitivity reactions, thus offering new possibilities, for therapeutic intervention. Pentoxifylline, a methylxanthine derivative used in the treatment

Agatha Schwarz; Christine Krone; Franz Trautinger; Yoshinori Aragane; Peter Neuner; Thomas A. Luger; Thomas Schwarz

1993-01-01

140

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. PMID:25278991

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

2014-01-01

141

Severe type IV hypersensitivity to 'black henna' tattoo.  

PubMed

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

142

Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece.  

PubMed

The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21·3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38·6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non-carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21·3% to 38·6% depending on the type of stimuli. Cervical non-carious lesions and gingival recessions were determined as significant predictors of dentin hypersensitivity. PMID:24180256

Rahiotis, C; Polychronopoulou, A; Tsiklakis, K; Kakaboura, A

2013-12-01

143

Testing for Drug Hypersensitivity Syndromes  

PubMed Central

Adverse drug reactions are a common cause of patient morbidity and mortality. Type B drug reactions comprise only 20% of all drug reactions but they tend to be primarily immunologically mediated and less dependent on the drug’s pharmacological action and dose. Common Type B reactions seen in clinical practice are those of the immediate, IgE, Gell-Coombs Type I reactions, and the delayed, T-cell mediated, Type IV reactions. Management of these types of reactions, once they have occurred, requires careful consideration and recognition of the utility of routine diagnostic tests followed by ancillary specialised diagnostic testing. For Type I, IgE mediated reactions this includes prick/intradermal skin testing and oral provocation. For Type IV, T-cell mediated reactions this includes a variety of in vivo (patch testing) and ex vivo tests, many of which are currently mainly used in highly specialised research laboratories. The recent association of many serious delayed (Type IV) hypersensitivity reactions to specific drugs with HLA class I and II alleles has created the opportunity for HLA screening to exclude high risk populations from exposure to the implicated drug and hence prevent clinical reactions. For example, the 100% negative predictive value of HLA-B*5701 for true immunologically mediated abacavir hypersensitivity and the development of feasible, inexpensive DNA-based molecular tests has led to incorporation of HLA-B*5701 screening in routine HIV clinical practice. The mechanism by which drugs specifically interact with HLA has been recently characterised and promises to lead to strategies for pre-clinical screening to inform drug development and design. PMID:23592889

Rive, Craig M; Bourke, Jack; Phillips, Elizabeth J

2013-01-01

144

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.

145

Hypersensitivity to contrast media and dyes.  

PubMed

This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds. PMID:25017677

Brockow, Knut; Sánchez-Borges, Mario

2014-08-01

146

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

PubMed

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

Richards, N; Dilley, A

2015-01-22

147

Dynamic hydrolase activities precede hypersensitive tissue collapse in tomato seedlings.  

PubMed

Hydrolases such as subtilases, vacuolar processing enzymes (VPEs) and the proteasome play important roles during plant programmed cell death (PCD). We investigated hydrolase activities during PCD using activity-based protein profiling (ABPP), which displays the active proteome using probes that react covalently with the active site of proteins. We employed tomato (Solanum lycopersicum) seedlings undergoing synchronized hypersensitive cell death by co-expressing the avirulence protein Avr4 from Cladosporium fulvum and the tomato resistance protein Cf-4. Cell death is blocked in seedlings grown at high temperature and humidity, and is synchronously induced by decreasing temperature and humidity. ABPP revealed that VPEs and the proteasome are not differentially active, but that activities of papain-like cysteine proteases and serine hydrolases, including Hsr203 and P69B, increase before hypersensitive tissue collapse, whereas the activity of a carboxypeptidase-like enzyme is reduced. Similar dynamics were observed for these enzymes in the apoplast of tomato challenged with C. fulvum. Unexpectedly, these challenged plants also displayed novel isoforms of secreted putative VPEs. In the absence of tissue collapse at high humidity, the hydrolase activity profile is already altered completely, demonstrating that changes in hydrolase activities precede hypersensitive tissue collapse. PMID:24890496

Sueldo, Daniela; Ahmed, Ali; Misas-Villamil, Johana; Colby, Tom; Tameling, Wladimir; Joosten, Matthieu H A J; van der Hoorn, Renier A L

2014-08-01

148

Gastric hypersensitivity in nonulcer dyspepsia: an inconsistent finding.  

PubMed

Visceral hypersensitivity is claimed to be involved in the pathogenesis of nonulcer dyspepsia (NUD). We evaluated whether gastric hypersensitivity is a consistent finding in an unselected group of NUD patients. In 11 patients and 20 healthy controls, a standardized gastric distension was performed using a gastric barostat. Perception was scored by a questionnaire and compared between the two groups. There was a linear pressure/volume relationship during gastric distension in both groups. The pain threshold in NUD patients was significantly lower compared to controls [5.5 +/- 4.0 mm Hg above minimal distending pressure (mdp) and 10.2 +/- 2.2 mm Hg above mdp, respectively, P < 0.004], irrespective of the H. pylori status. However, more than 50% of the NUD perception scores were in the control range at most distension levels. Gastric hypersensitivity could be confirmed in NUD patients as a group. However, there is a considerable overlap concerning perception in response to distension between unselected NUD patients and controls. PMID:9125638

Klatt, S; Pieramico, O; Guethner, C; Glasbrenner, B; Beckh, K; Adler, G

1997-04-01

149

Advanced phenotyping in hypersensitivity drug reactions to NSAIDs.  

PubMed

Non-steroidal anti-inflammatory drugs (NSAIDs) are the medications most frequently involved in hypersensitivity drug reactions. Because NSAIDs are prescribed for many conditions, this is a world-wide problem affecting patients of all ages. Various hypersensitivity reactions have been reported, mainly affecting the skin and/or the respiratory airways. The most frequent of these is acute urticaria, which can be induced by several different NSAIDs. Both specific and non-specific immunological pathways have been proposed as underlying mechanisms. This review presents the clinical phenotypes and the drugs involved in NSAID hypersensitivity. Five major clinical syndromes can be distinguished: aspirin-exacerbated respiratory disease (AERD), aspirin-exacerbated cutaneous disease (AECD), multiple NSAID-induced urticaria/angioedema (MNSAID-UA), single NSAID-IgE reactions and single NSAID T cell responses. However, further classification is possible within these five major entities, by detailed descriptions of the clinical characteristics enabling more phenotypes to be defined. This detailed differentiation now seems required in order to undertake appropriate pharmacogenetic studies. PMID:24074328

Ayuso, P; Blanca-López, N; Doña, I; Torres, M J; Guéant-Rodríguez, R M; Canto, G; Sanak, M; Mayorga, C; Guéant, J L; Blanca, M; Cornejo-García, J A

2013-10-01

150

HD mouse models reveal clear deficits in learning to perform a simple instrumental response  

PubMed Central

Mouse models of Huntington’s disease (HD) were trained to acquire one of two simple instrumental responses (a lever press or a nosepoke) to obtain food reinforcement. Animals from several HD strains revealed apparently progressive deficits in this task, being significantly less able than littermate controls to perform the required responses, at ages where motor function is only mildly affected. These data could provide a simple way to measure learning deficits in these mouse models, likely related to the characteristic pattern of neural damage observed in HD mouse models. PMID:22512000

Oakeshott, Stephen; Port, Russell G; Cummins-Sutphen, Jane; Watson-Johnson, Judy; Ramboz, Sylvie; Park, Larry; Howland, David; Brunner, Dani

2011-01-01

151

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

PubMed

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

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

1993-10-01

152

Type-based associations in grapheme-color synaesthesia revealed by response time distribution analyses.  

PubMed

Determining the nature of binding in grapheme-color synaesthesia has consequences for understanding the neural basis of synaesthesia and visual awareness in general. We evaluated type- and token-based letter-color binding using a synaesthetic version of the object-reviewing paradigm. Although mean response times failed to reveal any significant differences between synaesthetes and control participants, RT analyses with ex-Gaussian distributions revealed that the response facilitation in the synaesthesia group reflected type representations exclusively, while response facilitation in the control group, who learned letter-color associations, was dominated by token representations. Thus, letter-color associations in associator synaesthetes are type-based, and do not involve binding to object tokens, consistent with their subjective reports. Contrary to recent studies that failed to find differences between synaesthetes and non-synaesthetes with behavioral measures, response time distribution analyses indicate that color sensations in synaesthetes are not simply the extreme form of normal letter-color associations, and cannot be attributed to demand characteristics. PMID:21820323

Saiki, Jun; Yoshioka, Ayako; Yamamoto, Hiroki

2011-12-01

153

Integrated Metabolomic and Proteomic Analysis Reveals Systemic Responses of Rubrivivax benzoatilyticus JA2 to Aniline Stress.  

PubMed

Aromatic amines are widely distributed in the environment and are major environmental pollutants. Although degradation of aromatic amines is well studied in bacteria, physiological adaptations and stress response to these toxic compounds is not yet fully understood. In the present study, systemic responses of Rubrivivax benzoatilyticus JA2 to aniline stress were deciphered using metabolite and iTRAQ-labeled protein profiling. Strain JA2 tolerated high concentrations of aniline (30 mM) with trace amounts of aniline being transformed to acetanilide. GC-MS metabolite profiling revealed aniline stress phenotype wherein amino acid, carbohydrate, fatty acid, nitrogen metabolisms, and TCA (tricarboxylic acid cycle) were modulated. Strain JA2 responded to aniline by remodeling the proteome, and cellular functions, such as signaling, transcription, translation, stress tolerance, transport and carbohydrate metabolism, were highly modulated. Key adaptive responses, such as transcription/translational changes, molecular chaperones to control protein folding, and efflux pumps implicated in solvent extrusion, were induced in response to aniline stress. Proteo-metabolomics indicated extensive rewiring of metabolism to aniline. TCA cycle and amino acid catabolism were down-regulated while gluconeogenesis and pentose phosphate pathways were up-regulated, leading to the synthesis of extracellular polymeric substances. Furthermore, increased saturated fatty acid ratios in membranes due to aniline stress suggest membrane adaptation. The present study thus indicates that strain JA2 employs multilayered responses: stress response, toxic compound tolerance, energy conservation, and metabolic rearrangements to aniline. PMID:25388363

Mujahid, Md; Prasuna, M Lakshmi; Sasikala, Ch; Ramana, Ch Venkata

2015-02-01

154

Immunological mechanisms of contact hypersensitivity in mice.  

PubMed

Contact hypersensitivity (CHS) is an animal model in which the immunological mechanisms of allergic contact dermatitis (ACD) in humans can be studied but is also widely used in the study of many basic immunological mechanisms. In CHS, a pre-sensitized animal is re-exposed to an antigen, thereby eliciting an immunological reaction at the site of antigen exposure. CHS consists of two phases: sensitization and elicitation phase. In the sensitization phase, the first contact of the skin with a hapten leads to binding of the hapten to an endogenous protein in the skin where they form hapten-carrier complexes which are immunogenic. The hapten-carrier complex is taken up by Langerhans cells (LCs) and dermal dendritic cells (dDCs) which migrate from the epidermis to the draining lymph node. Here, they present the haptenated peptides to naive T cells which are subsequently activated. The newly activated T cells proliferate and migrate out of the lymph node and into circulation. In the elicitation phase, re-exposure of the skin to the hapten activates the specific T cells in the dermis and triggers the inflammatory process responsible for the cutaneous lesions. Originally CHS was regarded as being solely driven by T cells but recently other cell types such as B1 cells, natural killer (NK) T cells and NK cells have shown to mediate important functions during the response as well. Here, we have described the molecular and cellular pathways in the development of CHS and have focused on recent advances and novel knowledge in the understanding of the immunoregulatory mechanisms involved in CHS. PMID:22151305

Christensen, Anne Deen; Haase, Claus

2012-01-01

155

Hypersensitivity manifestations to the fruit mango.  

PubMed

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

Sareen, Richa; Shah, Ashok

2011-04-01

156

General aspects of hypersensitivity pneumonitis in Turkey.  

PubMed

Hypersensitivity pneumonitis prevalence rates are between 5 and 15% of the overall population exposed to known inciting antigens but a small number of cases have been reported from Turkey until now. We aimed to present a broad picture of hypersensitivity pneumonitis in Turkey, thus promoting interest in this relatively common disease in developing countries. Search engines were utilized to retrieve the cases reported from Turkey. Other published journals and meeting abstracts which have not been registered into electronic databases were manually reviewed. Twenty-two cases from 13 reports were characterized by demographics, clinical features, occupational and environmental exposures, diagnostic tools and prognostic data. The majority of the group consisted of women (68.2%) and had a positive history for contact with an avian (59%). Mean exposure period was 69 ± 77.6 months. The most common reported clinical form was chronic hypersensitivity pneumonitis (58.8%). Reticulonodular pattern was the basic pathological finding (45%). Restrictive impairments of the forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) of the lungs were the basic pathologies observed in pulmonary function tests. Interstitial fibrosis was the most common pathological finding (61.5%). Few cases reported with preponderance of chronic hypersensitivity pneumonitis with avian exposure from 70 million populations suggest that many hypersensitivity pneumonitis cases, especially acute forms, have been ignored. Also, hypersensitivity pneumonitis somehow appears to be a neglected occupational disease. The present situation should be considered as a common problem currently faced by developing countries and occupational groups under risk must be investigated promptly. PMID:21038134

C?mr?n, Arif Hikmet; Göksel, Ozlem; Demirel, Yavuz Selim

2010-01-01

157

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

158

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

PubMed Central

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.

2014-01-01

159

Adult-onset temporal lobe epilepsy, cognitive decline, multi-antiepileptic drug hypersensitivity, and Hashimoto's encephalopathy: Two case studies?  

PubMed Central

Hashimoto's encephalopathy is defined by the coexistence of encephalopathy and antithyroid antibodies. We report two cases of adult-onset temporal lobe epilepsy with subacute cognitive decline, high titers of antithyroid antibodies, multi-antiepileptic drug hypersensitivity, and good response to immunomodulatory treatment. The relevance of multidrug hypersensitivity in the setting of adult-onset epilepsy and the importance of searching for autoimmune causes for epilepsy are discussed.

Sadan, Ofer; Seyman, Estelle; Ash, Elissa L.; Kipervasser, Svetlana; Neufeld, Miri Y.

2013-01-01

160

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

161

TH1/TH2 balance in concomitant immediate and delayed-type hypersensitivity diseases.  

PubMed

In spite of the observation of mutual inhibitory properties of TH1 and TH2 CD4+ cells, a group of patients developed simultaneously immediate and delayed-type hypersensitivity reactions that are theoretically antagonistic. Patients presenting concomitant hypersensitivity reactions were evaluated for cytokine production. PBMC from 45 patients and 13 non-atopic individuals were cultured with mite allergen and mitogen and the supernatants obtained were evaluated for cytokine production by ELISA. The analysis of the cytokines levels revealed increased production of pro-inflammatory cytokine TNF-alpha in the non-atopic individuals after specific and mitogen stimulus. The IL-4 was largely observed on serum samples and IL-5 levels were higher in the double sensitized group (group DerpNi) after PHA stimulus. The IL-13 levels were increased in sensitized groups (Derp and DerpNi groups) after PHA stimuli. Atopic patients (Derp and DerpNi groups) presented lowest levels IFN-gamma and the analysis of TGF-beta production after rDER P I stimulation have shown increased levels among sensitized patients to Dermatophagoides pteronyssinus mite. IL-10 levels did not differ after antigen stimulation but basal production was higher on Derp and DerpNi groups. Furthermore, negative correlations were observed between IFN-gamma levels and IL-4, IL-13 and IL-10. This study has shown patients able to react, concomitantly, to the two types of antigens - rDER P I and NiSO4, present distinct pattern of cytokine production. The increased levels of IL-13 in the sensitive individuals to mite antigen (rDER P I) and IFN-gamma in NiSO4 sensitized individuals confirm the role of the type TH2 response in the atopies and TH1 type in DCA. PMID:19433108

de Mello, Luane Marques; Bechara, Monique Isabel Silveira; Solé, Dirceu; Rodrigues, Virmondes

2009-06-01

162

Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC  

PubMed Central

Gene expression mediated by viral vectors is subject to cell-to-cell variability, which limits the accuracy of gene delivery. When coupled with single-cell measurements, however, such variability provides an efficient means to quantify signaling dynamics in mammalian cells. Here, we illustrate the utility of this approach by mapping the E2f1 response to MYC, serum stimulation, or both. Our results revealed an underappreciated mode of gene regulation: E2f1 expression first increased then decreased as MYC input increased. This biphasic pattern was also reflected in other nodes of the network including the miR-17-92 micro RNA cluster and p19Arf. A mathematical model of the network successfully predicted modulation of the biphasic E2F response by serum and a CDK inhibitor. In addition to demonstrating how noise can be exploited to probe signaling dynamics, our results reveal how coordination of the MYC/RB/E2F pathway enables dynamic discrimination of aberrant and normal levels of growth stimulation. PMID:21292160

Wong, Jeffrey V.; Yao, Guang; Nevins, Joseph R.; You, Lingchong

2011-01-01

163

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

PubMed Central

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

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

2014-01-01

164

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

165

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

166

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

167

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

168

Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3  

PubMed Central

To characterize the endothelial dysfunction associated with Type II diabetes, we surveyed transcriptional responses in the vascular endothelia of mice receiving a diabetogenic, high-fat diet. Tie2-GFP mice were fed a diet containing 60% fat calories (HFD); controls were littermates fed normal chow. Following 4, 6, and 8 wk, aortic and leg muscle tissues were enzymatically dispersed, and endothelial cells were obtained by fluorescence-activated cell sorting. Relative mRNA abundance in HFD vs. control endothelia was measured with long-oligo microarrays; highly dysregulated genes were confirmed by real-time PCR and protein quantification. HFD mice were hyperglycemic by 2 wk and displayed vascular insulin resistance and decreased glucose tolerance by 5 and 6 wk, respectively. Endothelial transcripts upregulated by HFD included galectin-3 (Lgals3), 5-lipoxygenase-activating protein, and chemokine ligands 8 and 9. Increased LGALS3 protein was detected in muscle endothelium by immunohistology accompanied by elevated LGALS3 in the serum of HFD mice. Our comprehensive analysis of the endothelial transcriptional response in a model of Type II diabetes reveals novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Increased endothelial expression and elevated humoral levels of LGALS3 supports a role for this molecule in the vascular response to diabetes, and its potential as a direct biomarker for the inflammatory state in diabetes. PMID:21791638

Darrow, April L.; Maresh, J. Gregory

2011-01-01

169

Clinical and Radiologic Manifestations of Hypersensitivity Pneumonitis  

Microsoft Academic Search

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

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

170

Delayed-type hypersensitivity reaction against Nexplanon®.  

PubMed

Nexplanon® is an etonogestrel implant with a long-acting contraceptive effect. Although several studies underlined its safety profile, its implant can rarely lead to moderate or severe adverse event. Here, we presented a case of delayed-type hypersensitivity reaction against Nexplanon® that resolved after its removal. PMID:25284356

Serati, Maurizio; Bogani, Giorgio; Kumar, Sanjeev; Cromi, Antonella; Ghezzi, Fabio

2015-01-01

171

Immunotoxicology of Inhaled Compounds—Assessing Risks of Local Immune Suppression and Hypersensitivity  

Microsoft Academic Search

Immunotoxic risks associated with inhaled chemicals include (1) suppression of local defenses resulting in increased risk of pulmonary infection and (2) sensitization of the immune system resulting in respiratory hypersensitivity, including allergic asthma. Under laboratory conditions, environmentally relevant levels of many air pollutants enhance susceptibility to bacterial pneumonia in mice. Because these compounds do not necessarily affect systemic immune responses,

MaryJane K. Selgrade; M. Ian Gilmour

2006-01-01

172

Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway.  

PubMed

The central auditory system has traditionally been divided into lemniscal and nonlemniscal pathways leading from the midbrain through the thalamus to the cortex. This view has served as an organizing principle for studying, modeling, and understanding the encoding of sound within the brain. However, there is evidence that the lemniscal pathway could be further divided into at least two subpathways, each potentially coding for sound in different ways. We investigated whether such an interpretation is supported by the spatial distribution of response features in the central nucleus of the inferior colliculus (ICC), the part of the auditory midbrain assigned to the lemniscal pathway. We recorded responses to pure tone stimuli in the ICC of ketamine-xylazine-anesthetized guinea pigs and used three-dimensional brain reconstruction techniques to map the location of the recording sites. Compared with neurons in caudal-and-medial regions within an isofrequency lamina of the ICC, neurons in rostral-and-lateral regions responded with shorter first-spike latencies with less spiking jitter, shorter durations of spiking responses, a higher proportion of spikes occurring near the onset of the stimulus, lower thresholds, and larger local field potentials with shorter latencies. Further analysis revealed two distinct clusters of response features located in either the caudal-and-medial or the rostral-and-lateral parts of the isofrequency laminae of the ICC. Thus we report substantial differences in coding properties in two regions of the ICC that are consistent with the hypothesis that the lemniscal pathway is made up of at least two distinct subpathways from the midbrain up to the cortex. PMID:25128560

Straka, Ma?gorzata M; Schmitz, Samuel; Lim, Hubert H

2014-08-15

173

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

174

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

PubMed Central

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

Jiang, Yuanqing; Deyholos, Michael K

2006-01-01

175

Excess fertilizer responsive miRNAs revealed in Linum usitatissimum L.  

PubMed

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

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

2015-02-01

176

Comprehensive DNA adduct analysis reveals pulmonary inflammatory response contributes to genotoxic action of magnetite nanoparticles.  

PubMed

Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome) analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA) against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (?dC), revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, ?dC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice. PMID:25658799

Ishino, Kousuke; Kato, Tatsuya; Kato, Mamoru; Shibata, Tatsuhiro; Watanabe, Masatoshi; Wakabayashi, Keiji; Nakagama, Hitoshi; Totsuka, Yukari

2015-01-01

177

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

178

Airway Inflammation and Hypersensitivity Induced by Chronic Smoking  

PubMed Central

Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

2011-01-01

179

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 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

2014-01-01

180

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

181

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

182

Primary trigeminal neuralgia (algophoric deafferentation hypersensitivity syndrome).  

PubMed

In the article the author presents his theory of the pathogenesis of primary trigeminal neuralgia, explaining the occurrence of this mysterious disease by algophoric deafferentation hypersensitivity. Tooth extraction is the sole cause of algophoric deafferentation hypersensitivity, which, culminating in epileptiform discharges of the trigeminal nociceptive pathway neurons, leads to clinical features of characteristic neuralgic paroxysms. Trigger mechanism is explained by ephaptic transmission between the broken fibers for phasic pain of the tooth pulp and neighbouring fibers of epicritic and proprioceptive sensitivity. The typical occurrence of periods with remission of neuralgic paroxysms the author explains by his original theory of biorhythms neogenesis with the involvement of two antagonistic neural subsystems (nociceptive and antinociceptive system). The concept is based on indisputable clinical, anatomical, pathoanatomical, experimental and pharmacologic facts, which the author quotes as the contribution to his theory. PMID:2267050

Zurak, N

1990-01-01

183

Hypersensitivity to titanium: Clinical and laboratory evidence  

Microsoft Academic Search

OBJECTIVES: This study was carried out to investigate the potential of titanium to induce hypersensitivity in patients chronically exposed to titanium-based dental or endoprosthetic implants. METHODS: Fifty-six patients who had developed clinical symptoms after receiving titanium-based implants were tested in the optimized lymphocyte transforma - tion test MELISA® against 10 metals including titanium. Out of 56 patients, 54 were patch-tested

Kurt Müller; Elizabeth Valentine-Thon

2006-01-01

184

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

185

Immediate-Type Hypersensitivity to Succinylated Corticosteroids  

Microsoft Academic Search

Background: Despite their frequent use, systemic corticosteroids have rarely elicited immediate-type reactions. Objective: We report two male patients, aged 26 and 70 years, respectively, with severe immediate-type hypersensitivity secondary to the administration of corticosteroids esterified with succinate. Methods: Skin tests, basophil activation tests and challenge tests were performed for diagnostic evaluation. Results: In both patients, immediate-type skin test reactions were

Annett Isabel Walker; Helen-Caroline Räwer; Wolfgang Sieber; Bernhard Przybilla

2011-01-01

186

Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants  

PubMed Central

Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA), are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs) was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (p<0.05)). Sequential prime-boost immunizations with different adjuvants did not offer improvements over the use of FCA/FIA or MF59. Remarkably however, the concurrent use of the combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (p<0.05). This combination was not associated with any obvious local or systemic adverse effects. Antibody competition indicated that the majority of the neutralizing activities were directed to the CD4 binding site (CD4bs). Increased antibody titers to the gp41 membrane proximal external region (MPER) and gp120 V3 were detected when the more potent adjuvants were used. These data reveal that the combination of Carbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes. PMID:22509385

Lai, Rachel P. J.; Seaman, Michael S.; Tonks, Paul; Wegmann, Frank; Seilly, David J.; Frost, Simon D. W.; LaBranche, Celia C.; Montefiori, David C.; Dey, Antu K.; Srivastava, Indresh K.; Sattentau, Quentin; Barnett, Susan W.; Heeney, Jonathan L.

2012-01-01

187

Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples  

USGS Publications Warehouse

Background: Environmental endocrine disruptors (EED) are exogenous chemicals that mimic endogenous hormones, such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ER) in the larval heart compared to the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit similar tissue-specific effects as BPA and genistein or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue-specificity in ER activation is due to differences in the expression of estrogen receptor subtypes. ER? is expressed in developing heart valves but not in the liver, whereas ER?2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

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

2014-01-01

188

Stent hypersensitivity and infection in sinus cavities  

PubMed Central

Persistent mucosal inflammation, granulation tissue formation, hypersensitivity, and multifactorial infection are newly described complications of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. In an important report published in Allergy and Rhinology, a 45-year-old male patient suffering from recalcitrant chronic rhinosinusitis underwent functional endoscopic sinus surgery and was found, for the first time, to have steroid-eluting catheters that were inadvertently left in the ethmoid and frontal sinuses. The retained catheters had caused persistent mucosal inflammation and formation of granulation tissue denoting hypersensitivity reaction. These consequences had induced perpetuation of symptoms of chronic rhinosinusitis. Meticulous removal of the retained stents with the nitinol wings from inflamed tissues of the frontal, ethmoidal, and sphenoethmoidal recesses in which they were completely imbedded was successfully performed without polypoid regrowth. Cultures of specimens taken from both left and right stents showed heavy growth of Stenotrophomonas maltophilia and moderate growth of Klebsiella oxytoca, coagulase negative Staphylococcus, and beta-hemolytic Streptococcus anginosus. Fungal infection was not detected. The current knowledge and experience regarding stent hypersensitivity and infection in relation with the use of stents in sinus cavities is reviewed. PMID:24498522

Soufras, George D.; Hahalis, George

2013-01-01

189

TRPA1 contributes to cold hypersensitivity.  

PubMed

TRPA1 is a nonselective cation channel expressed by nociceptors. Although it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions in which reactive oxygen species and proinflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1(-/-) mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain. PMID:21068322

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

2010-11-10

190

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

USGS Publications Warehouse

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

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

2008-01-01

191

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

192

Identification of Direct Thyroid Hormone Response Genes Reveals the Earliest Gene Regulation Programs during Frog Metamorphosis*  

PubMed Central

Thyroid hormone (T3) is essential for normal development and organ function throughout vertebrates. Its effects are mainly mediated through transcriptional regulation by T3 receptor (TR). The identification and characterization of the immediate early, direct target genes are thus of critical importance in understanding the molecular pathways induced by T3. Unfortunately, this has been hampered by the difficulty to study gene regulation by T3 in uterus-enclosed mammalian embryos. Here we used Xenopus metamorphosis as a model for vertebrate postembryonic development to identify direct T3 response genes in vivo. We took advantage of the ability to easily induce metamorphosis with physiological levels of T3 and to carry out microarray analysis in Xenopus laevis and genome-wide sequence analysis in Xenopus tropicalis. This allowed us to identify 188 up-regulated and 249 down-regulated genes by T3 in the absence of new protein synthesis in whole animals. We further provide evidence to show that these genes contain functional TREs that are bound by TR in tadpoles and that their promoters are regulated by TR in vivo. More importantly, gene ontology analysis showed that the direct up-regulated genes are enriched in categories important for transcriptional regulation and protein degradation-dependent signaling processes but not DNA replication. Our findings thus revealed the existence of interesting pathways induced by T3 at the earliest step of metamorphosis. PMID:19801647

Das, Biswajit; Heimeier, Rachel A.; Buchholz, Daniel R.; Shi, Yun-Bo

2009-01-01

193

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

194

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, Aurélie; Holota, Hélène; Tamburini, Christian; Garel, Marc; Ollivier, Bernard; Imbert, Jean; Dolla, Alain; Pradel, Nathalie

2014-01-01

195

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

196

Trans vivo analysis of human delayed-type hypersensitivity reactivity.  

PubMed

There are clinical situations in which it may be advantageous to monitor delayed type hypersensitivity (DTH) responses, an index of cell-mediated immunity, without exposing patients directly to the challenge antigens. For example, transplant patients may be at risk for becoming sensitized to donor antigens if injected with donor antigen during traditional skin tests. We describe an alternative method for human DTH testing, which involves the transfer of human peripheral blood mononuclear cells plus antigen into the pinnae or footpads of naive mice. This induces a measurable DTH-like swelling response, which we refer to as the "trans vivo DTH response." As proof of principle, we provide data obtained during trans vivo DTH studies with tetanus toxoid, cytomegalovirus (CMV) and alloantigens. In general, human T cells must be co-localized with antigen and human macrophages to produce swelling responses, and such responses are antigen-specific and require prior antigen sensitization. Not only does this assay offer a simple, reliable clinical monitoring device, but it also provides a model with which to study the in vivo mechanisms of human DTH responses. PMID:10439310

Carrodeguas, L; Orosz, C G; Waldman, W J; Sedmak, D D; Adams, P W; VanBuskirk, A M

1999-08-01

197

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

PubMed Central

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

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

2011-01-01

198

Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity.  

PubMed

Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1-Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1-Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of naïve and memory T cells along with G(0)/G(1) cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions. PMID:19930044

Omiya, Ryusuke; Tsushima, Fumihiko; Narazaki, Hidehiko; Sakoda, Yukimi; Kuramasu, Atsuo; Kim, Youn; Xu, Haiying; Tamura, Hideto; Zhu, Gefeng; Chen, Lieping; Tamada, Koji

2009-12-01

199

Titanium hypersensitivity. A hidden threat for dental implant patients?  

PubMed

Titanium and its alloys have been widely used for dental prosthetic devices because of their superior mechanical properties and biocompatibility. However, the incidence of titanium hypersensitivity or allergy is still unknown and the discussion about its existence is ongoing. Unexplained implant failures have also forced dental clinicians to investigate the possibility of titanium hypersensitivity or allergy. This review focuses on the potential of dental implant-related titanium hypersensitivity or allergic reactions. It includes an examination of the existing scientific literature and current knowledge. Evidence-based data and studies related to titanium hypersensitivity in dental implant patients are also discussed. PMID:24027897

Bilhan, Hakan; Bural, Canan; Geckili, Onur

2013-01-01

200

X-ray induction of persistent hypersensitivity to mutation  

SciTech Connect

The progeny of x-irradiated V79 cells are hypersensitive to PUVA-(8-methoxypsoralen plus longwave ultraviolet light) induced mutation at the locus for hypoxanthine-guanine phosphoribosyl transferase. This hypersensitivity is most evident at low doses of pUVA that do not induce mutation in non-x-irradiated cells. The hypersensitivity is evoked by x-irradiation delivered as a single dose or as multiple fractions over a long period and persists for at least 108 days of exponential growth. This radiation-induced hypersensitivity to subsequent mutation is a new phenomenon that may be relevant to multistage carcinogenesis.

Frank, J.P.; Williams, J.R.

1982-04-16

201

Adrenergic Stimulation Mediates Visceral Hypersensitivity to Colorectal Distension following Heterotypic Chronic Stress  

PubMed Central

Background & Aims Chronic stress exacerbates or causes relapse of symptoms such as abdominal pain and cramping in patients with irritable bowel syndrome (IBS). We investigated whether chronic stress increases plasma norepinephrine and sensitizes colon-specific dorsal root ganglion (DRG) neurons by increasing the expression of nerve growth factor (NGF) in the colon wall. Methods Heterotypic chronic stress (HeCS) was induced in male Wistar rats and neurologic and molecular responses were analyzed. Tissues were analyzed for NGF expression. Results HeCS significantly increased the visceromoter response to colorectal distension; expression of NGF increased in colonic muscularis externa and mucosa/submucosa. Rheobase decreased, resting membrane potential was depolarized, and electrogenesis of action potentials increased in colon-specific thoracolumbar DRG neurons. Luminal administration of resiniferatoxin in distal colon, systemic administration of anti-NGF antibody, or inhibition of the NGF receptor TrkA by k252A or antisense oligonucleotides in thoracolumbar DRG blocked the chronic stress-induced visceral hypersensitivity to colorectal distension. Blockade of ?1/?2- and ?1/?2-adrenergic receptors prevented the stress-induced visceral hypersensitivity and increased expression of NGF in the colon wall. HeCS did not induce any inflammatory response in the colon wall. Conclusion The peripheral stress mediator norepinephrine induces visceral hypersensitivity to colorectal distension in response to HeCS by increasing the expression of NGF in the colon wall, which sensitizes primary afferents in the absence of an inflammatory response. PMID:19800336

Winston, John H.; Xu, Guang-Yin; Sarna, Sushil K.

2009-01-01

202

Distance in Motion: Response Trajectories Reveal the Dynamics of Number Comparison  

PubMed Central

Cognitive and neuroscientific evidence has challenged the widespread view that perception, cognition and action constitute independent, discrete stages. For example, in continuous response trajectories toward a target response location, evidence suggests that a decision on which target to reach for (i.e., the cognition stage) is not reached before the movement starts (i.e., the action stage). As a result, instead of a straight trajectory to the correct target response, movement trajectories may curve toward competing responses or away from inhibited responses. In the present study, we examined response trajectories during a number comparison task. Participants had to decide whether a target number was smaller or larger than 5. They had to respond by moving to a left or a right response location. Replicating previous results, response trajectories were more curved toward the incorrect response location when distance to 5 was small (e.g., target number 4) than when distance to 5 was large (e.g., target number 1). Importantly, we manipulated the response mapping, which allowed us to demonstrate that this response trajectory effect results from the relative amount of evidence for the available responses across time. In this way, the present study stresses the tight coupling of number representations (i.e., cognition) and response related processes (i.e., action) and shows that these stages are not separable in time. PMID:21966526

Santens, Seppe; Goossens, Sofie; Verguts, Tom

2011-01-01

203

[Immunopharmacological study of buckwheat hypersensitivity (author's transl)].  

PubMed

Effect of dialysate from buckwheat extract on immediate hypersensitivity reactions. To investigate the hypersensitivity reaction of buckwheat, the aqueous extract of buckwheat was separated into dialysate (BWD) and non-dialysate (BWND). BWD neither decreased a release of anaphylactic mediator from the chopped lung tissue nor inhibited Schultz-dale reaction in the ileum of guinea pig sensitized with BWND. Heterologous PCA mediated by rabbit anti-BWND serum in guinea pig and homologous PCA in rats using anti-BWND IgE serum were inhibited by i.d. or i.v. treatment of BWD. Radioallegosorbent test (RAST) and PK reaction were inhibited in a dose dependent fashion by BWD mixed with human serum sensitive to buckwheat, although BWD required approximately 10,000 times more than BWND to produce a RAST inhibition. RAST, however, was not affected when BWD was added to 125I-labelled anti-human IgE. Anti-buckwheat IgE antibody in sensitized animals and atopic patients was specifically absorbed with an insoluble copolymer of BWD-conjugated BSA. BWD did not form a precipitin line against anti-BWND IgG antibody in immunoelectrophoresis. Rat IgE serum-induced degranulation and histamine release from mast cells were inhibited in a dose dependent fashion by BWD and the inhibition was specific to anti-BWND IgE antibody. BWD may be useful as an hyposensitization agent in buckwheat hypersensitivity, since BWD is a haptenic substance capable of neutralizing specific IgE antibody on mast cells. PMID:94295

Yanagihara, Y; Koda, A

1979-07-01

204

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

205

Drug hypersensitivity syndrome induced by meglumine antimoniate.  

PubMed

We report a case of drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) induced by parenteral meglumine antimoniate (Glucantime) in a 40-year-old man who traveled to Bolivia and was treated for mucocutaneous leishmaniasis. Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm(3)). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug. Pentavalent antimonials should be definitively withdrawn in patients with hypereosinophilia > 1,000 cells/mm(3) accompanied by systemic manifestations consistent with DRESS. PMID:19478253

Jeddi, Fakhri; Caumes, Eric; Thellier, Marc; Jauréguiberry, Stéphane; Mazier, Dominique; Buffet, Pierre A

2009-06-01

206

Dentin hypersensitivity: differential diagnosis, tests, and etiology.  

PubMed

Dentin hypersensitivity (DHS) is a painful condition that affects up to 57 percent of the adult population. It occurs as a result of exposure of dentin to the oral environment. Ensuring the correct diagnosis of this condition is based on history and examination. An oral screening for DHS should encompass such elements as patient history, clinical examination that includes radiographs, a variety of tests, identification of risk factors, and a differential diagnosis. An understanding of dentinal fluid and odontoblasts is also beneficial for diagnosis. PMID:24571559

Trushkowsky, Richard D; Garcia-Godoy, Franklin

2014-02-01

207

Permanent scatterer InSAR reveals seasonal and long-term aquifer-system response to groundwater pumping and artificial  

E-print Network

characterize the storage properties of an aquifer system with a high degree of spatial resolution. Citation, resulting in a loss of aquifer storage, and because damage to engineered structures may be associatedPermanent scatterer InSAR reveals seasonal and long-term aquifer-system response to groundwater

Amelung, Falk

208

High-confidence mapping of chemical compounds and protein complexes reveals novel aspects of chemical stress response in yeastw  

E-print Network

High-confidence mapping of chemical compounds and protein complexes reveals novel aspects of chemical stress response in yeastw Thiago M. Venancio,*a S. Balajiab and L. Aravind*a Received 16th June.1039/b911821g Chemical genetics in yeast has shown great potential for clarifying the pharmacology

209

Acoustics Reveals the Presence of a Macrozooplankton Biocline in the Bay of Biscay in Response to Hydrological  

E-print Network

Acoustics Reveals the Presence of a Macrozooplankton Biocline in the Bay of Biscay in Response Chaigneau3 , Zaida Quiroz4¤a , Anne Lebourges-Dhaussy5 , Arnaud Bertrand2 1 AZTI-Tecnalia, Marine Research Bifrequency acoustic data, hydrological measurements and satellite data were used to study the vertical

210

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

211

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. PMID:25302070

2014-01-01

212

Assessment of allergic hypersensitivity to dental materials.  

PubMed

Some metallic materials in dental prostheses may cause allergic hypersensitivity. Symptoms appear not only in the oral cavity, but also on hands, feet or the entire body. Release of metal ions is thought to cause the allergic reactions; micro-particles of the corrosion products of the metal and/or ionic metal hydroxides/oxides may be the allergens. The study purpose was to review clinical surveillance of dental allergic hypersensitivity in our dental hospital. From July 2000 to June 2005, 212 patients with suspected dental metal allergy were patch tested with 26 reagents, including 19 ready-made patch test reagents (Patch test reagents, Torii Pharmaceutical Corporation, Tokyo, Japan) and 9 custom-made reagents. One-hundred-and-sixty-seven patients were females (78.8%) and 45 patients were males (21.2%). A total of 148 patients (69.8%) had one or more positive patch test reactions. The most common allergens were nickel (25.0%), palladium (24.4%), chromium (16.7%), cobalt (15.9%) and stannum (12.5%). Typical allergic symptoms and diagnoses were Pustulosis palmaris et plantaris, lichen planus, stomatitis and contact dermatitis. This study indicates that dentists and dental researchers should be concerned about the allergenic potential of dental metal materials. PMID:19458446

Hosoki, Maki; Bando, Eiichi; Asaoka, Kenzo; Takeuchi, Hisahiro; Nishigawa, Keisuke

2009-01-01

213

Central Hypersensitivity in Chronic Hemiplegic Shoulder Pain  

PubMed Central

Objective This study aimed to examine the association of hemiplegic shoulder pain with central hypersensitivity through pressure-pain thresholds (PPT) at healthy, distant tissues. Design This study is a cross-sectional study. A total of 40 patients (n=20 hemiplegic shoulder pain (HSP), n=20 stroke without HSP) were enrolled in this study. Pressure-pain thresholds were measured at the affected deltoid and contralateral deltoid and tibialis anterior using a handheld algometer. Differences in PPTs were analyzed by Wilcoxon Rank Sum test and with linear regression analysis controlling for gender, a known confounder of PPTs. Results Subjects with hemiplegic shoulder pain had lower local PPTs than stroke control subjects when comparing the painful to dominant shoulders and comparing the non-painful shoulder and tibialis anterior to the non-dominant side controls. Similarly, those with hemiplegic shoulder pain had lower PPTs when comparing to controls in contralesional-to-contralesional comparisons as well as ipsilesional-to-ipsilesional comparisons. Conclusions Subjects with hemiplegic shoulder pain have lower local and distal PPTs than subjects without hemiplegic shoulder pain. Our study suggests that chronic shoulder pain may be associated with widespread central hypersensitivity, which has been previously found to be associated with other chronic pain syndromes. This further understanding can then help develop better treatment options for those with this hemiplegic shoulder pain. PMID:23255268

Hoo, Jennifer Soo; Paul, Tracy; Chae, John; Wilson, Richard

2013-01-01

214

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

215

Comparison of pharmacovigilance algorithms in drug hypersensitivity reactions  

Microsoft Academic Search

Background: A firm diagnosis of drug hyper- sensitivity, because it may re-induce the reaction, is seldom confirmed. Causality assessment algorithms are therefore of interest. Aims: The objective of this work was to compare three algorithms in the diagnosis of drug hypersensitivity. Methods: Evaluation of 120 clinical histories of drug hypersensitivity was carried out: 60 involving b-lactams (50%) and 60 involving

Said Benahmed; Marie Christine Picot; Dominique Hillaire-Buys; Jean Pierre Blayac; Pierre Dujols; Pascal Demoly

2005-01-01

216

Common and unique components of response inhibition revealed by fMRI  

Microsoft Academic Search

The ability to inhibit inappropriate responses is central to cognitive control, but whether the same brain mechanisms mediate inhibition across different tasks is not known. We present evidence for a common set of frontal and parietal regions engaged in response inhibition across three tasks: a go\\/no-go task, a flanker task, and a stimulus–response compatibility task. Regions included bilateral anterior insula\\/frontal

Tor D. Wager; Ching-Yune C. Sylvester; Steven C. Lacey; Derek Evan Nee; Michael Franklin; John Jonides

2005-01-01

217

Metal hypersensitivity in total knee arthroplasty: revision surgery using a ceramic femoral component - a case report.  

PubMed

We present a case involving the revision of a total knee arthroplasty with a metal femoral component using a ceramic implant due to metal hypersensitivity. A 58-year-old female patient underwent total knee arthroplasty (TKA) with a standard metal bicondylar knee system. She suffered from persistent pain and strong limitations in her range of motion (ROM) associated with flexion during the early postoperative period. Arthroscopic arthrolysis of the knee joint and intensive active and passive physical treatment, in combination with a cortisone regime, temporarily increased the ROM and reduced pain. No signs of low grade infection or other causes of implant failure were evident. Histology of synovial tissue revealed lymphoplasmacellular fibrinous tissue, consistent with a type IV allergic reaction. Allergometry (skin reaction) revealed type IV hypersensitivity against nickel-II-sulfate and palladium chloride. Revision surgery of the metal components was performed with a cemented ceramic femoral component (same bicondylar design) and a cemented titanium alloy tibial component. Postoperative evaluations were performed 10days, and 3 and 12months after the revision surgery. There was an increased ROM in flexion to 90° at the 12month follow-up. No swelling or effusion was observed at all clinical examinations after the revision surgery. No pain at rest and moderate walking pain were evident. The presented case demonstrates that ceramic implants are a promising solution for patients suffering from hypersensitivity to metal ions in total knee arthroplasty. PMID:21292491

Bergschmidt, Philipp; Bader, Rainer; Mittelmeier, Wolfram

2012-03-01

218

Transcriptional profiling reveals adaptive responses to boron deficiency stress in Arabidopsis.  

PubMed

Boron (B) is a micronutrient for vascular plants, and B deficiency has been recognized as a limiting factor for crop production in many areas worldwide. To gain a better insight into the adaptability mechanism of plant responses to B starvation, an Arabidopsis whole genome Affymetrix GeneChip was used to evaluate global gene expression alterations in response to short- and long-term B deficiency stress. A large number of B deficiency-responsive genes were identified and grouped by their functions. Genes linked to jasmonic acid (JA) showed the most prominent response under B deficiency. The transcripts for biosynthesis and regulation of JA were constantly induced during short- and long-term B deficiency stress. A set of well-known JA-dependent process and responsive genes showed the same expression profile. This suggested that JA could be a pivotal player in the integration of adaptive responses to B deficiency stress. Moreover, other functional groups of B deficiency-responsive genes (including various encoding the biosynthesis of antioxidants, the basic components of Ca2+ signalling, protein kinases, cell wall-modifying enzymes and proteins, H+-ATPase, K transporters, and a set of enzymes involved in central metabolism and cellular growth) were also observed, and their physiological roles under B deficiency stress are discussed. These results provide some information for a better understanding of plant-adaptive responses to B deficiency stress and potential strategies to improve B efficiency in crops. PMID:23198409

Peng, Lishun; Zeng, Changying; Shi, Lei; Cai, Hongmei; Xu, Fangsen

2012-01-01

219

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

ERIC Educational Resources Information Center

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

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

2010-01-01

220

Hidden responses to environmental variation: maternal effects reveal species niche dimensions.  

PubMed

Species responses to fluctuating environments structure population and community dynamics in variable ecosystems. Although offspring number is commonly used to measure these responses, maternal effects on offspring quality may be an important but largely unrecognised determinant of long-term population growth. We selected 29 species across a Mediterranean annual plant phylogeny, and grew populations of each species in wet and dry conditions to determine responses in seed number and maternal effects (seed size, seed dormancy, and seedling growth). Maternal effects were evident in over 40% of species, but only 24% responded through seed number. Despite a strong trade-off between seed size and seed number among species, there was no consistent trade-off within species; we observed correlations that ranged from positive to negative. Overall, species in this plant guild show a complex range of responses to environmental variation that may be underestimated when only seed number responses are considered. PMID:24602193

Germain, Rachel M; Gilbert, Benjamin

2014-06-01

221

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

222

Absence of Correlation Between Delayed-Type Hypersensitivity and Protection in Experimental Systemic Candidiasis in Immunized Mice  

PubMed Central

We found that in mice which had been immunized intraperitoneally with 2 × 108 heat-killed Candida albicans cells there was a striking temporal relationship between resistance to systemic challenge with 106 living C. albicans cells and a number of measurable cellular parameters of the host response. These included the emergence of delayed-type hypersensitivity and the development of granulocytosis. Since it had been shown in previous work that granulocytosis was associated with an increase in resistance when nonspecific immunostimulation was used, we performed experiments to induce delayed-type hypersensitivity without any measurable modification of the granulocyte population. Adoptive transfer of delayed-type hypersensitivity with spleen cells from immune and resistant donor mice did not produce any increase in resistance in normal recipients. When separate groups of mice were immunized intraperitoneally or subcutaneously with varying doses of heat-killed C. albicans, we found that doses of less than 108 cells did induce significant delayed-type hypersensitivity without any increase in granulocytosis. In such mice, as well as in animals pretreated with immunomodulators before immunization with heat-killed C. albicans, the presence of cell-mediated immunity, as measured by the delayed-type hypersensitivity test, was not associated with an increase in resistance against systemic candidiasis. On the contrary, the results suggested that cell-mediated immunity was associated with an increase in the susceptibility of these mice. The same effect on candidiasis susceptibility was observed when animals were immunized with heat-killed filamentous C. albicans. PMID:7012009

Hurtrel, Bruno; Lagrange, Philippe H.; Michel, Jean-Claude

1981-01-01

223

Contact hypersensitivity: quantitative aspects, susceptibility and risk factors.  

PubMed

The development of allergic sensitisation by environmental chemicals results in allergic contact dermatitis and highly undesirable morbidity and disability. This form of hypersensitivity is mediated by specific T lymphocytes that recognise the chemical sensitiser bound to self-proteins. Use of deliberate experimental contact sensitisation with dinitrochlorobenzene (DNCB) has been used to investigate the human immune system which exhibits dose-related responses. Many factors contribute to whether sensitisation occurs and the nature and magnitude of the immune response. Chemicals vary in sensitising potency, mainly reflecting their intrinsic protein-binding properties. The amount of sensitiser reaching the immune system is determined by many factors of which the concentration (dose per unit area), the relative lipid solubility and molecular weight are the most critical. Host-related factors contributing to the nature and magnitude of immune responses are mainly genetically determined including gender, age, the biochemical/physical integrity of the epidermal barrier and the quality of the innate and adaptive immune systems. The underlying mechanisms must be elucidated before it will be possible to make reliable predictions of whether a given individual will develop allergic sensitisation by a given chemical. PMID:24214618

Friedmann, Peter S; Pickard, Christopher

2014-01-01

224

In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.  

PubMed

Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs. PMID:23964550

Mayorga, C; Sanz, M L; Gamboa, P; Garcia-Aviles, M C; Fernandez, J; Torres, M J

2013-01-01

225

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

226

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

227

Integrated analysis of the Wnt responsive proteome in human cells reveals diverse and cell-type specific networks  

PubMed Central

Wnt signalling is a fundamentally important signalling pathway that regulates many aspects of metazoan development and is frequently dysregulated in cancer. Although many of the core components of the Wnt signalling pathway, such as ?-catenin, have been extensively studied, the broad systems level responses of the mammalian cell to Wnt signalling are less well understood. In addition, the cell- or tissue-specific protein networks that modulate Wnt signalling in the diverse tissues or developmental stages in which it functions remain to be defined. To address these questions, we undertook a broad survey of the Wnt response in different human cell lines using both interaction and expression proteomics approaches. Our data reveal both similar and divergent responses of pathways and processes in the three cell-lines analyzed as well as a marked attenuation of the response to exogenous Wnt treatment in cells harbouring a stabilizing (activating) mutation of ?-catenin. We also identify cell-type specific components of the Wnt signalling network and find that by integrating expression and interaction proteomics data a more complete description of the Wnt interaction network can be achieved. Finally, our results attest to the power of LCMS/MS to reveal novel cellular responses in even relatively well studied biological pathways such as Wnt signalling. PMID:24201312

Song, J.; Wang, Z.; Ewing, R.M.

2013-01-01

228

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

229

Quantitative Proteomics and Dynamic Imaging of the Nucleolus Reveal Distinct Responses to UV and Ionizing Radiation*  

PubMed Central

The nucleolus is a nuclear organelle that coordinates rRNA transcription and ribosome subunit biogenesis. Recent proteomic analyses have shown that the nucleolus contains proteins involved in cell cycle control, DNA processing and DNA damage response and repair, in addition to the many proteins connected with ribosome subunit production. Here we study the dynamics of nucleolar protein responses in cells exposed to stress and DNA damage caused by ionizing and ultraviolet (UV) radiation in diploid human fibroblasts. We show using a combination of imaging and quantitative proteomics methods that nucleolar substructure and the nucleolar proteome undergo selective reorganization in response to UV damage. The proteomic responses to UV include alterations of functional protein complexes such as the SSU processome and exosome, and paraspeckle proteins, involving both decreases and increases in steady state protein ratios, respectively. Several nonhomologous end-joining proteins (NHEJ), such as Ku70/80, display similar fast responses to UV. In contrast, nucleolar proteomic responses to IR are both temporally and spatially distinct from those caused by UV, and more limited in terms of magnitude. With the exception of the NHEJ and paraspeckle proteins, where IR induces rapid and transient changes within 15 min of the damage, IR does not alter the ratios of most other functional nucleolar protein complexes. The rapid transient decrease of NHEJ proteins in the nucleolus indicates that it may reflect a response to DNA damage. Our results underline that the nucleolus is a specific stress response organelle that responds to different damage and stress agents in a unique, damage-specific manner. PMID:21778410

Moore, Henna M.; Bai, Baoyan; Boisvert, François-Michel; Latonen, Leena; Rantanen, Ville; Simpson, Jeremy C.; Pepperkok, Rainer; Lamond, Angus I.; Laiho, Marikki

2011-01-01

230

Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection  

Microsoft Academic Search

Background  Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early\\u000a events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription\\u000a profiles on host-pathogen interactions are strongly biased towards in vitro studies. To detail the local in vivo genetic response to infection, we here profiled host gene expression in a

Jorrit Boekel; Örjan Källskog; Monica Rydén-Aulin; Mikael Rhen; Agneta Richter-Dahlfors

2011-01-01

231

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

SciTech Connect

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

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

2006-04-08

232

Which Response Format Reveals the Truth about Donations to a Public Good?  

Microsoft Academic Search

Several contingent valuation studies have found that the open-ended format yields lower estimates of willingness to pay (WTP) than does the closed-ended, or dichotomous choice, format. In this study, WTP for a public environmental good was estimated under four conditions: actual payment in response to open-ended and closed-ended requests, and hypothetical payment in response to open-ended and closed-ended requests. The

Thomas C. Brown; Patricia A. Champ; Richard C. Bishop; Daniel W. McCollum

1996-01-01

233

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

PubMed

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

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

1996-05-01

234

Human cortical responses to slow and fast binaural beats reveal multiple mechanisms of binaural hearing.  

PubMed

When two tones with slightly different frequencies are presented to both ears, they interact in the central auditory system and induce the sensation of a beating sound. At low difference frequencies, we perceive a single sound, which is moving across the head between the left and right ears. The percept changes to loudness fluctuation, roughness, and pitch with increasing beat rate. To examine the neural representations underlying these different perceptions, we recorded neuromagnetic cortical responses while participants listened to binaural beats at a continuously varying rate between 3 Hz and 60 Hz. Binaural beat responses were analyzed as neuromagnetic oscillations following the trajectory of the stimulus rate. Responses were largest in the 40-Hz gamma range and at low frequencies. Binaural beat responses at 3 Hz showed opposite polarity in the left and right auditory cortices. We suggest that this difference in polarity reflects the opponent neural population code for representing sound location. Binaural beats at any rate induced gamma oscillations. However, the responses were largest at 40-Hz stimulation. We propose that the neuromagnetic gamma oscillations reflect postsynaptic modulation that allows for precise timing of cortical neural firing. Systematic phase differences between bilateral responses suggest that separate sound representations of a sound object exist in the left and right auditory cortices. We conclude that binaural processing at the cortical level occurs with the same temporal acuity as monaural processing whereas the identification of sound location requires further interpretation and is limited by the rate of object representations. PMID:25008412

Ross, Bernhard; Miyazaki, Takahiro; Thompson, Jessica; Jamali, Shahab; Fujioka, Takako

2014-10-15

235

Transcriptome analysis of sorbic acid-stressed Bacillus subtilis reveals a nutrient limitation response and indicates plasma membrane remodeling  

Microsoft Academic Search

The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses

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

2008-01-01

236

[Visceral hypersensitivity: a concept within our reach].  

PubMed

Despite significant advances in the recognition of etiological factors and pathological mechanisms, the pathophysiology of functional gastrointestinal disorders (FGD) is still not fully understood. Visceral hypersensitivity has been recognized as a characteristic of patients with FGD, especially in patients with irritable bowel syndrome (IBS). Visceral afferent input is modulated by a variety of mechanisms, operating between the gastrointestinal tract and the brain. Dysfunction of these regulatory mechanisms could distort gastrointestinal perceptions. Recent findings suggest that in the majority of cases of IBS the primary abnormality may be at the periphery with alterations of the motor and secretory sensory activity. Although imaging techniques indicate that there are also differences in cortical activation. Furthermore, selective serotonin reuptake inhibitors may benefit FGD. Recent pharmacological studies suggest that 5-HT3 antagonist such as alosetron and cilansetron, and 5-HT4 agonist such as legaserod and prucalopride may also have a potential use in FGD. PMID:12643225

Quera, Rodrigo; Valenzuela, Jorge

2003-01-01

237

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

238

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

PubMed Central

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

2013-01-01

239

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

PubMed

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

2013-11-22

240

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

241

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

PubMed Central

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

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

2012-01-01

242

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

PubMed Central

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

2010-01-01

243

The impact of the bystander effect on the low-dose hypersensitivity phenomenon.  

PubMed

The aim of this study was to investigate the possible relationship between the bystander effect and the low-dose hypersensitivity/increased radio-resistance phenomenon in BJ fibroblast cells taking as response criteria different end points of radiation damage such as cell survival, chromosomal damage (as detected by using micronucleus assay) and double strand breaks (DSBs) of the DNA. Although gamma-H2AX foci were observed in confluent bystander BJ cells, our data suggest that X-irradiation does not lead to a significant rate of DSBs in bystander cells. Thus, neither bystander effect induced unstable chromosomal aberrations nor bystander effect induced DSBs are sufficiently pronounced to explain the apparent relationship between bystander effect and low-dose hypersensitivity. The experiments described here suggest that the hyper-radiosensitivity phenomenon might be related to bystander factor induced cell inactivation in the low-dose region (lower than 1 Gy). PMID:18189143

Nuta, Otilia; Darroudi, Firouz

2008-04-01

244

Simultaneous dual-task performance reveals parallel response selection after practice  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

245

AKT-pathway Inhibition in Chronic Lymphocytic Leukemia Reveals Response Relationships Defined by TCL1.  

PubMed

Cell survival in chronic lymphocytic leukemia (CLL) largely depends on B-cell receptor-induced AKT activation. Gain-of-function genomic lesions of PI3K-AKT-mTOR pathway components are usually absent in CLL. We previously established that a BCR-mediated growth response in CLL is determined by the oncogene T-cell leukemia 1 (TCL1) through a sensitizer effect on AKT phospho-activation. Despite high clinical response rates following AKTcascade inhibition in CLL, resistances in a substantial proportion of patients call for reliable pre- and post-exposure strata to better predict compound responses. Using a panel of inhibitors with differential vertical affinities in the PI3K-AKTmTOR axis, we describe distinct patterns and determinants of sensitivities in 75 CLL samples. The compounds specifically impacted the BCR-induced physical TCL1-AKT interaction. In general, there was an efficient and tumorselective abrogation of cell survival in suspension or protective stromal-cell cultures. However, biochemical and survival responses were heterogeneous across CLL and showed only incomplete overlap across inhibitors. Sensitivity clusters could be defined by differential responses to selective pan-PI3K inhibition vs. compounds acting more down-stream. An elevated PI3K/AKT/mTOR activation state conferred sensitivity or resistance, depending on the applied inhibitor. In fact, down-stream interception by mTOR or dual mTOR/PI3K inhibition appears more efficient in cases expressing the BCRresponse and poor-risk determinants of ZAP70 or TCL1. Finally, exploiting the TCL1-AKT interaction, peptide-based TCL1-interphase mimics were potent in steric AKT antagonization and in reducing CLL cell survival. Overall, this study provides informative response relationships in AKT-pathway interception that can help refining predictive models in BCR-pathway inhibition in CLL. PMID:25348018

Schrader, Alexandra; Popal, Wagma; Lilienthal, Nils; Crispatzu, Giuliano; Mayer, Petra; Jones, Dan; Hallek, Michael; Herling, Marco

2014-01-01

246

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

247

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

248

Shadow response in the blind cavefish Astyanax reveals conservation of a functional pineal eye  

PubMed Central

SUMMARY The blind cavefish Astyanax mexicanus undergoes bilateral eye degeneration during embryonic development. Despite the absence of light in the cave environment, cavefish have retained a structurally intact pineal eye. We show here that contrary to visual degeneration in the bilateral eyes, the cavefish pineal eye has conserved the ability to detect light. Larvae of two different Astyanax cavefish populations and the con-specific sighted surface-dwelling form (surface fish) respond similarly to light dimming by shading the pineal eye. As a response to shading, cavefish larvae swim upward vertically. This behavior resembles that of amphibian tadpoles rather than other teleost larvae, which react to shadows by swimming downward. The shadow response is highest at 1.5-days post-fertilization (d.p.f.), gradually diminishes, and is virtually undetectable by 7.5 d.p.f. The shadow response was substantially reduced after surgical removal of the pineal gland from surface fish or cavefish larvae, indicating that it is based on pineal function. In contrast, removal of one or both bilateral eye primordia did not affect the shadow response. Consistent with its light detecting capacity, immunocytochemical studies indicate that surface fish and cavefish pineal eyes express a rhodopsin-like antigen, which is undetectable in the degenerating bilateral eyes of cavefish larvae. We conclude that light detection by the pineal eye has been conserved in cavefish despite a million or more years of evolution in complete darkness. PMID:18203983

Yoshizawa, Masato; Jeffery, William R.

2013-01-01

249

Rapid response to habitat restoration by the perennial Primula veris as revealed by demographic monitoring  

Microsoft Academic Search

The demography of Primula veris, a typical species of the species-rich Mesobromion grasslands, was investigated at two contrasting habitats in Eastern Belgium. Both a forested site and a clear-cut parcel were part of formerly larger calcareous grassland areas. By monitoring the demographic response of the target species, this study attempts to clarify the differences in fecundity, growth and survival between

Patrick Endels; Hans Jacquemyn; Rein Brys; Martin Hermy

2005-01-01

250

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

PubMed Central

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

Otálora-Luna, Fernando; Dickens, Joseph C.

2011-01-01

251

Cytip regulates dendritic-cell function in contact hypersensitivity  

PubMed Central

Cytohesin-interacting protein (Cytip) is induced during dendritic cell (DC) maturation and in T cells upon activation. It has also been shown to be involved in the regulation of immune responses. Here, we evaluated the functional consequences of Cytip deficiency in DCs using Cytip knockout (KO) mice. No difference in DC subpopulations in the skin draining lymph nodes (LNs) was found between Cytip KO mice and their wild-type counterparts, excluding a role in DC development. To investigate the function of Cytip in DCs in vivo, we used 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) as a model system. In the sensitization as well as in the elicitation phase, DCs derived from Cytip KO mice induced an increased inflammatory reaction indicated by more pronounced ear swelling. Furthermore, IL-12 production was increased in Cytip KO bone marrow-derived DCs (BMDCs) after CpG stimulation. Additionally, Cytip-deficient DCs loaded with ovalbumin induced stronger proliferation of antigen-specific CD4+ and CD8+ T cells in vitro. Finally, migration of skin DCs was not altered after TNCB application due to Cytip deficiency. Taken together, these data suggest a suppressive function for Cytip in mouse DCs in limiting immune responses. PMID:22488362

Heib, Valeska; Sparber, Florian; Tripp, Christoph H; Ortner, Daniela; Stoitzner, Patrizia; Heufler, Christine

2012-01-01

252

Cytip regulates dendritic-cell function in contact hypersensitivity.  

PubMed

Cytohesin-interacting protein (Cytip) is induced during dendritic cell (DC) maturation and in T cells upon activation. It has also been shown to be involved in the regulation of immune responses. Here, we evaluated the functional consequences of Cytip deficiency in DCs using Cytip knockout (KO) mice. No difference in DC subpopulations in the skin draining lymph nodes (LNs) was found between Cytip KO mice and their wild-type counterparts, excluding a role in DC development. To investigate the function of Cytip in DCs in vivo, we used 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) as a model system. In the sensitization as well as in the elicitation phase, DCs derived from Cytip KO mice induced an increased inflammatory reaction indicated by more pronounced ear swelling. Furthermore, IL-12 production was increased in Cytip KO bone marrow-derived DCs (BMDCs) after CpG stimulation. Additionally, Cytip-deficient DCs loaded with ovalbumin induced stronger proliferation of antigen-specific CD4(+) and CD8(+) T cells in vitro. Finally, migration of skin DCs was not altered after TNCB application due to Cytip deficiency. Taken together, these data suggest a suppressive function for Cytip in mouse DCs in limiting immune responses. PMID:22488362

Heib, Valeska; Sparber, Florian; Tripp, Christoph H; Ortner, Daniela; Stoitzner, Patrizia; Heufler, Christine

2012-03-01

253

Hypersensitivity to titanium: a less explored area of research.  

PubMed

Titanium is considered as an excellent biocompatible metal and it is used in implant dentistry. Literature suggests that Ti can induce clinically relevant hypersensitivity and other immune dysfunctions in certain patients chronically exposed to this reactive metal. At the same time, no standard patch test for Ti has so far been developed, and positive reactions to Ti have therefore only rarely been demonstrated with skin testing. This article reports about the corrosion of dental implants, their significance when hypersensitivity is present, and the literature available till date regarding hypersensitivity of titanium. PMID:24293916

Vijayaraghavan, Vasantha; Sabane, Ajay V; Tejas, K

2012-12-01

254

Dentin Hypersensitivity: Etiology, Diagnosis and Treatment; A Literature Review  

PubMed Central

The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms “dentin*”, “tooth”, “teeth”, “hypersensit*”, “desensitiz*”. Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used. PMID:24724135

Davari, AR; Ataei, E; Assarzadeh, H

2013-01-01

255

Successful Desensitization of a Patient with Rituximab Hypersensitivity  

PubMed Central

Rituximab is a monoclonal antibody which targets CD20 in B cells that is used for the treatment of CD20 positive oncologic and hematologic malignancies. Rituximab causes hypersensitivity reactions during infusions. The delay of treatment or loss of a highly efficient drug can be prevented by rapid drug desensitization method in patients who are allergic to rituximab. We report a low grade B cell non-Hodgkin lymphoma patient with rituximab hypersensitivity successfully treated with rapid drug desensitization. In experienced centers, drug desensitization is a novel modality to break through in case of hypersensitivity that should be considered.

Ataca, Pinar; Atilla, Erden; Kendir, Resat; Bavbek, Sevim; Ozcan, Muhit

2015-01-01

256

Dentin hypersensitivity: etiology, diagnosis and treatment; a literature review.  

PubMed

The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms "dentin*", "tooth", "teeth", "hypersensit*", "desensitiz*". Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used. PMID:24724135

Davari, Ar; Ataei, E; Assarzadeh, H

2013-09-01

257

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

PubMed

Interacting threats to ecosystem function, including climate change, wildfire, and invasive species necessitate native plant restoration in desert ecosystems. However, native plant restoration efforts often remain unguided by ecological genetic information. Given that many ecosystems are in flux from climate change, restoration plans need to account for both contemporary and future climates when choosing seed sources. In this study we analyze vegetative responses, including mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne ramosissima) common gardens that included 26 populations from a range-wide collection. This shrub occupies ecotones between the warm and cold deserts of Mojave and Colorado Plateau ecoregions in western North America. The variation observed in the vegetative responses of blackbrush populations was principally explained by grouping populations by ecoregions and by regression with site-specific climate variables. Aridity weighted by winter minimum temperatures best explained vegetative responses; Colorado Plateau sites were usually colder and drier than Mojave sites. The relationship between climate and vegetative response was mapped within the boundaries of the species-climate space projected for the contemporary climate and for the decade surrounding 2060. The mapped ecological genetic pattern showed that genetic variation could be classified into cool-adapted and warm-adapted ecotypes, with populations often separated by steep dines. These transitions are predicted to occur in both the Mojave Desert and Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted ecotype occupies the majority of climate space, climate projections predict that the cool-adapted ecotype could prevail as the dominant ecotype as the climate space of blackbrush expands into higher elevations and latitudes. This study provides the framework for delineating climate change-responsive seed transfer guidelines, which are needed to inform restoration and management planning. We propose four transfer zones in blackbrush that correspond to areas currently dominated by cool-adapted and warm-adapted ecotypes in each of the two ecoregions. PMID:24689151

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

2014-03-01

258

Adaptive responses reveal contemporary and future ecotypes in a desert shrub  

USGS Publications Warehouse

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

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

2014-01-01

259

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

PubMed Central

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

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

2013-01-01

260

Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM  

PubMed Central

Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy. PMID:25604826

Biswas, Nidhan K.; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N.; Tripathy, Laxmi N.; Basu, Sunandan K.; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

2015-01-01

261

Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.  

PubMed

Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy. PMID:25604826

Biswas, Nidhan K; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N; Tripathy, Laxmi N; Basu, Sunandan K; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

2015-01-01

262

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

PubMed Central

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

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

2014-01-01

263

lsolation od uvhl, an Arabidopsis Mutant Hypersensitive to Ultraviolet Light and lonizing Radiation  

Microsoft Academic Search

A genetic screen for mutants of Arabidopsis that are hypersensitive to UV light was developed and used to isolate a new mutant designated uvhl. UV hypersensitivity in uvhl was due to a single recessive trait that is probably located on chromosome 3. Although isolated as hypersensitive to an acute exposure to UV-C light, uvhl was also hypersensitive to UV-B wavelengths,

Greg R. Harlow; Michael E. Jenkins; Tabassum S. Pittalwala; David W. Mount

264

Combined Systems Approaches Reveal Highly Plastic Responses to Antimicrobial Peptide Challenge in Escherichia coli  

PubMed Central

Obtaining an in-depth understanding of the arms races between peptides comprising the innate immune response and bacterial pathogens is of fundamental interest and will inform the development of new antibacterial therapeutics. We investigated whether a whole organism view of antimicrobial peptide (AMP) challenge on Escherichia coli would provide a suitably sophisticated bacterial perspective on AMP mechanism of action. Selecting structurally and physically related AMPs but with expected differences in bactericidal strategy, we monitored changes in bacterial metabolomes, morphological features and gene expression following AMP challenge at sub-lethal concentrations. For each technique, the vast majority of changes were specific to each AMP, with such a plastic response indicating E. coli is highly capable of discriminating between specific antibiotic challenges. Analysis of the ontological profiles generated from the transcriptomic analyses suggests this approach can accurately predict the antibacterial mode of action, providing a fresh, novel perspective for previous functional and biophysical studies. PMID:24789011

Kozlowska, Justyna; Vermeer, Louic S.; Rogers, Geraint B.; Rehnnuma, Nabila; Amos, Sarah-Beth T. A.; Koller, Garrit; McArthur, Michael; Bruce, Kenneth D.; Mason, A. James

2014-01-01

265

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

Pérez-Cidoncha, Maite; Killip, Marian J.; Oliveros, Juan C.; Asensio, Víctor J.; Fernández, Yolanda; Bengoechea, José A.; Randall, Richard E.

2014-01-01

266

Proteomics reveals a core molecular response of Pseudomonas putida F1 to acute chromate challenge  

PubMed Central

Background Pseudomonas putida is a model organism for bioremediation because of its remarkable metabolic versatility, extensive biodegradative functions, and ubiquity in contaminated soil environments. To further the understanding of molecular pathways responding to the heavy metal chromium(VI) [Cr(VI)], the proteome of aerobically grown, Cr(VI)-stressed P. putida strain F1 was characterized within the context of two disparate nutritional environments: rich (LB) media and minimal (M9L) media containing lactate as the sole carbon source. Results Growth studies demonstrated that F1 sensitivity to Cr(VI) was impacted substantially by nutrient conditions, with a carbon-source-dependent hierarchy (lactate > glucose >> acetate) observed in minimal media. Two-dimensional HPLC-MS/MS was employed to identify differential proteome profiles generated in response to 1 mM chromate under LB and M9L growth conditions. The immediate response to Cr(VI) in LB-grown cells was up-regulation of proteins involved in inorganic ion transport, secondary metabolite biosynthesis and catabolism, and amino acid metabolism. By contrast, the chromate-responsive proteome derived under defined minimal growth conditions was characterized predominantly by up-regulated proteins related to cell envelope biogenesis, inorganic ion transport, and motility. TonB-dependent siderophore receptors involved in ferric iron acquisition and amino acid adenylation domains characterized up-regulated systems under LB-Cr(VI) conditions, while DNA repair proteins and systems scavenging sulfur from alternative sources (e.g., aliphatic sulfonates) tended to predominate the up-regulated proteome profile obtained under M9L-Cr(VI) conditions. Conclusions Comparative analysis indicated that the core molecular response to chromate, irrespective of the nutritional conditions tested, comprised seven up-regulated proteins belonging to six different functional categories including transcription, inorganic ion transport/metabolism, and amino acid transport/metabolism. These proteins might potentially serve as indicators of chromate stress in natural microbial communities. PMID:20482812

2010-01-01

267

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

Microsoft Academic Search

BACKGROUND: Roots are an attractive system for genomic and post-genomic studies of NaCl responses, due to their primary importance to agriculture, and because of their relative structural and biochemical simplicity. Excellent genomic resources have been established for the study of Arabidopsis roots, however, a comprehensive microarray analysis of the root transcriptome following NaCl exposure is required to further understand plant

Yuanqing Jiang; Michael K Deyholos

2006-01-01

268

Virus-encoded TLR ligands reveal divergent functional responses of mononuclear phagocytes in pathogenic SIV infection  

PubMed Central

The role of mononuclear phagocytes in the pathogenesis or control of HIV infection is unclear. Here, we monitored the dynamics and function of dendritic cells (DC) and monocytes/macrophages in rhesus macaques acutely infected with pathogenic SIVmac251 with and without antiretroviral therapy (ART). SIV infection was associated with monocyte mobilization and recruitment of plasmacytoid DC (pDC) and macrophages to lymph nodes which did not occur with ART treatment. SIVmac251 single-stranded RNA encoded several uridine-rich sequences that were potent TLR7/8 ligands in mononuclear phagocytes of naive animals, stimulating myeloid DC (mDC) and monocytes to produce TNF-? and pDC and macrophages to produce both TNF-? and IFN-?. Following SIV infection pDC and monocytes/macrophages rapidly became hyporesponsive to stimulation with SIV-encoded TLR ligands and influenza virus, a condition that was reversed by ART. The loss of pDC and macrophage function was associated with a profound but transient block in the capacity of lymph node cells to secrete IFN-? upon stimulation. In contrast to pDC and monocytes/macrophages, mDC increased TNF-? production in response to stimulation following acute infection. Moreover, SIV-infected rhesus macaques with stable infection had increased mDC responsiveness to SIV-encoded TLR ligands and influenza virus at set-point, whereas animals that progressed rapidly to AIDS had reduced mDC responsiveness. These findings indicate that SIV encodes immunostimulatory TLR ligands and that pDC, mDC and monocytes/macrophages respond to these ligands differently as a function of SIV infection. The data also suggest that increased responsiveness of mDC to stimulation following SIV infection may be beneficial to the host. PMID:23338235

Wonderlich, Elizabeth R.; Wijewardana, Viskam; Liu, Xiangdong; Barratt-Boyes, Simon M.

2013-01-01

269

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

PubMed Central

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

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

2014-01-01

270

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

PubMed

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

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

2014-10-01

271

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

272

Metagenomics reveals sediment microbial community response to Deepwater Horizon oil spill.  

PubMed

The Deepwater Horizon (DWH) oil spill in the spring of 2010 resulted in an input of ?4.1 million barrels of oil to the Gulf of Mexico; >22% of this oil is unaccounted for, with unknown environmental consequences. Here we investigated the impact of oil deposition on microbial communities in surface sediments collected at 64 sites by targeted sequencing of 16S rRNA genes, shotgun metagenomic sequencing of 14 of these samples and mineralization experiments using (14)C-labeled model substrates. The 16S rRNA gene data indicated that the most heavily oil-impacted sediments were enriched in an uncultured Gammaproteobacterium and a Colwellia species, both of which were highly similar to sequences in the DWH deep-sea hydrocarbon plume. The primary drivers in structuring the microbial community were nitrogen and hydrocarbons. Annotation of unassembled metagenomic data revealed the most abundant hydrocarbon degradation pathway encoded genes involved in degrading aliphatic and simple aromatics via butane monooxygenase. The activity of key hydrocarbon degradation pathways by sediment microbes was confirmed by determining the mineralization of (14)C-labeled model substrates in the following order: propylene glycol, dodecane, toluene and phenanthrene. Further, analysis of metagenomic sequence data revealed an increase in abundance of genes involved in denitrification pathways in samples that exceeded the Environmental Protection Agency (EPA)'s benchmarks for polycyclic aromatic hydrocarbons (PAHs) compared with those that did not. Importantly, these data demonstrate that the indigenous sediment microbiota contributed an important ecosystem service for remediation of oil in the Gulf. However, PAHs were more recalcitrant to degradation, and their persistence could have deleterious impacts on the sediment ecosystem. PMID:24451203

Mason, Olivia U; Scott, Nicole M; Gonzalez, Antonio; Robbins-Pianka, Adam; Bælum, Jacob; Kimbrel, Jeffrey; Bouskill, Nicholas J; Prestat, Emmanuel; Borglin, Sharon; Joyner, Dominique C; Fortney, Julian L; Jurelevicius, Diogo; Stringfellow, William T; Alvarez-Cohen, Lisa; Hazen, Terry C; Knight, Rob; Gilbert, Jack A; Jansson, Janet K

2014-07-01

273

Latex hypersensitivity: a closer look at considerations for dentistry.  

PubMed

Over the past several decades, latex hypersensitivity has become an increasingly common phenomenon in the dental setting. Exposure to latex via direct skin contact or inhalation of airborne allergens from powdered gloves poses the risk of sensitizing both clinicians and their patients. Adverse reactions to latex range from mild irritant contact dermatitis to potentially life-threatening hypersensitivity. The prevalence of these reactions is higher among medical and dental practitioners, those with prior allergies, patients with a history of multiple surgeries and those with spina bifida. The risk of developing latex hypersensitivity increases with prolonged and repeated exposure. The incidence of latex allergy may be reduced through such simple measures as using latex alternatives and powder-free, low-protein gloves. For patients with confirmed latex allergy or those at risk of hypersensitivity, it is critical for dental personnel to be familiar with the range of possibilities for latex exposure and to employ appropriate preventive procedures. PMID:19422750

Kean, Tara; McNally, Mary

2009-05-01

274

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2012 CFR

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

2012-04-01

275

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2013 CFR

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

2013-04-01

276

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2011 CFR

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

2011-04-01

277

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.  

Code of Federal Regulations, 2014 CFR

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

2014-04-01

278

Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity  

PubMed Central

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

Asnaashari, Mohammad; Moeini, Masoumeh

2013-01-01

279

Crosstalk between contact hypersensitivity reaction and antidepressant drugs.  

PubMed

Allergic contact dermatitis is a delayed-type hypersensitivity reaction mediated by hapten-specific T cells. Many cell types, inflammatory mediators and cytokines are involved in this reaction. Contact hypersensitivity is a self-limited reaction and can be regulated at different levels. Because it is known that disturbances in the immune system underpin the onset of depression and that antidepressant drugs have immunomodulatory effects, it can be hypothesized that antidepressants may have some efficacy in the treatment of contact hypersensitivity. There are some reports on the effectiveness of antidepressants in the inhibition of cutaneous sensitization in mice, and the aim of this narrative review is to assess the evidence for the effectiveness of antidepressant drugs in reducing the recurrence of contact hypersensitivity reactions. PMID:24553016

Curzytek, Katarzyna; Kubera, Marta; Szczepanik, Marian; Basta-Kaim, Agnieszka; Le?kiewicz, Monika; Budziszewska, Bogus?awa; Laso?, W?adys?aw; Maes, Michael

2013-01-01

280

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

SciTech Connect

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

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

2010-10-01

281

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

282

High-fat taste challenge reveals altered striatal response in women recovered from bulimia nervosa: A pilot study  

PubMed Central

Objectives Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) tend to have disordered thinking and eating behaviours in regards to fat containing foods. This is the first study to investigate neuronal pathways that may contribute to altered fat consumption in eating disordered patients. Methods We used functional magnetic resonance imaging (fMRI) to compare responses to a high-fat cream stimulus, water, and a non-caloric viscous stimulus (CMC) to control for response to viscosity in individuals recovered from AN (N = 15), BN (N = 14) and a healthy control sample (CW, N = 18). Results An interaction analysis (ANOVAR) comparing the three groups (AN, BN, CW) and the three conditions (cream, CMC, water) revealed significant differences in the left anterior ventral striatum (AVS). A post hoc analysis displayed a higher magnitude of response for the contrast cream/water in BN compared to AN or CW and for the contrast CMC/water in BN compared to AN. Conclusions BN showed an exaggerated AVS response for the cream/water contrast in comparison to AN or CW. Moreover, BN showed an exaggerated AVS response for the CMC/water contrast in comparison to AN. These findings support the possibility that BN have an altered hedonic and/or motivational drive to consume fats. PMID:22540408

RADELOFF, DANIEL; WILLMANN, KATHRIN; OTTO, LISA; LINDNER, MICHAEL; PUTNAM, KAREN; VAN LEEUWEN, SARA; KAYE, WALTER H; POUSTKA, FRITZ; WAGNER, ANGELA

2015-01-01

283

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

284

Conservation of Indole Responsive Odorant Receptors in Mosquitoes Reveals an Ancient Olfactory Trait  

PubMed Central

Aedes aegypti and Anopheles gambiae are among the best-characterized mosquito species within the Culicinae and Anophelinae mosquito clades which diverged ?150 million years ago. Despite this evolutionary distance, the olfactory systems of these mosquitoes exhibit similar morphological and physiological adaptations. Paradoxically, mosquito odorant receptors, which lie at the heart of chemosensory signal transduction pathways, belong to a large and highly divergent gene family. We have used 2 heterologous expression systems to investigate the functional characteristics of a highly conserved subset of Ors between Ae. aegypti and An. gambiae to investigate whether protein homology correlates with odorant-induced activation. We find that these receptors share similar odorant response profiles and that indole, a common and ecologically relevant olfactory cue, elicits strong responses from these homologous receptors. The identification of other highly conserved members of this Or clade from mosquito species of varying phylogenetic relatedness supports a model in which high sensitivity to indole represents an ancient ecological adaptation that has been preserved as a result of its life cycle importance. These results provide an understanding of how similarities and disparities among homologous OR proteins relate to olfactory function, which can lead to greater insights into the design of successful strategies for the control of mosquito-borne diseases. PMID:20956733

Bohbot, Jonathan D.; Jones, Patrick L.; Wang, Guirong; Pitts, R. Jason; Pask, Gregory M.

2011-01-01

285

Auditory brainstem response recovery in the dolphin as revealed by double sound pulses of different frequencies.  

PubMed

Recovery of auditory brainstem responses (ABR) in a bottlenose dolphin was studied in conditions of double-pip stimulation when two stimuli in a pair differed in frequency and intensity. When the conditioning and test stimuli were of equal frequencies, the test response was markedly suppressed at short interstimulus intervals; complete recovery appeared at intervals from about 2 ms (when two stimuli were of equal intensity) to 10-20 ms (when the conditioning stimulus exceeded the test by up to 40 dB). When the two stimuli were of different frequencies, the suppression diminished and was almost absent at a half-octave difference even if the conditioning stimulus exceeded the test one by 40 dB. Frequency-dependence curves (ABR amplitude dependence on frequency difference between the two stimuli) had equivalent rectangular bandwidth from +/-0.2 oct at test stimuli of 20 dB above threshold to +/-0.5 oct at test stimuli of 50 dB above threshold. PMID:11681398

Popov, V V; Supin AYa; Klishin, V O

2001-10-01

286

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

287

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

288

Differential proteome and gene expression reveal response to carbon ion irradiation in pubertal mice testes.  

PubMed

Heavy ion radiation, a high linear energy transfer (LET) radiation, has been shown to have adverse effects on reproduction in male mice. The aim of this study was to profile and investigate the differentially expressed proteins in pubertal male mice testes following carbon ion radiation (CIR). Male mice underwent whole-body irradiation with CIR (1 and 4 Gy), and MALDI-TOF/TOF analysis was used to investigate the alteration in protein expression in 2-DE (two-dimensional gel electrophoresis) gels of testes caused by irradiation after 14 days. 8 differentially expressed proteins were identified and these proteins were mainly involved in energy supply, the endoplasmic reticulum, cell proliferation, cell cycle, antioxidant capacity and mitochondrial respiration, which play important roles in the inhibition of testicular function in response to CIR. Furthermore, we confirmed the relationship between transcription of mRNA and the abundance of proteins. Our results indicated that these proteins may lead to new insights into the molecular mechanism of CIR toxicity, and suggested that the gene expression response to CIR involves diverse regulatory mechanisms from transcription of mRNA to the formation of functional proteins. PMID:24440814

Li, Hongyan; He, Yuxuan; Zhang, Hong; Miao, Guoying

2014-03-21

289

Failure analysis of porcupine quills under axial compression reveals their mechanical response during buckling.  

PubMed

Porcupine quills are natural structures formed by a thin walled conical shell and an inner foam core. Axial compression tests, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR) were all used to compare the characteristics and mechanical properties of porcupine quills with and without core. The failure mechanisms that occur during buckling were analyzed by scanning electron microscopy (SEM), and it was found that delamination buckling is mostly responsible for the decrease in the measured buckling stress of the quills with regard to predicted theoretical values. Our analysis also confirmed that the foam core works as an energy dissipater improving the mechanical response of an empty cylindrical shell, retarding the onset of buckling as well as producing a step wise decrease in force after buckling, instead of an instantaneous decrease in force typical for specimens without core. Cell collapse and cell densification in the inner foam core were identified as the key mechanisms that allow for energy absorption during buckling. PMID:25123434

Torres, Fernando G; Troncoso, Omar P; Diaz, John; Arce, Diego

2014-11-01

290

Optical imaging of visually evoked responses in prosimian primates reveals conserved features of the middle temporal visual area.  

PubMed

Optical imaging of intrinsic cortical responses to visual stimuli was used to characterize the organization of the middle temporal visual area (MT) of a prosimian primate, the bush baby (Otolemur garnetti). Stimulation with moving gratings revealed a patchwork of oval-like domains in MT. These orientation domains could, in turn, be subdivided into zones selective to directional movements that were mainly orthogonal to the preferred orientation. Similar, but not identical, zones were activated by movements of random dots in the preferred direction. Orientation domains shifted in preference systematically either around a center to form pinwheels or as gradual linear shifts. Stimuli presented in different portions of the visual field demonstrated a global representation of visual space in MT. As optical imaging has revealed similar features in MT of New World monkeys, MT appears to have retained these basic features of organization for at least the 60 million years since the divergence of prosimian and simian primates. PMID:14983049

Xu, Xiangmin; Collins, Christine E; Kaskan, Peter M; Khaytin, Ilya; Kaas, Jon H; Casagrande, Vivien A

2004-02-24

291

Hypersensitivity pneumonitis of a mushroom worker due to Aspergillus glaucus.  

PubMed

We present the first reported case of hypersensitivity pneumonitis (HP) due to Aspergillus glaucus in a mushroom worker. The Aspergillus glaucus group is one of the most popular storage fungi and a possible subsidiary etiologic agent of farmer's lung, but no case of hypersensitivity pneumonitis (HP) due to A. glaucus has been reported. This first case may demonstrate the etiologic role of A. glaucus in HP and in farmer's lung. PMID:2119164

Yoshida, K; Ando, M; Ito, K; Sakata, T; Arima, K; Araki, S; Uchida, K

1990-01-01

292

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

PubMed Central

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

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

2011-01-01

293

SMARCAL1 Deficiency Predisposes to Non-Hodgkin Lymphoma and Hypersensitivity to Genotoxic Agents In vivo  

PubMed Central

Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder with prominent skeletal, renal, immunological, and ectodermal abnormalities. It is caused by mutations of SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA stress response protein. To determine the relationship of this function to the SIOD phenotype, we profiled the cancer prevalence in SIOD and assessed if defects of nucleotide excision repair (NER) and of nonhomologous end joining (NHEJ), respectively, explained the ectodermal and immunological features of SIOD. Finally, we determined if Smarcal1del/del mice had hypersensitivity to irinotecan (CPT-11), etoposide and hydroxyurea (HU) and whether exposure to these agents induced features of SIOD. Among 71 SIOD patients, three had non-Hodgkin lymphoma (NHL) and one had osteosarcoma. We did not find evidence of defective NER or NHEJ; however, Smarcal1-deficient mice were hypersensitive to several genotoxic agents. Also, CPT-11, etoposide and HU caused decreased growth and loss of growth plate chondrocytes. These data, which identify an increased prevalence of NHL in SIOD and confirm hypersensitivity to DNA damaging agents in vivo, provide guidance for the management of SIOD patients. PMID:22888040

Baradaran-Heravi, Alireza; Raams, Anja; Lubieniecka, Joanna; Cho, Kyoung Sang; DeHaai, Kristi A.; Basiratnia, Mitra; Mari, Pierre-Olivier; Xue, Yutong; Rauth, Michael; Olney, Ann Haskins; Shago, Mary; Choi, Kunho; Weksberg, Rosanna A.; Nowaczyk, Malgorzata J.M.; Wang, Weidong; Jaspers, Nicolaas G.J.; Boerkoel, Cornelius F.

2012-01-01

294

Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.  

PubMed

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

295

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

296

Metabolic profiling reveals local and systemic responses of host plants to nematode parasitism.  

PubMed

The plant parasitic beet cyst nematode Heterodera schachtii induces syncytial feeding structures in Arabidopsis roots. The feeding structures form strong sink tissues that have been suggested to be metabolically highly active. In the present study, metabolic profiling and gene targeted expression analyses were performed in order to study the local and systemic effects of nematode infection on the plant host. The results showed increased levels of many amino acids and phosphorylated metabolites in syncytia, as well as high accumulation of specific sugars such as 1-kestose that do not accumulate naturally in Arabidopsis roots. A correlation-based network analysis revealed highly activated and coordinated metabolism in syncytia compared to non-infected control roots. An integrated analysis of the central primary metabolism showed a clear coherence of metabolite and transcript levels, indicating transcriptional regulation of specific pathways. Furthermore, systemic effects of nematode infection were demonstrated by correlation-based network analysis as well as independent component analysis. 1-kestose, raffinose, alpha,alpha-trehalose and three non-identified analytes showed clear systemic accumulation, indicating future potential for diagnostic and detailed metabolic analyses. Our studies open the door towards understanding the complex remodelling of plant metabolism in favour of the parasitizing nematode. PMID:20374527

Hofmann, Julia; El Ashry, Abd El Naser; Anwar, Shahbaz; Erban, Alexander; Kopka, Joachim; Grundler, Florian

2010-06-01

297

Apoplast proteome reveals that extracellular matrix contributes to multi-stress response in poplar  

SciTech Connect

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

Pechanova, Olga [Mississippi State University (MSU); Hsu, Chuan-Yu [Mississippi State University (MSU); Adams, Joshua P. [Mississippi State University (MSU); Pechan, Tibor [Mississippi State University (MSU); Vandervelde, Lindsay [Mississippi State University (MSU); Drnevich, Jenny [University of Illinois, Urbana-Champaign; Jawdy, Sara [ORNL; Adeli, Ardeshir [USDA-ARS, Mississippi State; Suttle, Jeffrey [USDA-ARS, Fargo, ND; Lawrence, Amanda [Mississippi State University (MSU); Tschaplinski, Timothy J [ORNL; Seguin, Armand [Canadian Forest Service, Sainte-Foy, Quebec; Yuceer, Cetin [Mississippi State University (MSU)

2010-01-01

298

Electrical responses reveal the temporal dynamics of brain events during involuntary attention switching.  

PubMed

Surviving in the natural environment requires the rapid switching of attention among potentially relevant stimuli. We studied electrophysiologically the involuntary switching time in humans performing a task designed to study brain mechanisms of involuntary attention and distraction (C. Escera et al., 1998, J. Cogn. Neurosci., 10, 590-604). Ten subjects were instructed to discriminate visual stimuli preceded by a task-irrelevant sound, this being either a repetitive tone (P = 0.8) or a distracting sound, i.e. a slightly higher deviant tone (P = 0.1) or an environmental novel sound (P = 0.1). In different conditions, the sounds preceded the visual stimuli by 245 or 355 ms. Deviant tones and novel sounds prolonged reaction times significantly to subsequent visual stimuli by 7.4 (P < 0.02) and 15.2 ms (P < 0.003), respectively. In addition to a mismatch negativity (MMN) and a positive-polarity, 320-ms latency, P3a event-related potential associated, respectively, with detection of the distracting sound and the subsequent orienting of attention to it, a late frontal negative deflection was observed in distracting trials. The peak latency of this brain response from sound onset was 580 ms in the 245-ms condition and 115 ms longer in the 355-ms condition (P < 0.001), peaking consequently at 340 ms from visual stimulus onset, irrespective of the onset of the distracting sound. We suggest that this late frontal negative response may signal over the scalp the process of reallocating attention back to the original task after momentary distraction, and therefore that recovering from distraction may take a similar shifting time as orienting attention involuntarily towards unexpected novelty. PMID:11576192

Escera, C; Yago, E; Alho, K

2001-09-01

299

Effects of gait speed on stability of walking revealed by simulated response to tripping perturbation.  

PubMed

The objective of this work was to study stability of walking over a range of gait speeds by means of muscle-driven simulations. Fast walking has previously been related to high likelihood of falling due to tripping. Various measures of stability have shown different relationships between walking speed and stability. These measures may not be associated with tripping, so it is unclear whether the increase in likelihood of falling is explicable by an increase in instability. Here, stability with respect to a constant tripping perturbation was quantified as the immediate passive response of torso to the perturbation. Subject-specific muscle-driven simulations of eight young healthy subjects walking at four speeds, created by combining a generic musculoskeletal model with gait data, were analyzed. In the simulations, short perturbations were performed several times throughout the swing-phase by applying a constant backward force to the swing-foot of the model. Maxima of changes in the torso (angular) velocity components during the swing-phase were studied. These changes in the velocity components correlated with the walking speed as follows: anterior-posterior r=0.37 (p<0.05), vertical r=0.41 (p<0.05), and medio-lateral r=-0.40 (p<0.05). Of the angular velocity components, only the vertical component correlated statistically significantly with speed, r=0.52 (p<0.01). The weak and varying speed effects suggest that fast walking is not necessarily more unstable than slow walking, in the sense of response to a constant perturbation. PMID:24091248

Klemetti, Rudolf; Moilanen, Petro; Avela, Janne; Timonen, Jussi

2014-01-01

300

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

301

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

302

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

PubMed

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

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

2010-12-01

303

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

PubMed Central

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

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

2013-01-01

304

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

305

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

PubMed

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

306

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

PubMed Central

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

2010-01-01

307

Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model  

PubMed Central

Visceral hypersensitivity is an important characteristic feature of functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). This study evaluated the effect of Schisandra chinensis on visceral hyperalgesia induced by neonatal maternal separation (NMS) in an IBS rat model. The visceromotor responses to colorectal balloon distension (CRD) were measured by abdominal withdrawal reflex (AWR) and electromyographic activities (EMG). NMS control rats (receiving vehicle) underwent aggravated visceral pain in response to CRD as compared to normal rats, evidenced by the reduced pain threshold, enhanced AWR scores and EMG responses. Treatment with a 70% ethanol extract of S. chinensis (0.3 g/kg and 1.5 g/kg per day) for seven days resulted in an increase in the pain threshold (NMS control: 19.1 ± 1.0 mmHg vs low-dose: 24.8 ± 1.3 mmHg and high-dose: 25.2 ± 1.8 mmHg, p<0.01), and abolished the elevated AWR and EMG responses to CRD in NMS rats (AUC values of EMG response curve were: 1952 ± 202 in NMS control group vs 1074 ± 90 in low-dose group and 1145 ± 92 in high-dose group, p<0.001), indicating that S. chinensis could reverse the visceral hypersensitivity induced by early-life stress event. The result of ELSA measurement shows that the elevated serotonin (5-HT) level in the distal colon of NMS rats returned to normal level after treatment with S. chinensis. Moreover, the increase in pain threshold in rats treated with S. chinensis was associated with a decline of the mRNA level of 5-HT3 receptor in the distal colon. All available results demonstrate that S. chinensis can reverse visceral hypersensitivity induced by neonatal-maternal separation, and the effect may be mediated through colonic 5-HT pathway in the rat. PMID:22230486

Yang, Jia-Ming; Xian, Yan-Fang; Ip, Paul SP; Wu, Justin CY; Lao, Lixing; Fong, Harry HS; Sung, Joseph JY; Berman, Brian; Yeung, John HK; Che, Chun-Tao

2012-01-01

308

Dentin hypersensitivity: Recent trends in management  

PubMed Central

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

Miglani, Sanjay; Aggarwal, Vivek; Ahuja, Bhoomika

2010-01-01

309

Hypersensitivity of lung vessels to catecholamines in systemic hypertension.  

PubMed Central

Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper-reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over-reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure. PMID:3089490

Guazzi, M D; Alimento, M; Fiorentini, C; Pepi, M; Polese, A

1986-01-01

310

Hypersensitivity to Aeroallergens in Patients with Nasobronchial Allergy  

PubMed Central

ABSTRACT Background: Aeroallergens are the most common causes of allergy. Aim: The aim of this study was to determine hypersensitivity to aeroallergens in patients with nasobronchial allergy. Methods: This retrospective population study included 2254 patients with nasobronchial allergy, from late adolescents to adults. Their response to aeroallergens was assessed by skin prick tests. Results: More patients had rhinitis (72.7%), than asthma (27.6%). Although majority of patients were female, allergy is more common in men than in women (p<0.05). Both groups of patients had the greatest number of positive skin prick tests for Dermatophagoides pteronyssinus (27.5%) and weed pollens (21.9%), followed by grass (18.3%) and tree pollens (10.1%). Ragweed is the most common positive weed pollen in both groups, more in patients with rhinitis (p=0.022). The cocksfoot is the most common grass pollen in rhinitis group (15.3%), but meadow grass (12.6%) in asthma patients. Birch is the most common tree allergen in the both groups. Conclusions: More patients with nasobronchial allergy have rhinitis than asthma. Skin prick tests are usually positive for Dermatophagoides pteronyssinus and weed pollens, followed by grass and tree pollens, and they are more common positive in patients with rhinitis than asthma. PMID:24937928

Balaban, Jagoda; Bijelic, Radojka; Milicevic, Snjezana

2014-01-01

311

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

PubMed Central

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

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

2013-01-01

312

A secretomics analysis reveals major differences in the macrophage responses towards different types of carbon nanotubes.  

PubMed

Abstract Certain types of carbon nanotubes (CNT) can evoke inflammation, fibrosis and mesothelioma in vivo, raising concerns about their potential health effects. It has been recently postulated that NLRP3 inflammasome activation is important in the CNT-induced toxicity. However, more comprehensive studies of the protein secretion induced by CNT can provide new information about their possible pathogenic mechanisms. Here, we studied protein secretion from human macrophages with a proteomic approach in an unbiased way. Human monocyte-derived macrophages (MDM) were exposed to tangled or rigid, long multi-walled CNT (MWCNT) or crocidolite asbestos for 6?h. The growth media was concentrated and secreted proteins were analyzed using 2D-DIGE and DeCyder software. Subsequently, significantly up- or down-regulated protein spots were in-gel digested and identified with an LC-MS/MS approach. Bioinformatics analysis was performed to reveal the different patterns of protein secretion induced by these materials. The results show that both long rigid MWCNT and asbestos elicited ample and highly similar protein secretion. In contrast, exposure to long tangled MWCNT induced weaker protein secretion with a more distinct profile. Secretion of lysosomal proteins followed the exposure to all materials, suggesting lysosomal damage. However, only long rigid MWCNT was associated with apoptosis. This analysis suggests that the CNT toxicity in human MDM is mediated via vigorous secretion of inflammation-related proteins and apoptosis. This study provides new insights into the mechanisms of toxicity of high aspect ratio nanomaterials and indicates that not all types of CNT are as hazardous as asbestos fibers. PMID:25325160

Palomäki, Jaana; Sund, Jukka; Vippola, Minnamari; Kinaret, Pia; Greco, Dario; Savolainen, Kai; Puustinen, Anne; Alenius, Harri

2014-10-17

313

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

PubMed Central

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

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

2012-01-01

314

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

315

Landau-Levich flow visualization: Revealing the flow topology responsible for the film thickening phenomena  

NASA Astrophysics Data System (ADS)

An extensive body of experimental work has proven the validity of the analysis of Landau and Levich, who were the first to determine theoretically the thickness of the film deposited by the withdrawal of a flat substrate from a bath of liquid with a clean interface. However, there are a number of experimental investigations that have shown that surfactants in the liquid may result in a thickening of the deposited film. Marangoni phenomena have usually been considered responsible for this effect. However, some careful experiments and numerical simulations reported in the literature seemed to rule out this view as the cause of the observed behavior. Despite all these studies and the number of reports of film thickening, an experimental study of the flow field close to the coated substrate in the presence of surfactants has never been undertaken. In this paper we will present a set of flow visualization experiments on coating of a planar substrate in the range of capillary numbers 10-4 ? Ca ? 10-3 for sodium dodecyl sulfate solutions with bulk concentrations of 0.25 CMC ? C ? 5.0 CMC (critical micelle concentration). It was evident during experiments that the flow field near the meniscus region exhibits patterns that can only be explained with a stagnation point residing in the bulk and not at the interface. As opposed to patterns with an interfacial stagnation point, the observed flow fields allow for the increase in film thickness due to the presence of surfactants compared to the clean interface case.

Mayer, H. C.; Krechetnikov, R.

2012-05-01

316

Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage.  

PubMed

Nuclear functions including gene expression, DNA replication and genome maintenance intimately rely on dynamic changes in chromatin organization. The movements of chromatin fibers might play important roles in the regulation of these fundamental processes, yet the mechanisms controlling chromatin mobility are poorly understood owing to methodological limitations for the assessment of chromatin movements. Here, we present a facile and quantitative technique that relies on photoactivation of GFP-tagged histones and paired-particle tracking to measure chromatin mobility in live cells. We validate the method by comparing live cells to ATP-depleted cells and show that chromatin movements in mammalian cells are predominantly energy dependent. We also find that chromatin diffusion decreases in response to DNA breaks induced by a genotoxic drug or by the ISceI meganuclease. Timecourse analysis after cell exposure to ionizing radiation indicates that the decrease in chromatin mobility is transient and precedes subsequent increased mobility. Future applications of the method in the DNA repair field and beyond are discussed. PMID:25501817

Liu, Jing; Vidi, Pierre-Alexandre; Lelièvre, Sophie A; Irudayaraj, Joseph M K

2015-02-01

317

Methyl jasmonate responsive proteins in Brassica napus guard cells revealed by iTRAQ-based quantitative proteomics.  

PubMed

Stomata on leaf epidermis formed by pairs of guard cells control CO(2) intake and water transpiration, and respond to different environmental conditions. Stress-induced stomatal closure is mediated via an intricate hormone network in guard cells. Although methyl jasmonate (MeJA) has been intensively studied for its function in plant defense, the molecular mechanisms underlying its function in stomatal movement are not fully understood. Here we report the effects of MeJA on Brassica napus stomatal movement and H(2)O(2) production. Using the isobaric tags for relative and absolute quantitation (iTRAQ) approach, we have identified 84 MeJA-responsive proteins in B. napus guard cells. Most of the genes encoding these proteins contain jasmonate-responsive elements in the promoters, indicating that they are potentially regulated at the transcriptional level. Among the identified proteins, five protein changes after MeJA treatment were validated using Western blot analysis. The identification of the MeJA-responsive proteins has revealed interesting molecular mechanisms underlying MeJA function in guard cells, which include homeostasis of H(2)O(2) production and scavenging, signaling through calcium oscillation and protein (de)phosphorylation, gene transcription, protein modification, energy balance, osmoregulation, and cell shape modulation. The knowledge of the MeJA-responsive proteins has improved our understanding of MeJA signaling in stomatal movement, and it may be applied to crop engineering for enhanced yield and stress tolerance. PMID:22639841

Zhu, Mengmeng; Dai, Shaojun; Zhu, Ning; Booy, Aaron; Simons, Brigitte; Yi, Sarah; Chen, Sixue

2012-07-01

318

Transcriptomic and Proteomic Analyses Reveal Key Innate Immune Signatures in the Host Response to the Gastrointestinal Pathogen Campylobacter concisus.  

PubMed

Pathogenic species within the genus Campylobacter are responsible for a considerable burden on global health. Campylobacter concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on Campylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to Campylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. concisus. Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. concisus-infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. concisus, which included the activation of key inflammatory pathways involving CREB1, NF-?B, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. concisus. PMID:25486993

Kaakoush, Nadeem O; Deshpande, Nandan P; Man, Si Ming; Burgos-Portugal, Jose A; Khattak, Faisal A; Raftery, Mark J; Wilkins, Marc R; Mitchell, Hazel M

2015-02-01

319

RNA-seq reveals regional differences in transcriptome response to heat stress in the marine snail Chlorostoma funebralis.  

PubMed

To investigate the role of gene expression in adaptation of marine ectotherms to different temperatures, we examined the transcriptome-wide thermal stress response in geographically separated populations of the intertidal snail Chlorostoma funebralis. Snails from two southern (heat tolerant) and two northern (heat sensitive) populations were acclimated to a common thermal environment, exposed to an environmentally relevant thermal stress and analysed using RNA-seq. Pooling across all populations revealed 306 genes with differential expression between control and heat-stressed samples, including 163 significantly upregulated and 143 significantly downregulated genes. When considered separately, regional differences in response were widely apparent. Heat shock proteins (Hsps) were upregulated in both regions, but the magnitude of response was significantly greater in northern populations for most Hsp70s, while the southern populations showed greater upregulation for approximately half of the Hsp40s. Of 177 stress-responsive genes in northern populations, 55 responded to heat stress only in northern populations. Several molecular chaperones and antioxidant genes that were not differentially expressed in southern populations showed higher expression under control conditions compared with northern populations. This suggests that evolution of elevated expression of these genes under benign conditions preadapts the southern populations to frequent heat stress and contributes to their higher thermal tolerance. These results indicate that evolution has resulted in different transcriptome responses across populations, including upregulation of genes in response to stress and preadaptation of genes in anticipation of stress (based on evolutionary history of frequent heat exposure). The relative importance of the two mechanisms differs among gene families and among populations. PMID:25524431

Gleason, Lani U; Burton, Ronald S

2015-02-01

320

Characterization of the immunogenetic basis of ultraviolet-B light effects on contact hypersensitivity induction.  

PubMed Central

Ultraviolet-B (UVB) light has proven to be deleterious to the skin immune system in mice, and one major consequence is impairment of the induction of contact hypersensitivity (CH) to haptens applied to UVB-exposed skin. It has been shown recently that the damaging effects of UVB on CH are mediated primarily by tumour necrosis factor-alpha (TNF-alpha). Moreover, not all strains of mice are equally susceptible to the deleterious effects of UVB. Mice that develop CH when hapten is applied to UVB-exposed skin are termed UVB-resistant (UVB-R), whereas mice that fail to acquire CH under these circumstances are termed UVB-susceptible (UVB-S). In the present experiments, we have characterized the UVB-susceptibility of numerous, genetically disparate inbred strains of mice by applying dinitrofluorobenzene (DNFB) epicutaneously to normal and to UVB-exposed body wall skin. The results indicate that the intensities of CH responses of these different strains were distributed in a bimodal fashion, with means at 92% and 28.5% of positive control responses. Among the strains with CH values distributed around the higher mean (i.e. UVB-R mice), the intensity of CH responses after UVB irradiation was uniformly greater than 75% of the intensity found among their positive controls. By contrast, among the strains with CH values distributed around the lower mean (i.e. UVB-S mice), the intensity of CH responses after UVB exposure was uniformly less than 60% of the intensity displayed by their positive controls. The phenotypic traits of UVB-S and UVB-R appear, therefore, to be genetically determined. To that end, we provide in this report additional evidence that UVB-S is a polygenically determined trait that is dictated by polymorphisms at a locus within H-2, and at the Lps locus. Resistance to UVB radiation is a recessive trait, and requires homozygosity of resistance alleles at one or both of the two participating loci, whereas UVB-S acts as a dominant trait. Among H-2 congenic strains of mice that are lipopolysaccharide (LPS)-sensitive (Lpsn), UVB radiation impaired the induction of CH to DNFB in all mice except those of the H-2d and H-2a haplotypes. Thus, UVB-susceptibility is dictated by alleles at two, independent genetic loci that can influence transcriptional and translational activity of the Tnf-alpha gene. The potential biological and medical meaning of regulatory polymorphisms governing TNF-alpha production in the skin may be revealed by the recent demonstration that UVB-susceptibility and UVB-resistance are phenotypic traits in humans.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8206509

Kurimoto, I; Streilein, J W

1994-01-01

321

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

PubMed Central

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

Atherton, Jeremy F.; Surmeier, D. James

2013-01-01

322

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, Jörg

2014-01-01

323

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

PubMed

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

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

2014-06-01

324

Prostaglandin I2-IP signaling promotes Th1 differentiation in a mouse model of contact hypersensitivity.  

PubMed

PGI(2), which exerts its actions via its specific Gs-coupled I prostanoid receptor (IP), is known to be present in the lymph nodes, but its roles in acquired cutaneous immune responses remain unclear. To investigate the role of PGI(2)-IP signaling in cutaneous immune responses, we applied IP-deficient (Ptgir(-/-)) mice to contact hypersensitivity as a model of acquired immune response and found that Ptgir(-/-) mice exhibited a significantly decreased contact hypersensitivity response. Lymph node cells from sensitized Ptgir(-/-) mice exhibited decreased IFN-gamma production and a smaller T-bet(+) subset compared with control mice. PGI synthase and IP expression were detected in dendritic cells and T cells, respectively, by quantitative real-time PCR analysis, suggesting that PGI(2) produced by dendritic cells acts on IP in T cells. In fact, in vitro Th1 differentiation was enhanced by an IP agonist, and this enhancement was nullified by protein kinase A inhibitor. These results suggest that PGI(2)-IP signaling promotes Th1 differentiation through a cAMP-protein kinase A pathway and thereby initiates acquired cutaneous immune responses. PMID:20400695

Nakajima, Saeko; Honda, Tetsuya; Sakata, Daiji; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Moniaga, Catharina Sagita; Watanabe, Takeshi; Miyachi, Yoshiki; Narumiya, Shuh; Kabashima, Kenji

2010-05-15

325

Fast periodic presentation of natural images reveals a robust face-selective electrophysiological response in the human brain.  

PubMed

We designed a fast periodic visual stimulation approach to identify an objective signature of face categorization incorporating both visual discrimination (from nonface objects) and generalization (across widely variable face exemplars). Scalp electroencephalographic (EEG) data were recorded in 12 human observers viewing natural images of objects at a rapid frequency of 5.88 images/s for 60 s. Natural images of faces were interleaved every five stimuli, i.e., at 1.18 Hz (5.88/5). Face categorization was indexed by a high signal-to-noise ratio response, specifically at an oddball face stimulation frequency of 1.18 Hz and its harmonics. This face-selective periodic EEG response was highly significant for every participant, even for a single 60-s sequence, and was generally localized over the right occipitotemporal cortex. The periodicity constraint and the large selection of stimuli ensured that this selective response to natural face images was free of low-level visual confounds, as confirmed by the absence of any oddball response for phase-scrambled stimuli. Without any subtraction procedure, time-domain analysis revealed a sequence of differential face-selective EEG components between 120 and 400 ms after oddball face image onset, progressing from medial occipital (P1-faces) to occipitotemporal (N1-faces) and anterior temporal (P2-faces) regions. Overall, this fast periodic visual stimulation approach provides a direct signature of natural face categorization and opens an avenue for efficiently measuring categorization responses of complex visual stimuli in the human brain. PMID:25597037

Rossion, Bruno; Torfs, Katrien; Jacques, Corentin; Liu-Shuang, Joan

2015-01-01

326

B cells are not required for T cell priming in low zone tolerance to contact allergens and contact hypersensitivity.  

PubMed

Low zone tolerance (LZT) to contact allergens is induced by epicutaneous exposure to haptens in subsensitizing doses resulting in an inhibition of contact hypersensitivity (CHS), which, in contrast, occurs after sensitization with immunogenic doses of allergens. Performing the protocol of tolerance induction resulted in robust LZT to allergens in B cell-deficient mice in vivo, indicating that B cells are not required for the induction and effector phase of LZT. However, CHS reactions in vivo were restricted in B cell-deficient mice as compared to wild-type (WT) mice. In contrast, analysis of hapten-specific T cell activation in vitro revealed a strong proliferative response of T cells derived from both WT and B cell-deficient sensitized mice. Similar to WT animals, T cells obtained from tolerized B cell-deficient mice produced a Tc2 cytokine pattern of LZT with high levels of IL-4 and IL-10, whereas sensitization of B cell-deficient mice resulted in the typical Tc1 cytokine profile of CHS. Adoptive transfer of CD8+ effector T cells from tolerized or sensitized B cell-deficient mice induced significant LZT or CHS reactions, respectively, in WT recipients, demonstrating that the development of hapten-specific effector CD8+ T cells of LZT and CHS is independent of B cells. PMID:15376190

Seidel-Guyenot, Wolfgang; Alt, Ruth; Perschon, Sylwia; Knop, Jürgen; Steinbrink, Kerstin

2004-11-01

327

Evaluation of the clinical efficacy of potassium nitrate desensitizing mouthwash and a toothpaste in the treatment of dentinal hypersensitivity  

PubMed Central

Potassium Nitrate has been used as a desensitizing agent to treat dentinal hypersensitivity. The effectiveness of a potassium nitrate is evaluated both in the form of a toothpaste and a mouthwash in a clinical study. Thirty patients were assessed using evaporative stimuli and thermal stimuli and response was evaluated using Visual Analogue Scale at baseline, at 2 weeks and 4 weeks. The patients were divided into. group I: fifteen patients who used toothpaste containing 5% potassium nitrate, sodium fluoride, xylitol and triclosan, group II: Fifteen patients who used mouthwash containing 3% potassium nitrate, sodium fluoride, xylitol and triclosan . The results of both the assessment methods indicated that potassium nitrate toothpaste as well as mouthwash showed statistically significant decrease in the sensitivity score on a Visual Analogue Scale. This was effective in reducing the symptoms of dentinal hypersensitivity when used either as toothpaste or as a mouthwash. But, there were no statistically significant differences between the groups, although both were effective in the treatment of hypersensitivity. Key words:Dentinal hypersensitivity, potassium nitrate toothpaste, potassium nitrate mouthwash, desensitizing agents. PMID:24558521

Sharma, Sunita; Uppoor, Ashita

2012-01-01

328

Revision total hip arthroplasty due to pain from hypersensitivity to cobalt-chromium in total hip arthroplasty.  

PubMed

We report a case with hypersensitivity to CoCr in total hip arthroplasty coupled with conventional polyethylene and CoCr femoral head. The patient complained of left hip pain and systemic fever, and computed tomography imaging revealed a periprosthetic cystic lesion, so we performed revision total hip arthroplasty using a titanium stem and ceramic head and highly crosslinked polyethylene. Hip pain and cystic lesion disappeared 3 years after revision surgery. PMID:21130600

Kosukegawa, Ima; Nagoya, Satoshi; Kaya, Mitsunori; Sasaki, Koichi; Sasaki, Mikito; Yamashita, Toshihiko

2011-09-01

329

520-d Isolation and confinement simulating a flight to Mars reveals heightened immune responses and alterations of leukocyte phenotype.  

PubMed

During interplanetary exploration, chronic stress caused by long term isolation and confinement in the spacecraft is one of the major concerns of physical and psychological health of space travelers. And for human on Earth, more and more people live in an isolated condition, which has become a common social problem in modern western society. Collective evidences have indicated prolonged chronic stress could bring big influence to human immune function, which may lead to a variety of health problems. However, to what extent long-term isolation can affect the immune system still remains largely unknow. A simulated 520-d Mars mission provided an extraordinary chance to study the effect of prolonged isolation. Six healthy males participated in this mission and their active neuroendocrine and immune conditions were studied with saliva and blood samples from all participants on chosen time points during the isolation period. As a typical neuroendocrine parameter, stress hormone cortisol was measured in the morning saliva samples. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. Using an ex vivo viral infection simulation assay we assessed the immune response changes characterized by the ability to produce representative endogenous pro-inflammatory cytokines. The results of this study revealed elevated cortisol levels, increased lymphocyte amount and heightened immune responses, suggesting that prolonged isolation acting as chronic stressors are able to trigger leukocyte phenotype changes and poorly controlled immune responses. PMID:24704568

Yi, B; Rykova, M; Feuerecker, M; Jäger, B; Ladinig, C; Basner, M; Hörl, M; Matzel, S; Kaufmann, I; Strewe, C; Nichiporuk, I; Vassilieva, G; Rinas, K; Baatout, S; Schelling, G; Thiel, M; Dinges, D F; Morukov, B; Choukèr, A

2014-08-01

330

Voltage Sensitive Dye Imaging Reveals Improved Topographic Activation of Cortex in Response to Manipulation of Thalamic Microstimulation Parameters  

PubMed Central

Voltage sensitive dye (VSD) 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 the 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 stimulating 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. PMID:22327024

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

2012-01-01

331

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

SciTech Connect

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

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

2013-08-15

332

A dose-response strategy reveals differences between normal-weight and obese men in their metabolic and inflammatory responses to a high-fat meal.  

PubMed

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. PMID:24812072

Schwander, Flurina; Kopf-Bolanz, Katrin A; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G; Piya, Milan K; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

2014-10-01

333

Effect of premedications in a murine model of asparaginase hypersensitivity.  

PubMed

A murine model was developed that recapitulates key features of clinical hypersensitivity to Escherichia coli asparaginase. Sensitized mice developed high levels of anti-asparaginase IgG antibodies and had immediate hypersensitivity reactions to asparaginase upon challenge. Sensitized mice had complete inhibition of plasma asparaginase activity (P = 4.2 × 10(-13)) and elevated levels of mouse mast cell protease 1 (P = 6.1 × 10(-3)) compared with nonsensitized mice. We investigated the influence of pretreatment with triprolidine, cimetidine, the platelet activating factor (PAF) receptor antagonist CV-6209 [2-(2-acetyl-6-methoxy-3,9-dioxo-4,8-dioxa-2,10-diazaoctacos-1-yl)-1-ethyl-pyridinium chloride], or dexamethasone on the severity of asparaginase-induced allergies. Combining triprolidine and CV-6209 was best for mitigating asparaginase-induced hypersensitivity compared with nonpretreated, sensitized mice (P = 1.2 × 10(-5)). However, pretreatment with oral dexamethasone was the only agent capable of mitigating the severity of the hypersensitivity (P = 0.03) and partially restoring asparaginase activity (P = 8.3 × 10(-4)). To rescue asparaginase activity in sensitized mice without requiring dexamethasone, a 5-fold greater dose of asparaginase was needed to restore enzyme activity to a similar concentration as in nonsensitized mice. Our results suggest a role of histamine and PAF in asparaginase-induced allergies and indicate that mast cell-derived proteases released during asparaginase allergy may be a useful marker of clinical hypersensitivity. PMID:25573198

Fernandez, Christian A; Smith, Colton; Karol, Seth E; Ramsey, Laura B; Liu, Chengcheng; Pui, Ching-Hon; Jeha, Sima; Evans, William E; Finkelman, Fred D; Relling, Mary V

2015-03-01

334

Suppression of tuberculin hypersensitivity during influenza infection in mice.  

PubMed Central

Tuberculin hypersensitivity was examined during acute influenza infection in mice. Employing the footpad test as a measure of delayed-type hypersensitivity, it was noted that tuberculin hypersensitivity was suppressed temporarily beginning on day 3 and continuing through days 10 to 16 following intranasal infection with influenza A/PR8. These changes occurred at a time when influenza virus was replicating in lung tissue. Suppression of footpad swelling was not detected when mice were administered live virus intravenously, were given Formalin-inactivated virus intranasally, or were immunized against influenza before intranasal infection. Transient reduction of total circulating lymphocytes also occurred during influenza infection but did not correlate with the duration of footpad suppression. Because this model system reproduces many of the alterations in immunological function reported to occur during influenza infection in humans, it should provide a useful tool for investigating mechanisms of influenza-induced immunosuppression. Images PMID:457284

Massanari, R M

1979-01-01

335

Atypical presentation of fever as hypersensitivity reaction to oxaliplatin.  

PubMed

Oxaliplatin, a third-generation, platinum-based agent is widely used, most commonly in the FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) regimen, which is the first-line therapy in metastatic colorectal adenocarcinoma and adjuvant chemotherapy in stage III colorectal cancer. Platinum-based products are well known for causing hypersensitivity reactions. Fever associated with oxaliplatin-hypersensitivity reactions typically follows a specific pattern. It usually starts during the oxaliplatin infusion or immediately after (within hours instead of days) and happens after several administrations (mean 2-25) with unpredictable clinical presentations. We report a case of oxaliplatin-induced hypersensitivity reaction manifesting as fever but with unusual presentation than the aforementioned features. PMID:25361599

Khurana, Arushi; Mitsis, Demytra; Kowlgi, Gurukripa N; Holle, Lisa M; Clement, Jessica M

2014-10-30

336

Transcriptomics of the Rice Blast Fungus Magnaporthe oryzae in Response to the Bacterial Antagonist Lysobacter enzymogenes Reveals Candidate Fungal Defense Response Genes  

PubMed Central

Plants and animals have evolved a first line of defense response to pathogens called innate or basal immunity. While basal defenses in these organisms are well studied, there is almost a complete lack of understanding of such systems in fungal species, and more specifically, how they are able to detect and mount a defense response upon pathogen attack. Hence, the goal of the present study was to understand how fungi respond to biotic stress by assessing the transcriptional profile of the rice blast pathogen, Magnaporthe oryzae, when challenged with the bacterial antagonist Lysobacter enzymogenes. Based on microscopic observations of interactions between M. oryzae and wild-type L. enzymogenes strain C3, we selected early and intermediate stages represented by time-points of 3 and 9 hours post-inoculation, respectively, to evaluate the fungal transcriptome using RNA-seq. For comparative purposes, we also challenged the fungus with L. enzymogenes mutant strain DCA, previously demonstrated to be devoid of antifungal activity. A comparison of transcriptional data from fungal interactions with the wild-type bacterial strain C3 and the mutant strain DCA revealed 463 fungal genes that were down-regulated during attack by C3; of these genes, 100 were also found to be up-regulated during the interaction with DCA. Functional categorization of genes in this suite included those with roles in carbohydrate metabolism, cellular transport and stress response. One gene in this suite belongs to the CFEM-domain class of fungal proteins. Another CFEM class protein called PTH11 has been previously characterized, and we found that a deletion in this gene caused advanced lesion development by C3 compared to its growth on the wild-type fungus. We discuss the characterization of this suite of 100 genes with respect to their role in the fungal defense response. PMID:24098512

Mathioni, Sandra M.; Patel, Nrupali; Riddick, Bianca; Sweigard, James A.; Czymmek, Kirk J.; Caplan, Jeffrey L.; Kunjeti, Sridhara G.; Kunjeti, Saritha; Raman, Vidhyavathi; Hillman, Bradley I.; Kobayashi, Donald Y.; Donofrio, Nicole M.

2013-01-01

337

Human CD4+CD25low adaptive T regulatory cells suppress delayed-type hypersensitivity during transplant tolerance.  

PubMed

Adaptive T regulatory (T(R)) cells mediate the suppression of donor-specific, delayed-type hypersensitivity (DTH) in tolerant organ transplant recipients. We hypothesized that cells belonging to the CD4(+)CD25(+) T cell subset but distinct from natural T(R) cells may fulfill this role. To test this hypothesis, PBMC and biopsy samples from two tolerant kidney transplant recipients (K1 and K2) were analyzed. When transferred with recipient APC into a SCID mouse footpad, CD4(+) T cells were hyporesponsive in DTH to donor type HLA-B Ags and derivative allopeptides. However, anti-human TGF-beta1 Ab revealed a response to immunodominant allopeptides in both patients, suggesting that CD4(+) T effector (T(E)) cells coexisted with suppressive, TGF-beta1-producing CD4(+) T(R) cells. During in vitro culture, allopeptide stimulation induced both IFN-gamma-producing and surface TGF-beta1(+) T cells. The relative strength of the latter response in patient K1 was inversely correlated with the level of systemic anti-donor DTH, which varied over a 6-year interval. Allopeptide-induced surface TGF-beta1 expression was found primarily in Forkhead box P3 (FoxP3)-negative CD4(+)CD25(low) T cells, which could adoptively transfer suppression of donor-specific DTH. Biopsy samples contained numerous surface TGF-beta1(+) mononuclear cells that costained for CD4 and, less frequently CD25, but were negative for FoxP3. The CD4(+)TGF-beta1(+) T cells were localized primarily to the tubulointerstitium, whereas TGF-beta1(-)FoxP3(+)CD25(+) cells were found mainly in lymphoid aggregates. Thus, adaptive T(R) cells suppressing T(E) cell responses to donor allopeptides in two tolerant patients appear to be functionally and phenotypically distinct from CD4(+)CD25(high)FoxP3(+) T cells. PMID:17339499

Xu, Qingyong; Lee, Junglim; Jankowska-Gan, Ewa; Schultz, Jackie; Roenneburg, Drew A; Roennburg, Drew A; Haynes, Lynn D; Kusaka, Satoshi; Sollinger, Hans W; Knechtle, Stuart J; VanBuskirk, Anne M; Torrealba, Jose R; Burlingham, William J

2007-03-15

338

A systems biology approach reveals the role of a novel methyltransferase in response to chemical stress and lipid homeostasis.  

PubMed

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

2011-10-01

339

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

SciTech Connect

High performance mass spectrometry instrumentation coupled with improved protein extraction techniques enable 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 Firmicutes dominated the biostimulated aquifer community. Proteome characterization revealed distinct differences in protein expression between the microbial biomass collected from groundwater influenced by biostimulation and groundwater collected up-gradient of the EVO injection points. In particular, proteins involved in ammonium assimilation, EVO degradation, and polyhydroxybutyrate (PHB) granule formation were prominent following biostimulation. Interestingly, the atypical NosZ of a Dechloromonas sp. was highly expressed suggesting active nitrous oxide (N2O) respiration. c-type cytochromes were barely detected, as was citrate synthase, a biomarker for hexavalent uranium reduction activity, suggesting that metal reduction has not commenced 4 days post EVO delivery. Environmental metaproteomics identified microbial community responses to biostimulation and elucidated active pathways demonstrating the value of this technique for complementing nucleic acid-based approaches.

Chourey, Karuna [ORNL] [ORNL; Nissen, Silke [ORNL] [ORNL; Vishnivetskaya, T. [University of Tennessee, Knoxville (UTK)] [University of Tennessee, Knoxville (UTK); Shah, Manesh B [ORNL] [ORNL; Pffifner, Susan [University of Tennessee, Knoxville (UTK)] [University of Tennessee, Knoxville (UTK); Hettich, Robert {Bob} L [ORNL; Loeffler, Frank E [ORNL] [ORNL

2013-01-01

340

Transcriptome analysis reveals coordinated spatiotemporal regulation of hemoglobin and nitrate reductase in response to nitrate in maize roots.  

PubMed

Given the importance of nitrogen for plant growth and the environmental costs of intense fertilization, an understanding of the molecular mechanisms underlying the root adaptation to nitrogen fluctuations is a primary goal for the development of biotechnological tools for sustainable agriculture. This research aimed to identify the molecular factors involved in the response of maize roots to nitrate. cDNA-amplified fragment length polymorphism was exploited for comprehensive transcript profiling of maize (Zea mays) seedling roots grown with varied nitrate availabilities; 336 primer combinations were tested and 661 differentially regulated transcripts were identified. The expression of selected genes was studied in depth through quantitative real-time polymerase chain reaction and in situ hybridization. Over 50% of the genes identified responded to prolonged nitrate starvation and a few were identified as putatively involved in the early nitrate signaling mechanisms. Real-time results and in situ localization analyses demonstrated co-regulated transcriptional patterns in root epidermal cells for genes putatively involved in nitric oxide synthesis/scavenging. Our findings, in addition to strengthening already known mechanisms, revealed the existence of a new complex signaling framework in which brassinosteroids (BRI1), the module MKK2-MAPK6 and the fine regulation of nitric oxide homeostasis via the co-expression of synthetic (nitrate reductase) and scavenging (hemoglobin) components may play key functions in maize responses to nitrate. PMID:21762167

Trevisan, S; Manoli, A; Begheldo, M; Nonis, A; Enna, M; Vaccaro, S; Caporale, G; Ruperti, B; Quaggiotti, S

2011-10-01

341

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

342

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

343

Comparative proteomic and physiological analyses reveal the protective effect of exogenous calcium on the germinating soybean response to salt stress.  

PubMed

Calcium enhances salt stress tolerance of soybeans. Nevertheless, the molecular mechanism of calcium's involvement in resistance to salt stress is unclear. A comparative proteomic approach was used to investigate protein profiles in germinating soybeans under NaCl-CaCl2 and NaCl-LaCl3 treatments. A total of 80 proteins affected by calcium in 4-day-old germinating soybean cotyledons and 71 in embryos were confidently identified. The clustering analysis showed proteins were subdivided into 5 and 6 clusters in cotyledon and embryo, respectively. Among them, proteins involved in signal transduction and energy pathways, in transportation, and in protein biosynthesis were largely enriched while those involved in proteolysis were decreased. Abundance of nucleoside diphosphate kinase and three antioxidant enzymes were visibly increased by calcium. Accumulation of gamma-aminobutyric acid and polyamines was also detected after application of exogenous calcium. This was consistent with proteomic results, which showed that proteins involved in the glutamate and methionine metabolism were mediated by calcium. Calcium could increase the salt stress tolerance of germinating soybeans via enriching signal transduction, energy pathway and transportation, promoting protein biosynthesis, inhibiting proteolysis, redistributing storage proteins, regulating protein processing in endoplasmic reticulum, enriching antioxidant enzymes and activating their activities, accumulating secondary metabolites and osmolytes, and other adaptive responses. Biological significance Soybean (Glycine max L.), as a traditional edible legume, is being targeted for designing functional foods. During soybean germination under stressful conditions especially salt stress, newly discovered functional components such as gamma-aminobutyric acid (GABA) are rapidly accumulated. However, soybean plants are relatively salt-sensitive and the growth, development and biomass of germinating soybeans are significantly suppressed under salt stress condition. According to previous studies, exogenous calcium counters the harmful effect of salt stress and increases the biomass and GABA content of germinating soybeans. Nevertheless, the precise molecular mechanism underlying the role of calcium in resistance to salt stress is still unknown. This paper is the first study employing comparative proteomic and physiological analyses to reveal the protective effect of exogenous calcium in the germinating soybean response to salt stress. Our study links the biological events with proteomic information and provides detailed peptide information on all identified proteins. The functions of those significantly changed proteins are also analyzed. The physiological and comparative proteomic analyses revealed the putative molecular mechanism of exogenous calcium treatment induced salt stress responses. The findings from this paper are beneficial to high GABA-rich germinating soybean biomass. Additionally, these findings also might be applicable to the genetic engineering of soybean plants to improve stress tolerance. PMID:25284050

Yin, Yongqi; Yang, Runqiang; Han, Yongbin; Gu, Zhenxin

2015-01-15

344

[Three cases of hypersensitivity pneumonitis in citrus farmers].  

PubMed

We report 3 cases of occupational hypersensitivity pneumonitis in citrus farmers. They were admitted to our hospital with abnormal chest shadows with coughs, fevers and breathlessness between January and February, but their symptoms disappeared with isolation from their workplace. The diagnoses were comprehensively confirmed by their occupational histories, radiological findings, and the positive findings of environmental provocation tests. Although we cannot clearly determine the pathogenic antigen of this hypersensitivity pneumonitis, Aspergillus and Penicillium might be the causative agents, because they were detected in the patients' workplaces and in double immunodiffusion tests. In Ouchterlony's immunodiffusion test, these antigens were positive in some patients. PMID:20184252

Yasui, Hideki; Matsui, Takashi; Yokomura, Koshi; Nakano, Yutaka; Suda, Takafumi; Chida, Kingo

2010-02-01

345

Successful desensitization to brentuximab vedotin after hypersensitivity reaction.  

PubMed

Monoclonal antibodies (mAb) have become the standard of care for numerous diseases. However, side effects including infusion and hypersensitivity reactions experienced by patients continue to be a limiting factor in their use. In the therapy of cancer, treatment choices are frequently limited and minimizing side effects of a life-saving or life-prolonging therapy becomes of the utmost importance. We report the successful use of a rapid desensitization protocol in a patient with NHL, treated with a novel antibody-drug conjugate, chimeric monoclonal antibody linked to the antimitotic agent monomethyl auristatin E (MMAE) Brentuximab vedotin, who had previously developed a hypersensitivity reaction. PMID:24918568

Story, Sara K; Petrov, Andrej A; Geskin, Larisa J

2014-06-01

346

Transcriptional Response of Zebrafish Embryos Exposed to Neurotoxic Compounds Reveals a Muscle Activity Dependent hspb11 Expression  

PubMed Central

Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sopfixe mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds. PMID:22205996

Klüver, Nils; Yang, Lixin; Busch, Wibke; Scheffler, Katja; Renner, Patrick; Strähle, Uwe; Scholz, Stefan

2011-01-01

347

Serum metabolomics reveals betaine and phosphatidylcholine as potential biomarkers for the toxic responses of processed Aconitum carmichaelii Debx.  

PubMed

We recently reported that processed Aconitum carmichaelii Debx (Bai-Fu-Pian in Chinese, BFP) elicits differential toxic responses in rats under various health conditions. The present study aimed to determine the graded toxicity of BFP so as to derive a safe therapeutic rationale in clinical practice. Sensitive and reliable biomarkers of toxicity were also identified, with the corresponding metabolic pathways being unveiled. Thirty male Sprague-Dawley rats were divided into five groups (n = 6) and received oral administration of BFP extract (0.32, 0.64, 1.28 or 2.56 g kg(-1) per day) or an equal volume of drinking water (control) for 15 days. The metabolomic profiles of rat serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry (LC-Q-TOF-MS). Linear regression analysis and Ingenuity Pathway Analysis (IPA) were used to elucidate the differentiated altered metabolites and associated network relationships. Results from biochemical and histopathological examinations revealed that BFP could induce prominent toxicity in the heart, liver and kidneys at a dose of 2.56 g kg(-1) per day. Betaine up-regulation and phosphatidylcholine down-regulation were detected in the serum samples of drug-treated groups in a dose-dependent manner. In summary, betaine and phosphatidylcholine could be regarded as sensitive biomarkers for the toxic responses of BFP. Perturbations of RhoA signaling, choline metabolism and free radical scavenging were found to be partly responsible for the toxic effects of the herbal drug. Based on the metabolomics findings, we could establish a safe therapeutic range in the clinical use of BFP, with promising predictions of possible drug toxicity. PMID:24949573

Tan, Yong; Ko, Joshua; Liu, Xinru; Lu, Cheng; Li, Jian; Xiao, Cheng; Li, Li; Niu, Xuyan; Jiang, Miao; He, Xiaojuan; Zhao, Hongyan; Zhang, Zhongxiao; Bian, Zhaoxiang; Yang, Zhijun; Zhang, Ge; Zhang, Weidong; Lu, Aiping

2014-07-29

348

Multiscale distribution and bioaccumulation analysis of clofazimine reveals a massive immune system-mediated xenobiotic sequestration response.  

PubMed

Chronic exposure to some well-absorbed but slowly eliminated xenobiotics can lead to their bioaccumulation in living organisms. Here, we studied the bioaccumulation and distribution of clofazimine, a riminophenazine antibiotic used to treat mycobacterial infection. Using mice as a model organism, we performed a multiscale, quantitative analysis to reveal the sites of clofazimine bioaccumulation during chronic, long-term exposure. Remarkably, between 3 and 8 weeks of dietary administration, clofazimine massively redistributed from adipose tissue to liver and spleen. During this time, clofazimine concentration in fat and serum significantly decreased, while the mass of clofazimine in spleen and liver increased by >10-fold. These changes were paralleled by the accumulation of clofazimine in the resident macrophages of the lymphatic organs, with as much as 90% of the clofazimine mass in spleen sequestered in intracellular crystal-like drug inclusions (CLDIs). The amount of clofazimine associated with CLDIs of liver and spleen macrophages disproportionately increased and ultimately accounted for a major fraction of the total clofazimine in the host. After treatment was discontinued, clofazimine was retained in spleen while its concentrations decreased in blood and other organs. Immunologically, clofazimine bioaccumulation induced a local, monocyte-specific upregulation of various chemokines and receptors. However, interleukin-1 receptor antagonist was also upregulated, and the acute-phase response pathways and oxidant capacity decreased or remained unchanged, marking a concomitant activation of an anti-inflammatory response. These experiments indicate an inducible, immune system-dependent, xenobiotic sequestration response affecting the atypical pharmacokinetics of a small molecule chemotherapeutic agent. PMID:23263006

Baik, Jason; Stringer, Kathleen A; Mane, Gerta; Rosania, Gus R

2013-03-01

349

Skin Hypersensitivity to Sun Light Due to Doxycycline Ingestion Causing Hand Partial-Thickness Burn  

PubMed Central

Drugs hypersensitivity should be remembered when placing patients on any form of medications. In this case we present skin hypersensitivity to sun light due to doxycycline ingestion causing hand partial-thickness burn. PMID:24527377

Simman, Richard; Raynolds, David

2013-01-01

350

The Arabidopsis J Protein AtJ1 is Essential for Seedling Growth, Flowering Time Control and ABA Response.  

PubMed

We describe the in planta function of an Arabidopsis J protein gene, AtJ1. We isolated an ABA-hypersensitive mutant, named as793 (ABA-hypersensitive 793), by activation tagging screen. Analysis of the mutant revealed that T-DNA was inserted into the gene encoding AtJ1, thereby abolishing its expression. as793 plants grew very poorly under normal growth conditions; their seed setting efficiency was lower and their flowering was delayed compared with wild-type plants. Moreover, as793 plants were ABA hypersensitive and drought tolerant. In parallel analyses, we found that another AtJ1 knockout mutant acquired from the Arabidopsis Stock Center exhibited the same phenotypes as as793 and that its phenotypes could be complemented by the wild-type AtJ1. At the molecular level, we found that the expression of a large number of genes involved in embryogenesis, flowering time control and stress response was altered in as793. Others previously reported that AtJ1 is a mitochondrial protein involved in thermotolerance. Our results further indicate that AtJ1 is essential for normal plant growth, from embryogenesis to flowering and seed setting. Additionally, the ABA hypersensitivity of as793 suggests that AtJ1 may function as a negative regulator of ABA response. PMID:25311198

Park, Min Young; Kim, Soo Young

2014-12-01

351

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

352

Comparative expression analysis of genes induced during development of bacterial rot and induction of hypersensitive cell death in lettuce.  

PubMed

The development of bacterial rot disease caused by Pseudomonas cichorii is closely associated with programmed cell death. To investigate the molecular events occurring during the development of bacterial rot, we isolated 20 P. cichorii-responsive genes (PcRGs) in lettuce by differential display. Among these PcRGs, signal transduction-, transcription/translation- and defense/stress responses-related PcRGs were subjected to a comparative expression study. We used RNA samples isolated from lettuce leaves inoculated with P. cichorii and hypersensitive response-inducing Pseudomonas syringae pv. syringae. Expression of PcRG1-5-5 (spliceosomal protein), 2-9-2 (protein kinase) and 1-6-2 (ACC oxidase), 7-5 (alternative oxidase) and BI-I (bax inhibitor I) significantly increased in lettuce leaves inoculated with both P. cichorii and P. syringae pv. syringae. Intriguingly, PcRG 1-2-6 (protein phosphatase 2C) and 4-D-5 (protein kinase) were only up-regulated in P. cichorii-inoculated lettuce, whereas expression of PcRG1-3-2 (ribonucleoprotein) was only enhanced in P. syringae pv. syringae-inoculated lettuce. Expressions of PcRG1-3-2, 1-5-5, 1-6-2, 2-9-2, 7-5 and BI-I were induced by treatments with salicylic acid and/or methyl jasmonate. However, expression of PcRG1-2-6 and 4-D-5, which were specifically up-regulated by P. cichorii, were scarcely affected by these chemicals. Pharmacological studies suggested that ethylene and alternative oxidase were commonly related to disease development and hypersensitive responses. By contrast, there may be a different role for protein synthesis and protein kinase during disease development and in hypersensitive responses. These results suggested the overall similarity of genes expressed during disease development and in hypersensitive responses. However, there were differences not only in induction kinetics and the level of gene expression but also in the signal transduction pathway between hypersensitive responses and disease development. PMID:18171591

Kiba, Akinori; Lee, Kyon-Ye; Ohnishi, Kouhei; Hikichi, Yasufumi

2008-11-28

353

Complex adaptive responses during antagonistic coevolution between Tribolium castaneum and its natural parasite Nosema whitei revealed by multiple fitness components  

PubMed Central

Background Host-parasite coevolution can lead to local adaptation of either parasite or host if there is specificity (GxG interactions) and asymmetric evolutionary potential between host and parasite. This has been demonstrated both experimentally and in field studies, but a substantial proportion of studies fail to detect such clear-cut patterns. One explanation for this is that adaptation can be masked by counter-adaptation by the antagonist. Additionally, genetic architecture underlying the interaction is often highly complex thus preventing specific adaptive responses. Here, we have employed a reciprocal cross-infection experiment to unravel the adaptive responses of two components of fitness affecting both parties with different complexities of the underlying genetic architecture (i.e. mortality and spore load). Furthermore, our experimental coevolution of hosts (Tribolium castaneum) and parasites (Nosema whitei) included paired replicates of naive hosts from identical genetic backgrounds to allow separation between host- and parasite-specific responses. Results In hosts, coevolution led to higher resistance and altered resistance profiles compared to paired control lines. Host genotype × parasite genotype interactions (GH × GP) were observed for spore load (the trait of lower genetic complexity), but not for mortality. Overall parasite performance correlated with resistance of its matching host coevolution background reflecting a directional and unspecific response to strength of selection during coevolution. Despite high selective pressures exerted by the obligatory killing parasite, and host- and parasite-specific mortality profiles, no general pattern of local adaptation was observed, but one case of parasite maladaptation was consistently observed on both coevolved and control host populations. In addition, the use of replicate control host populations in the assay revealed one case of host maladaptation and one case of parasite adaptation that was masked by host counter-adaptation, suggesting the presence of complex and probably dynamically changing fitness landscapes. Conclusions Our results demonstrate that the use of replicate naive populations can be a useful tool to differentiate between host and parasite adaptation in complex and dynamic fitness landscapes. The absence of clear local adaptation patterns during coevolution with a sexual host showing a complex genetic architecture for resistance suggests that directional selection for generality may be more important attributes of host-parasite coevolution than commonly assumed. PMID:22280468

2012-01-01

354

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

355

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

356

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

357

Health-related quality of life in food hypersensitive schoolchildren and their families: parents' perceptions  

Microsoft Academic Search

BACKGROUND: About 20% of schoolchildren and adolescents in Sweden suffer from perceived food hypersensitivity (e.g. allergy or intolerance). Our knowledge of how child food hypersensitivity affects parents HRQL and what aspects of the hypersensitivity condition relate to HRQL deterioration in the family is limited. Thus the aim of this study was to investigate the parent-reported HRQL in families with a

Birgitta Marklund; Staffan Ahlstedt; Gun Nordström

2006-01-01

358

Boolean ErbB network reconstructions and perturbation simulations reveal individual drug response in different breast cancer cell lines  

PubMed Central

Background Despite promising progress in targeted breast cancer therapy, drug resistance remains challenging. The monoclonal antibody drugs trastuzumab and pertuzumab as well as the small molecule inhibitor erlotinib were designed to prevent ErbB-2 and ErbB-1 receptor induced deregulated protein signalling, contributing to tumour progression. The oncogenic potential of ErbB receptors unfolds in case of overexpression or mutations. Dimerisation with other receptors allows to bypass pathway blockades. Our intention is to reconstruct the ErbB network to reveal resistance mechanisms. We used longitudinal proteomic data of ErbB receptors and downstream targets in the ErbB-2 amplified breast cancer cell lines BT474, SKBR3 and HCC1954 treated with erlotinib, trastuzumab or pertuzumab, alone or combined, up to 60 minutes and 30 hours, respectively. In a Boolean modelling approach, signalling networks were reconstructed based on these data in a cell line and time course specific manner, including prior literature knowledge. Finally, we simulated network response to inhibitor combinations to detect signalling nodes reflecting growth inhibition. Results The networks pointed to cell line specific activation patterns of the MAPK and PI3K pathway. In BT474, the PI3K signal route was favoured, while in SKBR3, novel edges highlighted MAPK signalling. In HCC1954, the inferred edges stimulated both pathways. For example, we uncovered feedback loops amplifying PI3K signalling, in line with the known trastuzumab resistance of this cell line. In the perturbation simulations on the short-term networks, we analysed ERK1/2, AKT and p70S6K. The results indicated a pathway specific drug response, driven by the type of growth factor stimulus. HCC1954 revealed an edgetic type of PIK3CA-mutation, contributing to trastuzumab inefficacy. Drug impact on the AKT and ERK1/2 signalling axes is mirrored by effects on RB and RPS6, relating to phenotypic events like cell growth or proliferation. Therefore, we additionally analysed RB and RPS6 in the long-term networks. Conclusions We derived protein interaction models for three breast cancer cell lines. Changes compared to the common reference network hint towards individual characteristics and potential drug resistance mechanisms. Simulation of perturbations were consistent with the experimental data, confirming our combined reverse and forward engineering approach as valuable for drug discovery and personalised medicine. PMID:24970389

2014-01-01

359

Hypersensitivity pneumonitis resulting from Aspergillus fumigatus in a greenhouse.  

PubMed

A 57-y-old female who had cultivated vegetables in a plastic greenhouse developed a case of hypersensitivity pneumonitis from Aspergillus fumigatus. This report exemplifies a potential hazard caused by a thermotolerant fungus, A. fumigatus, in a poorly constructed greenhouse. PMID:8357277

Yoshida, K; Ueda, A; Yamasaki, H; Sato, K; Uchida, K; Ando, M

1993-01-01

360

Can CT Distinguish Hypersensitivity Pneumonitis from Idiopathic Pulmonary Fibrosis?  

Microsoft Academic Search

OBJECTIVE. The clinical management of patients with idiopathic pulmonary fibrosis differs markedly from that of patients with hypersensitivity pneumonitis. However, the two diseases often cannot be differentiated on clinical grounds. The purpose of this study was to establish whether CT can be used to make the distinction. MATERIALS AND METHODS. Thirty-six patients with idiopathic pulmonary fibrosis and 27 patients with

David A. Lynch; John D. Newell; P. Mark Logan; Talmadge E. King; Nestor L. MUller

1995-01-01

361

Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis  

Microsoft Academic Search

Rationale: Manyofthe interstitiallungdiseases representa diagnos- tic and therapeutic challenge because their clinical and even histo- logic features are often nonspecific. Likewise, the transcriptional signatures of most of them are unknown. Objective: To compare the gene expression patterns from patients with idiopathic pulmonary fibrosis (IPF) hypersensitivity pneumoni- tis (HP),andnonspecificinterstitialpneumonia (NSIP)usingcustom oligonucleotide microarrays. Methods: We profiled lung biopsies from 15 patients with

Moises Selman; Annie Pardo; Lourdes Barrera; Andrea Estrada; Susan R. Watson; Keith Wilson; Natasha Aziz; Naftali Kaminski; Albert Zlotnik

362

Hypersensitivity Pneumonitis Due to Dove Antigens in an Adolescent  

Microsoft Academic Search

Hypersensitivity pneumonitis is infrequently reported in children. This article describes a 15-year-old girl who presented with insidious onset of dyspnea and weight loss. A hamster and doves were housed in her bedroom. Chest radiographs showed bilateral nodular infiltrates. Pulmonary function tests showed a restrictive pattern with O2 desaturation at rest. The diagnosis was substantiated by the presence of precipitating antibody

Susheela K. Balasubramaniam; Edward J. OConnell; John W. Yunginger; John C. McDougall; Martin I. Sachs

1987-01-01

363

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

364

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

365

Epidemiological Study to Evaluate the Prevalence of Dentine Hypersensitivity among Patients  

PubMed Central

Background: Dentine hypersensitivity (DH) is a common finding with different prevalence rate. The aim of this study was to evaluate the prevalence of DH and associated risk factors. Materials & Methods: This cross-sectional survey was done among patients coming to dental hospital. The diagnosis of DH was made as the result of both clinical examination and patient's response. A self-administered structured questionnaire was used to know demography profile, self-reported DH, the activating factors, preventive measures and frequency. Descriptive statistics were obtained and frequency distribution was calculated using Chi square t test at p value <0.05. Results: The total population compromised of 960 patients including 528 males and 432 females. The prevalence of dentine hypersensitivity in this sample was 42.5% and more common among male population (60.8%) and the peak age was between 30 to 39 years (39.2%). Lower anteriors were commonly involved (35.8%) and cold drinks (25.8%) are the main aggravating factor. 6.5% experience it all the time but still some do not take preventive measures. Conclusion: There is high prevalence rate of DH and mainly among males. Some of the patients had it all the time but still they do not want to control the problem. How to cite this article:Rane P, Pujari S, Patel P, Gandhewar M, Madria K, Dhume S. Epidemiological Study to Evaluate the Prevalence of Dentine Hypersensitivity among Patients. J Int Oral Health 2013; 5(5):15-9. PMID:24324299

Rane, Prasad; Pujari, Siddharth; Patel, Pawan; Gandhewar, Mahesh; Madria, Kunal; Dhume, Swaroop

2013-01-01

366

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

367

Mechanical flutter stimulation induces a lasting response in the sensorimotor cortex as revealed with BOLD fMRI.  

PubMed

It has been recently shown that 20 min of mechanical flutter stimulation induces lasting motor cortical excitability changes, as assessed by transcranial magnetic stimulation in relaxed hand muscles. The present functional magnetic resonance imaging (fMRI) study aims to examine if such neuromodulatory changes are reflected in the BOLD signal during a motor test. Therefore, two groups were recruited: one group receiving whole-hand flutter stimulation with a frequency of 25 Hz (FSTIM group, n = 22) and a second group receiving no stimulation (NOSTIM group, n = 22). As motor test finger-to-thumb tapping was performed to activate a wide sensorimotor network during the fMRI measurements. Three fMRI measurements were obtained with this test: before stimulation (PRE), after stimulation (POST1), and 1 h after stimulation (POST2). Three regions of interest (ROIs) were defined: primary motor area (M1), primary somatosensory area (S1), and supplementary motor area. In the absence of baseline differences between both groups, the FSTIM group showed increased movement-related brain activations compared with the NOSTIM group, both at POST1 and POST2. ROI analysis revealed increased blood-oxygenation-level-dependent (BOLD) responses within contralateral S1 (+20%) and M1 (+25%) at POST1, which lasted until POST2. These poststimulatory effects within S1 and M1 obviously reflect neuroplastic changes associated with augmented cortical excitability. These findings are of high clinical relevance, for example, to improve the treatment of stroke patients. PMID:22611041

Christova, Monica; Golaszewski, Stefan; Ischebeck, Anja; Kunz, Alexander; Rafolt, Dietmar; Nardone, Raffaele; Gallasch, Eugen

2013-11-01

368

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

369

Transcriptomic analysis of Staphylococcus xylosus in the presence of nitrate and nitrite in meat reveals its response to nitrosative stress  

PubMed Central

Staphylococcus xylosus is one of the major starter cultures used for meat fermentation because of its crucial role in the reduction of nitrate to nitrite which contributes to color and flavor development. Despite longstanding use of these additives, their impact on the physiology of S. xylosus has not yet been explored. We present the first in situ global gene expression profile of S. xylosus in meat supplemented with nitrate and nitrite at the levels used in the meat industry. More than 600 genes of S. xylosus were differentially expressed at 24 or 72 h of incubation. They represent more than 20% of the total genes and let us to suppose that addition of nitrate and nitrite to meat leads to a global change in gene expression. This profile revealed that S. xylosus is subject to nitrosative stress caused by reactive nitrogen species (RNS) generated from nitrate and nitrite. To overcome this stress, S. xylosus has developed several oxidative stress resistance mechanisms, such as modulation of the expression of several genes involved in iron homeostasis and in antioxidant defense. Most of which belong to the Fur and PerR regulons, respectively. S. xylosus has also counteracted this stress by developing DNA and protein repair. Furthermore, it has adapted its metabolic response—carbon and nitrogen metabolism, energy production and cell wall biogenesis—to the alterations produced by nitrosative stress. PMID:25566208

Vermassen, Aurore; de la Foye, Anne; Loux, Valentin; Talon, Régine; Leroy, Sabine

2014-01-01

370

Proteomic analyses of the time course responses of mice infected with Brucella abortus 544 reveal immunogenic antigens.  

PubMed

Brucellosis is a major zoonotic disease caused by pathogens of the genus Brucella. The eradication of brucellosis in domestic animals, associated with the prevention of human infection, can be attained through accurate diagnosis. However, the conventional serological diagnosis of brucellosis has limitations, particularly in detecting the infection period. Accordingly, the aim of this study was to determine reliable immunogenic proteins to detect Brucella abortus infection according to time course responses to aid in the appropriate management of this disease. Proteomic identification through two-dimensional electrophoresis (2DE), followed by immunoblotting, revealed 13, 24, and 55 immunodominant B. abortus 544 proteins that were reactive to sera from experimentally infected mice at early (10 days), middle (30 days), and late (60 days) infection periods, respectively. After excluding several spots reactive to sera from Yersinia enterocolitica O:9-infected and noninfected mice, 17 of the 67 immunodominant proteins were identified through MALDI-TOF MS. Consequently, the identified proteins showed time course-dependent immunogenicity against Brucella infection. Thus, the results of this study suggest that the production of immunogenic proteins during infection periods improves the diagnosis and discovery of vaccine candidates. PMID:24975114

Lee, Jin Ju; Simborio, Hannah Leah; Reyes, Alisha Wehdnesday Bernardo; Kim, Dae Geun; Hop, Huynh Tan; Min, Wongi; Her, Moon; Jung, Suk Chan; Yoo, Han Sang; Kim, Suk

2014-08-01

371

Analysis of the Virus Dynamics Model Reveals That Early Treatment of HCV Infection May Lead to the Sustained Virological Response  

PubMed Central

Considerable progress has been made towards understanding hepatitis C virus, its pathogenesis and the effect of the drug therapy on the viral load, yet around 50% of patients do not achieve the sustained virological response (SVR) by the standard treatment. Although several personalized factors such as patients’ age and weight may be important, by mathematical modeling we show that the time of the start of the therapy is a significant factor in determining the outcome. Toward this end, we first performed sensitivity analysis on the standard virus dynamics model. The analysis revealed four phases when the sensitivity of the infection to drug treatment differs. Further, we added a perturbation term in the model to simulate the drug treatment period and predict the outcome when the therapy is carried out during each of the four phases. The study shows that while the infection may be difficult to treat in the late phases, the therapy is likely to result in SVR if it is carried out in the first or second phase. Thus, development of newer and more sensitive screening methods is needed for the early detection of the infection. Moreover, the analysis predicts that the drug that blocks new infections is more effective than the drug that blocks the virus production. PMID:22911761

Gupta, Saurabh; Singh, Raghvendra

2012-01-01

372

Auditory profile and high resolution CT scan in autism spectrum disorders children with auditory hypersensitivity.  

PubMed

Autism is the third most common developmental disorder, following mental retardationand cerebral palsy. ASD children have been described more often as beingpreoccupied with or agitated by noise. The aim of this study was to evaluate theprevalence and clinical significance of semicircular canal dehiscence detected on CTimages in ASD children with intolerance to loud sounds in an attempt to find ananatomical correlate with hyperacusis.14 ASD children with auditory hypersensitivity and 15 ASD children without auditoryhypersensitivity as control group age and gender matched were submitted to historytaking, otological examination, tympanometry and acoustic reflex thresholdmeasurement. ABR was done to validate normal peripheral hearing and integrity ofauditory brain stem pathway. High resolution CT scan petrous and temporal boneimaging was performed to all participated children. All participants had normal hearingsensitivity in ABR testing. Absolute ABR peak waves of I and III showed no statisticallysignificant difference between the two groups, while absolute wave V peak andinterpeak latencies I-V and III-V were shorter in duration in study group whencompared to the control group. CT scans revealed SSCD in 4 out of 14 of the studygroup (29%), the dehiscence was bilateral in one patient and unilateral in threepatients. None of control group showed SSCD. In conclusion, we have reportedevidence that apparent hypersensitivity to auditory stimuli (short conduction time in ABR) despite the normal physiological measures in ASD children with auditoryhypersensitivity can provide a clinical clue of a possible SSCD. PMID:23580033

Thabet, Elsaeid M; Zaghloul, Hesham S

2013-08-01

373

TRPV1 channels make major contributions to behavioral hypersensitivity and spontaneous activity in nociceptors after spinal cord injury.  

PubMed

Chronic neuropathic pain is often a severe and inadequately treated consequence of spinal cord injury (SCI). Recent findings suggest that SCI pain is promoted by spontaneous activity (SA) generated chronically in cell bodies of primary nociceptors in dorsal root ganglia (DRG). Many nociceptors express transient receptor potential V1 (TRPV1) channels, and in a preceding study most dissociated DRG neurons exhibiting SA were excited by the TRPV1 activator, capsaicin. The present study investigated roles of TRPV1 channels in behavioral hypersensitivity and nociceptor SA after SCI. Contusive SCI at thoracic segment T10 increased expression of TRPV1 protein in lumbar DRG 1 month after injury and enhanced capsaicin-evoked ion currents and Ca2+ responses in dissociated small DRG neurons. A major role for TRPV1 channels in pain-related behavior was indicated by the ability of a specific TRPV1 antagonist, AMG9810, to reverse SCI-induced hypersensitivity of hind limb withdrawal responses to mechanical and thermal stimuli at a dose that did not block detection of noxious heat. Similar reversal of behavioral hypersensitivity was induced by intrathecal oligodeoxynucleotides antisense to TRPV1, which knocked down TRPV1 protein and reduced capsaicin-evoked currents. TRPV1 knockdown also decreased the incidence of SA in dissociated nociceptors after SCI. Prolonged application of very low concentrations of capsaicin produced nondesensitizing firing similar to SA, and this effect was enhanced by prior SCI. These results show that TRPV1 makes important contributions to pain-related hypersensitivity long after SCI, and suggest a role for TRPV1-dependent enhancement of nociceptor SA that offers a promising target for treating chronic pain after SCI. PMID:23811042

Wu, Zizhen; Yang, Qing; Crook, Robyn J; O'Neil, Roger G; Walters, Edgar T

2013-10-01

374

Fast, visual specialization for reading in English revealed by the topography of the N170 ERP response  

PubMed Central

Background N170 effects associated with visual words may be related to perceptual expertise effects that have been demonstrated for faces and other extensively studied classes of visual stimuli. Although face and other object expertise effects are typically bilateral or right-lateralized, the spatial topography of reading-related N170 effects are often left-lateralized, providing potential insights into the unique aspects of reading-related perceptual expertise. Methods Extending previous research in German [1], we use a high-density channel array to characterize the N170 topography for reading-related perceptual expertise in English, a language with inconsistent spelling-to-sound mapping. N170 effects related to overall reading-related expertise are defined by contrasting responses to visual words versus novel symbol strings. By contrasting each of these conditions to pseudowords, we examined how this reading-related N170 effect generalizes to well-ordered novel letter strings. Results A sample-by-sample permutation test computed on word versus symbol ERP topographies revealed differences during two time windows corresponding to the N170 and P300 components. Topographic centroid analysis of the word and symbol N170 demonstrated significant differences in both left-right as well as inferior-superior dimensions. Words elicited larger N170 negativities than symbols at inferior occipito-temporal channels, with the maximal effect over left inferior regions often unsampled in conventional electrode montages. Further contrasts produced inferior-superior topographic effects for the pseudoword-symbol comparison and left-lateralized topographic effects for the word-pseudoword comparison. Conclusion Fast specialized perception related to reading experience produces an N170 modulation detectable across different EEG systems and different languages. Characterization of such effects may be improved by sampling with greater spatial frequency recordings that sample inferior regions. Unlike in German, reading-related expertise effects in English produced only partial generalization in N170 responses to novel pseudowords. The topographic inferior-superior N170 differences may reflect general perceptual expertise for orthographic strings, as it was found for words and pseudowords across both languages. The topographic left-right N170 difference between words and pseudowords was only found in English, and may suggest that ambiguity in pronunciating novel pseudowords due to inconsistency in spelling-to-sound mapping influences early stages of letter string processing. PMID:16091138

Maurer, Urs; Brandeis, Daniel; McCandliss, Bruce D

2005-01-01

375

Enhanced delayed-type hypersensitivity and diminished immediate-type hypersensitivity in mice lacking the inducible VPAC(2) receptor for vasoactive intestinal peptide.  

PubMed

Vasoactive intestinal peptide (VIP) and its G protein-coupled receptors, VPAC(1)R and VPAC(2)R, are prominent in the immune system and regulate many aspects of T cell-dependent immunity. In mouse T cells, VPAC(1)R is expressed constitutively, whereas VPAC(2)R is induced by immune stimuli. VPAC(2)R-null (VPAC(2)R(-/-)) mice on a C57BL/6 background are shown here to have normal basic immune characteristics, including serum Ig concentrations, blood levels of all leukocytes, and spleen number of total T cells (CD3(+)) and T cells bearing CD4, CD8, and CD28. Hapten-evoked cutaneous delayed-type hypersensitivity (DTH) was significantly enhanced in VPAC(2)R-null mice compared with age- and sex-matched wild-type mice. In contrast, generation of IgE anti-hapten antibodies and active cutaneous anaphylaxis were > or =70% lower in VPAC(2)R-null mice than in wild-type controls. Cytokine production by splenic CD4(+) T cells, stimulated with adherent anti-CD3 plus anti-CD28 antibodies, revealed higher levels of IL-2 (mean = 3-fold) and IFN-gamma (mean = 3-fold), and lower levels of IL-4 (mean = one-fifth) in VPAC(2)R-null mice than wild-type controls. Loss of VIP-VPAC(2)R maintenance of the normal ratio of Th2/Th1 cytokines thus leads to a state of enhanced DTH and depressed immediate-type hypersensitivity, which may alter both host defense and susceptibility to immune-mediated diseases. PMID:11698667

Goetzl, E J; Voice, J K; Shen, S; Dorsam, G; Kong, Y; West, K M; Morrison, C F; Harmar, A J

2001-11-20

376

Lipidomic Profiling of Saccharomyces cerevisiae and Zygosaccharomyces bailii Reveals Critical Changes in Lipid Composition in Response to Acetic Acid Stress  

PubMed Central

When using microorganisms as cell factories in the production of bio-based fuels or chemicals from lignocellulosic hydrolysate, inhibitory concentrations of acetic acid, released from the biomass, reduce the production rate. The undissociated form of acetic acid enters the cell by passive diffusion across the lipid bilayer, mediating toxic effects inside the cell. In order to elucidate a possible link between lipid composition and acetic acid stress, the present study presents detailed lipidomic profiling of the major lipid species found in the plasma membrane, including glycerophospholipids, sphingolipids and sterols, in Saccharomyces cerevisiae (CEN.PK 113_7D) and Zygosaccharomyces bailii (CBS7555) cultured with acetic acid. Detailed physiological characterization of the response of the two yeasts to acetic acid has also been performed in aerobic batch cultivations using bioreactors. Physiological characterization revealed, as expected, that Z. bailii is more tolerant to acetic acid than S. cerevisiae. Z. bailii grew at acetic acid concentrations above 24 g L?1, while limited growth of S. cerevisiae was observed after 11 h when cultured with only 12 g L?1 acetic acid. Detailed lipidomic profiling using electrospray ionization, multiple-reaction-monitoring mass spectrometry (ESI-MRM-MS) showed remarkable changes in the glycerophospholipid composition of Z. bailii, including an increase in saturated glycerophospholipids and considerable increases in complex sphingolipids in both S. cerevisiae (IPC 6.2×, MIPC 9.1×, M(IP)2C 2.2×) and Z. bailii (IPC 4.9×, MIPC 2.7×, M(IP)2C 2.7×), when cultured with acetic acid. In addition, the basal level of complex sphingolipids was significantly higher in Z. bailii than in S. cerevisiae, further emphasizing the proposed link between lipid saturation, high sphingolipid levels and acetic acid tolerance. The results also suggest that acetic acid tolerance is associated with the ability of a given strain to generate large rearrangements in its lipid profile. PMID:24023914

Riezman, Howard; Olsson, Lisbeth; Bettiga, Maurizio

2013-01-01

377

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 diversity of indigenous microbial communities to transform and remediate a wide range of environmental contaminants. Understanding the response of communities to stimulation, including flanking taxa, presents important opportunities for optimizing remediation approaches. We used high-density PhyloChip microarray analysis to comprehensively determine community membership and abundance patterns amongst a suite of samples from U(VI) bioremediation experiments. Samples were unstimulated or collected during Fe(III) and sulfate reduction from an acetate-augmented aquifer in Rifle, Colorado, and from laboratory experiments using field-collected materials. Results showed the greatest diversity in abundant SRB lineages was present in naturally-reduced sediment. Desulfuromonadales and Desulfobacterales were consistently identified as the dominant Fe(III)- and sulfate-reducing bacteria (IRB and SRB) throughout acetate amendment experiments. Stimulated communities also exhibited a high degree of functional redundancy amongst enriched flanking members. Not surprisingly, competition for both sulfate and iron was evident amongst abundant taxa, but the distribution and abundance of these ancillary SRB (Peptococcaceae, Desulfovibrionales and Syntrophobacterales), and lineages containing IRB (excluding Desulfobacteraceae) was heterogeneous amongst sample types. Interesting, amongst the most abundant taxa, particularly during sulfate reduction, were Epsilonproteobacteria that perform microaerobic or nitrate-dependant sulfur oxidation, and a number of bacteria other than Geobacteraceae that may enzymatically reduce U(VI). Finally, in depth community probing with PhyloChip determined the efficacy of experimental approaches, notably revealing striking similarity amongst stimulated sediment (from drill cores and in-situ columns) and groundwater communities, and demonstrating that sediment-packed in-situ (down-well) columns served as an ideal method for subsurface biostimulation.

Handley, Kim M.; Wrighton, Kelly E.; Piceno, Y. M.; Anderson, Gary L.; DeSantis, Todd; Williams, Kenneth H.; Wilkins, Michael J.; N'Guessan, A. L.; Peacock, Aaron; Bargar, John R.; Long, Philip E.; Banfield, Jillian F.

2012-06-13

378

Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR)  

PubMed Central

BACKGROUND AND PURPOSE Pancreatic cancer is one of the leading cancer-related causes of death due to high chemo-resistance and fast metastasation. Nemorosone, a polycyclic polyprenylated acylphloroglucinol, has recently been identified as a promising anticancer agent. Here, we examine its growth-inhibitory effects on pancreatic cancer cells. Based on transcription profiling, a molecular mode of action is proposed. EXPERIMENTAL APPROACH Nemorosone cytotoxicity was assessed by the resazurin proliferation assay on pancreatic cancer cells and fibroblasts. Apoptosis was determined by Annexin V/propidium iodide staining as well as cytochrome c and caspase activation assays. Staining with the voltage-dependent dye JC-1 and fluorescence microscopy were used to detect effects on mitochondrial membrane potential. Total RNA was isolated from treated cell lines and subjected to microarray analysis, subsequent pathway identification and modelling. Gene expression data were validated by quantitative polymerase chain reaction and siRNA-mediated gene knock-down. KEY RESULTS Nemorosone significantly inhibited cancer cell growth, induced cytochrome c release and subsequent caspase-dependent apoptosis, rapidly abolished mitochondrial membrane potential and elevated cytosolic calcium levels, while fibroblasts were largely unaffected. Expression profiling revealed 336 genes to be affected by nemorosone. A total of 75 genes were altered in all three cell lines, many of which were within the unfolded protein response (UPR) network. DNA damage inducible transcript 3 was identified as a key regulator in UPR-mediated cell death. CONCLUSIONS AND IMPLICATIONS Nemorosone could be a lead compound for the development of novel anticancer drugs amplifying the already elevated UPR level in solid tumours, thus driving them into apoptosis. This study forms the basis for further investigations identifying nemorosone's direct molecular target(s). PMID:21091652

Holtrup, Frank; Bauer, Andrea; Fellenberg, Kurt; Hilger, Ralf A; Wink, Michael; Hoheisel, Jörg D

2011-01-01

379

Study of the Response Regulator Rrp1 Reveals Its Regulatory Role in Chitobiose Utilization and Virulence of Borrelia burgdorferi  

PubMed Central

Life cycle alternation between arthropod and mammals forces the Lyme disease spirochete, Borrelia burgdorferi, to adapt to different host milieus by utilizing diverse carbohydrates. Glycerol and chitobiose are abundantly present in the Ixodes tick. B. burgdorferi can utilize glycerol as a carbohydrate source for glycolysis and chitobiose to produce N-acetylglucosamine (GlcNAc), a key component of the bacterial cell wall. A recent study reported that Rrp1, a response regulator that synthesizes cyclic diguanylate (c-di-GMP), governs glycerol utilization in B. burgdorferi. In this report, we found that the rrp1 mutant had growth defects and formed membrane blebs that led to cell lysis when GlcNAc was replaced by chitobiose in the growth medium. The gene chbC encodes a key chitobiose transporter of B. burgdorferi. We found that the expression level of chbC was significantly repressed in the muta