Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AIRE Protein”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2006

Assessing the extent of protein intermolecular interactions at air-water interfaces using spectroscopic techniques.

There is an ongoing debate about whether a protein surface film at an air-water interface can be regarded as a gelled layer. There is literature reporting that such films show macroscopic fracture behavior and a rheology comparable to three-dimensional protein bulk-networks. If this is the case, a complete description of the formation of adsorbed layers should include a transition from single, freely moving proteins to a gelled layer. This report presents studies using spectroscopic techniques, such as infrared, fluorescence and neutron spectroscopy, or ellipsometry, to derive molecular insight in situ to substantiate the intermolecular networking in surface films of chicken egg ovalbumin. It is concluded that protein films, generated by equilibrium adsorption from the bulk, behave as a densely packed colloidal repulsive particle system, where the proteins still have a significant rotational mobility, have a predominantly retained globular fold, and show distinct (lateral) diffusion. Applied stresses on the surface film (by compressions of the interface) may result in protein denaturation and aggregation. This process renders a surface film from a colloidal particle into that of a gelled system.

Air↗
PubMed2002

[Autoimmune polyendocrine syndrome (APS)].

As a complement to basic research, thorough clinical investigation of rare diseases may provide fundamental elements which improve our understanding of still obscure pathophysiologic mechanisms. This is the case with immunoendocrinopathy syndromes. Since Addison's pioneer observations in the 19th century, physicians have known that some individuals and their families may be affected by several spontaneous endocrine insufficiencies that are associated with autoimmune extra-endocrine processes. APS-I or APECED syndrome appears in children firstly affected by recurrent muco-cutaneous candidiasis and hypoparathyroidism, followed by adrenocortical insufficiency and by other autoimmune processes. APS-I is a monogenic disorder resulting from one mutation in the AIRE gene. The protein encoded by AIRE is a nuclear transcription factor the precise target of which is still not known. AIRE is mainly expressed by cells playing a crucial role in the establishment of central T cell self-tolerance (medullary epithelium, macrophages and dendritic cells of the thymus). APS-I must be considered in children affected with recurrent candidiasis without any sign of primary immune deficiency. Scientific investigation of the biological nuclear events controlled by AIRE has to be pursued. Undoubtedly, their deciphering will increase our knowledge of the mechanisms responsible for the establishment of central T cell self-tolerance and will open novel strategies for managing many autoimmune diseases. APS-II is a more common syndrome characterized by adrenocortical insufficiency spontaneously occurring in non tuberculous adults and associated with autoimmune thyroiditis and/or type 1 diabetes. Contrary to APS-I, APS-II is linked to genetic loci of the major histocompatibility complex. There is no adrenal insufficiency in APS-III which includes autoimmune thyroiditis, type 1 diabetes, and other autoimmune extra-endocrine processes (like pernicious anemia and vitiligo).

Adrenal Glands↗
PubMed2006

Atomic tritium as an instrument for study of protein behavior at the air-water interface.

Atomic tritium was successfully applied as an instrument for study of protein behavior at the air-water interface. Samples of lysozyme solution in 20 mM phosphate buffer (pH 7.0) with concentration of 2 mg/ml incubated at the room temperature for 1 h were exposed to bombardment with tritium atoms generated on hot tungsten wire in special vacuum device. This procedure resulted in substitution of hydrogen atoms by radioactive tritium in the thin surface layer of studied preparations. Analysis of experimental data on intramolecular radioactivity distribution in lysozyme and computer simulation of tritium bombardment allowed us to suggest two equally probable opposite orientations of lysozyme molecule in the adsorption layer at the air-water interface.

Air↗
PubMed1995

Evaluation of the allergic/irritant potential of air pollutants: detection of proteins modified by volatile organic compounds from oilseed rape (Brassica napus ssp. oleifera) using electrospray ionization-mass spectrometry.

BACKGROUND: Upward trends in allergy and asthma rates have been reported in most western societies, including the UK, where around 15-20% of the population now suffer from allergy or asthma. Scientific proof of the causes of these increases relies on accurate assessment of exposure and standardized diagnostic tests, such as for specific IgE in blood serum and skin testing. For many air pollutants it has proven difficult to assess an individual's exposure outside an occupational environment and reliable test development is hampered by not knowing whether an allergic or irritant mechanism is involved. These problems are particularly evident in the controversial issue of whether airborne releases from oilseed rape can cause health effects. OBJECTIVE: To develop a method for evaluating the allergic/irritant potential of air pollutants and to assess whether the volatile organic compounds emitted by oilseed rape have this potential. METHODS: Proteins were exposed in vitro to volatile organic compounds emitted by oilseed rape. Electrospray ionization-mass spectrometry was used to detect any resultant protein modifications. RESULTS: Dimethyl disulphide, thiocyanic acid methyl ester and 2-methyl-propanenitrile were able to modify human proteins. In addition, two isothiocyanates which can be emitted by damaged oilseed rape also have this ability. The major products emitted by undamaged oilseed rape, terpenes, a sesquiterpene and a terpene alcohol did not have this property, but the possible role of their oxidized products is discussed. CONCLUSION: Some of the volatile organic compounds emitted by oilseed rape have the potential to be allergens/irritants. Standardized modified proteins produced by this method should prove useful for biomonitoring human exposure in molecular epidemiological studies as well as in diagnostic tests. This method should find further application in investigations into the possible health effects of other environmental pollutants.

Air Pollutants↗
PubMed1999

Cloning of Aire, the mouse homologue of the autoimmune regulator (AIRE) gene responsible for autoimmune polyglandular syndrome type 1 (ASP1).

The human autoimmune regulator gene (AIRE), responsible for autoimmune polyglandular syndrome Type 1 (APS1), has recently been identified by positional cloning. Here we report the cloning of Aire, the mouse homologue of AIRE, and the characterization of its genomic structure. The complete Aire gene is contained in 14 exons and encodes a protein of 552 amino acids. The coding region shares 77% nucleotide homology and 71% protein homology with human AIRE. As in its human homologue, Aire contains two PHD-type zinc-finger motifs, suggesting that the Aire protein may act as a transcription regulator.

Amino Acid Sequence↗
PubMed1981

Estimation of whole body protein synthesis in rats by single injection of L-[1-14C]leucine or DL-[1-14C]lysine.

We evaluated a method of estimating whole body protein synthesis in rats. Growing rats were given single injections of L-[1-14C]leucine, DL-[1-14C]lysine or D-[1-14C]lysine via a tail vein. Total 14C in expired air, body protein, body lipids, perchloric acid soluble material and excreta was recovered after 3 hours. After injections of L-[1-14C]leucine, 89% of injected 14C was recovered either in expired air or as protein-bound [14C]leucine. After correction for radiochemical purity of injected L-[1-14C]leucine, the total recovery of these two fractions was 95%. Only insignificant amounts of 14C were recovered in expired air and protein-bound [14C]lysine after injections of D-[1-14C]lysine. After correcting for radiochemical purity and stereoisomerism injected DL-[1-14C]lysine, we found 70% of the 14C from L-[1-14C]lysine in expired air or as protein-bound [14C]lysine. The results demonstrated that single injections of L-[1-14C]leucine provided valid estimates of whole body protein synthesis, whereas it was likely that a longer period of 14CO2 collection was required after injections of DL-[1-14C]lysine. By measuring nitrogen balance and absorption of dietary leucine, we estimated the rates of whole body protein synthesis, accretion and degradation to be 3.51, 0.90 and 2.61 g/day, respectively, for those rats injected with L-[1-14C]leucine.

Animals↗
PubMed2005

Combined surface pressure-interfacial shear rheology study of the effect of pH on the adsorption of proteins at the air-water interface.

The effect of pH on the adsorption of catalase and lysozyme at the air-water interface has been studied using a combined surface pressure-interfacial shear rheology technique. The results presented show that the rate of development of interfacial phenomena increases as the pH of the subphase approaches the isoelectric point of the protein under investigation. The development of the measured interfacial rheological parameters is due to an increased rate of cross-link formation within the resultant interfacial gel. The formation of the interfacial gels has been modeled using a combination of the Smoluchowski theory for the coagulation of an aerosol or fog and classic rubber elasticity theory. The enhanced rate of cross-link formation at the isoelectric point is a result of an in-surface phase separation brought about by cooperative deionization of the protein molecules near their isoelectric point. Simultaneous measurements of surface pressure and interfacial rheology have enabled us to show that the development of a gel-like interfacial network coincides with observed increases in surface pressure.

Adsorption↗
PubMed2003

Charged colloids and proteins at an air-water interface: the effect of dielectric substrates on interaction and phase behavior.

We study a two-dimensional (2D) system of macroions, trapped at the interface between air and an aqueous electrolyte solution, in the presence of a dielectric substrate approaching the air-water interface from the water side. Working within the linear Debye-Hückel theory, we investigate how the microion-averaged interaction potential between the macroions is affected by the presence of the dielectric substrate. Using these potentials in a Monte Carlo simulation, we further study the changes in the structural and phase behavior of the 2D colloidal system in response to the approaching substrate. Our scope of investigation covers two classes of colloidal particles, namely, highly charged latex particles of tens of nanometers radius, and protein particles of few nanometers radius carrying relatively small numbers of total charge. Probing the bond-orientational order parameter Phi(6) as a function of the 2D particle surface fraction phi(surf) and the air-water-substrate-water separation distance L, our simulations show that structural formations at the air-water interface are strongly influenced by the presence and the dielectric nature of the supporting substrate. Specifically, our [phi(surf): L] phase diagrams reveal that the transition from the fluid to the crystalline phase is shifted to higher surface fractions, if the approaching substrate is metallic, and to lower surface fractions, if it has a very low dielectric constant. These phase diagrams may be useful for finding materials and substrate interfaces for growing, e.g., 2D crystals of protein particles.

Journal Article↗
PubMed2006

EilA, a HilA-like regulator in enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAEC) is increasingly recognized as a diarrhoeal pathogen in developing and industrialized countries. Most EAEC virulence factors thus far described are encoded on virulence plasmid pAA, yet recent completion of the EAEC genome has suggested the presence of additional factors encoded on chromosomal islands. Previous reports have recognized the presence of a type III secretion system (T3SS), designated ETT2, at the glyU locus of prototype EAEC strain 042, along with possible T3SS effectors at the selC locus. The selC locus was also noted to harbour homologues of Salmonella enterica regulator HilA and of invasin from Yersinia spp., yet previous publications suggested that these loci may be silent. Here, we show that the genes of the selC locus are present inconsistently among a collection of well-characterized EAEC strains. Notably, however, there was perfect correlation between the presence of hilA-homologue eilA and predicted Yersinia invasin homologue gene eaeX. We hypothesized that if expressed, the putative gene product EilA would contribute to EAEC virulence in part by activation of the T3SS and its effectors. An eilA mutant was constructed in EAEC strain 042, and complementation was achieved by cloning the eilA gene under control of an arabinose-dependent promoter. In this system, we observed expression of at least seven genes to be affected by expression of eilA, either directly or indirectly: selC locus genes eipB, eipC, eipD, eicA and eaeX (renamed here air), as well as glyU ETT2 genes eivF and eivA. Notably, the eilA mutant was shown to be less adherent to epithelial cells in culture and to form less abundant biofilms than the isogenic parent. These effects were recapitulated in the air mutant, suggesting that the predicted outer membrane protein product of the air gene is involved as an accessory adhesin and aggregin of EAEC, coexpressed with the T3SS. Our data suggest that the T3SS of EAEC and presumed effectors located on different chromosomal islands may be coordinately activated by EilA, which also activates the genetically linked high molecular weight bacterial surface protein Air. Contributions of this new putative virulence-related regulon in EAEC may include adherence, aggregation, and as yet uncharacterized roles for the T3SS.

Bacterial Adhesion↗
PubMed1998

Incidence of latex sensitization among latex glove users.

BACKGROUND: Although there are several reports of the prevalence of latex sensitization among health care workers, the incidence of sensitization is unknown. OBJECTIVE: The objective of this study was to estimate the incidence of sensitization among latex glove users at a hospital in Hamilton, Ontario, Canada. METHODS: Workers with negative results to the skin test at baseline were followed prospectively over 1 year, some wearing powdered gloves and others using powder-free gloves. They were reevaluated in 1995 with a questionnaire and skin prick test (SPT) sensitivity to latex reagents, three common inhalants, and six foods. A conversion was defined as a (new) latex SPT with wheal diameter at least 4 mm greater than saline control. Glove extracts were assayed for antigenic protein, and air samples were obtained to estimate exposure to airborne latex protein. RESULTS: During powdered glove use, personal exposures ranged from 5 to 616 ng/m3, whereas during powder-free glove use, all but two results for air samples were below the limit of detection (about 0.1 ng/m3). During the study period, the protein concentration in the powdered gloves, initially mean 557 microg/gm of sample, declined at a rate of 295 microg/gm per year (p < 0.0001). Of the 1075 SPT-negative participants at baseline, 479 were working in eligible wards, and of these, 435 (91%) participated in follow-up, 227 using powder-free gloves and 208 using powdered gloves. We identified four conversions, two (1.0%) in the powdered glove group and two (0.9%) in the powder-free group. The two participants using powdered gloves were the only converters who were symptomatic. The significance of skin test conversions identified in the powder-free group, both asymptomatic patients, is unclear. The limitations of the study are discussed, including the limited power, the declines in latex protein concentrations, and the possibility of information (observer) bias. CONCLUSION: To our knowledge, this represents the first reported estimate (about 1%) of incidence of sensitization in hospital personnel using latex gloves.

Cross-Sectional Studies↗
PubMed2005

NMR structure of the first PHD finger of autoimmune regulator protein (AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disease.

Mutations in the autoimmune regulator protein AIRE1 cause a monogenic autosomal recessively inherited disease: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE1 is a multidomain protein that harbors two plant homeodomain (PHD)-type zinc fingers. The first PHD finger of AIRE1 is a mutational hot spot, to which several pathological point mutations have been mapped. Using heteronuclear NMR spectroscopy, we determined the solution structure of the first PHD finger of AIRE1 (AIRE1-PHD1), and characterized the peptide backbone mobility of the domain. We performed a conformational analysis of pathological AIRE1-PHD1 mutants that allowed us to rationalize the structural impact of APECED-causing mutations and to identify an interaction site with putative protein ligands of the AIRE1-PHD1 domain. The structure unequivocally exhibits the canonical PHD finger fold, with a highly conserved tryptophan buried inside the structure. The PHD finger is stabilized by two zinc ions coordinated in an interleaved (cross-brace) scheme. This zinc coordination resembles RING finger domains, which can function as E3 ligases in the ubiquitination pathway. Based on this fold similarity, it has been suggested that PHD fingers might also function as E3 ligases, although this hypothesis is controversial. At variance to a previous report, we could not find any evidence that AIRE1-PHD1 has an intrinsic E3 ubiquitin ligase activity, nor detect any direct interaction between AIRE1-PHD1 and its putative cognate E2. Consistently, we show that the AIRE1-PHD1 structure is clearly distinct from the RING finger fold. Our results point to a function of the AIRE1-PHD1 domain in protein-protein interactions, which is impaired in some APECED mutations.

Amino Acid Sequence↗
PubMed2001

Lateral phase separation in adsorbed binary protein films at the air-water interface.

Lateral phase separation in two-dimensional mixed films of soy 11S/beta-casein, acidic subunits of soy 11 (AS11S)/beta-casein, and alpha-lactalbumin/beta-casein adsorbed at the air-water interface has been studied using an epifluorescence microscopy method. No distinct lateral phase separation was observed in the mixed protein films when they were examined after 24 h of adsorption from the bulk phase. However, when the soy 11S/beta-casein and AS11S/beta-casein films were aged at the air-water interface for 96 h, phase-separated regions of the constituent proteins were evident, indicating that the phase separation process was kinetically limited by a viscosity barrier against lateral diffusion. In these films, beta-casein always formed the continuous phase and the other globular protein the dispersed phase. The morphology of the dispersed patches was affected by the protein composition in the film. In contrast with soy 11S/beta-casein and AS11S/beta-casein films, no lateral phase separation was observed in the alpha-lactalbumin/beta-casein film at both low and high concentration ratios in the film. The results of these studies proved that proteins in adsorbed binary films exhibit limited miscibility, and the deviation of competitive adsorption behavior of proteins at the air-water interface from that predicted by the ideal Langmuir model (Razumovsky, L.; Damodaran, S. J. Agric. Food Chem. 2001, 49, 3080-3086) is in fact due to thermodynamic incompatibility of mixing of the proteins in the binary film. It is hypothesized that phase separation in adsorbed mixed protein films at the air-water and possibly oil-water interfaces of foams and emulsions might be a source of instability in these dispersed systems.

Adsorption↗
PubMed2005

An odorant-binding protein facilitates odorant transfer from air to hydrophilic surroundings in the blowfly.

Chemical sense-related lipophilic ligand-binding protein (CRLBP) is an insect odorant-binding protein (OBP) found abundantly in the taste and olfactory organs of the blowfly, Phormia regina. Through computational construction, a three-dimensional molecular model of a CRLBP indicated good fitting to a fluorescent ligand, 7-hydroxycoumarin (7-HC), in its ligand-binding pocket. By showing that the fluorescence of 7-HC bound to CRLBP migrated in a native electrophoresis gel, we confirmed that CRLBP formed a stable complex with 7-HC. In an odorant-binding experiment, 7-HC vapor odor was introduced by aeration to the aquatic solution containing CRLBP and its binding to CRLBP fluorospectrometrically quantified. Because olfactory organs as well as taste organs of flies respond to vapors, we suggest that CRLBP effectively transfers odorants from the air into aquatic surroundings by forming stable complexes with airborne molecules in both chemosensory organs.

Air↗
PubMed1999

Protein folding at the air-water interface studied with x-ray reflectivity.

We report the results of x-ray reflectivity measurements of thin films formed by different water-soluble proteins at the air-aqueous solution interface. It is demonstrated that glucose oxidase, alcohol dehydrogenase, and urease molecules denaturate at the air-aqueous solution interface to form 8- to 14-A-thick peptide sheets. X-ray reflectivity data indicate that the spreading of a lipid monolayer at the aqueous solution surface before protein injection does not prevent proteins from unfolding. On the other hand, crosslinking of proteins results in intact enzyme layers at the subphase surface. A model that involves interaction of glucose oxidase molecules with a phospholipid monolayer is proposed. In this model, an observed decrease of the lipid electron density in the protein presence is explained in terms of "holes" in the monolayer film caused by protein molecule adsorption.

Animals↗