Izloženost alergenima plijesni u unutarnjem okolišu

Humid indoor environments may be colonised by allergenic fi lamentous microfungi (moulds), Aspergillus spp., Penicillium spp., Cladosporium spp., and Alternaria spp. in particular. Mould-induced respiratory diseases are a worldwide problem. In the last two decades, mould allergens and glucans have been used as markers of indoor exposure to moulds. Recently, mould allergens Alt a 1 (Alternaria alternata) and Asp f 1 (Aspergillus fumigatus) have been analysed in various environments (residential and occupational) with enzyme-linked immunosorbent assays, which use monoclonal or polyclonal antibodies. Household Alt a 1 and Asp f 1 levels were usually under the limit of the method detection. By contrast, higher levels of mould allergens were found in environments with high levels of bioaerosols such as poultry farms and sawmills. Data on allergen Alt a 1 and Asp f 1 levels in agricultural settings may provide information on possible colonisation of respective moulds and point out to mould-related diseases in occupants.Vlažni, unutarnji prostori mogu biti kolonizirani alergogenim, filamentoznim mikrogljivicama (plijesni) uglavnom rodova Aspergillus, Penicillium, Cladosporium i Alternaria. Respiratorne bolesti uzrokovane plijesnima zdravstveni su problem diljem svijeta. U posljednja dva desetljeća, neki sastavni dijelovi plijesni kao alergeni i glukan rabe se kao pokazatelji izloženosti plijesni u unutarnjem okolišu. Nedavno su alergeni plijesni Alt a 1 (Alternaria alternata) i Asp f 1 (Aspergillus fumigatus) određivani u različitom okolišu (kućnom i profesionalnom) enzim-imunokemijskom metodom koja rabi monoklonska ili poliklonska antitijela. Razina Alt a 1 i Asp f 1 u kućnoj prašini ispod je granice detekcije. Nasuprot tomu, alergeni plijesni su određeni u okolišu s visokom razinom bioaerosola kao peradarnici i pilane. Razine alergena Alt a 1 i Asp f 1 u nekim poljoprivrednim objektima pružaju informaciju o mogućoj kolonizaciji plijesnima, što upućuje na moguće zdravstvene učinke kod zaposlenika

A comparative analysis of the information content in long and short SAGE libraries

BACKGROUND: Serial Analysis of Gene Expression (SAGE) is a powerful tool to determine gene expression profiles. Two types of SAGE libraries, ShortSAGE and LongSAGE, are classified based on the length of the SAGE tag (10 vs. 17 basepairs). LongSAGE libraries are thought to be more useful than ShortSAGE libraries, but their information content has not been widely compared. To dissect the differences between these two types of libraries, we utilized four libraries (two LongSAGE and two ShortSAGE libraries) generated from the hippocampus of Alzheimer and control samples. In addition, we generated two additional short SAGE libraries, the truncated long SAGE libraries (tSAGE), from LongSAGE libraries by deleting seven 5' basepairs from each LongSAGE tag. RESULTS: One problem that occurred in the SAGE study is that individual tags may have matched to multiple different genes – due to the short length of a tag. We found that the LongSAGE tag maps up to 15 UniGene clusters, while the ShortSAGE and tSAGE tags map up to 279 UniGene clusters. Both long and short SAGE libraries exhibit a large number of orphan tags (no gene information in UniGene), implying the limitation of the UniGene database. Among 100 orphan LongSAGE tags, the complete sequences (17 basepairs) of nine orphan tags match to 17 genomic sequences; four of the orphan tags match to a single genomic sequence. Our data show the potential to resolve 4–9% of orphan LongSAGE tags. Finally, among 400 tSAGE tags showing significant differential expression between AD and control, 79 tags (19.8%) were derived from multiple non-significant LongSAGE tags, implying the false positive results. CONCLUSION: Our data show that LongSAGE tags have high specificity in gene mapping compared to ShortSAGE tags. LongSAGE tags show an advantage over ShortSAGE in identifying novel genes by BLAST analysis. Most importantly, the chances of obtaining false positive results are higher for ShortSAGE than LongSAGE libraries due to their specificity in gene mapping. Therefore, it is recommended that the number of corresponding UniGene clusters (gene or ESTs) of a tag for prioritizing the significant results be considered

Određivanje alergena Asp f 1 (Aspergillus fumigatus) u peradarniku enzimimunokemijskom metodom

Poultry farms contain high levels of allergenic fungi, and Aspergillus spp. is the most common genus of moulds. Aspergillus fumigatus antigens are responsible for the development of several respiratory diseases including asthma. The aim of this study was to measure the mass fraction of Asp f 1, a major allergen of Asperillus fumigatus in 37 indoor dust samples collected from four poultry farms in a rural area of the Zagreb County (Croatia) using the enzyme-linked immunosorbent assay. More than 62 % of dust samples had detectable Asp f 1 levels (limit of detection 3.6 ng g-1). The overall mean Asp f 1 level was 17.9 ng g-1 [range (3.8 to 72.4) ng g-1]. Satisfactory results were obtained for analytical within-run imprecision (6.7 %), between-run imprecision (10.5 %), and accuracy (91 % to 115 %). Microclimate parameters (air temperature, relative humidity, and velocity) were within the recommended ranges in all poultry farms. This study has shown that Asp f 1 settles on dust at poultry farms and that occupational exposure to this allergen deserves monitoring in livestock buildings.Peradarnici sadržavaju veliku koncentraciju alergenih plijesni, a rod Aspergillus najčešće je zastupljen. Antigeni soja Aspergillus fumigatus odgovorni su za nastanak nekoliko respiratornih bolesti uključujući astmu. Cilj ovoga rada bio je odrediti masenu frakciju Asp f 1, glavnog alergena soja Asperillus fumigatus u 37 uzoraka prašine uzorkovanih u četiri peradarnika sa šireg područja Zagrebačke županije rabeći enzimimunokemijsku metodu. Više od 62 % uzoraka prašine u tri peradarnika imalo je mjerljivu koncentraciju Asp f 1 (granica detekcije = 3.6 ng g-1). Ukupni srednji maseni udio Asp f 1 iznosio je 17.9 ng g-1 (raspon od 3.8 ng g-1 do 72.4 ng g-1). Dobiveni su zadovoljavajući rezultati za analitičku nepreciznost u seriji (6.7 %), nepreciznost iz dana u dan (10.5 %) i točnost (91 % do 115 %). Mikroklimatski parametri (temperatura zraka, relativna vlaga i protok zraka) u svim peradarnicima bili su u okviru preporučenih vrijednosti. Rezultati ovoga rada pokazuju da Asp f 1 sedimentira na prašinu u peradarnicima te da profesionalnu izloženost tom alergenu treba pratiti u jedinicama za uzgoj stoke

What People Believe about How Memory Works: A Representative Survey of the U.S. Population

Incorrect beliefs about the properties of memory have broad implications: The media conflate normal forgetting and inadvertent memory distortion with intentional deceit, juries issue verdicts based on flawed intuitions about the accuracy and confidence of testimony, and students misunderstand the role of memory in learning. We conducted a large representative telephone survey of the U.S. population to assess common beliefs about the properties of memory. Substantial numbers of respondents agreed with propositions that conflict with expert consensus: Amnesia results in the inability to remember one's own identity (83% of respondents agreed), unexpected objects generally grab attention (78%), memory works like a video camera (63%), memory can be enhanced through hypnosis (55%), memory is permanent (48%), and the testimony of a single confident eyewitness should be enough to convict a criminal defendant (37%). This discrepancy between popular belief and scientific consensus has implications from the classroom to the courtroom

Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

Background: Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings: We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions: Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of plasma biomarkers for pre-clinical AD. While studies of independent test sets are required to validate the signatures, these analyses provide a starting point for developing a cost-effective and minimally invasive test capable of diagnosing AD in its pre-clinical stages

Polymorphic Structures of Alzheimer's β-Amyloid Globulomers

Misfolding and self-assembly of Amyloid-β (Aβ) peptides into amyloid fibrils is pathologically linked to the development of Alzheimer's disease. Polymorphic Aβ structures derived from monomers to intermediate oligomers, protofilaments, and mature fibrils have been often observed in solution. Some aggregates are on-pathway species to amyloid fibrils, while the others are off-pathway species that do not evolve into amyloid fibrils. Both on-pathway and off-pathway species could be biologically relevant species. But, the lack of atomic-level structural information for these Aβ species leads to the difficulty in the understanding of their biological roles in amyloid toxicity and amyloid formation.Here, we model a series of molecular structures of Aβ globulomers assembled by monomer and dimer building blocks using our peptide-packing program and explicit-solvent molecular dynamics (MD) simulations. Structural and energetic analysis shows that although Aβ globulomers could adopt different energetically favorable but structurally heterogeneous conformations in a rugged energy landscape, they are still preferentially organized by dynamic dimeric subunits with a hydrophobic core formed by the C-terminal residues independence of initial peptide packing and organization. Such structural organizations offer high structural stability by maximizing peptide-peptide association and optimizing peptide-water solvation. Moreover, curved surface, compact size, and less populated β-structure in Aβ globulomers make them difficult to convert into other high-order Aβ aggregates and fibrils with dominant β-structure, suggesting that they are likely to be off-pathway species to amyloid fibrils. These Aβ globulomers are compatible with experimental data in overall size, subunit organization, and molecular weight from AFM images and H/D amide exchange NMR.Our computationally modeled Aβ globulomers provide useful insights into structure, dynamics, and polymorphic nature of Aβ globulomers which are completely different from Aβ fibrils, suggesting that these globulomers are likely off-pathway species and explaining the independence of the aggregation kinetics between Aβ globulomers and fibrils

Functional Studies on the IBD Susceptibility Gene IL23R Implicate Reduced Receptor Function in the Protective Genetic Variant R381Q

Genome-wide association studies (GWAS) in several populations have demonstrated significant association of the IL23R gene with IBD (Crohn's disease (CD) and ulcerative colitis (UC)) and psoriasis, suggesting that perturbation of the IL-23 signaling pathway is relevant to the pathophysiology of these diseases. One particular variant, R381Q (rs11209026), confers strong protection against development of CD. We investigated the effects of this variant in primary T cells from healthy donors carrying IL23RR381 and IL23RQ381 haplotypes. Using a proprietary anti-IL23R antibody, ELISA, flow cytometry, phosphoflow and real-time RT-PCR methods, we examined IL23R expression and STAT3 phosphorylation and activation in response to IL-23. IL23RQ381 was associated with reduced STAT3 phosphorylation upon stimulation with IL-23 and decreased number of IL-23 responsive T-cells. We also observed slightly reduced levels of proinflammatory cytokine secretion in IL23RQ381 positive donors. Our study shows conclusively that IL23RQ381 is a loss-of-function allele, further strengthening the implication from GWAS results that the IL-23 pathway is pathogenic in human disease. This data provides an explanation for the protective role of R381Q in CD and may lead to the development of improved therapeutics for autoimmune disorders like CD

Atorvastatin Therapy during the Peri-Infarct Period Attenuates Left Ventricular Dysfunction and Remodeling after Myocardial Infarction

Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dtmax, end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis