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51.
Keld Poulsen Justyna MC Bahl Anja H Simonsen Steen G Hasselbalch Niels HH Heegaard 《Clinical proteomics》2014,11(1):12
Background
Transthyretin (TTR), an abundant protein in cerebrospinal fluid (CSF), contains a free, oxidation-prone cysteine residue that gives rise to TTR isoforms. These isoforms may reflect conditions in vivo. Since increased oxidative stress has been linked to neurodegenerative disorders such as Alzheimer’s disease (AD) it is of interest to characterize CSF-TTR isoform distribution in AD patients and controls. Here, TTR isoforms are profiled directly from CSF by an optimized immunoaffinity-mass spectrometry method in 76 samples from patients with AD (n = 37), mild cognitive impairment (MCI, n = 17)), and normal pressure hydrocephalus (NPH, n = 15), as well as healthy controls (HC, n = 7). Fractions of three specific oxidative modifications (S-cysteinylation, S-cysteinylglycinylation, and S-glutathionylation) were quantitated relative to the total TTR protein. Results were correlated with diagnostic information and with levels of CSF AD biomarkers tau, phosphorylated tau, and amyloid β1-42 peptide.Results
Preliminary data highlighted the high risk of artifactual TTR modification due to ex vivo oxidation and thus the samples for this study were all collected using strict and uniform guidelines. The results show that TTR is significantly more modified on Cys(10) in the AD and MCI groups than in controls (NPH and HC) (p ≤ 0.0012). Furthermore, the NPH group, while having normal TTR isoform distribution, had significantly decreased amyloid β peptide but normal tau values. No obvious correlations between levels of routine CSF biomarkers for AD and the degree of TTR modification were found.Conclusions
AD and MCI patients display a significantly higher fraction of oxidatively modified TTR in CSF than the control groups of NPH patients and HC. Quantitation of CSF-TTR isoforms thus may provide diagnostic information in patients with dementia symptoms but this should be explored in larger studies including prospective studies of MCI patients. The development of methods for simple, robust, and reproducible inhibition of in vitro oxidation during CSF sampling and sample handling is highly warranted. In addition to the diagnostic information the possibility of using TTR as a CSF oxymeter is of potential value in studies monitoring disease activity and developing new drugs for neurodegenerative diseases. 相似文献52.
Hsyue-Jen Hsieh Ching-Ann Liu Bin Huang Anne HH Tseng Danny Ling Wang 《Journal of biomedical science》2014,21(1):1-15
Hemodynamic shear stress, the blood flow-generated frictional force acting on the vascular endothelial cells, is essential for endothelial homeostasis under normal physiological conditions. Mechanosensors on endothelial cells detect shear stress and transduce it into biochemical signals to trigger vascular adaptive responses. Among the various shear-induced signaling molecules, reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in vascular homeostasis and diseases. In this review, we explore the molecular, cellular, and vascular processes arising from shear-induced signaling (mechanotransduction) with emphasis on the roles of ROS and NO, and also discuss the mechanisms that may lead to excessive vascular remodeling and thus drive pathobiologic processes responsible for atherosclerosis. Current evidence suggests that NADPH oxidase is one of main cellular sources of ROS generation in endothelial cells under flow condition. Flow patterns and magnitude of shear determine the amount of ROS produced by endothelial cells, usually an irregular flow pattern (disturbed or oscillatory) producing higher levels of ROS than a regular flow pattern (steady or pulsatile). ROS production is closely linked to NO generation and elevated levels of ROS lead to low NO bioavailability, as is often observed in endothelial cells exposed to irregular flow. The low NO bioavailability is partly caused by the reaction of ROS with NO to form peroxynitrite, a key molecule which may initiate many pro-atherogenic events. This differential production of ROS and RNS (reactive nitrogen species) under various flow patterns and conditions modulates endothelial gene expression and thus results in differential vascular responses. Moreover, ROS/RNS are able to promote specific post-translational modifications in regulatory proteins (including S-glutathionylation, S-nitrosylation and tyrosine nitration), which constitute chemical signals that are relevant in cardiovascular pathophysiology. Overall, the dynamic interplay between local hemodynamic milieu and the resulting oxidative and S-nitrosative modification of regulatory proteins is important for ensuing vascular homeostasis. Based on available evidence, it is proposed that a regular flow pattern produces lower levels of ROS and higher NO bioavailability, creating an anti-atherogenic environment. On the other hand, an irregular flow pattern results in higher levels of ROS and yet lower NO bioavailability, thus triggering pro-atherogenic effects. 相似文献
53.
Karina Lauenborg M?ller Lau Caspar Thygesen Jasper Schipperijn Steffen Loft Jens Peter Bonde Sigurd Mikkelsen Charlotte Brauer 《PloS one》2014,9(9)
Background
Exposure to ultrafine particles (UFP) has been linked to cardiovascular and lung diseases. Combustion of jet fuel and diesel powered handling equipment emit UFP resulting in potentially high exposure levels among employees working at airports. High levels of UFP have been reported at several airports, especially on the apron, but knowledge on individual exposure profiles among different occupational groups working at an airport is lacking.Purpose
The aim of this study was to compare personal exposure to UFP among five different occupational groups working at Copenhagen Airport (CPH).Method
30 employees from five different occupational groups (baggage handlers, catering drivers, cleaning staff and airside and landside security) at CPH were instructed to wear a personal monitor of particle number concentration in real time and a GPS device. The measurements were carried out on 8 days distributed over two weeks in October 2012. The overall differences between the groups were assessed using linear mixed model.Results
Data showed significant differences in exposure levels among the groups when adjusted for variation within individuals and for effect of time and date (p<0.01). Baggage handlers were exposed to 7 times higher average concentrations (geometric mean, GM: 37×103 UFP/cm3, 95% CI: 25–55×103 UFP/cm3) than employees mainly working indoors (GM: 5×103 UFP/cm3, 95% CI: 2–11×103 UFP/cm3). Furthermore, catering drivers, cleaning staff and airside security were exposed to intermediate concentrations (GM: 12 to 20×103 UFP/cm3).Conclusion
The study demonstrates a strong gradient of exposure to UFP in ambient air across occupational groups of airport employees. 相似文献54.
We previously reported that cultured mammalian cells incubated with 4-
methylumbelliferyl (MU) or p -nitrophenyl (pNP) beta-xyloside synthesize an
alpha-GalNAc-terminated pentasaccharide resembling the
glycosaminoglycan-core protein linkage region. Here we show that human
melanoma M21 cells and human neuroblastoma cells incubated with Xylbeta-
MU/pNP also make an alpha-GalNAc-terminated heptasaccharide containing one
chondroitin disaccharide repeat. High performance liquid chromatography and
matrix-assisted laser desorption ionization mass spectrometry analysis of
intact or glycosidase-digested xyloside showed the structure as:
GalNAcalphaGlcAbeta1,3GalNAcbeta1,4GlcAbeta1,3Galbe ta1,3Galbeta1,
4Xylbeta-MU/pNP. The alpha-GalNAc-terminated xylosides can account for
approximately 10% of the total Xylbeta-MU/pNP products ( approximately 1.5
nmol/h/mg). These results show that GalNAcalphaGlcAbeta-modification is
relatively abundant, but not unique to the GAG-linkage tetrasaccharide.
alpha-GalNAc addition to the GlcA residue does not appear to be an
extension of general phase II detoxification of xenobiotics that involve
glucuronidation, since M21 cells incubated with MU synthesize only 0.3 pmol
GlcAbeta-MU/h/mg protein, and undetectable amount of GalNAcalphaGlcAbeta-MU
(<40 fmol/h/mg). Further, subcellular fractionation shows that the
alpha- N- acetylgalactosaminyltransferase activity colocalizes in the Golgi
with other glycosyl transferases and not in the ER, where xenobiotic
detoxification glucuronosyltransferases are found. Although
GalNAcalphaGlcAbeta-terminal modification has not been detected on
naturally occurring GAG chains, the substantial amount of alpha-GalNAc
transferase activity suggests that the alpha-GalNAc transferase could
utilize other GlcA-containing glycoconjugates as acceptors.
相似文献
55.
56.
Lisbeth Garbrecht Thygesen Budi Juliman Hidayat Katja Salomon Johansen Claus Felby 《Journal of industrial microbiology & biotechnology》2011,38(8):975-983
The study of biomass deconstruction by enzymatic hydrolysis has hitherto not focussed on the importance of supramolecular
structures of cellulose. In lignocellulose fibres, regions with a different organisation of the microfibrils are present.
These regions are called dislocations or slip planes and they are known to be more susceptible to various forms of degradation
such as acid hydrolysis. Traditionally the cellulose within these regions has been assumed to be amorphous, but in this study
it is shown by use of polarized light microscopy that dislocations are birefringent. This indicates that they have a crystalline
organisation. Dislocations may be entry points for endoglucanases. Using a fluorescent labelled endoglucanase combined with
confocal fluorescence microscopy, it is shown that the enzyme selectively binds to dislocations during the initial phase of
the hydrolysis. Using a commercial cellulase mixture on hydrothermally treated wheat straw, it was found that the fibres were
cut into segments corresponding to the sections between the dislocations initially present, as has previously been observed
for acid hydrolysis of softwood pulps. The results indicate that dislocations are important during the initial part of enzymatic
hydrolysis of cellulose. The implications of this phenomenon have not yet been recognized or explored within cellulosic biofuels. 相似文献
57.
目的:探讨应用ARIMA模型预测宝安区某街道其它感染性腹泻发病率的可行性。方法:应用SPSS13.0软件对2005年~2009年宝安区某街道其它感染性腹泻逐月发病率进行ARIMA模型建模拟合,用所得到的模型对2010年各月发病率进行预测,并评价其预测效果。结果:宝安区某街道其它感染性腹泻发病率每年11月为发病高峰,ARIMA(0,1,1)(0,1,0)12模型是其拟合的最佳模型,其预测结果和实际值绝对误差的绝对值最大为930.47,最小为1.96,平均值214.83,平均相对误差百分比39.04%。结论:模型虽然起到一定的预测效果,但预测精度仍存在误差,可通过积累新的周期数据对ARIMA模型进行修正和重新拟合,也可尝试新的预测方法或其他模型,才能加强和保证预测的精度。 相似文献
58.
目的:探讨应用ARIMA模型预测宝安区某街道其它感染性腹泻发病率的可行性。方法:应用SPSSl3.0软件对2005年~2009年宝安区某街道其它感染性腹泻逐月发病率进行ARIMA模型建模拟合,用所得到的模型对2010年各月发病率进行预测,并评价其预测效果。结果:宝安区桌街道其它感染性腹泻发病率每年11月为发病高峰,ARIMA(0,1,1)(0,1,0)12模型是其拟合的最佳模型,其预测结果和实际值绝对误差的绝对值最大为930.47,最小为1.96,平均值214.83,平均相对误差百分比39.04%。结论:模型虽然起到一定的预测效果,但预测精度仍存在误差,可通过积累新的周期数据对ARIMA模型进行修正和重新拟合,也可尝试新的预测方法或其他模型,才能加强和保证预测的精度。 相似文献
59.
The comb jelly Mertensia ovum, widely distributed in Arctic regions, has recently been discovered in the northern Baltic Sea. We show that M. ovum also exists in the central Baltic but that the population consists solely of small-sized larvae (less than 1.6 mm). Despite the absence of adults, eggs were abundant. Experiments revealed that the larvae were reproductively active. Egg production and anticipated mortality rates suggest a self-sustaining population. This is the first account of a ctenophore population entirely recruiting through larval reproduction (paedogenesis). We hypothesize that early reproduction is favoured over growth to compensate for high predation pressure. 相似文献
60.
BE Benediktsdóttir KK Sørensen MB Thygesen KJ Jensen T Gudjónsson O Baldursson M Másson 《Carbohydrate polymers》2012,90(3):1273-1280
Fluorescent labeling of chitosan and its derivatives is widely used for in vitro visualization and is accomplished by random introduction of the fluorophore to the polymer backbone, conceivably altering the bioactivity of the polymer. Here, we report for the first time the regioselective conjugation of a fluorophore to the reducing end of a fully N,N,N-trimethylated chitosan (TMC) by oxime formation. End-labeled conjugation of 5-(2-((aminooxyacetyl)amino)ethylamino)naphthalene-1-sulfonic acid (EDANS-O-NH(2)) fluorophore to TMC to form TMC-oxime-EDANS (f-TMC) was confirmed by (1)H NMR and fluorescence spectroscopy. Average molecular weight calculations of f-TMC with (1)H NMR and fluorescence spectroscopy gave similar results or ~7.7kDa. f-TMC in human bronchial epithelial cells was both cell membrane bound as well as intracellularly localized. This demonstrates the proof-of-concept for selective oxime formation at the reducing end of a chitosan derivative, which can be used for tracking chitosan in gene and drug delivery purposes and gives rise to further modifications with other functional groups. 相似文献