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181.
Obesity and Age‐Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations 下载免费PDF全文
182.
Shiqi Zhang Holger A. Lindner Sarah Kabtni Jaap van den Born Stephan Bakker Gerjan Navis Bernard Kr?mer Benito Yard Sibylle Hauske 《PloS one》2016,11(1)
Background and Aims
The proportion of serum carnosinase (CN-1) recognized by RYSK173 monoclonal antibody negatively correlates with CN-1 activity. We thus hypothesized that the epitope recognized by RYSK173 is accessible only in a catalytically incompetent conformation of the zinc dependent enzyme and we mapped its position in the CN-1 structure. Since patients with kidney failure are often deficient in zinc and other trace elements we also assessed the RYSK173 CN-1 proportion in serum of these patients and studied the influence of hemodialysis hereon in relation to Zn2+ and Cu2+ concentration during hemodialysis.Methods and Results
Epitope mapping using myc-tagged CN-1 fragments and overlapping peptides revealed that the RYSK173 epitope directly contributes to the formation of the dinuclear Zn center in the catalytic domain of homodimeric CN-1. Binding of RYSK173 to CN-1 was however not influenced by addition of Zn2+ or Cu2+ to serum. In serum of healthy controls the proportion of CN-1 recognized by RYSK173 was significantly lower compared to end-stage renal disease (ESRD) patients (1.12 ± 0.17 vs. 1.56 ± 0.40% of total CN-1; p<0.001). During hemodialysis the relative proportion of RYSK173 CN-1 decreased in parallel with increased serum Zn2+ and Cu2+ concentrations after dialysis.Conclusions
Our study clearly indicates that RYSK173 recognizes a sequence within the transition metal binding site of CN-1, thus supporting our hypothesis that metal binding to CN-1 masks the epitope. The CN-1 RYSK173 proportion appears overall increased in ESRD patients, yet it decreases during hemodialysis possibly as a consequence of a relative increase in transition metal bound enzyme. 相似文献183.
Stephan Zindel Vera Ehret Marina Ehret Madeleine Hentschel Samantha Witt Andreas Kr?mer David Fiebig Norbert Jüttner Sabrina Fr?ls Felicitas Pfeifer Hans-Lothar Fuchsbauer 《PloS one》2016,11(2)
Streptomyces mobaraensis DSM 40847 secretes transglutaminase that cross-links proteins via γ-glutamyl-ε-lysine isopeptide bonds. Characterized substrates are inhibitory proteins acting against various serine, cysteine and metalloproteases. In the present study, the bacterial secretome was examined to uncover additional transglutaminase substrates. Fractional ethanol precipitation of the exported proteins at various times of culture growth, electrophoresis of the precipitated proteins, and sequencing of a 39 kDa protein by mass spectrometry revealed the novel beta-lactamase Sml-1. As indicated by biotinylated probes, Sml-1, produced in E. coli, exhibits glutamine and lysine residues accessible for transglutaminase. The chromogenic cephalosporin analogue, nitrocefin, was hydrolyzed by Sml-1 with low velocity. The obtained Km and kcat values of the recombinant enzyme were 94.3±1.8 μM and 0.39±0.03 s-1, respectively. Penicillin G and ampicillin proved to be weak inhibitors of nitrocefin hydrolysis (Ki of 0.1 mM and 0.18 mM). Negligible influence of metals on β-lactamase activity ruled out that Sml-1 is a Zn2+-dependent class B beta-lactamase. Rather, sequence motifs such as SITK, YSN, and HDG forming the active core in a hypothetical structure may be typical for class C beta-lactamases. Based on the results, we assume that the novel transglutaminase substrate ensures undisturbed growth of aerial hyphae in Streptomyces mobaraensis by trapping and inactivating hostile beta-lactam antibiotics. 相似文献
184.
Stephan Rudolph Antonia Nicole Klein Markus Tusche Christine Schlosser Anne Elfgen Oleksandr Brener Charlotte Teunissen Lothar Gremer Susanne Aileen Funke Janine Kutzsche Dieter Willbold 《PloS one》2016,11(2)
Alzheimer´s disease is the most prominent type of dementia and currently no causative treatment is available. According to recent studies, oligomeric species of the amyloid beta (Aβ) peptide appear to be the most toxic Aβ assemblies. Aβ monomers, however, may be not toxic per se and may even have a neuroprotective role. Here we describe a competitive mirror image phage display procedure that allowed us to identify preferentially Aβ1–42 monomer binding and thereby stabilizing peptides, which destabilize and thereby eliminate toxic oligomer species. One of the peptides, called Mosd1 (monomer specific d-peptide 1), was characterized in more detail. Mosd1 abolished oligomers from a mixture of Aβ1–42 species, reduced Aβ1–42 toxicity in cell culture, and restored the physiological phenotype in neuronal cells stably transfected with the gene coding for human amyloid precursor protein. 相似文献
185.
We investigated beta-band intermuscular coherence (IMC) in 92 healthy adults stratified by decade of age, and analysed variability between and within subjects. In the dominant upper limb, IMC was estimated between extensor digitorum communis and first dorsal interosseous as well as between flexor digitorum superficialis and first dorsal interosseous. In the ipsilateral lower limb, IMC was measured between medial gastrocnemius and extensor digitorum brevis as well as between tibialis anterior and extensor digitorum brevis. Age-related changes in IMC were analysed with age as a continuous variable or binned by decade. Intrasession variance of IMC was examined by dividing sessions into pairs of epochs and comparing coherence estimates between these pairs. Eight volunteers returned for a further session after one year, allowing us to compare intrasession and intersession variance. We found no age-related changes in IMC amplitude across almost six decades of age, allowing us to collate data from all ages into an aggregate normative dataset. Interindividual variability ranged over two orders of magnitude. Intrasession variance was significantly greater than expected from statistical variability alone, and intersession variance was even larger. Potential contributors include fluctuations in task performance, differences in electrode montage and short-term random variation in central coupling. These factors require further exploration and, where possible, minimisation. This study provides evidence that coherence is remarkably robust to senescent changes in the nervous system and provides a large normative dataset for future applications of IMC as a biomarker in disease states. 相似文献
186.
Elisabeth J. Leehr Kathrin Schag Amelie Brinkmann Ann-Christine Ehlis Andreas J. Fallgatter Stephan Zipfel Katrin E. Giel Thomas Dresler 《PloS one》2016,11(4)
ObjectiveFood stimuli are omnipresent and naturally primary reinforcing stimuli. One explanation for the intake of high amounts of food in binge eating disorder (BED) is a deviant valuation process. Valuation of food stimuli is supposed to influence approach or avoidance behaviour towards food. Focusing on self-reported and indirect (facial electromyography) valuation process, motivational aspects in the processing of food stimuli were investigated.MethodsWe compared an overweight sample with BED (BED+) with an overweight sample without BED (BED-) and with normal weight controls (NWC) regarding their self-reported and indirect (via facial electromyography) valuation of food versus non-food stimuli.ResultsRegarding the self-reported valuation, the BED+ sample showed a significantly stronger food-bias compared to the BED- sample, as food stimuli were rated as significantly more positive than the non-food stimuli in the BED+ sample. This self-reported valuation pattern could not be displayed in the indirect valuation. Food stimuli evoked negative indirect valuation in all groups. The BED+ sample showed the plainest approach-avoidance conflict marked by a diverging self-reported (positive) and indirect (negative) valuation of food stimuli.ConclusionsBED+ showed a deviant self-reported valuation of food as compared to BED-. The valuation process of the BED+ sample seems to be characterized by a motivational ambivalence. This ambivalence should be subject of further studies and may be of potential use for therapeutic interventions. 相似文献
187.
We examine gender differences among the six PhD student cohorts 2004–2009 at the California Institute of Technology using a new dataset that includes information on trainees and their advisors and enables us to construct detailed measures of teams at the advisor level. We focus on the relationship between graduate student publications and: (1) their gender; (2) the gender of the advisor, (3) the gender pairing between the advisor and the student and (4) the gender composition of the team. We find that female graduate students co-author on average 8.5% fewer papers than men; that students writing with female advisors publish 7.7% more. Of particular note is that gender pairing matters: male students working with female advisors publish 10.0% more than male students working with male advisors; women students working with male advisors publish 8.5% less. There is no difference between the publishing patterns of male students working with male advisors and female students working with female advisors. The results persist and are magnified when we focus on the quality of the published articles, as measured by average Impact Factor, instead of number of articles. We find no evidence that the number of publications relates to the gender composition of the team. Although the gender effects are reasonably modest, past research on processes of positive feedback and cumulative advantage suggest that the difference will grow, not shrink, over the careers of these recent cohorts. 相似文献
188.
Stephan Gekle 《Biophysical journal》2016,110(2):514-520
Synthetic nanoparticles and other stiff objects injected into a blood vessel filled with red blood cells are known to marginate toward the vessel walls. By means of hydrodynamic lattice-Boltzmann simulations, we show that active particles can strongly accelerate their margination by moving against the flow direction: particles located initially in the channel center migrate much faster to their final position near the wall than in the nonactive case. We explain our findings by an enhanced rate of collisions between the stiff particles and the deformable red blood cells. Our results imply that a significantly faster margination can be achieved either technically by the application of an external magnetic field (if the particles are magnetic) or biologically by self-propulsion (if the particles are, e.g., swimming bacteria). 相似文献
189.
190.