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981.
Fluorescently labeled adrenomedullin allows real‐time monitoring of adrenomedullin receptor trafficking in living cells
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Ria Schönauer Anette Kaiser Cathleen Holze Stefanie Babilon Johannes Köbberling Bernd Riedl Annette G. Beck‐Sickinger 《Journal of peptide science》2015,21(12):905-912
The human adrenomedullin (ADM) is a 52 amino acid peptide hormone belonging to the calcitonin family of peptides, which plays a major role in the development and regulation of cardiovascular and lymphatic systems. For potential use in clinical applications, we aimed to investigate the fate of the peptide ligand after binding and activation of the adrenomedullin receptor (AM1), a heterodimer consisting of the calcitonin receptor‐like receptor (CLR), a G protein‐coupled receptor, associated with the receptor activity‐modifying protein 2 (RAMP2). Full length and N‐terminally shortened ADM peptides were synthesized using Fmoc/tBu solid phase peptide synthesis and site‐specifically labeled with the fluorophore carboxytetramethylrhodamine (Tam) either by amide bond formation or copper(I)‐catalyzed azide alkyne cycloaddition. For the first time, Tam‐labeled ligands allowed the observation of co‐internalization of the whole ligand‐receptor complex in living cells co‐transfected with fluorescent fusion proteins of CLR and RAMP2. Application of a fluorescent probe to track lysosomal compartments revealed that ADM together with the CLR/RAMP2‐complex is routed to the degradative pathway. Moreover, we found that the N‐terminus of ADM is not a crucial component of the peptide sequence in terms of AM1 internalization behavior. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
982.
Helge Taubert Sven Wach Rudolf Jung Michael Pugia Bastian Keck Simone Bertz Elke Nolte Robert Stoehr Jan Lehmann Carsten-H Ohlmann Michael St?ckle Bernd Wullich Arndt Hartmann 《Molecular medicine (Cambridge, Mass.)》2015,21(1):371-380
Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan-Meier analyses and univariate/multivariate Cox regression hazard models. In a multivariate Cox regression analysis, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (relative risk [RR] = 2.7, P = 0.004, and RR = 2.4, P = 0.027). Likewise, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR = 2.3, P = 0.023, and RR = 2.2, P = 0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P = 0.005) compared with patients with strong expression. Considering only patients with high-grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This indicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients. 相似文献
983.
Bernd Simon Pawel Masiewicz Anne Ephrussi Teresa Carlomagno 《RNA (New York, N.Y.)》2015,21(8):1444-1453
mRNA localization by active transport is a regulated process that requires association of mRNPs with protein motors for transport along either the microtubule or the actin cytoskeleton. oskar mRNA localization at the posterior pole of the Drosophila oocyte requires a specific mRNA sequence, termed the SOLE, which comprises nucleotides of both exon 1 and exon 2 and is assembled upon splicing. The SOLE folds into a stem–loop structure. Both SOLE RNA and the exon junction complex (EJC) are required for oskar mRNA transport along the microtubules by kinesin. The SOLE RNA likely constitutes a recognition element for a yet unknown protein, which either belongs to the EJC or functions as a bridge between the EJC and the mRNA. Here, we determine the solution structure of the SOLE RNA by Nuclear Magnetic Resonance spectroscopy. We show that the SOLE forms a continuous helical structure, including a few noncanonical base pairs, capped by a pentanucleotide loop. The helix displays a widened major groove, which could accommodate a protein partner. In addition, the apical helical segment undergoes complex dynamics, with potential functional significance. 相似文献
984.
Dennis Otieno Joseph Ondier Sebastian Arnhold Daniel Okach Marianne Ruidisch Bora Lee Andreas Kolb John Onyango Bernd Huwe 《Plant Ecology》2015,216(10):1441-1456
Factors governing the dynamics between woody and herbaceous vegetation in the savanna are of ecological interest since they determine ecosystem productivity and stability. Field measurements were conducted in a humid savanna in the Lambwe valley, western Kenya, to compare CO2 exchange of the herbaceous vegetation and trees and its regulation. Soil characteristics and root distribution patterns under tree canopies and in the open locations dominated by the herbaceous vegetation were profiled in 1-m-deep soil layers. Soil water content (SWC) was measured at 30 cm depth both in the herbaceous vegetation and also under the tree canopies. The mean maximum monthly gross primary production (GPPmax) in the herbaceous vegetation was determined from chamber measurements, while daily GPP (GPPday) in both the grass and tree canopies was simulated using the PIXGRO model. The highest mean GPPmax in the herbaceous vegetation was 26.2 ± 3.7 μmol m-2 s-1 during April. Seasonal fluctuations of GPP in the herbaceous vegetation were explained by soil water availability (R 2 = 0.78) within the upper 30-cm soil profile. Seasonal GPPday fluctuations were larger (between 1 gC m-2 d-1 and 10 gC m-2 d-1) in the herbaceous vegetation compared to the trees, which fluctuated around 4.3 ± 0.3 gC m-2 d-1 throughout most of the measurement period. Daily tree canopy transpiration (Ec), canopy conductance (Gc), and GPPday were decoupled from SWC in the top 30-cm soil profile. On average, ecosystem GPPday (mean of tree and herbaceous vegetation) was 14.3 ± 1.2 gC m-2 d-1 during the wet period and 6.1 ± 0.9 gC m-2 d-1 during drought. Differences between the herbaceous and tree canopy responses were attributed to soil moisture availability. 相似文献
985.
The vascularized periosteum flap as novel tissue engineering model for repair of cartilage defects
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986.
987.
Sylvio Redanz Kerstin Standar Andreas Podbielski Bernd Kreikemeyer 《The Journal of biological chemistry》2012,287(43):36111-36122
988.
Impact sports and vibration platforms trigger vibrations within soft tissues and the skeleton. Although the long-term effects of vibrations on the body have been studied extensively, the acute effects of vibrations are little understood. This study determined the influence of acute vibrations at different frequencies and elbow angles on maximal isometric elbow extension torque and muscle activity. Vibrations were generated by a pneumatic vibrator attached to the lever of a dynamometer, and were applied on the forearm of 15 healthy female subjects. The subjects were instructed to push maximally against the lever at three different elbow angles, while extension torque and muscle activity were quantified and compared between vibration and non-vibration (control) conditions. A change in vibration frequency had no significant effects on torque and muscle activity although vibrations in general decreased the maximal extension torque relative to the control by 1.8% (±5.7%, p>0.05), 7.4% (±7.9%, p<0.01), and 5.0% (±8.2%, p<0.01) at elbow angles of 60°, 90°, and 120°, respectively. Electromyographic activity increased significantly between ~30% and 40% in both triceps and biceps with vibrations. It is speculated that a similar increase in muscle activity between agonist and antagonist, in combination with an unequal increase in muscle moment arms about the elbow joint, limit the maximal extension torque during exposure to vibrations. This study showed that maximal extension torque decreased during vibration exposure while muscle activity increased and suggests that vibrations may be counterproductive during activities requiring maximal strength but potentially beneficial for strength training. 相似文献
989.
Lopez del Amo JM Fink U Dasari M Grelle G Wanker EE Bieschke J Reif B 《Journal of molecular biology》2012,421(4-5):517-524
The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease β-amyloid peptide (Aβ) neurotoxicity. Solution-state NMR allows probing initial EGCG-Aβ interactions. We show that EGCG-induced Aβ oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. We find that EGCG interferes with the aromatic hydrophobic core of Aβ. The C-terminal part of the Aβ peptide (residues 22-39) adopts a β-sheet conformation, whereas the N-terminus (residues 1-20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric Aβ aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development. 相似文献
990.
Krüger O Chakarov N Nielsen JT Looft V Grünkorn T Struwe-Juhl B Møller AP 《The Journal of animal ecology》2012,81(2):330-340
1. The habitat heterogeneity (HHH) and individual adjustment (IAH) hypotheses are commonly proposed to explain a decrease in reproduction rate with increasing population density. Higher numbers of low-quality territories with low reproductive success as density increases lead to a decrease in reproduction under the HHH, while more competition at high density decreases reproduction across all territories under the IAH. 2. We analyse the influence of density and habitat heterogeneity on reproductive success in eight populations of long-lived territorial birds of prey belonging to four species. Sufficient reliability in distinguishing between population-wide, site-specific and individual quality effects on reproduction was granted through the minimal duration of 20 years of all data sets and the ability to control for individual quality in five of them. 3. Density increased in five populations but reproduction did not decrease in these. Territory occupancy as a surrogate of territory quality correlated positively with reproductive success but only significantly so in large data sets with more than 100 territories. 4. Reproductive success was always best explained by measures of territory quality in multivariate models. Direct or delayed (t-1) population density entered very few of the best models. Mixed models controlling for individual quality showed an increasing reproductive performance in older individuals and in those laying earlier, but measures of territory quality were also always retained in the best models. 5. We find strong support for the habitat heterogeneity hypothesis but weak support for the individual adjustment hypothesis. Both individual and site characteristics are crucial for reproductive performance in long-lived birds. Proportional occupancy of territories enables recognition of high-quality territories as preferential conservation targets. 相似文献