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31.
Di Xiang Jing Zhang Yizhe Chen Yiping Guo Adrian Schalow Zhonghui Zhang Xiaojia Hu Hongjing Yu Mei Zhao Shunying Zhu Huili Lu Mingyuan Wu Yan Yu Anja Moldenhauer Wei Han 《Protein expression and purification》2010,69(2):153-158
Chemerin is a novel chemokine that binds to the G protein-coupled receptor (GPCR) ChemR23, also known as chemokine-like receptor 1 (CMKLR1). It is secreted as a precursor and executes pro-inflammatory functions when the last six amino acids are removed from its C-terminus by serine proteases. After maturation, Chemerin attracts dendritic cells and macrophages through binding to ChemR23. We report a new method for expression and purification of mature recombinant human Chemerin (rhChemerin) using a prokaryotic system. After being expressed in bacteria, rhChemerin in inclusion bodies was denatured using 6 M guanidine chloride. Soluble rhChemerin was prepared by the protein-specific renaturation solution under defined conditions. It was subsequently purified using ion-exchange columns to more than 95% purity with endotoxin level <1.0 EU/μg. We further demonstrated its biological activities for attracting migration of human dendritic cells and murine macrophages in vitro using established chemotaxis assays. 相似文献
32.
Baillie GS Huston E Scotland G Hodgkin M Gall I Peden AH MacKenzie C Houslay ES Currie R Pettitt TR Walmsley AR Wakelam MJ Warwicker J Houslay MD 《The Journal of biological chemistry》2002,277(31):28298-28309
Here we identify an 11-residue helical module in the unique N-terminal region of the cyclic AMP-specific phosphodiesterase PDE4A1 that determines association with phospholipid bilayers and shows a profound selectivity for interaction with phosphatidic acid (PA). This module contains a core bilayer insertion unit that is formed by two tryptophan residues, Trp(19) and Trp(20), whose orientation is optimized for bilayer insertion by the Leu(16):Val(17) pairing. Ca(2+), at submicromolar levels, interacts with Asp(21) in this module and serves to gate bilayer insertion, which is completed within 10 ms. Selectivity for interaction with PA is suggested to be achieved primarily through the formation of a charge network of the form (Asp(21-):Ca(2+):PA(2-):Lys(24+)) with overall neutrality at the bilayer surface. This novel phospholipid-binding domain, which we call TAPAS-1 (tryptophan anchoring phosphatidic acid selective-binding domain 1), is here identified as being responsible for membrane association of the PDE4A1 cAMP-specific phosphodiesterase. TAPAS-1 may not only serve as a paradigm for other PA-binding domains but also aid in detecting related phospholipid-binding domains and in generating simple chimeras for conferring membrane association and intracellular targeting on defined proteins. 相似文献
33.
34.
Giovanna Della Porta Jeroen A. M. Kenter Juan R. Bahamonde Adrian Immenhauser Elisa Villa 《Facies》2003,49(1):175-207
Summary The Carboniferous, particularly during the Serpukhovian and Bashkirian time, was a period of scarce shallow-water calcimicrobial-microbialite
reef growth. Organic frameworks developed on high-rising platforms are, however, recorded in the Precaspian Basin subsurface,
Kazakhstan, Russia, Japan and Spain and represent uncommon occurrences within the general trend of low accumulation rates
and scarcity of shallow-water reefs. Sierra del Cuera (Cantabrian Mountains, N Spain) is a well-exposed high-rising carbonate
platform of Late Carboniferous (Bashkirian-Moscovian) age with a microbial boundstone-dominated slope dipping from 20° up
to 45°. Kilometer-scale continuous exposures allow the detailed documentation of slope geometry and lithofacies spatial distribution.
This study aims to develop a depositional model of steep-margined Late Paleozoic platforms built by microbial carbonates and
to contribute to the understanding of the controlling factors on lithofacies characteristics, stacking patterns, accumulation
rates and evolution of the depositional architecture of systems, which differ from light-dependent coralgal platform margins.
From the platform break to depths of nearly 300 m, the slope is dominated by massive cement-rich boundstone, which accumulated
through the biologically induced precipitation of micrite. Boundstone facies (type A) with peloidal carbonate mud, fenestellid
and fistuliporid bryozoans, sponge-like molds and primary cavities filled by radiaxial fibrous cement occurs all over the
slope but dominates the deeper settings. Type B boundstone consists of globose centimeter-scale laminated accretionary structures,
which commonly host botryoidal cement in growth cavities. The laminae nucleate around fenestellid bryozoans, sponges, Renalcis and Girvanella-like filaments. Type B boundstone typically occurs at depths between 20–150 m to locally more than 300 m and forms the bulk
of the Bashkirian prograding slope. The uppermost slope boundstone (type C; between 0 and 20–100 m depth) includes peloidal
micrite, radiaxial fibrous cement, bryozoans, sponge molds, Donezella, Renalcis, Girvanella, Ortonella, calcareous algae and calcitornellid foraminifers.
From depths of 80–200 m to 450 m, 1–30 m thick lenses of crinoidal packstone, spiculitic wackestone, and bryozoan biocementstone
with red-stained micrite matrix are episodically intercalated with boundstone and breccias. These layers increase in number
from the uppermost Bashkirian to the Moscovian in parallel with the change from a rapidly prograding to an aggrading architecture.
The red-stained strata share comparable features with Lower Carboniferous deeper-water mud-mound facies and were deposited
during relative rises of sea level and pauses in boundstone production. Rapid relative sea-level rises might have been associated
with changes in oceanographic conditions not favourable for thecalcimicrobial boundstone growth, such as upwelling of colder,
nutrient-rich waters lifting the thermocline to depths of 80–200 m.
Downslope of 150–300 m, boundstones interfinger with layers of matrix-free breccias, lenses of matrix-rich breccias, platform-
and slope-derived grainstone and crinoidal packstone. Clast-supported breccias bound by radiaxial cement are produced by rock
falls and avalanches coeval to boundstone growth. Matrix-rich breccias are debris flow deposits triggered by the accumulation
of red-stained layers. Debris flows develop following the relative sea-level rises, which favour the deposition of micrite-rich
lithofacies on the slope rather than being related to relative sea-level falls and subaerial exposures. The steep slope angles
are the result of in situ growth and rapid stabilization by marine cement in the uppermost part, passing into a detrital talus, which rests at the
angle of repose of noncohesive material. In the Moscovian, the aggradational architecture and steeper clinoforms are the result
of increased accommodation space due to tectonic subsidence and due to a reduction of slope accumulation rates (from 240±45−605±35
m/My to 130±5 m/My). The increasing number of red-stained layers and the decrease of boundstone productivity are attributed
to environmental changes in the adjacent basin, in particular during relative rises of sea level and to possible cooling due
to icehouse conditions. The geometry of the depositional system appears to be controlled by boundstone growth rates. During
the Bashkirian, the boundstone growth potential is at least 10 times greater than average values for ancient carbonate systems.
The slope progradation rates (nearly 400–1000 m/My) are similar to the highest values deduced for the Holocene Bahamian prograding
platform margin. The fundamental differences with modern systems are that progradation of the microbial-boundstone dominated
steep slope is primarily controlled by boundstone growth rates rather than by highstand shedding from the platform top and
that boundstone growth is largely independent from light and controlled by the physicochemical characteristics of seawater. 相似文献
35.
The association of the prion protein (PrP) with sphingolipid- and cholesterol-rich lipid rafts is instrumental in the pathogenesis of the neurodegenerative prion diseases. Although the glycosylphosphatidylinositol (GPI) anchor is an exoplasmic determinant of raft association, PrP remained raft-associated in human neuronal cells even when the GPI anchor was deleted or substituted for a transmembrane anchor indicating that the ectodomain contains a raft localization signal. The raft association of transmembrane-anchored PrP occurred independently of Cu(II) binding as it failed to be abolished by either deletion of the octapeptide repeat region (residues 51-90) or treatment of cells with a Cu(II) chelator. Raft association of transmembrane-anchored PrP was only abolished by the deletion of the N-terminal region (residues 23-90) of the ectodomain. This region was sufficient to confer raft localization when fused to the N terminus of a non-raft transmembrane-anchored protein and suppressed the clathrin-coated pit localization signal in the cytoplasmic domain of the amyloid precursor protein. These data indicate that the N-terminal region of PrP acts as a cellular raft targeting determinant and that residues 23-90 of PrP represent the first proteinaceous raft targeting signal within the ectodomain of a GPI-anchored protein. 相似文献
36.
Claudia Siegl Patricia Hamminger Herbert Jank Uwe Ahting Benedikt Bader Adrian Danek Allison Gregory Monika Hartig Susan Hayflick Andreas Hermann Holger Prokisch Esther M. Sammler Zuhal Yapici Rainer Prohaska Ulrich Salzer 《PloS one》2013,8(10)
Neuroacanthocytosis (NA) refers to a group of heterogenous, rare genetic disorders, namely chorea acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s disease-like 2 (HDL2) and pantothenate kinase associated neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated with similar neurological symptoms. PKAN is also assigned to a group of rare neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron accumulation), associated with iron accumulation in the basal ganglia and progressive movement disorder. Acanthocytosis, the occurrence of misshaped erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS patients but less prevalent in PKAN (about 10%) and HDL2 patients. The pathological factors that lead to the formation of the acanthocytic red blood cell shape are currently unknown. The aim of this study was to determine whether NA/NBIA acanthocytes differ in their functionality from normal erythrocytes. Several flow-cytometry-based assays were applied to test the physiological responses of the plasma membrane, namely drug-induced endocytosis, phosphatidylserine exposure and calcium uptake upon treatment with lysophosphatidic acid. ChAc red cell samples clearly showed a reduced response in drug-induced endovesiculation, lysophosphatidic acid-induced phosphatidylserine exposure, and calcium uptake. Impaired responses were also observed in acanthocyte-positive NBIA (PKAN) red cells but not in patient cells without shape abnormalities. These data suggest an “acanthocytic state” of the red cell where alterations in functional and interdependent membrane properties arise together with an acanthocytic cell shape. Further elucidation of the aberrant molecular mechanisms that cause this acanthocytic state may possibly help to evaluate the pathological pathways leading to neurodegeneration. 相似文献
37.
Prat-Vericat Maria Marciszak Adrian Rufí Isaac Sorbelli Leonardo Llenas Manel Lucenti Saverio Bartolini Madurell-Malapeira Joan 《Journal of Mammalian Evolution》2022,29(3):547-569
Journal of Mammalian Evolution - Late Pleistocene cave lions are one of the most iconic species of Northern Hemisphere Quaternary taphocoenoses. Despite their often-scarce record in cave... 相似文献
38.
Jahnke U Higginbottom K Newland AC Cotter FE Allen PD 《Biochemical and biophysical research communications》2007,361(4):928-933
Etoposide is a potent inducer of mitotic catastrophe; a type of cell death resulting from aberrant mitosis. It is important in p53 negative cells where p53 dependent apoptosis and events at the G1 and G2 cell cycle checkpoints are compromised. Passenger proteins regulate many aspects of mitosis and siRNA interference or direct inhibition of Aurora B kinase results in mitotic catastrophe. However, there is little available data of clinical relevance in leukaemia models. Here, in p53 negative K562 myeloid leukemia cells, etoposide-induced mitotic catastrophe is shown to be time and/or concentration dependent. Survivin and Aurora remained bound to chromosomes. Survivin and Aurora were also associated with Cdk1 and were shown to form complexes, which in pull down experiments, included INCENP. There was no evidence of Aurora B kinase suppression. These data suggests etoposide will complement Aurora B kinase inhibitors currently in clinical trials for cancer. 相似文献
39.
Levels and determinants of inflammatory biomarkers in a Swiss population-based sample (CoLaus study)
Marques-Vidal P Bochud M Bastardot F Lüscher T Ferrero F Gaspoz JM Paccaud F Urwyler A von Känel R Hock C Waeber G Preisig M Vollenweider P 《PloS one》2011,6(6):e21002
Objective
to assess the levels and determinants of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) in a healthy Caucasian population.Methods
population sample of 2884 men and 3201 women aged 35 to 75. IL-1β, IL-6 and TNF-α were assessed by a multiplexed particle-based flow cytometric assay and CRP by an immunometric assay.Results
Spearman rank correlations between duplicate cytokine measurements (N = 80) ranged between 0.89 and 0.96; intra-class correlation coefficients ranged between 0.94 and 0.97, indicating good reproducibility. Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. Median (interquartile range) for participants with detectable values were 1.17 (0.48–3.90) pg/ml for IL-1β; 1.47 (0.71–3.53) pg/ml for IL-6; 2.89 (1.82–4.53) pg/ml for TNF-α and 1.3 (0.6–2.7) ng/ml for CRP. On multivariate analysis, greater age was the only factor inversely associated with IL-1β levels. Male sex, increased BMI and smoking were associated with greater IL-6 levels, while no relationship was found for age and leisure-time PA. Male sex, greater age, increased BMI and current smoking were associated with greater TNF-α levels, while no relationship was found with leisure-time PA. CRP levels were positively related to age, BMI and smoking, and inversely to male sex and physical activity.Conclusion
Population-based levels of several cytokines were established. Increased age and BMI, and to a lesser degree sex and smoking, significantly and differentially impact cytokine levels, while leisure-time physical activity has little effect. 相似文献40.
Electron paramagnetic resonance (EPR) spin-trapping experiments, employing the novel spin-trap DEPMPO, provide evidence for the formation of protein-peroxyl radicals from the reaction of bovine serum albumin (BSA) or lysozyme with HO · in the presence of O 2 . Spin-trapping leads to the detection of anisotropic spectra of partially immobilized protein-peroxyl spin-adducts; positive identification is based on a novel spectrum simulation approach (through which broadened anisotropic spectra are simulated and compared with experiment) and by comparison of results with those obtained when MeO 2 · is trapped and the adduct frozen in a solid matrix. 相似文献