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111.
    
Transactivation of epidermal growth factor receptor (EGFR) by G protein-coupled receptors (GPCRs) is currently understood to be mediated by matrix metalloproteases (MMPs) and the release of EGF-like ligands. This ligand-mediated process also suggests that downstream of EGFR the signalling in response to GPCR ligands or EGF appears to be indistinguishable. Here we provide evidence that transactivation of EGFR by the beta2-adrenergic receptor (beta2-AR) is independent of MMPs and results in an incomplete downstream signalling involving extracellular signal-activated kinase (ERK) but not PLCgamma1 and Akt. In contrast, beta2-AR has the ability to activate PLCgamma1 when the EGFR is primed either by co-stimulation with EGF or by increased basal activity due to over-expression. In that way but not via the beta2-AR-mediated transactivation the EGFR docking sites pY992 and pY1173 may be generated which are critical for PLCgamma1. This EGFR-supported transactivation is strongly dependent on EGFR tyrosine kinase, c-Src, and the c-Src-specific EGFR tyrosine residue 845 and represents a novel paradigm of EGFR transactivation.  相似文献   
112.

Background

Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance.

Objective

To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study.

Design

Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured.

Results

Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%.

Conclusions

A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss.

Registration

ClinicalTrials.gov NCT00390637  相似文献   
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BackgroundStent-assisted coil embolization (SACE) plays an important role in the treatment of intracranial aneurysms. The purpose of this study was to investigate geometrical changes caused by closed-cell design stents in bifurcation and sidewall aneurysms.Methods31 patients with 34 aneurysms underwent SACE with closed-cell design stents. Inflow angle α, determined by aneurysm neck and afferent vessel, and angle between afferent and efferent vessel close to (δ1), respectively, more remote from the aneurysm neck (δ2) were graphically determined in 2D angiography projections.ResultsStent assisted coiling resulted in a significant increase of all three angles from a mean value (±SEM) of α = 119° (±6.5°) pretreatment to 130° (±6.6°) posttreatment (P ≤ .001), δ1 = 129° (±6.4°) to 139° (±6.1°), (P ≤ .001) and δ2 = 115° (±8.4°) to 126° (±7.5°), (P ≤ .01). Angular change of δ1 in AcomA aneurysms was significant greater compared to sidewall aneurysms (26°±4.9° versus 8°± 2.3°, P ≤ .05). The initial angle of δ1 and δ2 revealed a significantly inverse relationship to the angle increase (δ1: r = -0.41, P ≤ .05 and δ2: r = -0.47, P ≤ .01). Moreover, angle δ1 was significantly higher in unruptured compared to ruptured aneurysms (135°±7.1° versus 103°±10.8°, P ≤ .05).ConclusionStent deployment modulates the geometry of the aneurysm-vessel complex, which may lead to favorable hemodynamic changes more similar to unruptured than to ruptured aneurysms. Our findings also suggest that the more acute-angled aneurysm-vessel anatomy, the larger the angular change. Further studies are needed to investigate whether these changes improve the clinical outcome.  相似文献   
115.
A novel function of NF-kappaB in the development of most ectodermal appendages, including two types of murine pelage hair follicles, was detected in a mouse model with suppressed NF-kappaB activity (c(IkappaBalphaDeltaN)). However, the developmental processes regulated by NF-kappaB in hair follicles has remained unknown. Furthermore, the similarity between the phenotypes of c(IkappaBADeltaN) mice and mice deficient in Eda A1 (tabby) or its receptor EdaR (downless) raised the issue of whether in vivo NF-kappaB regulates or is regulated by these novel TNF family members. We now demonstrate that epidermal NF-kappaB activity is first observed in placodes of primary guard hair follicles at day E14.5, and that in vivo NF-kappaB signalling is activated downstream of Eda A1 and EdaR. Importantly, ectopic signals which activate NF-kappaB can also stimulate guard hair placode formation, suggesting a crucial role for NF-kappaB in placode development. In downless and c(IkappaBalphaDeltaN) mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-kappaB signalling. We show that NF-kappaB activation is essential for induction of Shh and cyclin D1 expression and subsequent placode down growth. However, cyclin D1 induction appears to be indirectly regulated by NF-kappaB, probably via Shh and Wnt. The strongly decreased number of hair follicles observed in c(IkappaBalphaDeltaN) mice compared with tabby mice, indicates that additional signals, such as TROY, must regulate NF-kappaB activity in specific hair follicle subtypes.  相似文献   
116.
A novel hemoglobin variant was detected by electrospray ionization mass spectrometry. Hb Zurich-Hottingen is characterized by an Asn --> Ser replacement in the alpha-chain at position 9 as confirmed by DNA analysis. This hemoglobin variant is silent in isoelectric focusing, reversed-phase chromatography, and cation-exchange chromatography. The mutant alpha-chain was detectable only with electrospray mass spectrometry by its mass shift of -27 Da. The carrier was found to be heterozygous for the new hemoglobin variant. These results illustrate the power of ESI mass spectrometry for hemoglobin analysis.  相似文献   
117.
The quantification of phosphate bound to the C6 and C3 positions of glucose residues in starch has received increasing interest since the importance of starch phosphorylation for plant metabolism was discovered. The method described here is based on the observation that the isobaric compounds glucose-6-phosphate (Glc6P) and glucose-3-phosphate (Glc3P) exhibit significantly different fragmentation patterns in negative ion electrospray tandem mass spectrometry (MS/MS). A simple experiment involving collision-induced dissociation (CID) MS2 spectra of the sample and the two reference substances Glc3P and Glc6P permitted the quantification of the relative amounts of the two compounds in monosaccharide mixtures generated by acid hydrolysis of starch. The method was tested on well-characterized potato tuber starch. The results are consistent with those obtained by NMR analysis. In contrast to NMR, however, the presented method is fast and can be performed on less than 1 mg of starch. Starch samples of other origins exhibiting a variety of phosphorylation degrees were analyzed to assess the sensitivity and robustness of the method.  相似文献   
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We study the epidemiology of a viral disease with dose-dependent replication and transmission by nesting a differential-equation model of the within-host viral dynamics inside a between-host epidemiological model. We use two complementary approaches for nesting the models: an agent-based (AB) simulation and a mean-field approximation called the growth-matrix (GM) model. We find that although infection rates and predicted case loads are somewhat different between the AB and GM models, several epidemiological parameters, e.g. mean immunity in the population and mean dose received, behave similarly across the methods. Further, through a comparison of our dose-dependent replication model against two control models that uncouple dose-dependent replication from transmission, we find that host immunity in a population after an epidemic is qualitatively different than when transmission depends on time-varying viral abundances within hosts. These results show that within-host dynamics and viral dose should not be neglected in epidemiological models, and that the simpler GM approach to model nesting provides a reasonable tradeoff between model complexity and accuracy of results.  相似文献   
120.
The juvenile development and survival, and demographic parameters of the predatory mite Neoseiulus cucumeris (Oudemans) (Acari: Phytoseiidae) fed on pollen of castor bean, tulip, apple, Christmas cactus, horse-chestnut, maize, and birch were assessed under laboratory conditions. Deprivation of food and pollen of castor bean plants resulted in 100 % juvenile mite mortality. Feeding mites with tulip and horse-chestnut pollen resulted in the shortest development and the highest total fecundity. Adult mites fed on birch, tulip, maize, and apple pollen lived significantly longer compared with those fed on pollen of horse-chestnut and Christmas cactus. The intrinsic rate of natural increase ranged between 0.1013 ♀♀//day for maize and 0.1806 ♀♀//day for horse-chestnut pollen as food. Net reproductive rate was the lowest when fed with maize pollen and highest when fed with horse-chestnut pollen. Population doubling time was highest on maize pollen and shortest on horse-chestnut pollen. Our study revealed that birch, tulip, horse-chestnut, apple, and maize pollen can be used by N. cucumeris from early spring to late summer as a suitable alternative food in periods when prey in the field are scarce or absent.  相似文献   
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