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391.
392.
Santos JL De la Cruz R Holst C Grau K Naranjo C Maiz A Astrup A Saris WH MacDonald I Oppert JM Hansen T Pedersen O Sorensen TI Martinez JA;NUGENOB Consortium 《PloS one》2011,6(6):e19934
Introduction
The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets.Subjects and Methods
This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat) diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes.Results
No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04) and dominant models (p = 0.03). These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103–rs1543873 (p = 0.06), rs6014646–rs6024730 (p = 0.05) and rs3746619–rs3827103 (p = 0.10) displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes.Conclusion
The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans. 相似文献393.
Marijke Grau Sebastian Pauly Jamal Ali Katja Walpurgis Mario Thevis Wilhelm Bloch Frank Suhr 《PloS one》2013,8(2)
Background
Red blood cells (RBC) possess a nitric oxide synthase (RBC-NOS) whose activation depends on the PI3-kinase/Akt kinase pathway. RBC-NOS-produced NO exhibits important biological functions like maintaining RBC deformability. Until now, the cellular target structure for NO, to exert its influence on RBC deformability, remains unknown. In the present study we analyzed the modification of RBC-NOS activity by pharmacological treatments, the resulting influence on RBC deformability and provide first evidence for possible target proteins of RBC-NOS-produced NO in the RBC cytoskeletal scaffold.Methods/Findings
Blood from fifteen male subjects was incubated with the NOS substrate L-arginine to directly stimulate enzyme activity. Direct inhibition of enzyme activity was induced by L-N5-(1-Iminoethyl)-ornithin (L-NIO). Indirect stimulation and inhibition of RBC-NOS were achieved by applying insulin and wortmannin, respectively, substances known to affect PI3-kinase/Akt kinase pathway. The NO donor sodium nitroprusside (SNP) and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) were additionally applied as NO positive and negative controls, respectively. Immunohistochemical staining was used to determine phosphorylation and thus activation of RBC-NOS. As a marker for NO synthesis nitrite was measured in plasma and RBCs using chemiluminescence detection. S-nitrosylation of erythrocyte proteins was determined by biotin switch assay and modified proteins were identified using LC-MS. RBC deformability was determined by ektacytometry. The data reveal that activated RBC-NOS leads to increased NO production, S-nitrosylation of RBC proteins and RBC deformability, whereas RBC-NOS inhibition resulted in contrary effects.Conclusion/Significance
This study first-time provides strong evidence that RBC-NOS-produced NO modifies RBC deformability through direct S-nitrosylation of cytoskeleton proteins, most likely α- and β-spectrins. Our data, therefore, gain novel insights into biological functions of RBC-NOS by connecting impaired RBC deformability abilities to specific posttranslational modifications of RBC proteins. By identifying likely NO-target proteins in RBC, our results will stimulate new therapeutic approaches for patients with microvascular disorders. 相似文献394.
T. Bukovinszky N. R. Helmsing R. A. Grau E. S. Bakker T. M. Bezemer M. Vos H. Uittenhout A. M. Verschoor 《Journal of Insect Behavior》2013,26(4):453-465
In order to explore the behavioral mechanisms underlying aggregation of foragers on local resource patches, it is necessary to manipulate the location, quality and quantity of food patches. This requires careful control over the conditions in the foraging arena, which may be a challenging task in the case of aquatic resource-consumer systems, like that of freshwater zooplankton feeding on suspended algal cells. We present an experimental tool designed to aid behavioral ecologists in exploring the consequences of resource characteristics for zooplankton aggregation behavior and movement decisions under conditions where the boundaries and characteristics (quantity and quality) of food patches can be standardized. The aggregation behavior of Daphnia magna and D. galeata x hyalina was tested in relation to i) the presence or absence of food or ii) food quality, where algae of high or low nutrient (phosphorus) content were offered in distinct patches. Individuals of both Daphnia species chose tubes containing food patches and D. galeata x hyalina also showed a preference towards food patches of high nutrient content. We discuss how the described equipment complements other behavioral approaches providing a useful tool to understand animal foraging decisions in environments with heterogeneous resource distributions. 相似文献
395.
We examined the infiltration of acutely rejecting renal allografts (DA→LEW) by ED1+ and ED2+ macrophages and T lymphocytes at intervals of 24 h after transplantation. Donor and recipient macrophages were differentiated by MHC class II antigen expression in double-staining experiments with ED1. Proliferation was assayed after pulse-labelling with BrdU. We subdivided allograft infiltration into three consecutive phases: 1) During phase I on days 1 to 2 after allogeneic kidney transplantation, perivascular infiltrates developed that contained numerous donor and recipient macrophages. Allograft rejection could already be diagnosed 24?h after transplantation by perivascular infiltration of T lymphocytes, whereas T cells were rarely found in isografts. 2) Phase II of allograft rejection from day 3 to 4 was characterized by massive propagation of the infiltrate. About equal numbers of interstitial donor and recipient macrophages were counted. Both macrophages and T lymphocytes proliferated in situ and macrophages outnumbered T cells until complete rejection. 3) During phase III the allograft was destroyed. Large intravascular monocytes surprisingly expressed the ED2 antigen. In the interstitium of viable graft regions, the population of recipient macrophages grew, whereas the population of donor macrophages and of T lymphocytes decreased. 相似文献
396.
Evolutionary dynamics of tandem repeats in the mitochondrial DNA control region of the minnow Cyprinella spiloptera 总被引:3,自引:0,他引:3
Length variation due to tandem repeats is now recognized as a common
feature of animal mitochondrial DNA; however, the evolutionary dynamics of
repeated sequences are not well understood. Using phylogenetic analysis,
predictions of three models of repeat evolution were tested for arrays of
260-bp repeats in the cyprinid fish Cyprinella spiloptera. Variation at
different nucleotide positions in individual repeats supported different
models of repeat evolution. One set of characters included several
nucleotide variants found in all copies from a limited number of
individuals, while the other set included an 8- bp deletion found in a
limited number of copies in all individuals. The deletion and an associated
nucleotide change appear to be the result of a deterministic, rather than
stochastic, mutation process. Parallel origins of repeat arrays in
different mitochondrial lineages, possibly coupled with a homogenization
mechanism, best explain the distribution of nucleotide variation.
相似文献
397.
Conserved sequence motifs, alignment, and secondary structure for the third domain of animal 12S rRNA 总被引:17,自引:3,他引:14
Hickson RE; Simon C; Cooper A; Spicer GS; Sullivan J; Penny D 《Molecular biology and evolution》1996,13(1):150-169
Secondary structure models are an important step for aligning sequences,
understanding probabilities of nucleotide substitutions, and evaluating the
reliability of phylogenetic reconstructions. A set of conserved sequence
motifs is derived from comparative sequence analysis of 184 invertebrate
and vertebrate taxa (including many taxa from the same genera, families,
and orders) with reference to a secondary structure model for domain III of
animal mitochondrial small subunit (12S) ribosomal RNA. A template is
presented to assist with secondary structure drawing. Our model is similar
to previous models but is more specific to mitochondrial DNA, fitting both
invertebrate and vertebrate groups, including taxa with markedly different
nucleotide compositions. The second half of the domain III sequence can be
difficult to align precisely, even when secondary structure information is
considered. This is especially true for comparisons of anciently diverged
taxa, but well-conserved motifs assist in determining biologically
meaningful alignments. Patterns of conservation and variability in both
paired and unpaired regions make differential phylogenetic weighting in
terms of "stems" and "loops" unsatisfactory. We emphasize looking carefully
at the sequence data before and during analyses, and advocate the use of
conserved motifs and other secondary structure information for assessing
sequencing fidelity.
相似文献
398.
399.
400.
Carolin Walter Saeed Ghani Matthias Zepper Konstantin Agelopoulos Stephanie Lettermann Marie L Gebhardt Nancy Mah Andre Weilemann Michael Grau Verena Gröning Torsten Haferlach Dido Lenze Ruud Delwel Marco Prinz Miguel A Andrade‐Navarro Georg Lenz Martin Dugas Carsten Müller‐Tidow Frank Rosenbauer 《The EMBO journal》2016,35(22):2399-2416