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61.
Michael Meyer Maya Ben‐Yehuda Greenwald Theresa Rauschendorfer Catharina Snger Marko Jukic Haruka Iizuka Fumimasa Kubo Lin Chen David M. Ornitz Sabine Werner 《Journal of cellular and molecular medicine》2020,24(2):1774-1785
Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused fibroblast activation and fibrosis in the FGFR1/FGFR2 double‐knockout mice and even more in mice lacking all three FGFRs, revealing functional redundancy of FGFR3 with FGFR1 and FGFR2 for maintaining the epidermal barrier. Taken together, our study demonstrates that FGFR1, FGFR2 and FGFR3 act together to maintain epidermal integrity and cutaneous homeostasis, with FGFR2 being the dominant receptor. 相似文献
62.
Sarto-Jackson I Milenkovic I Smalla KH Gundelfinger ED Kaehne T Herrera-Molina R Thomas S Kiebler MA Sieghart W 《The Journal of biological chemistry》2012,287(17):14201-14214
γ-Aminobutyric acid type A (GABAA) receptors are pentameric ligand-gated ion channels that mediate fast inhibition in the central nervous system. Depending on their subunit composition, these receptors exhibit distinct pharmacological properties and differ in their ability to interact with proteins involved in receptor anchoring at synaptic or extra-synaptic sites. Whereas GABAA receptors containing α1, α2, or α3 subunits are mainly located synaptically where they interact with the submembranous scaffolding protein gephyrin, receptors containing α5 subunits are predominantly found extra-synaptically and seem to interact with radixin for anchorage. Neuroplastin is a cell adhesion molecule of the immunoglobulin superfamily that is involved in hippocampal synaptic plasticity. Our results reveal that neuroplastin and GABAA receptors can be co-purified from rat brain and exhibit a direct physical interaction as demonstrated by co-precipitation and Förster resonance energy transfer (FRET) analysis in a heterologous expression system. The brain-specific isoform neuroplastin-65 co-localizes with GABAA receptors as shown in brain sections as well as in neuronal cultures, and such complexes can either contain gephyrin or be devoid of gephyrin. Neuroplastin-65 specifically co-localizes with α1 or α2 but not with α3 subunits at GABAergic synapses. In addition, neuroplastin-65 also co-localizes with GABAA receptor α5 subunits at extra-synaptic sites. Down-regulation of neuroplastin-65 by shRNA causes a loss of GABAA receptor α2 subunits at GABAergic synapses. These results suggest that neuroplastin-65 can co-localize with a subset of GABAA receptor subtypes and might contribute to anchoring and/or confining GABAA receptors to particular synaptic or extra-synaptic sites, thus affecting receptor mobility and synaptic strength. 相似文献
63.
Sabine Castano Brigitte Delord Annie Février Jean-Marie Lehn Pierre Lehn Bernard Desbat 《Biochimie》2009
The lipid bis(guanidinium)-tren-cholesterol (BGTC) is a cationic cholesterol derivative bearing guanidinium polar headgroups used for gene transfection either alone or formulated as liposomes with the zwitterionic lipid 1,2-di-[cis-9-octadecenoyl]-sn-glycero-3-phosphoethanolamine (DOPE). Previous investigations have shown its ability to strongly interact with DNA and form asymmetric lipid bilayers at the air/water interface when mixed with DOPE. Here, with a view to further investigate its physicochemical behavior, we studied the interactions of mixtures of BGTC with another zwitterionic lipid, 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine, (DMPC), with DNA at the air/water interface by using the Langmuir monolayer technique coupled with Brewster Angle Microscopy (BAM) and Polarization Modulation Infra Red Reflexion Absorption (PMIRRAS) spectroscopy and we investigate DNA–BGTC/DMPC interactions. We demonstrate that when DNA is injected into the subphase in excess compared to the positive charges of BGTC, it adsorbs to BGTC/DMPC monolayers at 20 mN/m whatever the lipid monolayer composition (1/5, 2/3 or 3/2 BGTC/DMPC molar ratio) and forms an incomplete monolayer of either isotropic or anisotropic double strands depending on the BGTC content in the monolayer. Compression beyond the collapse of some mixed DNA–BGTC/DMPC (2/3 and 3/2 molar ratio) systems leads to the formation of DNA monolayers underneath asymmetric lipid bilayers characterized by a bottom layer of BGTC in contact with DNA and a top layer mainly constituted of DMPC. 相似文献
64.
65.
Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells 总被引:5,自引:0,他引:5 下载免费PDF全文
Höck J Weinmann L Ender C Rüdel S Kremmer E Raabe M Urlaub H Meister G 《EMBO reports》2007,8(11):1052-1060
Members of the Argonaute (Ago) protein family associate with small RNAs and have important roles in RNA silencing. Here, we analysed Ago1- and Ago2-containing protein complexes in human cells. Separation of Ago-associated messenger ribonucleoproteins (mRNPs) showed that Ago1 and Ago2 reside in three complexes with distinct Dicer and RNA-induced silencing complex activities. A comprehensive proteomic analysis of Ago-containing mRNPs identified a large number of proteins involved in RNA metabolism. By using co-immunoprecipitation experiments followed by RNase treatment, we biochemically mapped interactions within Ago mRNPs. Using reporter assays and knockdown experiments, we showed that the putative RNA-binding protein RBM4 is required for microRNA-guided gene regulation. 相似文献
66.
Budde BS Binner P Waldmüller S Höhne W Blankenfeldt W Hassfeld S Brömsen J Dermintzoglou A Wieczorek M May E Kirst E Selignow C Rackebrandt K Müller M Goody RS Vosberg HP Nürnberg P Scheffold T 《PloS one》2007,2(12):e1362
Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the alpha- and beta-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium. 相似文献
67.
de Brouwer SJ Kraaimaat FW Sweep FC Donders RT Eijsbouts A van Koulil S van Riel PL Evers AW 《PloS one》2011,6(12):e27432
Background
Stress management interventions may prove useful in preventing the detrimental effects of stress on health. This study assessed the effects of a stress management intervention on the psychophysiological response to stress in patients with rheumatoid arthritis (RA).Methods
Seventy-four patients with RA, who were randomly assigned to either a control group or a group that received short-term stress management training, performed a standardized psychosocial stress task (Trier Social Stress Test; TSST) 1 week after the stress management training and at a 9-week follow-up. Psychological and physical functioning, and the acute psychophysiological response to the stress test were assessed.Results
Patients in the intervention group showed significantly lower psychological distress levels of anxiety after the training than did the controls. While there were no between-group differences in stress-induced tension levels, and autonomic (α-amylase) or endocrine (cortisol) responses to the stress test 1 week after the intervention, levels of stress-induced tension and cortisol were significantly lower in the intervention group at the 9-week follow-up. Overall, the response to the intervention was particularly evident in a subgroup of patients with a psychological risk profile.Conclusion
A relatively short stress management intervention can improve psychological functioning and influences the psychophysiological response to stress in patients with RA, particularly those psychologically at risk. These findings might help understand how stress can affect health and the role of individual differences in stress responsiveness.Trial Registration
TrialRegister.nl NTR1193 相似文献68.
Ebner S Lang R Mueller EE Eder W Oeller M Moser A Koller J Paulweber B Mayr JA Sperl W Kofler B 《PloS one》2011,6(12):e27192
Background
Because mitochondria play an essential role in energy metabolism, generation of reactive oxygen species (ROS), and apoptosis, sequence variation in the mitochondrial genome has been postulated to be a contributing factor to the etiology of multifactorial age-related diseases, including cancer. The aim of the present study was to compare the frequencies of mitochondrial DNA (mtDNA) haplogroups as well as control region (CR) polymorphisms of patients with malignant melanoma (n = 351) versus those of healthy controls (n = 1598) in Middle Europe.Methodology and Principal Findings
Using primer extension analysis and DNA sequencing, we identified all nine major European mitochondrial haplogroups and known CR polymorphisms. The frequencies of the major mitochondrial haplogroups did not differ significantly between patients and control subjects, whereas the frequencies of the one another linked CR polymorphisms A16183C, T16189C, C16192T, C16270T and T195C were significantly higher in patients with melanoma compared to the controls. Regarding clinical characteristics of the patient cohort, none of the nine major European haplogroups was associated with either Breslow thickness or distant metastasis. The CR polymorphisms A302CC-insertion and T310C-insertion were significantly associated with mean Breslow thickness, whereas the CR polymorphism T16519C was associated with metastasis.Conclusions and Significance
Our results suggest that mtDNA variations could be involved in melanoma etiology and pathogenesis, although the functional consequence of CR polymorphisms remains to be elucidated. 相似文献69.
Ezhevskaya M Trandafir F Moens L Dewilde S Van Doorslaer S 《Journal of inorganic biochemistry》2011,105(9):1131-1137
The function of neuroglobin, a member of the vertebrate globin family, is still unknown. In human neuroglobin (NGB), the formation of a disulfide bridge between the CysCD7 and CysD5 is known to affect the heme environment and its ligand-binding kinetics. Here, we show by means of EPR that the PheB10 residue plays a key role in transmitting the structural information from the disulfide bridge to the heme-pocket region. While formation of a disulfide bridge in ferric wild-type NGB leads to a considerable change of its EPR parameters, only minor changes are observed in the case of ferric PheB10Leu NGB. Furthermore, wild-type NGB is found to be much more stable in the presence of H2O2 than its PheB10Leu or its HisE7Leu mutants. While tyrosyl radicals are induced in HisE7Leu NGB by the addition of H2O2, this is not the case for wild-type and PheB10Leu NGB. The results will be discussed in terms of the protein's putative functions. 相似文献
70.
Bacteria and archaea involved in anaerobic digestion of distillers grains with solubles 总被引:1,自引:0,他引:1
Ziganshin AM Schmidt T Scholwin F Il'inskaya ON Harms H Kleinsteuber S 《Applied microbiology and biotechnology》2011,89(6):2039-2052
Cereal distillers grains, a by-product from bioethanol industry, proved to be a suitable feedstock for biogas production in
laboratory scale anaerobic digesters. Five continuously stirred tank reactors were run under constant conditions and monitored
for biogas production and composition along with other process parameters. Iron additives for sulfide precipitation significantly
improved the process stability and efficiency, whereas aerobic pretreatment of the grains had no effect. The microbial communities
in the reactors were investigated for their phylogenetic composition by terminal restriction fragment length polymorphism
analysis and sequencing of 16S rRNA genes. The bacterial subcommunities were highly diverse, and their composition did not
show any correlation with reactor performance. The dominant phylotypes were affiliated to the Bacteroidetes. The archaeal
subcommunities were less diverse and correlated with the reactor performance. The well-performing reactors operated at lower
organic loading rates and amended with iron chloride were dominated by aceticlastic methanogens of the genus Methanosaeta. The well-performing reactor operated at a high organic loading rate and supplemented with iron hydroxide was dominated by
Methanosarcina ssp. The reactor without iron additives was characterized by propionate and acetate accumulation and high hydrogen sulfide
content and was dominated by hydrogenotrophic methanogens of the genus Methanoculleus. 相似文献