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21.
The GAAA tetraloop-receptor motif is a commonly occurring tertiary interaction in RNA. This motif usually occurs in combination with other tertiary interactions in complex RNA structures. Thus, it is difficult to measure directly the contribution that a single GAAA tetraloop-receptor interaction makes to the folding properties of a RNA. To investigate the kinetics and thermodynamics for the isolated interaction, a GAAA tetraloop domain and receptor domain were connected by a single-stranded A(7) linker. Fluorescence resonance energy transfer (FRET) experiments were used to probe intramolecular docking of the GAAA tetraloop and receptor. Docking was induced using a variety of metal ions, where the charge of the ion was the most important factor in determining the concentration of the ion required to promote docking {[Co(NH(3))(6)(3+)] < [Ca(2+)], [Mg(2+)], [Mn(2+)] < [Na(+)], [K(+)]}. Analysis of metal ion cooperativity yielded Hill coefficients of approximately 2 for Na(+)- or K(+)-dependent docking versus approximately 1 for the divalent ions and Co(NH(3))(6)(3+). Ensemble stopped-flow FRET kinetic measurements yielded an apparent activation energy of 12.7 kcal/mol for GAAA tetraloop-receptor docking. RNA constructs with U(7) and A(14) single-stranded linkers were investigated by single-molecule and ensemble FRET techniques to determine how linker length and composition affect docking. These studies showed that the single-stranded region functions primarily as a flexible tether. Inhibition of docking by oligonucleotides complementary to the linker was also investigated. The influence of flexible versus rigid linkers on GAAA tetraloop-receptor docking is discussed. 相似文献
22.
Benedetta Gualeni Marcella Facchini Fabio De Leonardis Ruggero Tenni Giuseppe Cetta Manuela Viola Alberto Passi Andrea Superti-Furga Antonella Forlino Antonio Rossi 《Matrix biology》2010,29(6):453-460
Mutations in the sulfate transporter gene, SCL26A2, lead to cartilage proteoglycan undersulfation resulting in chondrodysplasia in humans; the phenotype is mirrored in the diastrophic dysplasia (dtd) mouse. It remains unclear whether bone shortening and deformities are caused solely by changes in the cartilage matrix, or whether chondroitin sulfate proteoglycan undersulfation affects also signalling pathways involved in cell proliferation and differentiation. Therefore we studied macromolecular sulfation in the different zones of the dtd mouse growth plate and these data were related to growth plate histomorphometry and proliferation analysis.A 2-fold increase of non-sulfated disaccharide in dtd animals compared to wild-type littermates in the resting, proliferative and hypertrophic zones was detected indicating proteoglycan undersulfation; among the three zones the highest level of undersulfation was in the resting zone. The relative height of the hypertrophic zone and the average number of cells per column in the proliferative and hypertrophic zones were significantly reduced compared to wild-types; however the total height of the growth plate was within normal values. The chondrocyte proliferation rate, measured by bromodeoxyuridine labelling, was also significantly reduced in mutant mice. Immunohistochemistry combined with expression data of the dtd growth plate demonstrated that the sulfation defect alters the distribution pattern, but not expression, of Indian hedgehog, a long range morphogen required for chondrocyte proliferation and differentiation.These data suggest that in dtd mice proteoglycan undersulfation causes reduced chondrocyte proliferation in the proliferative zone via the Indian hedgehog pathway, therefore contributing to reduced long bone growth. 相似文献
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Ilaria Bassani Ruggero Bellini Arianna Vizzarro Christian Coti Vincenzo Pozzovivo Donatella Barbieri Candido Fabrizio Pirri Francesca Verga Barbara Menin 《Environmental microbiology》2023,25(12):3683-3702
Depleted gas reservoirs are a valuable option for underground hydrogen storage (UHS). However, different classes of microorganisms, which are capable of using free H2 as a reducing agent for their metabolism, inhabit deep underground formations and can potentially affect the storage. This study integrates metagenomics based on Illumina-NGS sequencing of bacterial and archaeal 16S rRNA and dsrB and mcrA functional genes to unveil the composition and the variability of indigenous microbial populations of four Italian depleted reservoirs. The obtained mcrA sequences allow us to implement the existing taxonomic database for mcrA gene sequences with newly classified sequences obtained from the Italian gas reservoirs. Moreover, the KEGG and COG predictive functional annotation was used to highlight the metabolic pathways potentially associated with hydrogenotrophic metabolisms. The analyses revealed the specificity of each reservoir microbial community, and taxonomic and functional data highlighted the presence of an enriched number of taxa, whose activity depends on both reservoir hydrochemical composition and nutrient availability, of potential relevance in the context of UHS. This study is the very first to address the profiling of the microbial population and allowed us to perform a preliminary assessment of UHS feasibility in Italy. 相似文献
25.
A New Medical Device Rigeneracons Allows to Obtain Viable Micro‐Grafts From Mechanical Disaggregation of Human Tissues 下载免费PDF全文
26.
A subpopulation of cancer cells is believed to be responsible for tumor initiation, propagation, and metastasis. In this issue of Cell Stem Cell, Dieter et?al. (2011) show that these functions in colon cancer can be ascribed to distinct tumor-initiating cell populations. 相似文献
27.
Bonaventure P Aluisio L Shoblock J Boggs JD Fraser IC Lord B Lovenberg TW Galici R 《PloS one》2011,6(6):e20210
The role of 5-HT7 receptor has been demonstrated in various animal models of mood disorders; however its function in cognition remains largely speculative. This study evaluates the effects of SB-269970, a selective 5-HT7 antagonist, in a translational model of working memory deficit and investigates whether it modulates cortical glutamate and/or dopamine neurotransmission in rats. The effect of SB-269970 was evaluated in the delayed non-matching to position task alone or in combination with MK-801, a non-competitive NMDA receptor antagonist, and, in separate experiments, with scopolamine, a non-selective muscarinic antagonist. SB-269970 (10 mg/kg) significantly reversed the deficits induced by MK-801 (0.1 mg/kg) but augmented the deficit induced by scopolamine (0.06 mg/kg). The ability of SB-269970 to modulate MK-801-induced glutamate and dopamine extracellular levels was separately evaluated using biosensor technology and microdialysis in the prefrontal cortex of freely moving rats. SB-269970 normalized MK-801 -induced glutamate but not dopamine extracellular levels in the prefrontal cortex. Rat plasma and brain concentrations of MK-801 were not affected by co-administration of SB-269970, arguing for a pharmacodynamic rather than a pharmacokinetic mechanism. These results indicate that 5-HT7 receptor antagonists might reverse cognitive deficits associated with NMDA receptor hypofunction by selectively normalizing glutamatergic neurotransmission. 相似文献
28.
Giusti L Cetani F Ciregia F Da Valle Y Donadio E Giannaccini G Banti C Pardi E Saponaro F Basolo F Berti P Miccoli P Pinchera A Marcocci C Lucacchini A 《Molecular bioSystems》2011,7(3):687-699
Parathyroid tumours are heterogeneous and in some cases the diagnosis may be difficult using histological features. In this study we used a two-dimensional electrophoresis (2D)/mass spectrometry (MS)-based approach to examine the global changes of parathyroid adenoma tissues protein profile compared to the parathyroid normal tissues. Validation of protein expression was performed by immunoblotting using specific antibodies. Ingenuity software was used to identify the biological processes to which these proteins belong and to construct a potential network. A total of 30 proteins were found to be differentially expressed, of which 22 resulted in being over-expressed. Proteins identified by 2D/MS/MS proteomics were classified into functional categories and a major change (≥ 2-fold) in terms of expression was found in proteins involved in response to biotic stimuli, cell organization and signal transduction. After Ingenuity analysis, 14-3-3 ζ/δ appears to be a key protein in the network of parathyroid adenoma, where it is linked to other proteins such as annexin A2, B box and SPRY domain-containing protein (BSPRY), p53 and epidermal growth factor receptor (EGFR). Our results suggest that the proteomic approach was able to differentiate the protein profiles of normal parathyroid and parathyroid adenoma and identify a panel of proteins which are differentially expressed. The functional role of these proteins in the network of intracellular pathways is discussed. 相似文献
29.
Paolo Perticone Caterina Tanzarella Fabrizio Palitti Ruggero Ricordy Pietro Di Chiara Giuseppe Di Pietro Franco Spirito Gianpietro Diana Rosella De Salvia Marco Rizzoni 《Chromosoma》1976,56(3):243-248
The composition in segregated haploid sets of paternal and maternal chromosomes has been studied in order to verify whether their composition is uniparental of mixed, fixed or variable. Primary cultures where prepared using kidneys from hybrids of strains of Mus musculus in which the parental chromosomes are distinguishable; the maternal set consists of 20 teleocentric chromosomes, the paternal set of 9 metacentric chromosomes, derived by Robertsonian fusion and 2 telocentrics. Applying Seabright's banding technique, an analysis of segregated haploid and diploid cells, which have originated spontaneously through polyploidisation-segregation processes was carried out. It was concluded that the haploid sets have a variable composition of paternal and maternal chromosomes. 相似文献
30.
Imino 1H–15N residual dipolar couplings (RDCs) provide additional structural information that complements standard 1H–1H NOEs leading to improvements in both the local and global structure of RNAs. Here, we report measurement of imino 1H–1H RDCs for the Iron Responsive Element (IRE) RNA and native E. coli tRNAVal using a BEST-Jcomp-HMQC2 experiment. 1H–1H RDCs are observed between the imino protons in G–U wobble base pairs and between imino protons on neighboring base pairs
in both RNAs. These imino 1H–1H RDCs complement standard 1H–15N RDCs because the 1H–1H vectors generally point along the helical axis, roughly perpendicular to 1H–15N RDCs. The use of longitudinal relaxation enhancement increased the signal-to-noise of the spectra by ~3.5-fold over the
standard experiment. The ability to measure imino 1H–1H RDCs offers a new restraint, which can be used in NMR domain orientation and structural studies of RNAs.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献