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51.
Learning involves a usually adaptive response to an input (an external stimulus or the organism℉s own behaviour) in which
the input-response relation is memorized; some physical traces of the relation persist and can later be the basis of a more
effective response. Using toy models we show that this characterization applies not only to the paradigmatic case of neural
learning, but also to cellular responses that are based on epigenetic mechanisms of cell memory. The models suggest that the
research agenda of epigenetics needs to be expanded. 相似文献
52.
Bollati M Milani M Mastrangelo E Ricagno S Tedeschi G Nonnis S Decroly E Selisko B de Lamballerie X Coutard B Canard B Bolognesi M 《Journal of molecular biology》2009,385(1):140-20077
The mRNA-capping process starts with the conversion of a 5′-triphosphate end into a 5′-diphosphate by an RNA triphosphatase, followed by the addition of a guanosine monophosphate unit in a 5′-5′ phosphodiester bond by a guanylyltransferase. Methyltransferases are involved in the third step of the process, transferring a methyl group from S-adenosyl-l-methionine to N7-guanine (cap 0) and to the ribose 2′OH group (cap 1) of the first RNA nucleotide; capping is essential for mRNA stability and proper replication. In the genus Flavivirus, N7-methyltransferase and 2′O-methyltransferase activities have been recently associated with the N-terminal domain of the viral NS5 protein. In order to further characterize the series of enzymatic reactions that support capping, we analyzed the crystal structures of Wesselsbron virus methyltransferase in complex with the S-adenosyl-l-methionine cofactor, S-adenosyl-l-homocysteine (the product of the methylation reaction), Sinefungin (a molecular analogue of the enzyme cofactor), and three different cap analogues (GpppG, N7MeGpppG, and N7MeGpppA). The structural results, together with those on other flaviviral methyltransferases, show that the capped RNA analogues all bind to an RNA high-affinity binding site. However, lack of specific interactions between the enzyme and the first nucleotide of the RNA chain suggests the requirement of a minimal number of nucleotides following the cap to strengthen protein/RNA interaction. Our data also show that, following incubation with guanosine triphosphate, Wesselsbron virus methyltransferase displays a guanosine monophosphate molecule covalently bound to residue Lys28, hinting at possible implications for the transfer of a guanine group to ppRNA. The structures of the Wesselsbron virus methyltransferase complexes obtained are discussed in the context of a model for N7-methyltransferase and 2′O-methyltransferase activities. 相似文献
53.
FOXM1 Transcription Factor: A New Component of Chronic Myeloid Leukemia Stem Cell Proliferation Advantage 下载免费PDF全文
Manuela Mancini Fausto Castagnetti Simona Soverini Elisa Leo Caterina De Benedittis Gabriele Gugliotta Gianantonio Rosti Luana Bavaro Sara De Santis Cecilia Monaldi Margherita Martelli Maria Alessandra Santucci Michele Cavo Giovanni Martinelli 《Journal of cellular biochemistry》2017,118(11):3968-3975
54.
Alice Toso Simona Schifano Charlotte Oxborough Krista McGrath Luke Spindler Anabela Castro Lucy Evangelista Vanessa Filipe Maria José Gonçalves Antonio Marques Inês Mendes da Silva Raquel Santos Maria João Valente Iona McCleery Michelle Alexander 《American journal of physical anthropology》2021,176(2):208-222
55.
Elisabetta Barocelli Vigilio Ballabeni Paola Ghizzardi Fiore Cattaruzza Simona Bertoni Costanza A M Lagrasta Mariannina Impicciatore 《Nitric oxide》2006,14(3):212-218
Nitric oxide (NO) involvement in intestinal ischemia-reperfusion (I/R) injury has been widely suggested but its protective or detrimental role remains still question of debate. Here, we examine the impact of supplementation or inhibition of NO availability on intestinal dysmotility and inflammation caused by mesenteric I/R in mice. Ischemia 45min and reperfusion 24h were performed by superior mesenteric artery occlusion in female Swiss mice. Saline-treated sham-operated (S) or normal mice without surgery (N) served as controls. Drugs were subcutaneously injected 0, 4, 8, and 18 h after ischemia. Upper gastrointestinal transit (GIT, estimated through black marker gavage), intestinal myeloperoxidase activity (MPO), intestinal malondialdehyde levels (MDA), Evans blue extravasation (EB), intestinal histological damage, and mean arterial pressure (MAP) were considered. In I/R mice, GIT was significantly delayed compared to S and N groups; MPO activity and EB extravasation enhanced, whereas MDA levels did not change. Compared to N and S groups, in I/R mice selective iNOS inhibitor P-BIT significantly prevented motor, MPO and EB changes; putative iNOS inhibitor aminoguanidine significantly counteracted GIT delay but not neutrophil recruitment and the increase in vascular permeability; NOS inhibitor l-NAME and NO precursor l-arginine were scarcely or no effective. Furthermore, in S mice aminoguanidine caused a significant increase of MPO activity reverted by H(1) histamine receptor antagonist pre-treatment. Unlike P-BIT, aminoguanidine and l-NAME injection increased MAP. These findings confirm a detrimental role for iNOS-derived NO overproduction during reperfusion. Aminoguanidine-associated neutrophil recruitment suggests that this drug could act through mechanisms additional to iNOS inhibition involving both eNOS blockade, as indicated by its hemodynamic effects, and indirect activation of H(1) histamine receptors. 相似文献
56.
Detlef Michel Hans Hartings Simona Lanzini Manuela Michel Mario Motto Giorgia Romina Riboldi Francesco Salamini Hans-Peter Döring 《Molecular & general genetics : MGG》1995,248(3):287-292
Eight independently isolated unstable alleles of theOpaque2 (O2) locus were analysed genetically and at the DNA level. The whole series of mutations was isolated from a maize strain carrying a wild-typeO2 allele and the transposable elementActivator (Ac) at thewx-m7 allele. Previous work with another unstable allele of the same series has shown that it was indeed caused by the insertion of anAc element. Unexpectedly, the remaining eight mutations were not caused by the designatedAc element, but by other insertions that are structurally similar or identical to one of two different autonomous transposable elements. Six mutations were caused by the insertion of a transposable element of theEnhancer/Suppressor-Mutator (En/Spm) family. Two mutations were the result of the insertion of a transposable element of theBergamo (Bg) family. Genetic tests carried out with plants carrying the unstable mutations demonstrated that all were caused by the insertion of an autonomous transposable element. 相似文献
57.
Simona Cinta Pinzaru Alexandra Falamas Cristina Adriana Dehelean 《Journal of cellular and molecular medicine》2013,17(2):277-286
An interdisciplinary approach employing functionalized nanoparticles and ultrasensitive spectroscopic techniques is reported here to track the molecular changes in early stage of malignancy. Melanoma tissue tracking at molecular level using both labelled and unlabelled silver and gold nanoparticles has been achieved using surface enhanced Raman scattering (SERS) technique. We used skin tissue from ex vivo mice with induced melanoma. Raman and SERS molecular characterization of melanoma tissue is proposed here for the first time. Optical nanosensors based on Ag and Au nanoparticles with chemisorbed cresyl violet molecular species as labels revealed sensitive capability to tissues tagging and local molecular characterization. Sensitive information originating from surrounding native biological molecules is provided by the tissue SERS spectra obtained either with visible or NIR laser line. Labelled nanoparticles introduced systematic differences in tissue response compared with unlabelled ones, suggesting that the label functional groups tag specific tissue components revealed by proteins or nucleic acids bands. Vibrational data collected from tissue are presented in conjunction with the immunohistochemical analysis. The results obtained here open perspectives in applied plasmonic nanoparticles and SERS for the early cancer diagnostic based on the appropriate spectral databank. 相似文献
58.
Tanja Dolinsek Bostjan Markelc Gregor Sersa Andrej Coer Monika Stimac Jaka Lavrencak Andreja Brozic Simona Kranjc Maja Cemazar 《PloS one》2013,8(3)
Endoglin is a transforming growth factor-β (TGF- β) co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA) molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11) by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches. 相似文献
59.
The mitochondrial carriers are a family of transport proteins that shuttle metabolites, nucleotides, and cofactors across the inner mitochondrial membrane. In Saccharomyces cerevisiae, NAD+ is synthesized outside the mitochondria and must be imported across the permeability barrier of the inner mitochondrial membrane. However, no protein responsible for this transport activity has ever been isolated or identified. In this report, the identification and functional characterization of the mitochondrial NAD+ carrier protein (Ndt1p) is described. The NDT1 gene was overexpressed in bacteria. The purified protein was reconstituted into liposomes, and its transport properties and kinetic parameters were characterized. It transported NAD+ and, to a lesser extent, (d)AMP and (d)GMP but virtually not alpha-NAD+, NADH, NADP+, or NADPH. Transport was saturable with an apparent Km of 0.38 mM for NAD+. The Ndt1p-GFP was found to be targeted to mitochondria. Consistently with Ndt1p localization and its function as a NAD+ transporter, cells lacking NDT1 had reduced levels of NAD+ and NADH in their mitochondria and reduced activity of mitochondrial NAD+-requiring enzymes. Similar results were also found in the mitochondria of cells lacking NDT2 that encodes a protein (Ndt2p) displaying 70% homology with Ndt1p. The delta ndt1 delta ndt2 double mutant exhibited lower mitochondrial NAD+ and NADH levels than the single deletants and a more pronounced delay in growth on nonfermentable carbon sources. The main role of Ndt1p and Ndt2p is to import NAD+ into mitochondria by unidirectional transport or by exchange with intramitochondrially generated (d)AMP and (d)GMP. 相似文献
60.
Panunzi S De Gaetano A Mingrone G 《American journal of physiology. Endocrinology and metabolism》2005,289(5):E915-E922
Dicarboxylic acids with an even number of carbon atoms have been proposed as an alternate energy substrate for enteral or parenteral nutrition in the acutely ill patient, due to their water solubility and their yielding TCA cycle intermediates upon beta-oxidation. In the present work, a nonlinear compartmental model of the kinetics of dodecanedioic acid is developed, and its parameters are estimated from time concentration experimental observations obtained from six healthy volunteers undergoing a per os administration of 3 g of the substance. Although the model is linear in the transfer of the free substance from plasma to the tissues, the exchange between gut and plasma compartments is represented as a saturable function. Albumin binding is then incorporated to obtain the final model in terms of the measured total concentrations. Estimates of the model's structural parameters were computed for each experimental subject, and the usual single-subject approximate confidence regions for the parameters were derived by inversion of the Hessian at the optimum. To verify the applicability of this approximation, the nonlinearity of the expectation surface at the optimum was measured by computing the normal (intrinsic) component of curvature. Because the model curvature was excessive in all subjects, the usual approximation could not be trusted to provide acceptable approximations to the parameter confidence regions. A suitable Monte Carlo simulation yielded empirical joint parameter distributions from which the approximate parameter variances could finally be obtained. 相似文献