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41.
Luca Fontanesi Michela Colombo Lucia Tognazzi Emilio Scotti Luca Buttazzoni Stefania Dall’Olio Roberta Davoli Vincenzo Russo 《Molecular biology reports》2011,38(2):1425-1431
TBC1D1 [TBC1 (tre-2/USP6, BUB2, cdc16) domain family, member 1] is a Rab-GTPase-activating related protein implicated in regulating
the trafficking of glucose transporter 4 (GLUT4 or SLC2A4) storage vesicles to the cell surface in response to insulin and
AMPK-activating stimuli in skeletal muscle. Mutations in the human and mouse TBC1D1 genes confer risk of obesity or leanness. We identified five single nucleotide polymorphisms (SNPs) in the porcine TBC1D1 gene. One of them (FN677935:g.219G>A) was genotyped either by high resolution melting and PCR-RFLP analyses to study allele
frequencies in a few pig breeds and evaluate association with meat production and carcass traits in five groups of sib-tested
pigs of Italian Large White and Italian Duroc breeds. The g.219G>A SNP was associated (P < 0.05) with ham weight, back fat thickness and lean cuts content in Italian Large White and with visible intermuscular fat
in Italian Duroc pigs. 相似文献
42.
Synergistic inhibition of pancreatic adenocarcinoma cell growth by trichostatin A and gemcitabine 总被引:1,自引:0,他引:1
Donadelli M Costanzo C Beghelli S Scupoli MT Dandrea M Bonora A Piacentini P Budillon A Caraglia M Scarpa A Palmieri M 《Biochimica et biophysica acta》2007,1773(7):1095-1106
We investigated the ability of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) to interact with gemcitabine (GEM) in inducing pancreatic cancer cell death. The combined treatment with TSA and GEM synergistically inhibited growth of four pancreatic adenocarcinoma cell lines and induced apoptosis. This effect was associated with the induction of reactive oxygen species (ROS) by GEM, increased expression of the pro-apoptotic BIM gene by both TSA and GEM and downregulation of the 5'-nucleotidase UMPH type II gene by TSA. The expression of other genes critical for GEM resistance (nucleoside transporters, deoxycytidine kinase, cytidine deaminase, and ribonucleotide reductase genes) was not affected by TSA. The functional role of ROS in cell growth inhibition by GEM was supported by (i) a significantly reduced GEM-associated growth inhibition by the free radical scavenger N-acetyl-L-cysteine, and (ii) a positive correlation between the basal level of ROS and sensitivity to GEM in 10 pancreatic cancer cell lines. The functional role of both Bim and 5'-nucleotidase UMPH type II in cell growth inhibition by TSA and GEM was assessed by RNA interference assays. In vivo studies on xenografts of pancreatic adenocarcinoma cells in nude mice showed that the association of TSA and GEM reduced to 50% the tumour mass and did not cause any apparent form of toxicity, while treatments with TSA or GEM alone were ineffective. In conclusion, the present study demonstrates a potent anti-tumour activity of TSA/GEM combination against pancreatic cancer cells in vitro and in vivo, strongly supporting the use of GEM in combination with an HDAC inhibitor for pancreatic cancer therapy. 相似文献
43.
44.
Pogni R Baratto MC Teutloff C Giansanti S Ruiz-Dueñas FJ Choinowski T Piontek K Martínez AT Lendzian F Basosi R 《The Journal of biological chemistry》2006,281(14):9517-9526
Versatile peroxidases are heme enzymes that combine catalytic properties of lignin peroxidases and manganese peroxidases, being able to oxidize Mn(2+) as well as phenolic and non-phenolic aromatic compounds in the absence of mediators. The catalytic process (initiated by hydrogen peroxide) is the same as in classical peroxidases, with the involvement of 2 oxidizing equivalents and the formation of the so-called Compound I. This latter state contains an oxoferryl center and an organic cation radical that can be located on either the porphyrin ring or a protein residue. In this study, a radical intermediate in the reaction of versatile peroxidase from the ligninolytic fungus Pleurotus eryngii with H(2)O(2) has been characterized by multifrequency (9.4 and 94 GHz) EPR and assigned to a tryptophan residue. Comparison of experimental data and density functional theory theoretical results strongly suggests the assignment to a tryptophan neutral radical, excluding the assignment to a tryptophan cation radical or a histidine radical. Based on the experimentally determined side chain orientation and comparison with a high resolution crystal structure, the tryptophan neutral radical can be assigned to Trp(164) as the site involved in long-range electron transfer for aromatic substrate oxidation. 相似文献
45.
Pasqualina Woodrow Giovanni Pontecorvo Stefania Fantaccione Amodio Fuggi Ioannis Kafantaris Danila Parisi Petronia Carillo 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(2):311-322
Long terminal repeat retrotransposons are the most abundant mobile elements in the plant genome and play an important role in the genome reorganization induced by environmental challenges. Their success depends on the ability of their promoters to respond to different signaling pathways that regulate plant adaptation to biotic and abiotic stresses. We have isolated a new Ty1-copia-like retrotransposon, named Ttd1a from the Triticum durum L. genome. To get insight into stress activation pathways in Ttd1a, we investigated the effect of salt and light stresses by RT-PCR and S-SAP profiling. We screened for Ttd1a insertion polymorphisms in plants grown to stress and showed that one new insertion was located near the resistance gene. Our analysis showed that the activation and mobilization of Ttd1a was controlled by salt and light stresses, which strengthened the hypothesis that stress mobilization of this element might play a role in the defense response to environmental stresses. 相似文献
46.
Emma-Jo Hayton Annie Rose Umar Ibrahimsa Mariarosaria Del Sorbo Stefania Capone Alison Crook Antony P. Black Lucy Dorrell Tomá? Hanke 《PloS one》2014,9(7)
Trial Design
HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee) adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported.Methods
Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination.Results
Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1) and predominantly transient (<48 hours). Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range) of 633 (231-1533) post-vaccination, which is of no safety concern.Conclusions
These data demonstrate safety and good tolerability of the pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines and together with their high immunogenicity support their further development towards efficacy studies.Trial Registration
ClinicalTrials.gov NCT01151319相似文献47.
In celiac disease (CD), gluten, the disease-inducing toxic component in wheat, induces the secretion of IgA-class autoantibodies which target tissue transglutaminase (tTG). These autoantibodies are produced in the small-intestinal mucosa, and, during gluten consumption, they can also be detected in patients' serum but disappear slowly from the circulation on a gluten-free diet. Interestingly, after adoption of a gluten-free diet the serum autoantibodies disappear from the circulation more rapidly than the small-intestinal mucosal autoantibody deposits. The finding of IgA deposits on extracellular tTG in the liver, kidney, lymph nodes and muscles of patients with CD indicates that tTG is accessible to the gut-derived autoantibodies. Although the specific autoantibody response directed against tTG is very characteristic in celiac patients, their role in the immunopathology of the celiac mucosal lesion is a matter of debate. Here we report a brief summary of anti-tTG antibody effects demonstrating that these antibodies are functional and not mere bystanders in the disease pathogenesis. In fact, they inhibit intestinal epithelial cell differentiation, induce intestinal epithelial cell proliferation, increase epithelial permeability and activate monocytes and disturb angiogenesis. 相似文献
48.
Beste Ozben Evrim Dursun Emanuela Monari Aurora Cuoghi Stefania Bergamini Aldo Tomasi Tomris Ozben 《Molecular and cellular biochemistry》2009,331(1-2):9-17
There is a great need for the identification of biomarkers for the early diagnosis of atherosclerosis and the agents to prevent its progression. The aim of this study was to explore the effect of 24 week of nebivolol (a third-generation vasodilatory beta-blocker) treatment on serum protein profiles in Apo E?/? mice during atherosclerosis progression. Nebivolol treated and non-treated (the control group) groups consisted of 10 genetically modified homozygous Apo E?/? mice. Proteomic analyses were performed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) in the serum samples from the nebivolol treated and non-treated Apo E?/? mice. The protein profiles obtained using three different chips, CM10 (weak cation-exchange), H50 (reverse phase), and IMAC30-Cu2+ (immobilized metal affinity capture) were statistically analyzed using the ProteinChip data manager 3.0 program. At the end of 24 week of nebivolol-treatment period, a total of 662 protein/peptide clustering peaks were detected using 12 different conditions and reading with high and low intensity laser energy. The highest total number of protein/peptide clusters was found on H50 chip array. The peak intensities of 95 of the 662 protein/peptide clusters were significantly different in the nebivolol-treated atherosclerotic group in comparison to the non-treated control mice groups (P < 0.05). Forty-three protein/peptides were up-regulated (high signal intensity) while 52 protein/peptides had lower signal intensity (down-regulated) in the nebivolol-treated atherosclerotic group. The proteomic profiles of nebivolol-treated Apo E?/? mice were different than the control group indicating a potential role of nebivolol in atherosclerosis. Our study contributes to understand the efficacy of nebivolol on serum protein/peptide profiles during atherosclerosis development. 相似文献
49.
Stefania Piantavigna Patricia Czihal Adam Mechler Monique Richter Ralf Hoffmann Lisandra L. Martin 《International journal of peptide research and therapeutics》2009,15(2):139-146
Apidaecin peptides from Apis mellifera hemolymph are believed to attack intracellular bacterial targets. Our in vivo results for apidaecins 1a and 1b confirm that
bacterial activity is non-lytic, however, the manner in which these peptides pass through the cell membrane to exert this
activity is unknown. These data are combined with fluorescence (dye leakage) and quartz crystal microbalance studies to investigate
the membrane interaction for these two wildtype peptides. It was found that the peptides penetrate the membrane in a trans-membrane
manner. The amount of peptide uptake by the membrane is proportional to the concentration of the peptide, however, this appears
to be a dynamic equilibrium which can be almost completely reversed by addition of buffer medium. Interestingly, a small residual
mass remains within the membrane and the amount of peptide remaining in the membrane is a function of the buffer-salt concentration
viz. in high salt, the residual peptide mass remaining is small whereas at low salt concentration, a larger mass of peptide
remains bound. These results support a direct membrane penetration mechanism by the wild type apidaecins 1a and 1b. In both
cases the peptide–membrane interaction has a negligible effect on the membrane, although, in high salt a permanent change
in the membrane does occur at the highest peptide concentration which does not recover following peptide removal.
Stefania Piantavigna and Patricia Czihal contributed equally to this article. 相似文献