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排序方式: 共有305条查询结果,搜索用时 15 毫秒
1.
Elisa Mascolo Francesco Liguori Lorenzo Stufera Mecarelli Noemi Amoroso Chiara Merigliano Susanna Amadio Cinzia Volont Roberto Contestabile Angela Tramonti Fiammetta Vernì 《International journal of molecular sciences》2021,22(2)
Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity. 相似文献
2.
3.
This paper presents a model of labor participation calibrated on a weekly basis; part-time and full-time employments are also
considered. By applying the theory of random utility maximization we model households’ choices. In order to have a good temporal
and spatial coverage the model is calibrated on three datasets, extracted from both national and regional travel surveys.
The results are applied to synthetic households that reproduce the Belgian population. The proposed innovative methodology
simulates synthetic agents by accounting both for households’ and individuals’ characteristics, while not suffering from the
problem of the “zero cell value”. The results indicate that there is major day-to-day variability in working activity participation;
in particular, on Wednesdays and Fridays the number of households working part-time or not working is particularly high. This
is consistent with what was expected by the analysts. Working participation is a fundamental component in activity based models
where work is considered a skeletal activity. The tools developed here can be useful to study how changes in population characteristics
(i.e. increases of flexible working arrangements and of the number of women in the work force) affect activity participation
and travel patterns. 相似文献
4.
Davide Barbagallo Angela Caponnetto Cristina Barbagallo Rosalia Battaglia Federica Mirabella Duilia Brex Michele Stella Giuseppe Broggi Roberto Altieri Francesco Certo Rosario Caltabiano Giuseppe Maria Vincenzo Barbagallo Carmelina Daniela Anfuso Gabriella Lupo Marco Ragusa Cinzia Di Pietro Thomas Birkballe Hansen Michele Purrello 《International journal of molecular sciences》2021,22(4)
Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential. 相似文献
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6.
Margaret Ottaviano Emilio Francesco Giunta Marianna Tortora Marcello Curvietto Laura Attademo Davide Bosso Cinzia Cardalesi Mario Rosanova Pietro De Placido Erica Pietroluongo Vittorio Riccio Brigitta Mucci Sara Parola Maria Grazia Vitale Giovannella Palmieri Bruno Daniele Ester Simeone 《International journal of molecular sciences》2021,22(7)
As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. 相似文献
7.
Valter Castelvetro Cinzia De Vita Giacomo Giannini Simone Giaiacopi 《应用聚合物科学杂志》2006,102(4):3083-3094
The evolution of the main colloidal parameters in the seeded starved‐feed semi‐continuous emulsion polymerization of butyl methacrylate (BMA) was investigated, with the main purpose of assessing the effectiveness of the semi‐empirical relationship S = K · SS · ΔA/AS as a tool to define the surfactant/monomer feed ratio (∝ K) best suited to achieve a target particle size. In particular, the effect of the type and amount of surfactant [i.e., anionic, sodium dodecyl sulfate (SDS), or nonionic, Brij 58P] added during the semi‐continuous stage was considered. Coagulum formation was never observed under the adopted experimental conditions. To detect the occurrence of secondary nucleation or particle aggregation, or both, the particle size and number of particles, the surface tension and the particle surface coverage ratio were correlated. The best results were obtained with SDS and 0.8 ≤ K ≤ 3. In fact, under the selected experimental conditions, only with SDS did the number of particles remain nearly constant throughout the polymerization at the value defined by the seed latex; the particle size distribution was highly monodisperse, and the final particle diameter closely matched the calculated one (~ 120 nm). The above semi‐empirical relationship based on the adjustable parameter K was validated by running test polymerizations aimed at lattices with well‐defined particle size. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3083–3094, 2006 相似文献
8.
K. J. Williams A. B. Boffa M. Salmeron A. T. Bell G. A. Somorjai 《Catalysis Letters》1991,9(5-6):415-426
Submonolayer deposits of titania on a Rh foil have been found to increase the rate of CO2 hydrogenation. The primary product, methane, exhibits a maximum rate at a TiO
x
coverage of 0.5 ML which is a factor of 15 higher than that over the clean Rh surface. The rate of ethane formation displays a maximum which is 70 times that over the unpromoted Rh foil; however, the selectivity for methane remains in excess of 99%. The apparent activation energy for methane formation and the dependence of the rate on H2 and CO2 partial pressure have been determined both for the bare Rh surface and the titania-promoted surface. These rate parameters show very small variations as titania is added to the Rh catalyst. The methanation of CO2 is proposed to start with the dissociation of CO2 into CO(a) and O(a), and then proceed through steps which are identical to those for the hydrogenation of CO. The increase in the rate of CO2 hydrogenation in the presence of titania is attributed to an interaction between the adsorbed CO, released by CO2 dissociation, and Ti3+ ions located at the edge of TiO
x
islands covering the surface. Differences in the effects of titania promotion on the methanation of CO2 and CO are discussed in terms of the mechanisms that have been proposed for these two reactions. 相似文献
9.
Sub-monolayer quantities of metal oxides are found to influence CO hydrogenation, CO2 hydrogenation, acetone hydrogenation, ethylene hydroformylation, ethylene hydrogenation, and ethane hydrogenolysis over Rh foils. The metal oxides investigated include AlOx, TiOx, VOx, FeOx, ZrOx, NbOx, TaOx, and WOx. Only those reactions involving the hydrogenation of C-O bonds are enhanced by the oxide overlayers. The coverage at which maximum rate enhancement occurs is approximately 0.5 ML for each oxide promoter. Titanium, niobium, and tantalum oxides are the most effective promoters. XPS measurements after reaction show that of the oxides studied titanium, niobium, and tantalum oxide overlayers are stable in the highest oxidation states. The trend in promotion effectiveness is attributed to the direct relationship between oxidation state and Lewis acidity. For the oxide promoters, bonding at the metal oxide/metal interface between the O-end of adsorbed CO and the Lewis acidic oxide is postulated to facilitate C-O bond dissociation and subsequent hydrogenation. 相似文献
10.