Search results for "I3"
showing 10 items of 278 documents
Repression of Human Papillomavirus Oncogene Expression under Hypoxia Is Mediated by PI3K/mTORC2/AKT Signaling
2019
Oncogenic HPV types are major human carcinogens. Under hypoxia, HPV-positive cancer cells can repress the viral E6/E7 oncogenes and induce a reversible growth arrest. This response could contribute to therapy resistance, immune evasion, and tumor recurrence upon reoxygenation. Here, we uncover evidence that HPV oncogene repression is mediated by hypoxia-induced activation of canonical PI3K/mTORC2/AKT signaling. AKT-dependent downregulation of E6/E7 is only observed under hypoxia and occurs, at least in part, at the transcriptional level. Quantitative proteome analyses identify additional factors as candidates to be involved in AKT-dependent E6/E7 repression and/or hypoxic PI3K/mTORC2/AKT ac…
GLI3 is rarely implicated in OFD syndromes with midline abnormalities
2011
A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining ninety-three probands here. This includes nineteen probands (twelve mutations) who fulfilled clinical criteria for GCPS or PHS, forty-eight probands (sixteen mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), twenty-one probands (six mutations) with featu…
De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome
2014
Activating mutations in genes encoding phosphatidylinositol 3-kinase (PI3K)-AKT pathway components cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH, OMIM 603387)(1-3). Here we report that individuals with MPPH lacking upstream PI3K-AKT pathway mutations carry de novo mutations in CCND2 (encoding cyclin D2) that are clustered around a residue that can be phosphorylated by glycogen synthase kinase 313 (GSK-3 beta)(4). Mutant CCND2 was resistant to proteasomal degradation in vitro compared to wild-type CCND2. The PI3K-AKT pathway modulates GSK-3 beta activity(4), and cells from individuals with PIK3CA, PIK3R2 or AKT3 mutations showed similar CCND2 accumulation. CCND…
Energy poverty in Italy
2014
Despite the existence of two targeted national programmes (�Bonus gas� and �Bonus energia�) in Italy there is no official definition of energy poverty (EP). The purpose of this study is to provide the reader with a set of indicators to fill this gap. We present a range of poverty measures which estimate that between 5 and 20 per cent of households was in EP in 2012. A selection based on qualitative criteria suggests the use of a low-income/high-costs indicator modified to include the economically vulnerable households with no heating expenses. According to this statistic the proportion of households in EP during the period 1997-2012 was broadly stable at around 8 per cent. Our simul…
Effects of combined hormone replacement therapy or its effective agents on the IGF-1 pathway in skeletal muscle.
2010
Objectives To investigate the effects of combined hormone replacement therapy (HRT) and its effective agents on the IGF-1 signaling pathway. Design and methods To examine the effects of HRT on skeletal muscle in vivo, we utilized pre- and post-intervention samples from a randomized double blinded trial with 50–57-year-old women. The intervention included the year-long use of either HRT preparation (2 mg 17β-estradiol, E2; 1 mg norethisterone acetate, NETA, n = 10) or placebo (CO, n = 9). Microarray technology and quantitative PCR (qPCR) were used to study the expression of insulin-like growth factor I (IGF-1) and its splice variants as well as IGF-1 receptor, Akt1, mTOR, FOXO1, FOXO3, atrog…
THE EFFECTS OF PEOPLES’ HEIGHT AND RELATIVE HEIGHT ON WELL-BEING
2011
Using a rich Italian survey, we investigate the effect of height on individual happiness. From our analysis it emerges that a large part of the effect of height on well-being is driven by a positive correlation between height and economic and health conditions. However, for young males the effect of height on happiness persists even after controlling for these variables, implying that height may produce some psycho-social direct effects on well-being. Consistent with this hypothesis, we find that males care not only about their own height but also about the height of people in their reference group. Well-being is greater for individuals who are taller than other subjects in their reference …
Perception du risque dépendance et demande d'assurance : une analyse à partir de l'enquête PATER
2013
Dans la littérature économique, de nombreux travaux tentent d'expliquer pourquoi les individus s’assurent aussi peu contre la dépendance. Du côté de l’offre, différents freins possibles au développement du marché de l’assurance dépendance ont d’ores et déjà été pointés du doigt par la littérature. Les estimations récentes montrent néanmoins que les limites imputables à l’offre ne suffisent pas à expliquer le faible développement du marché : même si les assurances étaient moins coûteuses et les couvertures proposées plus larges, la majorité des individus ne souscrirait toujours pas d’assurance. Il est donc nécessaire d’aller trouver des explications du côté de la demande d’assurance dépendan…
Inequality and poverty in a developing economy: Evidence from regional data (Spain, 1860-1930)
2015
Apart from measuring inequality and poverty at the provincial level in Spain between 1860 and 1930, this paper empirically assesses the relationship between economic growth and both inequality and destitution. The results, on the one hand, confirm the presence of a KuznetsÕ curve. However, although growing incomes did not directly contribute to reducing inequality, at least during the early stages of modern economic growth, other processes associated with economic growth significantly improved the situation of the bottom part of the population. On the other hand, growing incomes and lower inequality levels are shown to have been pro-poor.
Acetic Acid Mediated for One-Pot Synthesis of Novel Pyrazolyl s-Triazine Derivatives for the Targeted Therapy of Triple-Negative Breast Tumor Cells (…
2022
Here, we described the synthesis of novel pyrazole-s-triazine derivatives via an easy one-pot procedure for the reaction of β-dicarbonyl compounds (ethylacetoacetate, 5,5-dimethyl-1,3-cyclohexadione or 1,3-cyclohexadionone) with N,N-dimethylformamide dimethylacetal, followed by addition of 2-hydrazinyl-4,6-disubstituted-s-triazine either in ethanol-acetic acid or neat acetic acid to afford a novel pyrazole and pyrazole-fused cycloalkanone systems. The synthetic protocol proved to be efficient, with a shorter reaction time and high chemical yield with broad substrates. The new pyrazolyl-s-triazine derivatives were tested against the following cell lines: MCF-7 (breast cancer); MDA-MB-231 (tr…
Neural Stem Cells in the Adult Brain: From Benchside to Clinic
2012
Increasing evidence indicates that neural stem cells (NSCs) play an important role in sustaining cellular homeostasis and brain tissue restoration. The study of all mechanisms that control and modulate the function of NSC is a crucial step for the design of therapies against chronic neurodegenerative processes. In this special issue of the journal, we had the pleasure to edit the topic entitled “Neural Stem Cells in the Adult Brain: From Benchside to Clinic.” This special compilation of paper was aimed to provide a global forum for publications of original peer-reviewed manuscripts that reported original research findings in the field of adult neural stem cell, including short communication…