Search results for "CKD"
showing 10 items of 258 documents
Rad51 and BRCA2 - New Molecular Targets for Sensitizing Glioma Cells to Alkylating Anticancer Drugs
2011
First line chemotherapeutics for brain tumors (malignant gliomas) are alkylating agents such as temozolomide and nimustine. Despite growing knowledge of how these agents work, patients suffering from this malignancy still face a dismal prognosis. Alkylating agents target DNA, forming the killing lesion O(6)-alkylguanine, which is converted into DNA double-strand breaks (DSBs) that trigger apoptosis. Here we assessed whether inhibiting repair of DSBs by homologous recombination (HR) or non-homologous end joining (NHEJ) is a reasonable strategy for sensitizing glioma cells to alkylating agents. For down-regulation of HR in glioma cells, we used an interference RNA (iRNA) approach targeting Ra…
Changes in carnitine octanoyltransferase activity induce alteration in fatty acid metabolism
2011
The peroxisomal beta oxidation of very long chain fatty acids (VLCFA) leads to the formation of medium chain acyl-CoAs such as octanoyl-CoA. Today, it seems clear that the exit of shortened fatty acids produced by the peroxisomal beta oxidation requires their conversion into acyl-carnitine and the presence of the carnitine octanoyltransferase (CROT). Here, we describe the consequences of an overexpression and a knock down of the CROT gene in terms of mitochondrial and peroxisomal fatty acids metabolism in a model of hepatic cells. Our experiments showed that an increase in CROT activity induced a decrease in MCFA and VLCFA levels in the cell. These changes are accompanied by an increase in …
EphrinB2 controls vessel pruning through STAT1-JNK3 signalling
2014
Angiogenesis produces primitive vascular networks that need pruning to yield hierarchically organized and functional vessels. Despite the critical importance of vessel pruning to vessel patterning and function, the mechanisms regulating this process are not clear. Here we show that EphrinB2, a well-known player in angiogenesis, is an essential regulator of endothelial cell death and vessel pruning. This regulation depends upon phosphotyrosine-EphrinB2 signalling repressing c-jun N-terminal kinase 3 activity via STAT1. JNK3 activation causes endothelial cell death. In the absence of JNK3, hyaloid vessel physiological pruning is impaired, associated with abnormal persistence of hyaloid vessel…
The Playing Brain. The Impact of Video Games on Cognition and Behavior in Pediatric Age at the Time of Lockdown: A Systematic Review
2021
A growing number of children and adolescents play video games (VGs) for long amounts of time. The current outbreak of the Coronavirus pandemic has significantly reduced outdoor activities and direct interpersonal relationships. Therefore, a higher use of VGs can become the response to stress and fear of illness. VGs and their practical, academic, vocational and educational implications have become an issue of increasing interest for scholars, parents, teachers, pediatricians and youth public policy makers. The current systematic review aims to identify, in recent literature, the most relevant problems of the complex issue of playing VGs in children and adolescents in order to provide sugges…
COVID-19 and Changes in Social Habits. Restaurant Terraces, a Booming Space in Cities. The Case of Madrid
2021
The COVID-19 pandemic and the fear experienced by some of the population, along with the lack of mobility due to the restrictions imposed, has modified the social behaviour of Spaniards. This has had a significant effect on the hospitality sector, viewed as being an economic and social driver in Spain. From the analysis of data collected in two of our own non-probabilistic surveys (N ~ 8400 and N ~ 2000), we show how, during the first six months of the pandemic, Spaniards notably reduced their consumption in bars and restaurants, also preferring outdoor spaces to spaces inside. The restaurant sector has needed to adapt to this situation and, with the support of the authorities (regional and…
Physical Activity Levels and Related Energy Expenditure during COVID-19 Quarantine among the Sicilian Active Population: A Cross-Sectional Online Sur…
2020
Background: During the coronavirus disease 2019 (COVID-19) pandemic, the Italian government has adopted containment measures to control the virus’s spread, including limitations to the practice of physical activity (PA). The aim of this study was to estimate the levels of PA, expressed as energy expenditure (MET–minute/week), among the physically active Sicilian population before and during the last seven days of the COVID-19 quarantine. Furthermore, the relation between this parameter and specific demographic and anthropometric variables was analyzed. Methods: 802 Sicilian physically active participants (mean age: 32.27 ± 12.81 years; BMI: 23.44 ± 3.33 kg/m2) were included in the study and…
Physical activity using social media during the COVID-19 pandemic: the perceptions of sports science students
2021
Abstract During the period of the COVID-19 lockdown, sports organizations and companies had to look for new ways to connect with their customers by offering physical activity (PA) alternatives to do at home. This study explores the perceptions of 175 undergraduate sports science students regarding their social media (SM) and PA patterns during the first Spanish COVID-19 lockdown period (March to May 2020). From their homes, the students completed an ad hoc online questionnaire. The data was analyzed using SPSS 23.0 software to perform descriptive and inferential analysis (t-test). The results show that the participants used SM during the COVID-19 lockdown to visualize or practice PA, percei…
Targeting components of the alternative NHEJ pathway sensitizes KRAS mutant leukemic cells to chemotherapy.
2014
Abstract Activating KRAS mutations are detected in a substantial number of hematologic malignancies. In a murine T-cell acute lymphoblastic leukemia (T-ALL) model, we previously showed that expression of oncogenic Kras induced a premalignant state accompanied with an arrest in T-cell differentiation and acquisition of somatic Notch1 mutations. These findings prompted us to investigate whether the expression of oncogenic KRAS directly affects DNA damage repair. Applying divergent, but complementary, genetic approaches, we demonstrate that the expression of KRAS mutants is associated with increased expression of DNA ligase 3α, poly(ADP-ribose) polymerase 1 (PARP1), and X-ray repair cross-comp…
Excision of Uracil from Transcribed DNA Negatively Affects Gene Expression
2014
Uracil is an unavoidable aberrant base in DNA, the repair of which takes place by a highly efficient base excision repair mechanism. The removal of uracil from the genome requires a succession of intermediate products, including an abasic site and a single strand break, before the original DNA structure can be reconstituted. These repair intermediates are harmful for DNA replication and also interfere with transcription under cell-free conditions. However, their relevance for cellular transcription has not been proved. Here we investigated the influence of uracil incorporated into a reporter vector on gene expression in human cells. The expression constructs contained a single uracil opposi…
Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a target in LKB1 Mutant Lung Cancer
2013
Abstract The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non–small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetica…