Identification of a novel Sp1 splice variant as a strong transcriptional activator.

The transcription factor Sp1 regulates expression of numerous genes involved in many cellular processes. Different post-transcriptional modifications can influence the transcriptional control activity and stability of Sp1. In addition to these modifications, alternative splicing isoforms may also be the basis of its distinct functional activities. In this study, we identified a novel alternative splice isoform of Sp1 named Sp1c. This variant is generated by exclusion of a short domain, which we designate a, through alternative splice acceptor site usage in the exon 3. The existence of this new isoform was confirmed in vivo by Western blotting analysis. Although at very low levels, Sp1c is ubiquitously expressed, as seen in its fulllength Sp1. A preliminary characterization of Sp1c shows that: (a) Sp1c works as stronger activator of transcription than full-length Sp1; (b) percentage of HEK293 Sp1c-overexpressing cells is higher in G1 phase and lower in S phase than percentage of HEK293 Sp1-overexpressing cells

Efectos de un hidrocarburo aromático policíclico (ß naftoflavona) sobre biomarcadores de efecto en Corydoras paleatus en condiciones de campo y laboratorio

Polycyclic aromatic hydrocarbons (PAHs) are important anthropogenic sources of aquatic contamination. In this study, hepatic biomarker responses of Corydoras paleatus injected with one sublethal dose of a PAH (ß-naftoflavona, BNF) were assessed under laboratory and field conditions. Glutathion-S-transferase (GST) and catalase (CAT) hepatic activities, liver protein content (PC), condition factor (CF) and liver somatic index (LSI) were determined. Two bioassays were performed during winter time: laboratory (la) and field (ca). Fish were injected with 50 mg BNF/kg body weight dissolved in corn oil (ß-la y ßca); control fish received corn oil (C-la y C-ca). There were no differences between controls or in BNF injected fish in the assessed parameters. BNF provoked a tendency of increase in CAT and GST activities and lower values of CP; on the other hand, no differences were observed in the FC and IHS. In BNF field exposed fish (ß-ca) CAT activity was significantly stimulated vs. both field and laboratory controls; GST differences were detected both between ß-ca and ß-la and their respective controls. BNF exposure induced adverse effects principally in the enzymatic biomarkers of C. paleatus and those effects were modulated by the environmental conditions.Facultad de Ciencias Naturales y Muse

Efectos de un hidrocarburo aromático policíclico (ß naftoflavona) sobre biomarcadores de efecto en Corydoras paleatus en condiciones de campo y laboratorio

Polycyclic aromatic hydrocarbons (PAHs) are important anthropogenic sources of aquatic contamination. In this study, hepatic biomarker responses of Corydoras paleatus injected with one sublethal dose of a PAH (ß-naftoflavona, BNF) were assessed under laboratory and field conditions. Glutathion-S-transferase (GST) and catalase (CAT) hepatic activities, liver protein content (PC), condition factor (CF) and liver somatic index (LSI) were determined. Two bioassays were performed during winter time: laboratory (la) and field (ca). Fish were injected with 50 mg BNF/kg body weight dissolved in corn oil (ß-la y ßca); control fish received corn oil (C-la y C-ca). There were no differences between controls or in BNF injected fish in the assessed parameters. BNF provoked a tendency of increase in CAT and GST activities and lower values of CP; on the other hand, no differences were observed in the FC and IHS. In BNF field exposed fish (ß-ca) CAT activity was significantly stimulated vs. both field and laboratory controls; GST differences were detected both between ß-ca and ß-la and their respective controls. BNF exposure induced adverse effects principally in the enzymatic biomarkers of C. paleatus and those effects were modulated by the environmental conditions.Polycyclic aromatic hydrocarbons (PAHs) are important anthropogenic sources of aquatic contamination. In this study, hepatic biomarker responses of Corydoras paleatus injected with one sublethal dose of a PAH (ß-naftoflavona, BNF) were assessed under laboratory and field conditions. Glutathion-S-transferase (GST) and catalase (CAT) hepatic activities, liver protein content (PC), condition factor (CF) and liver somatic index (LSI) were determined. Two bioassays were performed during winter time: laboratory (la) and field (ca). Fish were injected with 50 mg BNF/kg body weight dissolved in corn oil (ß-la y ßca); control fish received corn oil (C-la y C-ca). There were no differences between controls or in BNF injected fish in the assessed parameters. BNF provoked a tendency of increase in CAT and GST activities and lower values of CP; on the other hand, no differences were observed in the FC and IHS. In BNF field exposed fish (ß-ca) CAT activity was significantly stimulated vs. both field and laboratory controls; GST differences were detected both between ß-ca and ß-la and their respective controls. BNF exposure induced adverse effects principally in the enzymatic biomarkers of C. paleatus and those effects were modulated by the environmental condition

Efectos de un hidrocarburo aromático policíclico (ß naftoflavona) sobre biomarcadores de efecto en Corydoras paleatus en condiciones de campo y laboratorio

Polycyclic aromatic hydrocarbons (PAHs) are important anthropogenic sources of aquatic contamination. In this study, hepatic biomarker responses of Corydoras paleatus injected with one sublethal dose of a PAH (ß-naftoflavona, BNF) were assessed under laboratory and field conditions. Glutathion-S-transferase (GST) and catalase (CAT) hepatic activities, liver protein content (PC), condition factor (CF) and liver somatic index (LSI) were determined. Two bioassays were performed during winter time: laboratory (la) and field (ca). Fish were injected with 50 mg BNF/kg body weight dissolved in corn oil (ß-la y ßca); control fish received corn oil (C-la y C-ca). There were no differences between controls or in BNF injected fish in the assessed parameters. BNF provoked a tendency of increase in CAT and GST activities and lower values of CP; on the other hand, no differences were observed in the FC and IHS. In BNF field exposed fish (ß-ca) CAT activity was significantly stimulated vs. both field and laboratory controls; GST differences were detected both between ß-ca and ß-la and their respective controls. BNF exposure induced adverse effects principally in the enzymatic biomarkers of C. paleatus and those effects were modulated by the environmental conditions.Facultad de Ciencias Naturales y Muse

Efectos de un hidrocarburo aromático policíclico (ß naftoflavona) sobre biomarcadores de efecto en Corydoras paleatus en condiciones de campo y laboratorio

Polycyclic aromatic hydrocarbons (PAHs) are important anthropogenic sources of aquatic contamination. In this study, hepatic biomarker responses of Corydoras paleatus injected with one sublethal dose of a PAH (ß-naftoflavona, BNF) were assessed under laboratory and field conditions. Glutathion-S-transferase (GST) and catalase (CAT) hepatic activities, liver protein content (PC), condition factor (CF) and liver somatic index (LSI) were determined. Two bioassays were performed during winter time: laboratory (la) and field (ca). Fish were injected with 50 mg BNF/kg body weight dissolved in corn oil (ß-la y ßca); control fish received corn oil (C-la y C-ca). There were no differences between controls or in BNF injected fish in the assessed parameters. BNF provoked a tendency of increase in CAT and GST activities and lower values of CP; on the other hand, no differences were observed in the FC and IHS. In BNF field exposed fish (ß-ca) CAT activity was significantly stimulated vs. both field and laboratory controls; GST differences were detected both between ß-ca and ß-la and their respective controls. BNF exposure induced adverse effects principally in the enzymatic biomarkers of C. paleatus and those effects were modulated by the environmental conditions.Facultad de Ciencias Naturales y Muse

Rtg signaling sustains mitochondrial respiratory capacity in hog1-dependent osmoadaptation

Mitochondrial RTG-dependent retrograde signaling, whose regulators have been characterized in Saccharomyces cerevisiae, plays a recognized role under various environmental stresses. Of special significance, the activity of the transcriptional complex Rtg1/3 has been shown to be modu-lated by Hog1, the master regulator of the high osmolarity glycerol pathway, in response to osmotic stress. The present work focuses on the role of RTG signaling in salt-induced osmotic stress and its interaction with HOG1. Wild-type and mutant cells, lacking HOG1 and/or RTG genes, are compared with respect to cell growth features, retrograde signaling activation and mitochondrial function in the presence and in the absence of high osmostress. We show that RTG2, the main upstream regulator of the RTG pathway, contributes to osmoadaptation in an HOG1-dependent manner and that, with RTG3, it is notably involved in a late phase of growth. Our data demonstrate that impairment of RTG signaling causes a decrease in mitochondrial respiratory capacity exclusively under os-mostress. Overall, these results suggest that HOG1 and the RTG pathway may interact sequentially in the stress signaling cascade and that the RTG pathway may play a role in inter-organellar metabolic communication for osmoadaptation

KRAS-regulated glutamine metabolism requires UCP2-mediated aspartate transport to support pancreatic cancer growth

The oncogenic KRAS mutation has a critical role in the initiation of human pancreatic ductal adenocarcinoma (PDAC) since it rewires glutamine metabolism to increase reduced nicotinamide adenine dinucleotide phosphate (NADPH) production, balancing cellular redox homeostasis with macromolecular synthesis1,2. Mitochondrial glutamine-derived aspartate must be transported into the cytosol to generate metabolic precursors for NADPH production2. The mitochondrial transporter responsible for this aspartate efflux has remained elusive. Here, we show that mitochondrial uncoupling protein 2 (UCP2) catalyses this transport and promotes tumour growth. UCP2-silenced KRASmut cell lines display decreased glutaminolysis, lower NADPH/NADP+ and glutathione/glutathione disulfide ratios and higher reactive oxygen species levels compared to wild-type counterparts. UCP2 silencing reduces glutaminolysis also in KRASWT PDAC cells but does not affect their redox homeostasis or proliferation rates. In vitro and in vivo, UCP2 silencing strongly suppresses KRASmut PDAC cell growth. Collectively, these results demonstrate that UCP2 plays a vital role in PDAC, since its aspartate transport activity connects the mitochondrial and cytosolic reactions necessary for KRASmut rewired glutamine metabolism2, and thus it should be considered a key metabolic target for the treatment of this refractory tumour

Integrating Multiple Biomarkers of Fish Health: A Case Study of Fish Health in Ports

Biomarkers of fish health are recognised as valuable biomonitoring tools that inform on the impact of pollution on biota. The integration of a suite of biomarkers in a statistical analysis that better illustrates the effects of exposure to xenobiotics on living organisms is most informative; however, most published ecotoxicological studies base the interpretation of results on individual biomarkers rather than on the information they carry as a set. To compare the interpretation of results from individual biomarkers with an interpretation based on multivariate analysis, a case study was selected where fish health was examined in two species of fish captured in two ports located in Western Australia. The suite of variables selected included chemical analysis of white muscle, body condition index, liver somatic index (LSI), hepatic ethoxyresorufin-O-deethylase activity, serum sorbitol dehydrogenase activity, biliary polycyclic aromatic hydrocarbon metabolites, oxidative DNA damage as measured by serum 8-oxo-dG, and stress protein HSP70 measured on gill tissue. Statistical analysis of individual biomarkers suggested little consistent evidence of the effects of contaminants on fish health. However, when biomarkers were integrated as a set by principal component analysis, there was evidence that the health status of fish in Fremantle port was compromised mainly due to increased LSI and greater oxidative DNA damage in fish captured within the port area relative to fish captured at a remote site. The conclusions achieved using the integrated set of biomarkers show the importance of viewing biomarkers of fish health as a set of variables rather than as isolated biomarkers of fish health

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects