9 research outputs found
Obese zebrafish: A small fish for a major human health condition
No full textObesity is becoming a silent worldwide epidemic, with a steady increase in both adults and children. To date, even though several drugs have been licensed for long‐term obesity treatment, none of them are yet used in routine clinical practice. So far the only successful intervention has been behavioral therapy. A suitable and economic experimental model mimicking the human condition would therefore be extremely useful to evaluate preventive measures and novel treatments. Zebrafish are emerging as an important model system to study obesity and related metabolic disease. Remarkable similarities have been reported in lipid metabolism and the adipogenic pathway between zebrafish and mammals. Moreover, the zebrafish possesses a number of features—the relative inexpensiveness of animal husbandry, its optical transparency and the ability to produce a large number of offspring at low cost—that make it ideal for large‐scale screening and for testing drugs and intervention. In this review, we summarize recent progress in using zebrafish as a model system to study obesity and obesity‐related metabolic disorders. We describe several zebrafish models (in both larvae and adult animals) that develop obesity and non‐alcoholic fatty liver disease (NAFLD) using different approaches, including gene manipulation, diet manipulation and modification of microbiota composition. For these models, we have outlined the specific aspects related to obesity and its development and we have summarized their advantages and limitations
Genome wide mapping of the MBF-1 binding sites during embryogenesis of the sea urchin reveals it is a chromatin organizer.
No full textThe Zinc-finger MBF1 factor is a transcription activator involved in the expression of the early histone genes during development of the sea urchin embryo (1). The DNA-binding domain of MBF1 shares high sequence similarity with that of the CTCF chromatin organizer but, unexpectedly, extensive in silico analysis failed to identify the sea urchin CTCF ortholog (2, 3). This led us to speculate that MBF1 could have co-opted the function of CTCF during evolution of the echinoderms. To support this hypothesis, we performed the genome-wide MBF1-binding sites mapping in the P. lividus genome, by chromatin immunoprecipitation coupled to next generation sequencing (ChIP-Seq). We observed that MBF1 binding motifs are spread across the genome, with a CCCTC core sequence showing perfect conservation with the mammalian CTCF binding element. In particular, MBF1 binds to the promoter regions of hundreds of target genes. Among others, we confirmed the specific interaction with the promoters of histone and Hox genes, and observed the full evolutionary conservation of these binding sites in P. lividus and S. purpuratus species.
Next, to appraise globally the functional meaning of binding events we analyzed the MBF1 occupancy in chromatin samples derived from embryos exposed to compounds, such as Lithium and Zinc, that impair axial pattering. Comparison with controls revealed differential MBF1 recruitment on selected genes reflecting differentially regulated mechanisms in treated embryos. The molecular pathways impacted by Li and Zn include cell signaling, gene transcription, DNA repair, and chromatin condensation.
Collectively, our observations highlight the DNA binding potency of MBF1, strongly suggesting that it could act both as a transcription factor of its target genes and a general chromatin organizer.
1. Cavalieri, V et al. (2009) Nucleic Acid Res, 37,7407-15.
2. Heger , P et al. (2012) PNAS, 109, 17507-12.
3. Cavalieri, V et al. (2013) Plos Genetics, 9, e1003847
Reevaluating the function of a transcription factor: MBF-1 as a sea urchin chromatin organizer ?
No full textThe Zinc-finger MBF-1 factor is involved in the expression of the early histone genes during devel-opment of the sea urchin embryo (1, 2). In spite of being a transcription activator, the DNA-binding domain of MBF-1 shares high sequence similarity with that of the chromatin organizer CTCF of vertebrates and drosophila (3). On the other hand, extensive in silico analysis failed to identify the sea urchin CTCF ortholog (4). This led us to speculate that MBF-1 somehow could have co-opted the function of CTCF during evolution of the echinoderms. Since in vertebrates CTCF binds Hox chromatin, to support our hypothesis, we first identified high-score putative binding sequences for CTCF/MBF-1 within the single sea urchin Hox gene cluster. Moreover, we observed the full evolu-tionary conservation of these binding sites in S. purpuratus and P. lividus species. Worth of men-tion, by chromatin immunoprecipitation (ChIP) assay, we detected the occupancy of MBF-1 on hox11/13-a, -b, and -c regulatory sequences at distinct stages of development. As expected from the binding of an activator, we found that the association of MBF-1 to the cis-regulatory sequences of both hox11/13-a and -b genes relates to the transcriptional status of these genes. Strikingly, we also mapped the physical binding of MBF-1 to hox11/13-c, which is instead not expressed during em-bryogenesis. Altogether, these observations indeed suggest the possibility that MBF-1, besides be-ing a transcription activator, could also function as a general chromatin organizer. To further support this hypothesis, we are planning ChIP-seq experiments to identify the association of MBF-1 to the sea urchin chromatin at a genome-wide level.
1. Di Caro, V. et al. (2007) J. Mol. Bio.,365, 1285-97.
2. Cavalieri,V et al. (2009) Nucleic Acid Res, 37,7407-7415.
3. Heger , P. et al. (2012) PNAS, 109, 17507–17512.
4. Cavalieri, V. et al. (2013) Plos Genetics, 9, e1003847
Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study
No full textIn HCC, tumor microenvironment, heavily influenced by the underlying chronic liver disease, etiology and stage of the tissue damage, affects tumor progression and determines the high heterogeneity of the tumor. Aim of this study was to identify the circulating and tissue components of the microenvironment immune-mediated response affecting the aggressiveness and the ensuing clinical outcome. We analyzed the baseline paired HCC and the surrounding tissue biopsies from a prospective cohort of 132 patients at the first diagnosis of HCC for immunolocalization of PD-1/PD-L1, FoxP3, E-cadherin, CLEC2 and for a panel of 82 microRNA associated with regulation of angiogenesis, cell proliferation, cell signaling, immune control and autophagy. Original microarray data were also explored. Serum samples were analyzed for a panel of 19 cytokines. Data were associated with biochemical data, histopathology and survival. Patients with a more aggressive disease and shorter survival, who we named fast-growing accordingly to the tumor doubling time, at presentation had significantly higher AFP levels, TGF-β1 and Cyphra 21-1 levels. Transcriptomic analysis evidenced a significant downregulation of CLEC2 and upregulation of several metalloproteinases. A marked local upregulation of both PD-1 and PD-L1, a concomitant FoxP3-positive lymphocytic infiltrate, a loss of E-cadherin, gain of epithelial-mesenchymal transition (EMT) phenotype and extreme poor differentiation at histology were also present. Upregulated microRNA in fast-growing HCCs are associated with TGF-β signaling, angiogenesis and inflammation. Our data show that fast HCCs are characterized not only by redundant neo-angiogenesis but also by unique features of distinctively immunosuppressed microenvironment, prominent EMT, and clear-cut activation of TGFβ1 signaling in a general background of long-standing and permanent inflammatory state
Liver Angiopoietin-2 is a key predictor of de novo or recurrent hepatocellular cancer after HCV direct-acting antivirals
No full textRecent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC).In Study 1,we studied the proangiogenic liver microenvironment in 242 DAAs-treated chronic Hepatitis C patients with advanced fibrosis.Angiopoietin-2 expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent,de novo,non-recurrent HCC or patients never developing HCC.Circulating Angiopoietin-2,vascular-endothelial growth factor (VEGF),and C-reactive protein were also measured. In Study 2,we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical,clinical,hemodynamic,endoscopic, elastographic,and echo-Doppler work-up was performed in both studies.In Study 1,none without cirrhosis developed HCC.Of 183 patients with cirrhosis,14/28 (50.0%) with previous HCC recurred while 21/155 (13.5%) developed de novo HCC.Recurrent and de novo HCCs had significantly higher liver fibrosis scores,portal pressure,and systemic inflammation than non-recurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients,tumor and non-tumor Angiopoietin-2 showed an inverse relationship with portal vein velocity (r=-0.412,p=0.037 and r= -0.409,p=0.047,respectively) and a positive relationship with liver stiffness (r=0.526,p=0.007;r=0.525,p=0.003,respectively).Baseline circulating VEGF and cirrhotic liver Angiopoietin-2 were significantly related (r=0.414,p=0.044).VEGF increased during DAAs, remaining stably elevated at 3 months follow-up, when it significantly related with serum Angiopoietin-2 (r=0.531,p=0.005).Angiopoietin-2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with the risk of HCC recurrence (OR 1.137,95%CI 1.044-1.137,p=0.003) or occurrence (OR 1.604,95% CI 1.080-2.382;p=0.019).In Study 2,DAA treatment (OR 4.770,95%CI 1.395-16.316,p=0.013) and large varices (OR 3.857,95%CI 1.127-13.203,p=0.032) were independent predictors of de novo HCC
Uso de videojuegos como herramienta pedagógica para el aprendizaje de inglés en estudiantes universitarios
No full textEste proyecto de investigación se centra en el estudio de cómo el uso de los videojuegos puede ser de gran aporte para el aprendizaje del idioma inglés teniendo en cuenta que este medio de entretenimiento últimamente ha tomado mayor fuerza conforme ha pasado el tiempo y la opinión publica frente a este ha cambiado notoriamente hasta el punto de considerarse como herramienta en el ámbito académico.
Se realizó una revisión en la parte teórica la cual era relevante para los puntos de investigación que fueron: videojuegos y comunicación, pedagogía, ludoliteracy, inglés en los videojuegos y como estos se han ido desarrollando. Autores como Duilio Faillaci y su texto de los videojuegos como medio de comunicación, Nádala Fernández con la historia de los videojuegos y Dani Aranda explicando la importancia de ludoliteracy, aportaron significativamente a la investigación en torno al marco teórico y diseño metodológico.
Se aplicaron técnicas de investigación como entrevistas a jóvenes universitarios, expertos en campos como comunicación, videojuegos, pedagogía y relatos de vida con el fin de dar respuesta a los objetivos de esta investigación. Con los resultados y los análisis obtenidos se logró demostrar que el uso de los videojuegos para el aprendizaje de un idioma extranjero que en este caso es inglés, es totalmente factible y se puede tener en cuenta en los procesos de aprendizaje de las personas si se aplica adecuadamente.
En cuanto a los resultados obtenidos en el diseño metodológico se encontró que los jóvenes universitarios que participaron de la entrevista en el 100% de los casos dijeron sentirse motivados con la idea de aprender inglés a través de los videojuegos y de la misma forma que en el tiempo que llevan jugando han aprendido y han mejorado su nivel de este idioma. La comunicación fue un pilar importante para ellos puesto que de una u otra forma tenían la necesidad de comunicarse con otras personas, buscando siempre la manera mas exacta de hacerse entender sobre todo en casos en donde la parte oral estaba implícita.
Para finalizar, las conclusiones de este trabajo reflejan el enorme valor comunicativo que transmiten los videojuegos a través de contenidos variados en lenguas extranjeras que a su vez potencian el aprendizaje de estas mediante chats, diálogos entre personajes o personas de otros países y, no menos importante, la comunicación en red que permite un mayor intercambio de saberesProyecto de grado (Comunicador Social - Periodista)-- Universidad Autónoma de Occidente, 2020PregradoComunicador(a) Social – Periodist
Uso de videojuegos como herramienta pedagógica para el aprendizaje de inglés en estudiantes universitarios
No full textEste proyecto de investigación se centra en el estudio de cómo el uso de los videojuegos puede ser de gran aporte para el aprendizaje del idioma inglés teniendo en cuenta que este medio de entretenimiento últimamente ha tomado mayor fuerza conforme ha pasado el tiempo y la opinión publica frente a este ha cambiado notoriamente hasta el punto de considerarse como herramienta en el ámbito académico.
Se realizó una revisión en la parte teórica la cual era relevante para los puntos de investigación que fueron: videojuegos y comunicación, pedagogía, ludoliteracy, inglés en los videojuegos y como estos se han ido desarrollando. Autores como Duilio Faillaci y su texto de los videojuegos como medio de comunicación, Nádala Fernández con la historia de los videojuegos y Dani Aranda explicando la importancia de ludoliteracy, aportaron significativamente a la investigación en torno al marco teórico y diseño metodológico.
Se aplicaron técnicas de investigación como entrevistas a jóvenes universitarios, expertos en campos como comunicación, videojuegos, pedagogía y relatos de vida con el fin de dar respuesta a los objetivos de esta investigación. Con los resultados y los análisis obtenidos se logró demostrar que el uso de los videojuegos para el aprendizaje de un idioma extranjero que en este caso es inglés, es totalmente factible y se puede tener en cuenta en los procesos de aprendizaje de las personas si se aplica adecuadamente.
En cuanto a los resultados obtenidos en el diseño metodológico se encontró que los jóvenes universitarios que participaron de la entrevista en el 100% de los casos dijeron sentirse motivados con la idea de aprender inglés a través de los videojuegos y de la misma forma que en el tiempo que llevan jugando han aprendido y han mejorado su nivel de este idioma. La comunicación fue un pilar importante para ellos puesto que de una u otra forma tenían la necesidad de comunicarse con otras personas, buscando siempre la manera mas exacta de hacerse entender sobre todo en casos en donde la parte oral estaba implícita.
Para finalizar, las conclusiones de este trabajo reflejan el enorme valor comunicativo que transmiten los videojuegos a través de contenidos variados en lenguas extranjeras que a su vez potencian el aprendizaje de estas mediante chats, diálogos entre personajes o personas de otros países y, no menos importante, la comunicación en red que permite un mayor intercambio de saberesProyecto de grado (Comunicador Social - Periodista)-- Universidad Autónoma de Occidente, 2020PregradoComunicador(a) Social – Periodist
AISF position paper on liver transplantation and pregnancy. Women in Hepatology Group, Italian Association for the Study of the Liver (AISF)
No full textAfter the first successful pregnancy in a liver transplant recipient in 1978, much evidence has accumulated on the course, outcomes and management strategies of pregnancy following liver transplantation. Generally, liver transplantation restores sexual function and fertility as early as a few months after transplant. Considering that one third of all liver transplant recipients are women, that approximately one-third of them are of reproductive age (18-49 years), and that 15% of female liver transplant recipients are paediatric patients who have a >70% probability of reaching reproductive age, the issue of pregnancy after liver transplantation is rather relevant, and obstetricians, paediatricians, and transplant hepatologists ever more frequently encounter such patients. Pregnancy outcomes for both the mother and infant in liver transplant recipients are generally good, but there is an increased incidence of preterm delivery, hypertension/preeclampsia, foetal growth restriction, and gestational diabetes, which, by definition, render pregnancy in liver transplant recipients a high-risk one. In contrast, the risk of congenital anomalies and the live birth rate are comparable to those of the general population. Currently there are still no robust guidelines on the management of pregnancies after liver transplantation. The aim of this position paper is to review the available evidence on pregnancy in liver transplant recipients and to provide national Italian recommendations for clinicians caring for these patients
Liver Angiopoietin-2 Is a Key Predictor of De Novo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct-Acting Antivirals
No full textAbstract
Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA-treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin-2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C-reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echoDoppler work-up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = –0.412, P = 0.037 and r = –0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3-month follow-up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044-1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080-2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395-16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127-13.203; P = 0.032) were independent predictors of de novo HCC. Conclusion: Our study indicates that DAA-mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo-angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 68:1010-1024)
