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They were inverted shortly afterwards to prevent their swallowing the toxic solution (Alberts and Galef, 1971 Brain, Goldsmith, Parmigiani and Mainardi, 1982). Each mouse was lightly anaesthetized with ether and then 25 ul of a 4% aqueous solution of zinc sulphate was introduced into each nostril. They were rendered anosmic 24 hours before agonistic encounters. One group of males (n = 60) was housed in groups of five in opaque plastic cages measuring 24.5 x 24.5 x 15 cm (PANLAB, Barcelona, Spain) and used as non-aggressive anosmic opponents. Ninety nine commercially-acquired (IFFA CREDO, Lyon, France) OF1 albino mice (86 males and 13 females) arrived at the laboratory at 42 days of age. The level of aggression induced by isolation which that induced by cohabitation To induce aggression than the «isolation» model, the present study compared In order to study the possibility of using a more natural paradigm Few studies have compared the level of aggression induced by isolation and by cohabitation with a female (Brain, Benton and Bolton, 1978 O´Donnell, Blanchard and Blanchard, 1981 Jones and Brain, 1987 Zochi, Cabib and Puglisi-Allegra, 1994 Moya-Albiol, Salvador, Martínez-Sanchis and Costa, 1995) and the results obtained are different depending on the strain. However, the studies employing this paradigm in mice are scanty (Brain, Homady, Castaño and Parmigiani, 1987 Parmigiani, Mainardi, Brain, Haug and Brunoni, 1989 Yoshimura and Kimura, 1991). In other rodent species such as rats the cohabitation with a female paradigm has been commonly used to induce aggression. All these changes have been described as the «isolation syndrome» (Valzelli, 1973, 1981) which may possibly influence the effect of pharmacological treatments on aggression in pre-clinical studies. It is well known that isolation has effects not only on aggression but also on other kinds of behavior, hormones and neurotransmitter systems (Valzelli, 1973 Valzelli and Bernasconi, 1979 Brain and Benton, 1983 Hilakivi, Ota and Lister, 1989 Cabib and Puglisi-Allegra, 1990). The level of aggressiveness increases with the duration of the isolation although it varies with strain and age (Valzelli and Garattini, 1968 Eleftheriou, Bailey and Denenberg, 1974 Eichelman et al., 1981 Siegfried, Alieva, Oliverio and Puglisi-Allegra, 1981 Puglisi-Allegra and Cabib, 1985). During this period, animals maintain visual, auditory and olfactory communication with other conspecifics in the same room. The most commonly used in mice is the isolation paradigm, in which animals are individually housed for a period of some weeks before being confronted with another male. Válido para inducir agresión en ratones machos OF1.ĭifferent animal models are used in the laboratory to induce aggression in male rodents (Eichelman, Elliot and Barchas, 1981). Este estudio sugiere que el paradigma de cohabitaciónĬon una hembra, siendo más natural que el aislamiento, es igualmente Además, no se observaron diferenciasĮn otras conductas. Los resultados muestran que ambos paradigmas inducen el mismo Se registraron los encuentros y se analizó la conductaĭe los animales. Los ratones machos con un oponente no agresivo en una área neutralĭurante 10 minutos. Tras cuatro semanasĭe aislamiento o cohabitación con una hembra, se confrontó a En este estudio, se ha comparadoĮl nivel de agresión inducido por aislamiento con el inducido medianteĬohabitación con una hembra en ratones machos OF1. Machos es el aislamiento o alojamiento individual, a pesar de las alteracionesįisiológicas y conductuales que produce. Unoĭe los paradigmas más utilizados para inducir agresión en ratones Nivel de agresión que el aislamiento en ratones macho OF1. La cohabitación con una hembra induce el mismo With a female is not only a more natural but also a valid paradigm to induce No differences in other behaviors were found. That both paradigms induced the same level of aggression in this strain. Were videotaped and the behavior of animals was analyzed. With a non-aggressive opponent in a neutral area for 10 minutes. Of either isolation or cohabitation with a female, male mice were confronted The level of aggression induced by isolation was compared with that inducedīy cohabitation with a female in OF1 male mice. Show alterations in some behavioral and physiological variables. Most frequently used in male mice, although animals submitted to this procedure The isolation or individually-housed paradigm is one of the Luis Moya-Albiol, Àngels Calvo-Torrent, Yolanda Martí-Lianes, Alicia Salvador and Manuela Martínez 351-356ĬOHABITATION WITH A FEMALE INDUCES THE SAME LEVEL OF AGGRESSION AS ISOLATION IN OF1 MALE MICE
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(B) Reads distribution of the top 10 most abundant mature miRNAs in human hepatocytes (left) and the top 10 most abundant miRNA precursors in human non-tumor liver tissues from HCC Cohort 2 (right). Un-paired t-test was used for Cohort 1 and non-parametric test was for Cohort 2. (A) Expression levels of mature miR-192–5p and mir-192 precursor in five groups of CSC + HCCs and CSC - HCCs from miRNA array data of HCC Cohort 1 (left) and Cohort 2 (right). (F) GSEA analysis was performed to identify functionally related “gene sets” with statistically significant enrichment, using miR-192–5p related genes identified from Cohort 1. (E) Kaplan-Meier curves of overall survival and time to recurrence according to miR-192–5p levels (tertile division). (D) Kaplan-Meier curves of overall survival and time to recurrence of two identified HCC groups by 14 CSC-miRNAs. The positive (Red bar) and negative (green bar) statuses of five CSC biomarkers are labeled correspondingly for each case. The relative intensity of miR-192–5p in tumor was ranked. (C) Hierarchical clustering analysis of 14 miRNAs revealed two different groups. The abundance of 14 miRNAs (representing 25 miRNA probes) in non-tumor tissues from HCC patients was shown in the heat map. (B) Venn Diagram analysis of miRNAs that were significantly (p<0.05) altered in CSC + HCCs vs. For each biomarker, red and green dots referred to HCC patients with the top 25% expression levels (CSC + HCCs), and patients with the bottom 25% levels (CSC - HCCs), respectively. (A) Relative levels of five different hepatic CSC biomarkers. ©2018 American Association for Cancer Research. SIGNIFICANCE: miR-192-5p and its regulatory pathway is significantly abolished in multiple groups of HCC expressing high levels of CSC markers, which may represent a key event for hepatic carcinogenesis. #ACTIVATION KEY FOR CSC ORION 18 DRIVER#This circuit may be the driver that steers liver cells toward hepatic CSC cells, leading to hepatic carcinogenesis. This study reveals the circuit from hypermethylation of the mir-192 promoter through the increase in PABPC4 as a shared genetic regulatory pathway in various groups of primary CSC + HCC. Both TP53 mutation and hypermethylation of the mir-192 promoter impeded transcriptional activation of miR-192-5p in HCC cell lines and primary CSC + HCC. 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