Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease

Previous studies showed that YAP1 is over-expressed in hepatocellular carcinoma (HCC). Here we observed higher expression of Yap1/Ctgf axis in dysplastic nodules and HCC chemically-induced in F344 rats, genetically susceptible to hepatocarcinogenesis, than in lesions induced in resistant BN rats. In BN rats, highest increase in Yap1-tyr357, p73 phosphorylation and Caspase 3 cleavage occurred. In human HCCs with poorer prognosis ( 3 years survival; HCCB). In the latter, higher levels of phosphorylated YAP1-ser127, YAP1-tyr357 and p73, YAP1 ubiquitination, and Caspase 3 cleavage occurred. Expression of stemness markers NANOG, OCT-3/4, and CD133 were highest in HCCP and correlated with YAP1 and YAP1-TEAD levels. In HepG2, Huh7, and Hep3B cells, forced YAP1 over-expression led to stem cell markers expression and increased cell viability, whereas inhibition of YAP1 expression by specific siRNA, or transfection of mutant YAP1 which does not bind to TEAD, induced opposite alterations. These changes were associated, in Huh7 cells transfected with YAP1 or YAP1 siRNA, with stimulation or inhibition of cell migration and invasivity, respectively. Furthermore, transcriptome analysis showed that YAP1 transfection in Huh7 cells induces over-expression of genes involved in tumor stemness. In conclusion, Yap1 post-translational modifications favoring its ubiquitination and apoptosis characterize HCC with better prognosis, whereas conditions favoring the formation of YAP1-TEAD complexes are associated with aggressiveness and acquisition of stemness features by HCC cells

A trans10-18:1 enriched fraction from beef fed a barley grain-based diet induces lipogenic gene expression and reduces viability of HepG2 cells.

Beef fat is a natural source of trans (t) fatty acids, and is typically enriched with either t10-18:1 or t11-18:1. Little is known about the bioactivity of individual t-18:1 isomers, and the present study compared the effects of t9-18:1, cis (c)9-18:1 and trans (t)-18:1 fractions isolated from beef fat enriched with either t10-18:1 (HT10) or t11-18:1 (HT11). All 18:1 isomers resulted in reduced human liver (HepG2) cell viability relative to control. Both c9-18:1 and HT11were the least toxic, t9-18:1had dose response increased toxicity, and HT10 had the greatest toxicity (P<0.05). Incorporation of t18:1 isomers was 1.8-2.5 fold greater in triacylglycerol (TG) than phospholipids (PL), whereas Δ9 desaturation products were selectively incorporated into PL. Culturing HepG2 cells with t9-18:1 and HT10 increased (P<0.05) the Δ9 desaturation index (c9-16:1/16:0) compared to other fatty acid treatments. HT10 and t9-18:1 also increased expression of lipogenic genes (FAS, SCD1, HMGCR and SREBP2) compared to control (P<0.05), whereas c9-18:1 and HT11 did not affect the expression of these genes. Our results suggest effects of HT11 and c9-18:1 were similar to BSA control, whereas HT10 and t-9 18:1 (i.e. the predominant trans fatty acid isomer found in partially hydrogenated vegetable oils) were more cytotoxic and led to greater expression of lipogenic genes

Ergonomia e Alzheimer: a contribuição dos fatores ambientais como recurso terapêutico nos cuidados de idosos portadores da demência tipo Alzheimer

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia de Produção.O presente estudo constitui em uma fundamentação teórica em que se procurou relacionar a Doença de Alzheimer (DA) e o ambiente físico, imediatamente ao redor do indivíduo acometido, como um recurso em potencial no tratamento dessa relevante doença da terceira idade. Os fatores físicos do ambiente determinados pela iluminação, temperatura, ruído, mobiliário e cores, os quais constituem parâmetros utilizados pela Ergonomia no planejamento de ambientes adequados para convivência do homem foram aqui aplicados, como importantes recursos no tratamento de Doença de Alzheimer. A revisão teórica apresentada foi complementada com um estudo de caso, através da observação da aplicabilidade prática e adequada de tais fatores em duas instituições geriátricas americanas de referência, nos cuidados diários de indivíduos acometidos por DA.. Na observação realizada comprovou-se a influência positiva que um ambiente adequadamente planejado exerce no comportamento e na qualidade de vida dos indivíduos acometidos. Que a proposta desse trabalho, ou seja, trazer este tema para receber um tratamento da Ergonomia, o que reforça a multidisciplinaridade dessa ciência, seja mais importante que o nível de detalhamento técnico do presente estudo. Espera-se que este estudo venha estimular novas investigações, servindo de base introdutória para os pesquisadores e profissionais atuantes nas diversas áreas concernentes ao tema pesquisado. The present study provides a theoretical understanding about people with Alzheimer's Disease and the environment in which they live. The physical environment was here identified as a therapeutic potential resource on the treatment of this most prevalent illness of the senior age. The sensory cues in such key areas as lighting, ventilation / thermal sensitivity, acoustics, furnishings and color which are Ergonomics issues on planning appropriate enviroments to the human living, were here applied as a therapeutic resource in the provision of care for people with Alzheimer's disease. The theoretical revision was completed and based on case studies wich describes and analyses two facilities designed in response to the care of people with Alzheimer's Disease located in the Unites States of America. The analyses demonstrate what positive effects of changes in the physical environment may exert on the behavior and quality of life of these population. Is expected that the proposal of the present study, whish means bringing a new issue to the field of Ergonomics, reinforcing the multidisciplinary audience of this science, be more significant than the technics approaches of this research. We hope this study will contribute to a more informed process of investigation suggesting starting points to researchers and professional related to the theme's field

Occurrence of Legionella spp. in Man-Made Water Sources: Isolates Distribution and Phylogenetic Characterization in the Emilia-Romagna Region

Legionella species distribution in the Emilia-Romagna region, involving hospital (H) and community (C) environments, was conducted. Legionella culture, agglutination test, and mip-gene sequencing were applied on 240 isolates. The analysis showed a higher prevalence of non-Legionellapneumophila (n-Lp) species (84.1%) compared with L. pneumophila (Lp) (15.9%), with a higher frequency of n-Lp with respect to Lp species in both environments (77.6% and 96.4%, in H and C, respectively). The Shannon index showed a significant difference in Legionella distribution (p = 0.00017), with a significant abundance of Lp in the H compared with C environment (p = 0.00028). The continuous disinfection treatment in H could contribute to adaptive survival of the Lp species. Phylogenetic analysis revealed a conservative clade distribution between H and C: L. feeleii clade with three subclades in C and the Lp clade with five subclades in H and two in C, respectively. Our findings suggest the importance of Legionella surveillance both in H and C, with a focus on n-Lp species less connected to human disease. The Legionella prevalence and diversity found here indicate that geographical and temporal isolate evolution should be considered during surveillance, particularly in the light of global warming and changes in population risk factors

Occurrence of quantitative genetic polymorphism at the caprine beta-CN locus, as determined by a proteomic approach

Genetic screening of caseins in caprine milk samples enabled the identification of two novel b-casein (b- CN) phenotypes, C2 and F1, expressed at lower levels (3.3 and 2.7 g L_1 per allele, respectively) than reference b-CN C (4.7 g L_1 per allele), and another lacking in aS-complex. The b-CN C2 and F1 primary structures, determined by MS analysis, corresponded to b-CN C and F, respectively. The reasonable hypothesis supporting the low expression of both variants considers the C2 and F1 alleles as deriving from b-CN C1 and b-CN A1 precursors, respectively, and characterised by a genic transition C/T negatively affecting the mRNA stability. Further, phosphorylation of Thr41 responsible for the 7P b-CN component was determined by a proteomic approach for the first time. Caprine milk containing low levels of antigenic aS1-, aS2- and b-CN can be used for infant formula production and drinking milk for people with cows' milk protein allergy

Exploration des mécanismes cognitifs, métacognitifs et autobiographiques dans le déficit d'insight dans la schizophrénie

Dans la schizophrénie, le déficit d insight est d une importance clinique majeure de fait de son lien étroit avec l observance médicamenteuse et l alliance thérapeutique. Ce travail propose au moyen de trois études l exploration du concept d insight, précisant les mécanismes cognitifs sous-tendus et évaluant les effets de 3 nouvelles prises en charge sur son niveau d évolution. Nous nous sommes basés pour cela sur trois modèles théoriques, celui de Conway (2005) qui établit des liens étroits entre le self et la mémoire autobiographique, celui de Larøi et al., (2004) suggérant à l origine du déficit d insight un trouble de la conscience autonoétique en lien avec la mémoire autobiographique, et enfin, celui de Agnew et Morris (1989) incriminant une palette de troubles cognitifs et métacognitifs dans le déficit d insight. Nos résultats soulignent le rôle primordial de la mémoire autobiographique dans le déficit d insight et notamment la qualité des souvenirs sur la période supérieur à >20 ans. De plus les résultats indiquent que, les modèles autobiographique et métacognitif prédisent mieux le déficit d insight comparés au modèle cognitif de base. Parmi les trois programmes thérapeutiques, le programme RECOS (Vianin, 2007), améliore de manière significative le fonctionnement cognitif. Le programme REMAu (Piolino, 2006), visant la reconstruction des souvenirs autobiographique en lien avec le self, améliore de façon significative la conscience du trouble mental et la qualité du rappel épisodique. Le programme MBCT (Segal, Williams et Teasdale, 2002), visant la prise de conscience du moment présent, améliore de façon significative la capacité à attribuer la symptomatologie à la maladie mentale, l estime de soi et la théorie de l esprit. Ces résultats nous amènent à proposer un modèle explicatif et multidimensionnel du déficit d insight dans la schizophrénie, intégrant les trois modèles étudiés ; cognitif, métacognitif et autobiographique.The origins of poor insight in schizophrenia are still unclear. We contrasted the changes in clinical insight, basic cognitive processes, autobiographical memory and metacognition in 63 outpatient s with schizophrenia pseudo-randomly assigned to one of three cognitive remediation groups: one targeting basic cognitive processes (RECOS), a second autobiographical memory (REMAu), and a third metacognitive deficits (MBCT). Three dimensions of insight (awareness of: mental illness, benefit of treatment, psychosocial consequences) improved after treatment, regardless of the group. In addition, the REMAu and MBCT showed an improvement on other dimensions of insight (symptomatic awareness and symptomatic attribution, respectively). Poor insight and its improvement after treatment were best predicted by a combination of basic cognitive, autobiographical and metacognitive measures. This study supports a multidimensional conception of insight and recommends the combination of remediation therapies to improve clinical insight in schizophrenia.PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

The transmembrane protein bacterioopsin affects the polarity of the hydrophobic core of the host lipid bilayer

AbstractInfluence of the transmembrane protein bacterioopsin (the retinal-free form of bacteriorhodopsin) on the polarity of egg-phosphatidylcholine bilayers was studied by means of a steady-state and time-resolved fluorescence approach exploiting the solvatochromic properties of the 2-anthroyl fluorophore. Introduced in phosphatidylcholine molecules in the form of 8-(2-anthroyl)octanoic acid, this fluorophore probed the hydrocarbon core of the lipid bilayer. As previously shown (E. Pérochon et al., Biochemistry 31 (1992) 7672–7682), water molecules were detected in this region of the terminal part of the lipid acyl chains. Their number was considerably reduced upon addition of bacterioopsin to the lipids. This was assessed by a blue shift in the fluorescence emission spectra of the probe and a marked decrease in the fractional population of fluorophores interacting with water, to the benefit of those experiencing a hydrophobic environment. In agreement with current theories, this decrease in the hydration of the bilayer may be linked to an increase in the acyl chain order and a decrease in the lateral diffusion coefficient of lipids near the protein. The data obtained at high protein concentration accounts for a protein/lipid interface which is much less hydrated than the hydrophobic core of a protein-free lipid bilayer