Serendipity

Author Posting. © American Society for Biochemistry and Molecular Biology, 2009. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 284 (2009): 10285-10290, doi:10.1074/jbc.X800013200.As I look back, I realize that serendipity has played a major role in my life. I grew up in Santiago, Chile. As far back as I can remember I was interested in plants and animals, enjoying my Aunt Olga's farm, where I could observe the reproduction of rabbits and crossed plants of different colors. When I was a teenager a devastating earthquake in the South killed an aunt and two infant cousins who happened to be at the epicenter just for one night. That unfair tragedy convinced me that life had been created by natural forces, and the way to prove it was by synthesizing a living cell in vitro

Preditor de qualidade de vida em indivíduos com doença de Parkinson moderada

The purpose of this study was to verify among the motor and nonmotor dysfunctions and the fear of falling the main predictors for poor quality of life in individuals in stages 2 and 3 of Parkinson ́s disease (PD). Thirty-nine individuals with PD (64.1±9.1 years, 10.3±4.7 duration of disease) evaluated in “on” state (fully medicated) participated of the study. Motor dysfunctions were assessed using the following tests: Unifi ed Parkinson’s Disease Rating Scale part III motor subscale score (UPDRS-III), timed up and go  test,  Balance  Evaluation  System  Test  (BESTest),  one-repetition  maximum  (1RM)  in  the  leg  press.  Nomotor dysfunctions were assessed using the following tests: Montreal Cognitive Assessment (MoCA), Beck Depression Inventory (BDI) and Pittsburgh Sleep Quality Index (PSQI). The fear of falling was as-sessed by Falls Effi cacy Scale-International (FES-I). Quality of life was assessed using the Parkinson ́s Disease Questionnaire- 39 (PDQ-39). A multiple regression linear, stepwise method was employed. Only the FES-I score entered into multiple linear regression model and showed a high ability to explain the quality of life score of individual with PD (R2 adjusted = 0.73, p<0.0001). Thus, as clinical implication, it is possible to suggest that physical training strategies that promote a decrease in fear of falling can positively impact on the quality of life of individuals with PD.O objetivo deste estudo foi verificar dentre os sintomas motores, sintomas não motores e o medo de cair quais seriam os principais preditores de qualidade de vida em indivíduos nos estágios 2 e 3 da doença de Parkinson (DP). Trinta e nove indivíduos com DP (64,1±9,1 anos, 10,3±4,7 duração da DP) avaliados no estado on da medicação participaram do estudo. A disfunção motora foi avaliada por meio dos seguintes testes: parte III da Escala Unificada de Avaliação da Doença de Parkinson (UPDRS-III), teste Timed up and Go (TUG), Teste de Sistema de Avaliação do Equilíbrio (BESTest) e uma repetição máxima dos membros inferiores (1RM no leg press). A disfunção não motora foi avaliada por meio dos seguintes testes: Avaliação Cognitiva de Montreal (MoCA), Inventário de Depressão de Beck (IDB) e o Índice de Qualidade do Sono de Pittsburgh (PSQI). O medo de cair foi avaliado por meio da Escala Internacional de Eficácia de Quedas (FES-I). A qualidade de vida foi avaliada por meio do teste Questionário da Doença de Parkinson (PDQ-39). Uma regressão múltipla linear, método stepwise foi empregada para verificar o principal preditor do escore da PDQ-39. A única variável independente que entrou no modelo de regressão múltipla linear (stepwise) e mostrou uma alta capacidade para explicar o escore de qualidade de vida de indivíduos com DP foi a FES-I (R2 ajustado = 0,73, P<0,0001). Assim, como implicação clínica, é possível sugerir que estratégias de treinamento físico que promovam diminuição no medo de cair podem impactar positivamente na qualidade de vida de indivíduos com DP moderada

Expression Profiling of Rectal Tumors Defines Response to Neoadjuvant Treatment Related Genes

To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.C, CC and AB were supported by projects CTS2200 and PI-0710-2013 of Junta de Andalucía, TIN2013-41990-R of Programa Estatal I+D+i MINECO, and GREIB PYR_2010-02 and 2010_05 of University of Granada

Essential Role of TGF-β/Smad Pathway on Statin Dependent Vascular Smooth Muscle Cell Regulation

BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins) exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta) in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs) statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII), and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs

Sphagnum (velvet) species used by rural communities at the Guaratuba EPA, Paraná State, Brazil=Espécies de Sphagnum (veludo) utilizadas pelas comunidades rurais da APA de Guaratuba, Estado do Paraná, Brasil

The results of a survey of Sphagnum used by the Descoberto and Empanturrado rural communities (Guaratuba municipality and Guaratuba Environmental Protected Area – EPA) are presented. The analysis was based on fresh material collected in different harvesting areas. Five species were recorded: S. capillifolium (Ehrh.) Hedw., S. cuspidatum Ehrh. ex Hoffm., S. erythrocalyx Hampe, S. perichaetiale Hampe and S. recurvum P. Beauv.. All of them are native species that grow spontaneously in that region and are intensively harvested by the local community. A key is presented to differentiate the species, and the botanical description, common names, geographic distribution and illustrations for each species are included.Apresenta-se resultado de levantamento das espécies de Sphagnum L. utilizadas pelas comunidades rurais de Descoberto e Empanturrado (Município de Guaratuba, APA de Guaratuba, Paraná). A partir de coletas e identificação de material botânico nos locais de extrativismo, foram registradas cinco espécies: S. capillifolium (Ehrh.) Hedw., S. cuspidatum Ehrh. ex Hoffm., S. erythrocalyx Hampe, S. perichaetiale Hampe e S. recurvum P. Beauv.. Todas com ocorrência natural na região de estudo e submetidas a intenso extrativismo pela demanda do segmento floricultor. Incluem-se chave dicotômica para identificação, descrições, caracterização do hábitat, distribuição geográfica e ilustrações para cada espécie identificada

Peroxisome-proliferator-activated receptor α agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1

Recent evidence indicates that PPAR (peroxisome-proliferator-activated receptor) α ligands possess anti-inflammatory and antitumoural properties owing to their inhibitory effects on the expression of genes that are involved in the inflammatory response. However, the precise molecular mechanisms underlying these effects are poorly understood. In the present study, we show that tumour promoter PMA-mediated induction of genes that are significantly associated with inflammation, tumour growth and metastasis, such as COX-2 (cyclo-oxygenase 2) and VEGF (vascular endothelial growth factor), is inhibited by PPARα ligands in the human colorectal carcinoma cell line SW620. PPARα activators LY-171883 and WY-14,643 were able to diminish transcriptional induction of COX-2 and VEGF by inhibiting AP-1 (activator protein-1)-mediated transcriptional activation induced by PMA or by c-Jun overexpression. The actions of these ligands on AP-1 activation and COX-2 and VEGF transcriptional induction were found to be dependent on PPARα expression. Our studies demonstrate the existence of a negative cross-talk between the PPARα- and AP-1-dependent signalling pathways in these cells. PPARα interfered with at least two steps within the pathway leading to AP-1 activation. First, PPARα activation impaired AP-1 binding to a consensus DNA sequence. Secondly, PPARα ligands inhibited c-Jun transactivating activity. Taken together, these findings provide new insight into the anti-inflammatory and anti-tumoural properties of PPARα activation, through the inhibition of the induction of AP-1-dependent genes that are involved in inflammation and tumour progression