02783nas a2200253 4500008004100000022001400041245015200055210006900207260001600276520178700292100002502079700002602104700002902130700003102159700002802190700002602218700002802244700002702272700003302299700002702332700001602359700002902375856012502404 2012 eng d a1097-021500aExpression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma.0 aExpression profiling shows differential molecular pathways and p c2012 Jun 143 aSerrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5-8.7% of CRCs. It has been shown that SAC has a poorer prognosis and has different molecular and immunohistochemical features compared to conventional carcinoma (CC) but, to date, only one previous study has analysed its mRNA expression profile by microarray. Using a different microarray platform, we have studied the molecular signature of 11 SACs and compared it with that of 15 matched CC with the aim of discerning the functions which characterize SAC biology and validating, at the mRNA and protein level, the most differentially expressed genes which were also tested using a validation set of 70 SACs and 70 CCs to assess their diagnostic and prognostic values. Microarray data showed a higher representation of morphogenesis-, hypoxia-, cytoskeleton- and vesicle transport-related functions and also an over-expression of fascin1 (actin-bundling protein associated with invasion) and the antiapoptotic gene hippocalcin in SAC all of which were validated both by qPCR and immunohistochemistry. Fascin1 expression was statistically associated with KRAS mutation with 88.6% sensitivity and 85.7% specificity for SAC diagnosis and the positivity of fascin1 or hippocalcin was highly suggestive of SAC diagnosis (sensitivity=100%). Evaluation of these markers in CRCs showing histological and molecular characteristics of high-level microsatellite instability (MSI-H) also helped to distinguish SACs from MSI-H CRCs. Molecular profiling demonstrates that SAC shows activation of distinct signalling pathways and that immunohistochemical fascin1 and hippocalcin expression can be reliably used for its differentiation from other CRC subtypes. © 2012 Wiley Periodicals, Inc.1 aConesa-Zamora, Pablo1 aGarcía-Solano, José1 aGarcia-Garcia, Francisco1 aTurpin, María, Del Carmen1 aTrujillo-Santos, Javier1 aTorres-Moreno, Daniel1 aOviedo-Ramírez, Isabel1 aCarbonell-Muñoz, Rosa1 aMuñoz-Delgado, Encarnación1 aRodriguez-Braun, Edith1 aConesa, Ana1 aPérez-Guillermo, Miguel uhttps://clinbioinfosspa.es/content/expression-profiling-shows-differential-molecular-pathways-and-provides-potential-new03516nas a2200493 4500008004100000022001400041245012700055210006900182260001600251300000700267490000600274520197600280653001202256653002302268653001802291653001602309653002002325653001102345653003102356653002902387653002302416653002802439653000902467653001202476653002402488653002002512653001502532653002402547653002702571653003602598100001802634700003002652700002302682700002902705700002102734700002002755700001902775700001602794700001602810700002002826700002402846700002302870856012902893 2011 eng d a1755-879400aEarly peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass.0 aEarly peroxisome proliferatoractivated receptor gamma regulated  c2011 Dec 30 a860 v43 a

BACKGROUND: The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion

RESULTS: Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell.

CONCLUSIONS: Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.

10aAnimals10aCell Proliferation10aCell Survival10aCholesterol10aDown-Regulation10aFemale10aGene Expression Regulation10aGene Knockout Techniques10aInsulin Resistance10aInsulin-Secreting Cells10aMice10aobesity10aOxidation-Reduction10aPhosphorylation10aPPAR gamma10aSignal Transduction10aTranscription, Genetic10aTransforming Growth Factor beta1 aVivas, Yurena1 aMartinez-Garcia, Cristina1 aIzquierdo, Adriana1 aGarcia-Garcia, Francisco1 aCallejas, Sergio1 aVelasco, Ismael1 aCampbell, Mark1 aRos, Manuel1 aDopazo, Ana1 aDopazo, Joaquin1 aVidal-Puig, Antonio1 aMedina-Gomez, Gema uhttps://clinbioinfosspa.es/content/early-peroxisome-proliferator-activated-receptor-gamma-regulated-genes-involved-expansion02590nas a2200217 4500008004100000245011200041210006900153260001600222300001200238490000800250520182000258100002902078700002202107700002902129700001802158700002102176700001902197700002302216700002202239856011102261 2011 eng d00aEarly transcriptional defence responses in Arabidopsis cell suspension culture under high light conditions.0 aEarly transcriptional defence responses in Arabidopsis cell susp c2011 Apr 29 a1439-560 v1563 a

The early transcriptional defence responses and ROS production in Arabidopsis cell suspension culture (ACSC), containing functional chloroplasts, were examined at high light (HL). The transcriptional analysis revealed that most of the ROS markers identified among the 449 transcripts with significant differential expression were transcripts specifically up-regulated by singlet oxygen (1O2). On the contrary, minimal correlation was established with transcripts specifically up-regulated by superoxide radical (O2•) or hydrogen peroxide (H2O2). The transcriptional analysis was supported by fluorescence microscopy experiments. The incubation of ACSC with the 1O2 sensor green reagent and 2’,7’-dichlorofluorescein diacetate showed that the 30-min-HL-treated cultures emitted fluorescence that corresponded with the production of 1O2, but not of H2O2. Furthermore, the in vivo photodamage of the D1 protein of photosystem II (PSII) indicated that the photogeneration of 1O2 took place within the PSII reaction centre. Functional enrichment analyses identified transcripts that are key components of the ROS signalling transduction pathway in plants as well as others encoding transcription factors that regulate both ROS scavenging and water deficit stress. A meta-analysis examining the transcriptional profiles of mutants and hormone treatments in Arabidopsis showed a high correlation between ACSC at HL and the flu mutant family of Arabidopsis, a producer of 1O2 in plastids. Intriguingly, a high correlation was also observed with aba1 and max4, two mutants with defects in the biosynthesis pathways of two key (apo)carotenoid-derived plant hormones (i.e. ABA and strigolactones, respectively). ACSC has proven to be a valuable system for studying early transcriptional responses to HL stress.

1 aGonzález-Pérez, Sergio1 aGutiérrez, Jorge1 aGarcia-Garcia, Francisco1 aOsuna, Daniel1 aDopazo, Joaquín1 aLorenzo, Oscar1 aRevuelta, José, L1 aArellano, Juan, B uhttp://www.plantphysiol.org/content/early/2011/04/29/pp.111.177766.short?keytype=ref&ijkey=ph5B6J2khjnqwzN03502nas a2200469 4500008004100000022001400041245011200055210006900167260001300236300001200249490000800261520192600269653001602195653002202211653002802233653002002261653001702281653002102298653003002319653003802349653002202387653001002409653001302419653004402432653003502476653002802511653003102539653005202570653001902622653002402641653002602665653002702691100002902718700002202747700002902769700001802798700002002816700001902836700002302855700002202878856013202900 2011 eng d a1532-254800aEarly transcriptional defense responses in Arabidopsis cell suspension culture under high-light conditions.0 aEarly transcriptional defense responses in Arabidopsis cell susp c2011 Jul a1439-560 v1563 a

The early transcriptional defense responses and reactive oxygen species (ROS) production in Arabidopsis (Arabidopsis thaliana) cell suspension culture (ACSC), containing functional chloroplasts, were examined at high light (HL). The transcriptional analysis revealed that most of the ROS markers identified among the 449 transcripts with significant differential expression were transcripts specifically up-regulated by singlet oxygen ((1)O(2)). On the contrary, minimal correlation was established with transcripts specifically up-regulated by superoxide radical or hydrogen peroxide. The transcriptional analysis was supported by fluorescence microscopy experiments. The incubation of ACSC with the (1)O(2) sensor green reagent and 2',7'-dichlorofluorescein diacetate showed that the 30-min-HL-treated cultures emitted fluorescence that corresponded with the production of (1)O(2) but not of hydrogen peroxide. Furthermore, the in vivo photodamage of the D1 protein of photosystem II indicated that the photogeneration of (1)O(2) took place within the photosystem II reaction center. Functional enrichment analyses identified transcripts that are key components of the ROS signaling transduction pathway in plants as well as others encoding transcription factors that regulate both ROS scavenging and water deficit stress. A meta-analysis examining the transcriptional profiles of mutants and hormone treatments in Arabidopsis showed a high correlation between ACSC at HL and the fluorescent mutant family of Arabidopsis, a producer of (1)O(2) in plastids. Intriguingly, a high correlation was also observed with ABA deficient1 and more axillary growth4, two mutants with defects in the biosynthesis pathways of two key (apo)carotenoid-derived plant hormones (i.e. abscisic acid and strigolactones, respectively). ACSC has proven to be a valuable system for studying early transcriptional responses to HL stress.

10aArabidopsis10aBlotting, Western10aCell Culture Techniques10aCells, Cultured10aChloroplasts10aCluster Analysis10aGene Expression Profiling10aGene Expression Regulation, Plant10aHydrogen Peroxide10aLight10amutation10aOligonucleotide Array Sequence Analysis10aPhotosystem II Protein Complex10aPlant Growth Regulators10aReproducibility of Results10aReverse Transcriptase Polymerase Chain Reaction10aRNA, Messenger10aSignal Transduction10aStress, Physiological10aTranscription, Genetic1 aGonzález-Pérez, Sergio1 aGutiérrez, Jorge1 aGarcia-Garcia, Francisco1 aOsuna, Daniel1 aDopazo, Joaquin1 aLorenzo, Oscar1 aRevuelta, José, L1 aArellano, Juan, B uhttps://clinbioinfosspa.es/content/early-transcriptional-defense-responses-arabidopsis-cell-suspension-culture-under-high-light