15 research outputs found
Identification and functional characterisation of ctr1, a Pleurotus ostreatus gene coding for a copper transporter
El activismo religioso conservador en Latinoamérica
Pertenece a la colección Religión, Género y Sexualidad / dirigida por Juan M. Vaggione ; v.3El libro reúne un conjunto de análisis que ponen en evidencia la heterogeneidad y la complejidad de las estrategias de influencia de la religión como uno de los principales sostenes de sistemas heteronormativos en nuestras sociedades contemporáneas. Tanto al nivel de los actores como de los discursos, las formas en que las religiones influencian las discusiones sobre políticas de sexualidad han adoptado diversas modalidades de actuación adaptándose a los momentos políticos. Así, los artículos que integran la compilación se dirigen a complejizar el rol de lo religioso en la política sexual contemporánea incluyendo en esta problematización distintos ejes de análisis y marcos teóricos. Haciendo foco en diferentes países de América Latina, con sus escenarios y problemas, los artículos abordan las variadas dimensiones del activismo religioso conservador en nuestra región
FOSL1 promotes cholangiocarcinoma via transcriptional effectors that could be therapeutically targeted
[EN] Background & Aims: Cholangiocarcinoma (CCA) is a neoplasia of
the biliary tract driven by genetic, epigenetic and transcriptional
mechanisms. Herein, we investigated the role of the transcription
factor FOSL1, as well as its downstream transcriptional effectors,
in the development and progression of CCA.
Methods: FOSL1 was investigated in human CCA clinical samples.
Genetic inhibition of FOSL1 in human and mouse CCA cell
lines was performed in in vitro and in vivo models using
constitutive and inducible short-hairpin RNAs. Conditional
FOSL1 ablation was done using a genetically engineered mouse
(GEM) model of CCA (mutant KRAS and Trp53 knockout). Followup
RNA and chromatin immunoprecipitation (ChIP) sequencing
analyses were carried out and downstream targets were validated
using genetic and pharmacological inhibition.
Results: An inter-species analysis of FOSL1 in CCA was conducted.
First, FOSL1 was found to be highly upregulated in human
and mouse CCA, and associated with poor patient survival.
Pharmacological inhibition of different signalling pathways in
CCA cells converged on the regulation of FOSL1 expression.
Functional experiments showed that FOSL1 is required for cell
proliferation and cell cycle progression in vitro, and for tumour
growth and tumour maintenance in both orthotopic and subcutaneous
xenograft models. Likewise, FOSL1 genetic abrogation
in a GEM model of CCA extended mouse survival by decreasing
the oncogenic potential of transformed cholangiocytes. RNA and
ChIP sequencing studies identified direct and indirect transcriptional
effectors such as HMGCS1 and AURKA, whose genetic
and pharmacological inhibition phenocopied FOSL1 loss.
Conclusions: Our data illustrate the functional and clinical
relevance of FOSL1 in CCA and unveil potential targets amenable
to pharmacological inhibition that could enable the implementation
of novel therapeutic strategies.
Lay summary: Understanding the molecular mechanisms
involved in cholangiocarcinoma (bile duct cancer) development
and progression stands as a critical step for the development of
novel therapies. Through an inter-species approach, this study
provides evidence of the clinical and functional role of the
transcription factor FOSL1 in cholangiocarcinoma. Moreover, we
report that downstream effectors of FOSL1 are susceptible to
pharmacological inhibition, thus providing new opportunities
for therapeutic intervention.A.V. was supported by ADA of the University of Navarra, Spain,
O.E. by FSE; MINECO; FJCI-2017-34233, Spain, R.E. by a donation
from Mauge Burgos de la Iglesia’s family, Spain, and P. Olaizola by
the Basque Government (PRE_2016_1_0269), Basque Country,
Spain. M.J.P. was funded by ISCIII [FIS PI14; 00399, PI17; 00022]
cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER),
Spain; Spanish Ministry of Economy and Competitiveness
(MINECO: “Ramón y Cajal” Program RYC-2015-17755), Spain.
M.A.A was funded by La Caixa Foundation, HEPACARE project,
Spain, ISCIII FIS PI16/01126 cofinanced by “Fondo Europeo de
Desarrollo Regional” (FEDER), Spain, and “Fundación Científica de
la Asociación Española Contra el Cáncer’’ (AECC Scientific Foundation)
Rare Cancers 2017, Spain. J.M.B. was funded by the
Spanish Carlos III Health Institute (ISCIII) (FIS PI15; 01132, PI18;
01075 and Miguel Servet Program CON14; 00129 and CPII19;
00008), Spain, co-financed by “Fondo Europeo de Desarrollo
Regional” (FEDER), Spain; “Euskadi RIS3” (2019222054) and
BIOEF (Basque Foundation for Innovation and Health Research:
EiTB Maratoia BIO15; CA; 016; BD), Basque Country, Spain;
“Fundación Científica de la Asociación Española Contra el Cáncer”
(AECC Scientific Foundation) Rare Cancers 2017, Spain. S.V. was
supported by FEDER; MINECO (SAF2017-89944-R), Spain, by the
Government of Navarra-Health Research Department (58; 2018),
Navarra, Spain, by La Caixa and Caja Navarra Foundation-CIMA
agreement, Spain. None of the funding sources were involved
in the decision to submit the article for publication. This article is
based upon work from COST Action CA18122 European Cholangiocarcinoma
Network, supported by COST (European Cooperation
in Science and Technology). COST (European Cooperation in Science and Technology) is a funding agency for research and
innovation networks (www.cost.eu)
Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism
Abstract: The composition of extracellular vesicles (EVs) is altered in many pathological conditions, and their molecular content provides essential information on features of parent cells and mechanisms of crosstalk between cells and organs. Metabolic Syndrome (MetS) is a cluster of clinical manifestations including obesity, insulin resistance, dyslipidemia and hypertension that increases the risk of cardiovascular disease and type 2 diabetes mellitus. Here, we investigated the crosstalk between liver and adipocytes by characterizing EVs secreted by primary hepatocytes isolated from Zucker rat model, and studied the effect they have on 3T3‐L1 adipocytes. We found that steatotic hepatocytes secrete EVs with significantly reduced exosomal markers in comparison with their lean counterpart. Moreover, proteomic analysis revealed that those EVs reflect the metabolic state of the parent cell in that the majority of proteins upregulated relate to fat metabolism, fatty acid synthesis, glycolysis, and pentose phosphate pathway. In addition, hepatocytes‐secreted EVs influenced lipolysis and insulin sensitivity in recipient 3T3‐L1 adipocytes. Untargeted metabolomic analysis detected alterations in different adipocyte metabolic pathways in cells treated with hepatic EVs. In summary, our work showed that steatosis has a significant impact in the amount and composition of EVs secreted by hepatocytes. Moreover, our data point to the involvement of hepatic‐EVs in the development of pathologies associated with MetS
Individualized, perioperative, hemodynamic goal-directed therapy in major abdominal surgery (iPEGASUS trial): Study protocol for a randomized controlled trial
Written informed consent. (PDF 53 kb
Nuevos horizontes en la investigación social : artículos seleccionados de las VI Jornadas de Jóvenes Investigadores del Instituto de Investigaciones Gino Germani
Las nuevas generaciones representan un estimulante presente y un promisorio futuro para nuestra institución. La nueva década nos encuentra en el desafío de seguir creciendo y consolidándonos como uno de los principales institutos de Investigación en América Latina.
Enfrentamos este reto basados en nuestra propia identidad institucional como espacio de investigación que retoma y articula lo mejor de la universidad pública: rigor investigativo, pluralismo, cogobierno, vinculación con la enseñanza de grado y posgrado, autonomía académica y compromiso social. Sin lugar a dudas, estas Jornadas representan un aporte en esta dirección.
De la Presentación de Julián Rebó