Search results for "R1"
showing 10 items of 1016 documents
NR1H4 rs35724 G>C variant modulates liver damage in nonalcoholic fatty liver disease
2021
Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G>C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n = 124). Results: The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic conf…
The apocryphal: prototype of a subjectivity in crisis
2013
The introduction of this paper reviews the concept of the subject, which originated in classical antiquity and developed in Western culture up to the Enlightenment and Romanticism with the addition of new aspects but without questioning its foundation as a substantial Subject. The first major crisis of this received view took place in the first quarter of the twentieth century after the assimilation of the works by Marx, Freud or Nietzsche, which laid the foundations of a thorough criticism on the subject. One important feature of this crisis was the proliferation of apocryphal writing, which reached new models in the works of Fernando Pessoa and Antonio Machado. Between them lies the scope…
Influences of TP53 and the anti-aging DDR1 receptor in controlling Raf/MEK/ERK and PI3K/Akt expression and chemotherapeutic drug sensitivity in prost…
2020
Background TP53 plays critical roles in sensitivity to chemotherapy, and aging. Collagen is very important in aging. The molecular structure and biochemical properties of collagen changes during aging. The discoidin domain receptor (DDR1) is regulated in part by collagen. Elucidating the links between TP53 and DDR1 in chemosensitivity and aging could improve therapies against cancer and aging. Results Restoration of WT-TP53 activity resulted in increased sensitivity to chemotherapeutic drugs and elevated expression of key components of the Raf/MEK/ERK, PI3K/Akt and DDR1 pathways. DDR1 could modulate the levels of Raf/MEK/ERK and PI3K/Akt pathways as well as sensitize the cells to chemothera…
Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration.
2014
The RAF family of kinases mediates RAS signaling, and RAF inhibitors can be effective for treating tumors with BRAF V600E mutant protein. However, RAF inhibitors paradoxically accelerate metastasis in RAS -mutant tumors and become ineffective in BRAF V600E tumors because of reactivation of downstream mitogen-activated protein kinase (MAPK) signaling. We found that the RAF isoform ARAF has an obligatory role in promoting MAPK activity and cell migration in a cell type–dependent manner. Knocking down ARAF prevented the activation of MAPK kinase 1 (MEK1) and extracellular signal–regulated kinase 1 and 2 (ERK1/2) and decreased the number of protrusions from tumor cell spheroids in three-dimensi…
National fiscal consolidations and regional inequality in Europe
2016
Using annual data for 13 European countries over the period 1980-2008, we assess the impact of national fiscal consolidations on the income inequality of European regions. Regional dispersion increases in the outcome of consolidation episodes, particularly, when packages are more severe and implemented through spending cuts rather than tax rises. From a policy perspective, these findings suggest that fiscal consolidations driven by reductions in government spending can exacerbate regional disparities and may ultimately counteract the European policy efforts to promote territorial cohesion. Our results are robust to alternative inequality measures, the occurrence of crisis episodes and the e…
A Novel Semi-Supervised Methodology for Extracting Tumor Type-Specific MRS Sources in Human Brain Data
2013
Background: The clinical investigation of human brain tumors often starts with a non-invasive imaging study, providing \ud information about the tumor extent and location, but little insight into the biochemistry of the analyzed tissue. Magnetic \ud Resonance Spectroscopy can complement imaging by supplying a metabolic fingerprint of the tissue. This study analyses \ud single-voxel magnetic resonance spectra, which represent signal information in the frequency domain. Given that a single \ud voxel may contain a heterogeneous mix of tissues, signal source identification is a relevant challenge for the problem of\ud tumor type classification from the spectroscopic signal.\ud Methodology/Princ…
Transgresión moral, enfermedad y salud holística en la Misión Livingstonia en Malawi a finales del siglo XIX y principios del siglo XX
2009
This article examines ideas of morality and health, and connections between moral transgression and disease in both Scottish missionary and Central African thought in the context of the Livingstonia Mission of the Presbyterian Free Church of Scotland in Malawi during the late nineteenth and early twentieth centuries.2 By concentrating on debates, conflicts and co-operation between missionaries and Africans over the key issues of beer drinking and sexual morality, this article explores the emergence of a new ‘moral hygiene’ among African Christian communities in Northern Malawi.
Moral transgression, disease and holistic health in the Livingstonia Mission in late nineteenth and early twenttieth-century Malawi
2009
This article examines ideas of morality and health, and connections between moral transgression and disease in both Scottish missionary and Central African thought in the context of the Livingstonia Mission of the Presbyterian Free Church of Scotland in Malawi during the late nineteenth and early twentieth centuries.2 By concentrating on debates, conflicts and co-operation between missionaries and Africans over the key issues of beer drinking and sexual morality, this article explores the emergence of a new ‘moral hygiene’ among African Christian communities in Northern Malawi.<br><br>Este artículo analiza las ideas sobre moralidad y salud, así como las relaciones entre transgre…
The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice
2019
Our results demonstrate a functional role for the commensal microbiota in atherothrombosis. In a ferric chloride injury model of the carotid artery, GF C57BL/6J mice had increased occlusion times compared to colonized controls. Interestingly, in late atherosclerosis, HFD-fed GF Ldlr−/− mice had reduced plaque rupture-induced thrombus growth in the carotid artery and diminished ex vivo thrombus formation under arterial flow conditions.
TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation
2018
IF 2.264; International audience; Pierpont syndrome is a rare and sporadic syndrome, including developmental delay, facial characteristics, and abnormal extremities. Recently, a recurrent de novo TBL1XR1 variant (c.1337A > G; p.Tyr446Cys) has been identified in eight patients by whole‐exome sequencing. A dominant‐negative effect of this mutation is strongly suspected, since patients with TBL1XR1 deletion and other variants predicting loss of function do not share the same phenotype. We report two patients with typical Pierpont‐like syndrome features. Exome sequencing allowed identifying a de novo heterozygous missense TBL1XR1 variant in both patients, different from those already reported: …