138 research outputs found
A Long-term Psychological Observation in an Adolescent affected with Gardner Diamond Syndrome
Gardner-Diamond syndrome (GDS) is an uncommon disease clinically characterized by a wide spectrum of psycho-emotive symptoms associated with painful ecchymoses/purpuric lesions and positivity of auto-erythrocyte sensitization skin test. Herein, a perspective clinical and psychological observation of an adolescent GDS is firstly reported focusing on her psychological features long-term monitored for a 1-year period. The administration of a standardized tools battery allowed us to define psychological features of the young patient over time and to monitored clinical course and response to treatment
Large Deviation Principle for One Dimensional Vector Spin Models with Kac Potentials
We consider the one dimensional planar rotator and classical Heisenberg models with a ferromagnetic Kac potential. Below the LebowitzÂPenrose critical temperature the limit mean field theory exhibits a phase transition with a continuum of equilibrium states, indexed by the magnetization vectors. We prove a large deviation principle for the associated Gibbs measures. Then we study the system in a certain limit
Semi-probabilistic Routing for Highly Dynamic Networks
Abstract. In this paper we describe a semi-probabilistic routing approach designed to enable content-based publish-subscribe on highly dynamic networks, e.g., mobile, peer-to-peer, or wireless sensor networks. We present the rationale and high level strategy of our approach, and then show its application in a link-based graph overlay as well as in a broadcast-based sensor network. Simulation results confirm that, in both scenarios, our semi-probabilistic approach strikes a balance between entirely deterministic and entirely probabilistic solutions, achieving high reliability with low overhead
Inferring the infection biology of the wood decay fungus Perenniporia fraxinea through an analysis of genotypic diversity: a case study in northern Italy
Long-term follow-up of systemic onset juvenile idiopathic arthritis patients treated with Anakinra
The co-existence of transcriptional activator and transcriptional repressor MEF2 complexes influences tumor aggressiveness
The contribution of MEF2 TFs to the tumorigenic process is still mysterious. Here we clarify that MEF2 can support both pro-oncogenic or tumor suppressive activities depending on the interaction with co-activators or co-repressors partners. Through these interactions MEF2 supervise histone modifications associated with gene activation/repression, such as H3K4 methylation and H3K27 acetylation. Critical switches for the generation of a MEF2 repressive environment are class IIa HDACs. In leiomyosarcomas (LMS), this two-faced trait of MEF2 is relevant for tumor aggressiveness. Class IIa HDACs are overexpressed in 22% of LMS, where high levels of MEF2, HDAC4 and HDAC9 inversely correlate with overall survival. The knock out of HDAC9 suppresses the transformed phenotype of LMS cells, by restoring the transcriptional proficiency of some MEF2-target loci. HDAC9 coordinates also the demethylation of H3K4me3 at the promoters of MEF2-target genes. Moreover, we show that class IIa HDACs do not bind all the regulative elements bound by MEF2. Hence, in a cell MEF2-target genes actively transcribed and strongly repressed can coexist. However, these repressed MEF2-targets are poised in terms of chromatin signature. Overall our results candidate class IIa HDACs and HDAC9 in particular, as druggable targets for a therapeutic intervention in LMS
Mechanisms of Activation of LRRC8 Volume Regulated Anion Channels.
Volume regulated anion channels (VRACs) are ubiquitously expressed in all vertebrate cells. Despite many years of research, the fundamental mechanisms underlying VRAC activation are not understood. The recent molecular identification of the LRRC8 genes underlying VRAC revealed that VRACs are formed by a hexameric assembly of members of the LRRC8 gene family. Knowing the genes underlying VRACs allowed the discovery of novel VRAC functions into cell volume regulation, and first structure function studies revealed important insight in channel activation mechanisms. The determination of cryo-EM structures of homomeric LRRC8A and LRRC8D complexes provide a framework for a rational approach to investigate biophysical mechanisms. We discuss several recent advances within the structural framework, and we critically review the literature on the main mechanisms proposed to be involved in VRAC activation, including low intracellular ionic strength, membrane unfolding, oxidation, phosphorylation and G-protein coupling
The RNA-binding protein ESRP1 promotes human colorectal cancer progression
Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RNA binding protein that controls several key cellular processes, like alternative splicing and translation. Previous studies have demonstrated a tumor suppressor role for this protein. Recently, however, a pro-metastatic function of ESRP1 has been reported. We thus aimed at clarifying the role of ESRP1 in Colorectal Cancer (CRC) by performing loss- and gain-of-function studies, and evaluating tumorigenesis and malignancy with in vitro and in vivo approaches. We found that ESRP1 plays a role in anchorage-independent growth of CRC cells. ESRP1-overexpressing cells grown in suspension showed enhanced fibroblast growth factor receptor (FGFR1/2) signalling, Akt activation, and Snail upregulation. Moreover, ESRP1 promoted the ability of CRC cells to generate macrometastases in mice livers. High ESRP1 expression may thus stimulate growth of cancer epithelial cells and promote colorectal cancer progression. Our findings provide mechanistic insights into a previously unreported, pro-oncogenic role for ESRP1 in CRC, and suggest that fine-tuning the level of this RNA-binding protein could be relevant in modulating tumor growth in a subset of CRC patients
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