Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation

Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones. Osteoblasts respond to FGF with increased proliferation and inhibition of differentiation. We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2. Most of these changes could be reproduced by treatment of osteoblasts with exogenous FGF. Wnt signals promote osteoblast function and regulate bone mass. Sox2 is expressed in calvarial osteoblasts in vivo and we show that constitutive expression of Sox2 inhibits osteoblast differentiation and causes down-regulation of the expression of numerous Wnt target genes. Sox2 associates with β-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain. Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt–β-catenin pathway

Two cases of angioimmunoblastic T-cell lymphoma with concomitant positive serology for acute Epstein-Barr virus infection

TL) is a rare type of peripheral T-celllymphoma. Epstein-Barr virus (EBV) isknown to be associated with pathogenesisand histological progression of AITL andthe onset of the disease often mimics aninfectious process. Here we describe twocases of patients with serology for acuteEBV infection at the onset of AITL.IntroductionAngioimmunoblastic T-cell lymphom

CT imaging of primary pancreatic lymphoma: experience from three referral centres for pancreatic diseases

To describe CT characteristics of primary pancreatic lymphoma (PPL), a rare disease with features in common with adenocarcinoma

Ecological effects of multiple stressors on a deep lake (Lago Maggiore, Italy) integrating neo and palaeolimnological approaches

To understand interactions of lake physical characteristics, trophic dynamics and climate in Lago Maggiore, we compare longterm limnological and meteorological monitoring data and results from sediment cores. We include analyses of nutrients, pigments, diatoms and cladoceran microfossils. Over the past decades, caloric content increased. Eutrophication from the 1960s to early 1980s was followed by oligotrophication. DDTs, PCBs and Hg showed high contamination in the \u2760s, compared to point source inputs in the \u2790s. Algal biomass was predicted by total pigments and some algal specific carotenoids. Following nutrient enrichment, Chydorus sphaericus, and total abundance of cladocerans changed inversely with trophic status. Fewer large Daphnia since the late \u2780s matched an increase in with subfossil Eubosmina mucro lengths. Both were explained by the 10-fold increase in Bythotrephes longimanus from 1987 to 1993, when an increase of its mean annual population density occurred during warmer winter and springs. Bythotrephes remained abundant and further increased during the following 10 years as water temperature increased. We conclude that warmer water affects food chains indirectly by changing habitat use and predator-prey interactions. Relative abundances of Daphnia and its peak population density in the warm year of the oligotrophic period (2003) were close to the record from the mesotrophic period in 1982, supporting the hypothesis that warming can produce a eutrophication-like signal. The study illustrates the complexity of biological responses to synchronous changes in multiple drivers (e.g., eutrophication, fish introduction, ban of fish harvesting, chemical pollution, and climate) and, despite this complexity, how Lago Maggiore responded to multiple stressors

Blood smear, a key diagnostic tool in hematology: Lessons from two cases of acute hemolysis in previously undiagnosed g6pd deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common worldwide distributed hereditary red cells enzymatic defect. The most common life-threatening clinical presentation of G6PD deficiency is acute hemolytic crisis triggered by exposition to oxidative agents such as fava beans, drugs, or infections. Management of acute hemolytic crisis in patients with no previous history of hereditary red cell disorders is particularly challenging for hematologists and emergency department (ED) physicians. We report two cases of acute hemolytic crisis in patients with previously unknown G6PD deficiency, where blood smear analysis played a key role in decision-making process. The trigger of acute hemolytic crisis was in both cases the recent intake of large amount of fava beans. Although Case 1 typically involved a male subject with unknown G6PD deficiency, Case 2 is of particular interest since the patient is a female with previously unknown G6PD deficiency. A recent study highlights the possible appearance of clinical signs for G6PD deficiency with aging in elder female population. Thus, hematologists should always take into account the possible lyonization effect on G6PD activity for G6PD deficiency inherited red cell disorder in the presence of unexplained acute hemolytic crisis in women with circulating hemi-ghosts

Integration of B-cell receptor-induced ERK1/2 phosphorylation and mutations of SF3B1 gene refines prognosis in treatment-na\uefve chronic lymphocytic leukemia

ADP-ribosyl Cyclase 1; Disease Progression; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable[no abstract available

Tollip Is a Mediator of Protein Sumoylation

Tollip is an interactor of the interleukin-1 receptor involved in its activation. The endosomal turnover of ubiquitylated IL-1RI is also controlled by Tollip. Furthermore, together with Tom1, Tollip has a general role in endosomal protein traffic. This work shows that Tollip is involved in the sumoylation process. Using the yeast two-hybrid technique, we have isolated new Tollip partners including two sumoylation enzymes, SUMO-1 and the transcriptional repressor Daxx. The interactions were confirmed by GST-pull down experiments and immunoprecipitation of the co-expressed recombinants. More specifically, we show that the TIR domain of the cytoplasmic region of IL-1RI is a sumoylation target of Tollip. The sumoylated and unsumoylated RanGAP-1 protein also interacts with Tollip, suggesting a possible role in RanGAP-1 modification and nuclear-cytoplasmic protein translocation. In fact, Tollip is found in the nuclear bodies of SAOS-2/IL-1RI cells where it colocalizes with SUMO-1 and the Daxx repressor. We conclude that Tollip is involved in the control of both nuclear and cytoplasmic protein traffic, through two different and often contrasting processes: ubiquitylation and sumoylation

Caratterizzazione di un nuovo sito funzionale dell'interleuchina-1 (beta((

Dottorato di ricerca in biologia e fisiologia cellulare. 6. ciclo. Coordinatore A. Melandri. Supervisore M. MelliConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal