Diffusion covariation and co-jumps in bidimensional asset price processes with stochastic volatility and infinite activity Levy jumps

In this paper we consider two processes driven by diffusions and jumps. The jump components are Levy processes and they can both have finite activity and infinite activity. Given discrete observations we estimate the covariation between the two diffusion parts and the co-jumps. The detection of the co-jumps allows to gain insight in the dependence structure of the jump components and has important applications in finance. Our estimators are based on a threshold principle allowing to isolate the jumps. This work follows Gobbi and Mancini (2006) where the asymptotic normality for the estimator of the covariation, with convergence speed given by the squared root of h, was obtained when the jump components have finite activity. Here we show that the speed is the squared root of h only when the activity of the jump components is moderate

Impact of sulphurous water Politzer inhalation on audiometric parameters in children with otitis media with effusion

Objectives: The positive effects of spa therapy on ear, nose, and throat pathology are known but robust literature in this field, is still lacking. The aim of this study was to assess through a retrospective analysis, the effects on otitis media with effusion of Politzer endotympanic inhalation of sulphurous waters in children aged 5-9 years. Methods: A cohort of 95 patients was treated with Politzer insufflations of sulphurous water: 58 patients did a cycle consisting of a treatment of 12 days per year for three consecutive years; 37 patients followed the same procedure for 5 years consecutively. The control population was represented by untreated, age-matched children. A standard audiometric test was used before and after each cycle of treatment. Results: One cycle of Politzer inhalation of sulphur-rich water improved the symptoms. Three cycles definitively stabilized the improvement of hearing function. Conclusion: Our results show that otitis media with effusion in children can be resolved by an appropriate non-pharmacological treatment of middle ear with sulphur-rich water

The glycan-binding protein galectin-1 controls survival of epithelial cells along the crypt-villus axis of small intestine

Abstract: Intestinal epithelial cells serve as mechanical barriers and active components of the mucosal immune system. These cells migrate from the crypt to the tip of the villus, where different stimuli can differentially affect their survival. Here we investigated, using in vitro and in vivo strategies, the role of galectin-1 (Gal-1), an evolutionarily conserved glycan-binding protein, in modulating the survival of human and mouse enterocytes. Both Gal-1 and its specific glyco-receptors were broadly expressed in small bowel enterocytes. Exogenous Gal-1 reduced the viability of enterocytes through apoptotic mechanisms involving activation of both caspase and mitochondrial pathways. Consistent with these findings, apoptotic cells were mainly detected at the tip of the villi, following administration of Gal-1. Moreover, Gal-1-deficient (Lgals-1-) mice showed longer villi compared with their wild-type counterparts in vivo. In an experimental model of starvation, fasted wild-type mice displayed reduced villi and lower intestinal weight compared with Lgals-1- mutant mice, an effect reflected by changes in the frequency of enterocyte apoptosis. Of note, human small bowel enterocytes were also prone to this pro-apoptotic effect. Thus, Gal-1 is broadly expressed in mucosal tissue and influences the viability of human and mouse enterocytes, an effect which might influence the migration of these cells from the crypt, the integrity of the villus and the epithelial barrier function.Facultad de Ciencias Exacta

Evolution led humans to bipedalism, but we live in a sedentary society: Will “Sunday running” protect us from NCDs at no cost?

Evolution led humans to bipedal stance and movement. However, we live in a sedentary society that strongly challenges our willingness to be physically active. We (mis)understand that being at least a Sunday runner could protect us from sedentary-related diseases, but what if this compromises the healthier life expectancy anyway? Citing Paul Gauguin, we know where we come from and what we are, the question arises about where we are going. And also, how

Activation and nuclear translocation of PKCε promotes skeletal muscle cell differentiation via HMGA1 downregulation

The role of novel PKCs in skeletal muscle differentiation has recently emerged. PKCθ is the most expressed isoform of PKCs in muscle and it promotes the fusion of myoblasts [1]. Recently, we have demonstrated that PKCε is implicated in myocardiocyte differentiation of bone marrow mesenchymal stem cells [2] but the role of PKCε in skeletal muscle cell regeneration has only recently emerged [3]. We here demonstrate that both nuclear and cytoplasmic fractions of PKCε are up-regulated during in vitro C2C12 cell line and satellite cell differentiation. We also show that PKCε is able to modulate myogenic differentiation genes via a downmodulation of HMGA1 proteins that promotes myogenin accumulation and mature myoblast formation. To study the effects of PKCε on muscle regeneration, we have used the in vivo model of CTX-induced skeletal muscle injury. We show that the upregulation of PKCε also occurs in vivo, particularly in the centro-nucleated regenerating fibers that are derived from the fusion process of the resident satellite cells, suggesting a role for PKCε in human satellite cell-driven muscle repair and substitution, with clinically relevant implications in human muscle pathology

PKC epsilon involvement in Th17 in vitro differentiation: implications in psoriasis pathogenesis

Psoriasis is a noncontagious, arytematous-squamose dermatitits affecting both sexes and all races. Although its exact etiology is largely unknown, it is now recognized as one of the most common immune-mediated disorders and several studies demonstrate an impairment of regulatory T-cells (Tregs) function and an up-regulation of IL-17 levels produced by T-helper 17 lymphocytes (Th17)(1,2). Protein kinase C epsilon (PKCε) is a serine/threonine kinase which plays a key role in the proliferation and differentiation of epidermal cells. We have previously demonstrated a role for PKCε in the pathogenesis of the autoimmune disease Hashimoto’s thyroiditis (3). PKCε is over-expressed in CD4+ T lymphocytes isolated from PBMC fraction in patients affected by this pathology and its forced down-modulation primed the TGF-mediated in vitro Treg polarization of human T CD4+ cells. Since it has been demonstrated that PKC-signalling is altered in psoriatic keratinocytes (4), we investigated the involvement of PKCε in Th17 in vitro differentiation and its potentially implication in immune response correlated to psoriasis. Using western blot and real time PCR, we have observed that PKCε protein levels and mRNA increase during Th17-lineage in vitro differentiation from naïve CD4+ T cells with a similar trend of Th17 markers of differentiation STAT3 and RoRyT. Moreover, PKCε overexpression significantly increases STAT3 and phosphorylated STAT3 levels, suggesting that PKCε boosts Th17 polarization. Thereafter, we sought to investigate PKCε expression in CD4+ lymphocytes obtained from peripheral blood of psoriatic patients and we observed that PKCε expression levels are significantly higher compared with healthy donors. Intriguingly, we observed a closely correlation of PKCε expression with PASI index, suggesting an involvement of the kinase with the severity of the disease. Collectively these data suggest that PKCε might be involved in Th17 differentiation, that it could be a key factor to regulate Th17 pathological expansion and therefore a potential psoriatic pharmacological target

Correlation between Protein Kinase Cε expression and thrombotic risk in Primary Myelofibrosis (PMFs)

Myelofibrosis (MF) - either primary (PMF) or arising from a previous PV or ET - is a Philadelphia-negative MPNs characterized by aberrant platelet production and consequent variable platelet count with altered hemostatic function (1). It has already been demonstrated that the risk of thrombotic events is one of the most common co-morbidities associated with PV and ET (2-5). However, risk of thrombotic events in PMF has not been investigated yet. We previously demonstrated that PKCepsilon (PKCε) is over-expressed in platelets from patients with acute myocardial infarction and accounts for their increased reactivity (6). Additionally, we recently showed that PKCε overexpression plays a crucial role in PMF MK impaired differentiation and that its levels correlated with the disease severity (expressed by the IPSS/DIPPS risk category) (7,8). On these bases, we analyzed PKCε expression in platelets from PMF patients, investigating a potential correlation with thrombotic risk and the aggressiveness of the disease. For this study, peripheral blood samples from 6 PMF patients and 3 healthy donors (HD) were collected in Na-citrate tubes. PKCε mRNA and protein levels were determined in platelets purified as described by Carubbi C, 2012. Finally, patients are stratified according to the history of cardio-vascular events and the IPSS/DIPSS risk category. PMF platelets showed significantly higher mRNA levels of PKCε as compared to HD. Protein analysis confirm PKCε over-expression in PMF platelets, almost reaching statistical significance. We then found that platelet from PMF patients who suffered from cardiovascular events display significantly higher levels of PKCε as compared to the one with a negative history. Finally, similarly to what observed in PMF magakaryocytes, we showed a positive correlation between PKCε platelets levels and IPSS/DIPSS risk category, with the lowest levels in low-risk patients and higher levels in high-risk patients. Collectively, our preliminary results indicate that PMF platelets show an aberrant expression of PKCε which correlates with the disease burden and a history of cardiovascular events. This suggests that the over-expression of PKCε may account for PMF platelet altered reactivity and function

A galectin-specific signature in the gut delineates Crohn’s disease and ulcerative colitis from other human inflammatory intestinal disorders

Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gastrointestinal tract including Crohn’s disease (CD) and ulcerative colitis (UC). Galectins, defined by shared consensus amino acid sequence and affinity for b-galactosides, are critical modulators of the inflammatory response. However, the relevance of the galectin network in the pathogenesis of human IBD has not yet been explored. Here, we analyzed the expression of relevant members of the galectin family in intestinal biopsies, and identified their contribution as novel mucosal markers in IBD. Colonic biopsies were obtained from 59 IBD patients (22 CD and 37 UC), 9 patients with gut rejection after transplantation, 8 adult celiac patients, and 32 non-IBD donors. Galectin mRNA expression was analyzed by RT-PCR and qPCR using specific primers for individual galectins. A linear discriminant analysis (LDA) was used to analyze galectin expression in individual intestinal samples. Expression of common mucosalassociated galectins (Gal-1, 23, 24, 29) is dysregulated in inflamed tissues of IBD patients compared with noninflamed IBD or control samples. LDA discriminated between different inflammation grades in active IBD and showed that remission IBD samples were clusterized with control samples. Galectin profiling could not distinguish CD and UC. Furthermore, inflamed IBD was discriminated from inflamed tissue of rejected gut in transplanted patients and duodenum of celiac patients, which could not be distinguished from control duodenum samples. The integrative analysis of galectins discriminated IBD from other intestinal inflammatory conditions and could be used as potential mucosal biomarker.Instituto de Estudios Inmunológicos y Fisiopatológico