Notch in memories: Points to remember

Memory is a temporally evolving molecular and structural process, which involves changes from local synapses to complex neural networks. There is increasing evidence for an involvement of developmental pathways in regulating synaptic communication in the adult nervous system. Notch signaling has been implicated in memory formation in a variety of species. Nevertheless, the mechanism of Notch underlying memory consolidation remains poorly understood. In this commentary, besides offering an overview of the advances in the field of Notch in memory, we highlight some of the weaknesses of the studies and attempt to cast light on the apparent discrepancies on the role of Notch in memory. We believe that future studies, employing high‐throughput technologies and targeted Notch loss and gain of function animal models, will reveal the mechanisms of Notch dependent plasticity and resolve whether this signaling pathway is implicated in the cognitive deficit associated with dementia. © 2015 Wiley Periodicals, Inc.     

Activation of an endothelial Notch1-Jagged1 circuit induces VCAM1 expression,an effect amplified by interleukin-1β

The Notch1 and Notch4 signaling pathways regulate endothelial cell homeostasis. Inflammatory cytokines induce the expression of endothelial adhesion molecules, including VCAM1, partly by downregulating Notch4 signaling. We investigated the role of endothelial Notch1 in this IL-1β-mediated process. Brief treatment with IL-1β upregulated endothelial VCAM1 and Notch ligand Jagged1. IL-1β decreased Notch1 mRNA levels, but levels of the active Notch1ICD protein remained constant. IL-1β-mediated VCAM1 induction was downregulated in endothelial cells subjected to pretreatment with a pharmacological inhibitor of the γ-secretase, which activates Notch receptors, producing NotchICD. It was also downregulated in cells in which Notch1 and/or Jagged1 were silenced.Conversely, the forced expression of Notch1ICD in naïve endothelial cells upregulated VCAM1 per se and amplified IL-1β-mediated VCAM1 induction. Jagged1 levels increased and Notch4 signaling was downregulated in parallel. Finally, Notch1ICD and Jagged1 expression was upregulated in the endothelium of the liver in a model of chronic liver inflammation.In conclusion, we describe here a cell-autonomous, pro-inflammatory endothelial Notch1-Jagged1 circuit (i) triggering the expression of VCAM1 even in the absence of inflammatory cytokines and (ii) enhancing the effects of IL-1β. Thus, IL-1β regulates Notch1 and Notch4 activity in opposite directions, consistent with a selective targeting of Notch1 in inflamed endothelium.     

Serological cross-sectional studies on salmonella incidence in eight European countries: no correlation with incidence of reported cases

ABSTRACT: BACKGROUND: Published incidence rates of human salmonella infections are mostly based on numbers of stool culture-confirmed cases reported to public health surveillance. These cases constitute only a small fraction of all cases occurring in the community. The extend of underascertainment is influenced by health care seeking behaviour and sensitivity of surveillance systems, so that reported incidence rates from different countries are not comparable. We performed serological cross-sectional studies to compare infection risks in eight European countries independent of underascertainment. METHODS: A total of 6,393 sera, mostly from existing serum collections representative of the adult population in Denmark, Finland, France, Italy, Poland, Romania, Sweden, and The Netherlands were analyzed. Immunoglobulin A (IgA), IgM, and IgG against salmonella lipopolysaccharides were measured by in-house mixed ELISA. We converted antibody concentrations to estimates of infection incidence ('sero-incidence') using a Bayesian backcalculation model, based on previously studied antibody decay profiles in persons with culture-confirmed salmonella infections. We compared sero-incidence with incidence of cases reported through routine public health surveillance and with published incidence estimates derived from infection risks in Swedish travellers to those countries. RESULTS: Sero-incidence of salmonella infections ranged from 56 (95% credible interval 8-151) infections per 1,000 person-years in Finland to 547 (343-813) in Poland. Depending on country, sero-incidence was approximately 100 to 2,000 times higher than incidence of culture-confirmed cases reported through routine surveillance, with a trend for an inverse correlation. Sero-incidence was significantly correlated with incidence estimated from infection risks in Swedish travellers. CONCLUSIONS: Sero-incidence estimation is a new method to estimate and compare the incidence of salmonella infections in human populations independent of surveillance artefacts. Our results confirm that comparison of reported incidence between countries can be grossly misleading, even within the European Union. Because sero-incidence includes asymptomatic infections, it is not a direct measure of burden of illness. But, pending further validation, it is a promising and cost-effective approach to assess infection risks and to evaluate the effectiveness of salmonella control programmes across countries.     

Radiation therapy in indolent primary cutaneous B cell lymphoma: a single institute experience

To report the clinical results after definitive radiotherapy (RT) for indolent primary cutaneous B cell lymphoma (pcBCL). The data concerning all patients treated for indolent pcBCL with RT with a curative intent between 1992 and 2012 were reviewed. All cases were (re)classified according to the World Health Organization (WHO) guidelines. A total of 42 patients with biopsy-proven primary cutaneous follicle center lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) were included. The median follow-up is 9.5 years. Treatment with RT resulted in complete response (CR) in all patients. Eight patients showed one or multiple relapses confined to the skin. No in-field recurrences were observed. For the entire cohort, the 10-year relapse-free survival (RFS) and overall survival (OS) were 71.1% and 87.1%, respectively. Univariate (UA) and multivariate (MA) analysis revealed extra-trunk primary lesion (MA) and multiple lesions (UA) as unfavorable prognostic factors. The 5-year RFS rate for patients with trunk lesion was 89.4% versus 66.9% for those with other location (p?=?0.02). The 5-year RFS rates were 83.5 and 57.1% in case of single and multiple lesions (p?=?0.04). An excellent survival can be achieved with definitive RT in indolent pcBCL. Patients with multiple and extra-trunk primary cutaneous lesions probably warrants intensification of therapy. Prospective studies are mandatory.     

Control of Dielectric and Mechanical Properties of Styrenic Block Copolymer by Graphite Incorporation

The structure–property relationship of dielectric elastomers, as well as the methods of improving the control of this relationship, has been widely studied over the last few years, including in some of our previous works. In this paper, we study the control, improvement, and correlation, for a significant range of temperatures, of the mechanical and dielectric properties of polystyrene-b-(ethylene-co-butylene)-b-styrene (SEBS) and maleic-anhydride-grafted SEBS (SEBS-MA) by using graphite (G) as filler in various concentrations. The aim is to analyze the suitability of these composites for converting electrical energy into mechanical energy or vice versa. The dielectric spectroscopy analysis performed in the frequency range of 10 to 1 MHz and at temperatures between 27 and 77 °C emphasized an exponential increase in real permittivity with G concentration, a low level of dielectric losses (≈10⁻³), as well as the stability of dielectric losses with temperature for high G content. These results correlate well with the increase in mechanical stiffness with an increase in G content for both SEBS/G and SEBS-MA/G composites. The activation energies for the dielectric relaxation processes detected in SEBS/G and SEBS-MA/G composites were also determined and discussed in connection with the mechanical, thermal, and structural properties resulting from thermogravimetric analysis, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses.