Hydrogen peroxide is a neuronal alarmin that triggers specific RNAs, local translation of Annexin A2, and cytoskeletal remodeling in Schwann cells

Schwann cells are key players in neuro-regeneration: They sense "alarm" signals released by degenerating nerve terminals and differentiate toward a proregenerative phenotype, with phagocytosis of nerve debris and nerve guidance. At the murine neuromuscular junction, hydrogen peroxide (H2O2) is a key signal of Schwann cells' activation in response to a variety of nerve injuries. Here we report that Schwann cells exposed to low doses of H2O2 rewire the expression of several RNAs at both transcriptional and translational levels. Among the genes positively regulated at both levels, we identified an enriched cluster involved in cytoskeleton remodeling and cell migration, with the Annexin (Anxa) proteins being the most represented family. We show that both Annexin A2 (Anxa2) transcript and protein accumulate at the tips of long pseudopods that Schwann cells extend upon H2O2 exposure. Interestingly, Schwann cells reply to this signal and to nerve injury by locally translating Anxa2 in pseudopods, and undergo an extensive cytoskeleton remodeling. Our results show that, similarly to neurons, Schwann cells take advantage of local protein synthesis to change shape and move toward damaged axonal terminals to facilitate axonal regeneration

Precision measurements of Linear Scattering Density using Muon Tomography

We demonstrate that muon tomography can be used to precisely measure the properties of various materials. The materials which have been considered have been extracted from an experimental blast furnace, including carbon (coke) and iron oxides, for which measurements of the linear scattering density relative to the mass density have been performed with an absolute precision of 10%. We report the procedures that are used in order to obtain such precision, and a discussion is presented to address the expected performance of the technique when applied to heavier materials. The results we obtain do not depend on the specific type of material considered and therefore they can be extended to any application.Comment: 16 pages, 4 figure

Noise reduction in muon tomography for detecting high density objects

The muon tomography technique, based on multiple Coulomb scattering of cosmic ray muons, has been proposed as a tool to detect the presence of high density objects inside closed volumes. In this paper a new and innovative method is presented to handle the density fluctuations (noise) of reconstructed images, a well known problem of this technique. The effectiveness of our method is evaluated using experimental data obtained with a muon tomography prototype located at the Legnaro National Laboratories (LNL) of the Istituto Nazionale di Fisica Nucleare (INFN). The results reported in this paper, obtained with real cosmic ray data, show that with appropriate image filtering and muon momentum classification, the muon tomography technique can detect high density materials, such as lead, albeit surrounded by light or medium density material, in short times. A comparison with algorithms published in literature is also presented

Risk Taking, Diversification Behavior and Financial Literacy of Individual Investors

This research investigates whether the financial literacy of individuals influences risk taking decisions and diversification behavior. This issue is relevant in that investors are increasingly in charge of their own financial security, but they have to deal with financial instruments whose increasing complexity often eventually prevents them from making conscious investment decisions. Prior empirical evidence shows that people are unable to perform a sophisticated portfolio diversification: what they do is to split equally their wealth among the asset classes available, in a naive way. We try to detect if the financial literacy is a driver of this kind of decisions. By submitting a questionnaire to 200 American individuals, we find that financial literacy plays a role in risk taking decisions, positively affecting how much risk individuals are willing to take. Moreover, only those who are literate in terms of diversification select less risky portfolios; the others merely increase their risk exposure, without managing it. Consistently with the previous literature, the strategy of diversification adopted by the literate ones is mainly naive. Instead, financial literacy turns out not being significant in explaining more sophisticated diversification strategies. As financial literacy affects positively the amount of risk taken by individuals, but only partially the diversification strategies pursued, there might be a dangerous pitfall in today's financial education programs promoted by governments and regulators, which, though they make investors more aware of their investment decisions, they eventually push them to assume more risks than they are able to manage. Two possible ways to tackle this issue could be: 1) to boost the financial literacy of the investors so as to make them able to use all the investment techniques required by the standard theory. This, however, seems difficult to obtain; 2) to promote advisory activity among investors. This may help them to apply the diversification principle in a sophisticated way

Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers

Mast cells (MC) are c-Kit-expressing cells, best known for their primary involvement in allergic reactions, but recently reappraised as important players in either cancer promotion or inhibition. Here, we assessed the role of MCs in prostate tumor development. In prostate tumors from both tumor-prone transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and human patients, MCs are specifically enriched and degranulated in areas of well-differentiated (WD) adenocarcinoma but not around poorly differentiated (PD) foci that coexist in the same tumors. We derived novel TRAMP tumor cell lines, representative of WD and PD variants, and through pharmacologic stabilization or genetic ablation of MCs in recipients mice, we showed that MCs promote WD adenocarcinoma growth but are dispensable for PD tumors. WD tumors rely on MCs for matrix metalloprotease 9 (MMP-9) provision, as reconstitution of MC-deficient mice with wild-type but not MMP-9 -/- MCs was sufficient to promote their growth. In contrast, PD tumors are MMP-9 self-competent, consistently with epithelial-to-mesenchymal transition. Such a dual source of MMP-9 was confirmed in human tumors, suggesting that MCs could be a good target for early-stage prostate cancer. Interestingly, in testing whether MC targeting could block or delay tumorigenesis in tumor-prone TRAMP mice, we observed a high incidence of early and aggressive tumors, characterized by a neuroendocrine (NE) signature and c-Kit expression. Taken together, these data underscore the contribution of MCs in tumor progression and uncover a new, opposite role of MCs in protecting against the occurrence of aggressive NE variants in prostate cancer. ©2011 AACR

Direct current measurements of the SPIDER beam: a comparison to existing beam diagnostics

For negative ion beam sources there are several methods of measuring the accelerated beam current, most commonly electrical measurements at the power supply and calorimetric measurements. On SPIDER, the ITER Heating Neutral Beam full-scale beam source prototype, electrical measurements at the acceleration grid power supply (AGPS) are complemented by polarizing the diagnostic calorimeter STRIKE to provide an additional electrical measurement of the accelerated current. This is in addition to the calorimetric measurements provided by STRIKE. These diagnostics give differing measurements of the beam current. Exploiting the reduced number of open apertures on SPIDER a new beam diagnostic has been installed to measure the individual beamlet currents directly. The so called Beamlet Current Monitor (BCM) has been used to measure the current of five beamlets during the most recent SPIDER campaign. This work compares the BCM current to the electrical measurements at the AGPS and STRIKE. The average BCM current agrees well with the STRIKE electrical measurements, indicating that the AGPS overestimates the beam current. The individual beamlets are compared to the STRIKE calorimetric measurements, showing similar current trends with the source parameters

A CXCR4 receptor agonist strongly stimulates axonal regeneration after damage

Objective: To test whether the signaling axis CXCL12\u3b1-CXCR4 is activated upon crush/cut of the sciatic nerve and to test the activity of NUCC-390, a new CXCR4 agonist, in promoting nerve recovery from damage. Methods: The sciatic nerve was either crushed or cut. Expression and localization of CXCL12\u3b1 and CXCR4 were evaluated by imaging with specific antibodies. Their functional involvement in nerve regeneration was determined by antibody-neutralization of CXCL12\u3b1, and by the CXCR4 specific antagonist AMD3100, using as quantitative read-out the compound muscle action potential (CMAP). NUCC-390 activity on nerve regeneration was determined by imaging and CMAP recordings. Results: CXCR4 is expressed at the injury site within the axonal compartment, whilst its ligand CXCL12\u3b1 is expressed in Schwann cells. The CXCL12\u3b1-CXCR4 axis is involved in the recovery of neurotransmission of the injured nerve. More importantly, the small molecule NUCC-390 is a strong promoter of the functional and anatomical recovery of the nerve, by acting very similarly to CXCL12\u3b1. This pharmacological action is due to the capability of NUCC-390 to foster elongation of motor neuron axons both in vitro and in vivo. Interpretation: Imaging and electrophysiological data provide novel and compelling evidence that the CXCL12\u3b1-CXCR4 axis is involved in sciatic nerve repair after crush/cut. This makes NUCC-390 a strong candidate molecule to stimulate nerve repair by promoting axonal elongation. We propose this molecule to be tested in other models of neuronal damage, to lay the basis for clinical trials on the efficacy of NUCC-390 in peripheral nerve repair in humans

Estudio preliminar de algunas variables de crecimiento y fertilidad en ratones de Bioterio

 In the present work, the results obtained in the comparative study of the growth and fertility of Balb/C and CF-1 mice from the Bioterium of the Faculty of Medicine of the National University of the Northeast are exposed, by modifying the environmental conditions of breeding and reproduction of the animals before and after the moving of the Center to its new facilities. The characteristics studied in both strains were: breeding number, weight according to sex before and after weaning, until to the 15th week of life, and fertility rate. The results obtained show that the moving caused stress in both murine strains, and the effect was manifested in the decrease of growth and fertility rates observed in the animals. These values were not statistically significant, which allows us to conclude that the enrichment of the habitat in the new facilities helped to alleviate in some way the stress of the move. This is the first systematic study carried out for this purpose and lays the foundations for others for monitoring the adaptation and production in the new facilities.En el presente trabajo se exponen los resultados obtenidos en el estudio comparativo del crecimiento y la fertilidad de ratones Balb/C y CF-1 del Bioterio de la Facultad de Medicina de la Universidad Nacional del Nordeste, al modificar las condiciones ambientales de cría y reproducción de los animales previa y posteriormente al traslado del Centro a sus nuevas instalaciones. Las características estudiadas en ambas cepas fueron: número de crías, peso según sexo previo y posterior al destete, hasta la semana 15 de vida y tasa de fertilidad. Los resultados obtenidos muestran que el traslado causó estrés en ambas cepas murinas, cuyo efecto se manifestó en la disminución de las tasas de crecimiento y fertilidad en estos animales experimentales. Estos valores resultaron no significativos estadísticamente, lo que nos permite concluir que el enriquecimiento del hábitat en las nuevas instalaciones ayudó a paliar de alguna manera el estrés de la mudanza. Este es el primer estudio sistemático realizado a este efecto y sienta las bases de otros para el seguimiento de la adaptación y producción en las nuevas instalaciones