Raphael, the Virgin Mary, and Holy Matrimony: Recontextualizing Franz Liszt's Sposalizio

Sposalizio, the piece opening the “Italian year” of Franz Liszt's Années de pèlerinage (first published in 1858), is one of the most analyzed and interpreted compositions in this piano cycle. Much attention has been paid to its connection with the painting of the same title by Raphael, which was printed as an internal title page for the piece's first edition at the explicit request of the composer. This connection has inspired many studies on the relationship between image and music, reinforcing the notion of Sposalizio as a musical realization of Raphael's painting as seen by Liszt for the first time in February 1838 at the Pinacoteca di Brera in Milan. Adopting a critical view of the hermeneutical tradition, which has an impact on the interpretation of the piece still today, and assuming that its composition began in Weimar only around 1848, the article proposes an alternative reading of the piece. By connecting pictorial and musical elements, Sposalizio seems to evoke several cultural discourses and practices fundamental to Liszt's artistic and biographical background, such as Raphael's image as a genius, the revival of Marian devotion, and marriage as a sacrament of the Catholic Church

Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

Single-molecule imaging reveals that small amyloid-β1-42 oligomers interact with the cellular prion protein (PrP(C)).

Oligomers of the amyloid-β peptide (Aβ) play a central role in the pathogenesis of Alzheimer's disease and have been suggested to induce neurotoxicity by binding to a plethora of cell-surface receptors. However, the heterogeneous mixtures of oligomers of varying sizes and conformations formed by Aβ42 have obscured the nature of the oligomeric species that bind to a given receptor. Here, we have used single-molecule imaging to characterize Aβ42 oligomers (oAβ42) and to confirm the controversial interaction of oAβ42 with the cellular prion protein (PrP(C)) on live neuronal cells. Our results show that, at nanomolar concentrations, oAβ42 interacts with PrP(C) and that the species bound to PrP(C) are predominantly small oligomers (dimers and trimers). Single-molecule biophysical studies can thus aid in deciphering the mechanisms that underlie receptor-mediated oAβ-induced neurotoxicity, and ultimately facilitate the discovery of novel inhibitors of these pathways.This is the final published version. It was first published by Wiley in ChemBioChem (http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1439-7633)

Co-transplantation of Human Embryonic Stem Cell-derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Co-transplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a way to overcome low rate of neuronal differentiation of NPs following transplantation in spinal cord injury (SCI) and the improvement of locomotor recovery. In this study, we initially generated NPs from human embryonic stem cells (hESCs) and investigated their potential for neuronal differentiation and functional recovery when co-cultured with SCs in vitro and co-transplanted in a rat acute model of contused SCI. Co-cultivation results revealed that the presence of SCs provided a consistent status for hESC-NPs and recharged their neural differentiation toward a predominantly neuronal fate. Following transplantation, a significant functional recovery was observed in all engrafted groups (NPs, SCs, NPs+SCs) relative to the vehicle and control groups. We also observed that animals receiving co-transplants established a better state as assessed with the BBB functional test. Immunohistofluorescence evaluation five weeks after transplantation showed invigorated neuronal differentiation and limited proliferation in the co-transplanted group when compared to the individual hESC-NPs grafted group. These findings have demonstrated that the co-transplantation of SCs with hESC-NPs could offer a synergistic effect, promoting neuronal differentiation and functional recovery

Validation of a General and Sport Nutrition Knowledge Questionnaire in Adolescents and Young Adults: GeSNK

Good knowledge of nutrition is widely thought to be an important aspect to maintaining a balanced and healthy diet. The aim of this study was to develop and validate a new reliable tool to measure the general and the sport nutrition knowledge (GeSNK) in people who used to practice sports at different levels. The development of (GeSNK) was carried out in six phases as follows: (1) item development and selection by a panel of experts; (2) pilot study in order to assess item difficulty and item discrimination; (3) measurement of the internal consistency; (4) reliability assessment with a 2-week test-retest analysis; (5) concurrent validity was tested by administering the questionnaire along with other two similar tools; (6) construct validity by administering the questionnaire to three groups of young adults with different general nutrition and sport nutrition knowledge. The final questionnaire, consisted of 62 items of the original 183 questions. It is a consistent, valid, and suitable instrument that can be applied over time, making it a promising tool to look at the relationship between nutrition knowledge, demographic characteristics, and dietary behavior in adolescents and young adults