'Il novello Orfeo' Farinelli: vocal profile, aesthetics, rhetoric

Although Farinelli has received a great deal of attention in scholarship, the early music performance scene and in popular culture, little has been written about his singing. The current perception of Farinelli’s musical profile is based almost entirely on the research of Franz Haböck from the beginning of the 20th century and the writings of Charles Burney. As a result of the emphasis of both writers on Farinelli’s bravura singing, the singer’s name has become synonymous with castrato virtuosity. This study takes a more diffentiated approach. It reconstructs the artistic persona of Farinelli from libretti, scores and documentary evidence, evaluates the veracity of anecdotal information pertaining to his singing that has so far been accepted largely at face value and considers the aesthetic implications of Farinelli’s singing. Part I of this study seeks to reconstruct Farinelli’s vocal profile. In chapter 1, contemporary descriptions by earwitnesses are examined and evaluated with regard to important aspects of his singing, i.e., the sound quality, volume and range of his voice, technical elements such as his trill, agility and breath control, ornamentation and improvisation and, finally, his acting. Chapter 2 summarises the main stages of the singer’s operatic career. The purpose of this chapter is not to reiterate biographical information, but to provide an outline that can serve as a framework for the discussion of the development of Farinelli’s vocal technique, personal style and reception. The chapter also identifies important points of professional interaction between Farinelli and other famous singers. Chapter 3 falls into two parts. Firstly, the main elements of vocal technique, as described in the vastly influential vocal treatises of Tosi and Mancini, are outlined in relation to notational practice of 18th-century manuscript scores and their relevance to the music sung by Farinelli. Secondly, the development of Farinelli’s voice in terms of the singer’s vocal technique, range, volume and details of style is discussed on the basis of the analysis of Farinelli’s operatic roles. Chapter 4 focuses on the analysis and contextualisation of important stylistic changes that occured during Farinelli’s career. Throughout, Farinelli’s stylistic choices are discussed in relation to the aesthetic preferences of the different audiences he encountered. Part 2 explores aspects of Farinelli’s artistic profile from the vantage points of aesthetics and rhetoric. Based on analyses of Farinelli’s arias on nightingale metaphors, chapter 5 discusses the conceptual frameworks and aesthetic issues that have often resulted in a critical reception of his virtuosity, both during his lifetime and in the 20th century. Chapter 6 examines the manner in which the principles of rhetoric have been applied to 18th-century music in recent scholarship. It argues for a different, more integrated approach that reflects the performance-centred period understanding of rhetoric, which, unlike the modern understanding, was not yet inflected by the author and work concepts. Chapter 7 analyses rhetorical strategies in Farinelli’s Venetian bravura arias and their implications with regard to the issues of authorship and the relationship between performer and audience. In chapter 8, the text-music relationship and communicative strategies in Farinelli’s slow expressive arias are scrutinised. The conclusion briefly assesses the impact of Farinelli on Italian opera, theatrical performance practice and musical aesthetics

The Effect of Mitochondrial Dysfunction on Cytosolic Nucleotide Metabolism

Several enzymes of the metabolic pathways responsible for metabolism of cytosolic ribonucleotides and deoxyribonucleotides are located in mitochondria. Studies described in this paper suggest dysfunction of the mitochondria to affect these metabolic pathways and limit the available levels of cytosolic ribonucleotides and deoxyribonucleotides, which in turn can result in aberrant RNA and DNA synthesis. Mitochondrial dysfunction has been linked to genomic instability, and it is possible that the limiting effect of mitochondrial dysfunction on the levels of nucleotides and resulting aberrant RNA and DNA synthesis in part can be responsible for this link. This paper summarizes the parts of the metabolic pathways responsible for nucleotide metabolism that can be affected by mitochondrial dysfunction

Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients

AIMS: Accurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics and DNA damage, in peripheral blood mononuclear cells (PBMCs) of AD and control participants, for biomarker discovery. METHODS: PBMCs were isolated from 53 patients with AD of mild to moderate degree and 30 age-matched healthy controls. Tests were performed on the PBMCs from as many of these participants as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer, mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay, and APE1 incision activity (in cell lysates) on a DNA substrate containing an AP site (to estimate DNA repair efficiency). RESULTS: In the PBMCs of AD patients, we found reduced basal mitochondrial oxygen consumption, reduced proton leak, higher dATP level, and lower AP endonuclease 1 activity, depending on adjustments for gender and/or age. CONCLUSIONS: This study reveals impaired mitochondrial respiration, altered dNTP pools and reduced DNA repair activity in PBMCs of AD patients, thus suggesting that these biochemical activities may be useful as biomarkers for AD

Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients

AIMS: Accurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics and DNA damage, in peripheral blood mononuclear cells (PBMCs) of AD and control participants, for biomarker discovery.METHODS: PBMCs were isolated from 53 patients with AD of mild to moderate degree and 30 age-matched healthy controls. Tests were performed on the PBMCs from as many of these participants as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer, mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay, and APE1 incision activity (in cell lysates) on a DNA substrate containing an AP site (to estimate DNA repair efficiency).RESULTS: In the PBMCs of AD patients, we found reduced basal mitochondrial oxygen consumption, reduced proton leak, higher dATP level, and lower AP endonuclease 1 activity, depending on adjustments for gender and/or age. CONCLUSIONS: This study reveals impaired mitochondrial respiration, altered dNTP pools and reduced DNA repair activity in PBMCs of AD patients, thus suggesting that these biochemical activities may be useful as biomarkers for AD.publishe