"When voices meet" : Sharon Katz as musical activist during the apartheid era and beyond

This study investigates the work of the performer, composer, educator, music therapist and activist Sharon Katz. Beginning in 1992, Katz made history in apartheid South Africa when she formed a 500-member choir that showcased both multi-cultural and multi- lingual songs in their staged the production, When Voices Meet, which incorporated music, songs and dance, intended to assist in promoting a peaceful transition to democracy in South Africa. The success of the concerts of When Voices Meet led to Katz securing sponsorships to hire a train, “The Peace Train”, which transported 130 performers from city to city with media crews in tow. The performers’ mission on this journey was to create an environment of trust, of joy, and of sharing through music, across the artificially-imposed barriers of a racially segregated society. This investigation includes several areas of inquiry: The South African Peace Train; the efforts of the non-profit Friends of the Peace Train; Katz’s work with Pennsylvania prisoners and boys at an American Reform School; the documentary When Voices Meet, and the American Peace Train Tour of July 2016, bringing the message of peace and harmony through song to racially and socio-economically divided Americans on a route that started in New York and culminated with a concert at UNESCO’s Mandela Day celebrations in Washington D. C. These endeavours are examined within the framework of musical activism. The multi-faceted nature of Katz’s activism lends itself to an in-depth multiple case study. Qualitative case study methodology will be used to understand and theorise musical activism through detailed contextual analyses of five significant sets of related events. These include Katz’s work as a music therapist with prisoners in Pennsylvania and a Boys’ Reform School; as activist with The South African Peace Train of 1993; as humanitarian with Friends of the Peace Train; in making the documentary, When Voices Meet, and as activist with the American Peace Train Tour of 2016. In documenting the grass-roots musical activism of Sharon Katz, I hope to contribute towards a gap in South African musicological history that would add to a more comprehensive understanding of musical activism and its role in social change.Art History, Visual Arts and MusicologyD. Litt. et Phil. (Musicology

Minimal ureagenesis is necessary for survival in the murine model of hyperargininemia treated by AAV-based gene therapy.

Hyperammonemia is less severe in arginase 1 deficiency compared with other urea cycle defects. Affected patients manifest hyperargininemia and infrequent episodes of hyperammonemia. Patients typically suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation, seizures and intellectual disability; death is less common than with other urea cycle disorders. In a mouse model of arginase I deficiency, the onset of symptoms begins with weight loss and gait instability, which progresses toward development of tail tremor with seizure-like activity; death typically occurs at about 2 weeks of life. Adeno-associated viral vector gene replacement strategies result in long-term survival of mice with this disorder. With neonatal administration of vector, the viral copy number in the liver greatly declines with hepatocyte proliferation in the first 5 weeks of life. Although the animals do survive, it is not known from a functional standpoint how well the urea cycle is functioning in the adult animals that receive adeno-associated virus. In these studies, we administered [1-13C] acetate to both littermate controls and adeno-associated virus-treated arginase 1 knockout animals and examined flux through the urea cycle. Circulating ammonia levels were mildly elevated in treated animals. Arginine and glutamine also had perturbations. Assessment 30 min after acetate administration demonstrated that ureagenesis was present in the treated knockout liver at levels as low at 3.3% of control animals. These studies demonstrate that only minimal levels of hepatic arginase activity are necessary for survival and ureagenesis in arginase-deficient mice and that this level of activity results in control of circulating ammonia. These results may have implications for potential therapy in humans with arginase deficiency

Late-onset nonketotic hyperglycinemia and spinocerebellar degeneration

Investigation of a 15-year old boy with progressive optic atrophy and spinocerebellar degeneration revealed elevated plasma, cerebrospinal fluid, and urine glycine concentrations. During an oral glycine loading test, the patient's plasma glycine concentration rose to a higher level than control values, although the initial rate of rise was slower; there was no concomitant rise in the plasma serine concentration. An oral serine loading test resulted in a prompt rise of both glycine and serine serum concentrations. The renal glycine clearance was elevated, and the renal tubular glycine reabsorption was diminished. These findings of decreased intestinal uptake and increased renal tubular glycine clearance suggest that a generalized derangement of glycine entry into cells may account for the phenotypic manifestations of the disorder

Stable Isotopic Profiling of Intermediary Metabolic Flux in Developing and Adult Stage Caenorhabditis elegans

Stable isotopic profiling has long permitted sensitive investigations of the metabolic consequences of genetic mutations and/or pharmacologic therapies in cellular and mammalian models. Here, we describe detailed methods to perform stable isotopic profiling of intermediary metabolism and metabolic flux in the nematode, Caenorhabditis elegans. Methods are described for profiling whole worm free amino acids, labeled carbon dioxide, labeled organic acids, and labeled amino acids in animals exposed to stable isotopes either from early development on nematode growth media agar plates or beginning as young adults while exposed to various pharmacologic treatments in liquid culture. Free amino acids are quantified by high performance liquid chromatography (HPLC) in whole worm aliquots extracted in 4% perchloric acid. Universally labeled 13C-glucose or 1,6-13C2-glucose is utilized as the stable isotopic precursor whose labeled carbon is traced by mass spectrometry in carbon dioxide (both atmospheric and dissolved) as well as in metabolites indicative of flux through glycolysis, pyruvate metabolism, and the tricarboxylic acid cycle. Representative results are included to demonstrate effects of isotope exposure time, various bacterial clearing protocols, and alternative worm disruption methods in wild-type nematodes, as well as the relative extent of isotopic incorporation in mitochondrial complex III mutant worms (isp-1(qm150)) relative to wild-type worms. Application of stable isotopic profiling in living nematodes provides a novel capacity to investigate at the whole animal level real-time metabolic alterations that are caused by individual genetic disorders and/or pharmacologic therapies

Safety and Efficacy of Salvage Therapy With Laser Interstitial Thermal Therapy for Malignant Meningioma Refractory to Cesium-131 Brachytherapy: Illustrative Case

BACKGROUND Anaplastic meningioma are rare, cancerous tumors of the central nervous system that often require multimodal therapy for tumor control. Both laser interstitial thermal therapy (LITT) and brachytherapy with implanted cesium-131 metallic seeds have demonstrated efficacy in the treatment of recurrent and resistant anaplastic meningioma; however, their safety as a dual therapy has never been reported. OBSERVATIONS In this report, the authors present a case of a 53-year-old female who received LITT in combination with brachytherapy after surgical and radiation treatment options had been exhausted. The authors discuss the unique safety concern of thermal injury with this treatment combination and demonstrate their method for the safe administration of these treatments together. Furthermore, the authors provide a review of the literature on LITT as an emerging therapy for anaplastic meningioma. LESSONS The use of LITT in combination with brachytherapy remains an option for salvage therapy in patients with recurrent meningioma that provides durable local control of tumor

Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress

Bioenergetics in diabetic neuropathy: what we need to know

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91209/1/j.1529-8027.2012.00389.x.pd