Mutations in the Mitochondrial Methionyl-tRNA Synthetase Cause a Neurodegenerative Phenotype in Flies and a Recessive Ataxia (ARSAL) in Humans

An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues. We further observed that these mutants display defects in oxidative phosphorylation, increased Reactive Oxygen Species (ROS), and an upregulated mitochondrial Unfolded Protein Response. With the aid of this knowledge, we identified MARS2 to be mutated in Autosomal Recessive Spastic Ataxia with Leukoencephalopathy (ARSAL) patients. We uncovered complex rearrangements in the MARS2 gene in all ARSAL patients. Analysis of patient cells revealed decreased levels of MARS2 protein and a reduced rate of mitochondrial protein synthesis. Patient cells also exhibited reduced Complex I activity, increased ROS, and a slower cell proliferation rate, similar to Drosophila Aats-met mutants.

A Conservative Approach for Restoring Anterior Guidance: A Case Report

One of the most common dental problems in today's clinics is tooth wear, specifically when related to bruxism. In such cases, the esthetics of anterior teeth may be compromised when excessive wear to the incisal surfaces occurs. Anterior tooth wear resulting from parafunctional bruxism can be conservatively treated with the use of direct resin composite restorations. This restorative approach has the advantages of presenting good predictability, load resistance, acceptable longevity, preservation of healthy dental tissues, and lower cost when compared with indirect restorations. The use of resin composites to solve esthetic problems, however, requires skill and practice. Thus, the present article demonstrates a conservative approach for restoring the esthetics and function of worn anterior teeth with the aid of direct resin composite restorations and selective occlusal adjustment. CLINICAL SIGNIFICANCE A conservative approach to restore anterior teeth with excessive wear is possible with direct resin composites. (J Esthet Restor Dent 24:171-184, 2011)