RESUMEN
Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Transcripción Genética , alfa-Glucosidasas/genética , Edad de Inicio , Niño , Preescolar , Femenino , Expresión Génica , Enfermedad del Almacenamiento de Glucógeno Tipo II/metabolismo , Humanos , Lactante , Recién Nacido , Masculino , Músculo Esquelético/metabolismo , Fenotipo , alfa-Glucosidasas/metabolismoRESUMEN
The objective of this case study was to examine the economics of three lignocellulose-to-ethanol conversion technologies: fast pyrolysis integrated with a fermentation step, simultaneous saccharification and fermentation (SSF), and dilute sulfuric acid hydrolysis and fermentation. All technologies were assumed to have an annual production rate of 25 million gallons of ethanol. The three technologies were compared in terms of capital costs, operating costs, and ethanol production costs. Sensitivity analyses were carried out to study the uncertainties of wood costs and ethanol production rates on ethanol production costs. Final economic analysis showed that fast pyrolysis integrated with a fermentation step is comparable with the other two processes and suggests that it should be considered for further development.