Journal of IiMER blood fractions from two small patient cohorts, each of 10 patients with age and gender matched controls, one of which was focussed on exercise intolerance and ‘post exertion malaise’. Initially we collected data on the immune cell expressed genes (transcriptome) and proteins (proteome) as well as plasma microRNAs and cytokines with an aim of integrating the data to elucidate linkages between different classes of molecules and give insight into physiological changes. We are currently extending these studies to mitochondrial function and epigenetic changes in the DNA following the recently published research suggesting energy delivery and modulation of expression of specific genes might be significant factors in changes in physiology for perpetuation of the disease. Can a model be developed that might explain most of the diverse symptoms? Evidence of chronic inflammation in the limbic system of the brain and glial cell activation has been shown in neuroimaging studies of Japanese ME/CFS patients, with a degree of inflammation that correlated with severity of disease symptoms. These observations, coupled with the known disturbance of the hypothalamus/pituitary/adrenal axis in ME/CFS, and the hypersensitivity of ME/CFS patients to stress of any kind, has lead us to develop a model whereby the paraventricular nucleus (PVN), the ‘stress centre ‘of the hypothalamus, might be a possible ME/CFS perpetuating centre. The PVN is responsible for absorbing and processing incoming stress signals and chronic fluctuating auto-inflammation in the brain affecting the threshold for managing stress could explain perpetuation of the disease and relapses in the chronic phase of ME/CFS. Detailed molecular and neuroimaging data from patients using cutting edge technologies will allow new models to explain ME/CFS and should provide meaningful benefits for patients for managing and living with their disease. Professor Ron Davis Professor of Biochemistry and Genetics at the Stanford School of Medicine in Stanford, California, USA Ronald W. Davis, Ph.D., is a Professor of Biochemistry and Genetics at the Stanford School of Medicine in Stanford, California. He is a world leader in the development of biotechnology, especially the development of recombinant DNA and genomic methodologies and their application to biological systems. At Stanford University, where he is Director of the Stanford Genome Technology Center, Dr. Davis focuses on the interface of nano-fabricated solid state devices and biological systems. He and his research team also develop novel technologies for the genetic, genomic, and molecular analysis of a wide range of model organisms as well as humans. The team's focus on practical application of these technologies is setting the standard for clinical www.investinme.org Page 78 of 82

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