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1.  The KC Channel in the cbb3-Type Respiratory Oxygen Reductase from Rhodobacter capsulatus Is Required for Both Chemical and Pumped Protons 
Journal of Bacteriology  2014;196(10):1825-1832.
The heme-copper superfamily of proton-pumping respiratory oxygen reductases are classified into three families (A, B, and C families) based on structural and phylogenetic analyses. Most studies have focused on the A family, which includes the eukaryotic mitochondrial cytochrome c oxidase as well as many bacterial homologues. Members of the C family, also called the cbb3-type oxygen reductases, are found only in prokaryotes and are of particular interest because of their presence in a number of human pathogens. All of the heme-copper oxygen reductases require proton-conducting channels to convey chemical protons to the active site for water formation and to convey pumped protons across the membrane. Previous work indicated that there is only one proton-conducting input channel (the KC channel) present in the cbb3-type oxygen reductases, which, if correct, must be utilized by both chemical protons and pumped protons. In this work, the effects of mutations in the KC channel of the cbb3-type oxygen reductase from Rhodobacter capsulatus were investigated by expressing the mutants in a strain lacking other respiratory oxygen reductases. Proton pumping was evaluated by using intact cells, and catalytic oxygen reductase activity was measured in isolated membranes. Two mutations, N346M and Y374F, severely reduced catalytic activity, presumably by blocking the chemical protons required at the active site. One mutation, T272A, resulted in a substantially lower proton-pumping stoichiometry but did not inhibit oxygen reductase activity. These are the first experimental data in support of the postulate that pumped protons are taken up from the bacterial cytoplasm through the KC channel.
PMCID: PMC4010999  PMID: 24563037
2.  Primary Osteosarcoma of the Heart: Experience of an Unusual Case 
Case Reports in Oncology  2013;6(1):224-228.
Primary cardiac osteosarcomas are uncommon tumors. They have an aggressive biology and hence poor prognosis. This report describes a 23-year-old male patient who was referred to our hospital with chest pain. Echocardiography showed a left atrial mass, and tumor excision revealed a cardiac osteosarcoma. Adjuvant cisplatin plus ifosfamide combination chemotherapy provided a disease-free survival of 9 months; unfortunately the patient died of metastatic disease thereafter.
PMCID: PMC3656682  PMID: 23687493
Cardiac tumor; Extraskeletal osteosarcoma; Mitral stenosis
3.  Systems medicine and integrated care to combat chronic noncommunicable diseases 
Genome Medicine  2011;3(7):43.
We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.
PMCID: PMC3221551  PMID: 21745417

Results 1-3 (3)