Health,Stem Cells, and Technology

Saturday, July 7, 2012

Metabolic Profiles Of Human Embryonic Stem Cells and Embryonal Carcinoma Cells


Dr. James Adjaye's lab in Berlin has profiled the metabolomics of stem cells and carcinoma cells. While human embryonic stem cells (hESCs) and human embryonal carcinoma cells (hECCs) have been studied extensively at the levels of the genome, transcriptome, proteome and epigenome our knowledge of their corresponding metabolomes is limited. This study presents the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry (GC-MS). While some metabolites are common to both cell types, representing the self-renewal and house-keeping signatures, others were either higher (e.g., octadecenoic acid, glycerol-3-phosphate, 4-hydroxyproline) or lower (e.g., glutamic acid, mannitol, malic acid, GABA) in hESCs (H9) compared to hECCs (NTERA2), these represent cell type specific signatures. Further, the results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O2 while oxidative phosphorylation (OXPHOS) is impaired or even shut down. In 1924, Dr. Otto Warburg, a Nobel Laureate and professor of biology in Berlin, hypothesized that cancer, malignant growth, and tumor growth generate energy (as e.g. adenosine triphosphate / ATP) by non-oxidative breakdown of glucose (a process called glycolysis) and the subsequent recycling of the metabolite NADH back to its oxidized form, for reuse in the glycolytic cycle to complete the process (known as fermentation, or anaerobic respiration). This is in contrast to normal cells under aerobic conditions that mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end-product of glycolysis, and is oxidized within the mitochondria. Therefore, and according to Warburg, cancer should be interpreted as a mitochondrial dysfunction. RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such asNDUFC1, UQCRB and COX, increase in TCA cycle activity and decreased lactate metabolism. These results better describe the metabolite profile of pluripotent stem cells and may help establish novel metabolic markers of self renewal and pluripotency for research and therapeutic purposes.

Thursday, July 5, 2012

Pacific Tuna Transport Fukushima-Derived Radionuclides From Japan To California

The Fukushima Dai-ichi release of radionuclides into ocean waters has caused significant local and global concern regarding the spread of radioactive material throughout the oceans. 

  • Nicholas S. Fisher of the Hopkins Marine Station at Stanford University
  •  report unequivocal evidence that Pacific bluefin tuna, Thunnus orientalis, transported Fukushima-derived radionuclides across the entire North Pacific Ocean. The authors measured γ-emitting radionuclides in California-caught tunas and found 134Cs (4.0 ± 1.4 Bq kg−1) and elevated 137Cs (6.3 ± 1.5 Bq kg−1) in 15 Pacific bluefin tuna sampled in August 2011. They found no 134Cs and background concentrations (∼1 Bq kg−1) of 137Cs in pre-Fukushima bluefin and post-Fukushima yellowfin tunas, ruling out elevated radiocesium uptake before 2011 or in California waters post-Fukushima. 

    These findings indicate that Pacific bluefin tuna can rapidly transport radionuclides from a point source in Japan to distant ecoregions and demonstrate the importance of migratory animals as transport vectors of radionuclides. Other large, highly migratory marine animals make extensive use of waters around Japan, and these animals may also be transport vectors of Fukushima-derived radionuclides to distant regions of the North and South Pacific Oceans. 

    The levels of radioactive cesium were 10 times higher than the amount measured in tuna off the California coast in previous years. But even so, that's still far below safe-to-eat limits set by the U.S. and Japanese governments. Previously, smaller fish and plankton were found with elevated levels of radiation in Japanese waters after a magnitude-9 earthquake in March 2011 triggered a tsunami that badly damaged the Fukushima Dai-ichi reactors.
    But scientists did not expect the nuclear fallout to linger in huge fish that sail the world because such fish can metabolize and shed radioactive substances. Simply remember to bring your Geiger-counter to the fish market or the seafood restaurant and all will be well.