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Biskup, T., Paulus, B., Okafuji, A., Hitomi, K., Getzoff, E. D., Weber, S., et al. (2013). Variable Electron Transfer Pathways in an Amphibian Cryptochrome: TRYPTOPHAN VERSUS TYROSINE-BASED RADICAL PAIRS. J Biol Chem, 288(13), 9249–9260.
Abstract: Electron transfer reactions play vital roles in many biological processes. Very often the transfer of charge(s) proceeds stepwise over large distances involving several amino acid residues. By using time-resolved electron paramagnetic resonance and optical spectroscopy, we have studied the mechanism of light-induced reduction of the FAD cofactor of cryptochrome/photolyase family proteins. In this study, we demonstrate that electron abstraction from a nearby amino acid by the excited FAD triggers further electron transfer steps even if the conserved chain of three tryptophans, known to be an effective electron transfer pathway in these proteins, is blocked. Furthermore, we were able to characterize this secondary electron transfer pathway and identify the amino acid partner of the resulting flavin-amino acid radical pair as a tyrosine located at the protein surface. This alternative electron transfer pathway could explain why interrupting the conserved tryptophan triad does not necessarily alter photoreactions of cryptochromes in vivo. Taken together, our results demonstrate that light-induced electron transfer is a robust property of cryptochromes and more intricate than commonly anticipated.
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Mori, H., Colman, S. M., Xiao, Z., Ford, A. M., Healy, L. E., Donaldson, C., et al. (2002). Chromosome translocations and covert leukemic clones are generated during normal fetal development. Proc Natl Acad Sci U S A, 99(12), 8242–8247.
Abstract: Studies on monozygotic twins with concordant leukemia and retrospective scrutiny of neonatal blood spots of patients with leukemia indicate that chromosomal translocations characteristic of pediatric leukemia often arise prenatally, probably as initiating events. The modest concordance rate for leukemia in identical twins ( approximately 5%), protracted latency, and transgenic modeling all suggest that additional postnatal exposure and/or genetic events are required for clinically overt leukemia development. This notion leads to the prediction that chromosome translocations, functional fusion genes, and preleukemic clones should be present in the blood of healthy newborns at a rate that is significantly greater than the cumulative risk of the corresponding leukemia. Using parallel reverse transcriptase-PCR and real-time PCR (Taqman) screening, we find that the common leukemia fusion genes, TEL-AML1 or AML1-ETO, are present in cord bloods at a frequency that is 100-fold greater than the risk of the corresponding leukemia. Single-cell analysis by cell enrichment and immunophenotype/fluorescence in situ hybridization multicolor staining confirmed the presence of translocations in restricted cell types corresponding to the B lymphoid or myeloid lineage of the leukemias that normally harbor these fusion genes. The frequency of positive cells (10(-4) to 10(-3)) indicates substantial clonal expansion of a progenitor population. These data have significant implications for the pathogenesis, natural history, and etiology of childhood leukemia.
Keywords: Base Sequence; Core Binding Factor Alpha 2 Subunit; DNA/blood; DNA Primers; *Embryonic and Fetal Development; Fetal Blood/chemistry; Humans; In Situ Hybridization, Fluorescence; Infant, Newborn; Leukemia/embryology/*genetics; Molecular Sequence Data; Oncogene Proteins, Fusion/*genetics; Polymerase Chain Reaction; RNA, Messenger/genetics; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors/*genetics; *Translocation, Genetic
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van Delft, F. W., Horsley, S., Colman, S., Anderson, K., Bateman, C., Kempski, H., et al. (2011). Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia. Blood, 117(23), 6247–6254.
Abstract: B-cell precursor childhood acute lymphoblastic leukemia with ETV6-RUNX1 (TEL-AML1) fusion has an overall good prognosis, but relapses occur, usually after cessation of treatment and occasionally many years later. We have investigated the clonal origins of relapse by comparing the profiles of genomewide copy number alterations at presentation in 21 patients with those in matched relapse (12-119 months). We identified, in total, 159 copy number alterations at presentation and 231 at relapse (excluding Ig/TCR). Deletions of CDKN2A/B or CCNC (6q16.2-3) or both increased from 38% at presentation to 76% in relapse, suggesting that cell-cycle deregulation contributed to emergence of relapse. A novel observation was recurrent gain of chromosome 16 (2 patients at presentation, 4 at relapse) and deletion of plasmocytoma variant translocation 1 in 3 patients. The data indicate that, irrespective of time to relapse, the relapse clone was derived from either a major or minor clone at presentation. Backtracking analysis by FISH identified a minor subclone at diagnosis whose genotype matched that observed in relapse approximately 10 years later. These data indicate subclonal diversity at diagnosis, providing a variable basis for intraclonal origins of relapse and extended periods (years) of dormancy, possibly by quiescence, for stem cells in ETV6-RUNX1(+) acute lymphoblastic leukemia.
Keywords: Child; Child, Preschool; Chromosomes, Human, Pair 16/*genetics/metabolism; Chromosomes, Human, Pair 6/*genetics/metabolism; Cyclin C; Cyclin-Dependent Kinase Inhibitor p15/genetics/metabolism; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism; Female; Humans; Male; Oncogene Proteins, Fusion/*genetics/metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/metabolism/mortality/therapy; Recurrence; *Sequence Deletion; *Translocation, Genetic
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Kos, B., ValiÄ, B., MiklavÄiÄ, D., Kotnik, T., & GajÅ¡ek, P. (2011). Pre- and post-natal exposure of children to EMF generated by domestic induction cookers. Phys. Med. Biol., 56(19), 6149–6160.
Abstract: Induction cookers are a type of cooking appliance that uses an intermediate-frequency magnetic field to heat the cooking vessel. The magnetic flux density produced by an induction cooker during operation was measured according to the EN 62233 standard, and the measured values were below the limits set in the standard. The measurements were used to validate a numerical model consisting of three vertically displaced coaxial current loops at 35 kHz. The numerical model was then used to compute the electric field (E) and induced current (J) in 26 and 30 weeks pregnant women and 6 and 11 year old children. Both E and J were found to be below the basic restrictions of the 2010 low-frequency and 1998 ICNRIP guidelines. The maximum computed E fields in the whole body were 0.11 and 0.66 V m(-1) in the 26 and 30 weeks pregnant women and 0.28 and 2.28 V m(-1) in the 6 and 11 year old children (ICNIRP basic restriction 4.25 V m(-1)). The maximum computed J fields in the whole body were 46 and 42 mA m(-2) in the 26 and 30 weeks pregnant women and 27 and 16 mA m(-2) in the 6 and 11 year old children (ICNIRP basic restriction 70 mA m(-2)).
Keywords: Exposure
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Ainsbury, E. A., & Henshaw, D. L. (2006). Observations on the relationship between magnetic field characteristics and exposure conditions. Phys Med Biol, 51(23), 6113–6123.
Abstract: The authors have been investigating metrics of extremely low frequency magnetic field exposure under different circumstances. In this paper, we describe the properties of magnetic fields in homes, in the vicinity of powerlines, on trains and from a library security system. We conclude that there are key differences between each of these fields. This suggests that there may be a characterizable pattern for magnetic fields in different situations.
Keywords: Biophysical Phenomena; Biophysics; Electric Power Supplies/adverse effects; Environmental Exposure; Great Britain; Housing; Humans; Libraries; Magnetics/*adverse effects; Railroads; Security Measures
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