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1.
Engel GS Calhoun TR Read EL Ahn TK Mancal T Cheng YC Blankenship RE Fleming GR 《Nature》2007,446(7137):782-786
Photosynthetic complexes are exquisitely tuned to capture solar light efficiently, and then transmit the excitation energy to reaction centres, where long term energy storage is initiated. The energy transfer mechanism is often described by semiclassical models that invoke 'hopping' of excited-state populations along discrete energy levels. Two-dimensional Fourier transform electronic spectroscopy has mapped these energy levels and their coupling in the Fenna-Matthews-Olson (FMO) bacteriochlorophyll complex, which is found in green sulphur bacteria and acts as an energy 'wire' connecting a large peripheral light-harvesting antenna, the chlorosome, to the reaction centre. The spectroscopic data clearly document the dependence of the dominant energy transport pathways on the spatial properties of the excited-state wavefunctions of the whole bacteriochlorophyll complex. But the intricate dynamics of quantum coherence, which has no classical analogue, was largely neglected in the analyses-even though electronic energy transfer involving oscillatory populations of donors and acceptors was first discussed more than 70 years ago, and electronic quantum beats arising from quantum coherence in photosynthetic complexes have been predicted and indirectly observed. Here we extend previous two-dimensional electronic spectroscopy investigations of the FMO bacteriochlorophyll complex, and obtain direct evidence for remarkably long-lived electronic quantum coherence playing an important part in energy transfer processes within this system. The quantum coherence manifests itself in characteristic, directly observable quantum beating signals among the excitons within the Chlorobium tepidum FMO complex at 77 K. This wavelike characteristic of the energy transfer within the photosynthetic complex can explain its extreme efficiency, in that it allows the complexes to sample vast areas of phase space to find the most efficient path. 相似文献
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Arboleda VA Lee H Parnaik R Fleming A Banerjee A Ferraz-de-Souza B Délot EC Rodriguez-Fernandez IA Braslavsky D Bergadá I Dell'Angelica EC Nelson SF Martinez-Agosto JA Achermann JC Vilain E 《Nature genetics》2012,44(7):788-792
IMAGe syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies) is an undergrowth developmental disorder with life-threatening consequences. An identity-by-descent analysis in a family with IMAGe syndrome identified a 17.2-Mb locus on chromosome 11p15 that segregated in the affected family members. Targeted exon array capture of the disease locus, followed by high-throughput genomic sequencing and validation by dideoxy sequencing, identified missense mutations in the imprinted gene CDKN1C (also known as P57KIP2) in two familial and four unrelated patients. A familial analysis showed an imprinted mode of inheritance in which only maternal transmission of the mutation resulted in IMAGe syndrome. CDKN1C inhibits cell-cycle progression, and we found that targeted expression of IMAGe-associated CDKN1C mutations in Drosophila caused severe eye growth defects compared to wild-type CDKN1C, suggesting a gain-of-function mechanism. All IMAGe-associated mutations clustered in the PCNA-binding domain of CDKN1C and resulted in loss of PCNA binding, distinguishing them from the mutations of CDKN1C that cause Beckwith-Wiedemann syndrome, an overgrowth syndrome. 相似文献
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Now that some genomes have been completely sequenced, the ability to direct specific mutations into genomes is particularly desirable. Here we present a method to create mutations in the Caenorhabditis elegans genome efficiently through transgene-directed, transposon-mediated gene conversion. Engineered deletions targeted into two genes show that the frequency of obtaining the desired mutation was higher using this approach than using standard transposon insertion-deletion approaches. We also targeted an engineered green fluorescent protein insertion-replacement cassette to one of these genes, thereby confirming that custom alleles of different types can be created in vitro to make the corresponding mutations in vivo. This approach should also be applicable to heterologous transposons in C. elegans and other organisms, including vertebrates. 相似文献
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Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors 总被引:5,自引:0,他引:5
Al-Tassan N Chmiel NH Maynard J Fleming N Livingston AL Williams GT Hodges AK Davies DR David SS Sampson JR Cheadle JP 《Nature genetics》2002,30(2):227-232
Inherited defects of base excision repair have not been associated with any human genetic disorder, although mutations of the genes mutM and mutY, which function in Escherichia coli base excision repair, lead to increased transversions of G:C to T:A. We have studied family N, which is affected with multiple colorectal adenomas and carcinoma but lacks an inherited mutation of the adenomatous polyposis coli gene (APC) that is associated with familial adenomatous polyposis. Here we show that 11 tumors from 3 affected siblings contain 18 somatic inactivating mutations of APC and that 15 of these mutations are G:C-->A transversions--a significantly greater proportion than is found in sporadic tumors or in tumors associated with familial adenomatous polyposis. Analysis of the human homolog of mutY, MYH, showed that the siblings were compound heterozygotes for the nonconservative missense variants Tyr165Cys and Gly382Asp. These mutations affect residues that are conserved in mutY of E. coli (Tyr82 and Gly253). Tyrosine 82 is located in the pseudo-helix-hairpin-helix (HhH) motif and is predicted to function in mismatch specificity. Assays of adenine glycosylase activity of the Tyr82Cys and Gly253Asp mutant proteins with 8-oxoG:A and G:A substrates show that their activity is reduced significantly. Our findings link the inherited variants in MYH to the pattern of somatic APC mutation in family N and implicate defective base excision repair in predisposition to tumors in humans. 相似文献
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Time-resolved optical spectroscopy is widely used to study vibrational and electronic dynamics by monitoring transient changes in excited state populations on a femtosecond timescale. Yet the fundamental cause of electronic and vibrational dynamics--the coupling between the different energy levels involved--is usually inferred only indirectly. Two-dimensional femtosecond infrared spectroscopy based on the heterodyne detection of three-pulse photon echoes has recently allowed the direct mapping of vibrational couplings, yielding transient structural information. Here we extend the approach to the visible range and directly measure electronic couplings in a molecular complex, the Fenna-Matthews-Olson photosynthetic light-harvesting protein. As in all photosynthetic systems, the conversion of light into chemical energy is driven by electronic couplings that ensure the efficient transport of energy from light-capturing antenna pigments to the reaction centre. We monitor this process as a function of time and frequency and show that excitation energy does not simply cascade stepwise down the energy ladder. We find instead distinct energy transport pathways that depend sensitively on the detailed spatial properties of the delocalized excited-state wavefunctions of the whole pigment-protein complex. 相似文献
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High concentrations (10 mM) of alanine, glycine, and glutamic acid in the culture medium had no effect on urea production in Amphiuma means liver in organ culture. Ammonia production was increased in media containing added alanine and glycine, but reduced in medium with added glutamic acid. 相似文献
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The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth 总被引:1,自引:0,他引:1
Christofk HR Vander Heiden MG Harris MH Ramanathan A Gerszten RE Wei R Fleming MD Schreiber SL Cantley LC 《Nature》2008,452(7184):230-233
Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago. How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase. Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 (adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo. 相似文献
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The use of microring resonators to assist in the evanescent field coupling between dissimilar waveguides is proposed and analyzed. Theoretical analysis based on the coupled mode theory and nu-merical example show that complete cross power transfers can be obtained near the microring resonances. Applications of the device include power dividers, low-power thermo-optic or electro-optic switches, and modulators. 相似文献