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681.
Raffaele Teperino Adelheid Lempradl J. Andrew Pospisilik 《Cellular and molecular life sciences : CMLS》2013,70(9):1609-1621
The DNA sequence largely defines gene expression and phenotype. However, it is becoming increasingly clear that an additional chromatin-based regulatory network imparts both stability and plasticity to genome output, modifying phenotype independently of the genetic blueprint. Indeed, alterations in this “epigenetic” control layer underlie, at least in part, the reason for monozygotic twins being discordant for disease. Functionally, this regulatory layer comprises post-translational modifications of DNA and histones, as well as small and large noncoding RNAs. Together these regulate gene expression by changing chromatin organization and DNA accessibility. Successive technological advances over the past decade have enabled researchers to map the chromatin state with increasing accuracy and comprehensiveness, catapulting genetic research into a genome-wide era. Here, aiming particularly at the genomics/epigenomics newcomer, we review the epigenetic basis that has helped drive the technological shift and how this progress is shaping our understanding of complex disease. 相似文献
682.
HENDERSON Andrew 《科学通报(英文版)》2011,56(16):1714-1720
The molecular distribution of long-chain n-alkanes in 62 soil samples collected from diverse locations across eastern China was analyzed.The long-chain n-alkanes were mostly dominated by n-C29 or n-C31,regardless of the overlying vegetation type at each site.The results were compared with those summarized from the literature,covering more than 100 soil samples within China and more than 300 genera of modern plants distributed worldwide.There were similar n-alkane distribution patterns for most genera, with no clear differences among grasses,shrubs,and trees.The evidence from analyses of surface soils and modern plants indicates that the relationship between the molecular distribution of long-chain n-alkanes of surface soils and source vegetation is highly complex,and is influenced by many factors.Further,it is suggested that source vegetation types should not be simply inferred from distribution patterns of long-chain n-alkanes in sediments. 相似文献
683.
In this paper, I argue that recent debates about Newton’s attitude toward action at a distance have been hampered by a lack of conceptual clarity. To clarify the metaphysical background of the debates, I distinguish three kinds of causes within Newton’s work: mechanical, dynamical, and substantial causes. This threefold distinction enables us to recognize that although Newton clearly regards gravity as an impressed force that operates across vast distances, he denies that this commitment requires him to think that some substance acts at a distance on another substance. (Dynamical causation is distinct from substantial causation.) Newton’s denial of substantial action at a distance may strike his interpreters as questionable, so I provide an argument to show that it is in fact acceptable. 相似文献
684.
For the last 20 years, a large volume of experimental and theoretical work has been undertaken to understand how chaperones
like GroEL can assist protein folding in the cell. The most accepted explanation appears to be the simplest: GroEL, like most
other chaperones, helps proteins fold by preventing aggregation. However, evidence suggests that, under some conditions, GroEL
can play a more active role by accelerating protein folding. A large number of models have been proposed to explain how this
could occur. Focused experiments have been designed and carried out using different protein substrates with conclusions that
support many different mechanisms. In the current article, we attempt to see the forest through the trees. We review all suggested
mechanisms for chaperonin-mediated folding and weigh the plausibility of each in light of what we now know about the most
stringent, essential, GroEL-dependent protein substrates. 相似文献
685.
Andrew Barker 《Studies in history and philosophy of science》2009,40(4):344-351
In his Harmonics, Ptolemy constructs a complex set of theoretically ‘correct’ forms of musical scale, represented as sequences of ratios, on the basis of mathematical principles and reasoning. But he insists that their credentials will not have been established until they have been submitted to the judgement of the ear. They cannot be audibly instantiated with the necessary accuracy without the help of specially designed instruments, which Ptolemy describes in detail, discussing the uses to which each can be put and cataloguing its limitations. The best known of these instruments is the monochord, but there are several more complex devices. This paper discusses one such instrument which is known from no other source, ancient or modern, whose design was prompted by the geometrical construction known as the helikôn. It has several remarkable peculiarities. I examine its design, its purposes, and the merits and shortcomings which Ptolemy attributes to it. An appendix describes an instrument I have built to Ptolemy’s specifications (possibly the first of its kind since the second century bc), in an attempt to find out how satisfactorily such a bizarre contraption will work; and it explains how various practical problems can be resolved. 相似文献
686.
Andrew J. Quantock Robert D. Young Tomoya O. Akama 《Cellular and molecular life sciences : CMLS》2010,67(6):891-906
Keratan sulphate (KS) is the predominant glycosaminoglycan (GAG) in the cornea of the eye, where it exists in proteoglycan
(PG) form. KS-PGs have long been thought to play a pivotal role in the establishment and maintenance of the array of regularly-spaced
and uniformly-thin collagen fibrils which make up the corneal stroma. This characteristic arrangement of fibrils allows light
to pass through the cornea. Indeed, perturbations to the synthesis of KS-PG core proteins in genetically altered mice lead
to structural matrix alterations and corneal opacification. Similarly, mutations in enzymes responsible for the sulphation
of KS-GAG chains are causative for the inherited human disease, macular corneal dystrophy, which is manifested clinically
by progressive corneal cloudiness starting in young adulthood. 相似文献
687.
688.
In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication 总被引:4,自引:0,他引:4
Baltus AE Menke DB Hu YC Goodheart ML Carpenter AE de Rooij DG Page DC 《Nature genetics》2006,38(12):1430-1434
The transition from mitosis to meiosis is a defining juncture in the life cycle of sexually reproducing organisms. In yeast, the decision to enter meiosis is made before the single round of DNA replication that precedes the two meiotic divisions. We present genetic evidence of an analogous decision point in the germ line of a multicellular organism. The mouse Stra8 gene is expressed in germ cells of embryonic ovaries, where meiosis is initiated, but not in those of embryonic testes, where meiosis does not begin until after birth. Here we report that in female embryos lacking Stra8 gene function, the early, mitotic development of germ cells is normal, but these cells then fail to undergo premeiotic DNA replication, meiotic chromosome condensation, cohesion, synapsis and recombination. Combined with previous findings, these genetic data suggest that active differentiation of ovarian germ cells commences at a regulatory point upstream of premeiotic DNA replication. 相似文献
689.
Sharp AJ Hansen S Selzer RR Cheng Z Regan R Hurst JA Stewart H Price SM Blair E Hennekam RC Fitzpatrick CA Segraves R Richmond TA Guiver C Albertson DG Pinkel D Eis PS Schwartz S Knight SJ Eichler EE 《Nature genetics》2006,38(9):1038-1042
Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions. 相似文献
690.
A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening 总被引:26,自引:0,他引:26
Manning K Tör M Poole M Hong Y Thompson AJ King GJ Giovannoni JJ Seymour GB 《Nature genetics》2006,38(8):948-952
A major component in the regulatory network controlling fruit ripening is likely to be the gene at the tomato Colorless non-ripening (Cnr) locus. The Cnr mutation results in colorless fruits with a substantial loss of cell-to-cell adhesion. The nature of the mutation and the identity of the Cnr gene were previously unknown. Using positional cloning and virus-induced gene silencing, here we demonstrate that an SBP-box (SQUAMOSA promoter binding protein-like) gene resides at the Cnr locus. Furthermore, the Cnr phenotype results from a spontaneous epigenetic change in the SBP-box promoter. The discovery that Cnr is an epimutation was unexpected, as very few spontaneous epimutations have been described in plants. This study demonstrates that an SBP-box gene is critical for normal ripening and highlights the likely importance of epialleles in plant development and the generation of natural variation. 相似文献