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991.
Meléndez A Tallóczy Z Seaman M Eskelinen EL Hall DH Levine B 《Science (New York, N.Y.)》2003,301(5638):1387-1391
Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans. 相似文献
992.
CENH3 is a centromere-specific histone H3 variant essential for kinetochore assembly. Despite its central role in centromere function, there has been no conclusive evidence supporting CENH3 as sufficient to determine centromere identity. To address this question, we artificially targeted Drosophila CENH3 (CENP-A/CID) as a CID-GFP-LacI fusion protein to stably integrated lac operator (lacO) arrays. This ectopic CID focus assembles a functional kinetochore and directs incorporation of CID molecules without the LacI-anchor, providing evidence for the self-propagation of the epigenetic mark. CID-GFP-LacI-bound extrachromosomal lacO plasmids can assemble kinetochore proteins and bind microtubules, resulting in their stable transmission for several cell generations even after eliminating CID-GFP-LacI. We conclude that CID is both necessary and sufficient to serve as an epigenetic centromere mark and nucleate heritable centromere function. 相似文献
993.
Within the bilaterally symmetric vertebrate body plan, many organs develop asymmetrically. Here, it is demonstrated that a cell adhesion molecule, N-cadherin, is one of the earliest proteins to be asymmetrically expressed in the chicken embryo and that its activity is required during gastrulation for proper establishment of the left-right axis. Blocking N-cadherin function randomizes heart looping and alters the expression of Snail and Pitx2, later components of the molecular cascade that regulate left-right asymmetry. However, the expression of other components of this cascade (Nodal and Lefty) was unchanged after blocking N-cadherin function, suggesting the existence of parallel pathways in the establishment of left-right morphogenesis. Here, the results suggest that N-cadherin-mediated cell adhesion events are required for establishment of left-right asymmetry. 相似文献
994.
Helgason A Pálsson S Gudbjartsson DF Kristjánsson T Stefánsson K 《Science (New York, N.Y.)》2008,319(5864):813-816
Previous studies have reported that related human couples tend to produce more children than unrelated couples but have been unable to determine whether this difference is biological or stems from socioeconomic variables. Our results, drawn from all known couples of the Icelandic population born between 1800 and 1965, show a significant positive association between kinship and fertility, with the greatest reproductive success observed for couples related at the level of third and fourth cousins. Owing to the relative socioeconomic homogeneity of Icelanders, and the observation of highly significant differences in the fertility of couples separated by very fine intervals of kinship, we conclude that this association is likely to have a biological basis. 相似文献
995.
996.
997.
Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease 总被引:57,自引:0,他引:57
A Wlodawer M Miller M Jaskólski B K Sathyanarayana E Baldwin I T Weber L M Selk L Clawson J Schneider S B Kent 《Science (New York, N.Y.)》1989,245(4918):616-621
The rational design of drugs that can inhibit the action of viral proteases depends on obtaining accurate structures of these enzymes. The crystal structure of chemically synthesized HIV-1 protease has been determined at 2.8 angstrom resolution (R factor of 0.184) with the use of a model based on the Rous sarcoma virus protease structure. In this enzymatically active protein, the cysteines were replaced by alpha-amino-n-butyric acid, a nongenetically coded amino acid. This structure, in which all 99 amino acids were located, differs in several important details from that reported previously by others. The interface between the identical subunits forming the active protease dimer is composed of four well-ordered beta strands from both the amino and carboxyl termini and residues 86 to 94 have a helical conformation. The observed arrangement of the dimer interface suggests possible designs for dimerization inhibitors. 相似文献
998.
Marta Crivos María Rosa Martínez María Lelia Pochettino Carolina Remorini Cynthia Saenz Anahí Sy 《Agriculture and Human Values》2004,21(2-3):111-125
Through the ethnographic record of the subsistence activities partially or completely performed in the domestic sphere in two Mbyá-Guaraní settlements in Misiones (Argentina), we outline factors important in describing the local natural environment. Data was collected through systematic observation and also through semi-structured interviews. Analysis indicates that the natural environment of the area is characterized by the indigenous community in several different ways. Thus, local people view the environment as made up of different “micro-environments,” and they consequently think of the elements that compose these “micro-environments” as having different, distinct characteristics. In the context of their daily activities, both these “micro-environments” and the elements that compose them are regarded as resources, in that they are viewed in terms of what is in them relevant to the subsistence of these groups in the rainforest. It is the intention of this study to initiate the systematic recording and processing of information on how these indigenous communities know and manage the natural resources available to them in their daily life. 相似文献
999.
Bakal C Linding R Llense F Heffern E Martin-Blanco E Pawson T Perrimon N 《Science (New York, N.Y.)》2008,322(5900):453-456
Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. Thus, genetic screens may not identify all the genes that regulate different biological processes. Moreover, although classical screening approaches have succeeded in providing parts lists of the essential components of signaling networks, they typically do not provide much insight into the hierarchical and functional relations that exist among these components. We describe a high-throughput screen in which we used RNA interference to systematically inhibit two genes simultaneously in 17,724 combinations to identify regulators of Drosophila JUN NH(2)-terminal kinase (JNK). Using both genetic and phosphoproteomics data, we then implemented an integrative network algorithm to construct a JNK phosphorylation network, which provides structural and mechanistic insights into the systems architecture of JNK signaling. 相似文献
1000.