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701.
Evidence for dynamically organized modularity in the yeast protein-protein interaction network 总被引:1,自引:0,他引:1
Han JD Bertin N Hao T Goldberg DS Berriz GF Zhang LV Dupuy D Walhout AJ Cusick ME Roth FP Vidal M 《Nature》2004,430(6995):88-93
In apparently scale-free protein-protein interaction networks, or 'interactome' networks, most proteins interact with few partners, whereas a small but significant proportion of proteins, the 'hubs', interact with many partners. Both biological and non-biological scale-free networks are particularly resistant to random node removal but are extremely sensitive to the targeted removal of hubs. A link between the potential scale-free topology of interactome networks and genetic robustness seems to exist, because knockouts of yeast genes encoding hubs are approximately threefold more likely to confer lethality than those of non-hubs. Here we investigate how hubs might contribute to robustness and other cellular properties for protein-protein interactions dynamically regulated both in time and in space. We uncovered two types of hub: 'party' hubs, which interact with most of their partners simultaneously, and 'date' hubs, which bind their different partners at different times or locations. Both in silico studies of network connectivity and genetic interactions described in vivo support a model of organized modularity in which date hubs organize the proteome, connecting biological processes--or modules--to each other, whereas party hubs function inside modules. 相似文献
702.
The Proterozoic aeon (2.5 to 0.54 billion years (Gyr) ago) marks the time between the largely anoxic world of the Archean (> 2.5 Gyr ago) and the dominantly oxic world of the Phanerozoic (< 0.54 Gyr ago). The course of ocean chemistry through the Proterozoic has traditionally been explained by progressive oxygenation of the deep ocean in response to an increase in atmospheric oxygen around 2.3 Gyr ago. This postulated rise in the oxygen content of the ocean is in turn thought to have led to the oxidation of dissolved iron, Fe(II), thus ending the deposition of banded iron formations (BIF) around 1.8 Gyr ago. An alternative interpretation suggests that the increasing atmospheric oxygen levels enhanced sulphide weathering on land and the flux of sulphate to the oceans. This increased rates of sulphate reduction, resulting in Fe(II) removal in the form of pyrite as the oceans became sulphidic. Here we investigate sediments from the approximately 1.8-Gyr-old Animikie group, Canada, which were deposited during the final stages of the main global period of BIF deposition. This allows us to evaluate the two competing hypotheses for the termination of BIF deposition. We use iron-sulphur-carbon (Fe-S-C) systematics to demonstrate continued ocean anoxia after the final global deposition of BIF and show that a transition to sulphidic bottom waters was ultimately responsible for the termination of BIF deposition. Sulphidic conditions may have persisted until a second major rise in oxygen between 0.8 to 0.58 Gyr ago, possibly reducing global rates of primary production and arresting the pace of algal evolution. 相似文献
703.
Deloukas P Earthrowl ME Grafham DV Rubenfield M French L Steward CA Sims SK Jones MC Searle S Scott C Howe K Hunt SE Andrews TD Gilbert JG Swarbreck D Ashurst JL Taylor A Battles J Bird CP Ainscough R Almeida JP Ashwell RI Ambrose KD Babbage AK Bagguley CL Bailey J Banerjee R Bates K Beasley H Bray-Allen S Brown AJ Brown JY Burford DC Burrill W Burton J Cahill P Camire D Carter NP Chapman JC Clark SY Clarke G Clee CM Clegg S Corby N Coulson A Dhami P Dutta I Dunn M Faulkner L Frankish A 《Nature》2004,429(6990):375-381
704.
Rajagopalan H Jallepalli PV Rago C Velculescu VE Kinzler KW Vogelstein B Lengauer C 《Nature》2004,428(6978):77-81
Aneuploidy, an abnormal chromosome number, has been recognized as a hallmark of human cancer for nearly a century; however, the mechanisms responsible for this abnormality have remained elusive. Here we report the identification of mutations in hCDC4 (also known as Fbw7 or Archipelago) in both human colorectal cancers and their precursor lesions. We show that genetic inactivation of hCDC4, by means of targeted disruption of the gene in karyotypically stable colorectal cancer cells, results in a striking phenotype associated with micronuclei and chromosomal instability. This phenotype can be traced to a defect in the execution of metaphase and subsequent transmission of chromosomes, and is dependent on cyclin E--a protein that is regulated by hCDC4 (refs 2-4). Our data suggest that chromosomal instability is caused by specific genetic alterations in a large fraction of human cancers and can occur before malignant conversion. 相似文献
705.
The quantum Hall effect arises from the interplay between localized and extended states that form when electrons, confined to two dimensions, are subject to a perpendicular magnetic field. The effect involves exact quantization of all the electronic transport properties owing to particle localization. In the conventional theory of the quantum Hall effect, strong-field localization is associated with a single-particle drift motion of electrons along contours of constant disorder potential. Transport experiments that probe the extended states in the transition regions between quantum Hall phases have been used to test both the theory and its implications for quantum Hall phase transitions. Although several experiments on highly disordered samples have affirmed the validity of the single-particle picture, other experiments and some recent theories have found deviations from the predicted universal behaviour. Here we use a scanning single-electron transistor to probe the individual localized states, which we find to be strikingly different from the predictions of single-particle theory. The states are mainly determined by Coulomb interactions, and appear only when quantization of kinetic energy limits the screening ability of electrons. We conclude that the quantum Hall effect has a greater diversity of regimes and phase transitions than predicted by the single-particle framework. Our experiments suggest a unified picture of localization in which the single-particle model is valid only in the limit of strong disorder. 相似文献
706.
707.
Cecchi C Liguri G Fiorillo C Bogani F Gambassi M Giannoni E Cirri P Baglioni S Ramponi G 《Cellular and molecular life sciences : CMLS》2004,61(14):1775-1784
An acylphosphatase (AcPase) overexpression study was carried out on SH-SY5Y neuroblastoma cells, using a
green fluorescent fusion protein (AcP-GFP), with GFP acting as a reporter protein. The cellular proliferation rate
was significantly reduced by overexpression of AcPase by a factor of ten. In contrast, clones transfected with two
inactive AcPase mutants showed a growth rate comparable to control cells. This suggests that AcPase catalyzes the
proliferative down-regulation. AcPase-overexpressing clones showed a physiological mortality rate as assessed by an
MTT reduction test and by evaluation of necrotic markers. DNA fragmentation analysis and assays of caspase-3 and
poly (ADP-ribose) polymerase (PARP)-active fragments showed no evidence of any apoptotic pattern. AcPase
overexpression led to a marked increase in PARP activity as well as Bcl-2 content; these are commonly up-regulated
during differentiative processes in neuronal cells. In fact, the typical differentiation marker,
growth-associated-protein 43, was significantly up-regulated. Microscopic observations also showed a clear
increase in the differentiative phenotype in AcPase-overexpressing cells. Our results clearly show that AcPase
plays a primary causative role in neuronal differentiation.Received 3 May 2004; accepted 25 May 2004 相似文献
708.
Involvement of penaeidins in defense reactions of the shrimp Litopenaeus stylirostris to a pathogenic vibrio 总被引:2,自引:0,他引:2
Munoz M Vandenbulcke F Garnier J Gueguen Y Bulet P Saulnier D Bachère E 《Cellular and molecular life sciences : CMLS》2004,61(7-8):961-972
The present study reports for the first time the involvement of an antimicrobial peptide in the defense reactions of a shrimp infected by a pathogenic Vibrio, Vibrio penaeicida. New members of the penaeidin family were characterized in the shrimp Litopenaeus stylirostris by RT-PCR and RACE-PCR from hemocyte total RNAs, and by mass spectrometry detection and immunolocalization of mature peptides in shrimp hemocytes. In infected shrimps, bacteria and penaeidin distribution colocalized in the gills and the lymphoid organ that represented the main infected sites. Moreover, the shrimp immune response to infection involved massive hemocyte recruitment to infection sites where released penaeidin may participate in the isolation and elimination of the bacteria, We show that the ability of the shrimps to circumvent shrimp infections is closely related to a recovery phase based on the hematopoietic process.Received 25 November 2003; received after revision 8 January 2004; accepted 21 January 2004 相似文献
709.
710.
Sex determination and gametogenesis are key processes in human reproduction, and any defect can lead to
infertility. We describe here the molecular mechanisms of male sex determination and testis formation; defects in
sex determination lead to a female phenotype despite the presence of a Y chromosome, more rarely to a male
phenotype with XX chromosomes, or to intersex phenotypes. Interestingly, these phenotypes are often associated
with other developmental malformations. In testis, spermatozoa are produced from renewable stem cells in a complex
differentiation process called spermatogenesis. Gene expression during spermatogenesis differs to a surprising
degree from gene expression in somatic cells, and we discuss here mechanistic differences and their effect on the
differentiation process and male fertility.Received 23 January 2004; received after revision 30 March 2004; accepted 6 April 2004 相似文献