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251.
One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 A resolution and compare it with the structure of the normal c-Ha-ras protein. One of the major differences is that the loop of the transforming ras protein that binds the beta-phosphate of the guanine nucleotide is enlarged. Such a change in the 'catalytic site' conformation could explain the reduced GTPase activity of the mutant, which keeps the protein in the GTP bound 'signal on' state for a prolonged period time, ultimately causing cell transformation.  相似文献   
252.
253.
This paper deals with the analysis of the number of tourists travelling to the Canary Islands by means of using different seasonal statistical models. Deterministic and stochastic seasonality is considered. For the latter case, we employ seasonal unit roots and seasonally fractionally integrated models. As a final approach, we also employ a model with possibly different orders of integration at zero and the seasonal frequencies. All these models are compared in terms of their forecasting ability in an out‐of‐sample experiment. The results in the paper show that a simple deterministic model with seasonal dummy variables and AR(1) disturbances produce better results than other approaches based on seasonal fractional and integer differentiation over short horizons. However, increasing the time horizon, the results cannot distinguish between the model based on seasonal dummies and another using fractional integration at zero and the seasonal frequencies. Copyright © 2008 John Wiley & Sons, Ltd.  相似文献   
254.
To locate their hosts, parasitic wasps can 'eavesdrop' on the intraspecific chemical communications of their insect hosts. Here we describe an example in which the information exploited by the parasitic wasp Trichogramma brassicae is a butterfly anti-aphrodisiac that is passed from male to female Pieris brassicae butterflies during mating, to render them less attractive to conspecific males. When the tiny wasp detects the odour of a mated female butterfly, it rides on her (Fig. 1) to her egg-laying sites and then parasitizes the freshly laid eggs. If this fascinating strategy is widespread in nature, it could severely constrain the evolution of sexual communication between hosts.  相似文献   
255.
The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 stable Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees ). The asteroid 617 Patroclus is the only known binary Trojan. The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system's centre of mass, describing a roughly circular orbit. Using this orbital information, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8(- 0.1)+0.2 g cm(-3). The components of 617 Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the Solar System.  相似文献   
256.
Ye JZ  de Lange T 《Nature genetics》2004,36(6):618-623
Telomere length in humans is partly controlled by a feedback mechanism in which telomere elongation by telomerase is limited by the accumulation of the TRF1 complex at chromosome ends. TRF1 itself can be inhibited by the poly(ADP-ribose) polymerase (PARP) activity of its interacting partner tankyrase 1, which abolishes its DNA binding activity in vitro and removes the TRF1 complex from telomeres in vivo. Here we report that the inhibition of TRF1 by tankyrase is in turn controlled by a second TRF1-interacting factor, TIN2 (ref. 6). Partial knockdown of TIN2 by small hairpin RNA in a telomerase-positive cell line resulted in telomere elongation, which is typical of reduced TRF1 function. Transient inhibition of TIN2 with small interfering RNA led to diminished telomeric TRF1 signals. This effect could be reversed with the PARP inhibitor 3-aminobenzamide and did not occur in cells overexpressing a PARP-dead mutant of tankyrase 1. TIN2 formed a ternary complex with TRF1 and tankyrase 1 and stabilized their interaction, an effect also observed with the PARP-dead mutant of tankyrase 1. In vitro, TIN2 protected TRF1 from poly(ADP-ribosyl)ation by tankyrase 1 without affecting tankyrase 1 automodification. These data identify TIN2 as a PARP modulator in the TRF1 complex and can explain how TIN2 contributes to the regulation of telomere length.  相似文献   
257.
In order to maximize their use of light energy in photosynthesis, plants have molecules that act as light-harvesting antennae, which collect light quanta and deliver them to the reaction centres, where energy conversion into a chemical form takes place. The functioning of the antenna responds to the extreme changes in the intensity of sunlight encountered in nature. In shade, light is efficiently harvested in photosynthesis. However, in full sunlight, much of the energy absorbed is not needed and there are vitally important switches to specific antenna states, which safely dissipate the excess energy as heat. This is essential for plant survival, because it provides protection against the potential photo-damage of the photosynthetic membrane. But whereas the features that establish high photosynthetic efficiency have been highlighted, almost nothing is known about the molecular nature of the dissipative states. Recently, the atomic structure of the major plant light-harvesting antenna protein, LHCII, has been determined by X-ray crystallography. Here we demonstrate that this is the structure of a dissipative state of LHCII. We present a spectroscopic analysis of this crystal form, and identify the specific changes in configuration of its pigment population that give LHCII the intrinsic capability to regulate energy flow. This provides a molecular basis for understanding the control of photosynthetic light-harvesting.  相似文献   
258.
Thoracic aortic aneurysms and dissections are a main feature of connective tissue disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis. We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused by mutations in SMAD3. This gene encodes a member of the TGF-β pathway that is essential for TGF-β signal transmission. SMAD3 mutations lead to increased aortic expression of several key players in the TGF-β pathway, including SMAD3. Molecular diagnosis will allow early and reliable identification of cases and relatives at risk for major cardiovascular complications. Our findings endorse the TGF-β pathway as the primary pharmacological target for the development of new treatments for aortic aneurysms and osteoarthritis.  相似文献   
259.
Summary Ethidium bromide was fed toD. melanogaster andD. simulans males in order to test its toxic capacity and potency for the induction of dominant lethals. Our results show that ethidium bromide has a high toxicity and likewise produces dominant lethals to a significant extent in both species, but more effectively inD. melanogaster.  相似文献   
260.
Summary Furocaulerpin, an acetylenic sesquiterpenoid possessing a furan ring, has been isolated from the marine algaCaulerpa prolifera, and its stereostructure elucidated mainly on the basis of physico-chemical data.This work was carried out in the frame work of the Progetto Finalizzato per l'Oceanografia e i Fondi Marini, CNR, Rome. Thanks are due to the Centro di Metodologie Chimico-Fisiche of the University of Naples (Mr I. Giudicianni) for the determination of PMR-spectra.  相似文献   
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