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Iacoboni M Molnar-Szakacs I Gallese V Buccino G Mazziotta JC Rizzolatti G 《PLoS biology》2005,3(3):e79
Understanding the intentions of others while watching their actions is a fundamental building block of social behavior. The neural and functional mechanisms underlying this ability are still poorly understood. To investigate these mechanisms we used functional magnetic resonance imaging. Twenty-three subjects watched three kinds of stimuli: grasping hand actions without a context, context only (scenes containing objects), and grasping hand actions performed in two different contexts. In the latter condition the context suggested the intention associated with the grasping action (either drinking or cleaning). Actions embedded in contexts, compared with the other two conditions, yielded a significant signal increase in the posterior part of the inferior frontal gyrus and the adjacent sector of the ventral premotor cortex where hand actions are represented. Thus, premotor mirror neuron areas—areas active during the execution and the observation of an action—previously thought to be involved only in action recognition are actually also involved in understanding the intentions of others. To ascribe an intention is to infer a forthcoming new goal, and this is an operation that the motor system does automatically. 相似文献
164.
Islam MT Majoros IJ Baker JR 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,828(1-2):21-26
6-OXO, a new nutritional supplement commercially available on the internet, is sold as an aromatase-inhibitor and contains androst-4-ene-3,6,17-trione as active ingredient. This anabolic steroid is a prohibited substance in sports. Androst-4-ene-3,6,17-trione is metabolised to androst-4-ene-6alpha-ol-3,17-dione and androst-4-ene-6alpha,17beta-diol-3-one. A fast, sensitive and accurate LC/MS method was developed and validated for the quantification of androst-4-ene-3,6,17-trione and its metabolites in urine. The method is capable of determining the stereochemical position of the hydroxy-group at C-6 of the metabolites and consists of a liquid-liquid extraction step with diethylether after enzymatic hydrolysis, followed by separation on a reversed phase column. Ionisation of the analytes is carried out using atmospheric pressure chemical ionisation. The limit of quantification of the method was 5 ng/mL for all compounds. The accuracy ranged from 14.8 to 1.3% for androst-4-ene-3,6,17-trione, 9.4 to 1.6% for androst-4-ene-6alpha-ol-3,17-dione and 4.1 to 3.2% for androst-4-ene-6alpha,17beta-diol-3-one in the range of 5-1000 ng/mL. Using this method androst-4-ene-6alpha-ol-3,17-dione was identified as a major urinary metabolite, whereas androst-4-ene-6alpha,17beta-diol-3-one as a minor metabolite. While the parent compound is predominantly excreted in conjugated form, both metabolites are solely excreted as conjugates. 相似文献
165.
Botos I Melnikov EE Cherry S Khalatova AG Rasulova FS Tropea JE Maurizi MR Rotanova TV Gustchina A Wlodawer A 《Journal of structural biology》2004,146(1-2):113-122
The crystal structure of the small, mostly helical alpha domain of the AAA+ module of the Escherichia coli ATP-dependent protease Lon has been solved by single isomorphous replacement combined with anomalous scattering and refined at 1.9A resolution to a crystallographic R factor of 17.9%. This domain, comprising residues 491-584, was obtained by chymotrypsin digestion of the recombinant full-length protease. The alpha domain of Lon contains four alpha helices and two parallel strands and resembles similar domains found in a variety of ATPases and helicases, including the oligomeric proteases HslVU and ClpAP. The highly conserved "sensor-2" Arg residue is located at the beginning of the third helix. Detailed comparison with the structures of 11 similar domains established the putative location of the nucleotide-binding site in this first fragment of Lon for which a crystal structure has become available. 相似文献
166.
A type V myosin (Myo2p) and a Rab-like G-protein (Ypt11p) are required for retention of newly inherited mitochondria in yeast cells during cell division 下载免费PDF全文
Two actin-dependent force generators contribute to mitochondrial inheritance: Arp2/3 complex and the myosin V Myo2p (together with its Rab-like binding partner Ypt11p). We found that deletion of YPT11, reduction of the length of the Myo2p lever arm (myo2-Delta6IQ), or deletion of MYO4 (the other yeast myosin V), had no effect on mitochondrial morphology, colocalization of mitochondria with actin cables, or the velocity of bud-directed mitochondrial movement. In contrast, retention of mitochondria in the bud was compromised in YPT11 and MYO2 mutants. Retention of mitochondria in the bud tip of wild-type cells results in a 60% decrease in mitochondrial movement in buds compared with mother cells. In ypt11Delta mutants, however, the level of mitochondrial motility in buds was similar to that observed in mother cells. Moreover, the myo2-66 mutant, which carries a temperature-sensitive mutation in the Myo2p motor domain, exhibited a 55% decrease in accumulation of mitochondria in the bud tip, and an increase in accumulation of mitochondria at the retention site in the mother cell after shift to restrictive temperatures. Finally, destabilization of actin cables and the resulting delocalization of Myo2p from the bud tip had no significant effect on the accumulation of mitochondria in the bud tip. 相似文献
167.
We performed a docking study followed by a 500-ps molecular dynamics simulation of R-state human adult hemoglobin (HbA) complexed to different heterotropic effectors [2,3-diphosphoglycerate (DPG), inositol hexaphosphate (IHP), and 2-[4-[(3,5-dichlorophenylcarbamoyl)-]methyl]-phenoxy]-2-methylpropionic acid (RSR13)) to propose a molecular basis for recently reported interactions of effectors with oxygenated hemoglobin. The simulations were carried out with counterions and explicit solvation. As reported for T-state HbA, the effector binding sites are also located in the central cavity of the R-state and differ depending on effector anionic character. DPG and IHP bind between the alpha-subunits and the RSR13 site spans the alpha1-, alpha2- and beta2-subunits. The generated models provide the first report of the molecular details of R-state HbA bound to heterotropic effectors. 相似文献
168.
Botos I Melnikov EE Cherry S Kozlov S Makhovskaya OV Tropea JE Gustchina A Rotanova TV Wlodawer A 《Journal of molecular biology》2005,351(1):144-157
The atomic-resolution crystal structure of the proteolytic domain (P-domain, residues 415-621) of Archaeoglobus fulgidus B-type Lon protease (wtAfLonB) and the structures of several mutants have revealed significant differences in the conformation of the active-site residues when compared to other known Lon P-domains, despite the conservation of the overall fold. The catalytic Ser509 is facing the solvent and is distant from Lys552, the other member of the catalytic dyad. Instead, the adjacent Asp508 forms an ion pair with the catalytic lysine residue. Glu506, an analog of the putative third catalytic residue from a related Methanococcus jannaschii LonB, also faces the solvent and does not interact with the catalytic dyad. We have established that full-length wtAfLonB is proteolytically active in an ATP-dependent manner. The loss of enzymatic activity of the S509A mutant confirms the functional significance of this residue, while retention of considerable level of activity by the D508A and E506A mutants rules out their critical involvement in catalysis. In contrast to the full-length enzymes, all individually purified P-domains (wild-type and mutants) were inactive, and the mutations had no influence on the active-site structure. These findings raise the possibility that, although isolated proteolytic domains of both AfLonB and E.coli LonA are able to assemble into expected functional hexamers, the presence of the other domains, as well as substrate binding, may be needed to stabilize the productive conformation of their active sites. Thus, the observed conformational variability may reflect the differences in the stability of active-site structures for the proteolytic counterparts of single-chain Lon versus independently folded proteolytic subunits of two-chain AAA+ proteases. 相似文献
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