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81.
Derikx LC Vis R Meinders T Verdonschot N Tanck E 《Computer methods in biomechanics and biomedical engineering》2011,14(2):183-193
Although asymmetric yielding in bone is widely shown in experimental studies, previous case-specific non-linear finite element (FE) studies have mainly adopted material behaviour using the Von Mises yield criterion (VMYC), assuming equal bone strength in tension and compression. In this study, it was verified that asymmetric yielding in FE models can be captured using the Drucker-Prager yield criterion (DPYC), and can provide better results than simulations using the VMYC. A sensitivity analysis on parameters defining the DPYC (i.e. the degree of yield asymmetry and the yield stress settings) was performed, focusing on the effect on bone failure. In this study, the implementation of a larger degree of yield asymmetry improved the prediction of the fracture location; variations in the yield stress mainly affected the predicted failure force. We conclude that the implementation of asymmetric yielding in case-specific FE models improves the prediction of femoral bone strength. 相似文献
82.
Mahmood NA Biemans-Oldehinkel E Patzlaff JS Schuurman-Wolters GK Poolman B 《The Journal of biological chemistry》2006,281(40):29830-29839
The ATPase subunit of the osmoregulatory ATP-binding cassette transporter OpuA from Lactococcus lactis has a C-terminal extension, the tandem cystathionine beta-synthase (CBS) domain, which constitutes the sensor that allows the transporter to sense and respond to osmotic stress (Biemans-Oldehinkel, E., Mahmood, N. A. B. N., and Poolman, B. (2006) Proc. Natl. Acad. Sci. U. S. A. 103, 10624-10629). C-terminal of the tandem CBS domain is an 18-residue anionic tail (DIPDEDEVEEIEKEEENK). To investigate the ion specificity of the full transporter, we probed the activity of inside-out reconstituted wild-type OpuA and the anionic tail deletion mutant OpuADelta12; these molecules have the tandem CBS domains facing the external medium. At a mole fraction of 40% of anionic lipids in the membrane, the threshold ionic strength for activation of OpuA was approximately 0.15, irrespective of the electrolyte composition of the medium. At equivalent concentrations, bivalent cations (Mg(2+) and Ba(2+)) were more effective in activating OpuA than NH(4)(+), K(+), Na(+), or Li(+), consistent with an ionic strength-based sensing mechanism. Surprisingly, Rb(+) and Cs(+) were potent inhibitors of wild-type OpuA, and 0.1 mM RbCl was sufficient to completely inhibit the transporter even in the presence of 0.2 M KCl. Rb(+) and Cs(+) were no longer inhibitory in OpuADelta12, indicating that the anionic C-terminal tail participates in the formation of a binding site for large alkali metal ions. Compared with OpuADelta12, wild-type OpuA required substantially less potassium ions (the dominant ion under physiological conditions) for activation. Our data lend new support for the contention that the CBS module in OpuA constitutes the ionic strength sensor whose activity is modulated by the C-terminal anionic tail. 相似文献
83.
84.
Enzymatic and nonenzymatic functions of viral RNA-dependent RNA polymerases within oligomeric arrays
Jeannie F. Spagnolo Evan Rossignol Esther Bullitt Karla Kirkegaard 《RNA (New York, N.Y.)》2010,16(2):382-393
Few antivirals are effective against positive-strand RNA viruses, primarily because the high error rate during replication of these viruses leads to the rapid development of drug resistance. One of the favored current targets for the development of antiviral compounds is the active site of viral RNA-dependent RNA polymerases. However, like many subcellular processes, replication of the genomes of all positive-strand RNA viruses occurs in highly oligomeric complexes on the cytosolic surfaces of the intracellular membranes of infected host cells. In this study, catalytically inactive polymerases were shown to participate productively in functional oligomer formation and catalysis, as assayed by RNA template elongation. Direct protein transduction to introduce either active or inactive polymerases into cells infected with mutant virus confirmed the structural role for polymerase molecules during infection. Therefore, we suggest that targeting the active sites of polymerase molecules is not likely to be the best antiviral strategy, as inactivated polymerases do not inhibit replication of other viruses in the same cell and can, in fact, be useful in RNA replication complexes. On the other hand, polymerases that could not participate in functional RNA replication complexes were those that contained mutations in the amino terminus, leading to altered contacts in the folded polymerase and mutations in a known polymerase–polymerase interaction in the two-dimensional protein lattice. Thus, the functional nature of multimeric arrays of RNA-dependent RNA polymerase supplies a novel target for antiviral compounds and provides a new appreciation for enzymatic catalysis on membranous surfaces within cells. 相似文献
85.
Juan L. Gutirrez‐Fisac Esther Lpez Jose R. Banegas Auxiliadora Graciani Fernando Rodríguez‐Artalejo 《Obesity (Silver Spring, Md.)》2004,12(4):710-715
Objective: To estimate the prevalence of obesity and overweight in the older adult population in Spain by sex, age, and educational level. Research Methods and Procedures: A cross‐sectional study was carried out in 2001 in a sample of 4009 persons representative of the noninstitutionalized population ≥60 years of age. Anthropometric measurements (BMI and waist circumference) were obtained using standardized techniques and equipment. Overweight was considered at a BMI of 25 to 29.9 kg/m2 and obesity at a BMI of ≥30 kg/m2. Central obesity was considered at a waist circumference of >102 cm in men and >88 cm in women. Results: The mean BMI was 28.2 kg/m2 in men and 29.3 kg/m2 in women. The prevalence of overweight and obesity in men was 49% and 31.5%, respectively. The corresponding percentages in women were 39.8% and 40.8%. The prevalence of obesity was higher in persons with no education than in those with third level education (i.e., university studies), especially among women (41.8% vs. 17.5%). The prevalence of central obesity was 48.4% in men and 78.4% in women. Differences by educational level were seen in only women, in whom the prevalence of central obesity was 80.9% in those with no education and 59% in those with third‐level education. Discussion: The prevalence of overweight and obesity in the Spanish adult elderly population is very high. Some other populations show similar prevalences, especially in Mediterranean countries. Socioeconomic conditions in Spain during the years these cohorts were born may partly explain the high‐frequency of obesity. 相似文献
86.
Leeuwenburgh C Gurley CM Strotman BA Dupont-Versteegden EE 《American journal of physiology. Regulatory, integrative and comparative physiology》2005,288(5):R1288-R1296
Muscle atrophy is associated with a loss of muscle fiber nuclei, most likely through apoptosis. We investigated age-related differences in the extent of apoptosis in soleus muscle of young (6 mo) and old (32 mo) male Fischer 344 x Brown Norway rats subjected to acute disuse atrophy induced by 14 days of hindlimb suspension (HS). HS-induced atrophy (reduction in muscle weight and cross-sectional area) was associated with loss of myofiber nuclei in soleus muscle of young, but not old, rats. This resulted in a significant decrease in the myonuclear domain (cross-sectional area per nucleus) in young and old rats, with changes being more pronounced in old animals. Levels of apoptosis (TdT-mediated dUTP nick end labeling and DNA fragmentation) were higher in soleus muscles of old control rats than young animals. Levels were significantly increased with HS in young and old rats, with the greatest changes in old animals. Caspase-3 activity in soleus muscle tended to be increased with age, but changes were not statistically significant (P=0.052). However, with HS, caspase-3 activity significantly increased in young, but not old, rats. Immunohistochemistry showed that the proapoptotic endonuclease G (EndoG, a mitochondrion-specific nuclease) was localized in the subsarcolemmal mitochondria in control muscles, and translocation to the nucleus occurred in old, but not young, control animals. There was no difference between EndoG total protein content in young and old control rats, but EndoG increased almost fivefold in soleus muscle of old, but not young, rats after HS. These results show that deregulation of myonuclear number occurs in old skeletal muscle and that the pathways involved in apoptosis are distinct in young and old muscles. Apoptosis in skeletal muscle is partly mediated by the subsarcolemmal mitochondria through EndoG translocation to the nucleus in response to HS. 相似文献
87.
Javier M. Rodríguez Francisco J. Chichón Esther Martín-Forero Fernando González-Camacho José L. Carrascosa José R. Castón Daniel Luque 《PLoS pathogens》2014,10(5)
The infectivity of rotavirus, the main causative agent of childhood diarrhea, is dependent on activation of the extracellular viral particles by trypsin-like proteases in the host intestinal lumen. This step entails proteolytic cleavage of the VP4 spike protein into its mature products, VP8* and VP5*. Previous cryo-electron microscopy (cryo-EM) analysis of trypsin-activated particles showed well-resolved spikes, although no density was identified for the spikes in uncleaved particles; these data suggested that trypsin activation triggers important conformational changes that give rise to the rigid, entry-competent spike. The nature of these structural changes is not well understood, due to lack of data relative to the uncleaved spike structure. Here we used cryo-EM and cryo-electron tomography (cryo-ET) to characterize the structure of the uncleaved virion in two model rotavirus strains. Cryo-EM three-dimensional reconstruction of uncleaved virions showed spikes with a structure compatible with the atomic model of the cleaved spike, and indistinguishable from that of digested particles. Cryo-ET and subvolume average, combined with classification methods, resolved the presence of non-icosahedral structures, providing a model for the complete structure of the uncleaved spike. Despite the similar rigid structure observed for uncleaved and cleaved particles, trypsin activation is necessary for successful infection. These observations suggest that the spike precursor protein must be proteolytically processed, not to achieve a rigid conformation, but to allow the conformational changes that drive virus entry. 相似文献
88.
Mario M. Müller Esther Klaile Olga Vorontsova Bernhard B. Singer Bj?rn ?brink 《The Journal of cell biology》2009,187(4):569-581
Carcinoembryonic antigen (CEA)–related cell adhesion molecule 1 (CAM1 [CEACAM1]) mediates homophilic cell adhesion and regulates signaling. Although there is evidence that CEACAM1 binds and activates SHP-1, SHP-2, and c-Src, knowledge about the mechanism of transmembrane signaling is lacking. To analyze the regulation of SHP-1/SHP-2/c-Src binding, we expressed various CFP/YFP-tagged CEACAM1 isoforms in epithelial cells. The supramolecular organization of CEACAM1 was examined by cross-linking, coclustering, coimmunoprecipitation, and fluorescence resonance energy transfer. SHP-1/SHP-2/c-Src binding was monitored by coimmunoprecipitation and phosphotyrosine-induced recruitment to CEACAM1-L in cellular monolayers. We find that trans-homophilic CEACAM1 binding induces cis-dimerization by an allosteric mechanism transmitted by the N-terminal immunoglobulin-like domain. The balance of SHP-2 and c-Src binding is dependent on the monomer/dimer equilibrium of CEACAM1-L and is regulated by trans-binding, whereas SHP-1 does not bind under physiological conditions. CEACAM1-L homodimer formation is reduced by coexpression of CEACAM1-S and modulated by antibody ligation. These data suggest that transmembrane signaling by CEACAM1 operates by alteration of the monomer/dimer equilibrium, which leads to changes in the SHP-2/c-Src–binding ratio. 相似文献
89.
Esther Giménez Manuel Melendo Francisco Valle Francisco Gómez-Mercado Eusebio Cano 《Biodiversity and Conservation》2004,13(14):2641-2660
The south of the Iberian Peninsula, with an altitudinal range varying from sea level to 3482m and annual average rainfall ranging from 206 to 2223mm, has 516 vascular endemic species or subspecies, that is, an endemicity rate of 13%. This survey deals with parameters such as species richness, originality, life forms and dispersal modes of these plants, in relation to altitudinal and rainfall gradients. Although most of the endemic plants occur between 600 and 1400m a.s.l. and in the range of 600–1000mm annual average rainfall, floristic originality (rate of endemic taxa per area unit) increases exponentially with altitude. The biological spectrum of this endemic flora does not follow the usual patterns observed either in local floras in the south of the Iberian Peninsula or in other regions of the Mediterranean Basin. Chamaephytes (46.08%) and hemicryptophytes (31.37%) are very abundant, whereas therophytes (11.96%) and phanerophytes (0.98%) are comparatively rare. There is a statistically significant correlation between life form and both altitudinal and rainfall gradients. Chamaephytes reach their highest density rates within 1400–2000m a.s.l., but these records tend to decrease as rainfall rates increase. Abundance of hemicryptophytes is directly dependent on rainfall rates and inversely dependent on temperature. The altitudinal distribution pattern of therophytes is opposite to that of hemicryptophytes, but there is no clear correlation as far as rainfall gradient is concerned. Considering both the endemic plants as a whole and each of the life form groups, the relationships between the dispersal modes used and the altitudinal and rainfall gradients are analysed. Up to 44.51% of the endemic plants do not present evident adaptations to promote the dispersion of their diaspores. However, only in the group of therophytes, whose occurrence is positively related to areas of minor altitude, does this difficulty of dispersion play a significant role in the maintenance of stenochory. 相似文献
90.
Priya A. Debisarun Katharina L. Gssling Ozlem Bulut Gizem Kilic Martijn Zoodsma Zhaoli Liu Marina Oldenburg Nadine Rüchel Bowen Zhang Cheng-Jian Xu Patrick Struycken Valerie A. C. M. Koeken Jorge Domínguez-Andrs Simone J. C. F. M. Moorlag Esther Taks Philipp N. Ostermann Lisa Müller Heiner Schaal Ortwin Adams Arndt Borkhardt Jaap ten Oever Reinout van Crevel Yang Li Mihai G. Netea 《PLoS pathogens》2021,17(10)