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951.
952.
Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine “hot spots” involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a “conformational selection model” of the Hsp90 mechanism, whereby the protein may exist in a dynamic equilibrium between different conformational states available on the energy landscape and binding of a specific partner can bias the equilibrium toward functionally relevant complexes. 相似文献
953.
Giulia Maurizi Antonella Poloni Domenico Mattiucci Spartaco Santi Angela Maurizi Valerio Izzi Angelica Giuliani Stefania Mancini Maria Cristina Zingaretti Jessica Perugini Ilenia Severi Massimo Falconi Marco Vivarelli Maria Rita Rippo Silvia Corvera Antonio Giordano Pietro Leoni Saverio Cinti 《Journal of cellular physiology》2017,232(10):i-i
954.
Arturo Nicola Natali Emanuele Luigi Carniel Chiara Giulia Fontanella Alessandro Frigo Silvia Todros Alessandro Rubini Giulia Maria De Benedictis Maria Angela Cerruto Walter Artibani 《Biomechanics and modeling in mechanobiology》2017,16(2):439-447
Urinary incontinence, often related to sphincter damage, is found in male patients, leading to a miserable quality of life and to huge costs for the healthcare system. The most effective surgical solution currently considered for men is the artificial urinary sphincter that exerts a pressure field on the urethra, occluding the duct. The evaluation of this device is currently based on clinical and surgical competences. The artificial sphincter design and mechanical action can be investigated by a biomechanical model of the urethra under occlusion, evaluating the interaction between tissues and prosthesis. A specific computational approach to urethral mechanics is here proposed, recalling the results of previous biomechanical experimental investigation. In this preliminary analysis, the horse urethra is considered, in the light of a significant correlation with human and in consideration of the relevant difficulty to get to human samples, which anyway represents the future advance. Histological data processing allow for the definition of a virtual and a subsequent finite element model of a urethral section. A specific hyperelastic formulation is developed to characterize the nonlinear mechanical behavior. The inverse analysis of tensile tests on urethra samples leads to the definition of preliminary constitutive parameters. The parameters are further refined by the computational analysis of inflation tests carried out on the entire urethral structure. The results obtained represent, in the light of the correlation reported, a valid preliminary support for the information to be assumed for prosthesis design, integrating surgical and biomechanical competences. 相似文献
955.
Insight into the roles of selection in speciation from genomic patterns of divergence and introgression in secondary contact in venomous rattlesnakes 下载免费PDF全文
Drew R. Schield Richard H. Adams Daren C. Card Blair W. Perry Giulia M. Pasquesi Tereza Jezkova Daniel M. Portik Audra L. Andrew Carol L. Spencer Elda E. Sanchez Matthew K. Fujita Stephen P. Mackessy Todd A. Castoe 《Ecology and evolution》2017,7(11):3951-3966
Investigating secondary contact of historically isolated lineages can provide insight into how selection and drift influence genomic divergence and admixture. Here, we studied the genomic landscape of divergence and introgression following secondary contact between lineages of the Western Diamondback Rattlesnake (Crotalus atrox) to determine whether genomic regions under selection in allopatry also contribute to reproductive isolation during introgression. We used thousands of nuclear loci to study genomic differentiation between two lineages that have experienced recent secondary contact following isolation, and incorporated sampling from a zone of secondary contact to identify loci that are resistant to gene flow in hybrids. Comparisons of patterns of divergence and introgression revealed a positive relationship between allelic differentiation and resistance to introgression across the genome, and greater‐than‐expected overlap between genes linked to lineage‐specific divergence and loci that resist introgression. Genes linked to putatively selected markers were related to prominent aspects of rattlesnake biology that differ between populations of Western Diamondback rattlesnakes (i.e., venom and reproductive phenotypes). We also found evidence for selection against introgression of genes that may contribute to cytonuclear incompatibility, consistent with previously observed biased patterns of nuclear and mitochondrial alleles suggestive of partial reproductive isolation due to cytonuclear incompatibilities. Our results provide a genome‐scale perspective on the relationships between divergence and introgression in secondary contact that is relevant for understanding the roles of selection in maintaining partial isolation of lineages, causing admixing lineages to not completely homogenize. 相似文献
956.
Species partitioning in a temperate mountain chain: Segregation by habitat vs. interspecific competition 下载免费PDF全文
Giulia Bastianelli Brendan A. Wintle Elizabeth H. Martin Javier Seoane Paola Laiolo 《Ecology and evolution》2017,7(8):2685-2696
Disentangling the relative influence of the environment and biotic interactions in determining species coexistence patterns is a major challenge in ecology. The zonation occurring along elevation gradients, or at bioclimatic contact zones, offers a good opportunity to improve such understanding because the small scale at which the partitioning occurs facilitates inference based on experiments and ecological modelling. We studied the influence of abiotic gradients, habitat types, and interspecific competition in determining the spatial turnover between two pipit and two bunting species in NW Spain. We explored two independent lines of evidence to draw inference about the relative importance of environment and biotic interactions in driving range partitioning along elevation, latitude, and longitude. We combined occurrence data with environmental data to develop joint species distribution models (JSDM), in order to attribute co‐occurrence (or exclusion) to shared (or divergent) environmental responses and to interactions (attraction or exclusion). In the same region, we tested for interference competition by means of playback experiments in the contact zone. The JSDMs highlighted different responses for the two species pairs, although we did not find direct evidence of interspecific aggressiveness in our playback experiments. In pipits, partitioning was explained by divergent climate and habitat requirements and also by the negative correlations between species not explained by the environment. This significant residual correlation may reflect forms of competition others than direct interference, although we could not completely exclude the influence of unmeasured environmental predictors. When bunting species co‐occurred, it was because of shared habitat preferences, and a possible limitation to dispersal might cause their partitioning. Our results indicate that no single mechanism dominates in driving the distribution of our study species, but rather distributions are determined by the combination of many small forces including biotic and abiotic determinants of niche, whose relative strengths varied among species. 相似文献
957.
Immune responses induced by oligogalacturonides are differentially affected by AvrPto and loss of BAK1/BKK1 and PEPR1/PEPR2 下载免费PDF全文
Matteo Gravino Federica Locci Silvio Tundo Felice Cervone Daniel Valentin Savatin Giulia De Lorenzo 《Molecular Plant Pathology》2017,18(4):582-595
Plants possess an innate immune system capable of restricting invasion by most potential pathogens. At the cell surface, the recognition of microbe‐associated molecular patterns (MAMPs) and/or damage‐associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs) represents the first event for the prompt mounting of an effective immune response. Pathogens have evolved effectors that block MAMP‐triggered immunity. The Pseudomonas syringae effector AvrPto abolishes immunity triggered by the peptide MAMPs flg22 and elf18, derived from the bacterial flagellin and elongation factor Tu, respectively, by inhibiting the kinase function of the corresponding receptors FLS2 and EFR, as well as their co‐receptors BAK1 and BKK1. Oligogalacturonides (OGs), a well‐known class of DAMPs, are oligomers of α‐1,4‐linked galacturonosyl residues, released on partial degradation of the plant cell wall homogalacturonan. We show here that AvrPto affects only a subset of the OG‐triggered immune responses and that, among these responses, only a subset is affected by the concomitant loss of BAK1 and BKK1. However, the antagonistic effect on auxin‐related responses is not affected by either AvrPto or the loss of BAK1/BKK1. These observations reveal an unprecedented complexity among the MAMP/DAMP response cascades. We also show that the signalling system mediated by Peps, another class of DAMPs, and their receptors PEPRs, contributes to OG‐activated immunity. We hypothesize that OGs are sensed through multiple and partially redundant perception/transduction complexes, some targeted by AvrPto, but not necessarily comprising BAK1 and BKK1. 相似文献
958.
Carmine Mancone Alessio Grimaldi Giulia Refolo Isabella Abbate Gabriella Rozera Dario Benelli Gian Maria Fimia Vincenzo Barnaba Marco Tripodi Mauro Piacentini Fabiola Ciccosanti 《Proteome science》2017,15(1):18
Background
Changes in iron metabolism frequently accompany HIV-1 infection. However, while many clinical and in vitro studies report iron overload exacerbates the development of infection, many others have found no correlation. Therefore, the multi-faceted role of iron in HIV-1 infection remains enigmatic.Methods
RT-qPCR targeting the LTR region, gag, Tat and Rev were performed to measure the levels of viral RNAs in response to iron overload. Spike-in SILAC proteomics comparing i) iron-treated, ii) HIV-1-infected and iii) HIV-1-infected/iron treated T lymphocytes was performed to define modifications in the host cell proteome. Data from quantitative proteomics were integrated with the HIV-1 Human Interaction Database for assessing any viral cofactors modulated by iron overload in infected T lymphocytes.Results
Here, we demonstrate that the iron overload down-regulates HIV-1 gene expression by decreasing the levels of viral RNAs. In addition, we found that iron overload modulates the expression of many viral cofactors. Among them, the downregulation of the REV cofactor eIF5A may correlate with the iron-induced inhibition of HIV-1 gene expression. Therefore, we demonstrated that eiF5A downregulation by shRNA resulted in a significant decrease of Nef levels, thus hampering HIV-1 replication.Conclusions
Our study indicates that HIV-1 cofactors influenced by iron metabolism represent potential targets for antiretroviral therapy and suggests eIF5A as a selective target for drug development.959.
Francesco Paoli Leonardo Marianelli Giulia Torrini Giuseppe Mazza Claudia Benvenuti Giovanni Bosio 《Biocontrol Science and Technology》2017,27(3):439-444
The scarab beetle Popillia japonica, a pest native to northern Japan, has been recently found in Italy. Entomopathogenic nematodes are useful for biological control of this invasive insect. Previous work showed that 1st and 2nd larval stages are more susceptible to nematodes than 3rd instars. We tested the effectiveness of Heterorhabditis bacteriophora in the laboratory against P. japonica 3rd instars. Experiments were conducted in Italy with larvae field collected in the fall, winter and spring, showing a significant decrease in effectiveness from the fall to spring. 相似文献
960.