In order to contribute to the structural basis for rational design of calmodulin (CaM) inhibitors, we analyzed the interaction of CaM with 14 classic antagonists and two compounds that do not affect CaM, using docking and molecular dynamics (MD) simulations, and the data were compared to available experimental data. The Ca2+-CaM-Ligands complexes were simulated 20 ns, with CaM starting in the “open” and “closed” conformations. The analysis of the MD simulations provided insight into the conformational changes undergone by CaM during its interaction with these ligands. These simulations were used to predict the binding free energies (ΔG) from contributions ΔH and ΔS, giving useful information about CaM ligand binding thermodynamics. The ΔG predicted for the CaM’s inhibitors correlated well with available experimental data as the r2 obtained was 0.76 and 0.82 for the group of xanthones. Additionally, valuable information is presented here: I) CaM has two preferred ligand binding sites in the open conformation known as site 1 and 4, II) CaM can bind ligands of diverse structural nature, III) the flexibility of CaM is reduced by the union of its ligands, leading to a reduction in the Ca2+-CaM entropy, IV) enthalpy dominates the molecular recognition process in the system Ca2+-CaM-Ligand, and V) the ligands making more extensive contact with the protein have higher affinity for Ca2+-CaM. Despite their limitations, docking and MD simulations in combination with experimental data continue to be excellent tools for research in pharmacology, toward a rational design of new drugs. 相似文献
Autophagy is mainly regulated by post-translational and lipid modifications of ATG proteins. In some scenarios, the induction of autophagy is accompanied by increased levels of certain ATG mRNAs such as MAP1LC3B/LC3B, ATG5 or ATG12. However, little is known about the regulation of ATG protein synthesis at the translational level. The cochaperone of the HSP70 system BAG3 (BCL2-associated athanogene 3) has been associated to LC3B lipidation through an unknown mechanism. In the present work, we studied how BAG3 controls autophagy in HeLa and HEK293 cells. Our results showed that BAG3 regulates the basal amount of total cellular LC3B protein by controlling its mRNA translation. This effect was apparently specific to LC3B because other ATG protein levels were not affected. BAG3 knockdown did not affect LC3B lipidation induced by nutrient deprivation or proteasome inhibition. We concluded that BAG3 maintains the basal amount of LC3B protein by controlling the translation of its mRNA in HeLa and HEK293 cells. 相似文献
Background: Large areas of heathland landscapes in Galicia, north-west Spain, have traditionally been extensively grazed by free-ranging cattle and wild ponies. Recently, a large reduction in the number of these larger herbivores has been observed, with unknown consequences for the habitat.
Aims: To evaluate the effects of grazing and herbivore density on plant diversity, community composition and vegetation structure of the endemic wet heathlands dominated by Erica mackayana in Galicia.
Methods: Field sampling of vascular plants, generalised linear models (GLMs), non-metric multidimensional distance scaling (NMDS).
Results: Grazed sites had significantly higher total and rare species richness and diversity than ungrazed sites. Higher densities of cattle resulted in lower numbers of rare species, while wild pony density had no effect on rare species richness. In grazed sites, vegetation was lower with greater variation in height, resulting in greater heterogeneity of the habitat. Precipitation and summer temperatures were related to plant diversity, mainly beta diversity. Soil organic matter negatively correlated with rare species.
Discussion: Grazing, mostly by wild ponies, was demonstrated to be positively related to plant diversity and vegetation structure. Lack of grazing or high cattle densities resulted in a negative effect on total and rare species richness and diversity. Future climate change may negatively affect heathland plant diversity. Galician wild ponies represent a unique case of sustainable management of a wild species and an invaluable cultural heritage. Moreover, they have a significant role in maintaining the endemic E. mackayana heathlands, what would justify specific conservation actions for these large herbivores. 相似文献
Naturally regenerating and restored second growth forests account for over 70% of tropical forest cover and provide key ecosystem services. Understanding climate change impacts on successional trajectories of these ecosystems is critical for developing effective large‐scale forest landscape restoration (FLR) programs. Differences in environmental conditions, species composition, dynamics, and landscape context from old growth forests may exacerbate climate impacts on second growth stands. We compile data from 112 studies on the effects of natural climate variability, including warming, droughts, fires, and cyclonic storms, on demography and dynamics of second growth forest trees and identify variation in forest responses across biomes, regions, and landscapes. Across studies, drought decreases tree growth, survival, and recruitment, particularly during early succession, but the effects of temperature remain unexplored. Shifts in the frequency and severity of disturbance alter successional trajectories and increase the extent of second growth forests. Vulnerability to climate extremes is generally inversely related to long‐term exposure, which varies with historical climate and biogeography. The majority of studies, however, have been conducted in the Neotropics hindering generalization. Effects of fire and cyclonic storms often lead to positive feedbacks, increasing vulnerability to climate extremes and subsequent disturbance. Fragmentation increases forests’ vulnerability to fires, wind, and drought, while land use and other human activities influence the frequency and intensity of fire, potentially retarding succession. Comparative studies of climate effects on tropical forest succession across biogeographic regions are required to forecast the response of tropical forest landscapes to future climates and to implement effective FLR policies and programs in these landscapes. 相似文献
Summary Species ofScelionidae, parasiting in eggs ofLymantria dispar (L.) are mentioned and the results of use of these parasites are added. A new egg-parasite of gipsy moth —Hadronotus lymantriae n.sp. — is described. A key to Scelionid egg-parasites living inLymantria dispar (L.) is given. Attention is drawn to the fact thatH. bernardi Manev. is a nomen nudum. Finally, the author discusses the phylogenetical and taxonomical internal relations inHadronotus Foerst.
Résumé L'auteur mentionne les différentes espèces de Scélionides parasites des œufs deLymantria dispar (L.) et rappelle les résultats obtenus par l'utilisation de ces parasites. Un nouveau parasite des œufs de ce Bombyx,Hadronotus lymantriae n. sp., est décrit. Il est montré en outre queH. bernardi Manev. doit être considérénomen nudum. Enfin l'auteur discute les relations phylogéniques et taxonomiques des espèces du genreHadronotus Foerst.
When recombinant DNA technology was developed more than 40 years ago, no one could have imagined the impact it would have on both society and the scientific community. In the field of genetic engineering, the most important tool developed was the plasmid vector. This technology has been continuously expanding and undergoing adaptations. Here, we provide a detailed view following the evolution of vectors built throughout the years destined to study microorganisms and their peculiarities, including those whose genomes can only be revealed through metagenomics. We remark how synthetic biology became a turning point in designing these genetic tools to create meaningful innovations. We have placed special focus on the tools for engineering bacteria and fungi (both yeast and filamentous fungi) and those available to construct metagenomic libraries. Based on this overview, future goals would include the development of modular vectors bearing standardized parts and orthogonally designed circuits, a task not fully addressed thus far. Finally, we present some challenges that should be overcome to enable the next generation of vector design and ways to address it. 相似文献