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61.
Franco Chimenti Daniela Secci Adriana Bolasco Paola Chimenti Arianna Granese Simone Carradori Elias Maccioni M. Cristina Cardia Matilde Yáñez Francisco Orallo Stefano Alcaro Francesco Ortuso Roberto Cirilli Rosella Ferretti Simona Distinto Johannes Kirchmair Thierry Langer 《Bioorganic & medicinal chemistry》2010,18(14):5063-5070
The present study reports on synthesis in high yields (70–99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1–45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds. 相似文献
62.
Daniel S. Maynard J. Timothy Wootton Carlos A. Servn Stefano Allesina 《Ecology letters》2019,22(6):1028-1037
Coexistence in ecological communities is governed largely by the nature and intensity of species interactions. Countless studies have proposed methods to infer these interactions from empirical data, yet models parameterised using such data often fail to recover observed coexistence patterns. Here, we propose a method to reconcile empirical parameterisations of community dynamics with species‐abundance data, ensuring that the predicted equilibrium is consistent with the observed abundance distribution. To illustrate the approach, we explore two case studies: an experimental freshwater algal community and a long‐term time series of displacement in an intertidal community. We demonstrate how our method helps recover observed coexistence patterns, capture the core dynamics of the system, and, in the latter case, predict the impacts of experimental extinctions. Collectively, these results demonstrate an intuitive approach for reconciling observed and empirical data, improving our ability to explore the links between species interactions and coexistence in natural systems. 相似文献
63.
The dynamic evolution of the PrP(C) from its NMR-derived conformation to a beta-sheet-rich, aggregation-prone conformation is studied through all-atom, explicit solvent molecular dynamics in different temperature and pH conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach aimed at identifying the key residues for the stabilization and folding of the protein. It is shown that under native conditions the stabilization energy is concentrated in regions of the helices H1 and H3, whereas under misfolding conditions (low pH, high temperature, or mutations in selected sites) it is spread out over helix H2. Misfolding appears to be a rearrangement of the chain that disrupts most of the native secondary structure of the protein, producing some beta-rich conformations with an energy distribution similar to that of the native state. 相似文献
64.
Aquilano K Filomeni G Di Renzo L Vito Md Stefano Cd Salimei PS Ciriolo MR Marfè G 《Free radical research》2007,41(4):452-460
In this study, we found that production of both reactive oxygen (ROS) and nitrogen (RNS) species is a very early event related to treatment with hyperosmotic concentration of sorbitol. The production of nitric oxide (NO) was paralleled by the increase of the mRNA and protein level of the inducible form of the nitric oxide synthase (iNOS). ROS and RNS enhancement, process concomitant to the failure of mitochondrial trans-membrane potential (ΔΨ), was necessary for the induction of apoptosis as demonstrated by the protection against sorbitol-mediated toxicity observed after treatment with ROS scavengers or NOS inhibitors. The synergistic action of ROS and RNS was finally demonstrated by pre-treatment with rosmarinic acid that, by powerfully buffering both these species, prevents impairment of ΔΨ and cell death. Overall results suggest that the occurrence of apoptosis upon sorbitol treatment is an event mediated by oxidative/nitrosative stress rather than a canonical hyperosmotic shock. 相似文献
65.
66.
We examined vertical migration and colonisation patterns of stream macroinvertebrates within the substratum of an Apennine
creek in NW Italy. Macrobenthos was sampled at three depths in the streambed (0–5, 5–10, 10–15 cm) by means of artificial
baskets filled with natural substratum. We placed 42 traps (5×5×15 cm), i.e. 21 top-opened (T-traps) and 21 bottom-opened
(B-traps), each composed of three overlapping baskets (high-H, medium-M and low-L), to evaluate differences in the vertical
movements. We also collected Surber samples to compare interstitial assemblages with streambed communities. The multilevel
traps yielded 42 taxa, compared with 60 taxa in the natural riverbed. Interstitial traps were rapidly colonised; both taxa
richness and organism number increased during the 42-day study period. We found active migration in both vertical directions,
but there were more invertebrates in the top-opened traps than in the bottom-opened traps. In the T-traps the most colonised
baskets were those placed at the H level, while in the B-traps the L level baskets were more rapidly colonised. The interstitial
assemblages differed markedly from the streambed communities in both composition and functional organisation, with more collector-gatherers
and predators in the interstitial zone and more filterers and scrapers in the natural riverbed. In Apennine lotic systems,
the interstitial zone is an important habitat for stream macrobenthos, although it may not be used by all species. 相似文献
67.
Giorgia Pedini Mariachiara Buccarelli Fabrizio Bianchi Laura Pacini Giulia Cencelli Quintino Giorgio DAlessandris Maurizio Martini Stefano Giannetti Franceschina Sasso Valentina Melocchi Maria Giulia Farace Tilmann Achsel Luigi M. Larocca Lucia Ricci-Vitiani Roberto Pallini Claudia Bagni 《Cell death & disease》2022,13(8)
68.
Dominique A. Cowart Stefano Schiaparelli Maria Chiara Alvaro Matteo Cecchetto AnneSophie Le Port Didier Jollivet Stephane Hourdez 《Ecology and evolution》2022,12(7)
The Antarctic marine environment hosts diversified and highly endemic benthos owing to its unique geologic and climatic history. Current warming trends have increased the urgency of understanding Antarctic species history to predict how environmental changes will impact ecosystem functioning. Antarctic benthic lineages have traditionally been examined under three hypotheses: (1) high endemism and local radiation, (2) emergence of deep‐sea taxa through thermohaline circulation, and (3) species migrations across the Polar Front. In this study, we investigated which hypotheses best describe benthic invertebrate origins by examining Antarctic scale worms (Polynoidae). We amassed 691 polynoid sequences from the Southern Ocean and neighboring areas: the Kerguelen and Tierra del Fuego (South America) archipelagos, the Indian Ocean, and waters around New Zealand. We performed phylogenetic reconstructions to identify lineages across geographic regions, aided by mitochondrial markers cytochrome c oxidase subunit I (Cox1) and 16S ribosomal RNA (16S). Additionally, we produced haplotype networks at the species scale to examine genetic diversity, biogeographic separations, and past demography. The Cox1 dataset provided the most illuminating insights into the evolution of polynoids, with a total of 36 lineages identified. Eunoe sp. was present at Tierra del Fuego and Kerguelen, in favor of the latter acting as a migration crossroads. Harmothoe fuligineum, widespread around the Antarctic continent, was also present but isolated at Kerguelen, possibly resulting from historical freeze–thaw cycles. The genus Polyeunoa appears to have diversified prior to colonizing the continent, leading to the co‐occurrence of at least three cryptic species around the Southern and Indian Oceans. Analyses identified that nearly all populations are presently expanding following a bottleneck event, possibly caused by habitat reduction from the last glacial episodes. Findings support multiple origins for contemporary Antarctic polynoids, and some species investigated here provide information on ancestral scenarios of (re)colonization. First, it is apparent that species collected from the Antarctic continent are endemic, as the absence of closely related species in the Kerguelen and Tierra del Fuego datasets for most lineages argues in favor of Hypothesis 1 of local origin. Next, Eunoe sp. and H. fuligineum, however, support the possibility of Kerguelen and other sub‐Antarctic islands acting as a crossroads for larvae of some species, in support of Hypothesis 3. Finally, the genus Polyeunoa, conversely, is found at depths greater than 150 m and may have a deep origin, in line with Hypothesis 2. These “non endemic” groups, nevertheless, have a distribution that is either north or south of the Antarctic Polar Front, indicating that there is still a barrier to dispersal, even in the deep sea. 相似文献
69.
Joseph Chadi Lemaitre Damiano Pasetto Mario Zanon Enrico Bertuzzo Lorenzo Mari Stefano Miccoli Renato Casagrandi Marino Gatto Andrea Rinaldo 《PLoS computational biology》2022,18(7)
While campaigns of vaccination against SARS-CoV-2 are underway across the world, communities face the challenge of a fair and effective distribution of a limited supply of doses. Current vaccine allocation strategies are based on criteria such as age or risk. In the light of strong spatial heterogeneities in disease history and transmission, we explore spatial allocation strategies as a complement to existing approaches. Given the practical constraints and complex epidemiological dynamics, designing effective vaccination strategies at a country scale is an intricate task. We propose a novel optimal control framework to derive the best possible vaccine allocation for given disease transmission projections and constraints on vaccine supply and distribution logistics. As a proof-of-concept, we couple our framework with an existing spatially explicit compartmental COVID-19 model tailored to the Italian geographic and epidemiological context. We optimize the vaccine allocation on scenarios of unfolding disease transmission across the 107 provinces of Italy, from January to April 2021. For each scenario, the optimal solution significantly outperforms alternative strategies that prioritize provinces based on incidence, population distribution, or prevalence of susceptibles. Our results suggest that the complex interplay between the mobility network and the spatial heterogeneities implies highly non-trivial prioritization strategies for effective vaccination campaigns. Our work demonstrates the potential of optimal control for complex and heterogeneous epidemiological landscapes at country, and possibly global, scales. 相似文献
70.
Seth Blumberg Phoebe Lu Ada T. Kwan Christopher M. Hoover James O. Lloyd-Smith David Sears Stefano M. Bertozzi Lee Worden 《PLoS computational biology》2022,18(7)
The explosive outbreaks of COVID-19 seen in congregate settings such as prisons and nursing homes, has highlighted a critical need for effective outbreak prevention and mitigation strategies for these settings. Here we consider how different types of control interventions impact the expected number of symptomatic infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a stochastic point process coupled to a branching process, while spread between residents is modeled via a deterministic compartmental model that accounts for depletion of susceptible individuals. Control is modeled as a proportional decrease in the number of susceptible residents, the reproduction number, and/or the proportion of symptomatic infections. This permits a range of assumptions about the density dependence of transmission and modes of protection by vaccination, depopulation and other types of control. We find that vaccination or depopulation can have a greater than linear effect on the expected number of cases. For example, assuming a reproduction number of 3.0 with density-dependent transmission, we find that preemptively reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. In some circumstances, it may be possible to reduce the risk and burden of disease outbreaks by optimizing the way a group of residents are apportioned into distinct residential units. The optimal apportionment may be different depending on whether the goal is to reduce the probability of an outbreak occurring, or the expected number of cases from outbreak dynamics. In other circumstances there may be an opportunity to implement reactive disease control measures in which the number of susceptible individuals is rapidly reduced once an outbreak has been detected to occur. Reactive control is most effective when the reproduction number is not too high, and there is minimal delay in implementing control. We highlight the California state prison system as an example for how these findings provide a quantitative framework for understanding disease transmission in congregate settings. Our approach and accompanying interactive website (https://phoebelu.shinyapps.io/DepopulationModels/) provides a quantitative framework to evaluate the potential impact of policy decisions governing infection control in outbreak settings. 相似文献