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171.
Ke Tao Sidoryk-Wegrzynowicz Marta Pajarillo Edward Rizor Asha Soares Félix Alexandre Antunes Lee Eunsook Aschner Michael 《Neurochemical research》2019,44(11):2449-2459
Neurochemical Research - Manganese (Mn) overexposure is a public health concern due to its widespread industrial usage and the risk for environmental contamination. The clinical symptoms of Mn... 相似文献
172.
173.
Yogavel Manickam Nipun Malhotra Siddhartha Mishra Palak Babbar Abhishek Dusane Benoît Laleu Valeria Bellini Mohamed-Ali Hakimi Alexandre Bougdour Amit Sharma 《PLoS pathogens》2022,18(3)
Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional ‘single target–single drug’ approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3’-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC50 and EC50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins. 相似文献
174.
175.
Zixin Peng Alexandre Maciel-Guerra Michelle Baker Xibin Zhang Yue Hu Wei Wang Jia Rong Jing Zhang Ning Xue Paul Barrow David Renney Dov Stekel Paul Williams Longhai Liu Junshi Chen Fengqin Li Tania Dottorini 《PLoS computational biology》2022,18(3)
Anthropogenic environments such as those created by intensive farming of livestock, have been proposed to provide ideal selection pressure for the emergence of antimicrobial-resistant Escherichia coli bacteria and antimicrobial resistance genes (ARGs) and spread to humans. Here, we performed a longitudinal study in a large-scale commercial poultry farm in China, collecting E. coli isolates from both farm and slaughterhouse; targeting animals, carcasses, workers and their households and environment. By using whole-genome phylogenetic analysis and network analysis based on single nucleotide polymorphisms (SNPs), we found highly interrelated non-pathogenic and pathogenic E. coli strains with phylogenetic intermixing, and a high prevalence of shared multidrug resistance profiles amongst livestock, human and environment. Through an original data processing pipeline which combines omics, machine learning, gene sharing network and mobile genetic elements analysis, we investigated the resistance to 26 different antimicrobials and identified 361 genes associated to antimicrobial resistance (AMR) phenotypes; 58 of these were known AMR-associated genes and 35 were associated to multidrug resistance. We uncovered an extensive network of genes, correlated to AMR phenotypes, shared among livestock, humans, farm and slaughterhouse environments. We also found several human, livestock and environmental isolates sharing closely related mobile genetic elements carrying ARGs across host species and environments. In a scenario where no consensus exists on how antibiotic use in the livestock may affect antibiotic resistance in the human population, our findings provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. Moreover, our original data analysis method has the potential to uncover AMR transmission pathways when applied to the study of other pathogens active in other anthropogenic environments characterised by complex interconnections between host species. 相似文献
176.
M G Doni R Deana S Bertoncello F Zoccarato A Alexandre 《Biochemical and biophysical research communications》1988,156(3):1316-1323
Platelet activation (cytosolic [Ca2+] increase, aggregation and ATP secretion) was induced with A1F-4. This agent presumably interacts with a G protein which appears to mediate the coupling of the receptors for Ca mobilizing hormones and phospholipase C. All the A1F-4 evoked responses were inhibited by treatment with forskolin or prostacyclin, agents known to increase cellular cAMP. Thus the G protein-phospholipase C system appears to be the site of cAMP inhibition. Unexpectedly forskolin and prostacyclin also inhibited secretion and aggregation induced by the activators of protein kinase C, diglyceride and phorbol ester, suggesting that cAMP can also inhibit directly the protein kinase C dependent responses. 相似文献
177.
Marcelo Massa Alexandre Moreira Renato A. Costa Marcelo R. Lima Carlos R. Thiengo Walter Q. Marquez Aaron J. Coutts Marcelo S. Aoki 《Biology of sport / Institute of Sport》2022,39(2):435
This study examined the influence of birth date, salivary testosterone [sT] concentration, sexual maturity status, and general strength on the selection process of an elite Brazilian soccer club during a 12-month period, which was a 2nd phase of a 24-month selection process. The stature, body mass, sT, sexual maturity status [Tanner scale], and hand grip strength were assessed for 143 players during 2 weeks. From these 143 players, 100 players were dismissed [DIS] and 43 players were selected to integrate the club’s under-14 squad. Following 1-year training period, the under-14 team was assembled with 9 players designated as starters [STA], and then, comparisons were conducted taking into account a group of non-starters (selected; SEL = 34 players) and STA (n = 09). The DIS, SEL, STA players, and reference population, were compared for birth distribution. A greater proportion of players was born in the first trimester in the STA [75.0%], SEL [57.1%] and DIS [50.0%] groups compared to the reference population [25.8%]. One-way ANOVA showed a higher sT for STA group [516.0 ± 129.9 pmol·L-1], compared to SEL [415.5 ± 117.9 pmol·L-1] and DIS groups [390.9 ± 84.9 pmol·L-1; p = 0.003), and Kruskall-Wallis test showed a higher gonadal development for STA compared to DIS [p = 0.001]. The current findings suggest a strong influence of birth date and biological maturation on young soccer players selection process. Soccer coaches should consider these influences when making decisions about player selection of elite youth players. 相似文献
178.
Lo Djaoui Adam Owen Matt Newton Pantelis Theodoros Nikolaidis Alexandre Dellal Karim Chamari 《Biology of sport / Institute of Sport》2022,39(2):307
The aim of the present study was to analyse the influence of congested periods of matches on the acceleration (Acc) and deceleration (Dec) profiles of elite soccer players. Twenty-three elite male professional soccer players participated in the study across 31 official matches. Assessed periods included: (i) congested periods (three to four days between games), and (ii) non-congested periods (more than four days between games). Physical activity during matches was recorded during games using a 10Hz global positioning system device, coupled with a 100 Hz accelerometer, and was analysed according to the periods. Maximal Acc- (73.2 ± 20.3 vs. 84.918.5 m), high Acc- (244.0 ± 49.5 vs. 267.0 ± 37.8 m), maximal Dec- (139.0 ± 44.8 vs. 152.039.3 m) and the total decelerating- distance (5132 ± 690 vs. 5245 ± 552 m) were lower in congested than in non-congested periods (p < 0.05, effect size 0.31–0.70). Neither a main effect of playing position nor a period*playing position interaction on Acc and Dec were observed (p > 0.05). It was concluded that Acc and Dec match activities were significantly affected during congested periods compared to non-congested highlighting a possible fatigue accumulation being responsible for the observed decrement in physical activity. Monitoring Acc and Dec metrics throughout particular periods of congested fixtures amongst professional soccer teams is advised and may be a way to assess physical and fatigue status. 相似文献
179.
Ritabrata Dutta Karim Zouaoui Boudjeltia Christos Kotsalos Alexandre Rousseau Daniel Ribeiro de Sousa Jean-Marc Desmet Alain Van Meerhaeghe Antonietta Mira Bastien Chopard 《PLoS computational biology》2022,18(3)
Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment. 相似文献
180.
Jeremy Carlot Hloïse Rouz Diego R. Barneche Alexandre Mercire Benoit Espiau Ulisse Cardini Simon J. Brandl Jordan M. Casey Gonzalo PrezRosales Mehdi Adjeroud Laetitia Hdouin Valeriano Parravicini 《Ecology and evolution》2022,12(3)
Coral reefs provide a range of important services to humanity, which are underpinned by community‐level ecological processes such as coral calcification. Estimating these processes relies on our knowledge of individual physiological rates and species‐specific abundances in the field. For colonial animals such as reef‐building corals, abundance is frequently expressed as the relative surface cover of coral colonies, a metric that does not account for demographic parameters such as coral size. This may be problematic because many physiological rates are directly related to organism size, and failure to account for linear scaling patterns may skew estimates of ecosystem functioning. In the present study, we characterize the scaling of three physiological rates — calcification, respiration, and photosynthesis — considering the colony size for six prominent, reef‐building coral taxa in Mo''orea, French Polynesia. After a seven‐day acclimation period in the laboratory, we quantified coral physiological rates for three hours during daylight (i.e., calcification and gross photosynthesis) and one hour during night light conditions (i.e., dark respiration). Our results indicate that area‐specific calcification rates are higher for smaller colonies across all taxa. However, photosynthesis and respiration rates remain constant over the colony‐size gradient. Furthermore, we revealed a correlation between the demographic dynamics of coral genera and the ratio between net primary production and calcification rates. Therefore, intraspecific scaling of reef‐building coral physiology not only improves our understanding of community‐level coral reef functioning but it may also explain species‐specific responses to disturbances. 相似文献