Apoptosis is one type of programmed cell death. Increasingly, non-apoptotic cell death is recognized as being genetically controlled, or 'regulated'. However, the full extent and diversity of ...alternative cell death mechanisms remain uncharted. Here we surveyed the landscape of pharmacologically accessible cell death mechanisms. In an examination of 56 caspase-independent lethal compounds, modulatory profiling showed that 10 compounds induced three different types of regulated non-apoptotic cell death. Optimization of one of those ten resulted in the discovery of FIN56, a specific inducer of ferroptosis. Ferroptosis has been found to occur when the lipid-repair enzyme GPX4 is inhibited. FIN56 promoted degradation of GPX4. FIN56 also bound to and activated squalene synthase, an enzyme involved in isoprenoid biosynthesis, independent of GPX4 degradation. These discoveries show that dysregulation of lipid metabolism is associated with ferroptosis. This systematic approach is a means to discover and characterize novel cell death phenotypes.
Oxidative stress has been linked to neurodegenerative diseases such as Huntington's, Parkinson's, Alzheimer's and amyotrophic lateral sclerosis diseases.
(LT) also known as Creosote Bush is an ...evergreen shrub found in the Chihuahuan desert which has been used medicinally by Native American tribes in southwestern North America and the Amerindians of South America. However, studies of the antioxidant capacity of the crude extract of LT towards the discovery of novel molecular therapies bearing antioxidants and drug-like properties are lacking. In this study, we assessed the antioxidant properties of
, collected specifically from the Chihuahuan desert in the region of El Paso del Norte, TX, USA. LT phytochemicals were obtained from three different extracts (ethanol; ethanol: water (60:40) and water). Then the extracts were evaluated in eight different assays (DPPH, ABTS, superoxide; FRAP activity, nitric oxide, phenolic content, UV visible absorption and cytotoxicity in non-cancerous HS27 cells). The three extracts were not affecting the HS27 cells at concentrations up to 120 µg/mL. Among the three extracts, we found that the mixture of ethanol: water (60:40) LT extract has the most efficient antioxidant properties (IC
(DPPH at 30 min) = 111.7 ± 3.8 μg/mL; IC
(ABTS) = 8.49 ± 2.28 μg/mL; IC
(superoxide) = 0.43 ± 0.17 μg/mL; IC
(NO) = 230.4 ± 130.4 μg/mL; and the highest phenolic content was estimated to 212.46 ± 7.05 mg GAE/L). In addition, there was a strong correlation between phenolic content and the free-radical scavenging activity assays. HPLC-MS study identified nine compounds from the LT-ethanol: water extract including Justicidin B and Beta peltain have been previously reported as secondary metabolites of
.
The global abundance of tree palms Emilio, Thaise; Baker, William J.; Eiserhardt, Wolf L. ...
Global ecology and biogeography,
September 2020, Letnik:
29, Številka:
9
Journal Article, Web Resource
Recenzirano
Odprti dostop
Aim
Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and ...physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change.
Location
Tropical and subtropical moist forests.
Time period
Current.
Major taxa studied
Palms (Arecaceae).
Methods
We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure.
Results
On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work.
Conclusions
Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests.
Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development ...of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients.
Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma.
The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 ± 13.9% and 117.4 ± 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates.
A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.
Tropical forests are global centres of biodiversity and carbon storage. Many tropical countries aspire to protect forest to fulfil biodiversity and climate mitigation policy targets, but the ...conservation strategies needed to achieve these two functions depend critically on the tropical forest tree diversity-carbon storage relationship. Assessing this relationship is challenging due to the scarcity of inventories where carbon stocks in aboveground biomass and species identifications have been simultaneously and robustly quantified. Here, we compile a unique pan-tropical dataset of 360 plots located in structurally intact old-growth closed-canopy forest, surveyed using standardised methods, allowing a multi-scale evaluation of diversity-carbon relationships in tropical forests. Diversity-carbon relationships among all plots at 1 ha scale across the tropics are absent, and within continents are either weak (Asia) or absent (Amazonia, Africa). A weak positive relationship is detectable within 1 ha plots, indicating that diversity effects in tropical forests may be scale dependent. The absence of clear diversity-carbon relationships at scales relevant to conservation planning means that carbon-centred conservation strategies will inevitably miss many high diversity ecosystems. As tropical forests can have any combination of tree diversity and carbon stocks both require explicit consideration when optimising policies to manage tropical carbon and biodiversity.
The no-wait job shop is an extension of the well-known job shop scheduling subject to the constraint that the operations of any job, once started, must be processed immediately, one after the other, ...until the completion of the job. The problem is NP-hard and exact methods can only solve small instances. In the last two decades of advances on this problem, one aspect became central for the success of metaheuristics to tackle it, namely the decomposition of solution into two parts: sequencing and timetabling. Most of these metaheuristics use a permutation to represent the sequencing part, while the timetabling part uses specific rules that differentiate one approach from the other. The main contribution of this work is the proposal of a cooperative coevolutionary algorithm where the sequencing and the timetabling parts interact with each other to evolve quasi-optimal sequencing and timetabling decisions. To this aim, the algorithm co-evolves a population of permutations with a population of binary chains. The permutation decides the sequencing while each bit in the binary chain decides whether or not a job is shifted to the left-most position on its corresponding machine. Therefore, the whole binary chain defines a timetabling rule that is automatically optimized during the evolution process. The algorithm also includes one-step perturbation mechanisms that help improve the solution quality. The proposed algorithm is tested on a set of benchmark instances to compare it with seven state-of-the-art methods. Computational experiments show that the proposed algorithm produces competitive results, furthermore, new best values for four instances are obtained.
•A novel cooperative co-evolutionary approach for the no-wait job shop problem.•A shift decoding algorithm to determine jobs’ start time to find good schedules.•A novel combination of a permutation and a binary vector for solution representation.•Comparison with four state-of-the-art approaches.•Four new best solutions for benchmark instances.
In the last two decades, many cities imposed environmental regulations that mandate companies to stop using fuel-powered vehicles once or twice weekly depending on the air quality and their ...identification numbers. The regulation limits the companies ability to fulfil client demands. Many companies may adopt alternative strategies to overcome this constraint by replacing the stopped vehicles with electric units. However, this replacement impacts the fleet’s performance. In the present study, we analyse the impact on fleet’s performances by modelling the problem as a Pareto front degradation, when replacing conventional vehicles (CVs) with electric vehicles (EVs). To this end, we base our analysis on a visual inspection of the non-dominated fronts and a coverage measure. To obtain good quality non-dominated fronts, we improve a multi-objective evolutionary algorithm (MOEA/D) by introducing a novel, simple and effective post-processing stage applied to each non-dominated solution obtained from the MOEA/D. The analysis and computational experiments offer three main results: i) The post-processing algorithm improves almost every single non-dominated front generated by the MOEA/D. ii) Contrary to the expected results, the number of CVs to be replaced without affecting the fleet performance is large, between half and two-thirds of the total number of vehicles, iii) The proposed model here will help companies to find the appropriate number of CVs to be replaced without affecting their service quality.
Background/Objective
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Research suggests an association between obesity and AD, although evidence is lacking from Latin American ...populations. This study evaluated the association of obesity with AD in children from Chile, a country with high obesity prevalence.
Methods
A case‐control study was performed in children with active AD (cases) and healthy controls (HCs) from Santiago, Chile. Body mass index was evaluated by z‐score (z‐BMI), with overweight defined as z‐BMI ≥+1 and <+2, and obesity as z‐BMI ≥+2. Abdominal obesity was defined by a waist circumference‐to‐height ratio (WHR) ≥0.5. AD severity was evaluated by Scoring AD (SCORAD) index.
Results
A total of 174 children with AD and 101 controls were included. AD patients had similar overweight (27% vs. 28%) and obesity (21% vs. 26%) rates as HCs (p = .65). Abdominal obesity rates were also comparable (64% vs. 62%, p = .81). In sex‐specific analyses, girls with AD had higher abdominal obesity rates than HCs (71% vs. 53%, p < .05) while boys with AD had lower abdominal obesity rates than HCs (53% vs. 75%, p = .03). Among children with AD, higher z‐BMI or WHR did not correlate with higher SCORAD, eosinophil counts or total IgE.
Conclusion
In our study, Chilean children with AD had high but similar rates of obesity as HCs, but showed sex‐specific associations of abdominal obesity and AD. Further research is needed to evaluate these associations and the roles that weight excess and weight loss could play in the pathogenesis and treatment of AD.
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