Highlights • The microbiota–gut–brain axis is a bidirectional neurohumoral communication system. • Autistic neurodevelopmental deficits are frequently associated with gastrointestinal symptoms and ...gut microbiota dysbiosis. • Disturbance of the gut microbiota has been implicated as a possible contributor to ASD behavioral deficits. • Modulating the microbiota–gut–brain axis is a promising strategy for treatment of ASD symptoms.
Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins that contain the evolutionarily conserved SET domain and plays a fundamental role in epigenetic regulation ...of gene activation and silencing in all eukaryotes. The recently determined three-dimensional structures of the SET domains from chromosomal proteins reveal that the core SET domain structure contains a two-domain architecture, consisting of a conserved anti-parallel β-barrel and a structurally variable insert that surround a unusual knot-like structure that comprises the enzyme active site. These structures of the SET domains, either in the free state or when bound to cofactor S-adenosyl-L-homocysteine and/or histone peptide, mimicking an enzyme/cofactor/substrate complex, further yield the structural insights into the molecular basis of the substrate specificity, methylation multiplicity and the catalytic mechanism of histone lysine methylation.
Histone acetylation marks are written by histone acetyltransferases (HATs) and read by bromodomains (BrDs), and less commonly by other protein modules. These proteins regulate many ...transcription-mediated biological processes, and their aberrant activities are correlated with several human diseases. Consequently, small molecule HAT and BrD inhibitors with therapeutic potential have been developed. Structural and biochemical studies of HATs and BrDs have revealed that HATs fall into distinct subfamilies containing a structurally related core for cofactor binding, but divergent flanking regions for substrate-specific binding, catalysis, and autoregulation. BrDs adopt a conserved left-handed four-helix bundle to recognize acetyllysine; divergent loop residues contribute to substrate-specific acetyllysine recognition.
The study analysed healthcare workers' (HCWs) knowledge, practices, and attitudes regarding coronavirus disease 2019 (COVID-19). A cross-sectional survey was conducted from February 4th to February ...8th, 2020, involving a total of 1357 HCWs across 10 hospitals in Henan, China. Of those surveyed, 89% of HCWs had sufficient knowledge of COVID-19, more than 85% feared self-infection with the virus, and 89.7% followed correct practices regarding COVID-19. In addition to knowledge level, some risk factors including work experience and job category influenced HCWs' attitudes and practice concerning COVID-19. Measures must be taken to protect HCWs from risks linked to job category, work experience, working hours, educational attainment, and frontline HCWs.
Histone lysine acetylation is central to epigenetic control of gene transcription. The bromodomain, found in chromatin-associated proteins and histone acetyltranferases, functions as the sole protein ...module known to bind acetyl-lysine motifs. Recent structural and functional analyses of bromodomains' recognition of lysine-acetylated peptides derived from major acetylation sites in histones and cellular proteins provide new insights into differences in ligand binding selectivity as well as unifying features of histone recognition by the bromodomains. These new findings highlight the functional importance of bromodomain/acetyl-lysine binding as a pivotal mechanism for regulating protein-protein interactions in histone-directed chromatin remodeling and gene transcription. These new studies also support the notion that functional diversity of a conserved bromodomain structural fold is achieved by evolutionary changes of structurally flexible amino-acid sequences in the ligand binding site such as the ZA and BC loops.
•An interval-fuzzy-chance-constraint programming method is proposed for land-use planning.•Model can tackle uncertainties described as intervals, probabilities and fuzzy sets.•The model ...systematically considers economic/environmental/social/ecological factors.•IFCCP is applied to a real case study of land-use planning in Nanjing.•Results can analyze the tradeoff between socio-economic and eco-environment.
In this study, an interval fuzzy chance-constrained land-use allocation (IFCC-LUA) model is developed for sustainable urban land-use planning management and land use policy analysis under uncertainty. This method is based on an integration of interval parameter programming (IPP), fuzzy flexible linear programming (FFLP) and chance-constrained programming (CCP) techniques. Complexities in land-use planning management system can be systematically reflected, thus applicability of the modeling process can be highly enhanced. The developed method is applied to planning land-use allocation practice in Nanjing city, China. The objective of the IFCC-LUA is maximizing net benefit from LUA system and the main constraints include investment constraints, land suitability constraints, water/power consumption constraints and wastewater/solid waste capacity constraints. Modeling results indicate that desired system benefit will be between 1.34, 1.74×1012 yuan under the minimum violating probabilities; the optimized areas of commercial land, industrial land, agricultural land, transportation land, residential land, water land, green land, landfill land and unused land will be 290, 393hm2, 176, 238hm2, 3245, 4390hm2, 126, 170hm2, 49, 66hm2, 1241, 1679hm2, 102, 138hm2, 7, 10hm2 and 178, 241hm2. They can be used for generating decision alternatives and thus help decision makers identify desired land use policies under various system-reliability constraints of economic development requirement and environmental capacity of pollutant. Tradeoffs between system benefits and constraint violation risks can also be tackled.
We report on the experimental studies of laser driven ion acceleration from a double-layer target where a near-critical density target with a few-micron thickness is coated in front of a ...nanometer-thin diamondlike carbon foil. A significant enhancement of proton maximum energies from 12 to ∼30 MeV is observed when a relativistic laser pulse impinges on the double-layer target under linear polarization. We attributed the enhanced acceleration to superponderomotive electrons that were simultaneously measured in the experiments with energies far beyond the free-electron ponderomotive limit. Our interpretation is supported by two-dimensional simulation results.
•We propose a recurrent neural network based microscopic car following model.•The model has a stronger performance in predict future traffic oscillations.•The model has a much stronger performance in ...capture oscillations caused by aggressive drivers.
This paper proposes a recurrent neural network based microscopic car following model that is able to accurately capture and predict traffic oscillation. Neural network models have gained increasing popularity in many fields and have been applied in modelling microscopic traffic flow dynamics due to their parameter-free and data-driven nature. We investigate the existing neural network based microscopic car following models, and find out that they are generally accurate in predicting traffic flow dynamics under normal traffic operational conditions. However, they do not maintain accuracy under conditions of traffic oscillation. To bridge this research gap, we first propose four neural network based models and evaluate their applicability to predict traffic oscillation. It is found that, with an appropriate structure and objective function, the recurrent neural network based model has the capability of perfectly re-establishing traffic oscillations and distinguish drivers characteristics. We further compare the proposed model with a classical car following model (Intelligent Driver Model). Based on our case study, the proposed model outperforms the classical car following model in predicting traffic oscillations with different driver characteristics.
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