Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk.

BackgroundThe development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment.Main bodyRecent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-β signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-β, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD.ConclusionThe understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods

Influence of wastewater composition on nutrient removal behaviors in the new anaerobic–anoxic/nitrifying/induced crystallization process

AbstractIn this study, the new anaerobic–anoxic/nitrifying/induced crystallization (A2N–IC) system was compared with anaerobic-anoxic/nitrifying (A2N) process to investigate nutrient removal performance under different influent COD and ammonia concentrations. Ammonia and COD removal rates were very stable in both processes, which were maintained at 84.9% and 86.6% when the influent ammonia varied from 30mgL−1 to 45mgL−1 and COD ranged from 250mgL−1 to 300mgL−1. The effluent phosphorus always maintained below 0.2mgL−1 in A2N–IC, whereas in A2N the effluent phosphorus concentration was 0.4–1.7mgL−1, demonstrating that A2N–IC is suitable to apply in a broader influent COD and ammonia concentration range. Under higher influent COD (300mgL−1) or lower ammonia conditions (30mgL−1), the main function of chemical induced crystallization was to coordinate better nutrient ratio for anoxic phosphorus uptake, whereas under high phosphorus concentration, it was to reduce phosphorus loading for biological system. Under the similar influent wastewater compositions, phosphorus release amounts were always lower in A2N–IC. To clarify the decrease procedure of phosphorus release in the A2N–IC, the equilibrium between chemical phosphorus removal and biological phosphorus removal in A2N–IC was analyzed by mass balance equations. During the long-term experiment, some undesirable phenomena were observed: the declining nitrification in post-aerobic tank and calcium phosphorus precipitation in the anaerobic tank. The reasons were analyzed; furthermore, the corresponding improvements were proposed. Nitrification effect could be enhanced in the post-aerobic tank, therefore ammonia removal rate could be increased; and biologically induced phosphorus precipitation could be inhibited by controlling pH at the anaerobic stage, so the phosphorus release and recovery could be improved

Towards Artistic Image Aesthetics Assessment: a Large-scale Dataset and a New Method

Image aesthetics assessment (IAA) is a challenging task due to its highly subjective nature. Most of the current studies rely on large-scale datasets (e.g., AVA and AADB) to learn a general model for all kinds of photography images. However, little light has been shed on measuring the aesthetic quality of artistic images, and the existing datasets only contain relatively few artworks. Such a defect is a great obstacle to the aesthetic assessment of artistic images. To fill the gap in the field of artistic image aesthetics assessment (AIAA), we first introduce a large-scale AIAA dataset: Boldbrush Artistic Image Dataset (BAID), which consists of 60,337 artistic images covering various art forms, with more than 360,000 votes from online users. We then propose a new method, SAAN (Style-specific Art Assessment Network), which can effectively extract and utilize style-specific and generic aesthetic information to evaluate artistic images. Experiments demonstrate that our proposed approach outperforms existing IAA methods on the proposed BAID dataset according to quantitative comparisons. We believe the proposed dataset and method can serve as a foundation for future AIAA works and inspire more research in this field. Dataset and code are available at: https://github.com/Dreemurr-T/BAID.gitComment: Accepted by CVPR 202

Migrant Resettlement by Evolutionary Multi-objective Optimization

Migration has been a universal phenomenon, which brings opportunities as well as challenges for global development. As the number of migrants (e.g., refugees) increases rapidly in recent years, a key challenge faced by each country is the problem of migrant resettlement. This problem has attracted scientific research attention, from the perspective of maximizing the employment rate. Previous works mainly formulated migrant resettlement as an approximately submodular optimization problem subject to multiple matroid constraints and employed the greedy algorithm, whose performance, however, may be limited due to its greedy nature. In this paper, we propose a new framework MR-EMO based on Evolutionary Multi-objective Optimization, which reformulates Migrant Resettlement as a bi-objective optimization problem that maximizes the expected number of employed migrants and minimizes the number of dispatched migrants simultaneously, and employs a Multi-Objective Evolutionary Algorithm (MOEA) to solve the bi-objective problem. We implement MR-EMO using three MOEAs, the popular NSGA-II, MOEA/D as well as the theoretically grounded GSEMO. To further improve the performance of MR-EMO, we propose a specific MOEA, called GSEMO-SR, using matrix-swap mutation and repair mechanism, which has a better ability to search for feasible solutions. We prove that MR-EMO using either GSEMO or GSEMO-SR can achieve better theoretical guarantees than the previous greedy algorithm. Experimental results under the interview and coordination migration models clearly show the superiority of MR-EMO (with either NSGA-II, MOEA/D, GSEMO or GSEMO-SR) over previous algorithms, and that using GSEMO-SR leads to the best performance of MR-EMO

Observation of a thermoelectric Hall plateau in the extreme quantum limit

The thermoelectric Hall effect is the generation of a transverse heat current upon applying an electric field in the presence of a magnetic field. Here we demonstrate that the thermoelectric Hall conductivity $\alpha_{xy}$ in the three-dimensional Dirac semimetal ZrTe$_5$ acquires a robust plateau in the extreme quantum limit of magnetic field. The plateau value is independent of the field strength, disorder strength, carrier concentration, or carrier sign. We explain this plateau theoretically and show that it is a unique signature of three-dimensional Dirac or Weyl electrons in the extreme quantum limit. We further find that other thermoelectric coefficients, such as the thermopower and Nernst coefficient, are greatly enhanced over their zero-field values even at relatively low fields.Comment: 17+21 pages, 3+14 figures; published versio

Fabrication and characteristics of flexible normally-off AlGaN/GaN HEMTs

In this paper, we present a method for removing a high electron mobility transistor (HEMT) silicon substrate using mechanical grinding and deep silicon etching technology and successfully transferred the epitaxial wafer to a PET substrate to achieve the flexible normally-off HEMT. By testing the output characteristics and transfer characteristics of the Si-substrate HEMT and PET-substrate HEMT, we have demonstrated that the PET-substrate HEMT has excellent performance and successfully achieved the mechanical flexibility. Furthermore, we analyzed the physical mechanisms of the change in PET-substrate and Si-substrate HEMT characteristics, as well as flexible HEMT performance under bent and flattened states. The flexible HEMT array demonstrates significant potential in integration with other flexible devices, such as GaN-based micro-LED arrays

SMA1, a homolog of the splicing factor Prp28, has a multifaceted role in miRNA biogenesis in Arabidopsis

MicroRNAs (miRNAs) are a class of small non-coding RNAs that repress gene expression. In plants, the RNase III enzyme Dicer-like (DCL1) processes primary miRNAs (pri-miRNAs) into miRNAs. Here, we show that SMALL1 (SMA1), a homolog of the DEADbox pre-mRNA splicing factor Prp28, plays essential roles in miRNA biogenesis in Arabidopsis. A hypomorphic sma1-1 mutation causes growth defects and reduces miRNA accumulation correlated with increased target transcript levels. SMA1 interacts with the DCL1 complex and positively influences primiRNA processing. Moreover, SMA1 binds the promoter region of genes encoding pri-miRNAs (MIRs) and is required for MIR transcription. Furthermore, SMA1 also enhances the abundance of the DCL1 protein levels through promoting the splicing of the DCL1 pre-mRNAs. Collectively, our data provide new insights into the function of SMA1/Prp28 in regulating miRNA abundance in plants

Overexpression of Kcnmb2 in Dorsal CA1 of Offspring Mice Rescues Hippocampal Dysfunction Caused by a Methyl Donor-Rich Paternal Diet

BK channels are known regulators of neuronal excitability, synaptic plasticity, and memory. Our previous study showed that a paternal methyl donor-rich diet reduced the expression of Kcnmb2, which encodes BK channel subunit beta 2, and caused memory deficits in offspring mice. To explore the underlying cellular mechanisms, we investigated the intrinsic and synaptic properties of CA1 pyramidal neurons of the F1 offspring mice whose fathers were fed with either a methyl donor-rich diet (MD) or regular control diet (CD) for 6 weeks before mating. Whole-cell patch-clamp recordings of CA1 pyramidal neurons revealed a decrease in intrinsic excitability and reduced frequency of inhibitory post-synaptic currents in MD F1 mice compared to the CD F1 controls. AAV-based overexpression of Kcnmb2 in dorsal CA1 ameliorated changes in neuronal excitability, synaptic transmission, and plasticity in MD F1 mice. Our findings thus indicate that a transient paternal exposure to a methyl donor-rich diet prior to mating alters Kcnmb2-sensitive hippocampal functions in offspring animals

Systems Biology Analysis of the Effect and Mechanism of Qi-Jing-Sheng-Bai Granule on Leucopenia in Mice

Qi-Jing-Sheng-Bai granule (QJSB) is a newly developed traditional Chinese medicine (TCM) formula. Clinically, it has been used for the treatment of leucopenia. However, its pharmacological mechanism needs more investigation. In this study, we firstly tested the effects of QJSB on leucopenia using mice induced by cyclophosphamide. Our results suggested that QJSB significantly raised the number of peripheral white blood cells, platelets and nucleated bone marrow cells. Additionally, it markedly enhanced the cell viability and promoted the colony formation of bone marrow mononuclear cells. Furthermore, it reversed the serum cytokines IL-6 and G-CSF disorders. Then, using transcriptomics datasets and metabonomic datasets, we integrated transcriptomics-based network pharmacology and metabolomics technologies to investigate the mechanism of action of QJSB. We found that QJSB regulated a series of biological processes such as hematopoietic cell lineage, homeostasis of number of cells, lymphocyte differentiation, metabolic processes (including lipid, amino acid, and nucleotide metabolism), B cell receptor signaling pathway, T cell activation and NOD-like receptor signaling pathway. In a summary, QJSB has protective effects to leucopenia in mice probably through accelerating cell proliferation and differentiation, regulating metabolism response pathways and modulating immunologic function at a system level