Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair.

Contrary to the long-held belief that DNA methylation of terminally differentiated cells is permanent and essentially immutable, post-mitotic neurons exhibit extensive DNA demethylation. The cellular function of active DNA demethylation in neurons, however, remains largely unknown. Tet family proteins oxidize 5-methylcytosine to initiate active DNA demethylation through the base-excision repair (BER) pathway. We found that synaptic activity bi-directionally regulates neuronal Tet3 expression. Functionally, knockdown of Tet or inhibition of BER in hippocampal neurons elevated excitatory glutamatergic synaptic transmission, whereas overexpressing Tet3 or Tet1 catalytic domain decreased it. Furthermore, dysregulation of Tet3 signaling prevented homeostatic synaptic plasticity. Mechanistically, Tet3 dictated neuronal surface GluR1 levels. RNA-seq analyses further revealed a pivotal role of Tet3 in regulating gene expression in response to global synaptic activity changes. Thus, Tet3 serves as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation

Geometrical and electrical modulation on the transport property of silicene constrictions

We study the electrical modulation of the transport properties of silicene constrictions with different geometrical structures by adopting the tight-binding model and non-equilibrium Green's function method. The band structure and transmission properties are discussed under the influence of the external electric field and potential energy. Especially, we investigate the effects of the position and width of the central scattering region on the conductance with increasing of Fermi energy. We find that the conductance significantly depends on the position and the width. Interestingly, the symmetrical structure of the central region can induce a resonance effect and significantly enlarge the system's conductance. Obviously, we obtain an effective method to adjust the transport property of the silicene heterojunctions. Correspondingly, we propose a novel two-channel structure with an excellent performance on the conductance compared to the one-channel structure with the same total width.Comment: 7 pages, 8 figure

Association between increased C-reactive protein and cardiovascular disease among patients with rectal cancer

PurposeThis study aimed to investigate the association between increased C-reactive protein (CRP) and cardiovascular disease (CVD) in individuals with rectal cancer, as well as to understand the effect of chemotherapy for cancer on increasing CRP and its underlying mechanisms.Patients and methodsFrom January 1, 2010 to December 31, 2020, individuals with rectal cancer were evaluated at the First Affiliated Hospital of Gannan Medical University. Then, in patients with rectal cancer, the relationship between increased CRP and CVD attributes was summarized, and the impact of chemotherapy on CRP levels was qualitatively assessed. For further investigation into potential regulatory mechanisms of CRP, differentially expressed genes (DEGs), GO and KEGG enrichment analyses were conducted.ResultsA total of 827 individuals were included in the study, including 175 with CVD (21.16%) and 652 without CVD. A significant association between increased CRP and CVD events was observed in rectal cancer patients (p < 0.01), and it significantly improved the classification performance of the CVD predictive model in the AUC (0.724 vs 0.707) and NRI (0.069, 95% CI 0.05-0.14). Furthermore, a comparison of CRP levels before and after chemotherapy revealed a significant increase among rectal cancers post-treatment (p < 0.001). Analysis of differentially expressed genes and co-expression indicated that 96 DEGs were involved in the pathophysiology of increased CRP after chemotherapy, and three hub genes were implicated in atherosclerotic susceptibility.ConclusionIn conclusion, our findings indicated that increased CRP levels following chemotherapy profoundly impacted CVD events in individuals with rectal cancer, and may be beneficial in promoting CVD prediction in clinical practice

YeastFab:the design and construction of standard biological parts for metabolic engineering in Saccharomyces cerevisiae

It is a routine task in metabolic engineering to introduce multicomponent pathways into a heterologous host for production of metabolites. However, this process sometimes may take weeks to months due to the lack of standardized genetic tools. Here, we present a method for the design and construction of biological parts based on the native genes and regulatory elements in Saccharomyces cerevisiae. We have developed highly efficient protocols (termed YeastFab Assembly) to synthesize these genetic elements as standardized biological parts, which can be used to assemble transcriptional units in a single-tube reaction. In addition, standardized characterization assays are developed using reporter constructs to calibrate the function of promoters. Furthermore, the assembled transcription units can be either assayed individually or applied to construct multi-gene metabolic pathways, which targets a genomic locus or a receiving plasmid effectively, through a simple in vitro reaction. Finally, using β-carotene biosynthesis pathway as an example, we demonstrate that our method allows us not only to construct and test a metabolic pathway in several days, but also to optimize the production through combinatorial assembly of a pathway using hundreds of regulatory biological parts

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders.

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders

Fuzzy logic based vehicle positioning systems in areas with high skyline

The objective of this project is to develop a reliable localization system for the vehicle to be used in areas with tall buildings around, such as the central business district in Singapore.Master of Engineering (SCE

Exploring the Use of Austin’s Theory of Illocutionary Acts in Different Social Interactions

This paper reviews how Austin’s illocutionary act theory is used in face-to-face communication and online communication. In the aspect of face-to-face interaction, this paper places attention on the use of polite language and interaction in ESL (English as a second language) classrooms. In terms of online interaction, this paper explored interaction on Facebook and the use of memes, emoticons, emojis and stickers. After reviewing several research, this paper concluded that when talking face-to-face, the level of formality, gender, and cultural background affects people’s polite language. In ESL classrooms, the power, distance and rate of imposition affect teachers’ and students’ choice of language. However, the result of speech acts preference on Facebook is conflict. Previous research pointed out that memes can be categorized as communicative speech acts. Evidence shows that positive emoticons are preferred, which can improve friendships and vice versa. The review of literature contributes to further studies on the illocutionary act analysis of ESL classrooms in China and the communicative effectiveness of memes on the receivers

A nitrogen-doped three-dimensional carbon framework for high performance sodium ion batteries

A three-dimensional nitrogen-doped carbon framework (NCF) has been synthesized by annealing a zeolitic imidazolate framework (ZIF-67), followed by removing the residual metal ions. The NCF shows a polyhedral outline with strong interconnected hollow nanospheres as its subunits. It is highly porous, with a large surface area of 623 m2 g−1, and a high nitrogen content of 12.3 wt%. When applied as an anode material for a sodium ion battery, the NCF exhibits an excellent electrochemical performance with a high reversible capacity (327 mA h g−1, and stable at 300 mA h g−1), good cycling stability, and excellent rate capability (175 mA h g−1 at 2000 mA g−1). The presence of N in the NCF is believed to provide more active sites for enhancing the electrochemical performance, and provide more defects and nanovoids to trap more Na+ ions