Methylated DNMT1 and E2F1 Are Targeted for Proteolysis by L3MBTL3 and CRL4DCAF5 Ubiquitin Ligase

Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4DCAF5. Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4DCAF5. Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated

A hybrid ensemble forecasting model of passenger flow based on improved variational mode decomposition and boosting

An accurate passenger flow forecast can provide key information for intelligent transportation and smart cities, and help promote the development of smart cities. In this paper, a mixed passenger flow forecasting model based on the golden jackal optimization algorithm (GJO), variational mode decomposition (VMD) and boosting algorithm was proposed. First, the data characteristics of the original passenger flow sequence were extended. Second, an improved variational modal decomposition method based on the Sobol sequence improved GJO algorithm was proposed. Next, according to the sample entropy of each intrinsic mode function (IMF), IMF with similar complexity is combined into a new subsequence. Finally, according to the determination rules of the sub-sequence prediction model, the boosting modeling and prediction of different sub-sequences were carried out, and the final passenger flow prediction result was obtained. Based on the experimental results of three scenic spots, the mean absolute percentage error (MAPE) of the mixed set model is 0.0797, 0.0424 and 0.0849, respectively. The fitting degree reached 95.33%, 95.63% and 95.97% simultaneously. The results show that the hybrid model proposed in this study has high prediction accuracy and can provide reliable information sources for relevant departments, scenic spot managers and tourists

Autonomy-Supportive Teaching and Basic Psychological Need Satisfaction among School Students: The Role of Mindfulness

Grounded in self-determination theory, the purpose of this study was to investigate the relationships between autonomy-supportive teaching, mindfulness, and basic psychological need satisfaction/frustration. Secondary school students (n = 390, Mage = 15) responded to a survey form measuring psychological constructs pertaining to the research purpose. A series of multiple regression analysis showed that autonomy-supportive teaching and mindfulness positively predicted need satisfaction and negatively predicted need frustration. In addition, the associations between autonomy-supportive teaching and need satisfaction/frustration were moderated by mindfulness. Students higher in mindfulness were more likely to feel need satisfaction and less likely to experience need frustration, even in a low autonomy-supportive teaching environment. These results speak to the relevance of creating autonomy-supportive teaching environments and highlight mindfulness as a potential pathway to basic psychological need satisfaction in educational settings

Proliferating Cell Nuclear Antigen Interacts with the CRL4 Ubiquitin Ligase Subunit CDT2 in DNA Synthesis-induced Degradation of CDT1

During DNA replication or repair, the DNA polymerase cofactor, proliferating cell nuclear antigen (PCNA), homotrimerizes and encircles the replicating DNA, thereby acting as a DNA clamp that promotes DNA polymerase processivity. The formation of the PCNA trimer is also essential for targeting the replication-licensing protein, chromatin-licensing, and DNA replication factor 1 (CDT1), for ubiquitin-dependent proteolysis to prevent chromosomal DNA re-replication. CDT1 uses its PCNA-interacting peptide box (PIP box) to interact with PCNA, and the CRL4 E3 ubiquitin ligase subunit CDT2 is recruited through the formation of PCNA–CDT1 complexes. However, it remains unclear how CDT1 and many other PIP box–containing proteins are marked for degradation by the CRL4CDT2 ubiquitin ligase during DNA replication or damage. Here, using recombinant protein expression coupled with site-directed mutagenesis, we report that CDT2 and PCNA directly interact and this interaction depends on the presence of a highly conserved, C-terminal PIP box–like region in CDT2. Deletion or mutation of this region abolished the CDT2–PCNA interaction between CDT2 and PCNA both in vitro and in vivo. Moreover, PCNA-dependent CDT1 degradation in response to DNA damage and replication during the cell cycle requires an intact PIP box in CDT2. The requirement of the PIP boxes in both CDT2 and its substrate CDT1 suggests that the formation of the PCNA trimeric clamp around DNA during DNA replication and repair may bring together CDT1 and CRL4CDT2 ubiquitin E3 ligase to target CDT1 for proteolysis in a DNA synthesis–dependent manner

A Bright Squeezed Light Source for Quantum Sensing

The use of optical sensing for in vivo applications is compelling, since it offers the advantages of non-invasiveness, non-ionizing radiation, and real-time monitoring. However, the signal-to-noise ratio (SNR) of the optical signal deteriorates dramatically as the biological tissue increases. Although increasing laser power can improve the SNR, intense lasers can severely disturb biological processes and viability. Quantum sensing with bright squeezed light can make the measurement sensitivity break through the quantum noise limit under weak laser conditions. A bright squeezed light source is demonstrated to avoid the deterioration of SNR and biological damage, which integrates an external cavity frequency-doubled laser, a semi-monolithic standing cavity with periodically poled titanyl phosphate (PPKTP), and a balanced homodyne detector (BHD) assembled on a dedicated breadboard. With the rational design of the mechanical elements, the optical layout, and the feedback control equipment, a maximum non-classical noise reduction of −10.7 ± 0.2 dB is observed. The average squeeze of −10 ± 0.2 dB in continuous operation for 60 min is demonstrated. Finally, the intracavity loss of degenerate optical parametric amplifier (DOPA) and the initial bright squeezed light can be calculated to be 0.0021 and −15.5 ± 0.2 dB, respectively. Through the above experimental and theoretical analysis, the direction of improving bright squeeze level is pointed out

Complete genome sequences of three sub-genotype 2.1b isolates of classical swine fever virus in China

Classical swine fever (CSF) has caused severe economic losses in pig production in many countries. Recent CSF outbreaks in China are mainly associated with sub-genotype 2.1 of CSF virus (CSFV). Although there is abundant information regarding 2.1 isolates, few data are available on whole-genome analysis

Characterisation of newly emerged isolates of classical swine fever virus in China, 2014–2015

Introduction: In 2014–2015, the epidemic of classical swine fever (CSF) occurred in many large-scale pig farms in different provinces of China, and a subgenotype 2.1d of CSF virus (CSFV) was newly identified

Complete genomic characteristics and pathogenic analysis of the newly emerged classical swine fever virus in China

Abstract Background Classical swine fever (CSF) is one of the most devastating and highly contagious viral diseases in the world. Since late 2014, outbreaks of a new sub-genotype 2.1d CSF virus (CSFV) had caused substantial economic losses in numbers of C-strain vaccinated swine farms in China. The objective of the present study was to explore the genomic characteristics and pathogenicity of the newly emerged CSFV isolates in China during 2014–2015. Results All the new 8 CSFV isolates belonged to genetic sub-genotype 2.1d. Some genomic variations or deletions were found in the UTRs and E2 of these new isolates. In addition, the pathogenicity of HLJ1 was less than Shimen, suggesting the HLJ1 of sub-genotype 2.1d may be a moderated pathogenic isolate and the C-strain vaccine can supply complete protection. Conclusions The new CSFV isolates with unique genomic characteristics and moderate pathogenicity can be epidemic in many large-scale C-strain vaccinated swine farms. This study provides the information should be merited special attention on establishing prevention and control policies for CSF