Molecular characterization and genetic diversity of parvoviruses prevalent in cats in Central and Eastern China from 2018 to 2022

Cats are a potential source of genetic diversity for parvoviruses. Herein, 134 samples were collected from cats with clinical gastroenteritis and analyzed for the presence of viral DNA via polymerase chain reaction, which revealed 48 positive samples. Identity analysis of VP2 nucleotide sequences indicated that these 48 strains, belonging to feline panleukopenia virus (FPV) and canine parvovirus type-2 (CPV-2; including new CPV-2a and CPV-2c genotypes), shared 94.59–99.94% nucleotide identity with the reference strains. The FPV strain F8 (isolated from Vietnam) appeared to be a recombinant of strains HB2003 and JS1901, whereas the Chinese CPV-2b strain BM-(11) isolated in 2011 was believed to be a recombinant of strains AH2008 and JS1901. In phylogenetic tree analysis based on VP2 nucleotide sequences, all obtained FPV strains and most reference FPV strains were clustered together, except strain BJ-22, which originated from monkeys. Further, two new CPV-2a strains (AH2005 and AH2008) were close to the newly reported Chinese CPV-2a strains but were distant from the other CPV-2a strains, namely CPV-339 (from the United States) and K022 (from South Korea). Additionally, the FPV and CPV-2 strains had high mutation rates in the antigenic regions of the VP2 protein. According to model prediction of the CPV–VP2 protein, these mutations may cause changes in the tertiary structure of VP2. The findings of this study can be used to improve the pre-evaluation of vaccination efficacy against diseases caused by FPV and CPV-2 in domestic cats and understand their genotypic transmission and mutation trends

Differential regulation of clathrin and its adaptor proteins during membrane recruitment for endocytosis

In plants, clathrin-mediated endocytosis (CME) is dependent on the function of clathrin and its accessory heterooligomeric adaptor protein complexes, ADAPTOR PROTEIN2 (AP-2) and the TPLATE complex (TPC), and is negatively regulated by the hormones auxin and salicylic acid (SA). The details for how clathrin and its adaptor complexes are recruited to the plasma membrane (PM) to regulate CME, however, are poorly understood. We found that SA and the pharmacological CME inhibitor tyrphostin A23 reduce the membrane association of clathrin and AP-2, but not that of the TPC, whereas auxin solely affected clathrin membrane association, in Arabidopsis (Arabidopsis thaliana). Genetic and pharmacological experiments revealed that loss of AP2 mu or AP2 sigma partially affected the membrane association of other AP-2 subunits and that the AP-2 subunit AP2 sigma, but not AP2 mu, was required for SA-and tyrphostin A23-dependent inhibition of CME. Furthermore, we show that although AP-2 and the TPC are both required for the PM recruitment of clathrin in wild-type cells, the TPC is necessary for clathrin PM association in AP-2-deficient cells. These results indicate that developmental signals may differentially modulate the membrane recruitment of clathrin and its core accessory complexes to regulate the process of CME in plant cells

N-Oxide Reduction of Quinoxaline-1,4-Dioxides Catalyzed by

ABSTRACT Quinoxaline-1,4-dioxides (QdNOs) are a class of quinoxaline derivatives that are widely used in humans or animals as drugs or feed additives. However, the metabolic mechanism, especially the involved enzymes, has not been reported in detail. In this study, the N-oxide reduction enzyme, porcine aldehyde oxidase SsAOX1 was identified and characterized. The SsAOX1 gene was cloned from pig liver through reverse-transcription polymerase chain reaction using degenerate primers, which encode a 147-kDa protein with typical aldehyde oxidase motifs, two [2Fe-2S] centers, a flavin adenine dinucleotide (FAD) binding domain, and a molybdenum cofactor domain. After heterologous expression in a prokaryote, purified SsAOX1 formed a functional homodimer under native conditions. Importantly, the SsAOX1 catalyzed the N-oxide reduction at the N1 position of three representative QdNOs (quinocetone, mequindox, and cyadox), which are commonly used as animal feed additives. SsAOX1 has the highest activity toward quinocetone, followed by mequindox and cyadox, with kcat/K m values of 1.94 6 0.04, 1.27 6 0.15, and 0.43 6 0.09 minute 21 mM 21 , respectively. However, SsAOX1 has the lowest substrate affinity for quinocetone, followed by the cyadox and mequindox, with K m values of 4.36 6 0.56, 3.16 6 0.48, and 2.96 6 0.51 mM, respectively. In addition, using site-directed mutagenesis, we found that substitution of glycine 1019 with threonine endows SsAOX1 with N-oxide reductive activity at the N4 position. The goal of this study was to identify and characterize the N-oxide reduction enzyme for a class of veterinary drugs, QdNOs, which will aid in the elucidation of the metabolic pathways of QdNOs and will provide a theoretical basis for their administration and new veterinary drug design

The large area detector onboard the eXTP mission

The Large Area Detector (LAD) is the high-throughput, spectral-timing instrument onboard the eXTP mission, a flagship mission of the Chinese Academy of Sciences and the China National Space Administration, with a large European participation coordinated by Italy and Spain. The eXTP mission is currently performing its phase B study, with a target launch at the end-2027. The eXTP scientific payload includes four instruments (SFA, PFA, LAD and WFM) offering unprecedented simultaneous wide-band X-ray timing and polarimetry sensitivity. The LAD instrument is based on the design originally proposed for the LOFT mission. It envisages a deployed 3.2 m2 effective area in the 2-30 keV energy range, achieved through the technology of the large-area Silicon Drift Detectors - offering a spectral resolution of up to 200 eV FWHM at 6 keV - and of capillary plate collimators - limiting the field of view to about 1 degree. In this paper we will provide an overview of the LAD instrument design, its current status of development and anticipated performance

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of rotation rate on the recovery of Nd–Fe–B sludge via rotation-reduction diffusion method

In recent years, calcium reduction diffusion has emerged as a new method for in situ regeneration of Nd–Fe–B sludge. In this work, rotation calcium thermal reduction diffusion technology was used for the first time to solve the issue of batch regeneration of Nd–Fe–B sludge to a certain extent, and regenerated Nd–Fe–B powder with uniform size and good dispensability was prepared. The effect of rotation rate on the properties of regenerated Nd–Fe–B powder was mainly studied. We found that the magnetic properties of the regenerated magnetic powder initially increased and then decreased with increasing rotation rate. When the rotation rate was 10 rpm, the magnetization of regenerated magnetic powder reached 138.22 emu/g, which was 10.2% higher than that of the purified sludge. The regenerated magnetic powder was doped with rare earth-rich alloy powder and high remanence alloy powder to control the composition, where the regenerated sintered magnet was prepared. The density reached 7.51 g/cm3 and the maximum magnetic energy product reached 42.87 MGOe, laying a foundation for the short-process in situ regeneration of Nd–Fe–B sludge

Hierarchical Contrastive Learning for Temporal Point Processes

As an important sequential model, the temporal point process (TPP) plays a central role in real-world sequence modeling and analysis, whose learning is often based on the maximum likelihood estimation (MLE). However, due to imperfect observations, such as incomplete and sparse sequences that are common in practice, the MLE of TPP models often suffers from overfitting and leads to unsatisfactory generalization power. In this work, we develop a novel hierarchical contrastive (HCL) learning method for temporal point processes, which provides a new regularizer of MLE. In principle, our HCL considers the noise contrastive estimation (NCE) problem at the event-level and at the sequence-level jointly. Given a sequence, the event-level NCE maximizes the probability of each observed event given its history while penalizing the conditional probabilities of the unobserved events. At the same time, we generate positive and negative event sequences from the observed sequence and maximize the discrepancy between their likelihoods through the sequence-level NCE. Instead of using time-consuming simulation methods, we generate the positive and negative sequences via a simple but efficient model-guided thinning process. Experimental results show that the MLE method assisted by the HCL regularizer outperforms classic MLE and other contrastive learning methods in learning various TPP models consistently. The code is available at https://github.com/qingmeiwangdaily/HCL_TPP