Few reports exist on QTL mapping of the important economic traits of hawthorn. We hybridized the cultivars 'Shandongdamianqiu' (female parent) and 'Xinbinruanzi' (male parent), and 130 F1 individuals ...and the two parents were used for RAD-seq, SNP development, and high-density linkage map construction. Three genetic maps were obtained, one for each of the parents and an integrated one. In these three maps, 17 linkage groups were constructed. The female and male parent maps contained 2657 and 4088 SNP markers, respectively, and had genetic distances of 2689.65 and 2558.41 cM, respectively, whereas the integrated map was 2470.02 cM, and contained 6,384 SNP markers. QTL mapping based on six agronomic traits, namely fruit transverse diameter, vertical diameter, single fruit weight, pericarp brittleness, pericarp puncture hardness, and average sarcocarp firmness were conducted, and 25 QTLs were detected in seven linkage groups. Explained phenotypic variation rate ranged from 17.7% to 35%. This genetic map contains the largest number of molecular markers ever obtained from hawthorn and will provide an important future reference for fine QTL mapping of economic traits and molecular assisted selection of hawthorn.
Influenza A virus (IAV) coopts numerous host factors to complete its replication cycle. Here, we identify free fatty acid receptor 2 (FFAR2) as a cofactor for IAV entry into host cells. We found that ...downregulation of FFAR2 or Ffar2 expression significantly reduced the replication of IAV in A549 or RAW 264.7 cells. The treatment of A549 cells with small interfering RNA (siRNA) targeting
or the FFAR2 pathway agonists 2-(4-chlorophenyl)-3-methyl-
-(thiazol-2-yl)butanamide (4-CMTB) and compound 58 (Cmp58) (
)-2-(4-chlorophenyl)-3,3-dimethyl-
-(5-phenylthiazol-2-yl)butanamide dramatically inhibited the nuclear accumulation of viral nucleoprotein (NP) at early time points postinfection, indicating that FFAR2 functions in the early stage of the IAV replication cycle. FFAR2 downregulation had no effect on the expression of sialic acid (SA) receptors on the cell membrane, the attachment of IAV to the SA receptors, or the activity of the viral ribonucleoprotein (vRNP) complex. Rather, the amount of internalized IAVs was significantly reduced in FFAR2-knocked-down or 4-CMTB- or Cmp58-treated A549 cells. Further studies showed that FFAR2 associated with β-arrestin1 and that β-arrestin1 interacted with the β2-subunit of the AP-2 complex (AP2B1), the essential adaptor of the clathrin-mediated endocytosis pathway. Notably, siRNA knockdown of either β-arrestin1 or AP2B1 dramatically impaired IAV replication, and AP2B1 knockdown or treatment with Barbadin, an inhibitor targeting the β-arrestin1/AP2B1 complex, remarkably decreased the amount of internalized IAVs. Moreover, we found that FFAR2 interacted with three G protein-coupled receptor (GPCR) kinases (i.e., GRK2, GRK5, and GRK6) whose downregulation inhibited IAV replication. Together, our findings demonstrate that the FFAR2 signaling cascade is important for the efficient endocytosis of IAV into host cells.
To complete its replication cycle, IAV hijacks the host endocytosis machinery to invade cells. However, the underlying mechanisms of how IAV is internalized into host cells remain poorly understood, emphasizing the need to elucidate the role of host factors in IAV entry into cells. In this study, we identified FFAR2 as an important host factor for the efficient replication of both low-pathogenic and highly pathogenic IAV. We revealed that FFAR2 facilitates the internalization of IAV into target cells during the early stage of infection. Upon further characterization of the role of FFAR2-associated proteins in virus replication, we found that the FFAR2-β-arrestin1-AP2B1 signaling cascade is important for the efficient endocytosis of IAV. Our findings thus further our understanding of the biological details of IAV entry into host cells and establish FFAR2 as a potential target for antiviral drug development.
Calibration transfer is an important field for near-infrared (NIR) spectroscopy in practical applications. However, most transfer methods are constructed with standard samples, which are expensive ...and difficult to obtain. Taking this problem into account, this paper proposes a calibration transfer method based on affine invariance without transfer standards (CTAI). Our method can be utilized to adjust the difference between two instruments by affine transformation. CTAI firstly establishes a partial least squares (PLS) model of the master instrument to obtain score matrices and predicted values of the two instruments, and then the regression coefficients between each of the score vectors and predicted values are computed for the master instrument and the slave instrument, respectively. Next, angles and biases are calculated between the regression coefficients of the master instrument and the corresponding regression coefficients of the slave instrument, respectively. Finally, by introducing affine transformation, new samples are predicted based on the obtained angles and biases. A comparative study between CTAI and the other five methods was conducted, and the performances of these algorithms were tested with two NIR spectral datasets. The obtained experimental results show clearly that, in general CTAI is more robust and can also achieve the best Root Mean Square Error of test sets (RMSEPs). In addition, the results of statistical difference with the Wilcoxon signed rank test show that CTAI is generally better than the others, and at least statistically the same.
In order to enable the calibration model to be effectively transferred among multiple instruments and correct the differences between the spectra measured by different instruments, a new feature ...transfer model based on partial least squares regression (PLS) subspace (PLSCT) is proposed in this paper. Firstly, the PLS model of the master instrument is built, meanwhile a PLS subspace is constructed by the feature vectors. Then the master spectra and the slave spectra are projected into the PLS subspace, and the features of the spectra are also extracted at the same time. In the subspace, the pseudo predicted feature of the slave spectra is transferred by the ordinary least squares method so that it matches the predicted feature of the master spectra. Finally, a feature transfer relationship model is constructed through the feature transfer of the PLS subspace. This PLS-based subspace transfer provides an efficient method for performing calibration transfer with only a small number of standard samples. The performance of the PLSCT was compared and assessed with slope and bias correction (SBC), piecewise direct standardization (PDS), calibration transfer method based on canonical correlation analysis (CCACT), generalized least squares (GLSW), multiplicative signal correction (MSC) methods in three real datasets, statistically tested by the Wilcoxon signed rank test. The obtained experimental results indicate that PLSCT method based on the PLS subspace is more stable and can acquire more accurate prediction results.
Host defense systems employ posttranslational modifications to protect against invading pathogens. Here, we found that protein inhibitor of activated STAT 1 (PIAS1) interacts with the nucleoprotein ...(NP), polymerase basic protein 1 (PB1), and polymerase basic protein 2 (PB2) of influenza A virus (IAV). Lentiviral-mediated stable overexpression of PIAS1 dramatically suppressed the replication of IAV, whereas siRNA knockdown or CRISPR/Cas9 knockout of PIAS1 expression significantly increased virus growth. The expression of PIAS1 was significantly induced upon IAV infection in both cell culture and mice, and PIAS1 was involved in the overall increase in cellular SUMOylation induced by IAV infection. We found that PIAS1 inhibited the activity of the viral RNP complex, whereas the C351S or W372A mutant of PIAS1, which lacks the SUMO E3 ligase activity, lost the ability to suppress the activity of the viral RNP complex. Notably, the SUMO E3 ligase activity of PIAS1 catalyzed robust SUMOylation of PB2, but had no role in PB1 SUMOylation and a minimal role in NP SUMOylation. Moreover, PIAS1-mediated SUMOylation remarkably reduced the stability of IAV PB2. When tested in vivo, we found that the downregulation of Pias1 expression in mice enhanced the growth and virulence of IAV. Together, our findings define PIAS1 as a restriction factor for the replication and pathogenesis of IAV.
This study investigates the impact of capitalizing educational resources on housing prices. As housing has gradually transitioned from a basic social right to a means of accumulating individual and ...familial wealth, it has emerged as a significant indicator of social stratification and has increasingly become a crucial tool for the intergenerational reproduction of social class. This paper takes Nanjing, China, as a case study and uses the geographically weighted regression model (GWR) and the hedonic pricing model (HPM) to investigate the impact of high-quality primary schools on housing prices. The results show that high-quality educational resources have become the most significant influencing factor on residential prices in Nanjing. The analysis in the mechanism section further indicates that the uneven distribution of educational resources in China is a continuation of the “danwei” system. Moreover, during the urbanization process, these high-quality educational resources are often leveraged by the government and developers, who see them as essential tools to attract investment and inflate housing prices. Therefore, the current overlap of the school district system and the marketization of housing in China not only intensifies residential segregation within the city, leading to severe residential inequality but also rebuilds social segregation within “danwei” and facilitates its reproduction.
Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition ...of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63-or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
Transcription and replication of the influenza A virus (IAV) genome occur in the nucleus of infected cells and are carried out by the viral ribonucleoprotein complex (vRNP). As a major component of ...the vRNP complex, the viral nucleoprotein (NP) mediates the nuclear import of the vRNP complex via its nuclear localization signals (NLSs). Clearly, an effective way for the host to antagonize IAV infection would be by targeting vRNP nuclear import. Here, we identified phospholipid scramblase 1 (PLSCR1) as a binding partner of NP by using a yeast two-hybrid (Y2H) screen. The interaction between NP and PLSCR1 in mammalian cells was demonstrated by using co-immunoprecipitation and pull-down assays. We found that the stable overexpression of PLSCR1 suppressed the nuclear import of NP, hindered the virus life cycle, and significantly inhibited the replication of various influenza subtypes. In contrast, siRNA knockdown or CRISPR/Cas9 knockout of PLSCR1 increased virus propagation. Further analysis indicated that the inhibitory effect of PLSCR1 on the nuclear import of NP was not caused by affecting the phosphorylation status of NP or by stimulating the interferon (IFN) pathways. Instead, PLSCR1 was found to form a trimeric complex with NP and members of the importin α family, which inhibited the incorporation of importin β, a key mediator of the classical nuclear import pathway, into the complex, thus impairing the nuclear import of NP and suppressing virus replication. Our results demonstrate that PLSCR1 negatively regulates virus replication by interacting with NP in the cytoplasm and preventing its nuclear import.
Avian influenza viruses (AIVs) must acquire mammalian-adaptive mutations before they can efficiently replicate in and transmit among humans. The PB2 E627K mutation is known to play a prominent role ...in the mammalian adaptation of AIVs. The H7N9 AIVs that emerged in 2013 in China easily acquired the PB2 E627K mutation upon replication in humans. Here, we generate a series of reassortant or mutant H7N9 AIVs and test them in mice. We show that the low polymerase activity attributed to the viral PA protein is the intrinsic driving force behind the emergence of PB2 E627K during H7N9 AIV replication in mice. Four residues in the N-terminal region of PA are critical in mediating the PB2 E627K acquisition. Notably, due to the identity of viral PA protein, the polymerase activity and growth of H7N9 AIV are highly sensitive to changes in expression levels of human ANP32A protein. Furthermore, the impaired viral polymerase activity of H7N9 AIV caused by the depletion of ANP32A led to reduced virus replication in
mice, abolishing the acquisition of the PB2 E627K mutation and instead driving the virus to acquire the alternative PB2 D701N mutation. Taken together, our findings show that the emergence of the PB2 E627K mutation of H7N9 AIV is driven by the intrinsic low polymerase activity conferred by the viral PA protein, which also involves the engagement of mammalian ANP32A.
The emergence of the PB2 E627K substitution is critical in the mammalian adaptation and pathogenesis of AIV. H7N9 AIVs that emerged in 2013 possess a prominent ability in gaining the PB2 E627K mutation in humans. Here, we demonstrate that the acquisition of the H7N9 PB2 E627K mutation is driven by the low polymerase activity conferred by the viral PA protein in human cells, and four PA residues are collectively involved in this process. Notably, the H7N9 PA protein leads to significant dependence of viral polymerase function on human ANP32A protein, and
knockout abolishes PB2 E627K acquisition in mice. These findings reveal that viral PA and host ANP32A are crucial for the emergence of PB2 E627K during adaptation of H7N9 AIVs to humans.
Bipolar DC–DC converter plays an important role in data center and distributed renewable energy unit with the advantages of high efficiency and low cost. In order to improve the power density of ...bipolar DC–DC converter, a high frequency and high power density bipolar DC–DC converter based on Gallium Nitride High Electron Mobility Transistor (GaN HEMT) is proposed under the development trend of miniaturization, lightweight and high power density of power electronic converter. By using gallium nitride (GaN) switch device, the switching frequency of the converter is increased to 1 MHz, which effectively reduces the volume and weight of the device. In addition, through the design of high frequency driver circuit, two separate pull-up/pull-down outputs are provided for the control signal, and the rising and falling rates of the switch signal are controlled by adjusting the resistance to obtain good performance and driving stability. The experimental results show that the total weight of the converter with radiator is only 121.6 g, the power density is 35.23 W/in3, and the maximum efficiency can reach 92.7%. Compared with the same type of converter, the volume and weight of the converter are greatly reduced, effectively realizing the goals of miniaturization, lightweight and high power density of the converter.
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