Biomedical subjects

Kun Luo

Publications and source records attributed to Kun Luo.

10 recordsLinked to original sources

PubMed2026

Pedigree-assisted genotype imputation enables cost-effective genomic prediction in Penaeus vannamei.

Genomic selection in Penaeus vannamei has long been constrained by the high cost of dense genotyping. To address this limitation, we evaluated genotype imputation from a low-density 1 K panel to a medium-density 55 K panel of the "Yellow Sea Array No. 1" and examined its impact on genomic prediction for harvest body weight in P. vannamei. A four-generation pedigree including 30 great-grandparents, 39 grandparents, 100 parents, and 608 offspring was genotyped using the 55 K panel. A two-step experimental design was implemented to (i) assess the performance of different imputation algorithms under reference population scenarios with varying proportions of siblings, and (ii) compare six alternative reference population structures incorporating parents, ancestors, and siblings. Genotype imputation using the pedigree-based method FImpute v3.0 consistently achieved higher accuracy than the population-based method Beagle v5.5. Using this pedigree-assisted approach, imputation accuracy increased from 0.73 when only parental genotypes were used to 0.84 with the inclusion of 10% siblings, and subsequently plateaued at 0.87-0.90 when sibling representation reached 20%. Across the six reference population structures, imputation accuracy was primarily driven by the availability of parental genotypes, ranging from 0.50 to 0.56 in the absence of parents to 0.88-0.89 when both parents and ancestral generations were included. Accuracy remained high when both parents were available (0.84-0.87 with siblings; 0.73 without siblings) but declined substantially when only one parent was genotyped (0.65-0.68). Imputation accuracy was positively associated with both minor allele frequency (MAF) and linkage disequilibrium (max r2LD), with LD exerting the stronger influence. Heritability estimates derived from imputed 55 K genotypes were highly consistent with those obtained from the original 55 K data (0.39 ± 0.14 vs. 0.41 ± 0.14), indicating that genotype imputation did not compromise variance component estimation. In predictive ability analyses, pedigree-based BLUP (PBLUP) achieved higher predictive ability than genomic BLUP (GBLUP) based on the 1 K panel, with predictive abilities of 0.42-0.44 for PBLUP compared with 0.34-0.35 for GBLUP. Using imputed genotypes for genomic prediction further improved predictive ability relative to the true 1 K panel, yielding values ranging from 0.35 to 0.47. Notably, when parental genotypes were included in the reference population, GBLUP based on imputed genotypes surpassed the predictive ability of PBLUP and approached that achieved with the original 55 K genotypes (0.45-0.47). Collectively, these results provide the first empirical evidence that low- to medium-density genotype imputation, combined with pedigree information, can effectively support genomic prediction in P. vannamei. This study establishes a cost-efficient and scalable framework for implementing genomic selection in P. vannamei and provides a practical reference for the application of genomic selection in other aquaculture species with constrained breeding budgets.

Animals↗

PubMed2005

Regulation of Apobec3F and human immunodeficiency virus type 1 Vif by Vif-Cul5-ElonB/C E3 ubiquitin ligase.

The human cytidine deaminase Apobec3F (h-A3F), a protein related to the previously recognized antiviral factor Apobec3G (h-A3G), has antiviral activity against human immunodeficiency virus type 1 (HIV-1) that is suppressed by the viral protein Vif. The mechanism of HIV-1 Vif-mediated suppression of h-A3F is not fully understood. Here, we demonstrate that while h-A3F, like h-A3G, was able to suppress primate lentiviruses other than HIV-1 (simian immunodeficiency virus from African green monkeys [SIVagm] and Rhesus macaques [SIVmac]), the interaction between Vif proteins and h-A3F appeared to differ from that with h-A3G. H-A3F showed no change in its species specificity against HIV-1 or SIVagm Vif when a negatively charged amino acid was replaced with a lysine at position 128, a residue critical for h-A3G recognition by HIV-1 Vif. However, HIV-1 Vif, but not SIVagm Vif, was able to bind h-A3F and induce its polyubiquitination and degradation through the Cul5-containing E3 ubiquitin ligase. Interference with Cul5-E3 ligase function by depletion of Cul5, through RNA interference or overexpression of Cul5 mutants, blocked the ability of HIV-1 Vif to suppress h-A3F. A BC-box mutant of HIV-1 Vif that failed to recruit Cul5-E3 ligase but was still able to interact with h-A3F failed to suppress h-A3F. Interestingly, interference with Cul5-E3 ligase function or overexpression of h-A3F or h-A3G also increased the stability of HIV-1 Vif, suggesting that like the substrate molecules h-A3F and h-A3G, the substrate receptor protein Vif is itself also regulated by Cul5-E3 ligase. Our results indicate that Cul5-E3 ligase appears to be a common pathway hijacked by HIV-1 Vif to defeat both h-A3F and h-A3G. Developing inhibitors to disrupt the interaction between Vif and Cul5-E3 ligase could be therapeutically useful, allowing multiple host antiviral factors to suppress HIV-1.

Antiviral Agents↗

PubMed2004

Direct numerical simulation of a near-field particle-laden plane turbulent jet.

The present study investigates the gas-particle two-phase flow in the turbulent plane jet by solving the two-dimensional and compressible flow fields numerically using direct-numerical-simulation technique. The flow fields are spatially developing, but we focus our study on the evolution of coherent vortex structures and dispersion patterns of particles in the near field at different Stokes numbers. The initial symmetric mode of flow changes its shape to the asymmetric mode after about three convection periods as the flow moves downstream. The concessive paring processes between two and three vortex structures are observed. The predicted mean velocity profiles show self-similar behavior and coincide well with previous experimental data. The profiles of turbulent intensity and Reynolds shear stress also display self-similar characteristics in the further downstream regions. The local-focusing phenomena of particles occur in the quasicoherent dispersion structure of particles. The higher density distribution at the outer boundary of large-scale vortex structure characterizes the dispersion pattern of particles at the Stokes numbers of order of unity. Furthermore, these particles disperse largely along the lateral direction and show the nonuniform distribution of concentration. For the particles at the Stokes number of 0.01, the dispersion along the lateral direction is considerable due to the small aerodynamics response time, but the particles are distributed evenly in the flow field. Particles at the Stokes numbers of 10 and 50 disperse much less along the lateral direction with the even density distribution. These results support the previous conclusions on the dispersion of particles in the free shear flows.

Journal Article↗

PubMed2004

IgSF13, a novel human inhibitory receptor of the immunoglobulin superfamily, is preferentially expressed in dendritic cells and monocytes.

A novel inhibitory receptor of immunoglobin superfamily (IgSF), IgSF member 13 (IgSF13), has been identified from human dendritic cells (DC). IgSF13 is a type I transmembrane protein containing an N-terminal signal peptide, a extracellular region with a single Ig V-like domain, a transmembrane region, and a cytoplasmic tail with two classical immunoreceptor tyrosine-based inhibitory motifs (ITIM), suggesting its inhibitory function. IgSF13 shows significant homology to human CMRF35 and pIgR. IgSF13 gene is mapped to chromosome 17q25.2, very close to that of CMRF35. IgSF13 is preferentially expressed in myelo-monocytic cells, including monocytes, monocyte-derived DC, and monocyte-related cell lines. Upon pervanadate treatment, IgSF13 was hyper-phosphorylated and associated with Src homology-2 domain-containing phosphatases SHP-1 and SHIP, but not SHP-2. The identification of IgSF13 as a novel ITIM-bearing receptor selectively expressed by DC and monocytes suggests that it may be potentially involved in the negative regulation of specific leukocyte population.

Amino Acid Sequence↗

PubMed2004

Large eddy simulation of the gas-particle turbulent wake flow.

To find out the detailed characteristics of the coherent structures and associated particle dispersion in free shear flow, large eddy simulation method was adopted to investigate a two-dimensional particle-laden wake flow. The well-known Sub-grid Scale mode introduced by Smagorinsky was employed to simulate the gas flow field and Lagrangian approach was used to trace the particles. The results showed that the typical large-scale vortex structures exhibit a stable counter rotating arrangement of opposite sign, and alternately form from the near wall region, shed and move towards the downstream positions of the wake with the development of the flow. For particle dispersion, the Stokes number of particles is a key parameter. At the Stokes numbers of 1.4 and 3.8 the particles concentrate highly in the outer boundary regions. While the particles congregate densely in the vortex core regions at the Stokes number of 0.15, and the particles at Stokes number of 15 assemble in the vortex braid regions and the rib regions between the adjoining vortex structures.

Aerosols↗

PubMed2004

Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging.

APOBEC3G exerts its antiviral activity by targeting to retroviral particles and inducing viral DNA hypermutations in the absence of Vif. However, the mechanism by which APOBEC3G is packaged into virions remains unclear. We now report that viral genomic RNA enhances but is not essential for human APOBEC3G packaging into human immunodeficiency virus type 1 (HIV-1) virions. Packaging of APOBEC3G was also detected in HIV-1 Gag virus-like particles (VLP) that lacked all the viral genomic RNA packaging signals. Human APOBEC3G could be packaged efficiently into a divergent subtype HIV-1, as well as simian immunodeficiency virus, strain mac, and murine leukemia virus Gag VLP. Cosedimentation of human APOBEC3G and intracellular Gag complexes was detected by equilibrium density and velocity sucrose gradient analysis. Interaction between human APOBEC3G and HIV-1 Gag was also detected by coimmunoprecipitation experiments. This interaction did not require p6, p1, or the C-terminal region of NCp7. However, the N-terminal region, especially the first 11 amino acids, of HIV-1 NCp7 was critical for HIV-1 Gag and APOBEC3G interaction and virion packaging. The linker region flanked by the two active sites of human APOBEC3G was also important for efficient packaging into HIV-1 Gag VLP. Association of human APOBEC3G with RNA-containing intracellular complexes was observed. These results suggest that the N-terminal region of HIV-1 NC, which is critical for binding to RNA and mediating Gag-Gag oligomerization, plays an important role in APOBEC3G binding and virion packaging.

APOBEC-3G Deaminase↗

PubMed2004

Influence of primate lentiviral Vif and proteasome inhibitors on human immunodeficiency virus type 1 virion packaging of APOBEC3G.

The Vif protein of human immunodeficiency virus type 1 (HIV-1) is essential for viral evasion of the host antiviral protein APOBEC3G, also known as CEM15. Vif mutant but not wild-type HIV-1 viruses produced in the presence of APOBEC3G have been shown to undergo hypermutations in newly synthesized viral DNA upon infection of target cells, presumably resulting from C-to-U modification during minus-strand viral DNA synthesis. We now report that HIV-1 Vif could induce rapid degradation of human APOBEC3G that was blocked by the proteasome inhibitor MG132. The efficiency of Vif-induced downregulation of APOBEC3G expression depended on the level of Vif expression. A single amino acid substitution in the conserved SLQXLA motif reduced Vif function. Vif proteins from distantly related primate lentiviruses such as SIVagm were unable to suppress the antiviral activity of human APOBEC3G or the packaging of APOBEC3G into HIV-1 Vif mutant virions, due to a lack of interaction with human APOBEC3G. In the presence of the proteasome inhibitor MG132, virion-associated Vif increased dramatically. However, increased virion packaging of Vif did not prevent virion packaging of APOBEC3G when proteasome function was impaired, and the infectivity of these virions was significantly reduced. These results suggest that Vif function is required during virus assembly to remove APOBEC3G from packaging into released virions. Once packaged, virion-associated Vif could not efficiently block the antiviral activity of APOBEC3G.

APOBEC-3G Deaminase↗

PubMed2003

Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex.

Human immunodeficiency virus-1 (HIV-1) Vif is essential for viral evasion of host antiviral factor CEM15/APOBEC3G. We report that Vif interacts with cellular proteins Cul5, elongins B and C, and Rbx1 to form an Skp1-cullin-F-box (SCF)-like complex. The ability of Vif to suppress antiviral activity of APOBEC3G was specifically dependent on Cul5-SCF function, allowing Vif to interact with APOBEC3G and induce its ubiquitination and degradation. A Vif mutant that interacted with APOBEC3G but not with Cul5-SCF was functionally inactive. The Cul5-SCF was also required for Vif function in distantly related simian immunodeficiency virus mac. These results indicate that the conserved Cul5-SCF pathway used by Vif is a potential target for antiviral development.

APOBEC-3G Deaminase↗

PubMed2003

Modulation on coherent vortex structures by dispersed solid particles in a three-dimensional mixing layer.

Large-scale vortex structures and their effects on the dispersion of particles in turbulent free shear flows are very important in many industrial applications, such as combustion, pollution control, and materials processing. In order to understand large-scale vortex structures and particle dispersion in depth, as well as their interaction effects, a two-way-coupled three-dimensional mixing layer laden with particles at a Stokes number of 5 initially located in the upper half region is studied numerically. A pseudospectral method was used to directly simulate the flow fluid, and the Lagrangian approach was used to trace particles. The concept of computational particles is introduced to vary the mass loading of particles. The momentum coupling effect introduced by a particle approximates to a point force. The simulation results show that coherent structures are still dominant in the mixing layer, but the flow dynamics and particle dispersion are modulated. The length of large-scale vortex structures is shortened and the pairing is delayed. Higher mass loading results in lower energy of the fluid in the phase of Kelvin-Helmholtz rolling up, while in the pairing process of large-scale vortex structures, the energy of the fluid increases as the mass loading increases. Higher mass loading also leads to larger mixed fluid thickness and Reynolds stresses of the flow. In addition, the particle dispersion along the transverse direction differs from that along the spanwise direction, which indicates that the effects of the addition of a particle on the spanwise large-scale vortex structures are different from those on the streamwise large-scale vortex structures.

Journal Article↗

PubMedDate not supplied

Large eddy simulation of a particle-laden turbulent plane jet.

Gas-solid two-phase turbulent plane jet is applied to many natural situations and in engineering systems. To predict the particle dispersion in the gas jet is of great importance in industrial applications and in the designing of engineering systems. A large eddy simulation of the two-phase plane jet was conducted to investigate the particle dispersion patterns. The particles with Stokes numbers equal to 0.0028, 0.3, 2.5, 28 (corresponding to particle diameter 1 microm, 10 microm, 30 microm, 100 microm, respectively) in Re = 11 300 gas flow were studied. The simulation results of gas phase motion agreed well with previous experimental results. And the simulation results of the solid particles motion showed that particles with different Stokes number have different spatial dispersion; and that particles with intermediate Stokes number have the largest dispersion ratio.

Aerosols↗