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Biomedical subjects

Yue Lu

Publications and source records attributed to Yue Lu.

11 recordsLinked to original sources

De novo Genes in Plants: Origins, Mechanisms, and Functional Implications.

De novo genes originate from previously non-coding genomic regions. They provide an important source of lineage-specific innovation. In plants, these genes may contribute to adaptation, trait diversity and crop evolution. This review summarizes recent progress in plant de novo gene research. It first discusses major routes of gene birth, including transcription-first, open reading frame (ORF)-first and concurrent models. It also examines how nascent loci acquire regulatory control and enter existing biological networks. The review then summarizes their evolutionary features, including weak early constraint, rapid molecular change, restricted expression and structural refinement. It further discusses plant de novo genes involved in stress responses, seed germination, kernel dehydration, subspecies divergence, reproductive isolation and floral scent diversification. Current methods for identifying de novo genes remain limited by rapid sequence evolution, genome annotation quality, polyploidy and transposable elements. Whole-genome synteny alignment, multi-omics evidence and machine-learning approaches can improve candidate discovery. However, each method has important limitations. Finally, this review highlights key future questions in functional validation, latent coding potential in long non-coding RNAs, epigenetic activation, regulatory-network integration and crop improvement. These perspectives clarify how de novo genes shape plant adaptation and how they may be used in precision breeding and synthetic biology.

adaptive evolution↗

Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation.

The histone H3K36-specific methyltransferase ASH1L plays a critical role in development and is frequently dysregulated in human diseases, particularly cancer. Here, we report on the biological functions of the C-terminal region of ASH1L encompassing a bromodomain (ASH1LBD), a plant homeodomain (ASH1LPHD) finger, and a bromo-adjacent homology (ASH1LBAH) domain, structurally characterize these domains, describe their mechanisms of action, and explore functional crosstalk between them. We find that ASH1LPHD recognizes H3K4me2/3, whereas the neighboring ASH1LBD and ASH1LBAH have DNA binding activities. The DNA binding function of ASH1LBAH is a driving force for the association of ASH1L with the linker DNA in the nucleosome, and the large interface with ASH1LPHD stabilizes the ASH1LBAH fold, merging two domains into a single module. We show that ASH1L is involved in embryonic stem cell differentiation and co-localizes with H3K4me3 but not with H3K36me2 at transcription start sites of target genes and genome wide, and that the interaction of ASH1LPHD with H3K4me3 is inhibitory to the H3K36me2-specific catalytic activity of ASH1L. Our findings shed light on the mechanistic details by which the C-terminal domains of ASH1L associate with chromatin and regulate the enzymatic function of ASH1L.

Histones↗

In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukemia.

For developing gene therapy for chronic myelogenous leukemia (CML), we evaluated the feasibility of using autologous bone marrow stromal cells (BMSCs) of one CML patient as a target cell population and studied the efficiency of recombinant adenovirus-mediated human Gamma Interferon (hIFN-gamma) gene transfer into BMSCs. BMSCs can be readily obtained, expanded, and successfully transduced with adenoviral vectors in vitro. We studied the in vitro expression of hIFN-gamma in human BMSCs following transduction with Ad/hIFN-gamma. On transduction of BMSCs at a MOI of 50, the expression and secretion of hIFN-gamma were achieved as high as 5492 +/- 660 approximately 50647 +/- 4049 ng/10(6) cells per 24 h over the course of 3 weeks. We further studied the effects of hIFN-gamma produced by transduced BMSCs on the proliferation of the human leukemia cell line K562 cells in vitro, proliferation of K562 cells was markedly inhibited in the experimental groups as compared with the other two control groups after 5 days of coculture. We also found that the percentage of K562 cells in the G(1) phase of cell cycle can be increased by treatment of hIFN-gamma produced by Ad/hIFN-gamma transduced BMSCs, but the percentage of K562 cells in the S phase of cell cycle can be decreased in the same time. Apoptosis rate of K562 cells in the experimental groups was 30.8 +/- 8.5%, as compared with the other two control groups (5.6 +/- 1.3% and 5.5 +/- 0.8%, respectively) (p < 0.01). Our results indicate that hIFN-gamma gene engineered BMSCs of CML donors could be successfully established and that local production of hIFN-gamma is sufficiently to inhibit the proliferation of K562 cells and induce apoptosis of K562 cells in vitro, suggesting an important potential use in the clinical gene therapy of CML.

Adenoviridae↗

A polynomial time solvable formulation of multiple sequence alignment.

Since traditional multiple alignment formulations are NP-hard, heuristics are commonly employed to find acceptable alignments with no guaranteed performance bound. This causes a substantial difficulty in understanding what the resulting alignment means and in assessing the quality of these alignments. We propose an alternative formulation of multiple alignment based on the idea of finding a multiple alignment of k sequences which preserves k - 1 pairwise alignments as specified by edges of a given tree. Although it is well known that such a preserving alignment always exists, it did not become a mainstream method for multiple alignment since it seems that a lot of information is lost from ignoring pairwise similarities outside the tree. In contrast, by using pairwise alignments that incorporate consistency information from other sequences, we show that it is possible to obtain very good accuracy with the preserving alignment formulation. We show that a reasonable objective function to use is to find the shortest preserving alignment, and, by a reduction to a graph-theoretic problem, that the problem of finding the shortest preserving multiple alignment can be solved in polynomial time. We demonstrate the success of this approach on three sets of benchmark multiple alignments by using consistency-based pairwise alignments from the first stage of two of the best performing progressive alignment algorithms TCoffee and ProbCons and replace the second heuristic progressive step of these algorithms by the exact preserving alignment step. We apply this strategy to TCoffee and show that our approach outperforms TCoffee on two of the three test sets. We apply the strategy to a variant of ProbCons with no iterative refinements and show that our approach achieves similar or better accuracy except on one test set. We also compare our performance to ProbCons with iterative refinements and show that our approach achieves similar or better accuracy on many subcategories even without further refinements. The most important advantage of the preserving alignment formulation is that we are certain that we can solve the problem in polynomial time without using a heuristic. A software program implementing this approach (PSAlign) is available at http://faculty.cs.tamu.edu/shsze/psalign.

Algorithms↗

[Regulatory expression of human interferon-gamma gene in murine bone marrow stromal cells by Tet-off system].

BACKGROUND & OBJECTIVE: The Tet-off system is a gene expression regulating system, which has high efficiency, low toxicity and strict turning-off function. This study was to investigate the regulatory expression of human interferon-gamma (IFNgamma) gene in murine bone marrow stromal cells (BMSCs) by Tet-off system. METHODS: Plasmid pTre and human IFNgamma gene were digested using Sac II and Xba I, purified, and ligated by T4 ligase. The recombinant pTre-IFNgamma was identified by restriction analysis and sequencing. pTet-off and pTre-IFNgamma were co-transfected into murine BMSCs. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect IFNgamma mRNA 48 h after transfection. ELISA was used to detect IFNgamma protein in the cell culture medium everyday to analyze the secretary mode of IFNgamma. Then, Tetracycline was added to the culture medium immediately after co-transfection in gradient concentration and 48 h after co-transfection to observe its effect on IFNgamma secretion. RESULTS: Restriction analysis and sequencing confirmed the orientation and sequence of the recombinant plasmid pTre-IFNgamma were correct. RT-PCR detected IFNgamma mRNA in BMSCs 48 h after co-transfection. ELISA showed the secretion of IFNgamma lasted 6 days and a peak appeared in the third 24 h, which was (720.09+/-241.51) pg per 1 x10(6) cells. Increasing tetracycline decreased the secretion of IFNgamma in the first 48 h: 10-100 ng/ml tetracycline decreased the secretion to nearly 0. When tetracycline was added 48 h after co-transfection, the secretion was obviously suppressed 8 h later, and the suppression was strengthened as time went by. CONCLUSION: The Tet-off system can efficiently and rapidly down-regulate the expression of human IFNgamma gene in murine BMSCs.

Animals↗

Single-nucleotide polymorphism versus microsatellite markers in a combined linkage and segregation analysis of a quantitative trait.

Increasingly, single-nucleotide polymorphism (SNP) markers are being used in preference to microsatellite markers. However, methods developed for microsatellites may be problematic when applied to SNP markers. We evaluated the results of using SNPs vs. microsatellites in Monte Carlo Markov chain (MCMC) oligogenic combined segregation and linkage analysis methods. These methods were developed with microsatellite markers in mind. We selected chromosome 7 from the Collaborative Study on the Genetics of Alcoholism dataset for analysis because linkage to an electrophysiological trait had been reported there. We found linkage in the same region of chromosome 7 with the Affymetrix SNP data, the Illumina SNP data, and the microsatellite marker data. The MCMC sampler appears to mix with both types of data. The sampler implemented in this MCMC oligogenic combined segregation and linkage analysis appears to handle SNP data as well as microsatellite data and it is possible that the localizations with the SNP data are better.

Chromosome Mapping↗

La4Cu(3-x)Zn(x)MoO12: zinc-doped cuprates with Kagomé lattices.

Two solid solutions, La4Cu(3-x)Zn(x)MoO12 (0.05 < or = x < or = 0.20, SS1) and La4Cu(3-x)Zn(x)MoO12 (0.30 < or = x < or = 2.40, SS2), were synthesized at ambient pressure and at temperatures from 1025 to 1200 degrees C by traditional solid-state reactions. Their structures were determined from X-ray powder diffraction with the help of electron and neutron diffraction. The atomic arrangements of SS1 and SS2 are similar, but their space groups are different, Pmnm for SS1 and P-1 for SS2, respectively. The copper, zinc, and molybdenum are coordinated by oxygen in corner-sharing trigonal bipyramids that are sandwiched between layers of lanthanum cations. In the transition metal cations layer of SS2, the copper and zinc cations order into a Kagomé-like lattice of triangular clusters. The magnetism has been measured from 2 to 300 K and is highly influenced by the geometric arrangement of the Cu(II) and Zn(II) cations. The number of free electrons per three Cu atoms is close to one for all samples in SS1 and SS2 indicating that the system can be well expressed by independent Cu(II)3 clusters. Spontaneous magnetization was observed in the system.

Copper↗

[Correlation of bone marrow stromal cells to leukemia and its research advancement in gene therapy for leukemia].

Bone marrow stromal cells (BMSCs) have a pluripotent characteristic, and can be readily isolated and expanded in vitro. After in vivo transplantation, BMSCs can home to blood marrow, and survive for a long time by self-renewing. They can influence the biological characteristics of leukemia cells from several aspects, and participate in the outbreak process and pathologic process of leukemia. BMSCs with normal functions have direct antitumur effects on leukemic cells. They can regulate the immunity remarkably. Genetically engineered BMSCs can deliver target therapeutic proteins over sufficient time after in vivo transplantation. Thus, BMSCs are considered to be an ideal therapeutic cell vehicle and target cells in the gene therapy for leukemia. Interferons, a cytokines family, are capable of producing multiplex biological effects, and have remarkable curative effects on hair cell leukemia and chronic myelogenous leukemia. Here we reviewed the possibility and perspective of molecular target therapy for leukemia by interferons-modified BMSCs.

Animals↗

Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter.

Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model.

Adenoviridae↗

Cyanobacterial signature genes.

A comparison of 8 cyanobacterial genomes reveals that there are 181 shared genes that do not have obvious orthologs in other bacteria. These signature genes define aspects of the genotype that are uniquely cyanobacterial. Approximately 25% of these genes have been associated with some function. These signature genes may or may not be involved in photosynthesis but likely they will be in many cases. In addition, several examples of widely conserved gene order involving two or more signature genes were observed. This suggests there may be regulatory processes that have been preserved throughout the long history of the cyanobacterial phenotype. The results presented here will be especially useful because they identify which of the many genes of unassigned function are likely to be of the greatest interest.

Journal Article↗

E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor.

Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

Adenovirus E1A Proteins↗