基于本体论的植物遗传资源数据整合研究

随着现代生物学的发展,全球范围内建立了大量的生物学数据共享中心,同时,在生物学发展的带动下,植物遗传资源数据变得更为复杂、异构化和海量。本文在分析国内外几大著名的数据整合共享中心的基础上,简要介绍了本体论的概念及其在生物学领域中的研究现状,提出了基于生物本体论将植物遗传数据、数据挖掘工具、科技文献和科技交流进行整合的设想,并对数据整合需要考虑的几个问题进行了讨论。     

Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro

Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by the adverse effects of cytotoxic agents. Targeted drug delivery may reduce the non-specific toxicity of chemotherapy by selectively directing anticancer drugs to tumor cells. MUC1 protein is an attractive target for tumor-specific drug delivery owning to its overexpression in most adenocarcinomas. In this study, a novel MUC1 aptamer is exploited as the targeting ligand for carrying doxorubicin (Dox) to cancer cells. We developed an 86-base DNA aptamer (MA3) that bound to a peptide epitope of MUC1 with a K(d) of 38.3 nM and minimal cross reactivity to albumin. Using A549 lung cancer and MCF-7 breast cancer cells as MUC1-expressing models, MA3 was found to preferentially bind to MUC1-positive but not MUC1-negative cells. An aptamer-doxorubicin complex (Apt-Dox) was formulated by intercalating doxorubicin into the DNA structure of MA3. Apt-Dox was found capable of carrying doxorubicin into MUC1-positive tumor cells, while significantly reducing the drug intake by MUC1-negative cells. Moreover, Apt-Dox retained the efficacy of doxorubicin against MUC1-positive tumor cells, but lowered the toxicity to MUC1-negative cells (P<0.01). The results suggest that the MUC1 aptamer may have potential utility as a targeting ligand for selective delivery of cytotoxic agent to MUC1-expressing tumors.     

New insights into the important roles of tumor cell-intrinsic PD-1

PD-1 (Programmed cell death protein-1) is mainly expressed in various immune cells, while its ligands PD-L1/PD-L2 (Programmed death ligand-1/Programmed death ligand-2) are mostly expressed in tumor cells. Generally, the binding of PD-L1/PD-L2 and PD-1 could lead to the tumor immune evasion. However, some recent studies showed that PD-1 could also be expressed in tumor cells and could activate mTOR (Mammalian Target of Rapamycin) or Hippo signaling pathway, therefore facilitating tumor proliferation independent of the immune system. While there was evidence that tumor cell-intrinsic PD-1 inhibited the activation of AKT and ERK1/2 pathways, thereby inhibiting tumor cell growth. Based on TCGA and CCLE database, we found that PD-1 was expressed in a variety of tumors and was associated with patient''s prognosis. Besides, we found that PD-1 may be involved in many carcinogenic signaling pathway on the basis of PD-1 gene enrichment analysis of cancer tissues and cancer cells. Our understanding of the tumor cell-intrinsic PD-1 function is still limited. This review is aimed at elaborating the potential effects of tumor cell-intrinsic PD-1 on carcinogenesis, providing a novel insight into the effects of anti-PD-1/PD-L1 immunotherapy, and helping to open a major epoch of combination therapy.     

Cloning and analysis of peptidoglycan recognition protein‐LC and immune deficiency from the diamondback moth,Plutella xylostella

Peptidoglycan (PGN) exists in both Gram‐negative and Gram‐positive bacteria as a component of the cell wall. PGN is an important target to be recognized by the innate immune system of animals. PGN recognition proteins (PGRP) are responsible for recognizing PGNs. In Drosophila melanogaster, PGRP‐LC and IMD (immune deficiency) are critical for activating the Imd pathway. Here, we report the cloning and analysis of PGRP‐LC and IMD (PxPGRP‐LC and PxIMD) from diamondback moth, Plutella xylostella (L.), the insect pest of cruciferous vegetables. PxPGRP‐LC gene consists of six exons encoding a polypeptide of 308 amino acid residues with a transmembrane region and a PGRP domain. PxIMD cDNA encodes a polypeptide of 251 amino acid residues with a death domain. Sequence comparisons indicate that they are characteristic of Drosophila PGRP‐LC and IMD homologs. PxPGRP‐LC and PxIMD were expressed in various tissues and developmental stages. Their mRNA levels were affected by bacterial challenges. The PGRP domain of PxPGRP‐LC lacks key residues for the amidase activity, but it can recognize two types of PGNs. Overexpression of full‐length and deletion mutants in Drosophila S2 cells induced expression of some antimicrobial peptide genes. These results indicate that PxPGRP‐LC and PxIMD may be involved in the immune signaling of P. xylostella. This study provides a foundation for further studies of the immune system of P. xylostella.     

中国东部南北样带森林优势植物叶片的水分利用效率和氮素利用效率

通过测定中国东部南北样带主要森林生态系统中10种优势植物(兴安落叶松、蒙古栎、水曲柳、紫椴、色木槭、红松、杉木、木荷、马尾松、锥栗)叶片的碳氮含量(Cmass、Nmass)、同位素丰度(δ13C、δ15N)以及光合响应曲线,分析了不同优势植物叶片的水分利用效率和氮素利用效率之间的差异及其相互关系.结果表明： 不同生活型植物叶片的Nmass和δ15N差异显著,表现为阔叶植物>针叶植物,落叶植物>常绿植物;最大光合速率(Pn max)表现为针叶植物>阔叶植物,落叶植物>常绿植物;植物叶片的瞬时水分利用效率(WUEi)和长期水分利用效率(WUE)均表现为阔叶植物>针叶植物,常绿植物>落叶植物;植物叶片的瞬时氮素利用效率(NUEi)和长期氮素利用效率(NUE)则表现出相反的规律,且常绿植物和落叶植物叶片的NUE差异显著;WUEi和WUE之间相关性不显著,而NUEi和NUE之间呈显著正相关.植物叶片的水分利用效率与氮素利用效率显著负相关.两种资源利用效率均受植物生活型的影响,并且存在一定的制约关系.     

Meta‐Analysis of the Association of the Trp64Arg Polymorphism in the β3 Adrenergic Receptor with Insulin Resistance

Objective: To clarify the possible association between the Trp64Arg polymorphism and insulin resistance (IR). Research Methods and Procedures: Articles evaluating the effect of the Trp64Arg polymorphism on IR were identified on the MEDLINE and PubMed databases from 1995 to February, 2004. After extraction of relevant data, main and subgroup meta‐analyses were performed to assess the differences in IR indices between Trp/Trp and Trp/Arg genotypes. Results: Forty eligible papers containing 56 subgroups were included in this meta‐analysis. Among a total of 12, 805 subjects, 21.9% had Trp64Arg mutation: 20.8%, heterozygotes and 1.1%, homozygotes. Significant associations were found between this mutation and some indices of IR. The weighted mean difference in fasting insulin, 120‐minute insulin level after oral glucose tolerance test, and homeostasis model assessment between Arg64 and Trp64 was 0.23 [95% confidence interval (CI), 0.05 to 0.42] pM, 0.89 (95% CI, 0.30 to 1.48) pM, and 0.55 (95% CI, 0.14 to 0.96), respectively. Subgroup analysis further indicated that this significant association existed only in the Asian population (p < 0.01) and in the obese (p = 0.02) and diabetes subgroups (p = 0.03). Discussion: Numerous studies have been conducted to examine the relationship between the β3‐adrenergic receptor Trp64Arg polymorphism and components of IR syndrome. However, the results have been inconsistent and have led to controversy about whether this polymorphism is associated with these clinical features. The current meta‐analysis demonstrated the moderate effects of the Trp64Arg polymorphism on IR in the Asian population and in obese and diabetic subgroups.     

Subdividing repressor function: DNA binding affinity, selectivity, and allostery can be altered by amino acid substitution of nonconserved residues in a LacI/GalR homologue

Many mutations that impact protein function occur at residues that do not directly contact ligand. To understand the functional contributions from the sequence that links the DNA-binding and regulatory domains of the LacI/GalR homologues, we have created a chimeric protein (LLhP), which comprises the LacI DNA-binding domain, the LacI linker, and the PurR regulatory domain. Although DNA binding site residues are identical in LLhP and LacI, thermodynamic measurements of DNA binding affinity show that LLhP does not discriminate between alternative DNA ligands as well as LacI. In addition, small-angle scattering experiments show that LLhP is more compact than LacI. When DNA is released, LacI shows a 20 A increase in length that was previously attributed to unfolding of the linker. This change is not seen in apo-LLhP, even though the linker sequences of the two proteins are identical. Together, results indicate that long-range functional and structural changes are propagated across the interface that forms between the linker and regulatory domain. These changes could be mediated via the side chains of several linker residues that contact the regulatory domains of the naturally occurring proteins, LacI and PurR. Substitution of these residues in LLhP leads to a range of functional effects. Four variants exhibit altered affinity for DNA, with no changes in selectivity or allosteric response. Another two result in proteins that bind operator DNA with very low affinity and no allosteric response, similar to LacI binding nonspecific DNA sequences. Two more substitutions simultaneously diminish affinity, enhance allostery, and profoundly alter DNA ligand selectivity. Thus, positions within the linker can be varied to modulate different aspects of repressor function.