Cyclophilin acts as a ribosome biogenesis factor by chaperoning the ribosomal protein (PlRPS15) in filamentous fungi

The rapid transport of ribosomal proteins (RPs) into the nucleus and their efficient assembly into pre-ribosomal particles are prerequisites for ribosome biogenesis. Proteins that act as dedicated chaperones for RPs to maintain their stability and facilitate their assembly have not been identified in filamentous fungi. PlCYP5 is a nuclear cyclophilin in the nematophagous fungus Purpureocillium lilacinum, whose expression is up-regulated during abiotic stress and nematode egg-parasitism. Here, we found that PlCYP5 co-translationally interacted with the unassembled small ribosomal subunit protein, PlRPS15 (uS19). PlRPS15 contained an eukaryote-specific N-terminal extension that mediated the interaction with PlCYP5. PlCYP5 increased the solubility of PlRPS15 independent of its catalytic peptide-prolyl isomerase function and supported the integration of PlRPS15 into pre-ribosomes. Consistently, the phenotypes of the PlCYP5 loss-of-function mutant were similar to those of the PlRPS15 knockdown mutant (e.g. growth and ribosome biogenesis defects). PlCYP5 homologs in Arabidopsis thaliana, Homo sapiens, Schizosaccharomyces pombe, Sclerotinia sclerotiorum, Botrytis cinerea and Metarhizium anisopliae were identified. Notably, PlCYP5-PlRPS15 homologs from three filamentous fungi interacted with each other but not those from other species. In summary, our data disclosed a unique dedicated chaperone system for RPs by cyclophilin in filamentous fungi.     

几种常用生物分析软件的特点及其使用简介

基于代表性、实用性的原则选择了RAPDistance ,PHYLIP ,MEGA ,TREECON ,AMOVA ,DIPLO MO和MAPMAKER等 7种系统发育及遗传图谱构建方面的免费共享生物分析软件 ,简要介绍了它们各自的特点、功能、使用及获得的方法。以期这些软件对于从事生物技术研究的人员具有一定的指导性 ,可操作性。     

Development of naringenin-O-alkylamine derivatives as multifunctional agents for the treatment of Alzheimer’s disease

In this study, a series of naringenin-O-alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The in vitro biological activity results revealed that compounds 5f and 7k showed good antioxidant activity with ORAC values of 2.3eq and 1.2eq, respectively. Compounds 5f and 7k were reversible and excellent huAChE inhibitors with IC₅₀ values of 0.91 μM and 0.57 μM, respectively. Moreover, compounds 5f and 7k could inhibit self-induced Aβ_1–42 aggregation with 62.1% and 43.8% inhibition rate, respectively, and significantly inhibited huAChE-Aβ_1–40 aggregation with 51.7% and 43.4% inhibition rate, respectively. In addition, compounds 5f and 7k were selective metal chelators and remarkably inhibited Cu²⁺-induced Aβ_1–42 aggregation with 73.5% and 68.7% inhibition rates, respectively. Furthermore, compounds 5f and 7k could cross the blood-brain barrier in vitro and displayed good neuroprotective effects and anti-inflammatory properties. Further investigation showed that compound 5f did not show obvious hepatotoxicity and displayed a good hepatoprotective effect by its antioxidant activity. The in vivo study displayed that compound 5f significantly improved scopolamine-induced mice memory impairment. Therefore, compound 5f was a potential multifunctional candidate for the treatment of AD.     

施肥对板栗林地土壤N2O通量动态变化的影响

2011年6月—2012年6月期间,在浙江省临安市典型板栗林地进行施肥对土壤N2O通量变化影响的试验研究。目的在于探明不同施肥处理下板栗林地土壤N2O通量的动态变化规律,并探讨土壤N2O通量和土壤环境因子之间的关系。试验设置4个处理:对照(不施肥)、无机肥、有机肥、有机无机混合肥。采用静态箱-气相色谱法测定了板栗林地土壤N2O通量,并测定了土壤温度、水分、水溶性有机碳(WSOC)和微生物量碳(MBC)含量。结果表明:板栗林土壤N2O通量呈显著季节性变化,最大值出现在夏季,最小值出现在冬季;而且,施肥处理显著提高土壤N2O年均通量和年累积量;在整个试验期间,无机肥、有机肥和有机无机混合肥处理下土壤N2O的排放系数分别达到0.96%、1.45%和1.29%。此外,施肥也显著增加了土壤WSOC和MBC的含量(P<0.05)。不同施肥处理条件下,土壤N2O通量与土壤5 cm处温度、WSOC含量间均呈极显著正相关(P<0.01),但与MBC含量之间的相关性不显著。土壤N2O排放与土壤含水量间除对照处理外均没有显著相关性。综上所述,施肥引起土壤WSOC含量的增加可能是施肥增加板栗林地土壤N2O排放速率的主要原因之一。     

苦豆籽中抑菌活性物质的跟踪筛选研究

目的:对苦豆籽中抑菌活性物质进行跟踪筛选。方法:采用溶剂萃取法获得苦豆籽不同极性溶剂萃取的浸膏,对其浸膏及实验室自制单体类化合物通过纸片扩散法(K-B)法进行抑菌试验研究。结果:苦豆籽粗提物对实验所用菌种都有不同程度的抑制作用,尤其是氯仿浸膏中可能含大量生物碱,因此表现出强的抑菌效果;苦豆籽单体类化合物对实验所用菌种都具有较强的抑制作用,苦参碱的抑菌效果最好。结论:苦豆籽中主要抑菌成分为生物碱类化合物,其中苦参碱的抑菌效果优于氧化苦参碱。     

Structural basis of ubiquitin recognition by translesion synthesis DNA polymerase ι

Cells have evolved mutagenic bypass mechanisms that prevent stalling of the replication machinery at DNA lesions. This process, translesion DNA synthesis (TLS), involves switching from high-fidelity DNA polymerases to specialized DNA polymerases that replicate through a variety of DNA lesions. In eukaryotes, polymerase switching during TLS is regulated by the DNA damage-triggered monoubiquitylation of PCNA. How the switch operates is unknown, but all TLS polymerases of the so-called Y-family possess PCNA and ubiquitin-binding domains that are important for their function. To gain insight into the structural mechanisms underlying the regulation of TLS by ubiquitylation, we have probed the interaction of ubiquitin with a conserved ubiquitin-binding motif (UBM2) of Y-family polymerase Polι. Using NMR spectroscopy, we have determined the structure of a complex of human Polι UBM2 and ubiquitin, revealing a novel ubiquitin recognition fold consisting of two α-helices separated by a central trans-proline residue conserved in all UBMs. We show that, different from the majority of ubiquitin complexes characterized to date, ubiquitin residue Ile44 only plays a modest role in the association of ubiquitin with Polι UBM2. Instead, binding of UBM2 is centered on the recognition of Leu8 in ubiquitin, which is essential for the interaction.     

Identification of key candidate genes and pathways in multiple myeloma by integrated bioinformatics analysis

Multiple myeloma (MM) is a common hematologic malignancy for which the underlying molecular mechanisms remain largely unclear. This study aimed to elucidate key candidate genes and pathways in MM by integrated bioinformatics analysis. Expression profiles GSE6477 and GSE47552 were obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) with p < .05 and [logFC] > 1 were identified. Functional enrichment, protein–protein interaction network construction and survival analyses were then performed. First, 51 upregulated and 78 downregulated DEGs shared between the two GSE datasets were identified. Second, functional enrichment analysis showed that these DEGs are mainly involved in the B cell receptor signaling pathway, hematopoietic cell lineage, and NF-kappa B pathway. Moreover, interrelation analysis of immune system processes showed enrichment of the downregulated DEGs mainly in B cell differentiation, positive regulation of monocyte chemotaxis and positive regulation of T cell proliferation. Finally, the correlation between DEG expression and survival in MM was evaluated using the PrognoScan database. In conclusion, we identified key candidate genes that affect the outcomes of patients with MM, and these genes might serve as potential therapeutic targets.     

Mutations in the novel mitochondrial protein REEP1 cause hereditary spastic paraplegia type 31

Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. For the novel SPG31 locus on chromosome 2p12, we identified six different mutations in the receptor expression-enhancing protein 1 gene (REEP1). REEP1 mutations occurred in 6.5% of the patients with HSP in our sample, making it the third-most common HSP gene. We show that REEP1 is widely expressed and localizes to mitochondria, which underlines the importance of mitochondrial function in neurodegenerative disease.     

Potent immunosuppressive activities of cytomegalovirus-encoded interleukin-10.

Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.