Recent progresses in the application of machine learning approach for predicting protein functional class independent of sequence similarity

Protein sequence contains clues to its function. Functional prediction from sequence presents a challenge particularly for proteins that have low or no sequence similarity to proteins of known function. Recently, machine learning methods have been explored for predicting functional class of proteins from sequence-derived properties independent of sequence similarity, which showed promising potential for low- and non-homologous proteins. These methods can thus be explored as potential tools to complement alignment- and clustering-based methods for predicting protein function. This article reviews the strategies, current progresses, and underlying difficulties in using machine learning methods for predicting the functional class of proteins. The relevant software and web-servers are described. The reported prediction performances in the application of these methods are also presented, which need to be interpreted with caution as they are dependent on such factors as datasets used and choice of parameters.     

生物素肼化学标记和DIG标记cDNA探针检测柑桔裂皮病类病毒

分别用生物素肼化学标记和ＤＩＧ标记我国柑桔裂皮病类病毒（ＣＥＶｄ）全长克隆ｃＤＮＡ,用以上探讨对不同来源的的核酸样品进行斑点杂交。两种探针可检出病柑桔总核酸的最低含量久为４００ｎｇ／斑点和８０ｎｇ／斑点;生物素肼标记ＣＥＶｄ－ＤＮＡ探讨针,可检出ＣＥＶｄ－ｃＤＮＡ的最低含量约为１０ｐｇ／斑点,研制的ＣＥＶｄ检测试剂盒能检测出发病和隐性带毒苗木中的ＣＥＶｄ,灵敏、特异、简便、快速。试剂盒已使用于检测     

不同的下丘脑肽和神经递质对鲤鱼促性腺激素和生长激素分泌活动的影响

以１龄性腺发育中期鲤鱼为材料,采用腹腔（ｉ．ｐ）注射的方法,研究不同的下丘脑肽和神经递质对鲤鱼促性腺激素（ＧｔＨ）和生长激素（ＧＨ）分泌的影响。结果表明：促甲状腺激素释放激素（ＴＲＨ）、Ｌ－多巴（Ｌ－ＤＯＰＡ）、甲基睾酮（ＭＴ）、γ－氨基丁酸（ＧＡＢＡ）、促黄体素释放激素类似物（ＬＨＲＨ－Ａ）和三碘甲状腺原氨酸（Ｔ３）都能显著刺激ＧｔＨ的分泌,但最大效应时间各不相同。ＴＲＨ和ＬＨＲＨ－Ａ能促进ＧＨ的分泌,Ｌ－ＤＯＰＡ、ＭＴ、ＧＡＢＡ对血清ＧＨ水平没有明显影响;Ｔ３则对ＧＨ分泌有一定的抑制作用。这说明鲤鱼ＧｔＨ和ＧＨ的分泌除了受各自的下丘脑释放因子和释放抑制因子的双重神经内分泌调控外,还受多种其它相同和不同调节因子的影响,也反映了鲤鱼ＧｔＨ和ＧＨ分泌的神经内分泌调控的复杂性。     

Overexpression of miR-26b-5p regulates the cell cycle by targeting CCND2 in GC-2 cells under exposure to extremely low frequency electromagnetic fields

The increasing prevalence of extremely low frequency electromagnetic fields (ELF-EMFs) exposure has raised considerable public concern regarding the potential hazardous effects of ELF-EMFs on male reproductive function. Increasing evidence indicates that miRNAs are necessary for spermatogenesis and male fertility. However, the regulation of miRNA expression and the roles of miRNAs in response to ELF-EMFs remain unclear. In our study, mouse spermatocyte-derived GC-2 cells were intermittently exposed to a 50 Hz ELF-EMF for 72 h (5 min on/10 min off) at magnetic field intensities of 1 mT, 2 mT and 3 mT. MiR-26b-5p was differentially expressed in response to different magnetic field intensities of ELF-EMFs. The host gene CTDSP1 showed an unmethylation status in GC-2 cells at different magnetic field intensities of ELF-EMF exposure. MiR-26b-5p had no significant, obvious influence on the cell viability, apoptosis or cell cycle of GC-2 cells. However, the overexpression of miR-26b-5p significantly decreased the percentage of G0/G1 phase cells and slightly increased the percentage of S phase cells compared to the sham group that was exposed to a 50 Hz ELF-EMF. Computational algorithms identified Cyclin D2 (CCND2) as a direct target of miR-26b-5p. MiR-26b-5p and a 50 Hz ELF-EMF altered the expression of CCND2 at both the mRNA and protein levels. Overexpressed miR-26b-5p in GC-2 cells can change the mRNA expression of CCND2 following 50 Hz ELF-EMF at 3 mT. These findings demonstrate that miR-26b-5p could serve as a potential biomarker following 50 Hz ELF-EMF exposure, and miR-26b-5p-CCND2-mediated cell cycle regulation might play a pivotal role in the biological effects of ELF-EMFs.     

Molecular Evidence for the Hybrid Origin of Ilex dabieshanensis (Aquifoliaceae)

Ilex, the largest genus of dioecious woody plants, is a good study system to assess the role of hybridization in speciation and evolution. Ilex dabieshanensis, a tree endemic to Dabieshan Mountains region, was initially described as a new species. Based on morphological intermediacy and sympatric distribution with its putative parental species, I. cornuta and I. latifolia, we proposed it as a natural hybrid between them. In this study, we sequenced one chloroplast intergenic spacer (trnH-psbA) and two nuclear genes (gapC and nepGS) in I. dabieshanensis and its putative parental species to test the hybrid origin hypothesis. Our results showed that there were one to two differentially fixed sequence differences between I. cornuta and I. latifolia at the two nuclear genes. Twelve of the 14 individuals of I. dabieshanensis exhibited additivity in chromatograms on these differentially fixed sites at both nuclear genes, and the remaining two exhibited additivity in chromatograms on the fixed site at only the nepGS gene. Except one haplotype of I. cornuta at the nepGS gene, all of the haplotypes of I. cornuta at the two nuclear genes were well separated from those of I. latifolia, and most haplotypes of I. dabieshanensis were shared with those of I. cornuta and I. latifolia. Phylogenetic analysis of these haplotypes was largely consistent with haplotype network analysis. I. cornuta and I. latifolia differed by two nucleotide substitutions in the chloroplast intergenic spacer, and 12 individuals of I. dabieshanensis had the same sequences as I. latifolia, while the remaining two were identical with I. cornuta. The molecular data provide convincing evidence for the hybrid origin of I. dabieshanensis and asymmetrical direction of hybridization. One haplotype of I. cornuta at the nepGS gene was nested with those of I. latifolia, indicating introgression to I. cornuta.     

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using ¹⁸F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as ¹⁸F-Fluorocholine (¹⁸F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer ¹⁸F-FCH/¹⁸F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to ¹⁸F-FCH and ¹⁸F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The ¹⁸F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in ¹⁸F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by ¹⁸F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of ¹⁸F-FCH/ ¹⁸F-FDG-PET imaging in this study, while the false-positive caused by ¹⁸F-FCH can be eliminated. Dual tracer ¹⁸F-FCH/¹⁸F-FDG PET imaging has the potential to improve the visualization of low grade glioma. ¹⁸F-FCH delineates tumor areas and the tumor can be identified by subtracting the ¹⁸F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.     

A photo‐responsive F‐box protein FOF2 regulates floral initiation by promoting FLC expression in Arabidopsis

Floral initiation is regulated by various genetic pathways in response to light, temperature, hormones and developmental status; however, the molecular mechanisms underlying the interactions between different genetic pathways are not fully understood. Here, we show that the photoresponsive gene FOF2 (F‐box of flowering 2) negatively regulates flowering. FOF2 encodes a putative F‐box protein that interacts specifically with ASK14, and its overexpression results in later flowering under both long‐day and short‐day photoperiods. Conversely, transgenic plants expressing the F‐box domain deletion mutant of FOF2 (FOF2ΔF), or double loss of function mutant of FOF2 and FOL1 (FOF2‐LIKE 1) present early flowering phenotypes. The late flowering phenotype of the FOF2 overexpression lines is suppressed by the flc‐3 loss‐of‐function mutation. Furthermore, FOF2 mRNA expression is regulated by autonomous pathway gene FCA, and the repressive effect of FOF2 in flowering can be overcome by vernalization. Interestingly, FOF2 expression is regulated by light. The protein level of FOF2 accumulates in response to light, whereas it is degraded under dark conditions via the 26S proteasome pathway. Our findings suggest a possible mechanistic link between light conditions and the autonomous floral promotion pathway in Arabidopsis.     

基于生态系统管理理论的海域集约利用评价——以河北沿海地级市为例

基于生态系统管理理论,从海洋投入强度、海洋利用强度、海洋经济效益及海洋生态环境质量层面,构建海域集约利用评价的指标体系,运用模糊决策分析理论计算各指标权重,得到河北省沿海地级市2005—2014年的海域集约利用综合指数,并利用聚类分析法及协调度指数对河北省海域集约利用的区域差异特征进行了分析。研究结果表明:2005—2014年河北省海域集约利用综合水平不断提高,除海洋生态环境质量准则层指数呈下降趋势外,海洋投入强度、海洋利用强度、海洋经济效益3个层面指数均呈上升趋势,其中持续增加趋势最明显的是海洋经济效益准则层;河北省沿海三市海域集约利用综合指数及各准则层指数的时序变化特征基本一致,但各区域之间仍体现着不同的变化特点,沧州市海域集约利用程度较高,唐山市海域集约利用经历了由低到高的过程,秦皇岛市海域集约利用的状况整体处于一般水平;河北省及沿海三市海域集约利用总体保持了较高的协调度,但各地区不同时段的变化特征有所不同。     

microRNA-489 Plays an Anti-Metastatic Role in Human Hepatocellular Carcinoma by Targeting Matrix Metalloproteinase-7

Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of hepatocellular carcinoma (HCC). miR-489 was found to play either oncogenic or tumor suppressive roles in human cancers. Recent study reported that the levels of miR-489 in late recurrent HCC patients were evidently higher than that in early recurrent cases, suggesting that miR-489 may function as a tumor suppressive miRNA in HCC. Yet, the clinical value and biological function of miR-489 remain rarely known in HCC. Here, we presented that miR-489 level in HCC tissues was notably reduced compared to matched non-cancerous specimens. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of HCC patients. Accordingly, the levels of miR-489 were obviously down-regulated in HCC cells. Ectopic expression of miR-489 in HCCLM3 and MHCC97H cells prominently inhibits the migration and invasion of tumor cells and reduced lung metastases in vivo, while miR-489 knockdown increased these behaviors of HepG2 and MHCC97L cells. Mechanically, miR-489 negatively regulated matrix metalloproteinase-7 (MMP7) abundance in HCC cells. Herein, MMP7 was found to be a downstream molecule of miR-489 in HCC. An inversely correlation between miR-489 and MMP7 was confirmed in HCC specimens. MMP7 knockdown prohibited cell migration and invasion while MMP7 overexpression showed opposite effects on HCC cells. Furthermore, restoration of MMP7 expression could abrogate the anti-metastatic effects of miR-489 on HCCLM3 cells with enhanced cell migration and invasion. Altogether, miR-489 potentially acts as a prognostic predictor and a drug-target for HCC patients.     

The institute for genomic research Osa1 rice genome annotation database

We have developed a rice (Oryza sativa) genome annotation database (Osa1) that provides structural and functional annotation for this emerging model species. Using the sequence of O. sativa subsp. japonica cv Nipponbare from the International Rice Genome Sequencing Project, pseudomolecules, or virtual contigs, of the 12 rice chromosomes were constructed. Our most recent release, version 3, represents our third build of the pseudomolecules and is composed of 98% finished sequence. Genes were identified using a series of computational methods developed for Arabidopsis (Arabidopsis thaliana) that were modified for use with the rice genome. In release 3 of our annotation, we identified 57,915 genes, of which 14,196 are related to transposable elements. Of these 43,719 non-transposable element-related genes, 18,545 (42.4%) were annotated with a putative function, 5,777 (13.2%) were annotated as encoding an expressed protein with no known function, and the remaining 19,397 (44.4%) were annotated as encoding a hypothetical protein. Multiple splice forms (5,873) were detected for 2,538 genes, resulting in a total of 61,250 gene models in the rice genome. We incorporated experimental evidence into 18,252 gene models to improve the quality of the structural annotation. A series of functional data types has been annotated for the rice genome that includes alignment with genetic markers, assignment of gene ontologies, identification of flanking sequence tags, alignment with homologs from related species, and syntenic mapping with other cereal species. All structural and functional annotation data are available through interactive search and display windows as well as through download of flat files. To integrate the data with other genome projects, the annotation data are available through a Distributed Annotation System and a Genome Browser. All data can be obtained through the project Web pages at http://rice.tigr.org.