[Show abstract][Hide abstract] ABSTRACT: Selenium (Se) is an important micronutrient for many organisms, which is required for the biosynthesis of selenocysteine, selenouridine and Se-containing cofactor. Several key genes involved in different Se utilization traits have been characterized; however, systematic studies on the evolution and ecological niches of Se utilization are very limited. Here, we analyzed more than 5200 sequenced organisms to examine the occurrence patterns of all Se traits in bacteria. A global species map of all Se utilization pathways has been generated, which demonstrates the most detailed understanding of Se utilization in bacteria so far. In addition, the selenophosphate synthetase gene, which is used to define the overall Se utilization, was also detected in some organisms that do not have any of the known Se traits, implying the presence of a novel Se form in this domain. Phylogenetic analyses of components of different Se utilization traits revealed new horizontal gene transfer events for each of them. Moreover, by characterizing the selenoproteomes of all organisms, we found a new selenoprotein-rich phylum and additional selenoprotein-rich species. Finally, the relationship between ecological environments and Se utilization was investigated and further verified by metagenomic analysis of environmental samples, which indicates new macroevolutionary trends of each Se utilization trait in bacteria. Our data provide insights into the general features of Se utilization in bacteria and should be useful for a further understanding of the evolutionary dynamics of Se utilization in nature.The ISME Journal advance online publication, 22 January 2016; doi:10.1038/ismej.2015.246.
[Show abstract][Hide abstract] ABSTRACT: G-quadruplexes are four-stranded DNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Accumulating studies have revealed that G-quadruplex structures are formed in vivo and play important roles in biological processes such as DNA replication, transcription, recombination, epigenetic regulation, meiosis, antigenic variation, and maintenance of telomeres stability. Mounting evidence indicates that a variety of proteins are capable of binding selectively and tightly to G-quadruplex and play essential roles in G-quadruplex-mediated regulation processes. Some of these proteins promote the formation or/and stabilization of G-quadruplex, while some other proteins act to unwind G-quadruplex preferentially. From a drug discovery perspective, many of these G-quadruplex binding proteins and/or their complexes with G-quadruplexes are potential drug targets. Here, we present a general summary of reported G-quadruplex binding proteins and their biological functions, with focus on those of medicinal research significance. We elaborated the possibility for some of these G-quadruplex binding proteins and their complexes with G-quadruplexes as potential drug targets.
No preview · Article · May 2015 · Current topics in medicinal chemistry
[Show abstract][Hide abstract] ABSTRACT: Background
Selenium (Se) and sulfur (S) are closely related elements that exhibit similar chemical properties. Some genes related to S metabolism are also involved in Se utilization in many organisms. However, the evolutionary relationship between the two utilization traits is unclear.
In this study, we conducted a comparative analysis of the selenophosphate synthetase (SelD) family, a key protein for all known Se utilization traits, in all sequenced archaea. Our search showed a very limited distribution of SelD and Se utilization in this kingdom. Interestingly, a SelD-like protein was detected in two orders of Crenarchaeota: Sulfolobales and Thermoproteales. Sequence and phylogenetic analyses revealed that SelD-like protein contains the same domain and conserved functional residues as those of SelD, and might be involved in S metabolism in these S-reducing organisms. Further genome-wide analysis of patterns of gene occurrence in different thermoproteales suggested that several genes, including SirA-like, Prx-like and adenylylsulfate reductase, were strongly related to SelD-like gene. Based on these findings, we proposed a simple model wherein SelD-like may play an important role in the biosynthesis of certain thiophosphate compound.
Our data suggest novel genes involved in S metabolism in hyperthermophilic S-reducing archaea, and may provide a new window for understanding the complex relationship between Se and S metabolism in archaea.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-908) contains supplementary material, which is available to authorized users.
[Show abstract][Hide abstract] ABSTRACT: Global change in protein turnover (protein degradome) constitutes a central part of cellular responses to intrinsic or extrinsic stimuli. However, profiling protein degradome remains technically challenging. Recently, inhibition of the proteasome, e.g., by using bortezomib (BTZ), has emerged as a major chemotherapeutic strategy for treating multiple myeloma and other human malignancies, but systematic understanding of the mechanisms for BTZ drug action and tumor drug resistance is yet to be achieved. Here we developed and applied a dual-fluorescence-based Protein Turnover Assay (ProTA) to quantitatively profile global changes in human protein degradome upon BTZ-induced proteasomal inhibition. ProTA and subsequent network analyses delineate potential molecular basis for BTZ action and tumor drug resistance in BTZ chemotherapy. Finally, combined use of BTZ with drugs targeting the ProTA-identified key genes or pathways in BTZ action reduced BTZ resistance in multiple myeloma cells. Remarkably, BTZ stabilizes proteasome subunit PSMC1 and proteasome assembly factor PSMD10, suggesting a previously under-appreciated mechanism for regulating proteasome homeostasis. Therefore, ProTA is a novel tool for profiling human protein degradome to elucidate potential mechanisms of drug action and resistance, which might facilitate therapeutic development targeting proteostasis to treat human disorders.Cell Research advance online publication 16 September 2014; doi:10.1038/cr.2014.122.
[Show abstract][Hide abstract] ABSTRACT: This study investigates the age-related differences in skeletal muscle mass (SM), muscle strength and physical performance in mainland Chinese. Based on available data, the reference values (criteria) for the definition of sarcopenia in elderly Chinese were explored. Body composition measurements were obtained using a bioelectrical impedance analyzer (BIA); muscle strength was determined by handgrip strength (HS); and physical function was evaluated by the subjects’ 6-m gait speed (GS). In this study, HS and GS declined significantly after 55 yr and very dramatically after 75 yr. Appendicular SM index of <7.61 kg/m2 (males) and <6.43 kg/m2 (females); HS of <27 kg (males) and <16 kg (females); and GS of <0.98 m/s (males) and <0.88 m/s (females) were considered as low SM, low HS and low GS. Applying these suggested criteria to the study population, there were 9.55% and 6.63% of the subjects with low SM, 20.10% and 18.46% with low GS, and 14.07% and 15.38% with low HS in elderly males and females, respectively. Utilizing AWGS criteria in our population results in a very low prevalence of low SM and low GS. If Western criteria for sarcopenia were adopted, the prevalence of low GS and low HS would be 2-4 times higher in the studied population, also exhibiting significant gender differences. These findings indicate that it is necessary to establish an outcomes-based and ethnic-specific set of reference values for the diagnosis of sarcopenia in elderly Chinese.
No preview · Article · Aug 2014 · Archives of Gerontology and Geriatrics
[Show abstract][Hide abstract] ABSTRACT: The developing of network drive the developing of information systems in campus. More and more business information systems are built in1990's. But most of these systems in campus are developed on different platform without standard. And some data in business information system should be shared between different departments. So the target of this paper is to solve the problem of sharing data in campus the through the web service. Web service is a service-oriented architecture (SOA) to provider service for service consumer. But the traditional model of web service is not suitable in digital campus. This paper designs a new model of web service for digital campus environment. And then a public-data platform is designed to realize the data sharing in heterogeneous systems. Next, the database designing and data processing flow is introduced. Finally, some monitor information of platform is showed.
No preview · Article · Jul 2014 · The Journal of China Universities of Posts and Telecommunications
[Show abstract][Hide abstract] ABSTRACT: Human longevity is always a biological hotspot and so much effort has been devoted to identifying genes and genetic variations associated with longer lives. Most of the demographic studies have highlighted that females have a longer life span than males. The reasons for this are not entirely clear. In this study, we carried out a pool-based, epigenome-wide investigation of DNA methylation profiles in male and female nonagenarians/centenarians using the Illumina 450 K Methylation Beadchip assays. Although no significant difference was detected for the average methylation levels of examined CpGs (or probes) between male and female samples, a significant number of differentially methylated probes (DMPs) were identified, which appeared to be enriched in certain chromosome regions and certain parts of genes. Further analysis of DMP-containing genes (named DMGs) revealed that almost all of them are solely hypermethylated or hypomethylated. Functional enrichment analysis of these DMGs indicated that DNA hypermethylation and hypomethylation may regulate genes involved in different biological processes, such as hormone regulation, neuron projection, and disease-related pathways. This is the first effort to explore the gender-based methylome difference in nonagenarians/centenarians, which may provide new insights into the complex mechanism of longevity gender gap of human beings.
[Show abstract][Hide abstract] ABSTRACT: Trace elements are essential for human metabolism and dysregulation of their homoeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires machinery involved in protein trafficking and post-translational modifications; and the iron levels are influenced by iron import and expression of the iron/haeme-containing enzymes. Our approach can be applied to a variety of disease models and/or nutritional conditions, and the generated data set opens new directions for studies of human trace element metabolism.
Full-text · Article · Feb 2014 · Nature Communications
[Show abstract][Hide abstract] ABSTRACT: Trace elements have been recognized to play an important role in the development of Parkinson's disease (PD). However, it is difficult to precisely identify the relationship between these elements and the progression of PD because of an insufficient number of patients. In this study, quantifications of selenium (Se), copper (Cu), iron (Fe) and zinc (Zn) by atomic absorption spectrophotometry were performed in plasma from 238 PD patients and 302 controls recruited from eastern China, which is so far the largest cohort of PD patients and controls for measuring plasma levels of these elements. We found that plasma Se and Fe concentrations were significantly increased whereas Cu and Zn concentrations decreased in PD patients as compared with controls. Meanwhile, these four elements displayed differential changes with regard to age. Linear and logistic regression analyses revealed that both Fe and Zn were negatively correlated with age in PD patients. Association analysis suggests that lower plasma Se and Fe levels may reduce the risk for PD, whereas lower plasma Zn is probably a PD risk factor. Finally, a model was generated to predict PD patients based on the plasma concentrations of these four trace elements as well as other features such as sex and age, which achieved an accuracy of 80.97±1.34% using 10-fold cross-validation. In summary, our data provide new insights into the roles of Se, Cu, Fe and Zn in PD progression.
[Show abstract][Hide abstract] ABSTRACT: Background. The selenocysteine(Sec)-containing proteins, selenoproteins, are an important group of proteins present in all three kingdoms of life. Although the selenoproteomes of many organisms have been analyzed, systematic studies on selenoproteins in platyhelminthes are still lacking. Moreover, comparison of selenoproteomes between free-living and parasitic animals is rarely studied.
Results. In this study, three representative organisms (Schmidtea mediterranea, Schistosoma japonicum and Taenia solium) were selected for comparative analysis of selenoproteomes in Platyhelminthes. Using a SelGenAmic-based selenoprotein prediction algorithm, a total of 37 selenoprotein genes were identified in these organisms. The size of selenoproteomes and selenoprotein families were found to be associated with different lifestyles: free-living organisms have larger selenoproteome whereas parasitic lifestyle corresponds to reduced selenoproteomes. Five selenoproteins, SelT, Sel15, GPx, SPS2 and TR, were found to be present in all examined platyhelminthes as well as almost all sequenced animals, suggesting their essential role in metazoans. Finally, a new splicing form of SelW that lacked the first exon was found to be present in S. japonicum.
Conclusions. Our data provide a first glance into the selenoproteomes of organisms in the phylum Platyhelminthes and may help understand function and evolutionary dynamics of selenium utilization in diversified metazoans.
[Show abstract][Hide abstract] ABSTRACT: Background
The naked mole rats (NMRs) are small-sized underground rodents with plenty of unusual traits. Their life expectancy can be up to thirty years, more than seven times longer than laboratory rat. Furthermore, they are resistant to both congenital and experimentally induced cancer genesis. These peculiar physiological and pathological characteristics allow them to become a suitable model for cancer and aging research.
In this paper, we carried out a genome-wide comparative analysis of rat and NMR using the recently published genome sequence of NMR. First, we identified all the rat-NMR orthologous genes and specific genes within each of them. The expanded and contracted numbers of protein families in NMR were also analyzed when compared to rat. Seven cancer-related protein families appeared to be significantly expanded, whereas several receptor families were found to be contracted in NMR. We then chose those rat genes that were inexistent in NMR and adopted KEGG pathway database to investigate the metabolic processes in which their proteins may be involved. These genes were significantly enriched in two rat cancer pathways, "Pathway in cancer" and "Bladder cancer". In the rat "Pathway in cancer", 9 out of 14 paths leading to evading apoptosis appeared to be affected in NMR. In addition, a significant number of other NMR-missing genes enriched in several cancer-related pathways have been known to be related to a variety of cancers, implying that many of them may be also related to tumorigenesis in mammals. Finally, investigation of sequence variations among orthologous proteins between rat and NMR revealed that significant fragment insertions/deletions within important functional domains were present in some NMR proteins, which might lead to expressional and/or functional changes of these genes in different species.
Overall, this study provides insights into understanding the possible anti-cancer mechanisms of NMR as well as searching for new cancer-related candidate genes.
Full-text · Article · Oct 2013 · BMC Systems Biology
[Show abstract][Hide abstract] ABSTRACT: Content center networking (CCN) is one of the most promising future network architectures. Current researches on CCN routing scheme mainly focus on finding the best single routing path, which may induce to low usage of the in-network caches. In order to overcome this problem, a reverse trace routing (RTR) scheme is proposed in this paper, in which Interest packet is sent to the edge-cache along with the reverse trace of the corresponding former Data packet. By doing this, the Interest packets will have better chances to be routed to the promising in-network caches before reaching the source server, which could increase the in-network hit rate, while decrease the server stress. The simulation results show clearly that the RTR scheme decreases the source server load, while reducing the mean hops of entire data retrieval process under certain circumstances.
No preview · Article · Oct 2013 · The Journal of China Universities of Posts and Telecommunications
[Show abstract][Hide abstract] ABSTRACT: Cellular zinc influx and efflux are maintained by two major transporter families, the ZIP (SLC39A) and ZnT (SLC30A or CDF) molecules. The functions of one molecule in this class, ZIP11/SLC39A11, remain unclear. Bioinformatics analysis of the distribution and evolutionary relationships of different ZIP members in eukaryotes and prokaryotes indicated that Zip11, the sole member of gufA subfamily, is an ancient ZIP family member that might have originated in early eukaryotic ancestors. Murine Zip11 mRNA is abundantly expressed in testes and the digestive system including stomach, ileum and cecum. Analysis of cellular zinc content, metallothionein levels, and cell viability under high or low zinc conditions in cells transfected with a murine Zip11 expression plasmid, suggest that Zip11 is a zinc importer. Further, cellular zinc concentrations and metallothionein levels decreased when Zip11 was knocked down. In mice supplemented with zinc, both mRNA and protein levels of Zip11 were slightly up-regulated in several tissues. The metal response element sequences (MREs) upstream of the first exon of Zip11 responded to elevated extracellular zinc concentrations, as assessed by luciferase reporter assays. Mutagenic analysis showed that several of the MREs could regulate Zip11 promoter activity, and metal-responsive transcription factor-1 (MTF-1) was shown to be involved in this process. Collectively, these data suggest that Zip11 has unique protein sequence and structure features, it functions as a cellular zinc transporter, and its expression is at least partially regulated by zinc via hMTF-1 binding to MREs of the Zip11 promoter.
Full-text · Article · May 2013 · The Journal of nutritional biochemistry
[Show abstract][Hide abstract] ABSTRACT: Biological trace metals are needed in small quantities, but used by all living organisms. They are employed in key cellular functions in a variety of biological processes, resulting in the various degree of dependence of organisms on metals. Most effort in the field has been placed on experimental studies of metal utilization pathways and metal-dependent proteins. On the other hand, systemic level analyses of metalloproteomes (or metallomes) have been limited for most metals. In this chapter, we focus on the recent advances in comparative genomics, which provides many insights into evolution and function of metal utilization. These studies suggested that iron and zinc are widely used in biology (presumably by all organisms), whereas some other metals such as copper, molybdenum, nickel, and cobalt, show scattered occurrence in various groups of organisms. For these metals, most user proteins are well characterized and their dependence on a specific element is evolutionarily conserved. We also discuss evolutionary dynamics of the dependence of user proteins on different metals. Overall, comparative genomics analysis of metallomes provides a foundation for the systemic level understanding of metal utilization as well as for investigating the general features, functions, and evolutionary dynamics of metal use in the three domains of life.
No preview · Article · Apr 2013 · Metal ions in life sciences
[Show abstract][Hide abstract] ABSTRACT: Each phase of eukaryotic cell cycle is tightly controlled by multi-component regulatory networks based on complex relationships of protein phosphorylation. In order to better understand the relationships between kinases and their substrate proteins during the progress of cell cycle, we analyzed phosphoproteome of HeLa cells during G1, S and G2/M phases of cell cycle using our developed quantitative phosphoproteomic approaches. A total of 4,776 high-confidence phosphorylation sites (phosphosites) in 1,177 proteins were identified. Bioinformatics analysis for predicting kinase groups revealed that 46 kinase groups could be assigned to 4,321 phosphosites. The majority of phosphoproteins harboring two or more phosphosites could be phosphorylated by different kinase groups, in which nine major kinase groups accounted for more than 90% phosphosites. Further analyses showed that approximately half of the examined two-phosphosite combinations were correlatively regulated, regardless of whether the kinase groups were same or not. In general, the majority of proteins containing correlated phosphosites had solely co-regulated or counter-regulated phosphosites, and co-regulation was significantly more frequent than counter-regulation, suggesting that the former may be more important for regulating the cell cycle. In conclusion, our findings provide new insights into the complex regulatory mechanisms of protein phosphorylation networks during eukaryotic cell cycle.
[Show abstract][Hide abstract] ABSTRACT: The trace element selenium (Se) is required for the biosynthesis of selenocysteine (Sec), the 21st amino acid in the genetic code, but its role in the ecology of harmful algal blooms (HABs) is unknown. Here, we examined the role of Se in the biology and ecology of the harmful pelagophyte, Aureococcus anophagefferens, through cell culture, genomic analyses, and ecosystem studies. This organism has the largest and the most diverse selenoproteome identified to date that consists of at least 59 selenoproteins, including known eukaryotic selenoproteins, selenoproteins previously only detected in bacteria, and novel selenoproteins. The A. anophagefferens selenoproteome was dominated by the thioredoxin fold proteins and oxidoreductase functions were assigned to the majority of detected selenoproteins. Insertion of Sec in these proteins was supported by a unique Sec insertion sequence. Se was required for the growth of A. anophagefferens as cultures grew maximally at nanomolar Se concentrations. In a coastal ecosystem, dissolved Se concentrations were elevated before and after A. anophagefferens blooms, but were reduced by >95% during the peak of blooms to 0.05 nM. Consistent with this pattern, enrichment of seawater with selenite before and after a bloom did not affect the growth of A. anophagefferens, but enrichment during the peak of the bloom significantly increased population growth rates. These findings demonstrate that Se inventories, which can be anthropogenically enriched, can support proliferation of HABs, such as A. anophagefferens through its synthesis of a large arsenal of Se-dependent oxidoreductases that fine-tune cellular redox homeostasis.The ISME Journal advance online publication, 7 March 2013; doi:10.1038/ismej.2013.25.
[Show abstract][Hide abstract] ABSTRACT: Content Centric Networking (CCN) is one of the most promising future network architectures. Current researches on CCN routing scheme mainly focus on finding the best single routing path and then transferring all the content chunks along this path. For an Interest packet who should have had opportunities to be routed along multiple paths to reach more repositories but only been routed along one single path due to the single path routing scheme, the problems of low utilization of the network resources and unbalance of the load of the faces and repositories are caused. This paper focuses on how to make best use of multiple paths to route the Interests, and further transfer different chunks of the content back along the paths. According to the different network-status parameters, a Multi-path Interests Routing (MIR) scheme is proposed for CCN routing, which is based on Analytical Hierarchy Process (AHP). AHP is a method for obtaining the optimized result of the Interest packets allocation. The simulation experiments have been performed to evaluate the proposed scheme in terms of a wide range of performance metrics. The results show that the proposed scheme significantly outperforms existing scheme.