ALBERT

Description: Protein modification is an extremely important post-translational regulation that adjusts the physical and chemical properties, conformation, stability and activity of a protein; thus altering protein function. Due to the high throughput of mass spectrometry (MS)-based methods in identifying site-specific post-translational modifications (PTMs), dbPTM ( http://dbPTM.mbc.nctu.edu.tw/ ) is updated to integrate experimental PTMs obtained from public resources as well as manually curated MS/MS peptides associated with PTMs from research articles. Version 3.0 of dbPTM aims to be an informative resource for investigating the substrate specificity of PTM sites and functional association of PTMs between substrates and their interacting proteins. In order to investigate the substrate specificity for modification sites, a newly developed statistical method has been applied to identify the significant substrate motifs for each type of PTMs containing sufficient experimental data. According to the data statistics in dbPTM, 〉60% of PTM sites are located in the functional domains of proteins. It is known that most PTMs can create binding sites for specific protein-interaction domains that work together for cellular function. Thus, this update integrates protein–protein interaction and domain–domain interaction to determine the functional association of PTM sites located in protein-interacting domains. Additionally, the information of structural topologies on transmembrane (TM) proteins is integrated in dbPTM in order to delineate the structural correlation between the reported PTM sites and TM topologies. To facilitate the investigation of PTMs on TM proteins, the PTM substrate sites and the structural topology are graphically represented. Also, literature information related to PTMs, orthologous conservations and substrate motifs of PTMs are also provided in the resource. Finally, this version features an improved web interface to facilitate convenient access to the resource.

Description: : S -nitrosylation (SNO), a selective and reversible protein post-translational modification that involves the covalent attachment of nitric oxide (NO) to the sulfur atom of cysteine, critically regulates protein activity, localization and stability. Due to its importance in regulating protein functions and cell signaling, a mass spectrometry-based proteomics method rapidly evolved to increase the dataset of experimentally determined SNO sites. However, there is currently no database dedicated to the integration of all experimentally verified S -nitrosylation sites with their structural or functional information. Thus, the dbSNO database is created to integrate all available datasets and to provide their structural analysis. Up to April 15, 2012, the dbSNO has manually accumulated 〉3000 experimentally verified S -nitrosylated peptides from 219 research articles using a text mining approach. To solve the heterogeneity among the data collected from different sources, the sequence identity of these reported S -nitrosylated peptides are mapped to the UniProtKB protein entries. To delineate the structural correlation and consensus motif of these SNO sites, the dbSNO database also provides structural and functional analyses, including the motifs of substrate sites, solvent accessibility, protein secondary and tertiary structures, protein domains and gene ontology. Availability : The dbSNO is now freely accessible via http://dbSNO.mbc.nctu.edu.tw . The database content is regularly updated upon collecting new data obtained from continuously surveying research articles. Contacts: francis@saturn.yu.edu.tw or yujuchen@gate.sinica.edu.tw Supplementary Information: Supplementary data are available at Bioinformatics online.

Description: Mutation in CUL4B , which encodes a scaffold protein of the E3 ubiquitin ligase complex, has been found in patients with X-linked mental retardation (XLMR). However, early deletion of Cul4b in mice causes prenatal lethality, which has frustrated attempts to characterize the phenotypes in vivo . In this report, we successfully rescued Cul4b mutant mice by crossing female mice in which exons 4–5 of Cul4b were flanked by loxP sequences with Sox2-Cre male mice. In Cul4b -deficient ( Cul4b /Y ) mice, no CUL4B protein was detected in any of the major organs, including the brain. In the hippocampus, the levels of CUL4A, CUL4B substrates (TOP1, β-catenin, cyclin E and WDR5) and neuronal markers (MAP2, tau-1, GAP-43, PSD95 and syn-1) were not sensitive to Cul4b deletion, whereas the number of parvalbumin (PV)-positive GABAergic interneurons was decreased in Cul4b /Y mice, especially in the dentate gyrus (DG). Some dendritic features, including the complexity, diameter and spine density in the CA1 and DG hippocampal neurons, were also affected by Cul4b deletion. Together, the decrease in the number of PV-positive neurons and altered dendritic properties in Cul4b /Y mice imply a reduction in inhibitory regulation and dendritic integration in the hippocampal neural circuit, which lead to increased epileptic susceptibility and spatial learning deficits. Our results identify Cul4b /Y mice as a potential model for the non-syndromic model of XLMR that replicates the CUL4B -associated MR and is valuable for the development of a therapeutic strategy for treating MR.

Description: : S -glutathionylation, the reversible protein posttranslational modification (PTM) that generates a mixed disulfide bond between glutathione and cysteine residue, critically regulates protein activity, stability and redox regulation. Due to its importance in regulating oxidative/nitrosative stress and balance in cellular response, a number of methods have been rapidly developed to study S -glutathionylation, thus expanding the dataset of experimentally determined glutathionylation sites. However, there is currently no database dedicated to the integration of all experimentally verified S -glutathionylation sites along with their characteristics or structural or functional information. Thus, the dbGSH database has been created to integrate all available datasets and to provide the relevant structural analysis. As of January 31, 2014, dbGSH has manually collected 〉2200 experimentally verified S -glutathionylated peptides from 169 research articles using a text-mining approach. To solve the problem of heterogeneity of the data collected from different sources, the sequence identity of the reported S -glutathionylated peptides is mapped to UniProtKB protein entries. To delineate the structural correlations and consensus motifs of these S -glutathionylation sites, the dbGSH database also provides structural and functional analyses, including the motifs of substrate sites, solvent accessibility, protein secondary and tertiary structures, protein domains and gene ontology. Availability and implementation: dbGSH is now freely accessible at http://csb.cse.yzu.edu.tw/dbGSH/ . The database content is regularly updated with new data collected by the continuous survey of research articles. Contact: francis@saturn.yzu.edu.tw or yujuchen@gate.sinica.edu.tw Supplementary information: Supplementary data are available at Bioinformatics online.

Description: The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein–DNA interactions as previously observed, and the two dimers retain all the protein–protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.

Description: Rayleigh–Stokes problems have in recent years received much attention due to their importance in physics. In this article, we focus on the variable-order Rayleigh–Stokes problem for a heated generalized second grade fluid with fractional derivative. Implicit and explicit numerical methods are developed to solve the problem. The convergence, stability of the numerical methods and solvability of the implicit numerical method are discussed via Fourier analysis. Moreover, a numerical example is given and the results support the effectiveness of the theoretical analysis.

Description: We construct a family of minimal smooth surfaces of general type with K 2 = 3 and p g = 0, which are finite (Z/2Z) 2 -covers of the 4-nodal cubic surface. This turns out to be a five-dimensional subfamily of the six-dimensional family constructed by Mendes Lopes and Pardini, which realizes the Keum–Naie surfaces with K 2 = 3 as degenerations. We show that the base of the Kuranishi family of a general surface in our subfamily is smooth. We prove that the closure of the corresponding subset of the Keum–Naie–Mendes Lopes–Pardini surfaces is an irreducible component of the Gieseker moduli space. As an important byproduct, it is shown that, for the surfaces in this irreducible component, the degree of the bicanonical map can only be 2 or 4.

Description: Aims (i) To explore variations in nutrient resorption of woody plants and their relationship with nutrient limitation and (ii) to identify the factors that control these variations in forests of eastern China. Methods We measured nitrogen (N) and phosphorus (P) concentrations in both green and senesced leaves of 172 woody species at 10 forest sites across eastern China. We compared the nutrient resorption proficiency (NuRP) and efficiency (NuRE) of N and P in plant leaves for different functional groups; we further investigated the latitudinal and altitudinal variations in NuRP and NuRE and the impacts of climate, soil and plant types on leaf nutrient resorptions. Important Findings On average, the leaf N resorption proficiency (NRP) and P resorption proficiency (PRP) of woody plants in eastern China were 11.1mg g – 1 and 0.65 mg g – 1 , respectively; and the corresponding N resorption efficiency (NRE) and P resorption efficiency (PRE) were 49.1% and 51.0%, respectively. Angiosperms have higher NRP (are less proficient) values and lower NRE and PRE values than gymnosperms, but there are no significant differences in NRP, PRP and PRE values between species with different leaf habits (evergreen vs. deciduous angiosperms). Trees have higher NRE and PRE than shrubs. Significant geographical patterns of plant nutrient resorption exist in forests of eastern China. In general, NRP and PRE decrease and PRP and NRE increase with increasing latitude/altitude for all woody species and for the different plant groups. Plant functional groups show more controls than environmental factors (climate and soil) on the N resorption traits (NRP and NRE), while site-related variables present more controls than plant types on PRP and PRE. NRP increases and PRP and NRE decrease significantly with increasing temperature and precipitation for the overall plants and for most groups, except that significant PRE–climate relationship holds for only evergreen angiosperms. Leaf nutrient resorption did not show consistent responses in relation to soil total N and P stoichiometry, probably because the resorption process is regulated by the relative costs of drawing nutrients from soil versus from senescing leaves. These results support our hypothesis that plants growing in P-limited habitats (low latitudes/altitudes or areas with high precipitation/temperature) should have lower PRP and higher PRE, compared with their counterparts in relatively N-limited places (high latitudes/altitudes or areas with low precipitation/temperature). Our findings can improve the understanding of variations in N and P resorption and their responses to global change, and thus facilitate to incorporate these nutrient resorption processes into future biogeochemical models.

Description: Motivation: Fragmented RNA immunoprecipitation combined with RNA sequencing enabled the unbiased study of RNA epigenome at a near single-base resolution; however, unique features of this new type of data call for novel computational techniques. Result: Through examining the connections of RNA epigenome sequencing data with two well-studied data types, ChIP-Seq and RNA-Seq, we unveiled the salient characteristics of this new data type. The computational strategies were discussed accordingly, and a novel data processing pipeline was proposed that combines several existing tools with a newly developed exome-based approach ‘exomePeak’ for detecting, representing and visualizing the post-transcriptional RNA modification sites on the transcriptome. Availability: The MATLAB package ‘exomePeak’ and additional details are available at http://compgenomics.utsa.edu/exomePeak/ . Contact: yufei.huang@utsa.edu or jmeng@mit.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands on HSPCs by α1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with α1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34 + cells, was used for these experiments. In vitro, FUT7-treated CB CD34 + cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34 + cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34 + cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2R null (NSG) mice. FUT7 also exhibited marginally—yet statistically significant—increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34 + cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients.