ALBERT

Description: Organismal aging is driven by interconnected molecular changes encompassing internal and extracellular factors. Combinational analysis of high-throughput ‘multi-omics’ datasets (gathering information from genomics, epigenomics, transcriptomics, proteomics, metabolomics and pharmacogenomics), at either populational or single-cell levels, can provide a multi-dimensional, integrated profile of the heterogeneous aging process with unprecedented throughput and detail. These new strategies allow for the exploration of the molecular profile and regulatory status of gene expression during aging, and in turn, facilitate the development of new aging interventions. With a continually growing volume of valuable aging-related data, it is necessary to establish an open and integrated database to support a wide spectrum of aging research. The Aging Atlas database aims to provide a wide range of life science researchers with valuable resources that allow access to a large-scale of gene expression and regulation datasets created by various high-throughput omics technologies. The current implementation includes five modules: transcriptomics (RNA-seq), single-cell transcriptomics (scRNA-seq), epigenomics (ChIP-seq), proteomics (protein–protein interaction), and pharmacogenomics (geroprotective compounds). Aging Atlas provides user-friendly functionalities to explore age-related changes in gene expression, as well as raw data download services. Aging Atlas is freely available at https://bigd.big.ac.cn/aging/index.

Description: P24 antigen is the main structural protein of HIV-1, its detection provide a means to aid the early diagnosis of HIV-1 infection. The aim of this study was to improve the selectivity and sensitivity of the HIV P24 diagnostic assay by developing a cohort of 9E8 affinity-matured antibodies through in vitro phage affinity maturation which was performed by complementarity determining region (CDR)-hot spot mutagenesis strategy. Antibody 9E8-491 had an affinity constant of 5.64 x 10 –11 M, which was 5.7-fold higher than that of the parent antibody (9E8). Furthermore, the affinity, sensitivity and specificity of 9E8-491 were higher than those of 9E8, which indicate that 9E8-491 is a good candidate detection antibody for HIV P24 assay. Structure analysis of matured variants revealed that most hydrogen bonds resided in HCDR3. Among the antibody–antigen predicted binding residues, Tyr 100A/100B was the original conserved residue that was commonly present in HCDR3 of 9E8 and variants. Arg 100 /Asp 100C was the major variant substitution that most likely influenced the binding differences among variants and 9E8 monoclonal antibody. Both efficient library panning and predicted structural data were in agreement that the binding residues were mostly located in HCDR3 and enabled identification of key residues that influence antibody affinity.

Description: O -GlcNAcylation is a ubiquitous, dynamic and reversible post-translational protein modification in metazoans, and it is catalysed and removed by O -GlcNAc transferase (OGT) and O -GlcNAcase, respectively. Prokaryotes lack endogenous OGT activity. It has been reported that coexpression of mammalian OGT with its target substrates in Escherichia coli produce O -GlcNAcylated recombinant proteins, but the plasmids used were not compatible, and the expression of both OGT and its target protein were induced by the same inducer. Here, we describe a compatible dual plasmid system for coexpression of OGT and its target substrate for O -GlcNAcylated protein production in E. coli . The approach was validated using the CKII and p53 protein as control. This compatible dual plasmid system contains an arabinose-inducible OGT expression vector with a pUC origin and an isopropyl β - d -thiogalactopyranoside-inducible OGT target substrate expression vector bearing a p15A origin. The dual plasmid system produces recombinant proteins with varying O -GlcNAcylation levels by altering the inducer concentration. More importantly, the O -GlcNAcylation efficiency was much higher than the previously reported system. Altogether, we established an adjustable compatible dual plasmid system that can effectively yield O -GlcNAcylated proteins in E. coli .

Description: Alu repetitive elements are known to be major contributors to genome instability by generating Alu -mediated copy-number variants (CNVs). Most of the reported Alu -mediated CNVs are simple deletions and duplications, and the mechanism underlying Alu – Alu -mediated rearrangement has been attributed to non-allelic homologous recombination (NAHR). Chromosome 17 at the p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for Alu repetitive elements, with a fraction of 30% of total sequence annotated in the human reference genome, compared with the 10% genome-wide and 18% on chromosome 17. We conducted mechanistic studies of the 17p13.3 CNVs by performing high-density oligonucleotide array comparative genomic hybridization, specifically interrogating the 17p13.3 region with ~150 bp per probe density; CNV breakpoint junctions were mapped to nucleotide resolution by polymerase chain reaction and Sanger sequencing. Studied rearrangements include 5 interstitial deletions, 14 tandem duplications, 7 terminal deletions and 13 complex genomic rearrangements (CGRs). Within the 17p13.3 region, Alu – Alu -mediated rearrangements were identified in 80% of the interstitial deletions, 46% of the tandem duplications and 50% of the CGRs, indicating that this mechanism was a major contributor for formation of breakpoint junctions. Our studies suggest that Alu repetitive elements facilitate formation of non-recurrent CNVs, CGRs and other structural aberrations of chromosome 17 at p13.3. The common observation of Alu -mediated rearrangement in CGRs and breakpoint junction sequences analysis further demonstrates that this type of mechanism is unlikely attributed to NAHR, but rather may be due to a recombination-coupled DNA replicative repair process.

Description: The ratios r 01 and r 10 of small-to-large separations of KIC 2837475 primarily exhibit an increasing behaviour in the observed frequency range. The calculations indicate that only the models with overshooting parameter ov between approximately 1.2 and 1.6 can reproduce the observed ratios r 01 and r 10 of KIC 2837475. The ratios r 01 and r 10 of the frequency separations of p modes with inner turning points that are located in the overshooting region of convective core can exhibit an increasing behaviour. The frequencies of the modes that can reach the overshooting region decrease with the increase in ov . Thus, the ratio distributions are more sensitive to ov than to other parameters. The increasing behaviour of the KIC 2837475 ratios results from a direct effect of the overshooting of convective core. The characteristic of the ratios provides a strict constraint on stellar models. Observational constraints point to a star with M  = 1.490 ± 0.018 M , R  = 1.67 ± 0.01 R , age =2.8 ± 0.4 Gyr, and 1.2   ov   1.6 for KIC 2837475.

Description: Motivation: A growing number of studies have explored the process of pre-implantation embryonic development of multiple mammalian species. However, the conservation and variation among different species in their developmental programming are poorly defined due to the lack of effective computational methods for detecting co-regularized genes that are conserved across species. The most sophisticated method to date for identifying conserved co-regulated genes is a two-step approach. This approach first identifies gene clusters for each species by a cluster analysis of gene expression data, and subsequently computes the overlaps of clusters identified from different species to reveal common subgroups. This approach is ineffective to deal with the noise in the expression data introduced by the complicated procedures in quantifying gene expression. Furthermore, due to the sequential nature of the approach, the gene clusters identified in the first step may have little overlap among different species in the second step, thus difficult to detect conserved co-regulated genes. Results: We propose a cross-species bi-clustering approach which first denoises the gene expression data of each species into a data matrix. The rows of the data matrices of different species represent the same set of genes that are characterized by their expression patterns over the developmental stages of each species as columns. A novel bi-clustering method is then developed to cluster genes into subgroups by a joint sparse rank-one factorization of all the data matrices. This method decomposes a data matrix into a product of a column vector and a row vector where the column vector is a consistent indicator across the matrices (species) to identify the same gene cluster and the row vector specifies for each species the developmental stages that the clustered genes co-regulate. Efficient optimization algorithm has been developed with convergence analysis. This approach was first validated on synthetic data and compared to the two-step method and several recent joint clustering methods. We then applied this approach to two real world datasets of gene expression during the pre-implantation embryonic development of the human and mouse. Co-regulated genes consistent between the human and mouse were identified, offering insights into conserved functions, as well as similarities and differences in genome activation timing between the human and mouse embryos. Availability and Implementation: The R package containing the implementation of the proposed method in C ++ is available at: https://github.com/JavonSun/mvbc.git and also at the R platform https://www.r-project.org/ . Contact: jinbo@engr.uconn.edu

Description: We analysed solar-like oscillations in 1523 Kepler red giants which have previously been misclassified as subgiants, with predicted max values [based on the Kepler Input Catalogue (KIC)] between 280 and 700 μHz. We report the discovery of 626 new oscillating red giants in our sample, in addition to 897 oscillators that were previously characterized by Hekker et al. from one quarter of Kepler data. Our sample increases the known number of oscillating low-luminosity red giants by 26 per cent (up to ~1900 stars). About three quarters of our sample are classified as ascending red giant branch stars, while the remainder are red-clump stars. A novel scheme was applied to determine for 108 stars with max close to the Nyquist frequency (387 μHz 〉 max 〉 387 μHz). Additionally, we identified 47 stars oscillating in the super-Nyquist frequency regime, up to 387 μHz, using long-cadence light curves. We show that the misclassifications are most likely due to large uncertainties in KIC surface gravities, and do not result from the absence of broad-band colours or from different physical properties such as reddening, spatial distribution, mass or metallicity. The sample will be valuable to study oscillations in low-luminosity red giants and to characterize planet candidates around those stars.

Description: SecReT4 ( http://db-mml.sjtu.edu.cn/SecReT4/ ) is an integrated database providing comprehensive information of type IV secretion systems (T4SSs) in bacteria. T4SSs are versatile assemblages that promote genetic exchange and/or effector translocation with consequent impacts on pathogenesis and genome plasticity. T4SSs have been implicated in conjugation, DNA uptake and release and effector translocation. The effectors injected into eukaryotic target cells can lead to alteration of host cellular processes during infection. SecReT4 offers a unique, highly organized, readily exploreable archive of known and putative T4SSs and cognate effectors in bacteria. It currently contains details of 10 752 core components mapping to 808 T4SSs and 1884 T4SS effectors found in representatives of 289 bacterial species, as well as a collection of more than 900 directly related references. A broad range of similarity search, sequence alignment, phylogenetic, primer design and other functional analysis tools are readily accessible via SecReT4. We propose that SecReT4 will facilitate efficient investigation of large numbers of these systems, recognition of diverse patterns of sequence-, gene- and/or functional conservation and an improved understanding of the biological roles and significance of these versatile molecular machines. SecReT4 will be regularly updated to ensure its ongoing maximum utility to the research community.

Description: APOBEC3s are a family of cytidine deaminases involved in innate cellular immunity against virus including hepatitis B virus (HBV). A germline deletion across APOBEC3A and APOBEC3B ( A3B ) genes results in complete removal of the A3B coding region and destroys A3B expression. To determine whether this deletion affects susceptibility to HBV infection and HBV-related hepatocellular carcinoma (HCC), A3B genotypes were analyzed in 1124 individuals with HCC, 510 individuals with persistent HBV infection and 826 healthy controls and the association was estimated by odds ratio (OR) and 95% confidence interval (CI) computed by logistic regression. We also examined the effects of A3B on HBV genome hypermutation and replication in HCC cells. We observed a significantly higher frequency of the A3B deletion allele in persistent HBV carriers (33.3%; P = 0.0015) and HCC patients (37.9%; P = 1.28 x 10 –11 ) compared with that in controls (27.5%). An increased risk for persistent HBV infection (OR = 1.35, 95% CI: 1.03–1.77) and HCC development (OR = 1.90, 95% CI: 1.58–2.28) was associated with at least one A3B deletion allele (+/– or –/– genotype) compared with the +/+ genotype. Transfection of A3B in HepG2 cells caused a substantial reduction of HBV RNA levels and G -〉 A hypermutation in the HBV genome. Interestingly, a cytidine deaminase null mutant of A3B (E255A) also inhibited HBV RNA production although it was unable to edit HBV. These results suggest that the deletion of A3B attenuates HBV clearance, which in turn may result in persistent HBV infection and increased risk for developing HCC. Further studies are needed to verify our findings.

Description: Aims The mechanisms of plant community assembly are hypothesized to vary at different stages of succession. Here, we explore the local assemblage structure of a herbaceous plant community at its early stage of succession in a supratidal wetland. Specifically, we assess the role of Chinese saltcedar ( Tamarix chinensis ), the lone dominant shrub species, in shaping the spatial structure and species composition in the local plant community, after landscape alteration. Methods We used the multivariate trend-surface analysis for analyzing the spatial structure of the community composition. A null model was also used to detect potential biotic interactions between species. Statistical significance was derived from a permutation test by randomizing the presence-absence matrix and functional traits independently. Sensitivity analysis by randomly selecting 50 subplots and repeating the null model tests was also done. Finally, rank correlation analysis was used to study the relationship between effect sizes and distance to nearest T. chinensis individuals. Important Findings The herbaceous plant community was highly structured and shaped by the presence of T. chinensis . At local scale, two functional traits, plant height and leaf area, were found to be significantly convergent. Dispersal, environmental stress and interspecific competition played a trivial effect on the local community assembly. The facilitating effect of T. chinensis on the pioneering herbaceous plants, through acting as a wind shelter, was put forward as the dominant community assembly process.