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Biomedical subjects

Hongwei Wu

Publications and source records attributed to Hongwei Wu.

14 recordsLinked to original sources

Computational mass spectrometry and genome mining guided discovery of metallophores produced by Microbulbifer.

Iron is an essential component of cellular biology. Thus, iron's low bioavailability is a key evolutionary pressure guiding microbial dynamics in the marine environment. Among marine bacteria, Microbulbifer is a chemically underexplored and functionally versatile bacterial genus, which is commonly associated with sponges, algae, corals, and sediments. Previously, genome analyses have revealed that Microbulbifer spp. can degrade polymers and synthesize natural products. Despite their recognized potential to produce secondary metabolites, siderophores are yet to be identified in Microbulbifer, and their iron acquisition strategies remain largely unknown. Here, we developed a comprehensive mass spectrometry-based query language code to determine siderophore production by Microbulbifer spp. in mono- and mixed cultures. Using this workflow, we discovered a new metallophore, which we named bulbichelin, as well as a suite of previously unreported petrobactins containing an unprecedented longer chain length acylation on the central spermidine moiety. We applied genome mining methods to describe the biosynthesis of these compounds. Using metal infusion mass spectrometry, we show that bulbichelins bind a variety of metals. Notably, neither of these compounds were produced in a co-culture of Microbulbifer with coral-derived pathogen Vibrio coralliilyticus Cn52-H1. Understanding how siderophores shape interspecies interactions between Microbulbifer spp. and other marine organisms will aid in unraveling the chemical and catalytic versatility of this genus and adaptation in nutrient deplete marine environment.

MassQL↗

Detecting uber-operons in prokaryotic genomes.

We present a study on computational identification of uber-operons in a prokaryotic genome, each of which represents a group of operons that are evolutionarily or functionally associated through operons in other (reference) genomes. Uber-operons represent a rich set of footprints of operon evolution, whose full utilization could lead to new and more powerful tools for elucidation of biological pathways and networks than what operons have provided, and a better understanding of prokaryotic genome structures and evolution. Our prediction algorithm predicts uber-operons through identifying groups of functionally or transcriptionally related operons, whose gene sets are conserved across the target and multiple reference genomes. Using this algorithm, we have predicted uber-operons for each of a group of 91 genomes, using the other 90 genomes as references. In particular, we predicted 158 uber-operons in Escherichia coli K12 covering 1830 genes, and found that many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments. For some of the predicted uber-operons that are not parts of known regulons or pathways, our analyses indicate that their genes are highly likely to work together in the same biological processes, suggesting the possibility of new regulons and pathways. We believe that our uber-operon prediction provides a highly useful capability and a rich information source for elucidation of complex biological processes, such as pathways in microbes. All the prediction results are available at our Uber-Operon Database: http://csbl.bmb.uga.edu/uber, the first of its kind.

Algorithms↗

Environmental-benign utilisation of fly ash as low-cost adsorbents.

Fly ash is a waste substance from thermal power plants, steel mills, etc. that is found in abundance in the world. In recent years, utilisation of fly ash has gained much attention in public and industry, which will help reduce the environmental burden and enhance economic benefit. In this paper, the technical feasibility of utilisation of fly ash as a low-cost adsorbent for various adsorption processes for removal of pollutants in air and water systems has been reviewed. Instead of using commercial activated carbon or zeolites, a lot of researches have been conducted using fly ash for adsorption of NO(x), SO(x), organic compounds, and mercury in air, and cations, anions, dyes and other organic matters in waters. It is recognised that fly ash is a promising adsorbent for removal of various pollutants. Chemical treatment of fly ash will make conversion of fly ash into a more efficient adsorbent for gas and water cleaning. Investigations also revealed that unburned carbon component in fly ash plays an important role in adsorption capacity. Directions for future research are also discussed.

Absorption↗

Computational inference and experimental validation of the nitrogen assimilation regulatory network in cyanobacterium Synechococcus sp. WH 8102.

Deciphering the regulatory networks encoded in the genome of an organism represents one of the most interesting and challenging tasks in the post-genome sequencing era. As an example of this problem, we have predicted a detailed model for the nitrogen assimilation network in cyanobacterium Synechococcus sp. WH 8102 (WH8102) using a computational protocol based on comparative genomics analysis and mining experimental data from related organisms that are relatively well studied. This computational model is in excellent agreement with the microarray gene expression data collected under ammonium-rich versus nitrate-rich growth conditions, suggesting that our computational protocol is capable of predicting biological pathways/networks with high accuracy. We then refined the computational model using the microarray data, and proposed a new model for the nitrogen assimilation network in WH8102. An intriguing discovery from this study is that nitrogen assimilation affects the expression of many genes involved in photosynthesis, suggesting a tight coordination between nitrogen assimilation and photosynthesis processes. Moreover, for some of these genes, this coordination is probably mediated by NtcA through the canonical NtcA promoters in their regulatory regions.

Bacterial Proteins↗

Synthesis of 2,5-thiazole butanoic acids as potent and selective alpha(v)beta3 integrin receptor antagonists with improved oral pharmacokinetic properties.

We describe a series of 2,5 thiazole containing compounds, which are potent antagonists of the integrin alpha(v)beta3 and show selectivity relative to the other integrins, such as alpha(IIb)beta3 and alpha(v)beta6. These analogs were demonstrated to have high bioavailability relative to other relative heterocyclic analogs.

Administration, Oral↗

Convergent, parallel synthesis of a series of beta-substituted 1,2,4-oxadiazole butanoic acids as potent and selective alpha(v)beta3 receptor antagonists.

We describe a series of 1,2,4-oxadiazoles, which are potent antagonists of the integrin alpha(v)beta3 and, in addition, show selectivity relative to the other beta3 integrin alpha(IIb)beta3. In whole cells, the majority of these analogs also demonstrated modest selectivity against other alpha(v) integrins such as alpha(v)beta1 and alpha(v)beta6.

Antigens, Neoplasm↗

Unburned carbon as a low-cost adsorbent for treatment of methylene blue-containing wastewater.

Fly ash, natural zeolite, and unburned carbon separated from fly ash have been employed as low-cost adsorbents for dye adsorption in methylene blue-containing wastewater. It is found that the unburned carbon exhibits a much higher adsorption capacity than raw fly ash and natural zeolite. The adsorption capacities of fly ash, natural zeolite, and unburned carbon for methylene blue are 2 x 10(-5), 5 x 10(-5), and 2.5 x 10(-4) mol/g, respectively. Investigation also indicates that adsorption is influenced by initial dye concentration, particle size, dye solution pH, and adsorption temperature. Adsorption on unburned carbon increases with the initial dye concentration, solution pH, and temperature, but reduces with the increasing particle size. Kinetic studies show that adsorption of methylene blue on fly ash, natural zeolite, and unburned carbon can be best described by the pseudo-second-order adsorption model and that adsorption is a two-step diffusion process. The apparent activation energies for methylene blue adsorption on unburned carbon in the first and second diffusion processes are 12.4 and 39.3 kJ/mol, respectively.

Adsorption↗

Prediction of functional modules based on comparative genome analysis and Gene Ontology application.

We present a computational method for the prediction of functional modules encoded in microbial genomes. In this work, we have also developed a formal measure to quantify the degree of consistency between the predicted and the known modules, and have carried out statistical significance analysis of consistency measures. We first evaluate the functional relationship between two genes from three different perspectives--phylogenetic profile analysis, gene neighborhood analysis and Gene Ontology assignments. We then combine the three different sources of information in the framework of Bayesian inference, and we use the combined information to measure the strength of gene functional relationship. Finally, we apply a threshold-based method to predict functional modules. By applying this method to Escherichia coli K12, we have predicted 185 functional modules. Our predictions are highly consistent with the previously known functional modules in E.coli. The application results have demonstrated that our approach is highly promising for the prediction of functional modules encoded in a microbial genome.

Bayes Theorem↗

Solution structure of the Tctex1 dimer reveals a mechanism for dynein-cargo interactions.

Tctex1 is a light chain found in both cytoplasmic and flagellar dyneins and is involved in many fundamental cellular activities, including rhodopsin transport within photoreceptors, and may function in the non-Mendelian transmission of t haplotypes in mice. Here, we present the NMR solution structure for the Tctex1 dimer from Chlamydomonas axonemal inner dynein arm I1. Structural comparisons reveal a strong similarity with the LC8 dynein light chain dimer, including formation of a strand-switched beta sheet interface. Analysis of the Tctex1 structure enables the dynein intermediate chain binding site to be identified and suggests a mechanism by which cargo proteins might be attached to this microtubule motor complex. Comparison with the alternate dynein light chain rp3 reveals how the specificity of dynein-cargo interactions mediated by these dynein components is achieved. In addition, this structure provides insight into the consequences of the mutations found in the t haplotype forms of this protein.

Amino Acid Sequence↗

Accurate prediction of orthologous gene groups in microbes.

We present a new computational method for the prediction of orthologous gene groups for microbial genomes based on the prediction of co-occurrences of homologous genes. The method is inspired by the observation that homologous genes are highly likely to be orthologous if their neighboring genes are also homologous. Based on co-occurrences of homologous genes, we have grouped the (predicted) operons of 77 selected sequenced microbial genomes so that operons of the same group are highly likely to be functionally similar or related. We then cluster the homologous genes in the same operon group so that genes of the same cluster are highly likely to be similar in terms of their sequences and functions, i.e., they are predicted to be orthologous genes. By comparing our predicted orthologous gene groups with the COG assignments and NCBI annotations, we conclude that our method is promising to provide more accurate and specific predictions than the existing methods.

Algorithms↗

Prediction of functional modules based on gene distributions in microbial genomes.

We present a computational method for prediction of functional modules that can be directly applied to the newly sequenced microbial genomes for predicting gene functions and the component genes of biological pathways. We first quantify the functional relatedness among genes based on their distribution (i.e., their existences and orders) across multiple microbial genomes, and obtain a gene network in which every pair of genes is associated with a score representing their functional relatedness. We then apply a threshold-based clustering algorithm to this gene network, and obtain modules for each of which the number of genes is bounded from above by a pre-specified value and the component genes are more strongly functionally related to each other than genes across the predicted modules. Particularly, when the module size is bounded by 130, we obtain 167 functional modules covering 813 genes for Escherichia coli K12, and 138 functional modules covering 731 genes for Bacillus subtilis subsp. subtilis str. 168. We have used the gene ontology (GO) information to assess the prediction results. The GO similarities among the genes of the same functional module are compared with the GO similarities among the genes that are randomly clustered together. This comparison reveals that our predicted functional modules are statistically and biologically significant, and the genes of the same functional module share more commonality in terms of biological process than in terms of molecular function or cellular component. We have also examined the predicted functional modules that are common to both Escherichia coli K12 and Bacillus subtilis subsp. subtilis str. 168, and provide explanations for some functional modules.

Cluster Analysis↗

Relaxation-based structure refinement and backbone molecular dynamics of the dynein motor domain-associated light chain.

The light chain 1 (LC1) polypeptide is a member of the leucine-rich repeat protein family and binds at or near the ATP hydrolytic site within the motor domain of the gamma heavy chain from Chlamydomonas outer arm dynein. It consists of an N-terminal helix, a central barrel formed from six leucine-rich repeats that fold as beta beta alpha units, and a C-terminal helical domain that protrudes from the main axis defined by the leucine-rich repeats. Interaction with the gamma heavy chain is likely mediated through a hydrophobic patch on the larger beta sheet face, and the C-terminal region is predicted to insert into the dynein ATP hydrolytic site. Here we have used 1H-15N heteronuclear relaxation measurements obtained at 500 and 600 MHz to refine and validate the LC1 solution structure. In this refined structure, the C-terminal helix is significantly reoriented by more than 20 degrees as compared to the control and provides a more precise understanding of the potential regulatory role of this domain. We also employed the refined structure to perform a dynamic analysis of LC1 using the 600 MHz data set. These results, which were cross validated using the 500 MHz data set, strongly support identification of the predicted LC1 binding surfaces and provide additional insight into the interaction mechanisms of leucine-rich repeat proteins.

Animals↗

beta-Silyl and beta-Germyl Carbocations Stable at Room Temperature.

Stable carbocations have been prepared at room temperature with benzene as solvent and tetrakis(pentafluorophenyl)borate (TPFPB) as anion by the addition of solvated triethylsilylium TPFPB or of tributylgermylium TPFPB to 1,1-diphenylethene. These carbocations are stabilized by sigma conjugation with nonadjacent group 14 atoms and respectively constitute stable saturated beta-silyl and beta-germyl carbocations. NMR parameters, including the (29)Si chemical shift, the (13)C chemical shifts of the cationic, aryl, and methylene carbons, and the one-bond (13)C-(1)H coupling constant of the methylene group adjacent to the group 14 element, define the distribution of positive charge between carbon and (through sigma conjugation) silicon or germanium. The extent of hyperconjugation is estimated quantitatively by comparison with models. The NMR parameters indicate that the cations are open rather than bridged.

Journal Article↗