PubMed Health⌕ Search

Biomedical subjects

Lei Qin

Publications and source records attributed to Lei Qin.

16 recordsLinked to original sources

In silico discovery of human natural antisense transcripts.

BACKGROUND: Several high-throughput searches for potential natural antisense transcripts (NATs) have been performed recently, but most of the reports were focused on cis type. A thorough in silico analysis of human transcripts will help expand our knowledge of NATs. RESULTS: We have identified 568 NATs from human RefSeq RNA sequences. Among them, 403 NATs are reported for the first time, and at least 157 novel NATs are trans type. According to the pairing region of a sense and antisense RNA pair, hNATs are divided into 6 classes, of which about 87% involve 5' or 3' UTR sequences, supporting the regulatory role of UTRs. Among a total of 535 NAT pairs related with splice variants, 77.4% (414/535) have their pairing regions affected or completely eliminated by alternative splicing, suggesting significant relationship of alternative splicing and antisense-directed regulation. The extensive occurrence of splice variants in hNATs and other multiple pairing patterns results in a one-to-many relationship, allowing the formation of complex regulation networks. Based on microarray data from Stanford Microarray Database, two hNAT pairs were found to display significant inverse expression patterns before and after insulin injection. CONCLUSION: NATs might carry out more extensive and complex functions than previously thought. Combined with endogenous micro RNAs, hNATs could be regarded as a special group of transcripts contributing to the complex regulation networks.

Algorithms↗

cvhA gene of Streptomyces hygroscopicus 10-22 encodes a negative regulator for mycelia development.

A five-gene cluster cvhABCDE was identified from Streptomyces hygroscopicus 10-22. As the first gene of this cluster, cvhA encoded a putative sensor histidine kinase with a predicted sensor domain consisting of two trans-membrane segments at the N-terminus and a conserved HATPase_c domain at the C-terminus. The C-terminus polypeptide of CvhA expressed in Escherichia coli was purified and shown to be autophosphorylated with [gamma-32P]ATP in vitro. The phosphoryl group was acid-labile and basic-stable, which supported histidine as the phosphorylation residue. No obvious difference of mycelia development was observed between the null mutant of cvhA generated by targeted gene replacement and the wild-type parental strain 10-22 grown on solid soya flour medium with 2%-8% glucose or sucrose, but the cvhA mutant could form much more abundant aerial mycelia and spores than the wild-type strain on solid soya flour medium supplemented with 6%-8% mannitol, 6%-8% sorbitol, 4%-6% mannose, or 4%-6% fructose. This phenotype was complemented by the cloned wild-type cvhA gene, and no difference was observed for growth curves of the cvhA mutant and the wild strain in liquid minimal medium with the tested sugars at a concentration of 4%, 6% and 8%. We thus propose that CvhA is likely a sensor histidine kinase and negatively regulates the morphological differentiation in a sugar-dependent manner in S. hygroscopicus 10-22.

Amino Acid Sequence↗

Aerobic granulation for organic carbon and nitrogen removal in alternating aerobic-anaerobic sequencing batch reactor.

Microbial granules with excellent settle-ability were successfully developed at different ammonium-N loadings in four sequencing batch reactors run under alternating aerobic-anaerobic conditions. Results showed that heterotrophic, nitrifying and denitrifying populations could co-exist in the microbial granules. The activity of denitrifying bacteria was highly determined by the availability of external carbon source in the anaerobic phase. Complete denitrification was achieved with supply of external carbon source, whereas only partial denitrification occurred with no addition of external carbon source. This study shows that microbial granules cultivated under the alternating aerobic-anaerobic condition could efficiently remove organic carbon and completely convert ammonia to nitrogen gas. A new generation of microbial granules-based bioreactor for organics and nitrogen removal can be envisaged.

Aerobiosis↗

A wavelet-based time-frequency analysis approach for classification of motor imagery for brain-computer interface applications.

Electroencephalogram (EEG) recordings during motor imagery tasks are often used as input signals for brain-computer interfaces (BCIs). The translation of these EEG signals to control signals of a device is based on a good classification of various kinds of imagination. We have developed a wavelet-based time-frequency analysis approach for classifying motor imagery tasks. Time-frequency distributions (TFDs) were constructed based on wavelet decomposition and event-related (de)synchronization patterns were extracted from symmetric electrode pairs. The weighted energy difference of the electrode pairs was then compared to classify the imaginary movement. The present method has been tested in nine human subjects and reached an averaged classification rate of 78%. The simplicity of the present technique suggests that it may provide an alternative method for EEG-based BCI applications.

Algorithms↗

Denitrification on poly-beta-hydroxybutyrate in microbial granular sludge sequencing batch reactor.

Microbial granules were successfully cultivated in an alternating aerobic-anaerobic sequencing batch reactor (SBR) for removing organic carbon and nitrogen. It was found that almost all input ammonium was converted to nitrite and nitrate in the aerobic phase, while the efficiency of denitrification was highly related to the availability of external carbon source in the anaerobic phase. Complete denitrification was achieved with sufficient supply of external carbon, while only partial denitrification was observed with no addition of external carbon. Results showed that in the absence of external carbon source, pre-accumulated poly-beta-hydroxybutyric acid (PHB) in microbial granules could be utilized for cell maintenance and denitrification. With supply of external carbon but no addition of nitrate, PHB accumulation accounted for the main mechanism of the organic removal. Under balanced growth conditions (with organic carbon and nitrogen supply), external organic carbon was consumed simultaneously for denitrification, PHB storage as well as for cell functions. It was revealed that the potential role of PHB for denitrification by microbial granules was very limited, i.e. less than 28 mg nitrate-nitrogen l(-1) was found to be denitrified with internally accumulated PHB. This study for the first time shows the limiting capacity of PHB as reducing power for denitrification by microbial granules.

Bacteria, Aerobic↗

Selection pressure-driven aerobic granulation in a sequencing batch reactor.

In recent years, the research on aerobic granulation has been intensive. So far, almost all aerobic granules can form only in sequencing batch reactors (SBR), while the reason is not yet understood. This paper attempts to review the factors involved in aerobic granulation in SBR, including substrate composition, organic loading rate, hydrodynamic shear force, feast-famine regime, feeding strategy, dissolved oxygen, reactor configuration, solids retention time, cycle time, settling time and exchange ratio. The major selection pressures responsible for aerobic granulation are identified as the settling time and exchange ratio. A concept of the minimal settling velocity of bioparticles is proposed; and it is quantitatively demonstrated that the effects of settling time and exchange ratio on aerobic granulation in SBR can be interpreted and unified on the basis of this concept very well. It appears that the formation and characteristics of aerobic granules can be manipulated through properly adjusting either the settling time or the exchange ratio in SBR. Consequently, theoretical and experimental evidence point to the fact that aerobic granulation is a selection pressure-driven cell-to-cell immobilization process.

Bacteria, Aerobic↗

Motor imagery classification by means of source analysis for brain-computer interface applications.

We report a pilot study of performing classification of motor imagery for brain-computer interface applications, by means of source analysis of scalp-recorded EEGs. Independent component analysis (ICA) was used as a spatio-temporal filter extracting signal components relevant to left or right motor imagery (MI) tasks. Source analysis methods including equivalent dipole analysis and cortical current density imaging were applied to reconstruct equivalent neural sources corresponding to MI, and classification was performed based on the inverse solutions. The classification was considered correct if the equivalent source was found over the motor cortex in the corresponding hemisphere. A classification rate of about 80% was achieved in the human subject studied using both the equivalent dipole analysis and the cortical current density imaging analysis. The present promising results suggest that the source analysis approach could manifest a clearer picture on the cortical activity, and thus facilitate the classification of MI tasks from scalp EEGs.

Algorithms↗

The influence of cell and substratum surface hydrophobicities on microbial attachment.

This study investigated the role of hydrophobic/hydrophilic interaction between bacterial and support surfaces in microbial adhesion, and a model that correlates microbial adhesion and relative cell-hydrophobicity defined as the ratio of cell-support surface hydrophobicity over cell-support hydrophilicity was derived. This model quantitatively describes how cell hydrophobic and hydrophilic interactions affect microbial adhesion, and offers deep insights into the thermodynamic mechanisms of microbial adhesion. The proposed model was verified by literature data. It appears that a high cell-hydrophobicity strongly facilitates microbial adhesion on both hydrophobic and hydrophilic support surfaces.

Bacterial Adhesion↗

Semantic search among heterogeneous biological databases based on gene ontology.

Semantic search is a key issue in integration of heterogeneous biological databases. In this paper, we present a methodology for implementing semantic search in BioDW, an integrated biological data warehouse. Two tables are presented: the DB2GO table to correlate Gene Ontology (GO) annotated entries from BioDW data sources with GO, and the semantic similarity table to record similarity scores derived from any pair of GO terms. Based on the two tables, multifarious ways for semantic search are provided and the corresponding entries in heterogeneous biological databases in semantic terms can be expediently searched.

Database Management Systems↗

Identification and characterization of hmr19 gene encoding a multidrug resistance efflux protein from Streptomyces hygroscopicus subsp. yingchengensis strain 10-22.

The hmr19 gene was cloned from Streptomyces hygroscopicus subsp. yingchengensis strain 10-22, a bacterium strain producing agricultural antibiotics. Sequence similarity comparison indicates that hmr19 gene may encode a predicted protein with 14 putative transmembrane alpha-helical spanners, belonging to the drug:H(+) antiporter-2 family of the major facilitator superfamily. The expression of hmr19 in the mycelium of strain 10-22 was detected by Western blotting analysis. Gene replacement technology was employed to construct an hmr19 disruption mutant. The growth inhibition test against different antibiotics indicated that the mutant strain was 5-20 fold more susceptible to tetracycline, vancomycin and mitomycin C than the parental wild type strain. The mutant took up tetracycline much faster and accumulated more antibiotics than the wild type strain 10-22. While with the addition of an energy uncoupler, carbonyl cyanide m-chlorophenylhydrazone, the characteristics of the accumulation of [(3)H]tetracycline in these two strains were almost the same. It was thus concluded that hmr19 encoded a multidrug resistance efflux protein.

Amino Acid Sequence↗

Putative hAPN receptor binding sites in SARS_CoV spike protein.

AIM: To obtain the information of ligand-receptor binding between the S protein of SARS-CoV and CD13, identify the possible interacting domains or motifs related to binding sites, and provide clues for studying the functions of SARS proteins and designing anti-SARS drugs and vaccines. METHODS: On the basis of comparative genomics, the homology search, phylogenetic analyses, and multi-sequence alignment were used to predict CD13 related interacting domains and binding sites in the S protein of SARS-CoV. Molecular modeling and docking simulation methods were employed to address the interaction feature between CD13 and S protein of SARS-CoV in validating the bioinformatics predictions. RESULTS: Possible binding sites in the SARS-CoV S protein to CD13 have been mapped out by using bioinformatics analysis tools. The binding for one protein-protein interaction pair (D757-R761 motif of the SARS-CoV S protein to P585-A653 domain of CD13) has been simulated by molecular modeling and docking simulation methods. CONCLUSION: CD13 may be a possible receptor of the SARS-CoV S protein, which may be associated with the SARS infection. This study also provides a possible strategy for mapping the possible binding receptors of the proteins in a genome.

Amino Acid Sequence↗

Identification of probable genomic packaging signal sequence from SARS-CoV genome by bioinformatics analysis.

AIM: To predict the probable genomic packaging signal of SARS-CoV by bioinformatics analysis. The derived packaging signal may be used to design antisense RNA and RNA interfere (RNAi) drugs treating SARS. METHODS: Based on the studies about the genomic packaging signals of MHV and BCoV, especially the information about primary and secondary structures, the putative genomic packaging signal of SARS-CoV were analyzed by using bioinformatic tools. Multi-alignment for the genomic sequences was performed among SARS-CoV, MHV, BCoV, PEDV and HCoV 229E. Secondary structures of RNA sequences were also predicted for the identification of the possible genomic packaging signals. Meanwhile, the N and M proteins of all five viruses were analyzed to study the evolutionary relationship with genomic packaging signals. RESULTS: The putative genomic packaging signal of SARS-CoV locates at the 3' end of ORF1b near that of MHV and BCoV, where is the most variable region of this gene. The RNA secondary structure of SARS-CoV genomic packaging signal is very similar to that of MHV and BCoV. The same result was also obtained in studying the genomic packaging signals of PEDV and HCoV 229E. Further more, the genomic sequence multi-alignment indicated that the locations of packaging signals of SARS-CoV, PEDV, and HCoV overlaped each other. It seems that the mutation rate of packaging signal sequences is much higher than the N protein, while only subtle variations for the M protein. CONCLUSIONS: The probable genomic packaging signal of SARS-CoV is analogous to that of MHV and BCoV, with the corresponding secondary RNA structure locating at the similar region of ORF1b. The positions where genomic packaging signals exist have suffered rounds of mutations, which may influence the primary structures of the N and M proteins consequently.

Amino Acid Sequence↗

A 3D model of SARS_CoV 3CL proteinase and its inhibitors design by virtual screening.

AIM: To constructed a three-dimensional (3D) model for the 3C like (3CL) proteinase of SARS coronavirus (SARS-CoV), and to design inhibitors of the 3CL proteinase based on the 3D model. METHODS: Bioinformatics analyses were performed to search the homologous proteins of the SARS-CoV 3CL proteinase from the GenBank and PDB database. A 3D model of the proteinase was constructed by using homology modeling technique. Targeting to the 3D model and its X-ray crystal structure of the main proteinase (Mpro) of transmissible gastroenteritis virus (TGEV), virtual screening was performed employing molecular docking method to identify possible 3CL proteinase inhibitors from small molecular databases. RESULTS: Sequence alignment indicated that the SARS-CoV 3CL proteinase was extremely homologous to TGEV Mpro, especially the substrate-binding pocket (active site). Accordingly, a 3D model for the SARS-CoV 3CL proteinase was constructed based on the crystal structure of TGEV Mpro. The 3D model adopts a similar fold of the TGEV Mpro, its structure and binding pocket feature are almost as same as that of TGEV Mpro. The tested virtual screening indicated that 73 available proteinase inhibitors in the MDDR database might dock into both the binding pockets of the TGEV Mpro and the SARS-CoV 3CL proteinase. CONCLUSIONS: Either the 3D model of the SARS-CoV 3CL proteinase or the X-ray crystal structure of the TGEV Mpro may be used as a starting point for design anti-SARS drugs. Screening the known proteinase inhibitors may be an appreciated shortcut to discover anti-SARS drugs.

Computational Biology↗

Small envelope protein E of SARS: cloning, expression, purification, CD determination, and bioinformatics analysis.

AIM: To obtain the pure sample of SARS small envelope E protein (SARS E protein), study its properties and analyze its possible functions. METHODS: The plasmid of SARS E protein was constructed by the polymerase chain reaction (PCR), and the protein was expressed in the E coli strain. The secondary structure feature of the protein was determined by circular dichroism (CD) technique. The possible functions of this protein were annotated by bioinformatics methods, and its possible three-dimensional model was constructed by molecular modeling. RESULTS: The pure sample of SARS E protein was obtained. The secondary structure feature derived from CD determination is similar to that from the secondary structure prediction. Bioinformatics analysis indicated that the key residues of SARS E protein were much conserved compared to the E proteins of other coronaviruses. In particular, the primary amino acid sequence of SARS E protein is much more similar to that of murine hepatitis virus (MHV) and other mammal coronaviruses. The transmembrane (TM) segment of the SARS E protein is relatively more conserved in the whole protein than other regions. CONCLUSION: The success of expressing the SARS E protein is a good starting point for investigating the structure and functions of this protein and SARS coronavirus itself as well. The SARS E protein may fold in water solution in a similar way as it in membrane-water mixed environment. It is possible that beta-sheet I of the SARS E protein interacts with the membrane surface via hydrogen bonding, this beta-sheet may uncoil to a random structure in water solution.

Circular Dichroism↗

A generalized model for settling velocity of aerobic granular sludge.

Aerobic granulation is a novel biotechnology recently receiving intensive research attention. Aerobic granules developed in SBR can be as big as several millimeters, thus the traditional models describing the settling velocity of activated sludge are no long valid in aerobic granules culture. In this study, a new type of model was developed for the settling velocity of aerobic granules. This model shows that the settling velocity of aerobic granules is the function of SVI, mean size of granules and biomass concentration of granules. When the size of bioparticle is small enough, the proposed model reduces to the well-known Vesilind equation. Results indicated that the proposed model could satisfactorily fit experimental results obtained in the course of aerobic granulation under different conditions, while the Vesilind equation failed to or very poorly fit the experimental data. In addition, the proposed model can also be extended to anaerobic granules. The settling velocity is one of the most important parameters in both aerobic and anaerobic granulation, and successful biogranulation is highly related to the manipulation of settling velocity. It was demonstrated that the proposed model can sever as a useful tool for design and operation engineers to properly select the settling velocity for enhanced aerobic and anaerobic granulation.

Aerobiosis↗