Biomedical subjects

Bin He

Publications and source records attributed to Bin He.

At least 19 recordsLinked to original sources

PubMed2026

Precisely designed keystone metabolites boost shrimp disease resistance by recruiting symbionts via the lipoxin A4-AP-1 pathway.

BACKGROUND: Gut metabolites and symbionts are indispensable for host health, yet the precise identification of keystone metabolites and construction of synthetic microbial communities (SynComs) to enhance disease resistance remains limited. RESULTS: Using Litopenaeus vannamei as a model, we identified pyruvic acid and DL-glutamine (1:2) as keystone metabolites by borrowing the microbial ecology principles of bio-indicators and driver taxa. Dietary supplementation with these metabolites sufficiently protected shrimp from white feces syndrome (WFS). Multi-omics analyses demonstrated that keystone metabolites exerted positive effects by enriching beneficial Ruegeria lacuscaerulensis, Bacillus subtilis and Nioella nitratireducens, strengthening the gut network stability, and enhancing shrimp immunity, which collectively potentiated WFS resistance. The recruited three strains were consumers and producers of the two keystone metabolites, and discriminative strains between healthy and diseased shrimp across global datasets. A SynCom constructed from the three strains (4:3:2) replicated the efficacy of keystone metabolites. Both keystone metabolites and SynCom elevated shrimp gut and hepatopancreas lipoxin A4 (LXA4) levels, which suppressed the pro-inflammatory transcription factor AP-1, as validated by in vivo inhibition assay. CONCLUSIONS: Our findings demonstrate that precisely designed keystone metabolites enhance shrimp disease resistance through the recruitment of key symbionts-LXA4-AP-1 axis. The rationally designed keystone metabolites and SynCom are compelling biocontrol solutions in improving host disease resistance. Video Abstract.

Animals↗

PubMed2005

Herpes simplex virus 1 infection activates the endoplasmic reticulum resident kinase PERK and mediates eIF-2alpha dephosphorylation by the gamma(1)34.5 protein.

The gamma(1)34.5 protein of herpes simplex virus (HSV) plays a crucial role in virus infection. Although the double-stranded RNA-dependent protein kinase (PKR) is activated during HSV infection, the gamma(1)34.5 protein inhibits the activity of PKR by mediating dephosphorylation of the translation initiation factor eIF-2alpha. Here we show that HSV infection also induces phosphorylation of an endoplasmic reticulum (ER) resident kinase PERK, a hallmark of ER stress response. The virus-induced phosphorylation of PERK is blocked by cycloheximide but not by phosphonoacetic acid, suggesting that the accumulation of viral proteins in the ER is essential. Notably, the maximal phosphorylation of PERK is delayed in PKR+/+ cells compared to that seen in PKR-/- cells. Further analysis indicates that hyperphosphorylation of eIF-2alpha caused by HSV is greater in PKR+/+ cells than in PKR-/- cells. However, expression of the gamma(1)34.5 protein suppresses the ER stress response caused by virus, dithiothreitol, and thapsigargin as measured by global protein synthesis. Interestingly, the expression of GADD34 stimulated by HSV infection parallels the status of eIF-2alpha phosphorylation. Together, these observations suggest that regulation of eIF-2alpha phosphorylation by the gamma(1)34.5 protein is an efficient way to antagonize the inhibitory activity of PKR as well as PERK during productive infection.

Animals↗

PubMed2005

Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the interdomain interaction.

Gene activation by steroid hormone receptors involves the recruitment of the steroid receptor coactivator (SRC)/p160 coactivator LXXLL motifs to activation function 2 (AF2) in the ligand binding domain. For the androgen receptor (AR), AF2 also serves as the interaction site for the AR NH(2)-terminal FXXLF motif in the androgen-dependent NH(2)-terminal and carboxyl-terminal (N/C) interaction. The relative importance of the AR AF2 site has been unclear, since the AR FXXLF motif interferes with coactivator recruitment by competitive inhibition of LXXLL motif binding. In this report, we identified the X chromosome-linked melanoma antigen gene product MAGE-11 as an AR coregulator that specifically binds the AR NH(2)-terminal FXXLF motif. Binding of MAGE-11 to the AR FXXLF alpha-helical region stabilizes the ligand-free AR and, in the presence of an agonist, increases exposure of AF2 to the recruitment and activation by the SRC/p160 coactivators. Intracellular association between AR and MAGE-11 is supported by their coimmunoprecipitation and colocalization in the absence and presence of hormone and by competitive inhibition of the N/C interaction. AR transactivation increases in response to MAGE-11 and the SRC/p160 coactivators through mechanisms that include but are not limited to the AF2 site. MAGE-11 is expressed in androgen-dependent tissues and in prostate cancer cell lines. The results suggest MAGE-11 is a unique AR coregulator that increases AR activity by modulating the AR interdomain interaction.

Amino Acid Motifs↗

PubMed2004

Highly enantioselective cyanosilylation of aldehydes catalyzed by novel beta-amino alcohol-titanium complexes.

The beta-amino alcohol 1b-Ti(Oi-Pr)(4) complex has been shown to catalyze the enantioselective cyanosilylation of aldehydes efficiently. In the presence of 5 mol % of 1b-Ti(Oi-Pr)(4) complex catalyst, the aromatic, conjugated, heteroaromatic, and aliphatic aldehydes were converted to their corresponding trimethylsilyl ethers of cyanohydrins in 90-99% yields with up to 94% ee under mild conditions.

Journal Article↗

PubMed2004

Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance.

The androgen receptor (AR) is required for male sex development and contributes to prostate cancer cell survival. In contrast to other nuclear receptors that bind the LXXLL motifs of coactivators, the AR ligand binding domain is preferentially engaged in an interdomain interaction with the AR FXXLF motif. Reported here are crystal structures of the ligand-activated AR ligand binding domain with and without bound FXXLF and LXXLL peptides. Key residues that establish motif binding specificity are identified through comparative structure-function and mutagenesis studies. A mechanism in prostate cancer is suggested by a functional AR mutation at a specificity-determining residue that recovers coactivator LXXLL motif binding. An activation function transition hypothesis is proposed in which an evolutionary decline in LXXLL motif binding parallels expansion and functional dominance of the NH(2)-terminal transactivation domain in the steroid receptor subfamily.

Amino Acid Motifs↗

PubMed2004

Synergistic activation of the CMV promoter by NF-kappaB P50 and PKG.

Several DNA binding NF-kappaB subunits are substrates for cGMP-dependent kinase (PKG) and their transactivation from cognate sites is induced by phosphorylation. This includes p50, which does not have a transcriptional activation domain and therefore needs to bind to other proteins to mediate gene expression. Here, we describe the synergistic transactivation by p50 and PKG from the CMV promoter. This is caused not only by phosphorylation of p50, leading to increased DNA binding, but also by PKG-dependent activation of CRE sites in the promoter. One of the CRE sites is located directly adjacent to a NF-kappaB site and is essential for p50-mediated induction of transcription. According to the binding of CREB to p50 in pull-down assays and according to the inhibition of p50-dependent transactivation by dominant-negative CREB, this reflects the formation of a transcription factor complex containing CREB and p50. The nuclear translocation of NF-kappaB is insufficient to distinguish among the multitude of promoters that harbor cognate recognition sites. The phosphorylation of multiple transcription factors by an upstream kinase, such as PKG, can lead to the formation of transcription factor complexes and differential transactivation from a subset of NF-kappaB sites. These interactions may be relevant for the activation of viral gene expression.

Animals↗

PubMed2004

Mathematical algorithm for discovering states of expression from direct genetic comparison by microarrays.

Highly specific direct genome-scale expression discovery from two biological samples facilitates functional discovery of molecular systems. Here, expression data from cDNA arrays are ranked and curve-fitted. The algorithm uses filters based on the derivatives (slopes) of the curve fits. The rules are set to (i) filter the largest number of artifactual ratios from same-to-same datasets and (ii) maximize discovery from direct comparisons of different samples. The unsupervised discovery is optimized without lowering specificity. The false discovery rates are significantly lower than other methods. The discovered states of genetic expression facilitate functional discovery and are validated by real-time RT-PCR. Better quality improves sensitivity.

Algorithms↗

PubMed2004

A second-order finite element algorithm for solving the three-dimensional EEG forward problem.

A finite element algorithm has been developed to solve the electroencephalogram (EEG) forward problem. A new computationally efficient approach to calculate the stiffness matrix of second-order tetrahedral elements has been developed for second-order tetrahedral finite element models. The present algorithm has been evaluated by means of computer simulations, by comparing with analytic solutions in a multi-spheres concentric head model. The developed finite element method (FEM) algorithm has also been applied to address questions of interest in the EEG forward problem. The present simulation study indicates that the second-order FEM provides substantially enhanced numerical accuracy and computational efficiency, as compared with the first-order FEM for comparable numbers of tetrahedral elements. The anisotropic conductivity distribution of the head tissue can be taken into account in the present FEM algorithm. The effects of dipole eccentricity, size of finite elements and local mesh refinement on solution accuracy are also addressed in the present simulation study.

Algorithms↗

PubMed2004

An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP).

The NH2-terminal sequence of steroid receptors is highly variable between different receptors and in the same receptor from different species. In this study, a primary sequence homology comparison identified a 14-amino acid NH2-terminal motif of the human androgen receptor (AR) that is common to AR from all species reported, including the lower vertebrates. The evolutionarily conserved motif is unique to AR, with the exception of a partial sequence in the glucocorticoid receptor of higher species. The presence of the conserved motif in AR and the glucocorticoid receptor and its absence in other steroid receptors suggests convergent evolution. The function of the AR NH2-terminal conserved motif was suggested from a yeast two-hybrid screen that identified the COOH terminus of the Hsp70-interacting protein (CHIP) as a binding partner. We found that CHIP functions as a negative regulator of AR transcriptional activity by promoting AR degradation. In support of this, two mutations in the AR NH2-terminal conserved motif previously identified in the transgenic adenocarcinoma of mouse prostate model reduced the interaction between CHIP and AR. Our results suggest that the AR NH2-terminal domain contains an evolutionarily conserved motif that functions to limit AR transcriptional activity. Moreover, we demonstrate that the combination of comparative sequence alignment and yeast two-hybrid screening using short conserved peptides as bait provides an effective strategy to probe the structure-function relationships of steroid receptor NH2-terminal domains and other intrinsically unstructured transcriptional regulatory proteins.

Amino Acid Motifs↗

PubMed2004

Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.

In a continuing effort to discover novel chemotypes as potent and selective PDE5 inhibitors for the treatment of male erectile dysfunction (ED), we have found that 4-benzylaminoquinoline derivatives are very potent and selective PDE5 inhibitors. Some compounds in this series had PDE5 IC(50)'s as low as 50 pM. While an electron withdrawing group at the C6-position of the quinoline substantially improved PDE5 potency, an ethyl group at the C8-position not only improved the PDE5 potency but also the isozyme selectivity. Substitutents at the C3-position can incorporate a variety of different groups. The synthesis and primary structure-activity relationship of this new series of potent PDE5 inhibitors are described.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

An alternative subspace approach to EEG dipole source localization.

In the present study, we investigate a new approach to electroencephalography (EEG) three-dimensional (3D) dipole source localization by using a non-recursive subspace algorithm called FINES. In estimating source dipole locations, the present approach employs projections onto a subspace spanned by a small set of particular vectors (FINES vector set) in the estimated noise-only subspace instead of the entire estimated noise-only subspace in the case of classic MUSIC. The subspace spanned by this vector set is, in the sense of principal angle, closest to the subspace spanned by the array manifold associated with a particular brain region. By incorporating knowledge of the array manifold in identifying FINES vector sets in the estimated noise-only subspace for different brain regions, the present approach is able to estimate sources with enhanced accuracy and spatial resolution, thus enhancing the capability of resolving closely spaced sources and reducing estimation errors. The present computer simulations show, in EEG 3D dipole source localization, that compared to classic MUSIC, FINES has (1) better resolvability of two closely spaced dipolar sources and (2) better estimation accuracy of source locations. In comparison with RAP-MUSIC, FINES' performance is also better for the cases studied when the noise level is high and/or correlations among dipole sources exist.

Algorithms↗

PubMed2004

GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor.

The cascade of phosphorylation is a pivotal event in transforming growth factor beta (TGFbeta) signaling. Reversible phosphorylation regulates fundamental aspects of cell activity. TGFbeta-induced Smad7 binds to type I receptor (TGFbeta type I receptor; TbetaRI) functioning as a receptor kinase antagonist. We found Smad7 interacts with growth arrest and DNA damage protein, GADD34, a regulatory subunit of the protein phosphatase 1 (PP1) holoenzyme, which subsequently recruits catalytic subunit of PP1 (PP1c) to dephosphorylate TbetaRI. Blocking Smad7 expression by RNA interference inhibits association of GADD34-PP1c complex with TbetaRI, indicating Smad7 acts as an adaptor protein in the formation of the PP1 holoenzyme that targets TbetaRI for dephosphorylation. SARA (Smad anchor for receptor activation) enhances the recruitment PP1c to the Smad7-GADD34 complex by controlling the specific subcellular localization of PP1c. Importantly, GADD34-PP1c recruited by Smad7 inhibits TGFbeta-induced cell cycle arrest and mediates TGFbeta resistance in responding to UV light irradiation. The dephosphorylation of TbetaRI mediated by Smad7 is an effective mechanism for governing negative feedback in TGFbeta signaling.

Activin Receptors, Type I↗

PubMed2004

Synthesis and cell affinity of functionalized poly(L-lactide-co-beta-malic acid) with high molecular weight.

A novel functionalized biodegradable poly(L-lactide-co-beta-benzyl malolactonate) (p-PLMA) with high molecular weight was synthesized through ring-opening copolymerization. Three p-PLMA copolymers with different beta-benzyl malolactonate content were synthesized. The molecular weight (M(w)) and tensile strength of the copolymer with 4 mol% beta-benzyl malolactonate content were 179,800 and 19.0MPa respectively, the molecular weight (M(w)) and tensile strength of p-PLMA decreased with beta-benzyl malolactonate content increasing. The hydrophilicity of the de-protected product: poly(L-lactide-co-beta-malic acid) (d-PLMA) increased with malic acid content increasing. The results of 3T3 mice fibroblasts cultivated on d-PLMA films showed that the cell adhesion on d-PLMA was better than that of PLLA and the cell attached efficiency of d-PLMA with 8 mol% malic acid content was the highest. The cells grew well both on the surface and inside of d-PLMA scaffolds. The cell affinity of d-PLMA was better than that of PLLA.

3T3 Cells↗

PubMed2004

Classifying EEG-based motor imagery tasks by means of time-frequency synthesized spatial patterns.

OBJECTIVE: To develop a single trial motor imagery (MI) classification strategy for the brain-computer interface (BCI) applications by using time-frequency synthesis approach to accommodate the individual difference, and using the spatial patterns derived from electroencephalogram (EEG) rhythmic components as the feature description. METHODS: The EEGs are decomposed into a series of frequency bands, and the instantaneous power is represented by the envelop of oscillatory activity, which forms the spatial patterns for a given electrode montage at a time-frequency grid. Time-frequency weights determined by training process are used to synthesize the contributions from the time-frequency domains. RESULTS: The present method was tested in nine human subjects performing left or right hand movement imagery tasks. The overall classification accuracies for nine human subjects were about 80% in the 10-fold cross-validation, without rejecting any trials from the dataset. The loci of MI activity were shown in the spatial topography of differential-mode patterns over the sensorimotor area. CONCLUSIONS: The present method does not contain a priori subject-dependent parameters, and is computationally efficient. The testing results are promising considering the fact that no trials are excluded due to noise or artifact. SIGNIFICANCE: The present method promises to provide a useful alternative as a general purpose classification procedure for MI classification.

Brain Mapping↗

PubMed2004

Speciation of heavy metals in marine sediments from the East China Sea by ICP-MS with sequential extraction.

Twelve elements (V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, Sn, Cd and Pb) in 24 sediment samples at eight sites (S1-S8) from the East China Sea were analyzed with the BCR sequential extraction (SE) protocol to obtain the metal distribution patterns in this region. The results showed that the heavy metal pollutions in S4 and S8 were more severe than in other sampling sites, especially Cd and Pb pollution. In the top sediments at S4 and S8, both the total contents and the most dangerous non-residual fractions of Cd and Pb were extremely high. More than 90% of the total concentrations of V, Cr, Mo and Sn existed in the residual fraction. Fe, Co, Ni, Cu and Zn mainly (more than 60%) occurred in the residual fraction. While Mn, Pb and Cd dominantly presented in the non-residual fractions in the top sediments. The metal distribution patterns with depth and the correlations between total organic carbon (TOC) and the total Fe-Mn content were also investigated. The results showed that, for most of the elements except Fe, the concentration of elements in fraction A in the top sediments was higher than that in other depth. The similar rule was also found in fraction B but not in fraction C. Besides, the distributions of V, Cd in fraction B and Pb, Cd, Cu in fraction C might be affected by TOC.

China↗

PubMed2004

Spatio-temporal cortical source imaging of brain electrical activity by means of time-varying parametric projection filter.

In the present study, we explore suitable spatio-temporal filters for inverse estimation of an equivalent dipole-layer distribution from the scalp electroencephalogram (EEG) for imaging of brain electric sources. We propose a time-varying parametric projection filter (tPPF) for the spatio-temporal EEG analysis. The performance of this tPPF algorithm was evaluated by computer simulation studies. An inhomogeneous three-concentric-spheres model was used in the present simulation study to represent the head volume conductor. An equivalent dipole layer was used to represent equivalently brain electric sources and estimated from the scalp potentials. The tPPF filter was tested to remove time-varying noise such as instantaneous artifacts caused by eyes-blink. The present simulation results indicate that the proposed time-variant tPPF method provides enhanced performance in rejecting time-varying noise, as compared with the time-invariant parametric projection filter.

Algorithms↗

PubMed2004

Replication of herpes simplex virus 1 depends on the gamma 134.5 functions that facilitate virus response to interferon and egress in the different stages of productive infection.

The ability of the gamma(1)34.5 protein to suppress the PKR response plays a crucial role in herpes simplex virus pathogenesis. In this process, the gamma(1)34.5 protein associates with protein phosphatase 1 to form a large complex that dephosphorylates eIF-2alpha and thereby prevents translation shutoff mediated by PKR. Accordingly, gamma(1)34.5 null mutants are virulent in PKR-knockout mice but not in wild-type mice. However, gamma(1)34.5 deletion mutants, with an extragenic compensatory mutation, inhibit PKR activity but remain avirulent, suggesting that the gamma(1)34.5 protein has additional functions. Here, we show that a substitution of the gamma(1)34.5 gene with the NS1 gene from influenza A virus renders viral resistance to interferon involving PKR. The virus replicates as efficiently as wild-type virus in SK-N-SH and CV-1 cells. However, in mouse 3T6 cells, the virus expressing the NS1 protein grows at an intermediate level between the wild-type virus and the gamma(1)34.5 deletion mutant. This decrease in growth, compared to that of the wild-type virus, is due not to an inhibition of viral protein synthesis but rather to a block in virus release or egress. Virus particles are predominantly present in the nucleus and cytoplasm. Notably, deletions in the amino terminus of the gamma(1)34.5 protein lead to a significant decrease in virus growth in mouse 3T6 cells, which is independent of eIF-2alpha dephosphorylation. In correlation, a series of deletions in the amino-terminal domain impair nuclear as well as cytoplasmic egress. These results indicate that efficient viral replication depends on the gamma(1)34.5 functions required to prevent the PKR response and to facilitate virus egress in the different stages during virus infection.

Animals↗

PubMed2004

Motor imagery task classification for brain computer interface applications using spatiotemporal principle component analysis.

Classification of single-trial imagined left- and right-hand movements recorded through scalp EEG are explored in this study. Classical event-related desynchronization/synchronization (ERD/ERS) calculation approach was utilized to extract ERD features from the raw scalp EEG signal. Principle Component Analysis (PCA) was used for feature extraction and applied on spatial, as well as temporal dimensions in two consecutive steps. A Support Vector Machine (SVM) classifier using a linear decision function was used to classify each trial as either left or right. The present approach has yielded good classification results and promises to have potential for further refinement for increased accuracy as well as application in online brain computer interface (BCI).

Brain↗