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Biomedical subjects

Ge Gao

Publications and source records attributed to Ge Gao.

At least 19 recordsLinked to original sources
PubMed2025

Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease.

Human leukocyte antigen (HLA) disparity between donors and recipients is a key determinant triggering intense alloreactivity, leading to a lethal complication, namely, acute graft-versus-host disease (aGVHD), after allogeneic transplantation. Moreover, aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation. Protocols for HLA-haploidentical hematopoietic cell transplantation (haploHCT) have been established successfully and widely applied, further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD. On the basis of our time-consecutive large haploHCT cohort (with a homogenous discovery set and an extended confirmatory set), we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors. In addition to identifying multiple loss-of-function (LoF) risk variations in non-HLA coding genes, our data-driven study revealed that non-HLA genetic variations, independent of HLA disparity, contributed the most to the occurrence of aGVHD. This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT. Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells. Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.

Humans↗
PubMed2006

NATsDB: Natural Antisense Transcripts DataBase.

Natural antisense transcripts (NATs) are reverse complementary at least in part to the sequences of other endogenous sense transcripts. Most NATs are transcribed from opposite strands of their sense partners. They regulate sense genes at multiple levels and are implicated in various diseases. Using an improved whole-genome computational pipeline, we identified abundant cis-encoded exon-overlapping sense-antisense (SA) gene pairs in human (7356), mouse (6806), fly (1554), and eight other eukaryotic species (total 6534). We developed NATsDB (Natural Antisense Transcripts DataBase, http://natsdb.cbi.pku.edu.cn/) to enable efficient browsing, searching and downloading of this currently most comprehensive collection of SA genes, grouped into six classes based on their overlapping patterns. NATsDB also includes non-exon-overlapping bidirectional (NOB) genes and non-bidirectional (NBD) genes. To facilitate the study of functions, regulations and possible pathological implications, NATsDB includes extensive information about gene structures, poly(A) signals and tails, phastCons conservation, homologues in other species, repeat elements, expressed sequence tag (EST) expression profiles and OMIM disease association. NATsDB supports interactive graphical display of the alignment of all supporting EST and mRNA transcripts of the SA and NOB genes to the genomic loci. It supports advanced search by species, gene name, sequence accession number, chromosome location, coding potential, OMIM association and sequence similarity.

Animals↗
PubMed2006

ZnO/PS core-shell hybrid microspheres prepared with miniemulsion polymerization.

The hybrid microspheres of ZnO/PS with different core-shell structures were prepared in miniemulsion polymerization. 3-(trimethoxysilyl)propyl methacrylate (MPS) was used as a functional co-monomer to enhance the surface polarity of ZnO nanoparticles and to prevent water from quenching the luminescent properties of ZnO. The morphology of hybrid particles was examined with a transmission electron microscope. The luminescence spectra were measured using a Shimadzu RF-5301 PC spectrofluorimeter (Xe source) at room temperature. The crystallization structure of samples was characterized with a Rigaku wide-angle X-ray diffractometer. The chemical composition and structure of the ZnO colloids, MPS-modified ZnO colloids, and ZnO/PS hybrid microspheres were analyzed with IR.

Journal Article↗
PubMed2006

Increased isoform-specific membrane translocation of conventional and novel protein kinase C in human neuroblastoma SH-SY5Y cells following prolonged hypoxia.

Several studies have suggested that protein kinase C (PKC) plays a key role in the mechanism of cerebral ischemic/hypoxic preconditioning (I/HPC). However, detailed information regarding PKC isoforms in response to brain ischemia/hypoxia and their potential role in neuroprotection is unclear. Previous studies in our laboratory have demonstrated that the levels in membrane translocation of conventional PKC (cPKC) betaII, gamma, and novel PKCepsilon (nPKC), but not cPKCalpha, betaI, nPKCdelta, eta, mu, theta, and atypical PKC (aPKC) zeta and iota/lambda, were increased significantly in the hippocampus and cortex of intact mice with hypoxic preconditioning. To further detect cPKC and nPKC isoforms activation following prolonged hypoxia in vitro, we tested the membrane translocation (an indicator of PKC activation) of cPKCalpha, betaI, betaII, and gamma, and nPKCdelta, epsilon, eta, mu, and theta in a human neuroblastoma SH-SY5Y cell line following sustained hypoxic exposure (1% O(2)/5% CO(2)/94% N(2)). Using Western blot and immunocytochemistry methods, we found that the levels of cPKCalpha, betaI, betaII, and nPKCepsilon, but not nPKCdelta, eta, mu, and theta, membrane translocation were increased significantly (P < 0.05, n = 8) in a time-dependent manner (from 0.5 to 24 h) following sustained hypoxic exposure. Similarly, the immunostaining experiment also showed a noticeable translocation of cPKCalpha, betaI, betaII, and nPKCepsilon from the cytosol to the perinuclear or membrane-related areas after 6 h posthypoxic exposure. In addition, no cPKCgamma was detected in this cell line under either a normoxic or hypoxic condition. These results suggested that prolonged hypoxia may induce the activation of cPKCalpha, betaI, betaII, and nPKCepsilon by triggering their membrane translocation in SH-SY5Y cells.

Blotting, Western↗
PubMed2006

DRTF: a database of rice transcription factors.

SUMMARY: DRTF contains 2025 putative transcription factors (TFs) in Oryza sativa L. ssp. indica and 2384 in ssp. japonica, distributed in 63 families, identified by computational prediction and manual curation. It includes detailed annotations of each TF including sequence features, functional domains, Gene Ontology assignment, chromosomal localization, EST and microarray expression information, as well as multiple sequence alignment of the DNA-binding domains for each TF family. The database can be browsed and searched with a user-friendly web interface. AVAILABILITY: DRTF is available at http://drtf.cbi.pku.edu.cn

Database Management Systems↗
PubMed2006

Decreased phosphorylation and protein expression of ERK1/2 in the brain of hypoxic preconditioned mice.

Accumulated reports have suggested that activation of protein kinase C (PKC) isoforms may involve the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the neuronal response to hypoxic stimuli. We have previously demonstrated that the membrane translocation or activation of conventional PKC (cPKC) betaII, gamma and novel PKC (nPKC) epsilon are increased in the early phase of cerebral hypoxic preconditioning in mice. However, the role of ERK1/2 in the development of cerebral hypoxic preconditioning is unclear. In the current study, we used Western blot analysis to investigate the effects of repetitive hypoxic exposure (H0-H6, n=6 for each group) on the levels of phosphorylation and protein expression of ERK1/2 in the frontal cortex and the whole hippocampus of mice. We found that the levels of phosphorylated ERK1/2, not protein expression of ERK1/2, decreased significantly in both cortex and hippocampus of the early hypoxic preconditioned mice (H1-H4), when compared to that of the normoxic group (p<0.05). In addition, a significant decrease (p<0.05) in the ERK1/2 protein expression, not the phosphorylated form of ERK1/2, was found both in the frontal cortex and hippocampus of mice followed hypoxia with previous hypoxia (H5 and H6). These results suggest that the decreased phosphorylation and downregulation of protein expression of ERK1/2 might be involved in the development of hypoxic preconditioning.

Animals↗
PubMed2005

Enhanced phosphorylation of cyclic AMP response element binding protein in the brain of mice following repetitive hypoxic exposure.

Cerebral ischemic/hypoxic preconditioning (I/HPC) is a phenomenon of endogenous protection that renders the brain tolerant to sustained ischemia/hypoxia. This profound protection induced by I/HPC makes it an attractive target for developing potential clinical therapeutic approaches. However, the molecular mechanism of I/HPC is unclear. Cyclic AMP (cAMP) response element binding protein (CREB), a selective nuclear transcriptional factor, plays a key role in the neuronal functions. Phosphorylation of CREB on Ser-133 may facilitate its transcriptional activity in response to various stresses. In the current study, we observed the changes in CREB phosphorylation (Ser-133) and protein expression in the brain of auto-hypoxia-induced HPC mice by using Western blot analysis. We found that the levels of phosphorylated CREB (Ser-133), but not protein expression of CREB, increased significantly (p<0.05) in the hippocampus and the frontal cortex of mice after repetitive hypoxic exposure (H2-H4, n=6 for each group), when compared to that of the normoxic (H0, n=6) or hypoxic exposure once group (H1, n=6). In addition, a significant enhancement (p<0.05) of CREB phosphorylation (Ser-133) could also be found in the nuclear extracts from the whole hippocampus of hypoxic preconditioned mice (H2-H4, n=6 for each group). These results suggest that the phosphorylation of CREB might be involved in the development of cerebral hypoxic preconditioning.

Animals↗
PubMed2005

Crystallization and photovoltaic properties of titania-coated polystyrene hybrid microspheres and their photocatalytic activity.

The hybrid microspheres with polystyrene core coated by titania nanoparticles were prepared by miniemulsion polymerization, and the as-prepared samples were characterized by SEM, XRD, TG-DTA, XPS, and SPS techniques. TiO2 nanoparticles experienced two processes of phase transition, i.e., amorphous to anatase and anatase to rutile at the calcining temperature range from 400 to 1000 degrees C. The phase transformation temperature of TiO2 hybrid microspheres from anatase to rutile was increased by about 300 degrees C due to the blocking function of calcined polymer remainder. SPS results present that the band-gap of hybrid microspheres is 3.2-3.4 eV, which is larger than that of pure TiO2. The maximum intensity of the SPS signal is about 3 times larger for the hybrid material as compared to the pure TiO2. In addition, the photocatalytic degradation rate of TiO2 hybrid microspheres was 15% faster than that of pure TiO2 in the experiment of the photocatalytic degradation of methyl orange.

Journal Article↗
PubMed2005

Testicular immune privilege promotes transplantation tolerance by altering the balance between memory and regulatory T cells.

Immune responses are suppressed in immunologically privileged sites, which may provide a unique opportunity to prolong allograft survival. However, it is unknown whether testicular immune privilege promotes transplantation tolerance. Mechanisms underlying immune privilege are also not well understood. Here we found that islet transplantation in the testis, an immunologically privileged site, generates much less memory CD8(+) T cells but induces more Ag-specific CD4(+)CD25(+) regulatory T cells than in a conventional site. These CD4(+)CD25(+) cells exhibited the suppression of alloimmune responses in vivo and in vitro. Despite the immune regulation, intratesticular islet allografts all were rejected within 42 days after transplantation although they survived longer than renal subcapsular islet allografts. However, blocking CD40/CD40L costimulation induced the tolerance of intratesticular, but not renal subcapsular, islet allografts. Tolerance to intratesticular islet allografts spread to skin allografts in the non-privileged sites. Either transfer of memory CD8(+) T cells or deletion of CD25(+) T cells in vivo broke islet allograft tolerance. Thus, transplantation tolerance requires both costimulatory blockade, which suppresses acute allograft rejection, and a favorable balance between memory and regulatory T cells that could favorably prevent late allograft failure. These findings reveal novel mechanisms of immune privilege and provide direct evidence that testicular immune privilege fosters the induction of transplantation tolerance to allografts in both immunologically privileged and non-privileged sites.

Animals↗
PubMed2005

SPD--a web-based secreted protein database.

With the improved secreted protein prediction approach and comprehensive data sources, including Swiss-Prot, TrEMBL, RefSeq, Ensembl and CBI-Gene, we have constructed secretomes of human, mouse and rat, with a total of 18 152 secreted proteins. All the entries are ranked according to the prediction confidence. They were further annotated via a proteome annotation pipeline that we developed. We also set up a secreted protein classification pipeline and classified our predicted secreted proteins into different functional categories. To make the dataset more convincing and comprehensive, nine reference datasets are also integrated, such as the secreted proteins from the Gene Ontology Annotation (GOA) system at the European Bioinformatics Institute, and the vertebrate secreted proteins from Swiss-Prot. All these entries were grouped via a TribeMCL based clustering pipeline. We have constructed a web-based secreted protein database, which has been publicly available at http://spd.cbi.pku.edu.cn. Users can browse the database via a GO assignment or chromosomal-location-based interface. Moreover, text query and sequence similarity search are also provided, and the sequence and annotation data can be downloaded freely from the SPD website.

Animals↗
PubMed2004

Highly enantioselective alkyne additions to aldehydes in the presence of 1,1'-bi-2-naphthol and hexamethylphosphoramide.

It is found that the addition of hexamethylphosphoramide to the solution of an alkyne, Et(2)Zn, and (S)-1,1'-bi-2-naphthol in methylene chloride allows the generation of an alkynylzinc at room temperature and shows highly enantioselective additions to aldehydes. The mild condition for the formation of the alkynylzinc reagent enables the use of functional alkynes in this asymmetric reaction with excellent enantioselectivity. It avoids the reflux of the toluene solutions of the alkynes and Et(2)Zn as previously reported.

Alkynes↗
PubMed2004

Titania-coated polystyrene hybrid microballs prepared with miniemulsion polymerization.

Hybrid microballs with polystyrene cores coated by titania nanoparticles were prepared in miniemulsion polymerization. Acrylic acid was used as a comonomer to promote locating titania nanoparticles on the polymer's surface. The addition of a hydrophobic agent effectively prevents monomer diffusing into the aqueous phase. The morphology of hybrid particles was examined with the transmission electron microscope, and its change pattern with reactive conditions was observed. The infrared spectra of hybrid nanoparticles showed that there existed a certain interaction between titania nanoparticles and polymers. The crystallization morphology of hybrid particles before and after calcination was characterized with X-ray diffraction.

Journal Article↗
PubMed2004

CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism.

CD4(+)CD25(+) regulatory T (Treg) cells suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Treg cells suppress allograft rejection mediated by memory T cells, as the latter mount faster and stronger immune responses than their naive counterparts. Here we show that antigen-induced, but not naive, Treg cells suppress allograft rejection mediated by memory CD8(+) T cells. Suppression was allospecific, as Treg cells induced by third-party antigens did not delay allograft rejection. In vivo and in vitro analyses revealed that the apoptosis of allospecific memory CD8(+) T cells is significantly increased in the presence of antigen-induced Treg cells, while their proliferation remains unaffected. Importantly, neither suppression of allograft rejection nor enhanced apoptosis of memory CD8(+) T cells was observed when Treg cells lacked CD30 or when CD30 ligand-CD30 interaction was blocked with anti-CD30 ligand Ab. This study therefore provides direct evidence that pathogenic memory T cells are amenable to suppression in an antigen-specific manner and identifies CD30 as a molecule that is critical for the regulation of memory T cell responses.

Animals↗