PubMed Health⌕ Search

Biomedical subjects

Yang Liu

Publications and source records attributed to Yang Liu.

At least 235 records · Page 13Linked to original sources

Assembly and characterization of novel hydrogen-bond-induced nanoscale rods.

A class of bis-urea compounds with perylene bisimide was synthesized and characterized successfully. (1)H NMR and fluorescence spectra confirmed that strong hydrogen-bonding interactions between neighboring urea groups were formed. Interestingly, the photocurrent measurement showed that the self-assembled films of bis-urea compounds could produce steady and rapid anodic photocurrent responses. The TEM images indicated that well-defined nanoscale rods with uniform diameter distribution could be fabricated by self-assembly of hydrogen-bonding interactions and pi-pi stacking interactions of perylene rings.

Journal Article↗

Mouse brain organization revealed through direct genome-scale TF expression analysis.

In the developing brain, transcription factors (TFs) direct the formation of a diverse array of neurons and glia. We identifed 1445 putative TFs in the mouse genome. We used in situ hybridization to map the expression of over 1000 of these TFs and TF-coregulator genes in the brains of developing mice. We found that 349 of these genes showed restricted expression patterns that were adequate to describe the anatomical organization of the brain. We provide a comprehensive inventory of murine TFs and their expression patterns in a searchable brain atlas database.

Animals↗

Short hairpin RNA and retroviral vector-mediated silencing of p53 in mammalian cells.

RNA interference (RNAi) is the process of gene silencing, in which the recognition of double-stranded RNA ultimately leads to post-transcriptional suppression of gene expression. RNAi induced by small interfering RNA (siRNA) or short hairpin RNA (shRNA) is an important research approach for the analysis of gene function in mammalian cells. Here we established a shRNA expression retroviral vector in which the sense and antisense sequences targeting wild type human p53 were linked together with a 9-nucleotide loop. Further, we found that shRNA expressed from a RNA polymerase III vector based on the human H1 RNA promoter could effectively inhibit gene expression in a sequence-specific manner. H1-driven shRNA dramatically reduced the expression of wild type human p53 in H1299 cells transfected with wtp53. We also found that the retroviral vector could circumvent the difficulty in transfection for the delivery of siRNA or shRNA and the generation of long-term gene silencing. The use of shRNA expression vector for RNAi might provide a rapid and versatile method for assessing gene function in mammalian cells with possible applications in the treatment of diseases.

Base Sequence↗

Electrochemical deposition of silver in room-temperature ionic liquids and its surface-enhanced Raman scattering effect.

The use of room-temperature ionic liquids (RTILs) as media for electrochemical application is very attractive. In this work, the electrochemical deposition of silver was investigated at a glassy carbon electrode in hydrophobic 1-n-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) and hydrophilic 1-n-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4) RTILs and in KNO3 aqueous solution by cyclic voltammetric and potentiostatic transient techniques. The voltammograms showed the presence of reduction and oxidation peaks associated with the deposition and dissolution of silver from AgBF4 in both BMIMPF6 and BMIMBF(4), resembling the redox behavior of AgNO3 in KNO3 aqueous solution. A crossover loop was observed in all the cyclic voltammograms of these electrochemical systems, indicating a nucleation process. From the analysis of the experimental current transients, it was shown that the electrochemical deposition process of silver in these media was characteristic of 3D nucleation with diffusion-controlled hemispherical growth, and the silver nucleation closely followed the response predicted for progressive nucleation in BMIMPF6 and instantaneous nucleation in KNO3 aqueous solution, respectively. Compared with these two cases, the electrochemical deposition of silver in BMIMBF4 deviated from both the instantaneous and progressive nucleation models, which could be controlled by mixed kinetics and diffusion. On the basis of the experimental results, it was shown that parameters such as viscosity and water miscibility of RTILs would affect the electrodeposition behavior of silver. Atom force microscopy was employed to probe the surface morphology of the silver deposit, and it showed that the shining electrodeposit of silver was fairly dense and separate nanoclusters of <100 nm were in evidence, corresponding to an island growth model. The strongly enhanced Raman scattering from the monolayer film of 4-mercaptobenzoic acid demonstrated that as-prepared silver nanoparticular film was surface-enhanced Raman scattering (SERS) active. The enhancement factor was calculated to be up to 9.0 x 10(5) and 1.0 x 10(6) for the silver film obtained in BMIMPF6 and BMIMBF4 RTILs, respectively.

Journal Article↗

Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2.

Adoptive immunotherapy with tumor-specific T cells has emerged as a valid approach for prevention or treatment of diseases, such as melanoma and EBV-associated lymphoma. As interleukin (IL) 15 promotes survival of CD8(+) memory CTLs, we hypothesized that it could be used to enhance antitumor immunity in vivo through the maintenance of adoptively transferred memory CTL. To test this, we treated mice bearing P1A(+) tumors with adoptively transferred T cells possessing a transgenic Valpha8(+) T-cell receptor specific for the P1A tumor antigen (called P1CTL). Mice were then randomized to receive daily low-dose IL-15 (0.5 microg/day) or PBS. Mice receiving the transgenic P1CTL and IL-15 experienced a significantly delayed tumor relapse or complete tumor regression (P < 0.002 compared with PBS), with a striking persistence of the CD8(+) Valpha8(+) P1CTL compared with mice receiving the CD8(+) Valpha8(+) P1CTL and PBS vehicle (26.3 versus 5.1% P < 10(-5)). Animals exhibiting complete tumor regression had a significant population of CD8(+) Valpha8(+) P1CTL (46%) that persisted with IL-15 treatment until 140 days after adoptive transfer and successfully defended them against tumor rechallenge without IL-15. Low-dose IL-2 afforded no protection over vehicle and resulted in lower percentages of T cells with an activated memory phenotype, lower Bcl-2 expression, and lower ex vivo antitumor cytotoxicity compared with mice treated with IL-15. Collectively, the data support the notion that exogenous low-dose IL-15 therapy can enhance and even reverse the limited efficacy of adoptively transferred tumor-specific T-cell therapy and may do so in a fashion that is superior and distinct from exogenous IL-2 therapy.

Animals↗

B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen-specific CD8+ cytolytic T cells.

B7-H3 is a B7 family molecule with T cell costimulatory function in vitro. The in vivo role of B7-H3 in the stimulation of tumor immunity is unclear. We report here that expression of B7-H3 by transfection of the mouse P815 tumor line enhances its immunogenicity, leading to the regression of tumors and amplification of a tumor-specific CD8+ CTL response in syngeneic mice. Tumor cells engineered to express B7-H3 elicit a rapid clonal expansion of P1A tumor Ag-specific CD8+ CTL in lymphoid organs in vivo and acquire the ability to directly stimulate T cell growth, division, and development of cytolytic activity in vitro. Our results thus establish a role for B7-H3 in the costimulation of T cell immune responses in vivo.

Adjuvants, Immunologic↗

Origins of cell selectivity of cationic steroid antibiotics.

A key factor in the potential clinical utility of membrane-active antibiotics is their cell selectivity (i.e., prokaryote over eukaryote). Cationic steroid antibiotics were developed to mimic the lipid A binding character of polymyxin B and are shown to bind lipid A derivatives with affinity greater than that of polymyxin B. The outer membranes of Gram-negative bacteria are comprised primarily of lipid A, and a fluorophore-appended cationic steroid antibiotic displays very high selectivity for Gram-negative bacterial membranes over Gram-positive bacteria and eukaryotic cell membranes. This cell selectivity of cationic steroid antibiotics may be due, in part, to the affinity of these compounds for lipid A.

Anti-Bacterial Agents↗

Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies.

When adopting basic principles learned in mice to clinical application in humans, it is often difficult to distinguish whether a "translation" fails because of an invalid target in the human disease or because the therapeutic agents are not optimal for the human target. It is, therefore, desirable to develop preclinical models to optimize therapies for human targets using in vivo settings. Although anti-mouse CTLA-4 antibodies are known to enhance immune responses in vivo, their effect on T-cell activation in vitro ranges from enhancement to inhibition. Here we use the hu-PBL-SCID mouse model of Epstein-Barr virus (EBV)-associated lymphoma development to screen a panel of anti-human CTLA-4 monoclonal antibodies (mAbs) for their effect on human lymphocytes in an in vivo "humanized" environment. We report significant heterogeneity of anti-human CTLA-4 mAbs in enhancing the expansion of human T cells in mice, and this heterogeneity cannot be attributed to immunoglobulin isotypes or affinity for CTLA-4. These data validate the development of additional screening tools, such as the one described, to further characterize functional activity of antihuman antibodies before proceeding with clinical translation to human studies.

Animals↗

CD24 expression on T cells is required for optimal T cell proliferation in lymphopenic host.

It is well established that T lymphocytes undergo homeostatic proliferation in lymphopenic environment. The homeostatic proliferation requires recognition of the major histocompatibility complex on the host. Recent studies have demonstrated that costimulation-mediated CD28, 4-1BB, and CD40 is not required for T cell homeostatic proliferation. It has been suggested that homeostatic proliferation is costimulation independent. Here, we report that T cells from mice with a targeted mutation of CD24 have a remarkably reduced rate of proliferation when adoptively transferred into syngeneic lymphopenic hosts. The reduced proliferation cannot be attributed to abnormal survival and homing properties of the CD24-deficient T cells. T cell proliferation in allogeneic hosts is less affected by this mutation. These results demonstrate a novel function of CD24 expressed on T cells. Thus, although distinct costimulatory molecules are involved in antigen-driven proliferation and homeostatic proliferation, both processes can be modulated by costimulatory molecules.

Adoptive Transfer↗

Wavelet multiscale regression from the perspective of data fusion: new conceptual approaches.

Wavelet regression is a very promising technique for modern multivariate calibration and calibration transfer. Multiscale analysis of wavelet scales provides a connection between wavelet regression and data fusion. In this paper, current wavelet regression methods are reviewed from the novel perspective of data fusion. Illustrated by analysis of a public domain near-infrared dataset, the advantages and drawbacks of these methods are examined. For wavelet regression, the non-uniformity of the wavelet components, the multiscale nature of the signal, and the prevention of information leakage are crucial issues that will be addressed.

Journal Article↗

Divergent potentials for cytoplasmic inheritance within the genus Syringa. A new trait associated with speciogenesis.

Epifluorescence microscopic detection of organelle DNA in the mature generative cell is a rapid method for determining the potential for the mode of cytoplasmic inheritance. We used this method to examine 19 of the known 22 to 27 species in the genus Syringa. Organelle DNA was undetectable in seven species, all in the subgenus Syringa, but was detected in the 12 species examined of the subgenera Syringa and Ligustrina. Therefore, species within the genus Syringa display differences in the potential cytoplasmic inheritance. Closer examination revealed that the mature generative cells of the species in which organelle DNA was detected contained both mitochondria and plastids, but cells of the species lacking detectable organelle DNA contained only mitochondria, and the epifluorescent organelle DNA signals from the mature generative cells corresponded to plastid DNA. In addition, semiquantitative analysis was used to demonstrate that, during pollen development, the amount of mitochondrial DNA decreased greatly in the generative cells of the species examined, but the amount of plastid DNA increased remarkably in the species containing plastids in the generative cell. The results suggest that all Syringa species exhibit potential maternal mitochondrial inheritance, and a number of the species exhibit potential biparental plastid inheritance. The difference between the modes of potential plastid inheritance among the species suggests different phylogenies for the species; it also supports recent conclusions of molecular, systematic studies of the Syringa. In addition, the results provide new evidence for the mechanisms of maternal mitochondrial inheritance in angiosperms.

Cytoplasm↗

Comprehensive analysis of pseudogenes in prokaryotes: widespread gene decay and failure of putative horizontally transferred genes.

BACKGROUND: Pseudogenes often manifest themselves as disabled copies of known genes. In prokaryotes, it was generally believed (with a few well-known exceptions) that they were rare. RESULTS: We have carried out a comprehensive analysis of the occurrence of pseudogenes in a diverse selection of 64 prokaryote genomes. Overall, we find a total of around 7,000 candidate pseudogenes. Moreover, in all the genomes surveyed, pseudogenes occur in at least 1 to 5% of all gene-like sequences, with some genomes having considerably higher occurrence. Although many large populations of pseudogenes arise from large, diverse protein families (for example, the ABC transporters), notable numbers of pseudogenes are associated with specific families that do not occur that widely. These include the cytochrome P450 and PPE families (PF00067 and PF00823) and others that have a direct role in DNA transposition. CONCLUSIONS: We find suggestive evidence that a large fraction of prokaryote pseudogenes arose from failed horizontal transfer events. In particular, we find that pseudogenes are more than twice as likely as genes to have anomalous codon usage associated with horizontal transfer. Moreover, we found a significant difference in the number of horizontally transferred pseudogenes in pathogenic and non-pathogenic strains of Escherichia coli.

Escherichia coli K12↗

Self-assembly and characterization of hydrogen-bond-induced nanostructure aggregation.

A supramolecular system of a perylene derivative containing bis(2,6-diacylaminopyridine) units and a perylene bisimide bound through three hydrogen-bonds was synthesized and characterized. 1H NMR spectra confirmed the existence of hydrogen-bonding interactions between the perylene derivative (3) and the perylene bisimide (7). The photocurrent generation of the self-assembled 3.7 film was measured, and a cathodic photocurrent response was obtained. SEM images indicated that well-defined long fibers could be fabricated by self-assembly, by exploiting the hydrogen bonding interactions and pi-pi stacking interactions of perylene rings.

Journal Article↗

CD24 controls expansion and persistence of autoreactive T cells in the central nervous system during experimental autoimmune encephalomyelitis.

In the development of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), autoreactive T cells must be activated and clonally expand in the lymphoid organs, and then migrate into the central nervous system (CNS) where they undergo further activation. It is unclear whether the autoreactive T cells further expand in the CNS and if so, what interactions are required for this process. We have demonstrated previously that expression by the host cells of the heat-stable antigen (CD24), which was recently identified as a genetic modifier for MS, is essential for their susceptibility to EAE. Here we show that CD24 is essential for local clonal expansion and persistence of T cells after their migration into the CNS, and that expression of CD24 on either hematopoietic cells or nonhematopoietic antigen-presenting cells in the recipient is sufficient to confer susceptibility to EAE.

Adoptive Transfer↗

A new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen.

Recent work demonstrates that costimulatory molecules play a critical role for clonal deletion of autoreactive T cells in the thymus. The role of CD28 in the survival of autoreactive T cells in the periphery, however, has not been reported. Here we demonstrate that while mutation of the CD28 gene consistently increased the burden of autoreactive T cells in the thymus, such an increase was not always found in the periphery, as the CD28(-/-) autoreactive T cells disappeared in the spleen over a period between 4 and 10 weeks. The disappearance of autoreactive T cells associates with a diminished induction of Bcl-2 protein by the self antigen and an increased proportion of apoptotic cells in the periphery. Moreover, the elimination of autoreactive T cells in the periphery requires chronic stimulation by the self antigen, as adoptive transfer analysis revealed no enhancement of apoptosis in CD28(-/-) T cells in antigen-bearing hosts over a 3 day period. Thus, CD28 plays a significant role in both clonal deletion and survival of autoreactive T cells after chronic exposure to autoantigens, resulting in opposite effects on the burden of autoreactive T cells.

Age Factors↗

Altered DNA polymerase iota expression in breast cancer cells leads to a reduction in DNA replication fidelity and a higher rate of mutagenesis.

The recently discovered human enzyme DNA polymerase iota (pol iota) has been shown to have an exceptionally high error rate on artificial DNA templates. Although there is a considerable body of in vitro evidence for a role for pol iota in DNA lesion bypass, there is no in vivo evidence to confirm this action. We report here that pol iota expression is elevated in breast cancer cells and correlates with a significant decrease in DNA replication fidelity. We also demonstrate that UV treatment of breast cancer cells additionally increases pol iota expression with a peak occurring between 30 min and 2 h after cellular insult. This implies that the change in pol iota expression is an early event after UV-mediated DNA damage. That pol iota may play a role in the higher mutation frequencies observed in breast cancer cells was suggested when a reduction in mutation frequency was found after pol iota was immunodepleted from nuclear extracts of the cells. Analysis of the UV-induced mutation spectra revealed that > 90% were point mutations. The analysis also demonstrated a decreased C --> T nucleotide transition and an increased C --> A transversion rate. Overall, our data strongly suggest that pol iota may be involved in the generation of both increased spontaneous and translesion mutations during DNA replication in breast cancer cells, thereby contributing to the accumulation of genetic damage.

Base Sequence↗

Coherent backscattering spectroscopy.

Coherent backscattering (CBS) of light in random media has been previously investigated by use of coherent light sources. Here we report a novel method of CBS measurement that combines low spatial coherence, broadband illumination, and spectrally resolved detection. We show that low spatial coherence illumination leads to an anomalously broad CBS peak and a dramatic speckle reduction; the latter is further facilitated by low temporal coherence detection. Thus CBS can be observed in biological tissue and other media that previously were beyond the reach of conventional CBS measurements. We also demonstrate, for the first time to our knowledge, spectroscopic analysis of CBS. CBS spectroscopy may find important applications in probing random media such as biological tissue in which depth-selective measurements are crucial.

Animals↗