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Biomedical subjects

Yang Liu

Publications and source records attributed to Yang Liu.

At least 91 records · Page 5Linked to original sources

Modeling low-coherence enhanced backscattering using Monte Carlo simulation.

Constructive interference between coherent waves traveling time-reversed paths in a random medium gives rise to the enhancement of light scattering observed in directions close to backscattering. This phenomenon is known as enhanced backscattering (EBS). According to diffusion theory, the angular width of an EBS cone is proportional to the ratio of the wavelength of light lambda to the transport mean-free-path length l(s)* of a random medium. In biological media a large l(s)* approximately 0.5-2 mm >> lambda results in an extremely small (approximately 0.001 degrees ) angular width of the EBS cone, making the experimental observation of such narrow peaks difficult. Recently, the feasibility of observing EBS under low spatial coherence illumination (spatial coherence length Lsc << l(s)*) was demonstrated. Low spatial coherence behaves as a spatial filter rejecting longer path lengths and thus resulting in an increase of more than 100 times in the angular width of low coherence EBS (LEBS) cones. However, a conventional diffusion approximation-based model of EBS has not been able to explain such a dramatic increase in LEBS width. We present a photon random walk model of LEBS by using Monte Carlo simulation to elucidate the mechanism accounting for the unprecedented broadening of the LEBS peaks. Typically, the exit angles of the scattered photons are not considered in modeling EBS in the diffusion regime. We show that small exit angles are highly sensitive to low-order scattering, which is crucial for accurate modeling of LEBS. Our results show that the predictions of the model are in excellent agreement with the experimental data.

Animals↗

Promotion by fibronectin of collagen gel contraction mediated by human corneal fibroblasts.

Collagen contraction mediated by corneal fibroblasts (CFs) is implicated in the maintenance of corneal shape. Given that fibronectin is expressed at sites of corneal stromal wounding, we investigated the effect of fibronectin on CF-mediated collagen gel contraction. Human CFs were cultured in a three-dimensional gel of type I collagen in the absence or presence of various extracellular matrix (ECM) components. The contraction of collagen gels mediated by CFs was evaluated by measurement of changes in gel diameter. The formation of stress fibers and focal adhesions in CFs was examined by fluorescence microscopy. The abundance of paxillin, phosphorylated paxillin, integrins alpha5, beta1, and alpha2, and alpha-smooth muscle actin in CFs was examined by immunoblot analysis. Fibronectin promoted CF-mediated collagen gel contraction in a concentration- and time-dependent manner. Other ECM proteins or glycosaminoglycans did not exhibit such an effect. Fibronectin also induced cell spreading, the formation of stress fibers, and the establishment of focal adhesions containing paxillin in CFs cultured in three-dimensional collagen gels. In addition, it increased the amounts of paxillin, phosphorylated paxillin, and integrins alpha5 and beta1 in these cells. The expression of integrin alpha2 and alpha-smooth muscle actin was not affected by fibronectin, however. Furthermore, the peptide GRGDSP (an antagonist of fibronectin receptors) blocked the stimulatory effect of fibronectin on CF-mediated collagen gel contraction. These results suggest that fibronectin promoted CF-mediated collagen gel contraction in a manner dependent on the formation of stress fibers and focal adhesions, the activation of paxillin, and the up-regulation of integrin alpha5beta1. Fibronectin may therefore contribute to the maintenance of corneal shape by CFs during the healing of stromal wounds.

Actins↗

Different lineages of P1A-expressing cancer cells use divergent modes of immune evasion for T-cell adoptive therapy.

Tumor evasion of T-cell immunity remains a significant obstacle to adoptive T-cell therapy. It is unknown whether the mode of immune evasion is dictated by the cancer cells or by the tumor antigens. Taking advantage of the fact that multiple lineages of tumor cells share the tumor antigen P1A, we adoptively transferred transgenic T cells specific for P1A (P1CTL) into mice with established P1A-expressing tumors, including mastocytoma P815, plasmocytoma J558, and fibrosarcoma Meth A. Although P1CTL conferred partial protection, tumors recurred in almost all mice. Analysis of the status of the tumor antigen revealed that all J558 tumors underwent antigenic drift whereas all P815 tumors experienced antigenic loss. Interestingly, although Meth A cells are capable of both antigenic loss and antigenic drift, the majority of recurrent Meth A tumors retained P1A antigen. The ability of Meth A to induce apoptosis of P1CTL in vivo alleviated the need for antigenic drift and antigenic loss. Our data showed that, in spite of their shared tumor antigen, different lineages of cancer cells use different mechanisms to evade T-cell therapy.

Animals↗

Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice.

The impact of timing of antigen introduction into fetus and neonates leads to the suggestion that pre-existing antigens are tolerogenic to immunocompetent cells generated thereafter. This hypothesis predicts that in patients with cancer who are undergoing bone marrow transplantation, newly produced T cells with specificity for pre-existing tumor cells will be inactivated by the tumor antigens in the host. Because the effect of tumor cells on developing cancer-reactive T cells has not been investigated, we set out to systematically analyze the impact of tumor cells in the periphery on the development of tumor-reactive T cells in the thymus and their immunocompetence in the periphery. Our data demonstrate that in the host in which a tumor is established in the periphery, the cancer-reactive T cells develop normally, remain fully immunocompetent, become activated in the periphery, and cause regression of large established tumors. The immunocompetence of T cells generated in an antigen-bearing host is also confirmed in a skin graft transplantation model.

Animals↗

Spectroscopic translation of cell-material interactions.

The characterization of cellular interactions with a biomaterial surface is important to the development of novel biomaterials. Traditional methods used to characterize processes such as cellular adhesion and differentiation on biomaterials can be time consuming, and destructive, and are not amenable to quantitative assessment in situ. As the development of novel biomaterials shifts towards small-scale, combinatorial, and high throughput approaches, new techniques will be required to rapidly screen and characterize cell/biomaterial interactions. Towards this goal, we assessed the feasibility of using 4-dimensional elastic light-scattering fingerprinting (4D-ELF) to describe the differentiation of human aortic smooth muscle cells (HASMCs), as well as the adhesion, and apoptotic processes of human aortic endothelial cells (HAECs), in a quantitative and non-perturbing manner. HASMC and HAEC were cultured under conditions to induce cell differentiation, attachment, and apoptosis which were evaluated via immunohistochemistry, microscopy, biochemistry, and 4D-ELF. The results show that 4D-ELF detected changes in the size distributions of subcellular organelles and structures that were associated with these specific cellular processes. 4D-ELF is a novel way to assess cell phenotype, strength of adhesion, and the onset of apoptosis on a biomaterial surface and could potentially be used as a rapid and quantitative screening tool to provide a more in-depth understanding of cell/biomaterial interactions.

Biocompatible Materials↗

Monte Carlo pedigree disequilibrium test for markers on the X chromosome.

Because of the need for fine mapping of disease loci and the availability of dense single-nucleotide-polymorphism markers, many forms of association tests have been developed. Most of them are applicable only to triads, whereas some are amenable to nuclear families (sibships). Although there are a number of methods that can deal with extended families (e.g., the pedigree disequilibrium test [PDT]), most of them cannot accommodate incomplete data. Furthermore, despite a large body of literature on association mapping, only a very limited number of publications are applicable to X-chromosomal markers. In this report, we first extend the PDT to markers on the X chromosome for testing linkage disequilibrium in the presence of linkage. This method is applicable to any pedigree structure and is termed "X-chromosomal pedigree disequilibrium test" (XPDT). We then further extend the XPDT to accommodate pedigrees with missing genotypes in some of the individuals, especially founders. Monte Carlo (MC) samples of the missing genotypes are generated and used to calculate the XMCPDT (X-chromosomal MC PDT) statistic, which is defined as the conditional expectation of the XPDT statistic given the incomplete (observed) data. This MC version of the XPDT remains a valid test for association under linkage with the assumption that the pedigrees and their associated affection patterns are drawn randomly from a population of pedigrees with at least one affected offspring. This set of methods was compared with existing approaches through simulation, and substantial power gains were observed in all settings considered, with type I error rates closely tracking their nominal values.

Chromosomes, Human, X↗

Theoretical study of photodissociation dynamics on the lowest-lying Rydberg state of ketene.

In the present study, an attempt is made to reveal the main mechanism of photodissociation on the lowest-lying Rydberg state (1)B(1) of ketene, referred to as the second singlet excited state S(2), by means of the complete active space self-consistent field and the second-order multiconfigurational perturbation theory methods. The located S(2)S(1)T(1) three-surface intersection plays an important role in the dissociation process. It is shown that the intersection permits an efficient internal conversion from S(2) to S(1) state, but prohibits the intersystem crossing from S(2) to T(1) state because of the small spin-orbital coupling value of 0.136 cm(-1). The main photodissociation process could be described as follows: after one photon absorption to the S(2) state, ketene preferentially relaxes to the minimum S(2)C(2v), and undergoes a transition state S(2)TS with small potential barrier along the C(s)-I (out-of-plane bent) symmetry, and passes through the S(2)S(1)T(1) intersection to reach S(1) surface, then arrives at the transition state S(1)TS along the minimum energy path. As is well known, S(1)-->S(0) internal conversion around the Franck-Condon region is expected to be very efficient, and eventually the hot S(0) molecule has accumulated enough energy to yield the CH(2) (a (1)A(1)) and CO (X (1)Sigma(+)) products.

Journal Article↗

Expression, purification and crystallization of a novel nonstructural protein VP9 from white spot syndrome virus.

The nonstructural protein VP9 from white spot syndrome virus (WSSV) has been identified and expressed in Escherichia coli. To facilitate purification, a cleavable His6 tag was introduced at the N-terminus. The native protein was purified and crystallized by vapour diffusion against mother liquor containing 2 M sodium acetate, 100 mM MES pH 6.3, 25 mM cadmium sulfate and 3% glycerol. Crystals were obtained within 7 d and diffracted to 2.2 angstroms; they belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 74.13, b = 78.21, c = 78.98 angstroms and four molecules in the asymmetric unit. The selenomethionine-labelled protein produced isomorphous crystals that diffracted to approximately 3.3 angstroms.

Cloning, Molecular↗

Combination therapy with anti-CTL antigen-4 and anti-4-1BB antibodies enhances cancer immunity and reduces autoimmunity.

The majority of cancer antigens identified thus far have limited expression in normal tissues. It has been suggested that autoimmune disease is a necessary price for cancer immunity. This notion is supported by a recent clinical trial involving an anti-CTL antigen-4 (CTLA-4) antibody that showed significant clinical responses but severe autoimmune diseases in melanoma patients. To selectively modulate cancer immunity and autoimmunity, we used anti-CTLA-4 and anti-4-1BB antibodies to treat mice with a preexisting cancer, MC38. The combination of the two antibodies led to CD8 T-cell-mediated rejection of large established MC38 tumors and long-lasting immunity to the same tumor cells, although the same regimen was not effective for B16 melanoma. More importantly, whereas individual antibodies induced inflammation and autoimmune manifestations, combination therapy increased cancer immunity while reducing autoimmunity. The reduction of autoimmune effects correlates with an increased function of regulatory T cells. Our results suggest a novel approach to simultaneously enhance cancer immunity and reduce autoimmunity.

Animals↗

Hierarchy of alpha fetoprotein (AFP)-specific T cell responses in subjects with AFP-positive hepatocellular cancer.

We identified a series of immunodominant and subdominant epitopes from alpha fetoprotein (AFP), restricted by HLA-A*0201, which are recognized by the human T cell repertoire. The four immunodominant epitopes have been tested for immunogenicity in vivo, in HLA-A*0201+AFP+ advanced stage hepatocellular cancer (HCC) patients, and have activated and expanded AFP-specific IFN-gamma-producing T cells in these patients, despite high serum levels of this self Ag. Here, we have examined the frequency, function, and avidity of the T cells specific for subdominant epitopes from AFP. We find that T cells specific for several of these epitopes are of similar or higher avidity than those specific for immunodominant epitopes. We then tested the peripheral blood of subjects ex vivo with different levels of serum AFP for the hierarchy of response to epitopes from this Ag and find that HCC patients have detectable frequencies of circulating IFN-gamma-producing AFP-specific CD8+ T cells to both immunodominant and subdominant epitopes. We find the immunodominant and subdominant peptide-specific T cells to be differentially expanded with different modes of Ag presentation. Whereas spontaneous and AFP protein-stimulated responses show evidence for immunodominance, AdVhAFP-transduced dendritic cell-stimulated responses were broader and not skewed. Importantly, these data identify subdominant epitopes from AFP that can activate high-avidity T cells, and that can be detected and expanded in HCC subjects. These subdominant epitope-specific T cells can also recognize tumor cells and may be important therapeutically.

Adenoviridae↗

[Relationship between pterygium onset and ultraviolet rays exposure time].

OBJECTIVE: To investigate the dose-effect relationship between the radiation of ultraviolet ray and the onset of pterygium quantitatively. METHODS: Interrogation was conducted to 95 patients with pterygium in Yacheng district, Sanya City, Hainan Province, 37 males and 58 females, aged 55.7 +/- 13.8 (20 - 80), and 95 local volunteers in 1:1 pairs matched in age, sex, race, and similar habits of wearing glasses and caps (control group). Both the pterygium group and control group were re-divided into three sub-groups: youth (aged < or = 40), middle-aged (aged 41 - 60), and elderly (aged > 60). The time of exposing to ultraviolet ray was calculated. Photo of the pterygium was taken. The length of the pterygium invading into cornea was measured. RESULTS: The ultraviolet ray exposure time of the youth subgroup, pterygium group, was 35,637 +/- 13,587 hours, significantly higher than that of the youth subgroup, control group (26,188 +/- 17,423 hours, t = 3.352, P = 0.006). The ultraviolet ray exposure time of the middle-aged subgroup, pterygium group, was 73,412 +/- 23,082 hours, significantly higher than that of the middle-aged subgroup, control group (63,368 +/- 25,091 hours, t = 2.322, P = 0.024). However, there was no significant difference in the ultraviolet ray exposure time between the elderly subgroups of both groups. The length of the pterygium invading into cornea was positively correlated with the ultraviolet ray exposure time (r = 0.361, P < 0.05), and the length showed a trend of increased with aging. CONCLUSION: There is a certain dose-effect correlation between ultraviolet ray exposure and the etiology of pterygium.

Adult↗

Components of the peptidome and transcriptome persist in lin wa pi: the dried skin of the Heilongjiang brown frog (Rana amurensis) as used in traditional Chinese medicine.

Although the ancient practice of traditional Chinese medicine (TCM) utilizes predominantly herbal ingredients, many of which are now the subject of intense scientific scrutiny, significant quantities of animal tissue-derived materials are also employed. Here we have used contemporary molecular techniques to study the material known as lin wa pi, the dried skin of the Heilongjiang brown frog, Rana amurensis, that is used commonly as an ingredient of many medicines, as a general tonic and as a topical antimicrobial/wound dressing. Using a simple technology that has been developed and validated over several years, we have demonstrated that components of both the skin granular gland peptidome and transcriptome persist in this material. Interrogation of the cDNA library constructed from the dried skin by entrapment and amplification of polyadenylated mRNA, using a "shotgun" primer approach and 3'-RACE, resulted in the cloning of cDNAs encoding the precursors of five putative antimicrobial peptides. Two (ranatuerin-2AMa and ranatuerin-2AMb) were obvious homologs of a previously described frog skin peptide family, whereas the remaining three were of sufficient structural novelty to be named amurins 1-3. Mature peptides were each identified in reverse phase HPLC fractions of boiling water extracts of skin and their structures confirmed by MS/MS fragmentation sequencing. Components of traditional Chinese medicines of animal tissue origin may thus contain biologically active peptides that survive the preparation procedures and that may contribute to therapeutic efficacy.

Air↗

Impact of intra-subunit domain-domain interactions on creatine kinase activity and stability.

Creatine kinase (CK) is a key enzyme in vertebrate excitable tissues. In this research, five conserved residues located on the intra-subunit domain-domain interface were mutated to explore their role in the activity and structural stability of CK. The mutations of Val72 and Gly73 decreased both the activity and stability of CK. The mutations of Cys74 and Val75, which had no significant effect on CK activity and structure, gradually decreased the stability and reactivation of CK. Our results suggested that the mutations might modify the correct positioning of the loop contributing to domain-domain interactions, and result in decreased stability against denaturation.

Amino Acid Sequence↗

Massive and destructive T cell response to homeostatic cue in CD24-deficient lymphopenic hosts.

In response to a lymphopenic cue, T lymphocytes undergo a slow-paced homeostatic proliferation in an attempt to restore T cell cellularity. The molecular interaction that maintains the pace of homeostatic proliferation is unknown. In this study, we report that in lymphopenic CD24-deficient mice, T cells launch a massive proliferation that results in the rapid death of the recipient mice. The dividing T cells have phenotypes similar to those activated by cognate antigens. The rapid homeostatic proliferation is caused by a lack of CD24 on dendritic cells (DCs). Interestingly, although CD24 expression in T cells is required for optimal homeostatic proliferation in the wild-type (WT) host, mice lacking CD24 on all cell types still mount higher homeostatic proliferation than the WT mice. Thus, a lack of CD24 in the non-T host cells bypassed the requirement for T cell expression of CD24 in homeostatic proliferation in the WT host. Our data demonstrate that CD24 expressed on the DCs limits T cell response to homeostatic cue and prevents fatal damage associated with uncontrolled homeostatic proliferation.

Animals↗

[The application of stapling device in surgery of carcinoma of the esophagus and cardia].

OBJECTIVE: To evaluate the application of circular stapler in upper digestive tract reconstruction. METHODS: We present a retrospective review of 3322 patients with Carcinoma of esophagus and cardia undergoing a stapled esophagogastric anastomosis from August 1980 to September 2004. There were 2642 males and 680 females with age ranged from 28 to 83 years old. Carcinoma of esophagus was present in 2312 patients and carcinoma of gastric cardia in 1010 patients. The anastomosis was performed in the cervical region in 102 cases, thoracic apex in 147 cases, up aortic in 1838 cases and below aortic in 1235 cases. RESULTS: Anastomotic leakage occurred in 18 patients with an overall incidence of 0.54%, including thoracic leakage in 11 cases and cervical leakage in 7 cases. nine patients were dead because of the thoracic leakage, and the mortality of thoracic leakage was 81.8%. Benign anastomotic stricture was found in 66 patients with a rate of 2.0%, and instrumental failure occurred in 36 patients with a rate of 1.1%. CONCLUSION: Circular stapler can be used safely and reliably in upper digestive tract surgery, and the stapled anastomosis is an effective technique to reduce the incidence of anastomotic leakage.

Adult↗

Genetic attributes of cerebrospinal fluid-derived HIV-1 env.

HIV-1 often invades the CNS during primary infection, eventually resulting in neurological disorders in up to 50% of untreated patients. The CNS is a distinct viral reservoir, differing from peripheral tissues in immunological surveillance, target cell characteristics and antiretroviral penetration. Neurotropic HIV-1 likely develops distinct genotypic characteristics in response to this unique selective environment. We sought to catalogue the genetic features of CNS-derived HIV-1 by analysing 456 clonal RNA sequences of the C2-V3 env subregion generated from CSF and plasma of 18 chronically infected individuals. Neuropsychological performance of all subjects was evaluated and summarized as a global deficit score. A battery of phylogenetic, statistical and machine learning tools was applied to these data to identify genetic features associated with HIV-1 neurotropism and neurovirulence. Eleven of 18 individuals exhibited significant viral compartmentalization between blood and CSF (P < 0.01, Slatkin-Maddison test). A CSF-specific genetic signature was identified, comprising positions 9, 13 and 19 of the V3 loop. The residue at position 5 of the V3 loop was highly correlated with neurocognitive deficit (P < 0.0025, Fisher's exact test). Antibody-mediated HIV-1 neutralizing activity was significantly reduced in CSF with respect to autologous blood plasma (P < 0.042, Student's t-test). Accordingly, CSF-derived sequences exhibited constrained diversity and contained fewer glycosylated and positively selected sites. Our results suggest that there are several genetic features that distinguish CSF- and plasma-derived HIV-1 populations, probably reflecting altered cellular entry requirements and decreased immune pressure in the CNS. Furthermore, neurological impairment may be influenced by mutations within the viral V3 loop sequence.

Amino Acid Sequence↗