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Biomedical subjects

Yi Jiang

Publications and source records attributed to Yi Jiang.

At least 19 recordsLinked to original sources

Primate-specific regulation of the human glycosphingolipid gatekeeper UGCG.

Glycosphingolipids are essential membrane components that organize lipid microdomains and orchestrate cellular signalling, differentiation and neuronal function1-4. In humans, these functions arise from a repertoire of several hundred glycosphingolipid species generated through stepwise glycan elaboration5,6. Entry into this network is controlled by a single committed reaction catalysed by UDP-glucose ceramide glucosyltransferase (UGCG), the gatekeeper that dictates the scale and composition of glycosphingolipid diversity. Despite its biological and therapeutic importance7,8, its mechanism and regulation have remained unknown. Here we report cryogenic electron microscopy structures of full-length human UGCG in eight functional states at 2.9-3.4 Å resolution. UGCG adopts a previously unrecognized triple-pass transmembrane architecture that anchors a GT-A core at the membrane interface and creates a bipartite active site engaging soluble and membrane-embedded substrates. Contrary to canonical GT-A enzymes, UGCG uses a metal-independent catalytic mechanism driven by an arginine network. We identify a primate-specific steric element that tunes lipid affinity and catalytic turnover, modulating glycosphingolipid entry. Structures with clinically used inhibitors reveal how this architecture governs their potency and selectivity. Together, these findings define the structural and evolutionary logic by which one enzyme controls glycosphingolipid diversity and provide a framework for precision modulation of membrane lipid homeostasis in disease.

Animals↗

A three-dimensional model of myxobacterial aggregation by contact-mediated interactions.

Myxobacteria provide one of the simplest models of cell-cell interaction and organized cell movement leading to cellular differentiation. When starved, tens of thousands of cells change their movement pattern from outward spreading to inward concentration; they form aggregates that become fruiting bodies. Cells inside fruiting bodies differentiate into round, nonmotile, environmentally resistant spores. Traditionally, cell aggregation has been considered to imply chemotaxis; a long-range cell interaction. However, myxobacterial aggregation is the consequence of direct cell-contact interactions, not chemotaxis. We present here a 3D stochastic lattice-gas cellular automata model of cell aggregation based on local cell-cell contact, and no chemotaxis. We demonstrate that a 3D discrete stochastic model can simulate two stages of cell aggregation. First, a "traffic jam" forms embedded in a field of motile cells. The jam then becomes an aggregation center that accumulates more cells. We show that, at high cell density, cells stream around the traffic jam, generating a 3D hemispherical mound. Later, when the nuclear traffic jam dissolves, the aggregation center becomes a 3D ring of streaming cells.

Models, Biological↗

Metavanadate suppresses desferrioxamine-induced leukemic cell differentiation with reduced hypoxia-inducible factor-1alpha protein.

We recently showed that moderate hypoxia and hypoxia-mimetic agents CoCl(2) and desferrioxamine (DFO) induce differentiation of acute myeloid leukemic cells via hypoxia-inducible factor-1alpha (HIF-1alpha) that interacts with and increases the transcriptional activity of CCAAT/enhancer-binding protein alpha (C/EBPalpha), a critical factor for granulocytic differentiation. Here, we show that metavanadate antagonizes DFO-induced growth arrest and differentiation with the inhibition of HIF-1alpha protein accumulation in leukemic cells. Furthermore, DFO also increased C/EBPalpha expression rapidly but transiently, which was inhibited by metavanadate. Taken together, these findings provide further evidence for the role of HIF-1alpha and C/EBPalpha in DFO-induced leukemic cell differentiation.

Animals↗

Aflatoxin B1 albumin adduct levels and cellular immune status in Ghanaians.

Although aflatoxins (AFs) have been shown to be immune-suppressive agents in animals, the potential role of AFs in modifying the distribution and function of leukocyte subsets in humans has never been assessed. We examined the cellular immune status of 64 Ghanaians in relation to levels of aflatoxin B1 (AFB1)-albumin adducts in plasma. The percentages of leukocyte immunophenotypes in peripheral blood, CD4+ T cell proliferative response, CD4+ T(h) and CD8+ T cell cytokine profiles and monocyte phagocytic activity were measured using flow cytometry. NK cell cytotoxic function was determined by perforin and tumor necrosis factor-alpha expression in CD3-CD56+ NK cells. AFB1-albumin adducts levels ranged from 0.3325 to 2.2703 (mean = 0.9972 +/- 0.40, median = 0.9068) pmol mg(-1) albumin. Study participants with high AFB1 levels had significantly lower percentages of CD3+ and CD19+ cells that showed the CD69+ activation marker (CD3+CD69+ and CD19+CD69+) than participants with low AFB1 levels (P = 0.002 for both). Also, the percentages of CD8+ T cells that contained perforin or both perforin and granzyme A were significantly lower in participants with high AFB1 levels compared with those with low AFB1 (P = 0.012 for both). Low levels of CD3+CD69+ (r = -0.32, P = 0.016) and CD19+CD69+ (r = -0.334, P = 0.010) cells were significantly associated with high AFB1 levels using correlation analysis. By multivariate analysis, there were strong negative correlations between the percentages of these cells (CD3+CD69+: b = -0.574, P = 0.001, and CD19+CD69+: b = -0.330, P = 0.032) and AFB1 levels. These alterations in immunological parameters in participants with high AFB1 levels could result in impairments in cellular immunity that could decrease host resistance to infections.

Adult↗

Ultrahigh-resolution optical coherence tomography with a fiber laser source at 1 microm.

We report a compact, high-power, fiber-based source for ultrahigh-resolution optical coherence tomography (OCT) near 1 microm. The practical source is based on a short-pulse, ytterbium-doped fiber laser and on generation of a continuum spectrum in a photonic crystal fiber. The broadband emission has an average power of 140 mW and offers an axial resolution of 2.1 microm in air (<1.6 microm in biological tissue). The generation of a broad bandwidth is robust and efficient. We demonstrate ultrahigh-resolution, time-domain OCT imaging of in vitro and in vivo biological tissues.

Equipment Design↗

Neural mechanisms of global/local processing of bilateral visual inputs: an ERP study.

OBJECTIVE: Examine the neural mechanisms of global/local processing of multiple hierarchical stimuli. METHODS: Event-related brain potentials (ERPs) were recorded from adults who selectively attended to the global or local level of two compound letters that were simultaneously presented in the left and right visual fields, respectively. The compound stimuli were either broadband in spatial frequency (SF) spectrum or contrast balanced to remove low SFs. Subjects were asked to detect the presence of a global or local target that might appear in either the left or the right visual field in separate blocks of trials. RESULTS: Attention to the local level of broadband stimuli elicited a positivity over lateral occipital sites at 80-120 ms (P1) with larger amplitude than those in the global attention condition. However, global attention produced an enhanced positivity at 240-320 ms (P2) over lateral occipital sites relative to local attention. Both the P1 and P2 waves in the global condition were of larger amplitudes over the left than right hemispheres. Contrast balancing eliminated the P1 and P2 effects and modulated the hemispheric asymmetry of the long-latency occipital positivity. CONCLUSIONS: The results provide ERP evidence for modulations of neural activities in the visual cortex by global/local attention to concurrently presented multiple compound letters. Moreover, the modulation of brain activities by global/local attention depends upon the presence of low SFs in the compound stimuli. SIGNIFICANCE: The ERP results of this study contribute to the understanding of neural mechanisms of the processing of simultaneously-presented multiple compound stimuli.

Adult↗

VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissue-inductive signals and reflects their developmental origin.

Although expression of vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells and its functional implications have been previously appreciated, VCAM-1 expression in other than endothelial cells, especially hematopoietic cells, has been recently recognized and has not been explored in detail. Using normal mice and mice with a conditional ablation of VCAM-1 through a Tie2-driven cre transgene, we have studied the biodistribution and the pattern of VCAM-1 expression in circulating versus tissue-residing cells before and after their enforced mobilization. In the normal mouse, both at basal hematopoiesis or following mobilization, VCAM-1 expression is confined to myeloid cells residing in hematopoietic tissues, whereas free cells in circulation or in body cavities are devoid of VCAM-1 messenger RNA (mRNA) and protein. However, following culture, proliferating myeloid cells, but not lymphoid cells, express VCAM-1. In the VCAM-1-ablated mouse, there is an increase in circulating progenitors as a consequence of their ongoing release from bone marrow, a process enhanced by splenectomy. We postulate that the main mechanism leading to their release is the ablation of VCAM-1 by fibroblastic and by endothelial cells. Ablation of VCAM-1 in fibroblasts by Tie2-driven cre is a novel finding and likely denotes their developmental ancestry by Tie2-expressing (mesenchymal?) progenitor cells during development.

Age Factors↗

Crystallographic determination of stereochemistry of biologically active 2'',3''-dibromo-7-epi-10-deacetylcephalomannine.

The stereochemistry at C2'' and C3'' of two diastereomers of 2'',3''-dibromo-7-epi-10-deacetylcephalomannine (6 and 7), which were synthesized by reacting 7-epi-10-deacetylcephalomannine (5) with bromine, were assigned unambiguously based on crystallographic studies of 6. The X-ray crystallographic analysis shows that 6 adopts an absolute configuration of (2''S,3''R), and 7 can be assigned as (2''R,3''S) configuration. The side-chain conformation of 6 was revealed to be different with the known hydrophobic collapse and the apolar conformations, as found in solid state and in solution. However, most side-chain torsion angles of 6 were found to be very similar to those of tubulin-bound T-shaped conformation (T-Taxol). Both 6 and 7 showed strong in vitro paclitaxel-like activity.

Antineoplastic Agents↗

Attentional modulation of perceptual grouping in human visual cortex: functional MRI studies.

When presented with a complex visual scene, our visual system has to organize the discrete entities present into useful perceptual units. The current work investigated the neural substrates of perceptual grouping defined by Gestalt laws of proximity and similarity of shape, and whether the neural substrates underlying perceptual grouping are modulated by task relevance and spatial attention. In visual discrimination tasks, subjects identified the orientations of perceptual groups formed by proximity or similarity of local elements or alternatively identified colors of either dots around the grouped stimuli or the fixation cross. Using functional magnetic resonance imaging (fMRI), we identified that the calcarine cortex was involved in proximity grouping but not in the grouping process defined by similarity of shape. Moreover, we showed evidence that the neural correlates of proximity grouping in the calcarine cortex were weakened when the elements were of low task relevance and fell outside an attended area of field. The findings reveal the neural basis for basic grouping operations, as well as illustrating how attention and proximity grouping interact in human visual cortex.

Adult↗

Attentional modulation of perceptual grouping in human visual cortex: ERP studies.

We sought to identify the neural substrates underlying perceptual grouping, and examined whether the grouping-related neural activities are modulated by task relevance and attention by recording high-density event-related potentials (ERPs). Participants were presented with stimulus arrays, in which local elements were either evenly distributed or grouped into rows or columns by proximity or similarity, and had to discriminate orientations of the perceptual groups, or to identify the colors of dots around stimulus displays or of the fixation cross. We found that proximity grouping was indexed by a positive activity over the medial occipital cortex with a peak latency of about 100 ms after stimulus onset (Pd100), whereas grouping by similarity of shape was reflected in a negative activity with longer latency over the occipito-temporal areas. Dipole modeling based on a realistic boundary element head model localized the Pd100 to the right calcarine cortex. Moreover, we showed that the grouping-related activities were weakened when stimulus arrays were of low task relevance and fell outside an attended area of field. The results suggest that human calcarine cortex is engaged in early grouping operations defined by proximity, reinforcing the previous fMRI findings. Moreover, our ERP results indicate that the neural bases underlying perceptual grouping in human visual cortex can be modulated by task relevance and attention as early as 100 ms after sensory stimulation. Hum Brain Mapp, 2005. (c) 2005 Wiley-Liss, Inc.

Adult↗

Accelerating MR diffusion tensor imaging via filtered reduced-encoding projection-reconstruction.

MR diffusion tensor imaging (DTI) is a promising tool for characterizing the microstructure of ordered tissues. However, its practical applications are hampered by relatively low signal-to-noise-ratio and spatial and temporal resolution. Reduced-encoding imaging (REI) via k-space sharing with constrained reconstruction has previously been shown to be effective for accelerating DTI, although the implementation was based on rectilinear k-space sampling. Due to the intrinsic oversampling of central k-space and allowance for isotropic downsampling, projection-reconstruction (PR) imaging may be better suited for REI. In this study, regularization procedures, including radial filtering and baseline signal correction to adequately reconstruct reduced encoded PR imaging data, are investigated. The proposed filtered reduced-encoding projection-reconstruction (FREPR) technique is applied to DTI tissue fiber orientation and fractional anisotropy (FA) measurements. Results show that FREPR offers improved reconstructions of the reduced encoded images and on an equal total scan-time basis provides more accurate fiber orientation and FA measurements compared to rectilinear k-space sampling-based REI methods or a control experiment consisting of only fully encoded images. These findings suggest a potentially significant role of FREPR in accelerating repeated imaging and improving the data acquisition-time efficiency of DTI experiments.

Computer Simulation↗

Streptomyces nanningensis sp. nov. a novel Streptomycete from forest soil.

A strain YIM 33098T (= CCTCC AA001027T = DSM 41831T) was isolated from a forest soil sample collected from Nanning in Guangxi Province, China, in the course of screening for producers of new drug lead compounds. This strain was identified by using a polyphasic approach. The results showed that it should be assigned to the genus Streptomyces. An almost complete 16S rRNA gene sequence of the strain was determined and compared with those of representative Streptomyces species. Strain YIM 33098T was clustered in the same subclade with Streptomyces tendae ATCC19812T and Streptomyces eurythermus ATCC14975T. Similarities of strain YIM 33098T with the two strains were 97.35% and 97.42%, respectively. Based on the phenotypic and genotypic evidence, it is therefore proposed that strain YIM 33098T should be classified in the genus Streptomyces as a new species under the name of Streptomyces nanningensis sp. nov.

Bacterial Typing Techniques↗

Streptomyces roseoalbus sp. nov., an actinomycete isolated from soil in Yunnan, China.

An actinomycete strain was isolated from a soil sample collected from a secondary forest at Yongsheng of Yunnan province, China. The isolate, YIM 31634T, was identified by a polyphasic approach. The 16S rDNA sequence analysis showed that the strain YIM 31634T belongs to the genus Streptomyces, with closest similarity to Streptomyces olivochromogenes DSM 40451T (97.66% similarity). Sequence similarities between strain YIM 31634T and other Streptomyces species in the same subclade ranged from 97.59% (with Streptomyces resistomycificus DSM 40133T) to 97.22% (with Streptomyces mirabilis ATCC 27447T). Key phenotypic characteristics as well as chemotaxonomic features of the actinomyces were congruent with the description of the genus Streptomyces. On the basis of phenotypic and phylogenetic analyses, strain YIM31634T was recognized as a new species of the genus Streptomyces for which the name Streptomyces roseoalbus sp. nov. is proposed. The strain YIM 31634T has been deposited in the Chinese Center of Type Culture Collection as strain CCTCC M 203016T and in the Deutsche Sammlung von Mikroorganismen (DSM 41833T).

Bacterial Typing Techniques↗

Helical myofiber orientation after myocardial infarction and left ventricular surgical restoration in sheep.

OBJECTIVES: It has been proposed that successful left ventricular surgical restoration should restore normal helical myofiber orientation. A magnetic resonance imaging technique, magnetic resonance diffusion tensor imaging, has been developed to measure myocyte orientation. By using magnetic resonance diffusion tensor imaging, this study tested the hypothesis that (1) myocyte orientation is altered after anteroapical myocardial infarction and (2) left ventricular surgical restoration restores normal helix angles. METHODS: Thirteen sheep underwent anteroapical myocardial infarction (25% of left ventricular mass). Ten weeks later, animals underwent either aneurysm plication (n = 8) or sham operations (n = 5). Six weeks after this operation, hearts were excised, perfusion fixed in diastole, and underwent magnetic resonance diffusion tensor imaging. Hearts from normal sheep (n = 5) were also harvested and imaged. Primary eigenvectors of the diffusion tensors from magnetic resonance diffusion tensor imaging were resolved into helix angles relative to a local wall coordinate system. Transmural samples of the helix angles were compared at the border zone of the aneurysm or repair (or a comparable distance from the base in normal sheep), 1 cm below the valves, and halfway between. RESULTS: The helical myofiber orientation did not change after myocardial infarction. However, aneurysm plication caused myofibers in the anterior border zone to rotate counterclockwise (-35.6 +/- 10.5 degrees , P = .028) and those in the lateral border zone to rotate clockwise (34.4 +/- 8.1 degrees , P = .031). CONCLUSIONS: Surgical restoration alters myocyte orientation adjacent to the surgical repair. However, myofiber orientation is not abnormal after myocardial infarction, and thus surgical restoration techniques intent on restoring normal helix angles might not be warranted.

Animals↗

Preparation and evaluation of new brominated paclitaxel analogues.

Two diastereomers of 2'',3''-dibromo-7-epi-10-deacetylcephalomannine, 4 and 5, have been synthesized, purified and identified for evaluation as antitumour drugs. The cytotoxicity of the two diastereomers, assessed in cell culture against MCF-7 breast cancer, A549 lung cancer and A2780 ovarian cancer, was slightly stronger than that of paclitaxel. The cytotoxicity of 5 outweighs that of 4. In the light of the difference in cytotoxicity between the two diastereomers, we can assume that the differing configurations of C-2'' and C-3'' of the two diastereomers may result in different bioactive conformations in solution and, consequently, different biologically relevant conformations for binding to tubulin/microtubules -- a matter we are studying further.

Antineoplastic Agents↗

Nocardia polyresistens sp. nov.

A novel actinomycete strain YIM 33361(T) was isolated from a soil sample collected from Yunnan, China. Comparative 16S rRNA gene sequencing showed that the strain constituted a distinct subclade within the genus Nocardia, displaying more than 3% sequence divergence from established species. Based on its morphological, chemotaxonomic, phenotypic and genotypic characteristics, strain YIM 33361(T) (=CCTCC AA 204004(T)=KCTC 19027(T)) is proposed as the type strain of a novel species, Nocardia polyresistens sp. nov.

Bacterial Typing Techniques↗

A hierarchical model for estimating response time distributions.

We present a statistical model for inference with response time (RT) distributions. The model has the following features. First, it provides a means of estimating the shape, scale, and location (shift) of RT distributions. Second, it is hierarchical and models between-subjects and within-subjects variability simultaneously. Third, inference with the model is Bayesian and provides a principled and efficient means of pooling information across disparate data from different individuals. Because the model efficiently pools information across individuals, it is particularly well suited for those common cases in which the researcher collects a limited number of observations from several participants. Monte Carlo simulations reveal that the hierarchical Bayesian model provides more accurate estimates than several popular competitors do. We illustrate the model by providing an analysis of the symbolic distance effect in which participants can more quickly ascertain the relationship between nonadjacent digits than that between adjacent digits.

Cognition↗

[Expression of small breast epithelial mucin mRNA in peripheral blood of breast cancer patients and its clinical significance].

BACKGROUND & OBJECTIVE: The major cause of death in breast cancer patients is distant metastasis. This study was to explore the expression and significance of small breast epithelial mucin (SBEM) mRNA, the specific marker of breast cancer, in peripheral blood of breast cancer patients. METHODS: Expression of SBEM mRNA in peripheral blood samples from 67 breast cancer patients, 16 benign breast disease patients, and 20 healthy volunteers was detected by nested reverse transcription-polymerase chain reaction (nested RT-PCR). RESULTS: SBEM mRNA was not detected in healthy volunteers and benign breast disease patients. Positive rate of SBEM mRNA was 50.7% (34/67) in breast cancer patients. Positive rate of SBEM mRNA was 25.0% (2/8) in stage I patients, 45.8% (11/24) in stage II patients, 43.8% (7/16) in stage III patients, and 73.7% (14/19) in stage IV patients, respectively. Positive rate of SBEM mRNA was significantly higher in stage IV patients than in stages I, II, and III patients (P0.05). The expression of SBEM mRNA in peripheral blood was not correlated with patient's age, primary tumor size, pathologic type, and estrogen or progestin receptor status (P0.05). CONCLUSION: SBEM mRNA is specifically expressed in peripheral blood of breast cancer patients, and may be a marker of micrometastasis of breast cancer.

Adenocarcinoma↗