Biomedical subjects

Yi Jiang

Publications and source records attributed to Yi Jiang.

At least 19 recordsLinked to original sources

PubMed2026

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↗

PubMed2006

The O-chain structure from the LPS of the bacterium Naxibacter alkalitolerans YIM 31775T.

The O-chain polysaccharide of the lipopolysaccharide from the bacterium Naxibacter alkalitolerans strain YIM 31775(T) was characterized. The structure was studied by means of chemical analysis and 2D NMR spectroscopy and shown to be built up by the following tetrasaccharide repeating unit: -->3)-alpha-D-FucpNAc-(1-->2)-beta-D-Quip3NHBu-(1-->2)-alpha-D-Rhap-(1-->)-beta-D-Galp-(1--> where HBu is hydroxy-butanoyl.

Alkalies↗

PubMed2006

A three-dimensional model of myxobacterial fruiting-body formation.

Myxobacterial cells are social; they swarm by gliding on surfaces as they feed cooperatively. When they sense starvation, tens of thousands of cells change their movement pattern from outward spreading to inward concentration and 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 that shares many features of chemical reaction-diffusion dynamics. The biological evidence, however, suggests that Myxococcus xanthus aggregation is the consequence of direct cell-contact interactions that are different from chemotaxis. To test whether local interactions suffice to explain the formation of fruiting bodies and the differentiation of spores within them, we have simulated the process. In this article, we present a unified 3D model that reproduces in one continuous simulation all the stages of fruiting-body formation that have been experimentally observed: nonsymmetric initial aggregates (traffic jams), streams, formation of toroidal aggregates, hemispherical 3D mounds, and finally sporulation within the fruiting body.

Cell Communication↗

PubMed2006

A gender- and sexual orientation-dependent spatial attentional effect of invisible images.

Human observers are constantly bombarded with a vast amount of information. Selective attention helps us to quickly process what is important while ignoring the irrelevant. In this study, we demonstrate that information that has not entered observers' consciousness, such as interocularly suppressed (invisible) erotic pictures, can direct the distribution of spatial attention. Furthermore, invisible erotic information can either attract or repel observers' spatial attention depending on their gender and sexual orientation. While unaware of the suppressed pictures, heterosexual males' attention was attracted to invisible female nudes, heterosexual females' attention was attracted to invisible male nudes, gay males behaved similarly to heterosexual females, and gay/bisexual females performed in-between heterosexual males and females.

Adult↗

PubMed2006

Cortical responses to invisible faces: dissociating subsystems for facial-information processing.

Perceiving faces is critical for social interaction. Evidence suggests that different neural pathways may be responsible for processing face identity and expression information. By using functional magnetic resonance imaging (fMRI), we measured brain responses when observers viewed neutral, fearful, and scrambled faces, either visible or rendered invisible through interocular suppression. The right fusiform face area (FFA), the right superior temporal sulcus (STS), and the amygdala responded strongly to visible faces. However, when face images became invisible, activity in FFA to both neutral and fearful faces was much reduced, although still measurable; activity in the STS was robust only to invisible fearful faces but not to neutral faces. Activity in the amygdala was equally strong in both the visible and invisible conditions to fearful faces but much weaker in the invisible condition for the neutral faces. In the invisible condition, amygdala activity was highly correlated with that of the STS but not with FFA. The results in the invisible condition support the existence of dissociable neural systems specialized for processing facial identity and expression information. When images are invisible, cortical responses may reflect primarily feed-forward visual-information processing and thus allow us to reveal the distinct functions of FFA and STS.

Amygdala↗

PubMed2006

WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4.

The epithelial Ca(2+) channel TRPV5 serves as a gatekeeper for active Ca(2+) reabsorption in the distal convoluted tubule and connecting tubule of the kidney. WNK4, a protein serine/threonine kinase with gene mutations that cause familial hyperkalemic hypertension (FHH), including a subtype with hypercalciuria, is also localized in the distal tubule of the nephron. To understand the role of WNK4 in modulation of Ca(2+) reabsorption, we evaluated the effect of WNK4 on TRPV5-mediated Ca(2+) transport in Xenopus laevis oocytes. Coexpression of TRPV5 with WNK4 resulted in a twofold increase in TRPV5-mediated Ca(2+) uptake. The increase in Ca(2+) uptake was due to the increase in surface expression of TRPV5. When the thiazide-sensitive Na(+)-Cl(-) cotransporter NCC was coexpressed, the effect of WNK4 on TRPV5 was weakened by NCC in a dose-dependent manner. Although the WNK4 disease-causing mutants E562K, D564A, Q565E, and R1185C retained their ability to upregulate TRPV5, the blocking effect of NCC was further strengthened when wild-type WNK4 was replaced by the Q565E mutant, which causes FHH with hypercalciuria. We conclude that WNK4 positively regulates TRPV5-mediated Ca(2+) transport and that the inhibitory effect of NCC on this process may be involved in the pathogenesis of hypercalciuria of FHH caused by gene mutation in WNK4.

Animals↗

PubMed2006

Significance of MHC class II haplotypes and IgG Fc receptors in SLE.

Systemic lupus erythematosus (SLE) is a systemic antibody-mediated autoimmune disease that develops under the control of multiple susceptibility genes. Genetic studies in murine and human SLE have identified several chromosomal intervals that contain candidate susceptibility genes. However, the ultimate identification of the genes and their roles in disease process need much further investigation. Spontaneous murine SLE models provide useful tools in this respect. In this chapter, we show this line of investigation, particularly focusing on the roles of major histocompatibility complex (MHC) class II and immunoglobulin G Fc receptors (FcgammaRs). The existence of high-affinity autoantibodies is evidence that autoimmunity in SLE is antigen-driven. Thereby, MHC class II haplotypes have been implicated in SLE susceptibility; however, because of the linkage disequilibrium that exists among the class I, II and III genes within the MHC complex, it has been difficult to discriminate the relative contributions of individual loci. On the other hand, the extent of antibody synthesis upon antigen stimulation and associated inflammatory cascades are controlled in several ways by the balance of stimulatory and inhibitory signaling molecules on immune cells. Stimulatory/inhibitory FcgammaRs mediate one such mechanism, and there are reports indicating the association between polymorphic FcgammaRs and SLE. However, as stimulatory and inhibitory FcgammaRs cluster on the telomeric chromosome 1, the absolute contribution of individual genes has been difficult to dissect. In studies of genetic dissection using interval-congenic and intragenic recombinant mouse strains of SLE models, we show evidence and discuss how and to what extent MHC class II molecules and stimulatory/inhibitory FcgammaRs are involved in SLE susceptibility.

Animals↗

PubMed2006

Hyperdynamics for entropic systems: time-space compression and pair correlation function approximation.

We develop a generalized hyperdynamics method that is able to simulate slow dynamics in atomistic general (both energy- and entropy-dominated) systems. We show that a few functionals of the pair correlation function, involving two-body entropy, form a low-dimensional collective space, which is a good approximation that is able to distinguish stable and transitional conformations. A bias potential, which raises the energy in stable regions, is constructed on the fly. We examine the slow nucleation processes of a Lennard-Jones gas and show that our method can generate correct long-time dynamics without prior knowledge.

Journal Article↗

PubMed2006

Bridging converts a noncytotoxic nor-paclitaxel derivative to a cytotoxic analogue by constraining it to the T-Taxol conformation.

The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test of the T-Taxol conformational hypothesis. Although the unbridged A-nor-paclitaxel 3 is essentially noncytotoxic, the bridged analogue 4 is strongly cytotoxic. This result provides strong evidence for the T-Taxol conformation as the bioactive tubulin-binding conformation of paclitaxel.

Animals↗

PubMed2006

Genetic dissection of the effects of stimulatory and inhibitory IgG Fc receptors on murine lupus.

Immune complex (IC)-mediated tissue inflammation is controlled by stimulatory and inhibitory IgG Fc receptors (FcgammaRs). Systemic lupus erythematosus is a prototype of IC-mediated autoimmune disease; thus, imbalance of these two types of FcgammaRs is probably involved in pathogenesis. However, how and to what extent each FcgammaR contributes to the disease remains unclear. In lupus-prone BXSB mice, while stimulatory FcgammaRs are intact, inhibitory FcgammaRIIB expression is impaired because of promoter region polymorphism. To dissect roles of stimulatory and inhibitory FcgammaRs, we established two gene-manipulated BXSB strains: one deficient in stimulatory FcgammaRs (BXSB.gamma(-/-)) and the other carrying wild-type Fcgr2b (BXSB.IIB(B6/B6)). The disease features were markedly suppressed in both mutant strains. Despite intact renal function, however, BXSB.gamma(-/-) had IC deposition in glomeruli associated with high-serum IgG anti-DNA Ab levels, in contrast to BXSB.IIB(B6/B6), which showed intact renal pathology and anti-DNA levels. Lymphocytes in BXSB.gamma(-/-) were activated, as in wild-type BXSB, but not in BXSB.IIB(B6/B6). Our results strongly suggest that both types of FcgammaRs in BXSB mice are differently involved in the process of disease progression, in which, while stimulatory FcgammaRs play roles in effecter phase of IC-mediated tissue inflammation, the BXSB-type impaired FcgammaRIIB promotes spontaneous activation of self-reactive lymphocytes and associated production of large amounts of autoantibodies and ICs.

Animals↗

PubMed2006

Determinants of aflatoxin levels in Ghanaians: sociodemographic factors, knowledge of aflatoxin and food handling and consumption practices.

Aflatoxins are among the most potent of carcinogens found in staple foods such as groundnuts, maize and other oil seeds. This study was conducted to measure the levels of aflatoxin B(1) (AFB(1)) albumin adducts in blood and aflatoxin M(1) (AFM(1)) metabolite in urine of people in a heavy peanut and maize consuming region of Ghana and to examine the association between aflatoxin levels and several socio-demographic factors and food handling and consumption practices. A cross-sectional study was conducted in four villages in the Ejura Sekyedumase district of Ghana. A socio-demographic survey was administered to 162 participants. Blood samples were collected from 140 and urine samples from 91 of the participants and AFB(1) albumin-adduct levels in blood and AFM(1) levels in urine were measured. High AFB(1) albumin-adduct levels were found in the plasma (mean+/-SD=0.89+/-0.46pmol/mg albumin; range=0.12-3.00pmol/mg; median=0.80pmol/mg) and high AFM(1) levels in the urine (mean+/-SD=1,800.14+/-2602.01pg/mg creatinine; range=non-detectable to 11,562.36pg/mg; median=472.67pg/mg) of most of the participants. There was a statistically significant correlation (r=0.35; p=0.007) between AFB(1)-albumin adduct levels in plasma and AFM(1) levels in urine. Several socio-demographic factors, namely, educational level, ethnic group, the village in which participants lived, number of individuals in the household, and number of children in the household attending secondary school, were found to be significantly associated with AFB(1) albumin-adduct levels by bivariate analysis. By multivariate analyses, ethnic group (p=0.04), the village in which participants live (p=0.02), and the number of individuals in the household (p=0.01), were significant predictors of high AFB(1) albumin-adducts. These findings indicate strongly that there is need for specifically targeted post-harvest and food handling and preparation interventions designed to reduce aflatoxin exposure among the different ethnic groups in this region of Ghana.

Aflatoxin B1↗

PubMed2006

Diastereomers of dibromo-7-epi-10-deacetylcephalomannine: crowded and cytotoxic taxanes exhibit halogen bonds.

The diastereomers of dibromo-7-epi-10-deacetylcephalomannine (6 and 7) have been isolated and characterized. Cytotoxicity and microtubule assembly assays demonstrate that cephalomannine analogue 6 possesses a potency profile very similar to that of Taxol, while isomer 7 is slightly less active. Solid state, solution, and tubulin-bound conformations of the two diastereomers were probed by using X-ray crystallography, 2-D NMR experiments in conjunction with the NAMFIS analysis, and the Glide docking protocol. In the crystal, isomer 7 exhibits an intermolecular halogen bond that may contribute to self-assembly. Neither crystal structure appears in the NAMFIS solution analysis, but both diastereomers are represented in solution by a T-shaped Taxol conformer. Glide docking demonstrates the latter to best fill the tubulin binding pocket, as has been shown for the parent Taxol drug. Each model of the bound complexes for 6 and 7 presents a single well-defined halogen bond from one of the ligand's bromines to Glu22 or Asp26 near the N-terminus of beta-tubulin, respectively. This first report of a halogen bond between taxanes and tubulin may prove useful in guiding the design and synthesis of other microtubule-stabilizing agents with a similar capacity.

Antineoplastic Agents↗

PubMed2006

Hypoxia inducible factor-1alpha and leukemic cell differentiation.

Arsenic trioxide (As2O3, ATO) is a recently developed drug for the effective treatment of acute promyelocytic leukemia (APL). Experimental studies showed that in vitro differentiation-inducing ability on APL cells of this drug is not significant compared with its in vivo activity. We unexpectedly found recently that hypoxia-mimetic agents and moderate real hypoxia triggered acute myeloid leukemic cells to undergo differentiation. Furthermore, intermittent hypoxia significantly prolonged the survival of the transplanted leukemic mice with inhibition of infiltration and induction of differentiation of leukemic cells. In the following works, molecular mechanisms of hypoxia-induced differentiation were investigated and some interesting results have been obtained. This review will shortly summarize the related progresses and discuss the questions remained to be further investigated.

Animals↗

PubMed2006

A novel fluorescence polarization based assay for 14 human papillomavirus genotypes in clinical samples.

A specific and practical method was developed for high throughput 14 human papillomavirus (HPV) genotypes assay in clinical samples by a single PCR. GP5+/6+ polymerase chain reaction (PCR) system was used to amplify HPV DNA in 1127 samples. The PCR product was assayed by AcycloPrime reaction with fluorescence polarization (FP). Fourteen HPV genotypes specific sequence primers designed within GP5+/GP6+ amplification polymorphism regions of L1 genes for corresponding HPV genotypes were annealed with the type specific PCR products and special fluorescent terminator was added to the end of the primer under direction of the PCR products. AcycloPrime-FP analysis showed specific anneal and incorporation without any cross-reaction. The types detected with FP showed an excellent overall agreement with sequence when the individual monotype results were taken into account. The proposed method could detect more than one type of HPV infection, but the sequence method was limited. AcycloPrime-FP could reach the detection level: 100 ag for representative phylogenetically distant HPV genotypes: HPV6, 18, 31, 39, 42, 51 and 58. The results of AcycloPrime-FP showed excellent reproducibility. The proposed method allowed an economical detection of HPV genotypes without any use of labeled probe. It is expected to be an extremely useful tool for HPV genotypes screening.

Capsid Proteins↗

PubMed2006

Neural correlates of within-level and across-level attention to multiple compound stimuli.

Event-related potentials (ERPs) were recorded to investigate the neural mechanisms of attention to the same or different levels of two compound letters presented concurrently in the left and right visual fields, respectively. Relative to the condition when attention was allocated to the global level of one compound stimulus and the local level of another one (across-level attention), attention to the same level of the two compound stimuli (within-level attention) increased an early positivity between 100 and 140 ms (P1) over the occipito-parietal cortex. A long-latency positivity between 320 and 560 ms (P3) over the central-parietal area was also increased in the within-level relative to across-level attention conditions. The ERP results suggest that, relative to across-level attention, within-level attention to multiple compound stimuli facilitates both early sensory-perceptual processing and late process of stimulus evaluation and identification in hierarchical analysis.

Attention↗

PubMed2006

Right hemisphere dominance in perceiving coherence of visual events.

The visual world consists of static pictures as well as of coherent visual events. The present study investigated neural substrates underlying the perception of coherence of visual events that evolves over time. We measured brain activity using functional magnetic resonance imaging (fMRI) while adults watched briefly presented static images that were extracted from movie clips depicting coherent visual events. The images were presented either in the coherent order as they were displayed in the movie clips or in a random order. Relative to the random order presentation condition, static images presented in the coherent order generated stronger activation in the right middle temporal cortex, the right posterior superior temporal cortex, and the right inferior postcentral gyrus. The results provide neuroimaging evidence for the dominance of the right hemisphere in perceiving coherent visual events.

Adult↗

PubMed2006

Stage-dependent Dishevelled-1 expression during mouse spermatogenesis suggests a role in regulating spermatid morphological changes.

Dishevelled (Dsh in Drosophila or DVL in mice) is a member of the highly conserved Wg/Wnt signaling pathway, which regulates important processes such as cell proliferation, polarity, and specification of cell fate. Three orthologous genes of Dishevelled (Dvl-1, Dvl-2, and Dvl-3) have been found in both humans and mice. They play pivotal roles in regulating cell morphology and a variety of changes in cell behaviors. In the present study, we show that the expression of Dvl-1 is stage-dependent during mouse spermatogenesis, although Dvl-2 and Dvl-3 show relative consistent expression. The expression of Dvl-1 mRNA first appears in pachytene spermatocytes, increases in round and elongating spermatids, and then turns to an undetectable level in mature sperm cells. Analyses of immunohistochemistry and immunofluorescence staining show that DVL-1 is present diffusely in the cytoplasm of pachytene spermatocytes and exhibits mainly a vesicular pattern and perinuclear distribution and a weak diffusely cytoplasmic signal in round and elongating spermatids. The vesicular pattern of DVL-1 has been observed by previous studies in somatic cells, and suggested to play roles in signal transduction. Immunoprecipitation experiments show that DVL-1 coimmunprecipitates with spermatogenic cells beta-actin rather than alpha-tubulin. These results indicate that DVL-1 may be involved in spermatid morphological changes during mouse spermiogenesis through mediating signal transduction and/or regulating actin cytoskeleton organization.

Actins↗

PubMed2006

Association of CTLA-4 gene microsatellite polymorphism with ulcerative colitis in Chinese patients.

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation as a result of an exaggerated T cell response. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4), expressed mainly in activated T cells, inhibits T cell activation and proliferation by combining B7 through competing CD28 and maintains immune homeostasis. Polymorphisms of the CTLA-4 gene are known to be associated with several autoimmune diseases. The aim of this study was to investigate the association between the CTLA-4 gene microsatellite polymorphism and UC in Chinese patients. Unrelated 100 Chinese patients with UC and 140 healthy controls were studied. The (AT) repeats in the 3' untranslated region of exon 4 of the CTLA-4 gene were amplified by allele-specific polymerase chain reaction (PCR). The amplified products were electrophoresed on a 12% polyacrylamide gel, followed by silver staining. Twenty alleles were found in Chinese patients and healthy controls. The 122-bp allele was increased in UC compared with healthy controls (9.5% vs 0.7%, P = 0.0001/Pc = 0.002, OR = 14.591, 95%CI 3.357-63.420). The frequency of the longer alleles (>or=118 bp) of UC was higher than that in healthy controls (26% vs 4%, P = 0.0001/Pc = 0.0002, OR = 7.644, 95%CI 3.950-14.792), but was not associated with location and severity of the disease. Furthermore, the longer alleles were not associated with haplotypes of C-318T/A+49G of the CTLA-4 gene in Chinese patients with UC. The longer alleles of the CTLA-4 gene microsatellite polymorphism were strongly associated with UC in Chinese patients.

Adolescent↗