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Yi Tang

Publications and source records attributed to Yi Tang.

At least 19 recordsLinked to original sources
PubMed2026

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N = 41) from a randomized controlled trial who underwent ultra-high-field 7 T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging↗
PubMed2025

Biosynthesis of the 5-Isoxazolidinone-Containing Hexacyclic Structure of Parnafungin.

Parnafungins A-D (1-4) are fungal natural products that inhibit eukaryotic poly(A)-polymerase and were first discovered by Merck & Co., Inc., through a Candida albicans Fitness Test (CaFT) screening program. The biological activity of parnafungins is a result of the unique fused hexacyclic structure highlighted by a 5-isoxazolidinone (5ILD) N-heterocycle. In this work, we characterize the complete biosynthetic pathway of parnafungins through heterologous reconstitution and enzymatic assays. Nearly half of the 26-gene biosynthetic gene cluster of parnafungin is responsible for the production of a known polyketide natural product, blennolide C. Starting from the blennolide C fragment, a three-enzyme cascade involving CoA-ligase ParJ, P450 ParO, and DUF829 ParD catalyzes the formal biaryl cross-coupling between blennolide C and anthranilate. Subsequent oxidative cyclization generates a phenanthridine product that is then reduced by atypical short-chain reductase ParT. N-Hydroxylation by flavin-dependent monooxygenase ParB and subsequent lactonization catalyzed by a homologue of dienenolactone hydrolase ParF form the 5ILD ring and complete the biosynthesis of 1 and 2. Methylation of 1 forms parnafungin C (3), and lastly epoxidation forms parnafungin D (4). Together, our work revealed the chemical logic and enzymology in extending the biosynthetic pathway of a well-characterized natural product, blennolide C, to introduce considerable additional structural diversity that affords parnafungins with unique biological activity.

Molecular Structure↗
PubMed2006

Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis.

Upon DNA damage and other types of stress, p53 induces either cell-cycle arrest or apoptosis depending on the cellular context. However, the molecular mechanisms that govern the choice between cell-cycle arrest and apoptosis are not well understood. Here, we show that Tip60 is required for both cell growth arrest and apoptosis mediated by p53 and also induces its acetylation specifically at lysine 120 (K120) within the DNA-binding domain. Interestingly, this modification is crucial for p53-dependent apoptosis but is dispensable for its mediated growth arrest. K120 is a recurrent site for p53 mutation in human cancer, and the corresponding acetylation-defective tumor mutant (K120R) abrogates p53-mediated apoptosis, but not growth arrest. Thus, our study demonstrates that Tip60-dependent acetylation of p53 at K120 modulates the decision between cell-cycle arrest and apoptosis, and it reveals that the DNA-binding core domain is an important target for p53 regulation by posttranslational modifications.

Acetylation↗
PubMed2006

High-fat- and lipid-induced insulin resistance in rats: the comparison of glucose metabolism, plasma resistin and adiponectin levels.

AIMS: In animal models, both an acute elevation in plasma free fatty acid (FFA) via intravenous infusion of a lipid emulsion and a chronic elevation in plasma FFA via high-fat feeding have been shown to induce skeletal muscle and liver insulin resistance. However, there have been very few studies comparing the effects of high-fat- and lipid-induced insulin resistance on glucose metabolism and adipocytokines. METHODS: In the current study, we used lipid infusion and a high-fat feed in combination with the hyperinsulinemic-euglycemic clamp technique to assess the impact of acute and chronically elevated FFA levels on overall glucose metabolism and insulin action; two adipocytokines, resistin and adiponectin, were used. RESULTS: At baseline, plasma FFA levels were significantly increased in the high-fat diet (HF) group compared to the control group (p < 0.05). During clamp steady-state, the FFA levels were reduced by approximately 25% in the control and approximately 48% in the HF groups. In contrast, there was a significant increase in the plasma FFA level in the lipid-infused group (from 0.82 +/- 0.03 to 2.87 +/- 0.18 mmol/l). The glucose infusion rates (GIRs) in the HF and lipid groups were obviously lower than in the control group (p < 0.01). Moreover, GIR was lower in the lipid group compared with the HF group (p < 0.05). The rate of glucose disappearance (G(Rd)) was significantly lower in the lipid group compared with the control group. Hepatic glucose production in the control group was suppressed by approximately 15% compared with the HF and lipid groups where it was suppressed by only approximately 72 and approximately 91%, respectively. The resistin level of muscle tissues in the lipid group was significantly higher compared with the control and HF groups (both p < 0.05). After the insulin clamp, the circulating adiponectin level was significantly decreased in the lipid group compared with the control and HF groups (p < 0.05). CONCLUSIONS: Lipid infusion, which was more effective than a high-fat diet, can induce peripheral and hepatic insulin resistance in rats. Insulin-induced resistance might be associated with elevated resistin and decreased adiponectin.

Adiponectin↗
PubMed2006

Structural and functional studies on SCO1815: a beta-ketoacyl-acyl carrier protein reductase from Streptomyces coelicolor A3(2).

Aromatic polyketides are medicinally important natural products produced by type II polyketide synthases (PKSs). Some aromatic PKSs are bimodular and include a dedicated initiation module which synthesizes a non-acetate primer unit. Understanding the mechanism of this initiation module is expected to further enhance the potential for regiospecific modification of bacterial aromatic polyketides. A typical initiation module is comprised of a ketosynthase (KS), an acyl carrier protein (ACP), a malonyl-CoA:ACP transacylase (MAT), an acyl-ACP thioesterase, a ketoreductase (KR), a dehydratase (DH), and an enoyl reductase (ER). Thus far, the identities of the ketoreductase, dehydratase, and enoyl reductase remain a mystery because they are not encoded within the PKS biosynthetic gene cluster. Here we report that SCO1815 from Streptomyces coelicolor A3(2), an uncharacterized homologue of a NADPH-dependent ketoreductase, recognizes and reduces the beta-ketoacyl-ACP intermediate from the initiation module of the R1128 PKS. SCO1815 exhibits moderate specificity for both the acyl chain and the thiol donor. The X-ray crystal structure of SCO1815 was determined to 2.0 A. The structure shows that SCO1815 adopts a Rossmann fold and suggests that a conformational change occurs upon cofactor binding. We propose that a positively charged patch formed by three conserved residues is the ACP docking site. Our findings provide new engineering opportunities for incorporating unnatural primer units into novel polyketides and shed light on the biology of yet another cryptic protein in the S. coelicolor genome.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗
PubMed2006

HS-48 alone has no enhancement role on the expression of human alpha-globin gene cluster.

To investigate the in vivo function of the newly defined DNase I hypersensitive site HS-48 on the whole human alpha-globin gene cluster, the region containing all the other known 5 hypersensitive sites HS-4 to HS-40 was deleted from a 117 kb bacterial artificial chromosome clone bearing the whole human alpha-globin gene cluster. Transgenic mice were generated from this construct. The RNase protection assays showed that with HS-48 left and all the other 5 hypersensitive sites deleted, the expression of human alpha-like globin genes was completely silenced in embryonic, fetal and adult stages in all tissues. This finding indicates that HS-48 alone has no enhancer activity on the expression of human alpha-like globin genes, and that the region of HS-4 to HS-40 already contains all the upstream cis-elements needed for regulating human alpha-like globin genes.

Animals↗
PubMed2006

Clonorchis sinensis: codon usage in nuclear genes.

Codon usage in Clonorchis sinensis was analyzed using 12,515 codons from 38 coding sequences. Total GC content was 49.83%, and GC1, GC2 and GC3 contents were 56.32%, 43.15% and 50.00%, respectively. The effective number of codons converged at 51-53 codons. When plotted against total GC content or GC3, codon usage was distributed in relation to GC3 biases. Relative synonymous codon usage for each codon revealed a single major trend, which was highly correlated with GC content at the third position when codons began with A or U at the first two positions. In codons beginning with G or C base at the first two positions, the G or C base rarely occurred at the third position. These results suggest that codon usage is shaped by a bias towards G or C at the third base, and that this is affected by the first and second bases.

Amino Acids↗
PubMed2006

Cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging.

Approaches to improve the oncolytic potency of replication-competent adenoviruses include the insertion of therapeutic transgenes into the viral genome. Little is known about the levels and duration of in vivo transgene expression by cells infected with such "armed" viruses. Using a tumor-selective adenovirus encoding firefly luciferase (AdDelta24CMV-Luc) we investigated these questions in an intracranial mouse model for malignant glioma. Luciferase expression was detected by bioluminescence imaging, and the effect of the immunosuppressive agent cyclophosphamide (CPA) on transgene expression was assessed. Intratumoral AdDelta24CMV-Luc injection led to a localized dose-dependent expression of luciferase. Surprisingly, this expression decreased rapidly during the course of 14 days. In contrast, mice injected with nonreplicating Ad.CMV-Luc demonstrated stable transgene expression. Treatment of mice with CPA in combination with AdDelta24CMV-Luc retarded the loss of transgene expression. Staining of mouse brains for inflammatory cells demonstrated decreased tumor infiltration by immune cells in CPA-treated mice. Moreover, in immunodeficient NOD/SCID mice loss of transgene expression was less rapid and not prevented by CPA treatment. Together, our data demonstrate that transgene expression and viral replication decrease rapidly after intratumoral injection of oncolytic adenovirus in mouse brains and that treatment with the immunomodulator CPA prolongs viral-mediated gene expression.

Adenoviridae↗
PubMed2006

Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog.

Thirty to eighty-seven percent of patients treated by radical prostatectomy experience erectile dysfunction (ED). The reduced efficacy of treatments in this population makes novel therapeutic approaches to treat ED essential. We propose that abundant apoptosis observed in penile smooth muscle when the cavernous nerve (CN) is cut (mimicking the neural injury which can result from prostatectomy) is a major contributing factor to ED development. We hypothesize that decreased Sonic hedgehog (SHH) signaling is a cause of ED in neurological models of impotence by increasing apoptosis in penile smooth muscle. We examined this hypothesis in a bilateral CN injury model of ED. We found that the active form of SHH protein was significantly decreased 1.2-fold following CN injury, that SHH inhibition causes a 12-fold increase in smooth muscle apoptosis in the penis, and that SHH treatment at the time of CN injury was able to decrease CN injury-induced apoptosis (1-3-fold) in a dose-dependent manner. These results show that SHH stabilizes the alterations of the corpora cavernosal smooth muscle following nerve injury.

Animals↗
PubMed2006

Cell cycle deregulation and loss of stem cell phenotype in the subventricular zone of TGF-beta adaptor elf-/- mouse brain.

The mammalian forebrain subependyma contains neural stem cells and other proliferating progenitor cells. Recent studies have shown the importance of TGF-beta family members and their adaptor proteins in the inhibition of proliferation in the nervous system. Previously, we have demonstrated that TGF-beta induces phosphorylation and association of ELF (embryonic liver fodrin) with Smad3 and Smad4 resulting in nuclear translocation. Elf(-/-) mice manifest abnormal neuronal differentiation, with loss of neuroepithelial progenitor cell phenotype in the subventricular zone (SVZ) with dramatic marginal cell hyperplasia and loss of nestin expression. Here, we have analyzed the expression of cell cycle-associated proteins cdk4, mdm2, p21, and pRb family members in the brain of elf(-/-) mice to verify the role of elf in the regulation of neural precursor cells in the mammalian brain. Increased proliferation in SVZ cells of the mutant mice coincided with higher levels of cdk4 and mdm2 expression. A lesser degree of apoptosis was observed in the mutant mice compared to the wild-type control. Elf(-/-) embryos showed elevated levels of hyperphosphorylated forms of pRb, p130 and p107 and decreased level of p21 compared to the wild-type control. These results establish a critical role for elf in the development of a SVZ neuroepithelial stem cell phenotype and regulation of neuroepithelial cell proliferation, suggesting that a mutation in the elf locus renders the cells susceptible to a faster entry into S phase of cell cycle and resistance to senescence and apoptotic stimuli.

Animals↗
PubMed2006

TGF-beta signaling pathway inactivation and cell cycle deregulation in the development of gastric cancer: role of the beta-spectrin, ELF.

We have shown that loss of ELF, a stem cell adaptor protein, disrupts TGF-beta signaling through Smad3 and Smad4 localization. Notably elf(+/-)/smad4(+/-) mice develop gastric cancer presenting this as an important model for analyzing molecular event in gastric carcinogenesis. To gain further insight into the functional role of ELF in gastric cancer suppression, we carried out a detailed characterization of cell cycle events leading to gastric tumorigenesis. elf(-/-) cells and elf(+/-)/smad4(+/-) mice demonstrate a marked alteration of cell cycle regulators, such as Cdk4, K-Ras, and p21. Levels of Cdk4 increased compared to normal controls, suggesting loss of ELF results in functional abnormalities in cell cycle regulation. We further demonstrate that the elf(-/-) MEFs show a disruption of G1/S cell cycle transition and a significant reduction in senescence. Thus, in response to ELF deficiency, the abnormalities of G1/S checkpoint and senescence contribute their increment of susceptibility to malignant transformation.

Aging↗
PubMed2006

A dishevelled-1/Smad1 interaction couples WNT and bone morphogenetic protein signaling pathways in uncommitted bone marrow stromal cells.

Genetic evidence from both humans and mice suggests that Wnt/beta-catenin and bone morphogenetic protein (BMP) signaling pathways are essential for bone marrow mesenchymal stem cells to differentiate into osteoblasts. Here we describe a mechanism through which BMPs antagonize Wnt signaling and retard bone marrow mesenchymal stem cell proliferation. Treatment with Wnt3a, but not BMP-2, stimulated Lef1-mediated transcriptional activity, whereas co-stimulation with both Wnt3a and BMP-2 markedly reduced Wnt3a-induced reporter activity. Immunoprecipitation assays in 293T cells transfected with individual Smads and Wnt pathway components revealed a specific interaction between Dvl-1 and Smad1 that was dependent on the presence of Wnt3a or BMP-2. Under unstimulated conditions, Dvl-1 and Smad1 are co-immunoprecipitated and form a complex through the linker region of Smad1. Wnt3a treatment transiently disrupted the Dvl-1/Smad1 interaction coincident with nuclear accumulation of beta-catenin. In contrast, when cells were exposed to both Wnt3a and BMP-2, there was an enhanced accumulation of the Dvl-1-Smad1 complex and a decreased nuclear accumulation of beta-catenin. Expression of a mutant Smad1 protein, which cannot be phosphorylated in response to BMP, eliminated the inhibitory effect of BMP on Wnt-inducedbeta-catenin accumulation and transcriptional activity. These results identify a potential mechanism whereby BMP-2 antagonizes Wnt signaling in osteoblast progenitors by promoting an interaction between Smad1 and Dvl-1 that restricts beta-catenin activation.

Adaptor Proteins, Signal Transducing↗
PubMed2006

TGFbeta/BMP inhibits the bone marrow transformation capability of Hoxa9 by repressing its DNA-binding ability.

Homeobox (Hox) gene mutations and their altered expressions are frequently linked to human leukemia. Here, we report that transforming growth factor beta (TGFbeta)/bone morphogenetic protein (BMP) inhibits the bone marrow transformation capability of Hoxa9 and Nup98-Hoxa9, the chimeric fusion form of Hoxa9 identified in human acute myeloid leukemia (AML), through Smad4, the common Smad (Co-Smad) in the TGFbeta/BMP signaling pathway. Smad4 interacts directly with the homeodomain of Hoxa9 and blocks the ability of Nup98-Hoxa9 to bind DNA, thereby suppressing its ability to regulate downstream gene transcription. Mapping data revealed that the amino-terminus of Smad4 mediates this interaction and overexpression of the Hoxa9 interaction domain of Smad4 was sufficient to inhibit the enhanced serial replating ability of primary bone marrow cells induced by Nup98-Hoxa9. These studies establish a novel mechanism by which TGFbeta/BMP regulates hematopoiesis and suggest that modification of Hox DNA-binding activity may serve as a novel therapeutic intervention for those leukemias that involve deregulation of Hox.

Animals↗
PubMed2006

Zeolite nanoparticle modified microchip reactor for efficient protein digestion.

An enzymatic microreactor has been fabricated based on the poly(methyl methacrylate) (PMMA) microchchip surface-modified with zeolite nanoparticles. By introducing the silanol functional groups, the surface of PMMA microchannel has been successfully modified with silicalite-1 nanoparticle for the first time due to its large external surface area and high dispersibility in solutions. Trypsin can be stably immobilized in the microchannel to form a bioreactor using silica sol-gel matrix. The immobilization of enzyme can be realized with a stable gel network through a silicon-oxygen-silicon bridge via tethering to those silanol groups, which has been investigated by scanning electron microscopy and microchip capillary electrophoresis with laser-induced fluorescence detection. The maximum proteolytic rate constant of the immobilized trypsin is measured to be about 6.6 mM s(-1). Using matrix assisted laser desorption and ionization time-of-flight mass spectrometry, the proposed microreactor provides an efficient digestion of cytochrome c and bovine serum albumin at a fast flow rate of 4.0 microL min(-1), which affords a very short reaction time of less than 5 s.

Amino Acid Sequence↗
PubMed2006

Iron-assisted vapor-phase hydrothermal method: a low-temperature approach to synthesize blue light emissive SiOx nanowires with single-crystal structure of P2(1)2(1)2.

A novel and facile approach, named iron-assisted vapor-phase hydrothermal method, is proposed to fabricate the long and stable bright blue light emitting SiOx nanowires (SiONWs) at a low temperature. The obtained SiONWs possess a brand-new single-crystalline structure of space group P21212. This new type of bright blue light emitting SiONW with a new single-crystalline structure may initiate a new 1D optical material and offer new opportunities for the research in science and technology.

Journal Article↗
PubMed2006

Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim.

Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, promotes invasion, metastasis, and growth and survival of malignant cells and confers resistance to some chemotherapeutic drugs. However, the molecular mechanisms underlying the actions of EMMPRIN are not fully understood. In this study we sought to determine whether EMMPRIN contributes to the malignant phenotype of breast cancer by inhibiting anoikis, a form of apoptosis induced by loss or alteration of cell-cell or cell-matrix anchorage, and to explore the signaling pathways involved. We found that in the absence of attachment, human breast carcinoma cells expressing high levels of EMMPRIN formed less compact aggregates with larger surface area and less fibronectin matrix assembly, had higher viability, and were resistant to anoikis. Knockdown of EMMPRIN expression by RNA interference (small interfering RNA or short hairpin RNA) sensitized cancer cells to anoikis, as demonstrated by activation of caspase-3, increased DNA fragmentation, and decreased cellular viability. Furthermore, we observed that the accumulation of Bim, a proapoptotic BH3-only protein, was reduced in EMMPRIN-expressing cells and that silencing of EMMPRIN expression elevated Bim protein levels and enhanced cellular sensitivity to anoikis. Treatment of cells with a MEK inhibitor (U0126) or proteasome inhibitor (epoxomicin) also up-regulated Bim accumulation and rendered cells more sensitive to anoikis. These results indicated that expression of EMMPRIN protects cancer cells from anoikis and that this effect is mediated at least in part by a MAP kinase-dependent reduction of Bim. Because anoikis deficiency is a key feature of neoplastic transformation and invasive growth of epithelial cancer cells, our study on the role of EMMPRIN in anoikis resistance and the mechanism involved underscores the potential of EMMPRIN expression as a prognostic marker and novel target for cancer therapy.

Anoikis↗