Biomedical subjects

Feng Liu

Publications and source records attributed to Feng Liu.

At least 163 records · Page 9Linked to original sources

PubMed2004

Effect of variations in the structure of a polyleucine-based alpha-helical transmembrane peptide on its interaction with phosphatidylglycerol bilayers.

High-sensitivity differential scanning calorimetry and Fourier transform infrared spectroscopy were used to study the interaction of a cationic alpha-helical transmembrane peptide, acetyl-Lys(2)-Leu(24)-Lys(2)-amide (L(24)), and members of the homologous series of anionic n-saturated diacyl phosphatidylglycerols (PGs). Analogues of L(24), in which the lysine residues were replaced by 2,3-diaminopropionic acid (L(24)DAP), or in which a leucine residue at each end of the polyleucine sequence was replaced by a tryptophan (WL(22)W), were also studied to investigate the roles of lysine side-chain snorkeling and aromatic side-chain interactions with the interfacial region of phospholipid bilayers. The gel/liquid-crystalline phase transition temperature of the host PG bilayers is altered by these peptides in a hydrophobic mismatch-dependent manner, as previously found with zwitterionic phosphatidylcholine (PC) bilayers. However, all three peptides reduce the phase transition temperature and enthalpy to a greater extent in anionic PG bilayers than in zwitterionic PC bilayers, with WL(22)W having the largest effect. All three peptides form very stable alpha-helices in PG bilayers, but small conformational changes are induced in response to a mismatch between peptide hydrophobic length and gel-state lipid bilayer hydrophobic thickness. Moreover, electrostatic and hydrogen-bonding interactions occur between the terminal lysine residues of L(24) and L(24)DAP and the polar headgroups of PG bilayers. However, such interactions were not observed in PG/WL(22)W bilayers, suggesting that the cation-pi interactions between the tryptophan and lysine residues predominate. These results indicate that the lipid-peptide interactions are affected not only by the hydrophobic mismatch between these peptides and the host lipid bilayer, but also by the tryptophan-modulated electrostatic and hydrogen-bonding interactions between the positively charged lysine residues at the termini of these peptides and the negatively charged polar headgroups of the PG bilayers.

Calorimetry, Differential Scanning↗

PubMed2004

Geometric constant defining shape transitions of carbon nanotubes under pressure.

We demonstrate that when a single-walled carbon nanotube is under pressure it undergoes a series of shape transitions, first transforming from a circle to an oval and then from an oval to a peanut. Most remarkably, the ratio of the area of the tube cross sections at the second transition over that at the first transition appears as a constant, independent of the tube radius. Its accurate value is computed to be G=0.819 469, by formulating a variational geometry problem to represent single-walled carbon nanotubes with a family of closed plane curves of fixed length and minimum bending energy. The implications of such a geometric constant in designing nanotube electromechanical pressure sensors are discussed.

Journal Article↗

PubMed2004

Protein kinase A attenuates endothelial cell barrier dysfunction induced by microtubule disassembly.

Cross talk between the actin cytoskeleton and the microtubule (MT) network plays a critical role in regulation of endothelial permeability. We have previously demonstrated that MT disruption by nocodazole results in increases in MLC phosphorylation, actomyosin contraction, cell retraction, and paracellular gap formation, cardinal features of endothelial barrier dysfunction (Verin AD, Birukova A, Wang P, Liu F, Becker P, Birukov K, and Garcia JG. Am J Physiol Lung Cell Mol Physiol 281: L565-L574, 2001; Birukova AA, Smurova K, Birukov KG, Usatyuk P, Liu F, Kaibuchi K, Ricks-Cord A, Natarajan V, Alieva A, Garcia JG, and Verin AD. J Cell Physiol. In press.). Although activation of PKA opposes barrier-disrupting effects of edemagenic agents on confluent EC monolayers, information about the molecular mechanisms of PKA-mediated EC barrier protection is limited. Our results suggest that MT disassembly alters neither intracellular cAMP levels nor PKA enzymatic activity; however, elevation of cAMP levels and PKA activation by either cholera toxin or forskolin dramatically attenuates the decline in transendothelial electrical resistance induced by nocodazole in human pulmonary EC. Barrier-protective effects of PKA on EC were associated with PKA-mediated inhibition of nocodazole-induced stress fiber formation, Rho activation, phosphorylation of myosin phosphatase regulatory subunit at Thr696, and decreased MLC phosphorylation. In addition, forskolin pretreatment attenuated MT disassembly induced by nocodazole. These results suggest a critical role for PKA activity in stabilization of MT cytoskeleton and provide a novel mechanism for cAMP-mediated regulation of Rho-induced actin cytoskeletal remodeling, actomyosin contraction, and EC barrier dysfunction induced by MT disassembly.

Actins↗

PubMed2004

Impact of spatially correlated noise on neuronal firing.

We explore the impact of spatially correlated noise on neuronal firing when uncoupled Hodgkin-Huxley model neurons are subjected to a common subthreshold signal. Noise can play a positive role in optimizing neuronal behavior. Although the output signal-to-noise ratio decreases with enhanced noise correlation, both the degree of synchronization among neurons and the spike timing precision are improved. This suggests that there can exist precisely synchronized firings in the presence of correlated noise and that the nervous system can exploit temporal patterns of neural activity to convey more information than just using rate codes. The mechanisms underlying these noise-induced effects are also discussed in detail.

Action Potentials↗

PubMed2004

Local strain-mediated chemical potential control of quantum dot self-organization in heteroepitaxy.

From observations of self-assembly of Ge quantum dots directed by substrate morphology, we propose the concept of control of ordering in heteroepitaxy by a local strain-mediated surface chemical potential. Using quite simple lithography, we demonstrate directed quantum dot ordering. The strain part of the chemical potential is caused by the spatially nonuniform relaxation of the strained layer, which in our study is the Ge wetting layer, but, more generally, can be a deposited strained buffer layer. This model provides a consistent picture of prior literature.

Journal Article↗

PubMed2004

Grb10: more than a simple adaptor protein.

Grb10 is a member of a superfamily of adaptor proteins that includes Grb7 and Grb14. This family of proteins shares a common overall structure, including an N-terminal region harboring a conserved proline-rich motif, a central Pleckstrin homology (PH) domain, a C-terminal Src homology 2 (SH2) domain, and a conserved region located between the PH and the SH2 domains (BPS). Grb10 directly interacts with a number of mitogenic receptor tyrosine kinases including the insulin (IR) and insulin-like growth factor-I (IGF-IR) receptor. Grb10 binds to the regulatory kinase loop of the insulin receptor (IR) via its SH2 and BPS domains. In addition to receptor tyrosine kinases, Grb10 has also been found to interact with non-receptor tyrosine kinases such as Tec and Bcr-Abl, and other cellular signaling molecules such as Raf-1 and the mitogen activated protein (MAP) kinase kinase, MEK. Overexpression of Grb10 has been shown to inhibit or stimulate insulin/IGF-I signaling depending on the expression levels of the specific isoforms, specific cell context, and/or physiologic endpoint. Genetic imprinting of Grb10 has been linked to the congenital disease, Silver-Russell syndrome, which is characterized by pre- and post-natal growth deficiency. This data suggests that Grb10 may function during embryogenesis in regulating insulin/IGF-I signaling as these growth factors play important roles during development. A role of Grb10 as a potent growth inhibitor during was implicated when disruption of the mGrb10 gene in mice resulted in overgrowth of mutant embryos and neonates. Grb10 is expressed in the central nervous system of mice and rats, which suggests that this protein may regulate neuronal insulin signaling and energy metabolism, consistent with its reported role in metabolic insulin action in fat and muscle cells. An important area of future investigation will be to elucidate the mechanism underlying Grb10's ability to regulate peptide hormone action including insulin/IGF-I signaling and to study the physiological role of this adaptor protein in cellular and animal models.

Animals↗

PubMed2004

Microtubule disassembly induces cytoskeletal remodeling and lung vascular barrier dysfunction: role of Rho-dependent mechanisms.

Barrier dysfunction of pulmonary endothelial monolayer is associated with dramatic cytoskeletal reorganization, activation of actomyosin contractility, and gap formation. The linkage between the microtubule (MT) network and the contractile cytoskeleton has not been fully explored, however, clinical observations suggest that intravenous administration of anti-cancer drugs and MT inhibitors (such as the vinca alkaloids) can lead to the sudden development of pulmonary edema in breast cancer patients. In this study, we investigated the crosstalk between MT and actomyosin cytoskeleton and characterized specific molecular mechanisms of endothelial cells (EC) barrier dysfunction induced by MT inhibitor nocodazole (ND). Our results demonstrate that MT disassembly by ND induced rapid decreases in transendothelial electrical resistance (TER) and actin cytoskeletal remodeling, indicating EC barrier dysfunction. These effects involved ND-induced activation of Rho GTPase. Rho-mediated activation of its downstream target, Rho-kinase, induced phosphorylation of Rho-kinase effector EC MLC phosphatase (MYPT1) at Thr(696) and Thr(850) resulting in MYPT1 inactivation. Phosphatase inhibition leaded to accumulation of diphospho-MLC, which induced acto-myosin polymerization, stress fiber formation and gap formation. Inhibition of Rho-kinase by Y27632 abolished ND-induced MYPT1 phosphorylation, MLC phosphorylation, and stress fiber formation. In addition, MT preservation via the MT stabilizer paclitaxel, Rho inhibition (via C3 exotoxin, or dominant negative (DN)-Rho, or DN-Rho-kinase) attenuated ND-induced TER decreases, stress fiber formation and MLC phosphorylation. Collectively, our results demonstrate a leading role for Rho-dependent mechanisms in crosstalk between the MT and actomyosin cytoskeleton, and suggest Rho-kinase and MYPT1 as major Rho effectors mediating pulmonary EC barrier disruption in response to ND-induced MT disassembly.

Actin Cytoskeleton↗

PubMed2004

Characterization of a salivary lysozyme in larval Helicoverpa zea.

The cDNA sequence of a salivary lysozyme in Helicoverpa zea (Lepidoptera: Noctuidae) was determined. The full-length cDNA is 1,032 bp, and it encodes a protein of 142 amino acids. This lysozyme has 90% identity with Heliothis virescens lysozyme and 76% identity with Manduca sexta lysozyme. There is a signal peptide of 20 amino acids at the N-terminus. The mature protein is about 14.4 kDa without the signal peptide. The pI value is greater than 9.5 as determined by isoelectric focusing. From genomic DNA, two introns and three exons were within the open reading frame (ORF). Southern blot analysis indicated that it is a single-copy gene. A time-course study revealed that the H. zea lysozyme gene was differentially expressed in the labial glands during the development of fifth-instar larvae, with the peak level of lysozyme mRNA being detected on day 1. Dot blot analysis showed different levels of H. zea lysozyme expression when the caterpillars fed on different plants. Further, the H. zea lysozyme could be detected with antibodies raised against the M. sexta lysozyme, and it was one of the most abundant secreted proteins in saliva collected directly from the caterpillar's spinneret. The potential role of the lysozyme on host plants in mediating susceptibility to bacterial disease is discussed in the context of tritrophic interactions.

Amino Acid Sequence↗

PubMed2004

The role of insulin and insulin-like growth factor-I in mammalian ageing.

Research with invertebrates over the past 10 years has suggested that alterations in insulin and/or insulin-like growth factor I (IGF-I) signalling result in increased lifespan and retard ageing. In this chapter, we describe the current research in mammalian systems with respect to the role of insulin or IGF-I in ageing. Using rodent models of caloric restriction and genetic mouse models, e.g. the Ames and Snell dwarf mice, fat-specific insulin receptor knockout mice (FIRKO) and mice that are heterozygous for the IGF-I receptor (Igf1r+/-), investigators have shown that a reduction in plasma levels of insulin and/or IGF-I or reductions in insulin/IGF-I signalling appear to be correlated with increased longevity and retarded ageing.

Aging↗

PubMed2004

Expression of NALP1 in cerebellar granule neurons stimulates apoptosis.

NAcht Leucine-rich-repeat Protein 1 (NALP1) contains a putative nucleotide binding site, a region of leucine-rich repeats, and death domain folds at both termini providing protein/protein association functions such as caspase recruitment. We report here that NALP1 gene expression was induced in primary cerebellar granule neurons (CGN) upon injury. Up-regulation of NALP1 was also observed in a model of transient focal ischemia induced by middle cerebral artery occlusion. We investigated the biological consequence of over-expression of NALP1 in both HeLa cells and in CGN. Expression of recombinant NALP1 stimulated cell death in both HeLa cells and CGN by an apoptotic mechanism, demonstrated by the induction of apoptotic nuclear morphology and activation of the apoptotic enzyme caspase-3. Also described here are studies on the mechanism of action studies including deletion analyses and investigations of nucleotide binding, which begin to elucidate a regulatory function for NALP1 in neuronal apoptosis.

Adaptor Proteins, Signal Transducing↗

PubMed2004

A distributed equivalent magnetic current based FDTD method for the calculation of E-fields induced by gradient coils.

This paper evaluates a new, low-frequency finite-difference time-domain method applied to the problem of induced E-fields/eddy currents in the human body resulting from the pulsed magnetic field gradients in MRI. In this algorithm, a distributed equivalent magnetic current is proposed as the electromagnetic source and is obtained by quasistatic calculation of the empty coil's vector potential or measurements therein. This technique circumvents the discretization of complicated gradient coil geometries into a mesh of Yee cells, and thereby enables any type of gradient coil modelling or other complex low frequency sources. The proposed method has been verified against an example with an analytical solution. Results are presented showing the spatial distribution of gradient-induced electric fields in a multi-layered spherical phantom model and a complete body model.

Algorithms↗

PubMed2004

Mechanism of liver gene transfer by mechanical massage.

Many metabolic diseases are caused by defects in the metabolic pathways in the liver. Others result from the absence of specific proteins normally produced and secreted by the liver. Because these metabolic disorders are usually caused by single gene defect, they are ideal candidates for gene therapy. We have previously shown that mouse liver can be transfected by mechanically massaging the liver (MML) after intravenous injection of naked plasmid DNA. We now show a significant linear relationship between the level of liver gene expression and the venous blood pressure, supporting the idea that gene transfer by MML is due, at least in part, to pressure-mediated effect. Liver transfection could not be blocked by co-injection of excess irrelevant DNA or poly I, suggesting that there is no involvement of receptors, including the scavenger receptor, in MML. Moreover, the level of gene expression could be further enhanced by a combination of MML and an increase in DNA retention-time in the liver. Persistence of gene expression could be significantly improved using an EBV-based plasmid vector. Our data suggest the mechanical massage produces transient membrane defects through which naked DNA can enter into the liver cells by simple diffusion.

Animals↗

PubMed2004

Overexpression of GSK3betaS9A resulted in tau hyperphosphorylation and morphology reminiscent of pretangle-like neurons in the brain of PDGSK3beta transgenic mice.

It has been demonstrated that GSK3beta is involved in Alzheimer Disease (AD) pathogenesis. In order to understand the underlying mechanism, we have generated and characterized transgenic mice in which the constitutively active human GSK3beta (with S9A mutation) was overexpressed in the brain under the control of the platelet-derived growth factor (PDGF) B-chain promoter. Varying levels of human GSK3betaS9A transgene protein expression was observed in six of the seven founders generated. Line 3083, 3107, 3112 and 3125 displayed higher GSK3betaS9A protein expression levels. Immunostaining analysis demonstrated that transgene expression was observed mainly in cortex and hippocampus of transgenic brain. Expression of human GSK3beta transgene did not significantly change the brain total GSK3beta protein levels in any of the generated mouse lines, as comparing to age matched wild type mice. Although significant kinase activity was detected in human GSK3betaS9A transgene protein extracted from brains of all six expressing lines, significant increase in total GSK3betaS9A kinase activity was observed only in the offspring of line 3083 and 3107. By analyzing the offspring from several transgenic mouse lines, including lines other than 3083 and 3107, it was found that overexpressed constitutively active human GSK3betaS9A resulted in hyperphosphorylation of tau and morphology reminiscent of pretangle-like neurons in cortex and hippocampus.

Amino Acid Substitution↗

PubMed2004

p38 MAP kinase-dependent regulation of endothelial cell permeability.

We have previously shown that thrombin induces endothelial cell barrier dysfunction via cytoskeleton activation and contraction and have determined the important role of endothelial cell myosin light chain kinase (MLCK) in this process. In the present study we explored p38 MAP kinase as a potentially important enzyme in thrombin-mediated endothelial cell contractile response and permeability. Thrombin induces significant p38 MAP kinase activation in a time-dependent manner with maximal effect at 30 min, which correlates with increased phosphorylation of actin- and myosin-binding protein, caldesmon. Both SB-203580 and dominant negative p38 adenoviral vector significantly attenuated thrombin-induced declines in transendothelial electrical resistance. Consistent with these data SB-203580 decreased actin stress fiber formation produced by thrombin in endothelium. In addition, dominant negative p38 had no effect on thrombin-induced myosin light chain diphosphorylation. Thrombin-induced total and site-specific caldesmon phosphorylation (Ser789) as well as dissociation of caldesmon-myosin complex were attenuated by SB-203580 pretreatment. These results suggest the involvement of p38 MAP kinase activities and caldesmon phosphorylation in the MLCK-independent regulation of thrombin-induced endothelial cell permeability.

Animals↗

PubMed2004

Effect of variations in the structure of a polyleucine-based alpha-helical transmembrane peptide on its interaction with phosphatidylethanolamine Bilayers.

High-sensitivity differential scanning calorimetry and Fourier transform infrared spectroscopy were used to study the interaction of a cationic alpha-helical transmembrane peptide, acetyl-Lys2-Leu24-Lys2-amide (L24), and members of the homologous series of zwitterionic n-saturated diacyl phosphatidylethanolamines (PEs). Analogs of L24, in which the lysine residues were replaced by 2,3-diaminopropionic acid (acetyl-DAP2-Leu24-DAP2-amide (L24DAP)) or in which a leucine residue at each end of the polyleucine sequence was replaced by a tryptophan (Ac-K2-W-L22-W-K2-amide (WL22W)), were also studied to investigate the roles of lysine side-chain snorkeling and aromatic side-chain interactions with the interfacial region of phospholipid bilayers. The gel/liquid-crystalline phase transition temperature of the PE bilayers is altered by these peptides in a hydrophobic mismatch-independent manner, in contrast to the hydrophobic mismatch-dependent manner observed previously with zwitterionic phosphatidylcholine (PC) and anionic phosphatidylglycerol (PG) bilayers. Moreover, all three peptides reduce the phase transition temperature to a greater extent in PE bilayers than in PC and PG bilayers, indicating a greater disruption of PE gel-phase bilayer organization. Moreover, the lysine-anchored L24 reduces the phase transition temperature, enthalpy, and the cooperativity of PE bilayers to a much greater extent than DAP-anchored L24DAP, whereas replacement of the terminal leucines by tryptophan residues (Ac-K2-W-L22-W-K2-amide) only slightly attenuates the effects of this peptide on the chain-melting phase transition of the host PE bilayers. All three peptides form very stable alpha-helices in PE bilayers, but small conformational changes occur in response to mismatch between peptide hydrophobic length and gel-state lipid bilayer hydrophobic thickness. These results suggest that the lysine snorkeling plays a significant role in the peptide-PE interactions and that cation-pi-interactions between lysine and tryptophan residues may modulate these interactions. Altogether, these results suggest that the lipid-peptide interactions are affected not only by the hydrophobic mismatch between these peptides and the host lipid bilayer but also by the electrostatic and hydrogen-bonding interactions between the positively charged lysine residues at the termini of these peptides and the polar headgroups of PE bilayers.

Binding Sites↗

PubMed2004

[Influence of terrestrial nutrient input on biogenic production of dimethylsulfide in Quingdao coastal water].

Nearshore water is one of the most important emission area of dimethylsulfide(DMS), at the same time, nearshore water is highly disturbed by human activities. The objectives of this study were to investigate the DMS concentration of coastal water and try to analyze the factors governing its distribution. Four situ investigations were made in the coastal water of Qingdao, which is located at west coast of Yellow Sea. DMS concentrations of surface water showed a clear seasonal variation with peak values during the summer. Spatial and temporal distributions of DMS in three studied areas(havey polluted area, light polluted area, and clean area) were irregular, but when the concentrations of DMS were moralized to chlorophyll a as a measure of phytoplankton biomass, there was significant difference of DMS/Chl a among the three areas, with the nutrient concentration improved, the DMS/Chl a decreased. And there was the positive relation between transparency and DMS/Chl a, especially in summer.

Biomass↗

PubMed2004

[Sildenafil citrate for erectile dysfunction in male kidney transplant recipients].

OBJECTIVE: To evaluate the efficacy and safety of sildenafil citrate in man kidney transplant recipients with erectile dysfunction. METHODS: One hundred and seventy married males, aged 26 approximately 50 years, who had received kidney transplantations at least half a year before and whose serum creatinine was under 133 umol/l, were selected randomly in the study. Their sexual function was investigated according to the International Index of Erectile Function-5 (IIEF-5), and those with erectile dysfunction (ED) were treated with oral sildenafil citrate for 6 months. The efficacy was assessed by IIEF-5. RESULTS: Fifty-three men with ED received oral sildenafil citrate for 6 months. At the end of the treatment, each index in IIEF-5 increased significantly. There were no interactions between sildenafil and cyclosporine and there was no significant adverse effect of sildenafil on the graft function. CONCLUSION: Sildenafil is an effective and safe agent for the treatment of ED in kidney transplant recipients.

Adult↗

PubMed2004

[Single-lung transplantation and contralateral lung volume reduction for emphysema].

OBJECTIVE: To report the operation technique, patient selection and curative effect of single-lung transplantation with contralateral lung volume reduction for a patient with end-stage emphysema. METHODS: A 47-year-old male patient who was dependent on mechanical ventilation because of end-stage emphysema received left-lung transplantation on 20 June, 2003. The surgical technique used was similar to that mentioned in the literature. The donor lung was perfused by low-potassium dextran solutions (LPD) with a cold ischemic time of 390 minutes. The patient received contralateral lung volume reduction because of subacute native lung hyperinflation on the 7th day after operation. He was received tracheostomy on 15th day after operation and was weaned from ventilator on the 26th day post-operation. Immunosuppression included cyclosporine, mycophenolate mofetil and corticosteroid. The acute rejection occurred on the 9th and 15th days after operation and was cured successfully. RESULTS: The lung function was improved significantly and the patient was discharged from hospital 71 days after operation. CONCLUSIONS: Single-lung transplantation combined with contralateral lung volume reduction for end-stage emphysema is an effective measure for subacute native lung hyperinflation. Further follow-up is required to assess the long term results of this procedure.

Graft Rejection↗