Covalent bond formation to a carbon nanotube metal.
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Journal Article↗
Biomedical subjects
H Hu
Publications and source records attributed to H Hu.
Tunneling into multiwalled carbon nanotubes: coulomb blockade and the Fano resonance.
Tunneling spectroscopy measurements of single tunnel junctions formed between multiwalled carbon nanotubes (MWNTs) and a normal metal are reported. Intrinsic Coulomb interactions in the MWNTs give rise to a strong zero-bias suppression of a tunneling density of states that can be fitted numerically to the environmental quantum-fluctuation theory. An asymmetric conductance anomaly near zero bias is found at low temperatures and interpreted as Fano resonance in the strong tunneling regime.
Journal Article↗
Glycoprotein IIb/IIIa inhibition attenuates platelet-activating factor-induced platelet activation by reducing protein kinase C activity.
Glycoprotein (GP)IIb/IIIa inhibition may abolish activated leukocyte-induced platelet activation, in which leukocyte-released platelet-activating factor (PAF) is a major mediator. The present study thus investigated if and how GPIIb/IIIa inhibitors interfere with PAF-induced platelet activation. Platelet and leukocyte activation were monitored by flow cytometry and immunoblotting. GPIIb/IIIa inhibitors (c7E3, non-peptide SR121566, and MAb RFGP56) attenuated PAF-induced, but not adenosine diphosphate (ADP)- or thrombin receptor activating peptide (TRAP)-induced platelet P-selectin expression in whole blood. GPIIb/IIIa blockade enhanced ADP- or TRAP-induced leukocyte CD11b expression, but not the response to PAF. GPIIb/IIIa blockade attenuated PAF-induced, but enhanced ADP- or TRAP-induced platelet-leukocyte aggregation. Under the present experimental conditions, thromboxane A2 receptor antagonism did not significantly influence PAF-induced platelet activation, and GPIIb/IIIa inhibition did not interfere with calcium mobilization/influx in platelets. Protein kinase C (PKC) blockade inhibited PAF-induced platelet P-selectin expression, and PAF-induced PKC activity was reduced by GPIIb/IIIa inhibition. PAF (=1 micro m) did not induce MEK 1/2 or ERK 1/2 phosphorylation, whilst thrombin induced marked responses, which were enhanced by GPIIb/IIIa blockade. Thus, GPIIb/IIIa inhibition attenuates PAF-induced platelet activation via inhibiting PKC activity. GPIIb/IIIa blockade enhances thrombin-induced platelet MEK 1/2 and ERK 1/2 activation, and augments ADP- and TRAP-induced leukocyte activation by enhancing platelet-leukocyte aggregation.
Adenosine Diphosphate↗
Chemistry of single-walled carbon nanotubes.
In this Account we highlight the experimental evidence in favor of our view that carbon nanotubes should be considered as a new macromolecular form of carbon with unique properties and with great potential for practical applications. We show that carbon nanotubes may take on properties that are normally associated with molecular species, such as solubility in organic solvents, solution-based chemical transformations, chromatography, and spectroscopy. It is already clear that the nascent field of nanotube chemistry will rival that of the fullerenes.
Journal Article↗
Neurobehavioural testing in workers occupationally exposed to lead.
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Humans↗
A high efficient approach used for BAC-contig extension of Oryza sativa with PCR screening the BAC clone pools.
To extend 8 BAC contigs, which were previously located in the 56.1-68 cM region of the chromosome 4 of the Oryza sativa indica GuangLuAi4, 14 pairs of primers were designed according to the terminal sequences of the existing seed BACs and were deliberately divided into 3 groups. With the 3 groups of primer mixtures, 233 pools of BAC DNA that represent 22 368 BAC clones from O.sativa indica GuangLuAi4 genomic library were screened. 65 positive clones corresponding to the 8 contigs were isolated and 29 clones of them were confirmed to be extended to the seed BACs by end-sequencing and fingerprinting. The protocol greatly enhanced the efficiency of the contig extension and was also superior for its specificity, sensitivity and reusability to the colony in situ hybridization which is a conventional method employed in contig extension and physical map construction.
Chromosomes, Artificial, Bacterial↗
A novel Dbl family RhoGEF promotes Rho-dependent axon attraction to the central nervous system midline in Drosophila and overcomes Robo repulsion.
The key role of the Rho family GTPases Rac, Rho, and CDC42 in regulating the actin cytoskeleton is well established (Hall, A. 1998. Science. 279:509-514). Increasing evidence suggests that the Rho GTPases and their upstream positive regulators, guanine nucleotide exchange factors (GEFs), also play important roles in the control of growth cone guidance in the developing nervous system (Luo, L. 2000. Nat. Rev. Neurosci. 1:173-180; Dickson, B.J. 2001. Curr. Opin. Neurobiol. 11:103-110). Here, we present the identification and molecular characterization of a novel Dbl family Rho GEF, GEF64C, that promotes axon attraction to the central nervous system midline in the embryonic Drosophila nervous system. In sensitized genetic backgrounds, loss of GEF64C function causes a phenotype where too few axons cross the midline. In contrast, ectopic expression of GEF64C throughout the nervous system results in a phenotype in which far too many axons cross the midline, a phenotype reminiscent of loss of function mutations in the Roundabout (Robo) repulsive guidance receptor. Genetic analysis indicates that GEF64C expression can in fact overcome Robo repulsion. Surprisingly, evidence from genetic, biochemical, and cell culture experiments suggests that the promotion of axon attraction by GEF64C is dependent on the activation of Rho, but not Rac or Cdc42.
Animals↗
Presynaptic Ca2+-activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release.
Large-conductance Ca(2+)-activated K(+) channels (BK, also called Maxi-K or Slo channels) are widespread in the vertebrate nervous system, but their functional roles in synaptic transmission in the mammalian brain are largely unknown. By combining electrophysiology and immunogold cytochemistry, we demonstrate the existence of functional BK channels in presynaptic terminals in the hippocampus and compare their functional roles in somata and terminals of CA3 pyramidal cells. Double-labeling immunogold analysis with BK channel and glutamate receptor antibodies indicated that BK channels are targeted to the presynaptic membrane facing the synaptic cleft in terminals of Schaffer collaterals in stratum radiatum. Whole-cell, intracellular, and field-potential recordings from CA1 pyramidal cells showed that the presynaptic BK channels are activated by calcium influx and can contribute to repolarization of the presynaptic action potential (AP) and negative feedback control of Ca(2+) influx and transmitter release. This was observed in the presence of 4-aminopyridine (4-AP, 40-100 microm), which broadened the presynaptic compound action potential. In contrast, the presynaptic BK channels did not contribute significantly to regulation of action potentials or transmitter release under basal experimental conditions, i.e., without 4-AP, even at high stimulation frequencies. This is unlike the situation in the parent cell bodies (CA3 pyramidal cells), where BK channels contribute strongly to action potential repolarization. These results indicate that the functional role of BK channels depends on their subcellular localization.
4-Aminopyridine↗
Chromatographic purification and properties of soluble single-walled carbon nanotubes.
We report an improved chromatographic purification of soluble single-walled carbon nanotubes (s-SWNTs) using gel permeation chromatography. Three fractions are separated by gel permeation chromatography, and the first fraction contains 74% of the s-SWNTs as detected by atomic force microscopy and UV and near-infrared spectroscopy.
Journal Article↗
Src kinases Fyn and Lck facilitate the accumulation of phosphorylated CTLA-4 and its association with PI-3 kinase in intracellular compartments of T-cells.
Src kinases bind to surface receptors and mediate signaling events at the surface of cells. Little is known regarding whether these kinases can mediate events within intracellular compartments. The T-cell antigen CTLA-4 resides primarily in the trans-Golgi network (TGN), and as such could serve as a model to study the intracellular function of src kinases in their ability to phosphorylate the receptor. In this study, we show that tyrosine kinases p56lck and p59fyn phosphorylate the cytoplasmic domain of CTLA-4 in T-cells. Most interestingly, these kinases are also found in the Golgi apparatus, the intracellular compartment where most of CTLA-4 is localized. Transfection of Lck or Fyn resulted in increased phosphorylation of intracellular CTLA-4 and recruitment of PI-3 kinase. By contrast, phosphorylation did not influence the presence of the receptor in the TGN. These data demonstrate that src kinases operate to modulate receptor binding to intracellular signaling proteins introducing the possibility that intracellular forms of receptors may generate growth signals.
Abatacept↗
Interaction between synaptic excitation and slow afterhyperpolarization current in rat hippocampal pyramidal cells.
1. Whole cell recordings from CA1 pyramidal cells were performed to investigate the interaction between excitatory postsynaptic potentials (EPSPs) or currents (EPSCs), and the slow Ca(2+)-dependent K(+) current, I(sAHP). Blockers of the slow afterhyperpolarization (sAHP) such as isoprenaline (ISO) or noradrenaline (NA) reduced the hyperpolarization that followed a short train of EPSPs, and slowed the decay of summated EPSPs or EPSCs. 2. ISO/NA action on synaptic responses was observed in the absence of action potentials, but was curtailed by Ca(2+) chelation (10 mM EGTA in the electrode) and was not observed with a caesium-based recording solution. This suggests the involvement of an ISO/NA-sensitive Ca(2+)-dependent K(+) current without a requirement for regenerative spiking. 3. An ISO/NA-sensitive sAHP was observed following both NMDA and non-NMDA receptor-mediated EPSP trains in nominally zero Mg(2+) medium. Isoprenaline sensitivity was blocked by hyperpolarization during EPSPs or by isradipine, suggesting a requirement for voltage-dependent Ca(2+) influx during EPSPs. The data indicate that bursts of EPSPs can activate voltage-gated Ca(2+) channels, which trigger I(sAHP) during synaptic responses. 4. A decrease in EPSP temporal summation occurred during both spike-evoked sAHPs and persistent activation of sAHP conductance following internal dialysis with diazo-2 (2 mM). At constant membrane potential, diazo-2 caused a decrease in membrane time constant and input resistance and accelerated the rate of EPSP decay. Photolysis of diazo-2 or application of NA reduced the resting sAHP conductance, causing an increased membrane time constant and input resistance in association with an increase in EPSP half-width. 5. These results indicate that short bursts of EPSPs can activate a Ca(2+)-dependent K(+) current resembling I(sAHP), and that activation of this current reduces the postsynaptic response to high-frequency synaptic input. The findings imply that modulation of I(sAHP) can regulate synaptic efficacy and may influence the threshold for tetanus-induced synaptic plasticity.
Adrenergic alpha-Agonists↗
[Clinical analysis of pulmonary lymphangioleiomyomatosis].
OBJECTIVE: To study the clinical features, treatment, and prognosis of pulmonary lymphangioleiomyomatosis (LAM). METHODS: A retrospective analysis of 16 cases of LAM was made, among which two were diagnosed and treated in the Chinese PLA General Hospital, and the clinical data of the other fourteen cases were studied by literature review. RESULTS: Among the 16 patients, 15 were female (94%) and 1 was male (6%). The age of onset ranged 5 - 69 years, with an average age of onset of 35 +/- 15 years. Thirteen patients (81%) were women of childbearing age. The main clinical menifestations included dyspnea (15 cases, 94%), hemoptysis (10 cases, 62%), pneumothorax (7 cases, 44%), and chylothorax (7 cases, 44%). High-resolution computerized tomography conducted in 14 cases showed thin-walled air-filled cysts throughout both lungs. Seven patients took pulmonary function test with the results of obstructive ventilatory disturbance in 5 cases, mixed ventilatory disturbance in 2 cases, and reduction of carbon dioxide duffusing capacity in all cases. Arterial blood gas analysis was made among 11 patients and showed hypoxemia (blood oxygen < 80 mm Hg) in 8 cases and respiratory failure in 5 cases. All of the patients were misdiagnosed as other diseases at the first visit. The time between onset of symptoms and confirmation of diagnosis ranged 2 - 276 months (median 28 months). Six patients were treated with medroxyprogesterone for 6-50 months. Among them two patient' condition remained stable, two patients' condition was worsened, and two died. Six out of the 16 patients (38%) died of respiratory failure, pneumothorax, or lung infection 1.5 to 26 years after the onset. CONCLUSION: The main clinical manifestations of LAM are dyspnea, hemoptysis, pneumothorax, and chylothorax. Medroxyprogesterone is of little curative effect on LAM. The main task in LAM research is to find out its etiology and effective treatment.
Adolescent↗
Plexin B mediates axon guidance in Drosophila by simultaneously inhibiting active Rac and enhancing RhoA signaling.
Plexins are neuronal receptors for the repulsive axon guidance molecule Semaphorins. Previous studies showed that Plexin B (PlexB) binds directly to the active, GTP-bound form of the Rac GTPase. Here, we define a seven amino acid sequence in PlexB required for Rac(GTP) binding. The interaction of PlexB with Rac(GTP) is necessary for Plexin-mediated axon guidance in vivo. A different region of PlexB binds to RhoA. Dosage-sensitive genetic interactions suggest that PlexB suppresses Rac activity and enhances RhoA activity. Biochemical evidence indicates that PlexB sequesters Rac(GTP) from its downstream effector PAK. These results suggest a model whereby PlexB mediates repulsion by coordinately regulating two small GTPases in opposite directions: PlexB binds to Rac(GTP) and downregulates its output by blocking its access to PAK and, at the same time, binds to and increases the output of RhoA.
Amino Acid Sequence↗
Antibody response to Epstein-Barr virus Rta protein in patients with nasopharyngeal carcinoma: a new serologic parameter for diagnosis.
BACKGROUND: Nasopharyngeal carcinoma (NPC) is associated closely with Epstein-Barr virus (EBV). The authors previously reported that an EBV immediate-early gene, BRLF1, was expressed frequently in NPC tumors, and a significant elevation in immunoglobulin G (IgG) antibodies directed against BRLF1 gene product Rta was detected in NPC sera by a radioactive immunoprecipitation assay. To simplify and to make the detection more quantitative, an enzyme-linked immnunosorbent assay (ELISA) was developed in this study. METHODS: Antigen domains of Rta were identified further using an immunoprecipitation assay. Two glutathione-S-transferase (GST) recombinant Rta fragments (R150-GST and R185-GST) were prepared subsequently and were used as antigens in the ELISA. Serum samples derived from 51 patients with NPC patients, 115 non-NPC ENT patients, and 47 healthy volunteers were examined for the presence of antibodies directed against Rta. RESULTS: Among the patients with NPC, 74.5% showed a positive IgG response to R150-GST, and 62.7% showed a positive IgG response to R185-GST, with 80.4% positive for either fragment. In contrast, the reactions were positive in only 8.5% of healthy volunteers and 13.0% of control patients. When using a mixture of the two recombinant Rta proteins as coating antigens, the IgG positive responses were 82.3%, 10.6%, and 14.8%, respectively, in patients with NPC, healthy volunteers, and control patients. It is noteworthy that 51.0% of the NPC sera showed a positive immunoglobulin A (IgA) response, with none of the control patients showing obvious reactivity. Both the IgG response and the IgA response to Rta protein in patients with NPC were correlated with the IgA response to EBV early antigens and virus capsid antigens, the classic serologic markers used to diagnose NPC. CONCLUSIONS: The ELISA method described for the detection of IgG antibodies directed against recombinant Rta proteins is simple and reliable and may be useful as a serologic parameter for the screening and diagnosis of patients with NPC.
Antibodies, Viral↗
Fragmented condensate ground state of trapped weakly interacting bosons in two dimensions.
The ground state and its structure for a rotating, harmonically trapped N-boson system with a weak repulsive contact interaction are studied as the angular momentum L increases up to 3N. We show that the ground state is generally a fragmented condensate due to angular momentum conservation. In response to an (arbitrarily weak) asymmetric perturbation of the trap, however, the fragmented ground state can be transformed into a single condensate state. We manifest this intrinsic instability by calculating the conditional probability distributions, which show patterns analogous to the boson density distributions predicted by mean-field theory.
Journal Article↗
Mesoscopic Kondo screening effect in a single-electron transistor embedded in a metallic ring.
We study the Kondo screening effect generated by a single-electron transistor or quantum dot embedded in a small metallic ring. When the ring circumference L becomes comparable to the fundamental length scale xi(0)(K) = Planck's constant over upsilon(F)/T(0)(K) associated with the bulk Kondo temperature, the Kondo resonance is strongly affected, depending on the total number of electrons (mod4) and magnetic flux threading the ring. The resulting Kondo-assisted persistent currents are also calculated in both Kondo and mixed-valence regimes, and the maximum values are found in the crossover region.
Journal Article↗
Long-term efficacy after [E1-, polymerase-] adenovirus-mediated transfer of human acid-alpha-glucosidase gene into glycogen storage disease type II knockout mice.
Glycogen storage disease type II (GSD-II) is a lethal, autosomal recessive metabolic myopathy caused by a lack of acid-alpha-glucosidase (GAA) activity in the cardiac and skeletal muscles. Absence of adequate intralysosomal GAA activity results in massive amounts of glycogen accumulation in multiple muscle groups, resulting in morbidity and mortality secondary to respiratory embarrassment and/or cardiomyopathy. In a mouse model of GSD-II, we demonstrate that infection of the murine liver with a modified adenovirus (Ad) vector encoding human GAA (hGAA) resulted in long-term persistence of the vector in liver tissues for at least 6 months. Despite both a rapid shutdown of hGAA mRNA expression from the vector, as well as the elicitation of anti-hGAA antibody responses (hGAA is a foreign antigen in this model), the hGAA secreted by the liver was taken up by all muscle groups analyzed and, remarkably, persisted in them for at least 6 months. The persistence of the protein also correlated with long-term correction of pathologic intramuscular glycogen accumulations in all muscle groups tested, but most notably the cardiac tissues, which demonstrated a significantly decreased glycogen content for at least 190 days after a single vector injection. The results suggest that gene therapy strategies may have the potential to significantly improve the clinical course for GSD-II patients.
Adenoviridae↗
Biochemical characterization of the thioredoxin domain of Escherichia coli DsbE protein reveals a weak reductant.
Thioredoxin (Trx) domain is a typical fold functioning in thiol/disulfide exchange. DsbE protein is one of the Trx-domain containing proteins involved in electron transfer for cytochrome c maturation in the periplasm of Escherichia coli. The soluble C-terminal Trx domain of DsbE protein was overexpressed and purified to homogeneity. We herein report biochemical characterization of the structural and redox properties of this domain. During redox reaction, the domain undergoes a structural transformation resulting in a more stable reduced form with a free energy difference (DeltaDeltaG(Redox)) of ca. 5 kcal/mol, but the thiol/disulfide exchange exhibits very low reactivity. The standard redox potential (E0') for the active thiol/disulfide is -0.175 V and the pK(a) value of the active cysteine is around 6.8, indicating that the domain acts as a weak reductant. This implies that the membrane-anchored DsbE protein may provide driven reducing power for the redox reaction in the thiol/disulfide exchange pathway.
Circular Dichroism↗